Chylothorax is a disease that has various causes such as neoplasm, infection, post-surgery trauma, congenital, and venous thrombosis. In approximately 15% of cases of chylothorax, the exact cause is unknown. W...
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Cancer Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Κυριακή 9 Απριλίου 2017
Delayed right chylothorax after left blunt chest trauma: a case report
Remarkable response to fluorouracil, leucovorin, oxaliplatin, and irinotecan therapy in urothelial cancer of the renal pelvis: a case report
No standard chemotherapy regimen for advanced urothelial cancer has been established, except for cisplatin-based regimens. We report the case of a patient with double primary cancer, urothelial carcinoma of th...
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Retraction: ‘Dose-dependent dual effect of HTLV-1 tax oncoprotein on p53-dependent nucleotide excision repair in human T-cells’ by Yana Schavinsky-Khrapunsky, Esther Priel and Mordechai Aboud
The above article, published online on 4 October 2007 in Wiley Online Library (wileyonlinelibrary.com), and in Volume 122, pp. 305-316, has been retracted by agreement between the journal Editor in Chief, Professor Peter Lichter, and John Wiley & Sons Ltd. The retraction has been agreed as the bands in Figs 1, 2, 5 and 6 appear to have been manipulated.
Reference
Schavinsky-Khrapunsky, Y., Priel, E. and Aboud, M. (2008), Dose-dependent dual effect of HTLV-1 tax oncoprotein on p53-dependent nucleotide excision repair in human T-cells. Int. J. Cancer, 122: 305–316. doi:10.1002/ijc.23091
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Retraction: ‘Dose-dependent dual effect of HTLV-1 tax oncoprotein on p53-dependent nucleotide excision repair in human T-cells’ by Yana Schavinsky-Khrapunsky, Esther Priel and Mordechai Aboud
The above article, published online on 4 October 2007 in Wiley Online Library (wileyonlinelibrary.com), and in Volume 122, pp. 305-316, has been retracted by agreement between the journal Editor in Chief, Professor Peter Lichter, and John Wiley & Sons Ltd. The retraction has been agreed as the bands in Figs 1, 2, 5 and 6 appear to have been manipulated.
Reference
Schavinsky-Khrapunsky, Y., Priel, E. and Aboud, M. (2008), Dose-dependent dual effect of HTLV-1 tax oncoprotein on p53-dependent nucleotide excision repair in human T-cells. Int. J. Cancer, 122: 305–316. doi:10.1002/ijc.23091
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Characterization of the effect of a new commercial transmission detector on radiotherapy beams
Publication date: Available online 9 April 2017
Source:Practical Radiation Oncology
Author(s): Joey P. Cheung, Angelica Perez-Andujar, Olivier Morin
PurposeTo evaluate the influence of a new commercial transmission detector on radiotherapy beams.Methods and MaterialsA transmission detector designed for online treatment monitoring was characterized on a TrueBeam STx linear accelerator with 6MV, 6FFF, 10MV, and 10FFF beams. Measurements of PDDs, inplane and crossplane off-axis profiles at different depths, transmission factors, and skin dose were acquired with 3x3cm2, 5x5cm2, 10x10cm2, 20x20cm2, and 40x40cm2 field sizes at 100 cm and 80 cm SSD. A CC04 chamber was used for all profile and transmission factor measurements. Skin dose was assessed at 100 cm, 90 cm, and 80 cm SSD using a variety of detectors (Roos and Markus parallel-plate chambers, and OSLD). Skin dose was also assessed for various patient sample plans with OSLDs.ResultsThe PDDs showed small differences between the unperturbed and perturbed beams for 100 cm SSD (≤4 mm dmax difference, <1.2% average profile difference) for all field sizes. At 80 cm SSD, the differences were larger (≤8 mm dmax difference, <3% average profile difference). The differences were larger for the flattened beams and larger field sizes. The off-axis profiles showed similar trends. Field penumbras looked similar with and without the transmission detector. Comparisons in the profile central 80% showed a maximum average (maximum) profile difference between all field sizes of 1.0% (2.6%) and 1.4% (6.3%) for 100 cm and 80 cm SSD, respectively. The average measured skin dose increase at 100 cm (80 cm) SSD for 10x10cm2 field size was <4% (<35%) for all energies. For 40x40cm2 field size, this increased to <31% (≤63%). For the sample patient plans, the average skin dose difference was 0.53% (range−6.6% to 10.4%).ConclusionsThe transmission detector has minimal effect on clinically relevant radiotherapy beams for IMRT and VMAT (field sizes 10x10cm2 and less). For larger field sizes, some perturbations are observable which would need to be assessed for clinical impact.
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Clinical outcomes of helical conformal versus non-conformal palliative radiotherapy for axial skeletal metastases
Publication date: Available online 9 April 2017
Source:Practical Radiation Oncology
Author(s): Kara D. Romano, Daniel M. Trifiletti, Kristine Bauer-Nilsen, Nolan A. Wages, William T. Watkins, Paul W. Read, Timothy N. Showalter
PurposePalliative radiotherapy (RT) for bone metastases has traditionally been delivered with conventional, non-conformal RT (NCRT). Conformal RT (CRT) is potentially more complex and expensive than NCRT, but may reduce normal tissue dose and subsequently toxicity. In this retrospective analysis, we compared CRT versus NCRT to investigate the association between conformality and toxicity.Methods/MaterialsA retrospective analysis of patients receiving palliative RT for axial skeletal bone metastases from 2012-2014 was conducted. Patient and treatment characteristics were obtained including dosimetric variables, acute toxicity, and subjective pain during treatment and in the acute post-treatment period (≤ 60 days after completion). Statistical analyses included t-tests, Chi-square tests, and multivariate logistic regression (MVA).Results179 patients and 254 bone metastases were identified (142 CRT, 112 NCRT). The CRT and NCRT groups were well matched for baseline characteristics (number of fractions, field size, treatment sites, and concurrent chemotherapy). In MVA models, technique (CRT vs. NCRT) was not associated with development of acute toxicity. Regarding toxicity, ECOG performance status and total dose were significantly associated with a higher rate of acute toxicity during radiotherapy (OR 0.649 and 1.129 and p = 0.027 and 0.044, respectively); and only a higher number of vertebral bodies in the treatment field was significantly associated with acute toxicity post-treatment (OR 1.219, p = 0.028). CRT was associated with improvement in bone pain during and post treatment (p = 0.049 and 0.045, respectively).ConclusionOur results demonstrate no difference in acute toxicity following palliative radiotherapy with CRT compared to NCRT for painful bone metastases; however, treatment volume did predict for increased toxicity. Larger studies may further elucidate the value of CRT including the impact of dose escalation for bone metastases and differences in patient reported outcomes between RT techniques.SummaryConformal radiotherapy (CRT) may provide improved sparing of normal tissues compared to non-conformal radiotherapy (NCRT), and thus reduce toxicity for patients receiving palliative radiotherapy for bone metastases. In this retrospective analysis, we observed no difference in acute toxicity between treatment techniques (CRT versus NCRT); however, larger treatment volumes were associated with increased toxicity. CRT was associated with improvement in bone pain control.
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Characterization of the effect of a new commercial transmission detector on radiotherapy beams
Publication date: Available online 9 April 2017
Source:Practical Radiation Oncology
Author(s): Joey P. Cheung, Angelica Perez-Andujar, Olivier Morin
PurposeTo evaluate the influence of a new commercial transmission detector on radiotherapy beams.Methods and MaterialsA transmission detector designed for online treatment monitoring was characterized on a TrueBeam STx linear accelerator with 6MV, 6FFF, 10MV, and 10FFF beams. Measurements of PDDs, inplane and crossplane off-axis profiles at different depths, transmission factors, and skin dose were acquired with 3x3cm2, 5x5cm2, 10x10cm2, 20x20cm2, and 40x40cm2 field sizes at 100 cm and 80 cm SSD. A CC04 chamber was used for all profile and transmission factor measurements. Skin dose was assessed at 100 cm, 90 cm, and 80 cm SSD using a variety of detectors (Roos and Markus parallel-plate chambers, and OSLD). Skin dose was also assessed for various patient sample plans with OSLDs.ResultsThe PDDs showed small differences between the unperturbed and perturbed beams for 100 cm SSD (≤4 mm dmax difference, <1.2% average profile difference) for all field sizes. At 80 cm SSD, the differences were larger (≤8 mm dmax difference, <3% average profile difference). The differences were larger for the flattened beams and larger field sizes. The off-axis profiles showed similar trends. Field penumbras looked similar with and without the transmission detector. Comparisons in the profile central 80% showed a maximum average (maximum) profile difference between all field sizes of 1.0% (2.6%) and 1.4% (6.3%) for 100 cm and 80 cm SSD, respectively. The average measured skin dose increase at 100 cm (80 cm) SSD for 10x10cm2 field size was <4% (<35%) for all energies. For 40x40cm2 field size, this increased to <31% (≤63%). For the sample patient plans, the average skin dose difference was 0.53% (range−6.6% to 10.4%).ConclusionsThe transmission detector has minimal effect on clinically relevant radiotherapy beams for IMRT and VMAT (field sizes 10x10cm2 and less). For larger field sizes, some perturbations are observable which would need to be assessed for clinical impact.
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Clinical outcomes of helical conformal versus non-conformal palliative radiotherapy for axial skeletal metastases
Publication date: Available online 9 April 2017
Source:Practical Radiation Oncology
Author(s): Kara D. Romano, Daniel M. Trifiletti, Kristine Bauer-Nilsen, Nolan A. Wages, William T. Watkins, Paul W. Read, Timothy N. Showalter
PurposePalliative radiotherapy (RT) for bone metastases has traditionally been delivered with conventional, non-conformal RT (NCRT). Conformal RT (CRT) is potentially more complex and expensive than NCRT, but may reduce normal tissue dose and subsequently toxicity. In this retrospective analysis, we compared CRT versus NCRT to investigate the association between conformality and toxicity.Methods/MaterialsA retrospective analysis of patients receiving palliative RT for axial skeletal bone metastases from 2012-2014 was conducted. Patient and treatment characteristics were obtained including dosimetric variables, acute toxicity, and subjective pain during treatment and in the acute post-treatment period (≤ 60 days after completion). Statistical analyses included t-tests, Chi-square tests, and multivariate logistic regression (MVA).Results179 patients and 254 bone metastases were identified (142 CRT, 112 NCRT). The CRT and NCRT groups were well matched for baseline characteristics (number of fractions, field size, treatment sites, and concurrent chemotherapy). In MVA models, technique (CRT vs. NCRT) was not associated with development of acute toxicity. Regarding toxicity, ECOG performance status and total dose were significantly associated with a higher rate of acute toxicity during radiotherapy (OR 0.649 and 1.129 and p = 0.027 and 0.044, respectively); and only a higher number of vertebral bodies in the treatment field was significantly associated with acute toxicity post-treatment (OR 1.219, p = 0.028). CRT was associated with improvement in bone pain during and post treatment (p = 0.049 and 0.045, respectively).ConclusionOur results demonstrate no difference in acute toxicity following palliative radiotherapy with CRT compared to NCRT for painful bone metastases; however, treatment volume did predict for increased toxicity. Larger studies may further elucidate the value of CRT including the impact of dose escalation for bone metastases and differences in patient reported outcomes between RT techniques.SummaryConformal radiotherapy (CRT) may provide improved sparing of normal tissues compared to non-conformal radiotherapy (NCRT), and thus reduce toxicity for patients receiving palliative radiotherapy for bone metastases. In this retrospective analysis, we observed no difference in acute toxicity between treatment techniques (CRT versus NCRT); however, larger treatment volumes were associated with increased toxicity. CRT was associated with improvement in bone pain control.
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Half knowledge is worse than ignorance....... Imperfect understanding is often more dangerous than ignorance
Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480
Reduced rate of human papillomavirus infection and genetic overtransmission of TP53 72C polymorphic variant lower cervical cancer incidence
BACKGROUND
Cervical cancer is a predominantly human papillomavirus (HPV)-driven disease worldwide. However, its incidence is unexplainably low in western Asia, including Saudi Arabia. Using this paradigm, we investigated the role of HPV infection rate and host genetic predisposition in TP53 G72C single nucleotide polymorphism (SNP) presumed to affect cancer incidence.
METHODS
Patients treated between 1990 and 2012 were reviewed, and a series of 232 invasive cervical cancer cases were studied and compared with 313 matched controls without cancer. SNP was genotyped by way of direct sequencing. HPV linear array analysis was used to detect and genotype HPV in tumor samples.
RESULTS
The incidence of cervical cancer revealed bimodal peaks at 42.5 years, with a slighter rebound at 60.8 years. Among all cases, 77% were HPV-positive and 16 HPV genotypes were detected—mostly genotypes 16 (75%) and 18 (9%)—with no difference by age, histology, or geographical region. Although the TP53 G72C genotype was not associated with overall cervical cancer risk, it was significantly associated with HPV positivity (odds ratio, 0.57; 95% confidence interval, 0.36-0.90; P = .016). Furthermore, the variant C allele was significantly overtransmitted in the population (P < .0003).
CONCLUSION
Cervical cancer incidence displays bimodal curve peaking at a young age with secondary rebound at older age. The combination of relative low HPV infection and variant TP53 72C allele overtransmission provide a plausible explanation for the low incidence of cervical cancer in our population. Therefore, HPV screening and host SNP genotyping may provide more relevant biomarkers to gauge the risk of developing cervical cancer. Cancer 2017. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.
http://ift.tt/2ogS0Os
Reduced rate of human papillomavirus infection and genetic overtransmission of TP53 72C polymorphic variant lower cervical cancer incidence
BACKGROUND
Cervical cancer is a predominantly human papillomavirus (HPV)-driven disease worldwide. However, its incidence is unexplainably low in western Asia, including Saudi Arabia. Using this paradigm, we investigated the role of HPV infection rate and host genetic predisposition in TP53 G72C single nucleotide polymorphism (SNP) presumed to affect cancer incidence.
METHODS
Patients treated between 1990 and 2012 were reviewed, and a series of 232 invasive cervical cancer cases were studied and compared with 313 matched controls without cancer. SNP was genotyped by way of direct sequencing. HPV linear array analysis was used to detect and genotype HPV in tumor samples.
RESULTS
The incidence of cervical cancer revealed bimodal peaks at 42.5 years, with a slighter rebound at 60.8 years. Among all cases, 77% were HPV-positive and 16 HPV genotypes were detected—mostly genotypes 16 (75%) and 18 (9%)—with no difference by age, histology, or geographical region. Although the TP53 G72C genotype was not associated with overall cervical cancer risk, it was significantly associated with HPV positivity (odds ratio, 0.57; 95% confidence interval, 0.36-0.90; P = .016). Furthermore, the variant C allele was significantly overtransmitted in the population (P < .0003).
CONCLUSION
Cervical cancer incidence displays bimodal curve peaking at a young age with secondary rebound at older age. The combination of relative low HPV infection and variant TP53 72C allele overtransmission provide a plausible explanation for the low incidence of cervical cancer in our population. Therefore, HPV screening and host SNP genotyping may provide more relevant biomarkers to gauge the risk of developing cervical cancer. Cancer 2017. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.
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Squamous cell carcinoma arising from lupus vulgaris with a >60-year history
Abstract
We report the case of a 71-year-old Japanese man with squamous cell carcinoma arising from lupus vulgaris on the face, >60 years after the appearance of the lupus vulgaris. The red plaque on the patient's face had been diagnosed as a hemangioma or rosacea at several hospitals, although he had had lung tuberculosis at the age of 4 and his father died from lung tuberculosis at 38 years of age. Although lupus vulgaris was the most frequent clinical form of true skin tuberculosis until the 1960s, it has become rare since then. Malignant tumors are known to occur in individuals with lupus vulgaris, with a reported rate of 0.5–10.5%. In light of Japan's "graying society," tuberculosis is still an important disorder, and clinicians must remain aware of cutaneous tuberculosis.
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First report of stereotactic body radiotherapy for large-volume spinal tumors
Abstract
Stereotactic body radiotherapy (SBRT) for spinal metastases is very effective for pain relief and local tumor control. However, high-level evidence is limited to lesions in a single vertebra or in 2 contiguous vertebrae. To clarify the toxicities, we report herein the results of treatment for 4 patients who received SBRT to large-volume spinal tumors. The lesions comprised bone metastasis from renal cancer, local recurrence of rectal cancer invading the spine, osteosarcoma, and giant cell tumor of bone in 1 case each. Tumor volumes ranged from 738 to 1,766 ml. Doses ranging from 24 Gy in 2 fraction to 35 Gy in 5 fractions were delivered. The median follow-up was 24 months (range 4–35 months). Pain reduction was achieved in all patients in 4 weeks after SBRT. The outcomes were partial response in 1 patient, stable disease in 2, and tumor progression in 1. One patient showed grade 3 acute radiation dermatitis 4 weeks after SBRT, and another patient showed grade 3 late radiation dermatitis.
http://ift.tt/2nYrUxi
Squamous cell carcinoma arising from lupus vulgaris with a >60-year history
Abstract
We report the case of a 71-year-old Japanese man with squamous cell carcinoma arising from lupus vulgaris on the face, >60 years after the appearance of the lupus vulgaris. The red plaque on the patient's face had been diagnosed as a hemangioma or rosacea at several hospitals, although he had had lung tuberculosis at the age of 4 and his father died from lung tuberculosis at 38 years of age. Although lupus vulgaris was the most frequent clinical form of true skin tuberculosis until the 1960s, it has become rare since then. Malignant tumors are known to occur in individuals with lupus vulgaris, with a reported rate of 0.5–10.5%. In light of Japan's "graying society," tuberculosis is still an important disorder, and clinicians must remain aware of cutaneous tuberculosis.
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First report of stereotactic body radiotherapy for large-volume spinal tumors
Abstract
Stereotactic body radiotherapy (SBRT) for spinal metastases is very effective for pain relief and local tumor control. However, high-level evidence is limited to lesions in a single vertebra or in 2 contiguous vertebrae. To clarify the toxicities, we report herein the results of treatment for 4 patients who received SBRT to large-volume spinal tumors. The lesions comprised bone metastasis from renal cancer, local recurrence of rectal cancer invading the spine, osteosarcoma, and giant cell tumor of bone in 1 case each. Tumor volumes ranged from 738 to 1,766 ml. Doses ranging from 24 Gy in 2 fraction to 35 Gy in 5 fractions were delivered. The median follow-up was 24 months (range 4–35 months). Pain reduction was achieved in all patients in 4 weeks after SBRT. The outcomes were partial response in 1 patient, stable disease in 2, and tumor progression in 1. One patient showed grade 3 acute radiation dermatitis 4 weeks after SBRT, and another patient showed grade 3 late radiation dermatitis.
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Mitochondrial DNA variants in colorectal carcinogenesis: Drivers or passengers?
Abstract
Introduction
Mitochondrial DNA alterations have widely been reported in many age-related degenerative diseases and tumors, including colorectal cancer. In the past few years, the discovery of inter-genomic crosstalk between nucleus and mitochondria has reinforced the role of mitochondrial DNA variants in perturbing this essential signaling pathway and thus indirectly targeting nuclear genes involved in tumorigenic and invasive phenotype.
Findings
Mitochondrial dysfunction is currently considered a crucial hallmark of carcinogenesis as well as a promising target for anticancer therapy. Mitochondrial DNA alterations include point mutations, deletions, inversions, and copy number variations, but numerous studies investigating their pathogenic role in cancer have provided inconsistent evidence. Furthermore, the biological impact of mitochondrial DNA variants may vary tremendously, depending on the proportion of mutant DNA molecules carried by the neoplastic cells (heteroplasmy).
Conclusions
In this review, we discuss the role of different type of mitochondrial DNA alterations in colorectal carcinogenesis and, in particular, we revisit the issue of whether they may be considered as causative driver or simply genuine passenger events. The advent of high-throughput techniques as well as the development of genetic and pharmaceutical interventions for the treatment of mitochondrial dysfunction in colorectal cancer are also explored.
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Mitochondrial DNA variants in colorectal carcinogenesis: Drivers or passengers?
Abstract
Introduction
Mitochondrial DNA alterations have widely been reported in many age-related degenerative diseases and tumors, including colorectal cancer. In the past few years, the discovery of inter-genomic crosstalk between nucleus and mitochondria has reinforced the role of mitochondrial DNA variants in perturbing this essential signaling pathway and thus indirectly targeting nuclear genes involved in tumorigenic and invasive phenotype.
Findings
Mitochondrial dysfunction is currently considered a crucial hallmark of carcinogenesis as well as a promising target for anticancer therapy. Mitochondrial DNA alterations include point mutations, deletions, inversions, and copy number variations, but numerous studies investigating their pathogenic role in cancer have provided inconsistent evidence. Furthermore, the biological impact of mitochondrial DNA variants may vary tremendously, depending on the proportion of mutant DNA molecules carried by the neoplastic cells (heteroplasmy).
Conclusions
In this review, we discuss the role of different type of mitochondrial DNA alterations in colorectal carcinogenesis and, in particular, we revisit the issue of whether they may be considered as causative driver or simply genuine passenger events. The advent of high-throughput techniques as well as the development of genetic and pharmaceutical interventions for the treatment of mitochondrial dysfunction in colorectal cancer are also explored.
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Squamous cell carcinoma arising from lupus vulgaris with a >60-year history
Abstract
We report the case of a 71-year-old Japanese man with squamous cell carcinoma arising from lupus vulgaris on the face, >60 years after the appearance of the lupus vulgaris. The red plaque on the patient's face had been diagnosed as a hemangioma or rosacea at several hospitals, although he had had lung tuberculosis at the age of 4 and his father died from lung tuberculosis at 38 years of age. Although lupus vulgaris was the most frequent clinical form of true skin tuberculosis until the 1960s, it has become rare since then. Malignant tumors are known to occur in individuals with lupus vulgaris, with a reported rate of 0.5–10.5%. In light of Japan's "graying society," tuberculosis is still an important disorder, and clinicians must remain aware of cutaneous tuberculosis.
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First report of stereotactic body radiotherapy for large-volume spinal tumors
Abstract
Stereotactic body radiotherapy (SBRT) for spinal metastases is very effective for pain relief and local tumor control. However, high-level evidence is limited to lesions in a single vertebra or in 2 contiguous vertebrae. To clarify the toxicities, we report herein the results of treatment for 4 patients who received SBRT to large-volume spinal tumors. The lesions comprised bone metastasis from renal cancer, local recurrence of rectal cancer invading the spine, osteosarcoma, and giant cell tumor of bone in 1 case each. Tumor volumes ranged from 738 to 1,766 ml. Doses ranging from 24 Gy in 2 fraction to 35 Gy in 5 fractions were delivered. The median follow-up was 24 months (range 4–35 months). Pain reduction was achieved in all patients in 4 weeks after SBRT. The outcomes were partial response in 1 patient, stable disease in 2, and tumor progression in 1. One patient showed grade 3 acute radiation dermatitis 4 weeks after SBRT, and another patient showed grade 3 late radiation dermatitis.
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Tumor-specific circulating angiogenic progenitors in breast and renal cell cancer: What prospects?
Source:European Journal of Cancer
Author(s): Caroline Bailleux, Fabrice André, Suzette Delaloge
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Real-world treatment patterns in advanced pancreatic neuroendocrine tumors in the era of targeted therapy: perspectives from an academic tertiary center and community oncology practices
Abstract
Pancreatic neuroendocrine tumors (pNETs) are rare, slow-growing cancers. Optimal treatment of advanced pNETs is unclear. The aim of this study was to examine treatment patterns and preferences among an academic tertiary medical center and community-based oncology practices. Retrospective chart review was performed for patients with newly diagnosed locally advanced, metastatic, or unresectable pNET diagnosed between January 2010 and December 2013 at an academic tertiary cancer center [University of California, San Francisco (UCSF)] or a large network of community oncology practices [Altos Solutions' OncoEMR database (ALTOS)]. Fifty-four eligible patients (N UCSF = 23; N ALTOS = 31) were identified. Median time to treatment initiation was 1.1 months; median follow-up time was 22.9 months. UCSF patients underwent more lines of therapy than ALTOS patients despite similar follow-up times. UCSF tended toward more invasive treatment than ALTOS. The median time to treatment discontinuation was statistically significantly shorter for patients on chemotherapy than on targeted therapy in the combined UCSF and ALTOS groups (chemotherapy = 2.1 months vs. targeted = 18.6 months, p < 0.001). Treatment patterns and duration for newly diagnosed advanced pNETs vary widely both within and between different practice settings. Further studies are warranted to investigate the significant difference in duration of targeted therapy compared to chemotherapy.
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Real-world treatment patterns in advanced pancreatic neuroendocrine tumors in the era of targeted therapy: perspectives from an academic tertiary center and community oncology practices
Abstract
Pancreatic neuroendocrine tumors (pNETs) are rare, slow-growing cancers. Optimal treatment of advanced pNETs is unclear. The aim of this study was to examine treatment patterns and preferences among an academic tertiary medical center and community-based oncology practices. Retrospective chart review was performed for patients with newly diagnosed locally advanced, metastatic, or unresectable pNET diagnosed between January 2010 and December 2013 at an academic tertiary cancer center [University of California, San Francisco (UCSF)] or a large network of community oncology practices [Altos Solutions' OncoEMR database (ALTOS)]. Fifty-four eligible patients (N UCSF = 23; N ALTOS = 31) were identified. Median time to treatment initiation was 1.1 months; median follow-up time was 22.9 months. UCSF patients underwent more lines of therapy than ALTOS patients despite similar follow-up times. UCSF tended toward more invasive treatment than ALTOS. The median time to treatment discontinuation was statistically significantly shorter for patients on chemotherapy than on targeted therapy in the combined UCSF and ALTOS groups (chemotherapy = 2.1 months vs. targeted = 18.6 months, p < 0.001). Treatment patterns and duration for newly diagnosed advanced pNETs vary widely both within and between different practice settings. Further studies are warranted to investigate the significant difference in duration of targeted therapy compared to chemotherapy.
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Luteolin induces apoptosis by ROS/ER stress and mitochondrial dysfunction in gliomablastoma
Abstract
Objective
Luteolin, a common dietary flavonoid, induces apoptosis of many types of cancer cells. However, its role in glioblastoma and the potential mechanisms remain unknown. In this research, we studied the molecular mechanisms of the anti-cancer effect of luteolin in glioblastoma cancer cell lines.
Methods
Both U251MG and U87MG human glioblastoma cell lines were tested. Cell growth was assessed by the cell counting kit-8. Cell apoptosis was detected with flow cytometry and caspase-3 immunofluorescence staining. The protein levels of caspase-3/Bax/Bcl-2 and p-PERK/p-eIF2α/ATF4/CHOP/caspase-12 pathway were analyzed using western blots. Reactive oxygen species generation was measured with DCFH-DA staining using flow cytometry. Mitochondrial membrane potential was tested with JC-1 staining. Anti-cancer effect in vivo was measured using tumor xenograft mode in nude mice.
Results
Luteolin induced a lethal endoplasmic reticulum stress response and mitochondrial dysfunction in glioblastoma cells by increasing intracellular reactive oxygen species (ROS) levels. Luteolin induced expression of ER stress-associated proteins, including phosphorylation of PERK, eIF2α, ATF4, CHOP and cleaved-caspase 12. Inhibition of ROS production by anti-oxidant N-acetylcysteine could reverse luteolin-induced ER stress and mitochondrial pathways activation as well as apoptosis. What's more, we also showed the anticancer effect of luteolin in vivo.
Conclusions
Our results suggest that luteolin induces apoptosis through activating ER stress and mitochondrial dysfunction in glioblastoma cell lines and in vivo, which provides the anti-cancer candidate to treat glioblstoma.
http://ift.tt/2omGYYu
Luteolin induces apoptosis by ROS/ER stress and mitochondrial dysfunction in gliomablastoma
Abstract
Objective
Luteolin, a common dietary flavonoid, induces apoptosis of many types of cancer cells. However, its role in glioblastoma and the potential mechanisms remain unknown. In this research, we studied the molecular mechanisms of the anti-cancer effect of luteolin in glioblastoma cancer cell lines.
Methods
Both U251MG and U87MG human glioblastoma cell lines were tested. Cell growth was assessed by the cell counting kit-8. Cell apoptosis was detected with flow cytometry and caspase-3 immunofluorescence staining. The protein levels of caspase-3/Bax/Bcl-2 and p-PERK/p-eIF2α/ATF4/CHOP/caspase-12 pathway were analyzed using western blots. Reactive oxygen species generation was measured with DCFH-DA staining using flow cytometry. Mitochondrial membrane potential was tested with JC-1 staining. Anti-cancer effect in vivo was measured using tumor xenograft mode in nude mice.
Results
Luteolin induced a lethal endoplasmic reticulum stress response and mitochondrial dysfunction in glioblastoma cells by increasing intracellular reactive oxygen species (ROS) levels. Luteolin induced expression of ER stress-associated proteins, including phosphorylation of PERK, eIF2α, ATF4, CHOP and cleaved-caspase 12. Inhibition of ROS production by anti-oxidant N-acetylcysteine could reverse luteolin-induced ER stress and mitochondrial pathways activation as well as apoptosis. What's more, we also showed the anticancer effect of luteolin in vivo.
Conclusions
Our results suggest that luteolin induces apoptosis through activating ER stress and mitochondrial dysfunction in glioblastoma cell lines and in vivo, which provides the anti-cancer candidate to treat glioblstoma.
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Evaluating which dose-function metrics are most critical for functional-guided radiotherapy with CT ventilation imaging
Publication date: Available online 8 April 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Austin M. Faught, Tokihiro Yamamoto, Richard Castillo, Edward Castillo, Jingjing Zhang, Moyed Miften, Yevgeniy Vinogradskiy
Purpose4DCT-ventilation imaging is increasingly being used to calculate lung ventilation and implement functional-guided radiotherapy in clinical trials. There has been little exhaustive work evaluating which dose-function metrics should be used for treatment planning and plan evaluation. The purpose of our study was to evaluate which dose-function metrics best predict for radiation pneumonitis (RP).Methods and MaterialsSeventy lung cancer patients with 4DCT imaging and pneumonitis grading were used. Pre-treatment 4DCTs of each patient were used to calculate ventilation images. We evaluated 3 types of dose function metrics that combined that patient's 4DCT-ventilation image and treatment planning dose distribution: 1) structure-based approaches 2) image-based approaches using the dose-function histogram (DFH) and 3) non-linear weighting schemes. Log-likelihood methods were used to generate normal tissue complication probability (NTCP) models predicting grade 3+ pneumonitis for all dose-function schemes. The area under the curve (AUC) was used to assess the predictive power of the models. All techniques were compared to NTCP models based on traditional, total lung dose metrics.ResultsThe most predictive models were structure-based approaches that focused on the volume of functional lung receiving ≥20Gy (AUC=0.70). Probability of grade 3+ RP of 20% and 10% correspond to V20Gy to the functional sub-volumes of 26.8% and 9.3%, respectively. Imaging-based analysis with the DFH and non-linear weighted ventilation values yielded AUCs of 0.66 and 0.67, respectively, when evaluating the percentage of functionality receiving ≥20Gy. All dose-function metrics outperformed the traditional dose metrics (mean lung dose, AUC=0.55).ConclusionA full range of dose-function metrics and functional thresholds were examined. The calculated AUC values for the most predictive functional models occupied a narrow range (0.66-0.70) and all demonstrated notable improvements over AUC from traditional lung dose metrics (0.55). Identifying the combinations most predictive of grade 3+ RP provides valuable data to inform the functional-guided radiotherapy process.
Teaser
We performed a retrospective analysis of 70 lung cancer patients with 4DCT images to assess which dose-function metrics are most predictive of clinical radiation pneumonitis and should be used in functional-guided radiotherapy. Normal tissue complication probability models were developed based on standard lung dose metrics and four additional functional schemes that considered lung function as determined from 4DCT ventilation imaging. Results provide valuable data in the guidance of prospective clinical trials in functional-guided radiotherapy.http://ift.tt/2nuj8Lb
PERK signalling pathway mediates single prolonged stress-induced dysfunction of medial prefrontal cortex neurons
Abstract
Post-traumatic stress disorder (PTSD) is characterized with abnormal learning and memory. Impairments in learning and memory are closely associated with apoptosis in the medial prefrontal cortex (mPFC). We previously examined the endoplasmic reticulum (ER) stress was involved in the apoptosis in the mPFC of PTSD. The PERK pathway plays the important role in the ER stress-induced apoptosis. The aim of the present study was to explore the role of PERK pathway in neuronal apoptosis in the mPFC of rat models of PTSD. We used the single prolonged stress (SPS) to mimic PTSD in rats and studied the effects of the PERK pathway in mPFC. Learning and memory behavior were examined by Morris water maze and novel object recognition tests. Apoptosis in mPFC was detected by TUNEL staining. Our results showed decreased learning memory and increased apoptosis of mPFC neurons in rats exposed to SPS. SPS exposure upregulate mRNA expressions of PERK, p-PERK, eIF2α, p-eIF2α, nuclear ATF4 and C/EBP-homologous protein (CHOP) in mPFC neurons, but the protein levels of these molecules showed difference in magnitude and time course. GSK2606414 (an antagonist of PERK) treatment successfully reversed the above changes. These results suggested that the PERK pathway mediated SPS-induced neural apoptosis in the mPFC. These findings will be helpful in understanding mPFC-related pathogenesis of PTSD.
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Rivaroxaban as an effective alternative to warfarin in a patient with atrial fibrillation, thrombophilia, and left atrial appendage thrombus: a case report
Atrial fibrillation is the most common cardiac arrhythmia. It is responsible for up to 20% of all ischemic strokes. Rate control and anticoagulation are crucial for atrial fibrillation management and stroke pr...
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Background noise lowers the performance of anaesthesiology residents' clinical reasoning when measured by script concordance: A prospective randomised crossover volunteer study.
BACKGROUND: Noise, which is omnipresent in operating rooms and ICUs, may have a negative impact not only patients but also on the concentration of and communication between clinical staff. OBJECTIVE: The present study attempted to evaluate the impact of noise on the performance of anaesthesiology residents' clinical reasoning. Changes in clinical reasoning were measured by script concordance tests (SCTs). DESIGN: This was a prospective, randomised and crossover study. SETTING: Single centre at Rouen University Hospital in April 2014. POPULATION: All year 1 to 4 residents enrolled in the anaesthesiology training programme were included. INTERVENTION: Performance was assessed using a 56-item SCT. Two resident groups were formed, and each was exposed to both quiet and noisy atmospheres during SCT assessment. Group A did the first part of the assessment (28 SCT) in a quiet atmosphere and the second part (28 SCT) in a noisy atmosphere. Group B did the same in reverse order. MAIN OUTCOME MEASURES: The primary outcome of this study was residents' performance as measured by SCT, with and without noise (mean of 100 points 95% confidence interval). RESULTS: Forty-two residents were included. Residents' performance, measured by SCT, was weaker in a noisy environment than in a quiet environment [59.0 (56.0 to 62.0) vs 62.8 (60.8 to 64.9), P = 0.04]. This difference lessened as medical training advanced, as this difference in performance in noisy vs quiet environments was not observed in year 3 and 4 residents [62.9 (59.2 to 66.5) vs 64.0 (61.9 to 66.1), P = 0.60], whereas it was higher for year 1 and 2 residents [54.8 (50.6 to 59.1) vs 61.5 (57.9 to 65.1), P = 0.02]. CONCLUSION: Our study suggests that noise affects clinical reasoning of anaesthesiology residents especially junior residents when measured by SCT. This observation supports the hypothesis that noise should be prevented in operating rooms especially when junior residents are providing care. This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://ift.tt/OBJ4xP (C) 2017 European Society of Anaesthesiology
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