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Cancer Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Τετάρτη 2 Μαΐου 2018
A TGF‐β1 genetic variant at the miRNA187 binding site significantly modifies risk of HPV16‐associated oropharyngeal cancer
International Journal of Cancer, EarlyView.
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A TGF‐β1 genetic variant at the miRNA187 binding site significantly modifies risk of HPV16‐associated oropharyngeal cancer
International Journal of Cancer, EarlyView.
https://ift.tt/2HK0QzH
PKCα in colon cancer cells promotes M1 macrophage polarization via MKK3/6‐P38 MAPK pathway
Molecular Carcinogenesis, EarlyView.
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Differential ability of formononetin to stimulate proliferation of endothelial cells and breast cancer cells via a feedback loop involving MicroRNA‐375, RASD1, and ERα
Molecular Carcinogenesis, EarlyView.
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Phenylbutyl isoselenocyanate induces reactive oxygen species to inhibit androgen receptor and to initiate p53‐mediated apoptosis in LNCaP prostate cancer cells
Molecular Carcinogenesis, EarlyView.
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Interaction with SP1, but not binding to the E‐box motifs, is responsible for BHLHE40/DEC1‐induced transcriptional suppression of CLDN1 and cell invasion in MCF‐7 cells
Molecular Carcinogenesis, EarlyView.
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Targeting HSP60 by subcutaneous injections of jetPEI/HSP60‐shRNA destabilizes cytoplasmic survivin and inhibits hepatocellular carcinoma growth
Molecular Carcinogenesis, EarlyView.
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MiR‐193a‐3p and miR‐224 mediate renal cell carcinoma progression by targeting alpha‐2,3‐sialyltransferase IV and the phosphatidylinositol 3 kinase/Akt pathway
Molecular Carcinogenesis, EarlyView.
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PIEZO1 functions as a potential oncogene by promoting cell proliferation and migration in gastric carcinogenesis
Molecular Carcinogenesis, EarlyView.
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Differential ability of formononetin to stimulate proliferation of endothelial cells and breast cancer cells via a feedback loop involving MicroRNA‐375, RASD1, and ERα
Molecular Carcinogenesis, EarlyView.
https://ift.tt/2JOhDxY
PKCα in colon cancer cells promotes M1 macrophage polarization via MKK3/6‐P38 MAPK pathway
Molecular Carcinogenesis, EarlyView.
https://ift.tt/2I9A2YY
Phenylbutyl isoselenocyanate induces reactive oxygen species to inhibit androgen receptor and to initiate p53‐mediated apoptosis in LNCaP prostate cancer cells
Molecular Carcinogenesis, EarlyView.
https://ift.tt/2JQwxEb
Interaction with SP1, but not binding to the E‐box motifs, is responsible for BHLHE40/DEC1‐induced transcriptional suppression of CLDN1 and cell invasion in MCF‐7 cells
Molecular Carcinogenesis, EarlyView.
https://ift.tt/2I5AwPQ
Targeting HSP60 by subcutaneous injections of jetPEI/HSP60‐shRNA destabilizes cytoplasmic survivin and inhibits hepatocellular carcinoma growth
Molecular Carcinogenesis, EarlyView.
https://ift.tt/2JOw0m4
MiR‐193a‐3p and miR‐224 mediate renal cell carcinoma progression by targeting alpha‐2,3‐sialyltransferase IV and the phosphatidylinositol 3 kinase/Akt pathway
Molecular Carcinogenesis, EarlyView.
https://ift.tt/2I8gZyo
PIEZO1 functions as a potential oncogene by promoting cell proliferation and migration in gastric carcinogenesis
Molecular Carcinogenesis, EarlyView.
https://ift.tt/2JNldII
Clinicopathological characteristics and survival outcomes in Paget disease: a SEER population‐based study
Cancer Medicine, EarlyView.
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Clinicopathological characteristics and survival outcomes in Paget disease: a SEER population‐based study
Cancer Medicine, EarlyView.
https://ift.tt/2w9sKQ7
Pulsus alternans induced by spinal anesthesia
Pulsus alternans is attributed to an alteration of the stroke volume with every other cardiac cycle, and reduced venous return is considered an important causative factor. Tachycardia can exacerbate this process as diastolic filling becomes further impaired. During pulsus alternans, increased end-diastolic volume can increase wall stress, which further reduces systolic performance [1], making appropriate treatment essential, even if the patient shows no signs or symptoms of heart failure.
https://ift.tt/2HRwlnC
Whether time of operation does not increase the mortality rate in emergency surgery?
In a retrospective analysis, Rodney AG and colleagues [1] claim that time of operation (after-hours versus day-time hours) was not associated with death in emergency surgery, and those patients who undergoing intrathoracic or intraabdominal surgery, older patients and patients with a higher ASA PS may be at a higher risk of intraoperative mortality. However, we think it is inappropriate to reach the conclusion that no association of perioperative mortality with time of day in emergency surgery.
https://ift.tt/2jpTu5C
Airtraq® reduces the hemodynamic response to tracheal intubation using single-lumen tubes in adults compared with the Macintosh laryngoscope: A systematic review and meta-analysis of randomized control trials
To investigate whether Airtraq® attenuate the hemodynamic responses to tracheal intubation using single-lumen tubes in adults as compared with the Macintosh laryngoscope.
https://ift.tt/2HR3f7x
Ultrasound-guided erector spinae plane block elicits sensory loss around the lateral, but not the parasternal, portion of the thorax
Ultrasound-guided erector spinae plane block (US-ESPB) has been recently reported to be an effective technique for thoracic surgery [1,2]. US-ESPB is a type of fascial block requiring a sufficient dose of drug to adequately cover the interfascial plane [3]. We performed US-ESPB for 12 patients in cases of thoracoscopic lobectomy and assessed the anesthetized area from anterior to lateral thorax, as well as postoperative pain scores, to verify the analgesic features for thoracic surgery. After obtaining written informed consent from all patients and approval from the Institutional Review Board of Ehime Prefectural Central Hospital, patients with American Society of Anesthesiologists physical status 1–3, who were scheduled to undergo complete video-assisted lobectomy without rib spreading, underwent US-ESPB followed by the induction of general anesthesia.
https://ift.tt/2reABau
Bilateral continuous erector spinae plane blocks for sternotomy in a pediatric cardiac patient
Effectiveness of continuous erector spinae plane (ESP) block as an alternative to thoracic epidural anesthesia have been reported for pain management in pulmonary malignancy [1]. In fact, there are multiple reports [2–5] can provide good analgesia for selective major thoracic procedures when epidural anesthesia is contraindicated, or if there are other concerns about administering an epidural.
https://ift.tt/2HR2Y4v
Transnasal sphenopalatine nerve block for patients with headaches
Letter to the editor
https://ift.tt/2rheksB
A novel plasma circular RNA circFARSA is a potential biomarker for non‐small cell lung cancer
Cancer Medicine, EarlyView.
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Efficacy and safety of first-line sunitinib in Chinese patients with metastatic renal cell carcinoma
Future Oncology, Ahead of Print.
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The importance of food, nutrition and physical activity in cancer prevention: an interview with Dr Kate Allen
Future Oncology, Ahead of Print.
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A novel plasma circular RNA circFARSA is a potential biomarker for non‐small cell lung cancer
Cancer Medicine, EarlyView.
https://ift.tt/2I8oMfv
Efficacy and safety of first-line sunitinib in Chinese patients with metastatic renal cell carcinoma
Future Oncology, Ahead of Print.
https://ift.tt/2HLFC4o
The importance of food, nutrition and physical activity in cancer prevention: an interview with Dr Kate Allen
Future Oncology, Ahead of Print.
https://ift.tt/2w9h4gf
The Influence of Patient Identification and Narrative Transportation on Intentions to Participate in Cancer Research
Abstract
Cancer decision-making interventions commonly utilize narratives as a persuasive strategy to increase identification with the message source, promote involvement with the topic, and elicit greater willingness to adopt recommended behaviors. However, there is little empirical research examining the mechanisms underlying the effectiveness of this strategy in the context of cancer research participation. Data for the current manuscript were collected as part of a larger study conducted with cancer patients (N = 413) from the USA, UK, and the Republic of Ireland. Participants viewed and evaluated video-recorded vignettes, illustrating different strategies for discussing clinical trials participation with family members. Results showed nationality was a significant predictor of identification with the main character (i.e., patient) in the vignette. Unexpectedly, these cross-national differences in identification disappeared when patients currently undergoing treatment had higher perceived susceptibility of their cancer. Identification with the main character in the vignettes was a significant predictor of intentions to participate in cancer research, but only when the mediating role of narrative transportation was considered. The findings demonstrate the importance of considering how individual and social identities influence identification with characters in cancer narratives and yield practical guidance for developing arts-based interventions to increase cancer research participation.
https://ift.tt/2HKgT0x
The Influence of Patient Identification and Narrative Transportation on Intentions to Participate in Cancer Research
Abstract
Cancer decision-making interventions commonly utilize narratives as a persuasive strategy to increase identification with the message source, promote involvement with the topic, and elicit greater willingness to adopt recommended behaviors. However, there is little empirical research examining the mechanisms underlying the effectiveness of this strategy in the context of cancer research participation. Data for the current manuscript were collected as part of a larger study conducted with cancer patients (N = 413) from the USA, UK, and the Republic of Ireland. Participants viewed and evaluated video-recorded vignettes, illustrating different strategies for discussing clinical trials participation with family members. Results showed nationality was a significant predictor of identification with the main character (i.e., patient) in the vignette. Unexpectedly, these cross-national differences in identification disappeared when patients currently undergoing treatment had higher perceived susceptibility of their cancer. Identification with the main character in the vignettes was a significant predictor of intentions to participate in cancer research, but only when the mediating role of narrative transportation was considered. The findings demonstrate the importance of considering how individual and social identities influence identification with characters in cancer narratives and yield practical guidance for developing arts-based interventions to increase cancer research participation.
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The Influence of Patient Identification and Narrative Transportation on Intentions to Participate in Cancer Research
Abstract
Cancer decision-making interventions commonly utilize narratives as a persuasive strategy to increase identification with the message source, promote involvement with the topic, and elicit greater willingness to adopt recommended behaviors. However, there is little empirical research examining the mechanisms underlying the effectiveness of this strategy in the context of cancer research participation. Data for the current manuscript were collected as part of a larger study conducted with cancer patients (N = 413) from the USA, UK, and the Republic of Ireland. Participants viewed and evaluated video-recorded vignettes, illustrating different strategies for discussing clinical trials participation with family members. Results showed nationality was a significant predictor of identification with the main character (i.e., patient) in the vignette. Unexpectedly, these cross-national differences in identification disappeared when patients currently undergoing treatment had higher perceived susceptibility of their cancer. Identification with the main character in the vignettes was a significant predictor of intentions to participate in cancer research, but only when the mediating role of narrative transportation was considered. The findings demonstrate the importance of considering how individual and social identities influence identification with characters in cancer narratives and yield practical guidance for developing arts-based interventions to increase cancer research participation.
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Targeting the mevalonate pathway suppresses VHL-deficient CC-RCC through a HIF-dependent mechanism
Clear Cell Renal Cell Carcinoma (CC-RCC) is a devastating disease with limited therapeutic options available for advance stages. The objective of this study was to investigate HMG-CoA Reductase inhibitors, also known as statins, as potential therapeutics for CC-RCC. Importantly, treatment with statins was found to be synthetically lethal with the loss of the von Hippel-Lindau (VHL) tumor suppressor gene, which occurs in 90% of CC-RCC driving the disease. This effect has been confirmed in three different CC-RCC cell lines with three different lipophilic statins. Inhibition of mevalonate synthesis by statins causes a profound cytostatic effect at nanomolar concentrations and becomes cytotoxic at low micromolar concentrations in VHL-deficient CC-RCC. The synthetic lethal effect can be fully rescued by both mevalonate and geranylgeranylpyrophosphate, but not squalene, indicating that the effect is due to disruption of small GTPase isoprenylation and not the inhibition of cholesterol synthesis. Inhibition of Rho and Rho kinase (ROCK) signaling contributes to the synthetic lethality effect, and overactivation of Hypoxia Inducible Factor signaling resulting from VHL loss is required. Finally, statin treatment is able to inhibit both tumor initiation and progression of subcutaneous 786-OT1-based CC-RCC tumors in mice. Thus, statins represent potential therapeutics for the treatment of VHL-deficient CC-RCC.
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Androgen Receptor Signaling Reduces Radiosensitivity in Bladder Cancer
Although radiotherapy often with chemotherapy has been shown to offer a survival benefit comparable to that of radical cystectomy in select patients with bladder cancer, the development of radiosensitization strategies may significantly enhance its application. Notably, emerging preclinical evidence has indicated the involvement of androgen receptor (AR) signaling in urothelial cancer progression. We here assessed whether AR signals could contribute to modulating radiosensitivity in bladder cancer cells. Ionizing radiation reduced the numbers of viable cells or colonies of AR-negative lines more significantly than those of AR-positive lines. Similarly, in AR-positive cells cultured in androgen-depleted conditions, dihydrotestosterone treatment lowered the effects of irradiation. Meanwhile, an anti-androgen hydroxyflutamide enhanced them in AR-positive cells cultured in the presence of androgens. AR knockdown or hydroxyflutamide treatment also resulted in a delay in DNA double-strand break repair 4-24 hours after irradiation. We then established "radiation-resistant" sublines and found considerable elevation of the expression of AR as well as DNA repair genes, such as ATR, CHEK1, and PARP-1, in these sublines, compared with respective controls. Furthermore, dihydrotestosterone induced the expression of these DNA repair genes in irradiated AR-positive cells, and hydroxyflutamide antagonized the androgen effects. Finally, in a mouse xenograft model, low-dose flutamide was found to enhance the inhibitory effects of irradiation, and its tumor size was similar to that of AR knockdown line with radiation alone. These findings suggest that AR activity inversely correlates with radiosensitivity in bladder cancer. Accordingly, anti-androgenic drugs may function as sensitizers of irradiation, especially in patients with AR-positive urothelial cancer.
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A Raf-competitive K-Ras binder can fail to functionally antagonize signaling
Mutated in approximately 30% of human cancers, Ras GTPases are the most common drivers of oncogenesis and render tumors unresponsive to many standard therapies. Despite decades of research, no drugs directly targeting Ras are currently available. We have previously characterized a small protein antagonist of K-Ras, R11.1.6, and demonstrated its direct competition with Raf for Ras binding. Here we evaluate the effects of R11.1.6 on Ras signaling and cellular proliferation in a panel of human cancer cell lines. Through lentiviral transduction, we generated cell lines that constitutively or through induction with doxycycline express R11.1.6 or a control protein YW1 and show specific binding by R11.1.6 to endogenous Ras through microscopy and co-immunoprecipitation experiments. Genetically-encoded intracellular expression of this high-affinity Ras antagonist, however, fails to measurably disrupt signaling through either the MAPK or PI3K pathway. Consistently, cellular proliferation was unaffected as well. To understand this lack of signaling inhibition, we quantified the number of molecules of R11.1.6 expressed by the inducible cell lines and developed a simple mathematical model describing the competitive binding of Ras by R11.1.6 and Raf. This model supports a potential mechanism for the lack of biological effects that we observed, suggesting stoichiometric and thermodynamic barriers that should be overcome in pharmacological efforts to directly compete with downstream effector proteins localized to membranes at very high effective concentrations.
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The Influence of Patient Identification and Narrative Transportation on Intentions to Participate in Cancer Research
Abstract
Cancer decision-making interventions commonly utilize narratives as a persuasive strategy to increase identification with the message source, promote involvement with the topic, and elicit greater willingness to adopt recommended behaviors. However, there is little empirical research examining the mechanisms underlying the effectiveness of this strategy in the context of cancer research participation. Data for the current manuscript were collected as part of a larger study conducted with cancer patients (N = 413) from the USA, UK, and the Republic of Ireland. Participants viewed and evaluated video-recorded vignettes, illustrating different strategies for discussing clinical trials participation with family members. Results showed nationality was a significant predictor of identification with the main character (i.e., patient) in the vignette. Unexpectedly, these cross-national differences in identification disappeared when patients currently undergoing treatment had higher perceived susceptibility of their cancer. Identification with the main character in the vignettes was a significant predictor of intentions to participate in cancer research, but only when the mediating role of narrative transportation was considered. The findings demonstrate the importance of considering how individual and social identities influence identification with characters in cancer narratives and yield practical guidance for developing arts-based interventions to increase cancer research participation.
https://ift.tt/2HKgT0x
Targeting the mevalonate pathway suppresses VHL-deficient CC-RCC through a HIF-dependent mechanism
Clear Cell Renal Cell Carcinoma (CC-RCC) is a devastating disease with limited therapeutic options available for advance stages. The objective of this study was to investigate HMG-CoA Reductase inhibitors, also known as statins, as potential therapeutics for CC-RCC. Importantly, treatment with statins was found to be synthetically lethal with the loss of the von Hippel-Lindau (VHL) tumor suppressor gene, which occurs in 90% of CC-RCC driving the disease. This effect has been confirmed in three different CC-RCC cell lines with three different lipophilic statins. Inhibition of mevalonate synthesis by statins causes a profound cytostatic effect at nanomolar concentrations and becomes cytotoxic at low micromolar concentrations in VHL-deficient CC-RCC. The synthetic lethal effect can be fully rescued by both mevalonate and geranylgeranylpyrophosphate, but not squalene, indicating that the effect is due to disruption of small GTPase isoprenylation and not the inhibition of cholesterol synthesis. Inhibition of Rho and Rho kinase (ROCK) signaling contributes to the synthetic lethality effect, and overactivation of Hypoxia Inducible Factor signaling resulting from VHL loss is required. Finally, statin treatment is able to inhibit both tumor initiation and progression of subcutaneous 786-OT1-based CC-RCC tumors in mice. Thus, statins represent potential therapeutics for the treatment of VHL-deficient CC-RCC.
https://ift.tt/2Id7tKs
Androgen Receptor Signaling Reduces Radiosensitivity in Bladder Cancer
Although radiotherapy often with chemotherapy has been shown to offer a survival benefit comparable to that of radical cystectomy in select patients with bladder cancer, the development of radiosensitization strategies may significantly enhance its application. Notably, emerging preclinical evidence has indicated the involvement of androgen receptor (AR) signaling in urothelial cancer progression. We here assessed whether AR signals could contribute to modulating radiosensitivity in bladder cancer cells. Ionizing radiation reduced the numbers of viable cells or colonies of AR-negative lines more significantly than those of AR-positive lines. Similarly, in AR-positive cells cultured in androgen-depleted conditions, dihydrotestosterone treatment lowered the effects of irradiation. Meanwhile, an anti-androgen hydroxyflutamide enhanced them in AR-positive cells cultured in the presence of androgens. AR knockdown or hydroxyflutamide treatment also resulted in a delay in DNA double-strand break repair 4-24 hours after irradiation. We then established "radiation-resistant" sublines and found considerable elevation of the expression of AR as well as DNA repair genes, such as ATR, CHEK1, and PARP-1, in these sublines, compared with respective controls. Furthermore, dihydrotestosterone induced the expression of these DNA repair genes in irradiated AR-positive cells, and hydroxyflutamide antagonized the androgen effects. Finally, in a mouse xenograft model, low-dose flutamide was found to enhance the inhibitory effects of irradiation, and its tumor size was similar to that of AR knockdown line with radiation alone. These findings suggest that AR activity inversely correlates with radiosensitivity in bladder cancer. Accordingly, anti-androgenic drugs may function as sensitizers of irradiation, especially in patients with AR-positive urothelial cancer.
https://ift.tt/2w7w1jb
A Raf-competitive K-Ras binder can fail to functionally antagonize signaling
Mutated in approximately 30% of human cancers, Ras GTPases are the most common drivers of oncogenesis and render tumors unresponsive to many standard therapies. Despite decades of research, no drugs directly targeting Ras are currently available. We have previously characterized a small protein antagonist of K-Ras, R11.1.6, and demonstrated its direct competition with Raf for Ras binding. Here we evaluate the effects of R11.1.6 on Ras signaling and cellular proliferation in a panel of human cancer cell lines. Through lentiviral transduction, we generated cell lines that constitutively or through induction with doxycycline express R11.1.6 or a control protein YW1 and show specific binding by R11.1.6 to endogenous Ras through microscopy and co-immunoprecipitation experiments. Genetically-encoded intracellular expression of this high-affinity Ras antagonist, however, fails to measurably disrupt signaling through either the MAPK or PI3K pathway. Consistently, cellular proliferation was unaffected as well. To understand this lack of signaling inhibition, we quantified the number of molecules of R11.1.6 expressed by the inducible cell lines and developed a simple mathematical model describing the competitive binding of Ras by R11.1.6 and Raf. This model supports a potential mechanism for the lack of biological effects that we observed, suggesting stoichiometric and thermodynamic barriers that should be overcome in pharmacological efforts to directly compete with downstream effector proteins localized to membranes at very high effective concentrations.
https://ift.tt/2HK8j1R
microRNA-451a regulates colorectal cancer proliferation in response to radiation
Abstract
Background
Colorectal cancer (CRC) is a leading cause of cancer-related death. The biologic response of CRC to standard of care adjuvant therapies such as chemotherapy and radiation are poorly understood. MicroRNAs (miRs) have been shown to affect CRC progression and metastasis. Therefore, we hypothesized that specific miRs modulate CRC response to chemoradiation.
Methods
In this study, we used miR expression profiling and discovered a set of microRNAs upregulated rapidly in response to either a single 2 Gy dose fraction or a 10 Gy dose of γ-radiation in mouse colorectal carcinoma models. We used gain and loss-of-function studies in 2D and 3Dcell proliferation assays and colony formation assays to understand the role of the top miR candidate from our profiling. We used Student's T-tests for simple comparisons and two-factor ANOVA for evaluating significance.
Results
The most upregulated candidate at early time points in our signature, miR-451a inhibited tumor cell proliferation and attenuated surviving fraction in longer-term cultures. Conversely, inhibition of miR-451a increased proliferation, tumorsphere formation, and surviving fraction of tumor cells. Using a bioinformatics approach, we identified four genes, CAB39, EMSY, MEX3C, and EREG, as targets of miR-451a. Transfection of miR-451a decreased both mRNA and protein levels of these targets. Importantly, we found miR-451a expression was high and CAB39, EMSY levels were low in a small subset of rectal cancer patients who had a partial response to chemoradiation when compared to patients that had no response. Finally, analysis of a TCGA colorectal cancer dataset revealed that CAB39 and EMSY are upregulated at the protein level in a significant number of CRC patients. Higher levels of CAB39 and EMSY correlated with poorer overall survival.
Conclusions
Taken together, our data indicates miR-451a is induced by radiation and may influence colorectal carcinoma proliferation via CAB39 and EMSY pathways.
https://ift.tt/2JOg2bC
Emotional predictors of bowel screening: the avoidance-promoting role of fear, embarrassment, and disgust
Abstract
Background
Despite considerable efforts to address practical barriers, colorectal cancer screening numbers are often low. People do not always act rationally, and investigating emotions may offer insight into the avoidance of screening. The current work assessed whether fear, embarrassment, and disgust predicted colorectal cancer screening avoidance.
Methods
A community sample (N = 306) aged 45+ completed a questionnaire assessing colorectal cancer screening history and the extent that perceptions of cancer risk, colorectal cancer knowledge, doctor discussions, and a specifically developed scale, the Emotional Barriers to Bowel Screening (EBBS), were associated with previous screening behaviours and anticipated bowel health decision-making.
Results
Step-wise logistic regression models revealed that a decision to delay seeking healthcare in the hypothetical presence of bowel symptoms was less likely in people who had discussed risk with their doctor, whereas greater colorectal cancer knowledge and greater fear of a negative outcome predicted greater likelihood of delay. Having previously provided a faecal sample was predicted by discussions about risk with a doctor, older age, and greater embarrassment, whereas perceptions of lower risk predicted a lower likelihood. Likewise, greater insertion disgust predicted a lower likelihood of having had an invasive bowel screening test in the previous 5 years.
Conclusions
Alongside medical and demographic factors, fear, embarrassment and disgust are worthy of consideration in colorectal cancer screening. Understanding how specific emotions impact screening decisions and behaviour is an important direction for future work and has potential to inform screening development and communications in bowel health.
https://ift.tt/2IbSYXc
Telmisartan attenuates hydrogen peroxide-induced apoptosis in differentiated PC12 cells
Abstract
The present study investigated the protective actions of telmisartan, an angiotensin II type 1 receptor blocker (ARBs), against the cell apoptosis induced by exposure to hydrogen peroxide (H2O2) in differentiated PC12 cells. Preincubation of PC12 cells with telmisartan prevented H2O2-induced cytotoxicity as indicated by increased MTT (3,(4,5-dimethylthiazole-2-yl)2,5-diphenyl-tetrazolium bromide) reduction, decreased lactate dehydrogenase (LDH) release, and improved morphological changes. Hoechst 33,258 staining showed that telmisartan markedly reduced shrunken nuclei of the cells, and Western blot analysis indicated that telmisartan significantly attenuated caspase-3 activity, as indicated by decreased ratio of cleaved Caspase-3 to its precursor and increased ratio of Bcl-2/Bax. The present findings showed that telmisartan protected against cellular oxidative damages by inhibiting apoptotic response.
https://ift.tt/2wafz1s
Exosomes: Definition, Role in Tumor Development and Clinical Implications
Abstract
Exosomes are microvesicles released by cells in both physiological and pathological situations. They are surrounded by a lipid bilayer with proteins derived from the origin cell, and contain a variety of molecules, such as nucleic acids. They represent an emerging mechanism of intercellular communication, and they play an important role in the pathogenesis of cancer, stimulating proliferation and aggressiveness of cancer cells, inducing a microenvironment favorable to tumor development and controlling immune responses. Because of the growing understanding of the potential implications of extracellular vesicles in the development of malignancies, research on exosomes, and its role as a diagnostic and therapeutic tool, constitutes nowadays a very exciting and promising field.
https://ift.tt/2w7fXh3
Induction of Neoantigen-specific Cytotoxic T Cells and Construction of T-cell Receptor-engineered T cells for Ovarian Cancer
Purpose: Current evolution of cancer immunotherapies, such as immune checkpoint blockade, has implicated neoantigens as major targets of anti-cancer cytotoxic T cells. Adoptive T cell therapy with neoantigen-specific T cell receptor (TCR)-engineered T cells would be an attractive therapeutic option for advanced cancers where the host anti-tumor immune function is strongly inhibited. We previously developed a rapid and efficient pipeline for production of neoantigen-specific TCR-engineered T cells using peripheral blood from an HLA-matched healthy donor. Our protocol required only two weeks from stimulation of T cells with neoantigen-loaded dendritic cells to the identification of neoantigen-specific TCRs. We conducted the pilot study to validate our protocol. Experimental Design: We used tumors from 7 ovarian cancer patients to validate our protocol. Results: We chose 14 candidate neoantigens from 7 ovarian tumors (1-3 candidates for each patient), and then successfully induced 3 neoantigen-specific T cells from one healthy donor and identified their TCR sequences. Moreover, we validated functional activity of the three identified TCRs by generating TCR-engineered T cells which recognized the corresponding neoantigens and showed cytotoxic activity in an antigen-dose-dependent manner. However, one case of neoantigen-specific TCR-engineered T cells showed cross-reactivity against the corresponding wild-type peptide. Conclusion/Discussions: This pilot study demonstrated the feasibility of our efficient process from identification of neoantigen to production of the neoantigen-targeting cytotoxic TCR-engineered T cells for ovarian cancer and revealed the importance of careful validation of neoantigen-specific-TCR-engineered T cells to avoid severe immune-related adverse events.
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Induction of Neoantigen-specific Cytotoxic T Cells and Construction of T-cell Receptor-engineered T cells for Ovarian Cancer
Purpose: Current evolution of cancer immunotherapies, such as immune checkpoint blockade, has implicated neoantigens as major targets of anti-cancer cytotoxic T cells. Adoptive T cell therapy with neoantigen-specific T cell receptor (TCR)-engineered T cells would be an attractive therapeutic option for advanced cancers where the host anti-tumor immune function is strongly inhibited. We previously developed a rapid and efficient pipeline for production of neoantigen-specific TCR-engineered T cells using peripheral blood from an HLA-matched healthy donor. Our protocol required only two weeks from stimulation of T cells with neoantigen-loaded dendritic cells to the identification of neoantigen-specific TCRs. We conducted the pilot study to validate our protocol. Experimental Design: We used tumors from 7 ovarian cancer patients to validate our protocol. Results: We chose 14 candidate neoantigens from 7 ovarian tumors (1-3 candidates for each patient), and then successfully induced 3 neoantigen-specific T cells from one healthy donor and identified their TCR sequences. Moreover, we validated functional activity of the three identified TCRs by generating TCR-engineered T cells which recognized the corresponding neoantigens and showed cytotoxic activity in an antigen-dose-dependent manner. However, one case of neoantigen-specific TCR-engineered T cells showed cross-reactivity against the corresponding wild-type peptide. Conclusion/Discussions: This pilot study demonstrated the feasibility of our efficient process from identification of neoantigen to production of the neoantigen-targeting cytotoxic TCR-engineered T cells for ovarian cancer and revealed the importance of careful validation of neoantigen-specific-TCR-engineered T cells to avoid severe immune-related adverse events.
https://ift.tt/2HMRLG8
Treatment patterns and survival among older adults in the United States with advanced soft-tissue sarcomas
Abstract
Background
To describe patient and tumor characteristics, treatments, and survival among older adults in the United States with advanced soft-tissue sarcoma (STS), across and by categories of specifically defined histologic subtypes.
Methods
We conducted a retrospective cohort analysis using the SEER. The study population comprised patients ≥ 65 years old with advanced STS (excluding osteosarcoma, Kaposi sarcoma, and gastrointestinal stromal tumors) diagnosed from January 1, 2001 to December 31, 2011.
Results
Of 4274 study patients, 2103 (49.2%) were male. Mean age was 77.8 years, and 1539 (36.0%) had distant disease at initial diagnosis. The most common histologic categories were leiomyosarcoma (922[21.6%]), undifferentiated pleomorphic sarcoma (652[15.3%]), and liposarcoma (554[13.0%]). Overall, 1227 (28.7%) patients received first-line systemic therapy. Among these patients, 325 (26.5%) received docetaxel plus gemcitabine and 231 (18.8%) received doxorubicin alone. Only 476 patients received second-line therapy (11.1%), most commonly doxorubicin alone (n = 101). Median overall survival (95% confidence interval) from advanced STS diagnosis was 8.9 (8.3, 9.7) months.
Conclusions
Although previous studies of younger populations reported anthracycline-based therapy predominated in first line, our study of older advanced STS patients found that docetaxel plus gemcitabine was most commonly used. Despite variation by histologic category, prognosis remains poor for older adult patients with advanced STS.
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Current Consensus on I-131 MIBG Therapy
Abstract
Metaiodobenzylguanidine (MIBG) is structurally similar to the neurotransmitter norepinephrine and specifically targets neuroendocrine cells including some neuroendocrine tumors. Iodine-131 (I-131)-labeled MIBG (I-131 MIBG) therapy for neuroendocrine tumors has been performed for more than a quarter-century. The indications of I-131 MIBG therapy include treatment-resistant neuroblastoma (NB), unresectable or metastatic pheochromocytoma (PC) and paraganglioma (PG), unresectable or metastatic carcinoid tumors, and unresectable or metastatic medullary thyroid cancer (MTC). I-131 MIBG therapy is one of the considerable effective treatments in patients with advanced NB, PC, and PG. On the other hand, I-131 MIBG therapy is an alternative method after more effective novel therapies are used such as radiolabeled somatostatin analogs and tyrosine kinase inhibitors in patients with advanced carcinoid tumors and MTC. No-carrier-aided (NCA) I-131 MIBG has more favorable potential compared to the conventional I-131 MIBG. Astatine-211-labeled meta-astatobenzylguanidine (At-211 MABG) has massive potential in patients with neuroendocrine tumors. Further studies about the therapeutic protocols of I-131 MIBG including NCA I-131 MIBG in the clinical setting and At-211 MABG in both the preclinical and clinical settings are needed.
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Treatment patterns and survival among older adults in the United States with advanced soft-tissue sarcomas
Abstract
Background
To describe patient and tumor characteristics, treatments, and survival among older adults in the United States with advanced soft-tissue sarcoma (STS), across and by categories of specifically defined histologic subtypes.
Methods
We conducted a retrospective cohort analysis using the SEER. The study population comprised patients ≥ 65 years old with advanced STS (excluding osteosarcoma, Kaposi sarcoma, and gastrointestinal stromal tumors) diagnosed from January 1, 2001 to December 31, 2011.
Results
Of 4274 study patients, 2103 (49.2%) were male. Mean age was 77.8 years, and 1539 (36.0%) had distant disease at initial diagnosis. The most common histologic categories were leiomyosarcoma (922[21.6%]), undifferentiated pleomorphic sarcoma (652[15.3%]), and liposarcoma (554[13.0%]). Overall, 1227 (28.7%) patients received first-line systemic therapy. Among these patients, 325 (26.5%) received docetaxel plus gemcitabine and 231 (18.8%) received doxorubicin alone. Only 476 patients received second-line therapy (11.1%), most commonly doxorubicin alone (n = 101). Median overall survival (95% confidence interval) from advanced STS diagnosis was 8.9 (8.3, 9.7) months.
Conclusions
Although previous studies of younger populations reported anthracycline-based therapy predominated in first line, our study of older advanced STS patients found that docetaxel plus gemcitabine was most commonly used. Despite variation by histologic category, prognosis remains poor for older adult patients with advanced STS.
https://ift.tt/2I9O5xO
Current Consensus on I-131 MIBG Therapy
Abstract
Metaiodobenzylguanidine (MIBG) is structurally similar to the neurotransmitter norepinephrine and specifically targets neuroendocrine cells including some neuroendocrine tumors. Iodine-131 (I-131)-labeled MIBG (I-131 MIBG) therapy for neuroendocrine tumors has been performed for more than a quarter-century. The indications of I-131 MIBG therapy include treatment-resistant neuroblastoma (NB), unresectable or metastatic pheochromocytoma (PC) and paraganglioma (PG), unresectable or metastatic carcinoid tumors, and unresectable or metastatic medullary thyroid cancer (MTC). I-131 MIBG therapy is one of the considerable effective treatments in patients with advanced NB, PC, and PG. On the other hand, I-131 MIBG therapy is an alternative method after more effective novel therapies are used such as radiolabeled somatostatin analogs and tyrosine kinase inhibitors in patients with advanced carcinoid tumors and MTC. No-carrier-aided (NCA) I-131 MIBG has more favorable potential compared to the conventional I-131 MIBG. Astatine-211-labeled meta-astatobenzylguanidine (At-211 MABG) has massive potential in patients with neuroendocrine tumors. Further studies about the therapeutic protocols of I-131 MIBG including NCA I-131 MIBG in the clinical setting and At-211 MABG in both the preclinical and clinical settings are needed.
https://ift.tt/2JO2UTY
An unusual cause of thunderclap headache after eating the hottest pepper in the world - "The Carolina Reaper"
Satish Kumar Boddhula<br />Apr 9, 2018; 2018:bcr-2017-224085-bcr-2017-224085<br />Images in...
https://ift.tt/2HO7rcA
Patient safety in external beam radiotherapy, results of the ACCIRAD project: Recommendations for radiotherapy institutions and national authorities on assessing risks and analysing adverse error-events and near misses
The ACCIRAD project, commissioned by the European Commission (EC) to develop guidelines for risk analysis of accidental and unintended exposures in external beam radiotherapy (EBRT), was completed in the year 2014. In 2015, the "General guidelines on risk management in external beam radiotherapy" were published as EC report Radiation Protection (RP)-181. The present document is the third and final report of the findings from the ACCIRAD project. The main aim of this paper is to describe the key features of the risk management process and to provide general guidelines for radiotherapy departments and national authorities on risk assessment and analysis of adverse error-events and near misses.
https://ift.tt/2jpvOyA
SIOPE – Brain tumor group consensus guideline on craniospinal target volume delineation for high-precision radiotherapy
To develop a consensus guideline for craniospinal target volume (TV) delineation in children and young adults participating in SIOPE studies in the era of high-precision radiotherapy.
https://ift.tt/2FCvHbs
Plan optimization for mediastinal radiotherapy: Estimation of coronary arteries motion with ECG-gated cardiac imaging and creation of compensatory expansion margins
Inadvertent heart and coronary arteries (CA) irradiation may increase the risk of coronary artery disease (CAD) in patients receiving thoracic irradiation. To date, the entity of cardiac-related CA displacement and the possible margins to be used for planning organs at risk volume (PRV) have been poorly described. Aim of this study was to quantify CA displacement and to estimate PRV through the use of ECG-gated computed tomography (CT) scans.
https://ift.tt/2Kwtulr
Issue Information ‐ Ed Board
Molecular Carcinogenesis, Volume 57, Issue 6, Page 685-685, June 2018.
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Issue Information ‐ Ed Board
Molecular Carcinogenesis, Volume 57, Issue 6, Page 685-685, June 2018.
https://ift.tt/2JP3voh
Study Shows Experimental Screening Test Can Detect Endometrial and Ovarian Cancers
Scientists have struggled to come up with a simple test to detect endometrial and ovarian cancers early, when they are most likely to respond to treatment. Can a liquid biopsy test called PapSEEK change that?
https://ift.tt/2JJuotR
Study Shows Experimental Screening Test Can Detect Endometrial and Ovarian Cancers
Scientists have struggled to come up with a simple test to detect endometrial and ovarian cancers early, when they are most likely to respond to treatment. Can a liquid biopsy test called PapSEEK change that?
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Current utilization and procedural practices in pediatric whole-body MRI
Abstract
Background
Whole-body magnetic resonance imaging (MRI) is an evolving and increasingly powerful imaging tool with a variety of applications in the pediatric patient population. Variability exists among radiology practices in how this MRI tool is used and how it performed.
Objective
Our objective was to gain an improved understanding of technical and utilization practices in pediatric whole-body MRI across North America by exploring indications for exam performance, determining referral patterns, and assessing technical protocols and procedures.
Materials and methods
A 19-question survey was generated in Survey Monkey and distributed in 2016 to the Society for Pediatric Radiology membership. The survey asked questions that included practice type, imaging modality preferences for diseases commonly evaluated with whole-body MRI, MRI field strength and sequence selection, and billing practices.
Results
Data were obtained from 62 unique responses to the survey, representing 471 physicians. The majority (93%) practice in an academic institution or private practice with academic affiliation and most practices have utilized whole-body MRI for less than 6 years. Whole-body MRI is performed in pediatric patients 0 to 18 years of age, and was the preferred imaging modality for diagnosis/staging/follow-up in neurofibromatosis, type 1 (75%), chronic recurrent multifocal osteomyelitis (CRMO) (74%), cancer predisposition syndromes (75%), vasculopathies (50%) and disseminated/multifocal infection (49%). The most commonly utilized sequences are coronal short tau inversion recovery (STIR) (90%), coronal T1 with or without fat saturation (65%), and axial diffusion-weighted imaging (DWI) (48%). No preference was shown for either 1.5-T or 3-T systems. Wide variability was seen in preference for billing code utilization, though the majority use chest/abdomen/pelvis (57%) or unlisted MRI (37%) codes.
Conclusion
Radiology practitioners – represented by the Society for Pediatric Radiology pediatric radiologists – are using whole-body MRI in the imaging care of pediatric patients for a variety of indications. Survey results reveal some variability in exam utilization and technical performance practices among those pediatric radiologists who perform whole-body MRI.
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Optimization of magnetization-prepared rapid gradient echo (MP-RAGE) sequence for neonatal brain MRI
Abstract
Background
Sequence optimization in neonates might improve detection sensitivity of abnormalities for a variety of conditions. However this has been historically challenging because tissue properties such as the longitudinal relaxation time and proton density differ significantly between neonates and adults.
Objective
To optimize the magnetization-prepared rapid gradient echo (MP-RAGE) sequence to enhance both signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) efficiencies.
Materials and methods
We optimized neonatal MP-RAGE sequence through (1) reducing receive bandwidth to decrease noise, (2) shortening acquisition train length (acquisition number per repetition time or total number of read-out radiofrequency rephrasing pulses) using slice partial Fourier acquisition and (3) simulating the solution of Bloch's equation under optimal receive bandwidth and acquisition train length. Using the optimized sequence parameters, we scanned 12 healthy full-term infants within 2 weeks of birth and four preterm infants at 40 weeks' corrected age.
Results
Compared with a previously published neonatal protocol, we were able to reduce the total scan time by reduce the total scan time by 60% and increase the average SNR efficiency by 160% (P<0.001) and the average CNR efficiency by 26% (P=0.029).
Conclusion
Our in vivo neonatal brain imaging experiments confirmed that both SNR and CNR efficiencies significantly increased with our proposed protocol. Our proposed optimization methodology could be readily extended to other populations (e.g., older children, adults), as well as different organ systems, field strengths and MR sequences.
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Current utilization and procedural practices in pediatric whole-body MRI
Abstract
Background
Whole-body magnetic resonance imaging (MRI) is an evolving and increasingly powerful imaging tool with a variety of applications in the pediatric patient population. Variability exists among radiology practices in how this MRI tool is used and how it performed.
Objective
Our objective was to gain an improved understanding of technical and utilization practices in pediatric whole-body MRI across North America by exploring indications for exam performance, determining referral patterns, and assessing technical protocols and procedures.
Materials and methods
A 19-question survey was generated in Survey Monkey and distributed in 2016 to the Society for Pediatric Radiology membership. The survey asked questions that included practice type, imaging modality preferences for diseases commonly evaluated with whole-body MRI, MRI field strength and sequence selection, and billing practices.
Results
Data were obtained from 62 unique responses to the survey, representing 471 physicians. The majority (93%) practice in an academic institution or private practice with academic affiliation and most practices have utilized whole-body MRI for less than 6 years. Whole-body MRI is performed in pediatric patients 0 to 18 years of age, and was the preferred imaging modality for diagnosis/staging/follow-up in neurofibromatosis, type 1 (75%), chronic recurrent multifocal osteomyelitis (CRMO) (74%), cancer predisposition syndromes (75%), vasculopathies (50%) and disseminated/multifocal infection (49%). The most commonly utilized sequences are coronal short tau inversion recovery (STIR) (90%), coronal T1 with or without fat saturation (65%), and axial diffusion-weighted imaging (DWI) (48%). No preference was shown for either 1.5-T or 3-T systems. Wide variability was seen in preference for billing code utilization, though the majority use chest/abdomen/pelvis (57%) or unlisted MRI (37%) codes.
Conclusion
Radiology practitioners – represented by the Society for Pediatric Radiology pediatric radiologists – are using whole-body MRI in the imaging care of pediatric patients for a variety of indications. Survey results reveal some variability in exam utilization and technical performance practices among those pediatric radiologists who perform whole-body MRI.
https://ift.tt/2rgCD90
Optimization of magnetization-prepared rapid gradient echo (MP-RAGE) sequence for neonatal brain MRI
Abstract
Background
Sequence optimization in neonates might improve detection sensitivity of abnormalities for a variety of conditions. However this has been historically challenging because tissue properties such as the longitudinal relaxation time and proton density differ significantly between neonates and adults.
Objective
To optimize the magnetization-prepared rapid gradient echo (MP-RAGE) sequence to enhance both signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) efficiencies.
Materials and methods
We optimized neonatal MP-RAGE sequence through (1) reducing receive bandwidth to decrease noise, (2) shortening acquisition train length (acquisition number per repetition time or total number of read-out radiofrequency rephrasing pulses) using slice partial Fourier acquisition and (3) simulating the solution of Bloch's equation under optimal receive bandwidth and acquisition train length. Using the optimized sequence parameters, we scanned 12 healthy full-term infants within 2 weeks of birth and four preterm infants at 40 weeks' corrected age.
Results
Compared with a previously published neonatal protocol, we were able to reduce the total scan time by reduce the total scan time by 60% and increase the average SNR efficiency by 160% (P<0.001) and the average CNR efficiency by 26% (P=0.029).
Conclusion
Our in vivo neonatal brain imaging experiments confirmed that both SNR and CNR efficiencies significantly increased with our proposed protocol. Our proposed optimization methodology could be readily extended to other populations (e.g., older children, adults), as well as different organ systems, field strengths and MR sequences.
https://ift.tt/2KxUUHJ
Prodigiosin stimulates endoplasmic reticulum stress and induces autophagic cell death in glioblastoma cells
Abstract
Prodigiosin, a secondary metabolite isolated from marine Vibrio sp., has antimicrobial and anticancer properties. This study investigated the cell death mechanism of prodigiosin in glioblastoma. Glioblastoma multiforme (GBM) is an aggressive primary cancer of the central nervous system. Despite treatment, or standard therapy, the median survival of glioblastoma patients is about 14.6 month. The results of the present study clearly showed that prodigiosin significantly reduced the cell viability and neurosphere formation ability of U87MG and GBM8401 human glioblastoma cell lines. Moreover, prodigiosin with fluorescence signals was detected in the endoplasmic reticulum and found to induce excessive levels of autophagy. These findings were confirmed by observation of LC3 puncta formation and acridine orange staining. Furthermore, prodigiosin caused cell death by activating the JNK pathway and decreasing the AKT/mTOR pathway in glioblastoma cells. Moreover, we found that the autophagy inhibitor 3-methyladenine reversed prodigiosin induced autophagic cell death. These findings of this study suggest that prodigiosin induces autophagic cell death and apoptosis in glioblastoma cells.
https://ift.tt/2FCOKCy
A phase 1 study of eribulin mesylate (E7389), a novel microtubule‐targeting chemotherapeutic agent, in children with refractory or recurrent solid tumors: A Children's Oncology Group Phase 1 Consortium study (ADVL1314)
Pediatric Blood &Cancer, EarlyView.
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Hepatoblastoma in patients with molecularly proven familial adenomatous polyposis: Clinical characteristics and rationale for surveillance screening
Pediatric Blood &Cancer, EarlyView.
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A phase 1 study of eribulin mesylate (E7389), a novel microtubule‐targeting chemotherapeutic agent, in children with refractory or recurrent solid tumors: A Children's Oncology Group Phase 1 Consortium study (ADVL1314)
Pediatric Blood &Cancer, EarlyView.
https://ift.tt/2rlYZaf
Hepatoblastoma in patients with molecularly proven familial adenomatous polyposis: Clinical characteristics and rationale for surveillance screening
Pediatric Blood &Cancer, EarlyView.
https://ift.tt/2JM4yVX
Causal null hypotheses of sustained treatment strategies: What can be tested with an instrumental variable?
Abstract
Sometimes instrumental variable methods are used to test whether a causal effect is null rather than to estimate the magnitude of a causal effect. However, when instrumental variable methods are applied to time-varying exposures, as in many Mendelian randomization studies, it is unclear what causal null hypothesis is tested. Here, we consider different versions of causal null hypotheses for time-varying exposures, show that the instrumental variable conditions alone are insufficient to test some of them, and describe additional assumptions that can be made to test a wider range of causal null hypotheses, including both sharp and average causal null hypotheses. Implications for interpretation and reporting of instrumental variable results are discussed.
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Expression of cytosolic malic enzyme (ME1) is associated with disease progression in human oral squamous cell carcinoma
Cancer Science, EarlyView.
https://ift.tt/2rbJyBh
Tumor necrosis factor‐α induces prostate cancer cell migration in lymphatic metastasis through CCR7 upregulation
Cancer Science, EarlyView.
https://ift.tt/2HNZkbM
Endoscopy screening effect on stage distributions of esophageal cancer: A cluster randomized cohort study in China
Cancer Science, EarlyView.
https://ift.tt/2jn57KM
MicroRNA‐708‐3p mediates metastasis and chemoresistance through inhibition of epithelial‐to‐mesenchymal transition in breast cancer
Cancer Science, EarlyView.
https://ift.tt/2HPLAx1
Early disease progression in patients with localized natural killer/T‐cell lymphoma treated with concurrent chemoradiotherapy
Cancer Science, EarlyView.
https://ift.tt/2joYFmB
Synthetic α‐mangostin dilaurate strongly suppresses wide‐spectrum organ metastasis in a mouse model of mammary cancer
Cancer Science, EarlyView.
https://ift.tt/2HObX6O
Induction of chemokine (C‐C motif) ligand 5 by Epstein–Barr virus infection enhances tumor angiogenesis in nasopharyngeal carcinoma
Cancer Science, EarlyView.
https://ift.tt/2joYMyx
Long non‐coding RNA‐CTD‐2108O9.1 represses breast cancer metastasis by influencing leukemia inhibitory factor receptor
Cancer Science, EarlyView.
https://ift.tt/2rgGzH3
Molecular genomic landscapes of hepatobiliary cancer
Cancer Science, EarlyView.
https://ift.tt/2rfaSOP
The PLGF/c‐MYC/miR‐19a axis promotes metastasis and stemness in gallbladder cancer
Cancer Science, EarlyView.
https://ift.tt/2rhBluo
Expression of cytosolic malic enzyme (ME1) is associated with disease progression in human oral squamous cell carcinoma
Cancer Science, EarlyView.
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Tumor necrosis factor‐α induces prostate cancer cell migration in lymphatic metastasis through CCR7 upregulation
Cancer Science, EarlyView.
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Endoscopy screening effect on stage distributions of esophageal cancer: A cluster randomized cohort study in China
Cancer Science, EarlyView.
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MicroRNA‐708‐3p mediates metastasis and chemoresistance through inhibition of epithelial‐to‐mesenchymal transition in breast cancer
Cancer Science, EarlyView.
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Early disease progression in patients with localized natural killer/T‐cell lymphoma treated with concurrent chemoradiotherapy
Cancer Science, EarlyView.
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Synthetic α‐mangostin dilaurate strongly suppresses wide‐spectrum organ metastasis in a mouse model of mammary cancer
Cancer Science, EarlyView.
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Induction of chemokine (C‐C motif) ligand 5 by Epstein–Barr virus infection enhances tumor angiogenesis in nasopharyngeal carcinoma
Cancer Science, EarlyView.
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Long non‐coding RNA‐CTD‐2108O9.1 represses breast cancer metastasis by influencing leukemia inhibitory factor receptor
Cancer Science, EarlyView.
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Molecular genomic landscapes of hepatobiliary cancer
Cancer Science, EarlyView.
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The PLGF/c‐MYC/miR‐19a axis promotes metastasis and stemness in gallbladder cancer
Cancer Science, EarlyView.
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Clinical trial cytology: Use of on‐site evaluation of small biopsy and FNA samples for clinical trials and biomarker research studies
Cancer Cytopathology, EarlyView.
https://ift.tt/2rineoy
Clinical trial cytology: Use of on‐site evaluation of small biopsy and FNA samples for clinical trials and biomarker research studies
Cancer Cytopathology, EarlyView.
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Causal null hypotheses of sustained treatment strategies: What can be tested with an instrumental variable?
Abstract
Sometimes instrumental variable methods are used to test whether a causal effect is null rather than to estimate the magnitude of a causal effect. However, when instrumental variable methods are applied to time-varying exposures, as in many Mendelian randomization studies, it is unclear what causal null hypothesis is tested. Here, we consider different versions of causal null hypotheses for time-varying exposures, show that the instrumental variable conditions alone are insufficient to test some of them, and describe additional assumptions that can be made to test a wider range of causal null hypotheses, including both sharp and average causal null hypotheses. Implications for interpretation and reporting of instrumental variable results are discussed.
https://ift.tt/2HJfS8H
Causal null hypotheses of sustained treatment strategies: What can be tested with an instrumental variable?
Abstract
Sometimes instrumental variable methods are used to test whether a causal effect is null rather than to estimate the magnitude of a causal effect. However, when instrumental variable methods are applied to time-varying exposures, as in many Mendelian randomization studies, it is unclear what causal null hypothesis is tested. Here, we consider different versions of causal null hypotheses for time-varying exposures, show that the instrumental variable conditions alone are insufficient to test some of them, and describe additional assumptions that can be made to test a wider range of causal null hypotheses, including both sharp and average causal null hypotheses. Implications for interpretation and reporting of instrumental variable results are discussed.
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Prediction of survival in patients affected by glioblastoma: histogram analysis of perfusion MRI
Abstract
Purpose
The identification of prognostic biomarkers plays a pivotal role in the management of glioblastoma. The aim of this study was to assess the role of magnetic resonance dynamic susceptibility contrast imaging (DSC-MRI) with histogram analysis in the prognostic evaluation of patients suffering from glioblastoma.
Materials and methods
Sixty-eight patients with newly diagnosed pathologically verified GBM were retrospectively evaluated. All patients underwent MRI investigations, including DSC-MRI, surgical procedure and received postoperative focal radiotherapy plus daily temozolomide (TMZ), followed by adjuvant TMZ therapy. Relative cerebral blood volume (rCBV) histograms were generated from a volume of interest covering the solid portions of the tumor and statistically evaluated for kurtosis, skewness, mean, median and maximum value of rCBV. To verify if histogram parameters could predict survival at 1 and 2 years, receiver operating characteristic (ROC) curves were obtained. Kaplan–Meier method was used to calculate patient's overall survival.
Results
rCBV kurtosis and rCBV skewness showed significant differences between subjects surviving > 1 and > 2 years, According to ROC analysis, the rCBV kurtosis showed the best statistic performance compared to the other parameters; respectively, values of 1 and 2.45 represented an optimised cut-off point to distinguish subjects surviving over 1 or 2 years. Kaplan–Meier curves showed a significant difference between subjects with rCBV kurtosis values higher or lower than 1 (respectively 1021 and 576 days; Log-rank test: p = 0.007), and between subjects with rCBV kurtosis values higher or lower than 2.45 (respectively 802 and 408 days; Log-rank test: p = 0.001).
Conclusion
The histogram analysis of perfusion MRI proved to be a valid method to predict survival in patients affected by glioblastoma.
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Prediction of survival in patients affected by glioblastoma: histogram analysis of perfusion MRI
Abstract
Purpose
The identification of prognostic biomarkers plays a pivotal role in the management of glioblastoma. The aim of this study was to assess the role of magnetic resonance dynamic susceptibility contrast imaging (DSC-MRI) with histogram analysis in the prognostic evaluation of patients suffering from glioblastoma.
Materials and methods
Sixty-eight patients with newly diagnosed pathologically verified GBM were retrospectively evaluated. All patients underwent MRI investigations, including DSC-MRI, surgical procedure and received postoperative focal radiotherapy plus daily temozolomide (TMZ), followed by adjuvant TMZ therapy. Relative cerebral blood volume (rCBV) histograms were generated from a volume of interest covering the solid portions of the tumor and statistically evaluated for kurtosis, skewness, mean, median and maximum value of rCBV. To verify if histogram parameters could predict survival at 1 and 2 years, receiver operating characteristic (ROC) curves were obtained. Kaplan–Meier method was used to calculate patient's overall survival.
Results
rCBV kurtosis and rCBV skewness showed significant differences between subjects surviving > 1 and > 2 years, According to ROC analysis, the rCBV kurtosis showed the best statistic performance compared to the other parameters; respectively, values of 1 and 2.45 represented an optimised cut-off point to distinguish subjects surviving over 1 or 2 years. Kaplan–Meier curves showed a significant difference between subjects with rCBV kurtosis values higher or lower than 1 (respectively 1021 and 576 days; Log-rank test: p = 0.007), and between subjects with rCBV kurtosis values higher or lower than 2.45 (respectively 802 and 408 days; Log-rank test: p = 0.001).
Conclusion
The histogram analysis of perfusion MRI proved to be a valid method to predict survival in patients affected by glioblastoma.
https://ift.tt/2HHNsvU
Esophageal pulmonary fistula – a rare complication of radiation therapy: a case report
Esophageal respiratory fistulae are abnormal communications between the esophagus and the respiratory system. They are either congenital or acquired. Most acquired esophageal respiratory fistulae are of the es...
https://ift.tt/2w4P6lM
The influence of mutational status and biological characteristics of acute myeloid leukemia on xenotransplantation outcomes in NOD SCID gamma mice
Abstract
Purpose
This study aimed at analyzing the association of gene mutations and other acute myeloid leukemia (AML) characteristics with engraftment outcomes in immunodeficient mice and to select the engraftment outcomes that best reflect patient survival.
Methods
Mutations in 19 genes as well as leukemia- and patient-related characteristics were analyzed for a group of 47 de novo AML samples with respect to three engraftment outcomes: engraftment ability, engraftment intensity (percentage of hCD45+ cells) and engraftment latency. Leukemia-related characteristics were additionally analyzed in an extended group of 68 samples that included the 47 de novo samples, and additional 21 samples from refractory and relapsed cases. Engraftment outcomes were compared with overall and event-free survival of the patients.
Results
For the 47 de novo samples, no single mutation influenced engraftment, whereas the NPM1mut /DNMT3Amut co-mutation was associated with higher engraftment ability. NPM1mut /FLT3-ITDneg had lower engraftment intensity. Among leukemia-related characteristics, a complex karyotype was associated with higher engraftment intensity. Among patient-related characteristics, higher cytogenetic risk was associated with higher engraftment intensity, and failure to achieve clinical remission was associated with shorter engraftment latency. In the extended group of 68 samples, white blood count was associated with higher engraftment ability, and the presence of a complex karyotype was associated with higher engraftment intensity. Association with patient overall survival was seen only for engraftment intensity.
Conclusions
The engraftment of AML was influenced by mutation-interactions and other AML characteristics, rather than by single mutated genes, and engraftment intensity best reflected clinical penetrance of AML.
https://ift.tt/2rbwagv
Author Correction: Mitochondrial DNA variants in colorectal carcinogenesis: Drivers or passengers?
The affiliation detail for the corresponding author, Edoardo Errichiello, was published incorrectly. The correct detail read as follows:
https://ift.tt/2rgtvBd
Life quality of patients who underwent breast reconstruction after prophylactic mastectomy: systematic review
Abstract
Background
Prophylactic mastectomy is used to reduce the incidence of breast cancer in women with genetic predisposition and family history of breast cancer, and the rate of application is increased nowadays. Chronic pain, body image, and sexuality may negatively affect quality of life, while patients generally have increased quality of life and satisfaction after prophylactic mastectomy. The aim of this study is the evaluation of the results of the studies about quality of life of patients who underwent breast reconstruction after prophylactic mastectomy.
Methods
For the 1996–2016 literature, we searched the databases of Scopus, Science Direct, PubMed, EBSCO, Cochrane, Medline Complete, Ovid, Springer Link, Google Academic, Taylor & Francis, PsychINFO databases. For the gray literature, National Thesis Center and ULAKBIM databases were searched. Seven studies complying with the criteria were included in the review.
Results
Seven studies included in this study aimed to investigate the effect of prophylactic mastectomy on breast pain, numbness, sexuality and quality of life. When the studies were reviewed, we were found that the majority of the patients were satisfied with the results of the procedure, although the body image perception and pain/ movement/ perception and sexual problems were experienced after the breast surgery.
Conclusions
While overall satisfaction with cosmetic results was high, most women were not satisfied with the softness of the reconstructed breasts, and had problems with breast hardness, numbness and sex. Therefore, it is very important to inform the patients about the complications that may develop after the operation, while there is not enough data about the importance of informing the patients before the operation.
https://ift.tt/2jpiNFf
The influence of mutational status and biological characteristics of acute myeloid leukemia on xenotransplantation outcomes in NOD SCID gamma mice
Abstract
Purpose
This study aimed at analyzing the association of gene mutations and other acute myeloid leukemia (AML) characteristics with engraftment outcomes in immunodeficient mice and to select the engraftment outcomes that best reflect patient survival.
Methods
Mutations in 19 genes as well as leukemia- and patient-related characteristics were analyzed for a group of 47 de novo AML samples with respect to three engraftment outcomes: engraftment ability, engraftment intensity (percentage of hCD45+ cells) and engraftment latency. Leukemia-related characteristics were additionally analyzed in an extended group of 68 samples that included the 47 de novo samples, and additional 21 samples from refractory and relapsed cases. Engraftment outcomes were compared with overall and event-free survival of the patients.
Results
For the 47 de novo samples, no single mutation influenced engraftment, whereas the NPM1mut /DNMT3Amut co-mutation was associated with higher engraftment ability. NPM1mut /FLT3-ITDneg had lower engraftment intensity. Among leukemia-related characteristics, a complex karyotype was associated with higher engraftment intensity. Among patient-related characteristics, higher cytogenetic risk was associated with higher engraftment intensity, and failure to achieve clinical remission was associated with shorter engraftment latency. In the extended group of 68 samples, white blood count was associated with higher engraftment ability, and the presence of a complex karyotype was associated with higher engraftment intensity. Association with patient overall survival was seen only for engraftment intensity.
Conclusions
The engraftment of AML was influenced by mutation-interactions and other AML characteristics, rather than by single mutated genes, and engraftment intensity best reflected clinical penetrance of AML.
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Author Correction: Mitochondrial DNA variants in colorectal carcinogenesis: Drivers or passengers?
The affiliation detail for the corresponding author, Edoardo Errichiello, was published incorrectly. The correct detail read as follows:
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Complete Posterior Sagittal Anorectal Mobilization (PSAM): A new surgical approach for pediatric pelvic‐perineal tumor resections
Journal of Surgical Oncology, EarlyView.
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Review of diagnostic, prognostic, and predictive biomarkers in melanoma
Abstract
Melanoma is an aggressive cutaneous malignancy with rapidly rising incidence. Diagnosis of controversial melanocytic lesions, correct prognostication of patients, selection of appropriate adjuvant and systemic therapies, and prediction of response to a given therapy remain very real challenges. Despite these challenges, multiple high throughput, nucleic-acid based biomarkers have been developed that can be assayed from histologic tissue specimens. FISH, CGH, Decision-Dx, and other multi-marker assays have been combined to improve overall predictability. This review discusses some of the most promising nucleic acid based assays that can be obtained from tissue specimens to assist with diagnosis, prognostication, and prediction of treatment response.
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Genetics of metastasis: melanoma and other cancers
Abstract
Melanoma is a malignant neoplasm of melanocytes that accounts for the majority of skin cancer deaths despite comprising less than 5% of all cutaneous malignancies. Its incidence has increased faster than that of any other cancer over the past half-century and the annual costs of treatment in the United States alone have risen rapidly. Although the majority of primary melanomas are cured with local excision, metastatic melanoma historically carries a grim prognosis, with a median survival of 9 months and a long-term survival rate of 10%. Given the urgent need to develop treatment strategies for metastatic melanoma and the explosion of genetic technologies over the past 20 years, there has been extensive research into the genetic alterations that cause melanocytes to become malignant. More recently, efforts have focused on the genetic changes that drive melanoma metastasis. This review aims to summarize the current knowledge of the genetics of primary cutaneous and ocular melanoma, the genetic changes associated with metastasis in melanoma and other cancer types, and non-genetic factors that may contribute to metastasis.
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Cystatin C takes part in melanoma-microglia cross-talk: possible implications for brain metastasis
Abstract
The development of melanoma brain metastasis is largely dependent on mutual interactions between the melanoma cells and cells in the brain microenvironment. Here, we report that the extracellular cysteine protease inhibitor cystatin C (CysC) is involved in these interactions. Microglia-derived factors upregulated CysC secretion by melanoma. Similarly, melanoma-derived factors upregulated CysC secretion by microglia. Whereas CysC enhanced melanoma cell migration through a layer of brain endothelial cells, it inhibited the migration of microglia cells toward melanoma cells. CysC was also found to promote the formation of melanoma three-dimensional structures in matrigel. IHC analysis revealed increased expression levels of CysC in the brain of immune-deficient mice bearing xenografted human melanoma brain metastasis compared to the brain of control mice. Based on these in vitro and in vivo experiments we hypothesize that CysC promotes melanoma brain metastasis. Increased expression levels of CysC were detected in the regenerating brain of mice after stroke. Post-stroke brain with melanoma brain metastasis showed an even stronger expression of CysC. The in vitro induction of stroke-like conditions in brain microenvironmental cells increased the levels of CysC in the secretome of microglia cells, but not in the secretome of brain endothelial cells. The similarities between melanoma brain metastasis and stroke with respect to CysC expression by and secretion from microglia cells suggest that CysC may be involved in shared pathways between brain metastasis and post-stroke regeneration. This manifests the tendency of tumor cells to highjack physiological molecular pathways in their progression.
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Review of diagnostic, prognostic, and predictive biomarkers in melanoma
Abstract
Melanoma is an aggressive cutaneous malignancy with rapidly rising incidence. Diagnosis of controversial melanocytic lesions, correct prognostication of patients, selection of appropriate adjuvant and systemic therapies, and prediction of response to a given therapy remain very real challenges. Despite these challenges, multiple high throughput, nucleic-acid based biomarkers have been developed that can be assayed from histologic tissue specimens. FISH, CGH, Decision-Dx, and other multi-marker assays have been combined to improve overall predictability. This review discusses some of the most promising nucleic acid based assays that can be obtained from tissue specimens to assist with diagnosis, prognostication, and prediction of treatment response.
https://ift.tt/2HHI2AY
Genetics of metastasis: melanoma and other cancers
Abstract
Melanoma is a malignant neoplasm of melanocytes that accounts for the majority of skin cancer deaths despite comprising less than 5% of all cutaneous malignancies. Its incidence has increased faster than that of any other cancer over the past half-century and the annual costs of treatment in the United States alone have risen rapidly. Although the majority of primary melanomas are cured with local excision, metastatic melanoma historically carries a grim prognosis, with a median survival of 9 months and a long-term survival rate of 10%. Given the urgent need to develop treatment strategies for metastatic melanoma and the explosion of genetic technologies over the past 20 years, there has been extensive research into the genetic alterations that cause melanocytes to become malignant. More recently, efforts have focused on the genetic changes that drive melanoma metastasis. This review aims to summarize the current knowledge of the genetics of primary cutaneous and ocular melanoma, the genetic changes associated with metastasis in melanoma and other cancer types, and non-genetic factors that may contribute to metastasis.
https://ift.tt/2rhq6Ca
Cystatin C takes part in melanoma-microglia cross-talk: possible implications for brain metastasis
Abstract
The development of melanoma brain metastasis is largely dependent on mutual interactions between the melanoma cells and cells in the brain microenvironment. Here, we report that the extracellular cysteine protease inhibitor cystatin C (CysC) is involved in these interactions. Microglia-derived factors upregulated CysC secretion by melanoma. Similarly, melanoma-derived factors upregulated CysC secretion by microglia. Whereas CysC enhanced melanoma cell migration through a layer of brain endothelial cells, it inhibited the migration of microglia cells toward melanoma cells. CysC was also found to promote the formation of melanoma three-dimensional structures in matrigel. IHC analysis revealed increased expression levels of CysC in the brain of immune-deficient mice bearing xenografted human melanoma brain metastasis compared to the brain of control mice. Based on these in vitro and in vivo experiments we hypothesize that CysC promotes melanoma brain metastasis. Increased expression levels of CysC were detected in the regenerating brain of mice after stroke. Post-stroke brain with melanoma brain metastasis showed an even stronger expression of CysC. The in vitro induction of stroke-like conditions in brain microenvironmental cells increased the levels of CysC in the secretome of microglia cells, but not in the secretome of brain endothelial cells. The similarities between melanoma brain metastasis and stroke with respect to CysC expression by and secretion from microglia cells suggest that CysC may be involved in shared pathways between brain metastasis and post-stroke regeneration. This manifests the tendency of tumor cells to highjack physiological molecular pathways in their progression.
https://ift.tt/2KuvElH
Combined neutrophil/platelet/lymphocyte/differentiation score predicts chemosensitivity in advanced gastric cancer
Abstract
Background
Gastric cancer is common in developing regions, and we hope to find out an economical but practical prognostic indicator. It was reported that pre-treatment peripheral neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), as well as differentiation status, were associated with cancer progression. Hence, we introduced a novel combined Neutrophil/platelet/lymphocyte/differentiation Score (cNPLDS) to improve the prediction value of palliative chemotherapeutic response in advanced gastric cancer.
Methods
According to statistical sample size estimation, 136 primary diagnosed unresectable advanced ptaients were included for a retrospective study. The follow-up end-point was progression free survival (PFS) during the first-line palliative chemotherapy. Differentiation stratified patients into well, medium and poor groups by score 1 to 3, while patients with neither elevated NLR and PLR, only one elevated, or both elevated were of the combined NLR-PLR score (cNPS) 1 to 3, respectively. The cNPLDS was calculated by multiplying the tumor differentiation score and cNPS.
Results
Determined by the receiver operating characteristic (ROC) curve, the optimal cut-off points for NLR and PLR were 3.04 and 223. Through univariate analysis and survival analysis, poor differentiation, high NLR, high PLR, high cNPS, and high cNPLDS respectively indicated inferior PFS during the first-line palliative chemotherapy. Patients were furhter classified into low to high risk groups by cNPLDS. Groups of elevated NLR, PLR, cNPS, and cNPLDS showed lower disease control rate. Compared to other parameters, cNPLDS significantly improved the accuracy in predicing the first-progression.
Conclusions
This study indicates that the novel parameter cNPLDS is superior to NLR or PLR alone, or even cNPS, in predicting the first-line chemosensitivity in advanced gastric cancer.
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Combined neutrophil/platelet/lymphocyte/differentiation score predicts chemosensitivity in advanced gastric cancer
Abstract
Background
Gastric cancer is common in developing regions, and we hope to find out an economical but practical prognostic indicator. It was reported that pre-treatment peripheral neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), as well as differentiation status, were associated with cancer progression. Hence, we introduced a novel combined Neutrophil/platelet/lymphocyte/differentiation Score (cNPLDS) to improve the prediction value of palliative chemotherapeutic response in advanced gastric cancer.
Methods
According to statistical sample size estimation, 136 primary diagnosed unresectable advanced ptaients were included for a retrospective study. The follow-up end-point was progression free survival (PFS) during the first-line palliative chemotherapy. Differentiation stratified patients into well, medium and poor groups by score 1 to 3, while patients with neither elevated NLR and PLR, only one elevated, or both elevated were of the combined NLR-PLR score (cNPS) 1 to 3, respectively. The cNPLDS was calculated by multiplying the tumor differentiation score and cNPS.
Results
Determined by the receiver operating characteristic (ROC) curve, the optimal cut-off points for NLR and PLR were 3.04 and 223. Through univariate analysis and survival analysis, poor differentiation, high NLR, high PLR, high cNPS, and high cNPLDS respectively indicated inferior PFS during the first-line palliative chemotherapy. Patients were furhter classified into low to high risk groups by cNPLDS. Groups of elevated NLR, PLR, cNPS, and cNPLDS showed lower disease control rate. Compared to other parameters, cNPLDS significantly improved the accuracy in predicing the first-progression.
Conclusions
This study indicates that the novel parameter cNPLDS is superior to NLR or PLR alone, or even cNPS, in predicting the first-line chemosensitivity in advanced gastric cancer.
https://ift.tt/2JMR0JW
Exposure–response relationship for ramucirumab from the randomized, double-blind, phase 3 REVEL trial (docetaxel versus docetaxel plus ramucirumab) in second-line treatment of metastatic non-small cell lung cancer
Abstract
Purpose
Ramucirumab plus docetaxel improved survival in REVEL, a randomized phase 3 trial for patients with Stage IV non-small cell lung cancer after standard platinum-based chemotherapy. This exploratory analysis evaluated the exposure–response relationship of ramucirumab from REVEL.
Methods
Patients received ramucirumab (10 mg/kg) or placebo plus docetaxel (75 mg/m2) every 3 weeks. Pharmacokinetic samples were collected. A population pharmacokinetic analysis predicted ramucirumab minimum concentration after first-dose administration (Cmin,1) and average concentration at steady state (Cave,ss). Predicted Cmin,1 and Cave,ss were used to evaluate the relationship between ramucirumab exposure and efficacy and safety, respectively. Exposure–efficacy was assessed by Kaplan–Meier and Cox regression analyses; exposure–safety was assessed by ordered categorical analyses.
Results
Analyses included 376 patients treated with ramucirumab plus docetaxel and 366 patients treated with placebo plus docetaxel (364 for safety population). After adjusting for corresponding prognostic factors, the association between overall survival (OS) and Cmin,1 was statistically significant (p = 0.0110), although progression-free survival (PFS) showed a marginal association (p = 0.0515). At high ramucirumab exposures (Cmin,1), greater improvements (smaller hazard ratios) were seen for OS and PFS when stratified by Cmin,1 exposure quartiles. A statistically significant correlation was observed between ramucirumab Cave,ss and grade ≥ 3 febrile neutropenia and hypertension.
Conclusions
An association was observed between ramucirumab exposure and efficacy. Higher ramucirumab exposure was associated with improved clinical outcomes and increased toxicity in this analysis. Two exposure–response prospective randomized trials are being conducted to address causation (NCT02443883 and NCT02514551), with encouraging preliminary results (Ajani et al. in Ann Oncol 28:abstr 698P, 2017).
https://ift.tt/2HKdpuX
Exposure–response relationship for ramucirumab from the randomized, double-blind, phase 3 REVEL trial (docetaxel versus docetaxel plus ramucirumab) in second-line treatment of metastatic non-small cell lung cancer
Abstract
Purpose
Ramucirumab plus docetaxel improved survival in REVEL, a randomized phase 3 trial for patients with Stage IV non-small cell lung cancer after standard platinum-based chemotherapy. This exploratory analysis evaluated the exposure–response relationship of ramucirumab from REVEL.
Methods
Patients received ramucirumab (10 mg/kg) or placebo plus docetaxel (75 mg/m2) every 3 weeks. Pharmacokinetic samples were collected. A population pharmacokinetic analysis predicted ramucirumab minimum concentration after first-dose administration (Cmin,1) and average concentration at steady state (Cave,ss). Predicted Cmin,1 and Cave,ss were used to evaluate the relationship between ramucirumab exposure and efficacy and safety, respectively. Exposure–efficacy was assessed by Kaplan–Meier and Cox regression analyses; exposure–safety was assessed by ordered categorical analyses.
Results
Analyses included 376 patients treated with ramucirumab plus docetaxel and 366 patients treated with placebo plus docetaxel (364 for safety population). After adjusting for corresponding prognostic factors, the association between overall survival (OS) and Cmin,1 was statistically significant (p = 0.0110), although progression-free survival (PFS) showed a marginal association (p = 0.0515). At high ramucirumab exposures (Cmin,1), greater improvements (smaller hazard ratios) were seen for OS and PFS when stratified by Cmin,1 exposure quartiles. A statistically significant correlation was observed between ramucirumab Cave,ss and grade ≥ 3 febrile neutropenia and hypertension.
Conclusions
An association was observed between ramucirumab exposure and efficacy. Higher ramucirumab exposure was associated with improved clinical outcomes and increased toxicity in this analysis. Two exposure–response prospective randomized trials are being conducted to address causation (NCT02443883 and NCT02514551), with encouraging preliminary results (Ajani et al. in Ann Oncol 28:abstr 698P, 2017).
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Exploring cancer survivors' views of health behaviour change: “Where do you start, where do you stop with everything?”
Psycho-Oncology, EarlyView.
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Point: Moral distress can indicate inappropriate care at end‐of‐Life
Psycho-Oncology, EarlyView.
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Focusing on cancer patients' intentions to use psychooncological support: A longitudinal, mixed‐methods study
Psycho-Oncology, EarlyView.
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The interactive effect of advanced cancer patient and caregiver prognostic understanding on patients' completion of Do Not Resuscitate orders
Psycho-Oncology, EarlyView.
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Life stress and symptoms of anxiety and depression in women after cancer: The mediating effect of stress appraisal and coping
Psycho-Oncology, EarlyView.
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Socioeconomic status and quality of life among Chinese American breast cancer survivors: The mediating roles of social support and social constraints
Psycho-Oncology, EarlyView.
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A single‐session intervention (the Mini‐AFTERc) for fear of cancer recurrence: A feasibility study
Psycho-Oncology, EarlyView.
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Exploring cancer survivors' views of health behaviour change: “Where do you start, where do you stop with everything?”
Psycho-Oncology, EarlyView.
https://ift.tt/2wf5xML
Point: Moral distress can indicate inappropriate care at end‐of‐Life
Psycho-Oncology, EarlyView.
https://ift.tt/2HJ0oln
Focusing on cancer patients' intentions to use psychooncological support: A longitudinal, mixed‐methods study
Psycho-Oncology, EarlyView.
https://ift.tt/2wbSJ9U
The interactive effect of advanced cancer patient and caregiver prognostic understanding on patients' completion of Do Not Resuscitate orders
Psycho-Oncology, EarlyView.
https://ift.tt/2I97f6R
Life stress and symptoms of anxiety and depression in women after cancer: The mediating effect of stress appraisal and coping
Psycho-Oncology, EarlyView.
https://ift.tt/2w5VOrH
Socioeconomic status and quality of life among Chinese American breast cancer survivors: The mediating roles of social support and social constraints
Psycho-Oncology, EarlyView.
https://ift.tt/2I420p0
A single‐session intervention (the Mini‐AFTERc) for fear of cancer recurrence: A feasibility study
Psycho-Oncology, EarlyView.
https://ift.tt/2w9aZk2
PGE2/EP4 antagonism enhances tumor chemosensitivity by inducing extracellular vesicle‐mediated clearance of cancer stem cells
International Journal of Cancer, EarlyView.
https://ift.tt/2jqfxJE
Impact of iASPP on chemoresistance through PLK1 and autophagy in ovarian clear cell carcinoma
International Journal of Cancer, EarlyView.
https://ift.tt/2jmlFm0
Proton pump inhibitor use and cancer mortality
International Journal of Cancer, EarlyView.
https://ift.tt/2FA0Z2T
Prenatal diethylstilbestrol exposure and mammographic density
International Journal of Cancer, EarlyView.
https://ift.tt/2Ks6WSS
Cervical cancer risk in HPV‐positive women after a negative FAM19A4/mir124‐2 methylation test: A post hoc analysis in the POBASCAM trial with 14 year follow‐up
International Journal of Cancer, EarlyView.
https://ift.tt/2FAtTje
PGE2/EP4 antagonism enhances tumor chemosensitivity by inducing extracellular vesicle‐mediated clearance of cancer stem cells
International Journal of Cancer, EarlyView.
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Impact of iASPP on chemoresistance through PLK1 and autophagy in ovarian clear cell carcinoma
International Journal of Cancer, EarlyView.
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Proton pump inhibitor use and cancer mortality
International Journal of Cancer, EarlyView.
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Prenatal diethylstilbestrol exposure and mammographic density
International Journal of Cancer, EarlyView.
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Cervical cancer risk in HPV‐positive women after a negative FAM19A4/mir124‐2 methylation test: A post hoc analysis in the POBASCAM trial with 14 year follow‐up
International Journal of Cancer, EarlyView.
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Genomic status of MET potentiates sensitivity to MET and MEK inhibition in NF1-related malignant peripheral nerve sheath tumors
Malignant Peripheral Nerve Sheath Tumors (MPNSTs) are highly resistant sarcomas that occur in up to 13% of individuals with Neurofibromatosis Type 1 (NF1). Genomic analysis of longitudinally collected tumor samples in a case of MPNST disease progression revealed early hemizygous microdeletions in NF1 and TP53, with progressive amplifications of MET, HGF, and EGFR. To examine the role of MET in MPNST progression, we developed mice with enhanced MET expression and Nf1 ablation (Nf1fl/KO;lox-stop-loxMETtg/+;Plp-creERTtg/+; referred to as NF1 MET). NF1-MET mice express a robust MPNST phenotype in the absence of additional mutations. A comparison of NF1-MET MPNSTs with MPNSTs derived from Nf1KO/+;p53R172H;Plp-creERTtg/+ (NF1-P53) and Nf1KO/+;Plp-creERTtg/+ (NF1) mice revealed unique Met, Ras, and PI3K signaling patterns. NF1-MET MPNSTs were uniformly sensitive to the highly selective MET inhibitor, capmatinib, whereas a heterogeneous response to MET inhibition was observed in NF1-P53 and NF1 MPNSTs. Combination therapy of capmatinib and the MEK inhibitor trametinib resulted in reduced response variability, enhanced suppression of tumor growth, and suppressed RAS/ERK and PI3K/AKT signaling. These results highlight the influence of concurrent genomic alterations on RAS effector signaling and therapy response to tyrosine kinase inhibitors. Moreover, these findings expand our current understanding of the role of MET signaling in MPNST progression and identify a potential therapeutic niche for NF1-related MPNSTs.
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Complete Posterior Sagittal Anorectal Mobilization (PSAM): A new surgical approach for pediatric pelvic‐perineal tumor resections
Journal of Surgical Oncology, EarlyView.
https://ift.tt/2HKdL0A
Genomic status of MET potentiates sensitivity to MET and MEK inhibition in NF1-related malignant peripheral nerve sheath tumors
Malignant Peripheral Nerve Sheath Tumors (MPNSTs) are highly resistant sarcomas that occur in up to 13% of individuals with Neurofibromatosis Type 1 (NF1). Genomic analysis of longitudinally collected tumor samples in a case of MPNST disease progression revealed early hemizygous microdeletions in NF1 and TP53, with progressive amplifications of MET, HGF, and EGFR. To examine the role of MET in MPNST progression, we developed mice with enhanced MET expression and Nf1 ablation (Nf1fl/KO;lox-stop-loxMETtg/+;Plp-creERTtg/+; referred to as NF1 MET). NF1-MET mice express a robust MPNST phenotype in the absence of additional mutations. A comparison of NF1-MET MPNSTs with MPNSTs derived from Nf1KO/+;p53R172H;Plp-creERTtg/+ (NF1-P53) and Nf1KO/+;Plp-creERTtg/+ (NF1) mice revealed unique Met, Ras, and PI3K signaling patterns. NF1-MET MPNSTs were uniformly sensitive to the highly selective MET inhibitor, capmatinib, whereas a heterogeneous response to MET inhibition was observed in NF1-P53 and NF1 MPNSTs. Combination therapy of capmatinib and the MEK inhibitor trametinib resulted in reduced response variability, enhanced suppression of tumor growth, and suppressed RAS/ERK and PI3K/AKT signaling. These results highlight the influence of concurrent genomic alterations on RAS effector signaling and therapy response to tyrosine kinase inhibitors. Moreover, these findings expand our current understanding of the role of MET signaling in MPNST progression and identify a potential therapeutic niche for NF1-related MPNSTs.
https://ift.tt/2JKLmIa
Status and future directions in the management of pancreatic cancer: potential impact of nanotechnology
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is typically diagnosed at a late stage, has limited treatments, and patients have poor survival rates. It currently ranks as the seventh leading cause of cancer deaths globally and has increasing rates of diagnosis. Improved PDAC treatment requires the development of innovative, effective, and economical therapeutic drugs. The late stage diagnosis limits options for surgical resection, and traditional PDAC chemotherapeutics correlate with increased organ and hematologic toxicity. In addition, PDAC tumor tissue is dense and highly resistant to many traditional chemotherapeutic applications, making the disease difficult to treat and impeding options for palliative care. New developments in nanotechnology may offer innovative options for targeted PDAC therapeutic drug delivery. Nanotechnology can be implemented using multimodality methods that offer increased opportunities for earlier diagnosis, precision enhanced imaging, targeted long-term tumor surveillance, and controlled drug delivery, as well as improved palliative care and patient comfort. Nanoscale delivery methods have demonstrated the capacity to infiltrate the dense, fibrous tumor tissue associated with PDAC, increasing delivery and effectiveness of chemotherapeutic agents and reducing toxicity through the loading of multiple drug therapies on a single nano delivery vehicle. This review presents an overview of nanoscale drug delivery systems and multimodality carriers at the forefront of new PDAC treatments.
https://ift.tt/2jlBGZt
Status and future directions in the management of pancreatic cancer: potential impact of nanotechnology
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is typically diagnosed at a late stage, has limited treatments, and patients have poor survival rates. It currently ranks as the seventh leading cause of cancer deaths globally and has increasing rates of diagnosis. Improved PDAC treatment requires the development of innovative, effective, and economical therapeutic drugs. The late stage diagnosis limits options for surgical resection, and traditional PDAC chemotherapeutics correlate with increased organ and hematologic toxicity. In addition, PDAC tumor tissue is dense and highly resistant to many traditional chemotherapeutic applications, making the disease difficult to treat and impeding options for palliative care. New developments in nanotechnology may offer innovative options for targeted PDAC therapeutic drug delivery. Nanotechnology can be implemented using multimodality methods that offer increased opportunities for earlier diagnosis, precision enhanced imaging, targeted long-term tumor surveillance, and controlled drug delivery, as well as improved palliative care and patient comfort. Nanoscale delivery methods have demonstrated the capacity to infiltrate the dense, fibrous tumor tissue associated with PDAC, increasing delivery and effectiveness of chemotherapeutic agents and reducing toxicity through the loading of multiple drug therapies on a single nano delivery vehicle. This review presents an overview of nanoscale drug delivery systems and multimodality carriers at the forefront of new PDAC treatments.
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Radiotherapy volume delineation using 18F-FDG-PET/CT modifies gross node volume in patients with oesophageal cancer
Abstract
Purpose
Evidence supporting the use of 18F-FDG-PET/CT in the segmentation process of oesophageal cancer for radiotherapy planning is limited. Our aim was to compare the volumes and tumour lengths defined by fused PET/CT vs. CT simulation.
Materials and methods
Twenty-nine patients were analyzed. All patients underwent a single PET/CT simulation scan. Two separate GTVs were defined: one based on CT data alone and another based on fused PET/CT data. Volume sizes for both data sets were compared and the spatial overlap was assessed by the Dice similarity coefficient (DSC).
Results
The gross tumour volume (GTVtumour) and maximum tumour diameter were greater by PET/CT, and length of primary tumour was greater by CT, but differences were not statistically significant. However, the gross node volume (GTVnode) was significantly greater by PET/CT. The DSC analysis showed excellent agreement for GTVtumour, 0.72, but was very low for GTVnode, 0.25.
Conclusions
Our study shows that the volume definition by PET/CT and CT data differs. CT simulation, without taking into account PET/CT information, might leave cancer-involved nodes out of the radiotherapy-delineated volumes.
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A survey of perceptions, attitudes, knowledge and practices of medical oncologists about cancer pain management in Spain
Abstract
Purpose
To monitor oncologists' perspective on cancer pain management.
Methods
An anonymized survey was conducted in two waves. First, over a convenience sample of oncologists known to be particularly concerned with the management of pain. Second, using a random sample of oncologists.
Results
In total, 73 and 82 oncologists participated in the first and second wave, respectively. Many oncologists reported to have good knowledge of analgesic drugs (95.9%), the mechanism of action of opioids (79.5%), and good skills to manage opioid-related bowel dysfunction (76.7%). Appropriate adjustment of background medication to manage breakthrough pain was reported by 95.5% of oncologists. Additionally, 87.7% (68.3% in the second wave, p = 0.035) of oncologists reported suitable opioid titration practices, and 90.4% reported to use co-adjuvant medications for neuropathic pain confidently. On the other hand, just 9.6% of oncologists participated in multidisciplinary pain management teams, and merely 30.3 and 27.1% reported to routinely collaborate with the Pain Clinics or involve other staff, respectively. Only 26.4% of the oncologists of the second wave gave priority to pain pathophysiology to decide therapies, and up to 75.6% reported difficulties in treating neuropathic pain. Significantly less oncologists of the second wave (82.9 vs. 94.5%, p = 0.001) used opioid rotation routinely.
Conclusions
Unlike in previous surveys, medical oncologists reported in general good knowledge and few perceived limitations and barriers for pain management. However, multi-disciplinary management and collaboration with other specialists are still uncommon. Oncologists' commitment to optimize pain management seems important to improve and maintain good practices.
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Focal dose escalation for prostate cancer using 68Ga-HBED-CC PSMA PET/CT and MRI: a planning study based on histology reference
Focal radiation therapy has gained of interest in treatment of patients with primary prostate cancer (PCa). The question of how to define the intraprostatic boost volume is still open. Previous studies showed ...
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Preexisting radiological interstitial lung abnormalities are a risk factor for severe radiation pneumonitis in patients with small-cell lung cancer after thoracic radiation therapy
Previous studies reported that patients with preexisting radiological interstitial lung abnormalities (ILAs) were more susceptible to developing radiation pneumonitis (RP) after thoracic radiation therapy (TRT...
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