Future Oncology, Ahead of Print.
https://ift.tt/2qJw5Qc
Cancer Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Τετάρτη 18 Απριλίου 2018
CD47 is a novel potent immunotherapy target in human malignancies: current studies and future promises
CD47 is a novel potent immunotherapy target in human malignancies: current studies and future promises
Future Oncology, Ahead of Print.
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Review of targeted therapy in chronic lymphocytic leukemia: what a radiologist needs to know about CT interpretation
Abstract
The last 5 years have been marked by profound innovation in the targeted treatment of chronic lymphocytic leukemia (CLL) and indolent lymphomas. Using CLL as a case study, we present a timeline and overview of the current treatment landscape for the radiologist, including an overview of clinical and radiological features of CLL, discussion of the targeted agents themselves, and the role of imaging in response and toxicity assessment. The goal is to familiarize the radiologist with multiple Food and Drug Administration (FDA)-approved targeted agents used in this setting and associated adverse events which are commonly observed in this patient population.
https://ift.tt/2J5LYrE
Review of targeted therapy in chronic lymphocytic leukemia: what a radiologist needs to know about CT interpretation
Abstract
The last 5 years have been marked by profound innovation in the targeted treatment of chronic lymphocytic leukemia (CLL) and indolent lymphomas. Using CLL as a case study, we present a timeline and overview of the current treatment landscape for the radiologist, including an overview of clinical and radiological features of CLL, discussion of the targeted agents themselves, and the role of imaging in response and toxicity assessment. The goal is to familiarize the radiologist with multiple Food and Drug Administration (FDA)-approved targeted agents used in this setting and associated adverse events which are commonly observed in this patient population.
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Warming "Cold" Melanoma with TLR9 Agonists [News in Depth]
Responses seen in patients resistant to PD-1 blockade alone, when CMP-001 or SD-101 is added.
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Rho Kinase Inhibition by AT13148 Blocks Pancreatic Ductal Adenocarinoma Invasion and Tumor Growth
The high mortality of pancreatic cancer demands that new therapeutic avenues be developed. The orally available small molecule inhibitor AT13148 potently inhibits ROCK1 and ROCK2 kinases that regulate the actomyosin cytoskeleton. We previously reported that ROCK kinase expression increases with human and mouse pancreatic cancer progression and that conditional ROCK activation accelerates mortality in a genetically modified LSL-KrasG12D; LSL-p53R172H; Pdx1-Cre; (KPC) mouse pancreatic cancer model. In this study, we show that treatment of KPC mouse and human TKCC5 patient-derived pancreatic tumor cells with AT13148, as well as the ROCK selective inhibitors Y27632 and H1152, act comparably in blocking ROCK substrate phosphorylation. AT13148, Y27632, and H1152 induced morphological changes and reduced cellular contractile force generation, motility on pliable discontinuous substrates, and three-dimensional collagen matrix invasion. AT13148 treatment reduced subcutaneous tumor growth and blocked invasion of healthy pancreatic tissue by KPC tumor cells in vivo without affecting proliferation, suggesting a role for local tissue invasion as a contributor to primary tumor growth. These results suggest that AT13148 has anti-tumor properties that may be beneficial in combination therapies or in the adjuvant setting to reduce pancreatic cancer cell invasion and slow primary tumor growth. AT13148 might also have the additional benefit of enabling tumor resection by maintaining separation between tumor and healthy tissue boundaries.
https://ift.tt/2H9YoC8
YAP/TAZ initiates gastric tumorigenesis via upregulation of MYC
YAP and TAZ play oncogenic roles in various organs, but the role of YAP/TAZ in gastric cancer remains unclear. Here we show that YAP/TAZ activation initiates gastric tumorigenesis in vivo and verify its significance in human gastric cancer. In mice, YAP/TAZ activation in the pyloric stem cell led to step-wise tumorigenesis. RNA sequencing identified MYC as a decisive target of YAP, which controls MYC at transcriptional and post-transcriptional levels. These mechanisms tightly regulated MYC in homeostatic conditions, but YAP activation altered this balance by impeding miRNA processing, causing a shift towards MYC upregulation. Pharmacological inhibition of MYC suppressed YAP-dependent phenotypes in vitro and in vivo, verifying its functional role as a key mediator. Human gastric cancer samples also displayed a significant correlation between YAP and MYC. We re-analyzed human transcriptome data to verify enrichment of YAP signatures in a subpopulation of gastric cancers and found that our model closely reflected the molecular pattern of patients with high YAP activity. Overall, these results provide genetic evidence of YAP/TAZ as oncogenic initiators and drivers for gastric tumors with MYC as the key downstream mediator. These findings are also evident in human gastric cancer, emphasizing the significance of YAP/TAZ signaling in gastric carcinogenesis.
https://ift.tt/2qHwnXu
Enhancer remodeling and microRNA alterations are associated with acquired resistance to ALK inhibitors
Anaplastic lymphoma kinase (ALK) inhibitors are highly effective in ALK fusion-positive lung cancer patients, but acquired resistance invariably emerges. Identification of secondary mutations has received considerable attention, but most cases cannot be explained by genetic causes alone, raising the possibility of epigenetic mechanisms in acquired drug resistance. Here we investigated the dynamic changes in the transcriptome and enhancer landscape during development of acquired resistance to ALK inhibitors. Histone H3 lysine 27 acetylation (H3K27ac) was profoundly altered during acquisition of resistance, and enhancer remodeling induced expression changes in both miRNAs and mRNAs. Decreased H3K27ac levels and reduced miR-34a expression associated with the activation of target genes such as AXL. Panobinostat, a pan-histone deacetylase inhibitor, altered the H3K27ac profile and activated tumor suppressor miRNAs such as miR-449, another member of the miR-34 family, and synergistically induced anti-proliferative effects with ALK inhibitors on resistant cells, xenografts, and EML4-ALK transgenic mice. Paired analysis of patient samples before and after treatment with ALK inhibitors revealed that repression of miR-34a or miR-449a and activation of AXL were mutually exclusive of secondary mutations in ALK. Our findings indicate that enhancer remodeling and altered expression of miRNAs play key roles in cancer drug resistance and suggest that strategies targeting epigenetic pathways represent a potentially effective method for overcoming acquired resistance to cancer therapy.
https://ift.tt/2Heahaf
Multi-kinase inhibitor CT-707 targets liver cancer by interrupting the hypoxia-activated IGF-1R-YAP axis
Given that YAP signaling acts as a critical survival input for hypoxic cancer cells in hepatocellular carcinoma (HCC), disruption of YAP function and the maintenance of hypoxia is an attractive way to treat HCC. Utilizing a cell-based YAP-TEAD luciferase reporter assay and functional analyses, we identified CT-707, a China-FDA approved multi-kinase inhibitor under clinical trial with remarkable inhibitory activity against YAP function. CT-707 exhibited prominent cytotoxicity under hypoxia on HCC cells, which was attributable to the inhibition of YAP signaling. CT-707 arrested tumor growth in HepG2-, Bel-7402-, and HCC patient-derived xenografts. Mechanistically, the inhibitory activity of CT-707 on YAP signaling was due to the interruption of hypoxia-activated IGF-1R. Overall, these findings not only identify CT-707 as a promising hypoxia-targeting agent against HCC, but they also unveil IGF-1R as a new modulator specifically regulating hypoxia-activated YAP signaling.
https://ift.tt/2qHwhPC
Silencing of long non-coding RNA MIR22HG triggers cell survival/death signaling via oncogenes YBX1, MET, and p21 in lung cancer
The long non-coding RNA (lncRNA) MIR22HG has previously been identified as a prognostic marker in hepatocellular carcinoma. Here we performed a comprehensive analysis of lncRNA expression profiles from RNA-seq data and report that MIR22HG plays a similar role in lung cancer. Analysis of 918 lung cancer and normal lung tissues and lung cancer cell lines revealed that MIR22HG was significantly downregulated in lung cancer; this decreased expression was associated with poor patient survival. MIR22HG bound and stabilized the YBX1 protein. Silencing of MIR22HG triggered both cell survival and cell death signaling through dysregulation of the oncogenes YBX1, MET, and p21. In this MIR22HG network, p21 played an oncogenic role by promoting cell proliferation and anti-apoptosis in lung cancers. MIR22HG played a tumor suppressor role as indicated by inhibition of multiple cell cycle-related genes in human primary lung tumors. These data show that MIR22HG has potential as a new diagnostic and prognostic marker and as a therapeutic target for lung cancer.
https://ift.tt/2Hea7Qb
Rho Kinase Inhibition by AT13148 Blocks Pancreatic Ductal Adenocarinoma Invasion and Tumor Growth
The high mortality of pancreatic cancer demands that new therapeutic avenues be developed. The orally available small molecule inhibitor AT13148 potently inhibits ROCK1 and ROCK2 kinases that regulate the actomyosin cytoskeleton. We previously reported that ROCK kinase expression increases with human and mouse pancreatic cancer progression and that conditional ROCK activation accelerates mortality in a genetically modified LSL-KrasG12D; LSL-p53R172H; Pdx1-Cre; (KPC) mouse pancreatic cancer model. In this study, we show that treatment of KPC mouse and human TKCC5 patient-derived pancreatic tumor cells with AT13148, as well as the ROCK selective inhibitors Y27632 and H1152, act comparably in blocking ROCK substrate phosphorylation. AT13148, Y27632, and H1152 induced morphological changes and reduced cellular contractile force generation, motility on pliable discontinuous substrates, and three-dimensional collagen matrix invasion. AT13148 treatment reduced subcutaneous tumor growth and blocked invasion of healthy pancreatic tissue by KPC tumor cells in vivo without affecting proliferation, suggesting a role for local tissue invasion as a contributor to primary tumor growth. These results suggest that AT13148 has anti-tumor properties that may be beneficial in combination therapies or in the adjuvant setting to reduce pancreatic cancer cell invasion and slow primary tumor growth. AT13148 might also have the additional benefit of enabling tumor resection by maintaining separation between tumor and healthy tissue boundaries.
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YAP/TAZ initiates gastric tumorigenesis via upregulation of MYC
YAP and TAZ play oncogenic roles in various organs, but the role of YAP/TAZ in gastric cancer remains unclear. Here we show that YAP/TAZ activation initiates gastric tumorigenesis in vivo and verify its significance in human gastric cancer. In mice, YAP/TAZ activation in the pyloric stem cell led to step-wise tumorigenesis. RNA sequencing identified MYC as a decisive target of YAP, which controls MYC at transcriptional and post-transcriptional levels. These mechanisms tightly regulated MYC in homeostatic conditions, but YAP activation altered this balance by impeding miRNA processing, causing a shift towards MYC upregulation. Pharmacological inhibition of MYC suppressed YAP-dependent phenotypes in vitro and in vivo, verifying its functional role as a key mediator. Human gastric cancer samples also displayed a significant correlation between YAP and MYC. We re-analyzed human transcriptome data to verify enrichment of YAP signatures in a subpopulation of gastric cancers and found that our model closely reflected the molecular pattern of patients with high YAP activity. Overall, these results provide genetic evidence of YAP/TAZ as oncogenic initiators and drivers for gastric tumors with MYC as the key downstream mediator. These findings are also evident in human gastric cancer, emphasizing the significance of YAP/TAZ signaling in gastric carcinogenesis.
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Enhancer remodeling and microRNA alterations are associated with acquired resistance to ALK inhibitors
Anaplastic lymphoma kinase (ALK) inhibitors are highly effective in ALK fusion-positive lung cancer patients, but acquired resistance invariably emerges. Identification of secondary mutations has received considerable attention, but most cases cannot be explained by genetic causes alone, raising the possibility of epigenetic mechanisms in acquired drug resistance. Here we investigated the dynamic changes in the transcriptome and enhancer landscape during development of acquired resistance to ALK inhibitors. Histone H3 lysine 27 acetylation (H3K27ac) was profoundly altered during acquisition of resistance, and enhancer remodeling induced expression changes in both miRNAs and mRNAs. Decreased H3K27ac levels and reduced miR-34a expression associated with the activation of target genes such as AXL. Panobinostat, a pan-histone deacetylase inhibitor, altered the H3K27ac profile and activated tumor suppressor miRNAs such as miR-449, another member of the miR-34 family, and synergistically induced anti-proliferative effects with ALK inhibitors on resistant cells, xenografts, and EML4-ALK transgenic mice. Paired analysis of patient samples before and after treatment with ALK inhibitors revealed that repression of miR-34a or miR-449a and activation of AXL were mutually exclusive of secondary mutations in ALK. Our findings indicate that enhancer remodeling and altered expression of miRNAs play key roles in cancer drug resistance and suggest that strategies targeting epigenetic pathways represent a potentially effective method for overcoming acquired resistance to cancer therapy.
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Multi-kinase inhibitor CT-707 targets liver cancer by interrupting the hypoxia-activated IGF-1R-YAP axis
Given that YAP signaling acts as a critical survival input for hypoxic cancer cells in hepatocellular carcinoma (HCC), disruption of YAP function and the maintenance of hypoxia is an attractive way to treat HCC. Utilizing a cell-based YAP-TEAD luciferase reporter assay and functional analyses, we identified CT-707, a China-FDA approved multi-kinase inhibitor under clinical trial with remarkable inhibitory activity against YAP function. CT-707 exhibited prominent cytotoxicity under hypoxia on HCC cells, which was attributable to the inhibition of YAP signaling. CT-707 arrested tumor growth in HepG2-, Bel-7402-, and HCC patient-derived xenografts. Mechanistically, the inhibitory activity of CT-707 on YAP signaling was due to the interruption of hypoxia-activated IGF-1R. Overall, these findings not only identify CT-707 as a promising hypoxia-targeting agent against HCC, but they also unveil IGF-1R as a new modulator specifically regulating hypoxia-activated YAP signaling.
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Silencing of long non-coding RNA MIR22HG triggers cell survival/death signaling via oncogenes YBX1, MET, and p21 in lung cancer
The long non-coding RNA (lncRNA) MIR22HG has previously been identified as a prognostic marker in hepatocellular carcinoma. Here we performed a comprehensive analysis of lncRNA expression profiles from RNA-seq data and report that MIR22HG plays a similar role in lung cancer. Analysis of 918 lung cancer and normal lung tissues and lung cancer cell lines revealed that MIR22HG was significantly downregulated in lung cancer; this decreased expression was associated with poor patient survival. MIR22HG bound and stabilized the YBX1 protein. Silencing of MIR22HG triggered both cell survival and cell death signaling through dysregulation of the oncogenes YBX1, MET, and p21. In this MIR22HG network, p21 played an oncogenic role by promoting cell proliferation and anti-apoptosis in lung cancers. MIR22HG played a tumor suppressor role as indicated by inhibition of multiple cell cycle-related genes in human primary lung tumors. These data show that MIR22HG has potential as a new diagnostic and prognostic marker and as a therapeutic target for lung cancer.
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Targeting Merkel cell carcinoma by engineered T cells specific to T-antigens of Merkel cell polyomavirus
Purpose: The causative agent of most cases of Merkel cell carcinoma (MCC) has been identified as the Merkel cell polyomavirus (MCV). MCV-encoded T-antigens (Tags) are essential not only for virus-mediated tumorigenesis but also for maintaining MCC cell lines in vitro. MCV Tags are thus an appealing target for viral oncoprotein-directed T cell therapy for MCC. With this study, we aimed to isolate and characterize Tag-specific T cell receptors (TCR) for potential use in gene therapy clinical trials. Experimental Design: T cell responses against MCV Tag epitopes were investigated by immunizing transgenic mice that express a diverse human TCR repertoire restricted to HLA-A2. Human lymphocytes genetically engineered to express Tag-specific TCRs were tested for specific reactivity against MCC cell lines. The therapeutic potential of Tag-specific TCR gene therapy was tested in a syngeneic cancer model. Results: We identified naturally processed epitopes of MCV Tags and isolated Tag-specific TCRs. T cells expressing these TCRs were activated by HLA-A2-positive cells loaded with cognate peptide or cells that stably expressed MCV Tags. We showed cytotoxic potential of T cells engineered to express these TCRs in vitro and demonstrated regression of established tumors in a mouse model upon TCR gene therapy. Conclusions: Our findings demonstrate that MCC cells can be targeted by MCV Tag-specific TCRs. Although recent findings suggest that approximately half of MCC patients benefit from PD1 pathway blockade, additional patients may benefit if their endogenous T cell response can be augmented by infusion of transgenic MCV-specific T cells such as those described here.
https://ift.tt/2qJDbE5
Targeting Merkel cell carcinoma by engineered T cells specific to T-antigens of Merkel cell polyomavirus
Purpose: The causative agent of most cases of Merkel cell carcinoma (MCC) has been identified as the Merkel cell polyomavirus (MCV). MCV-encoded T-antigens (Tags) are essential not only for virus-mediated tumorigenesis but also for maintaining MCC cell lines in vitro. MCV Tags are thus an appealing target for viral oncoprotein-directed T cell therapy for MCC. With this study, we aimed to isolate and characterize Tag-specific T cell receptors (TCR) for potential use in gene therapy clinical trials. Experimental Design: T cell responses against MCV Tag epitopes were investigated by immunizing transgenic mice that express a diverse human TCR repertoire restricted to HLA-A2. Human lymphocytes genetically engineered to express Tag-specific TCRs were tested for specific reactivity against MCC cell lines. The therapeutic potential of Tag-specific TCR gene therapy was tested in a syngeneic cancer model. Results: We identified naturally processed epitopes of MCV Tags and isolated Tag-specific TCRs. T cells expressing these TCRs were activated by HLA-A2-positive cells loaded with cognate peptide or cells that stably expressed MCV Tags. We showed cytotoxic potential of T cells engineered to express these TCRs in vitro and demonstrated regression of established tumors in a mouse model upon TCR gene therapy. Conclusions: Our findings demonstrate that MCC cells can be targeted by MCV Tag-specific TCRs. Although recent findings suggest that approximately half of MCC patients benefit from PD1 pathway blockade, additional patients may benefit if their endogenous T cell response can be augmented by infusion of transgenic MCV-specific T cells such as those described here.
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Nested case–control study of telomere length and lung cancer risk among heavy smokers in the β-Carotene and Retinol Efficacy Trial
Nested case–control study of telomere length and lung cancer risk among heavy smokers in the β-Carotene and Retinol Efficacy Trial
Nested case–control study of telomere length and lung cancer risk among heavy smokers in the β-Carotene and Retinol Efficacy Trial, Published online: 19 April 2018; doi:10.1038/s41416-018-0075-0
Nested case–control study of telomere length and lung cancer risk among heavy smokers in the β-Carotene and Retinol Efficacy Trial
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Paracrine roles of cellular senescence in promoting tumourigenesis
Paracrine roles of cellular senescence in promoting tumourigenesis
Paracrine roles of cellular senescence in promoting tumourigenesis, Published online: 19 April 2018; doi:10.1038/s41416-018-0066-1
Paracrine roles of cellular senescence in promoting tumourigenesis
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The surgical intelligent knife distinguishes normal, borderline and malignant gynaecological tissues using rapid evaporative ionisation mass spectrometry (REIMS)
The surgical intelligent knife distinguishes normal, borderline and malignant gynaecological tissues using rapid evaporative ionisation mass spectrometry (REIMS)
The surgical intelligent knife distinguishes normal, borderline and malignant gynaecological tissues using rapid evaporative ionisation mass spectrometry (REIMS), Published online: 19 April 2018; doi:10.1038/s41416-018-0048-3
The surgical intelligent knife distinguishes normal, borderline and malignant gynaecological tissues using rapid evaporative ionisation mass spectrometry (REIMS)
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Nested case–control study of telomere length and lung cancer risk among heavy smokers in the β-Carotene and Retinol Efficacy Trial
Nested case–control study of telomere length and lung cancer risk among heavy smokers in the β-Carotene and Retinol Efficacy Trial
Nested case–control study of telomere length and lung cancer risk among heavy smokers in the β-Carotene and Retinol Efficacy Trial, Published online: 19 April 2018; doi:10.1038/s41416-018-0075-0
Nested case–control study of telomere length and lung cancer risk among heavy smokers in the β-Carotene and Retinol Efficacy Trialhttps://ift.tt/2HMEHxe
Paracrine roles of cellular senescence in promoting tumourigenesis
Paracrine roles of cellular senescence in promoting tumourigenesis
Paracrine roles of cellular senescence in promoting tumourigenesis, Published online: 19 April 2018; doi:10.1038/s41416-018-0066-1
Paracrine roles of cellular senescence in promoting tumourigenesishttps://ift.tt/2vqnBD5
The surgical intelligent knife distinguishes normal, borderline and malignant gynaecological tissues using rapid evaporative ionisation mass spectrometry (REIMS)
The surgical intelligent knife distinguishes normal, borderline and malignant gynaecological tissues using rapid evaporative ionisation mass spectrometry (REIMS)
The surgical intelligent knife distinguishes normal, borderline and malignant gynaecological tissues using rapid evaporative ionisation mass spectrometry (REIMS), Published online: 19 April 2018; doi:10.1038/s41416-018-0048-3
The surgical intelligent knife distinguishes normal, borderline and malignant gynaecological tissues using rapid evaporative ionisation mass spectrometry (REIMS)https://ift.tt/2HJxVZj
Association Between Proportion of Nuclei With High Chromatin Entropy and Prognosis in Gynecological Cancers
Abstract
Background
Nuclear texture analysis measuring differences in chromatin structure has provided prognostic biomarkers in several cancers. There is a need for improved cell-by-cell chromatin analysis to detect nuclei with highly disorganized chromatin. The purpose of this study was to develop a method for detecting nuclei with high chromatin entropy and to evaluate the association between the presence of such deviating nuclei and prognosis. Methods
A new texture-based biomarker that characterizes each cancer based on the proportion of high–chromatin entropy nuclei (<25% vs ≥25%) was developed on a discovery set of 175 uterine sarcomas. The prognostic impact of this biomarker was evaluated on a validation set of 179 uterine sarcomas, as well as on independent validation sets of 246 early-stage ovarian carcinomas and 791 endometrial carcinomas. More than 1 million images of nuclei stained for DNA were included in the study. All statistical tests were two-sided. Results
An increased proportion of high–chromatin entropy nuclei was associated with poor clinical outcome. The biomarker predicted five-year overall survival for uterine sarcoma patients with a hazard ratio (HR) of 2.02 (95% confidence interval [CI] = 1.43 to 2.84), time to recurrence for ovarian cancer patients (HR = 2.91, 95% CI = 1.74 to 4.88), and cancer-specific survival for endometrial cancer patients (HR = 3.74, 95% CI = 2.24 to 6.24). Chromatin entropy was an independent prognostic marker in multivariable analyses with clinicopathological parameters (HR = 1.81, 95% CI = 1.21 to 2.70, for sarcoma; HR = 1.71, 95% CI = 1.01 to 2.90, for ovarian cancer; and HR = 2.03, 95% CI = 1.19 to 3.45, for endometrial cancer). Conclusions
A novel method detected high–chromatin entropy nuclei, and an increased proportion of such nuclei was associated with poor prognosis. Chromatin entropy supplemented existing prognostic markers in multivariable analyses of three gynecological cancer cohorts.https://ift.tt/2qHuEm1
A New Framework for Patient Engagement in Cancer Clinical Trials Cooperative Group Studies
Abstract
For the past two decades, the National Cancer Institute (NCI) has supported the involvement of patient advocates in both internal advisory activities and funded research projects to provide a patient perspective. Implementation of the inclusion of patient advocates has varied considerably, with inconsistent involvement of patient advocates in key phases of research such as concept development. Despite this, there is agreement that patient advocates have improved the patient focus of many cancer research studies. This commentary describes our experience designing and pilot testing a new framework for patient engagement at SWOG, one of the largest cancer clinical trial network groups in the United States and one of the four adult groups in the NCI's National Clinical Trials Network (NCTN). Our goal is to provide a roadmap for other clinical trial groups that are interested in bringing the patient voice more directly into clinical trial conception and development. We developed a structured process to engage patient advocates more effectively in the development of cancer clinical trials and piloted the process in four SWOG research committees, including implementation of a new Patient Advocate Executive Review Form that systematically captures patient advocates' input at the concept stage. Based on the positive feedback to our approach, we are now developing training and evaluation metrics to support meaningful and consistent patient engagement across the SWOG clinical trial life cycle. Ultimately, the benefits of more patient-centered cancer trials will be measured in the usefulness, relevance, and speed of study results to patients, caregivers, and clinicians.https://ift.tt/2J6LNfz
PACHE Spotlight: Yamilé Molina, Ph.D.
Dr. Yamilé Molina, an Assistant Professor at the University of Illinois-Chicago, discusses her work comparing intervention approaches' effects on cancer disparities. Dr. Molina also describes what CRCHD diversity training programs, including PACHE, have meant to her career.
https://ift.tt/2qI9VxG
PACHE Spotlight: Yamilé Molina, Ph.D.
Dr. Yamilé Molina, an Assistant Professor at the University of Illinois-Chicago, discusses her work comparing intervention approaches' effects on cancer disparities. Dr. Molina also describes what CRCHD diversity training programs, including PACHE, have meant to her career.
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Preoperative radiotherapy and local excision of rectal cancer: Long-term results of a randomised study
It is uncertain whether local control is acceptable after preoperative radiotherapy and local excision (LE). An optimal preoperative dose/fractionation schedule has not yet been established.
https://ift.tt/2HdW5tM
Dose-response in choroidal melanoma
In choroidal melanoma the radiation threshold dose for local control remains largely unknown. The present study examined a group of patients that received a wide range of minimum tumor dose in order to investigate a dose-response relationship. A literature review is performed to compare our results with available evidence in brachytherapy and charged particle external beam radiotherapy.
https://ift.tt/2JUO52C
The Radish, Raphanus sativus L. Var. caudatus reduces anxiety-like behavior in mice
Abstract
Inclusion of vegetables in the diet not only provides dietary fiber, vitamins, minerals, trace elements but also significantly reduces the risk of several diseases. Raphanus sativus L. Var. caudatus belongs to the family Brassicaceae are pods of Radish, and are commonly known as Mungra or Sungra in Pakistan and India. The English name for this species is Rat-tailed radish. This variety of radish is unique, less familiar to the population, and not commonly used as a food source. Furthermore there have been very few studies that report on the potential antioxidant and anti-cancer capabilities of this radish. The present study was designed to evaluate anxiolytic potential of Raphanus caudatus in mice using different behavioral paradigms. The ethanol extract of the plant was evaluated at three different doses i.e. 250, 500 and 1000 mg/kg. The extract at doses of 250 and 500 mg/kg produced a significant (p < 0.05) reduction of anxiety-like behavior in mice and results are comparable to standard anxiolytic drug diazepam.
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Indian Ginseng (Withania somnifera) supplementation ameliorates oxidative stress and mitochondrial dysfunctions in experimental model of stroke
Abstract
Stroke is an increasingly prevalent clinical condition and second leading cause of death globally. The present study evaluated the therapeutic potential of Indian Ginseng, also known as Withania somnifera (WS), supplementation on middle cerebral artery occlusion (MCAO) induced mitochondrial dysfunctions in experimental model of ischemic stroke. Stroke was induced in animals by occluding the middle cerebral artery, followed by reperfusion injury. Ischemia reperfusion injury resulted in increased oxidative stress indicated by increased reactive oxygen species and protein carbonyl levels; compromised antioxidant system; in terms of reduced superoxide dismutase and catalase activity, along with reduction in GSH levels and the redox ratio, impaired mitochondrial functions and enhanced expression of apoptosis markers. Ischemia reperfusion injury induced mitochondrial dysfunctions in terms of (i) reduced activity of the mitochondrial respiratory chain enzymes, (ii) reduced histochemical staining of complex-II and IV, (iii) reduced in-gel activity of mitochondrial complex-I to V, (iv) mitochondrial structural changes in terms of increased mitochondrial swelling, reduced mitochondrial membrane potential and ultrastructural changes. Additionally, an increase in the activity of caspase-3 and caspase-9 was also observed, along with altered expression of apoptotic proteins Bcl-2 and Bax in MCAO animals. MCAO animals also showed significant impairment in cognitive functions assessed using Y maze test. WS pre-supplementation, on the other hand ameliorated MCAO induced oxidative stress, mitochondrial dysfunctions, apoptosis and cognitive impairments. The results show protective effect of WS pre-supplementation in ischemic stroke and are suggestive of its potential application in stroke management.
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Unique barriers to well‐being for pathology residents and how to address them
Cancer Cytopathology, EarlyView.
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Analysis of histologic follow‐up and risk of malignancy for salivary gland neoplasm of uncertain malignant potential proposed by the milan system for reporting salivary gland cytopathology
Cancer Cytopathology, EarlyView.
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The Radish, Raphanus sativus L. Var. caudatus reduces anxiety-like behavior in mice
Abstract
Inclusion of vegetables in the diet not only provides dietary fiber, vitamins, minerals, trace elements but also significantly reduces the risk of several diseases. Raphanus sativus L. Var. caudatus belongs to the family Brassicaceae are pods of Radish, and are commonly known as Mungra or Sungra in Pakistan and India. The English name for this species is Rat-tailed radish. This variety of radish is unique, less familiar to the population, and not commonly used as a food source. Furthermore there have been very few studies that report on the potential antioxidant and anti-cancer capabilities of this radish. The present study was designed to evaluate anxiolytic potential of Raphanus caudatus in mice using different behavioral paradigms. The ethanol extract of the plant was evaluated at three different doses i.e. 250, 500 and 1000 mg/kg. The extract at doses of 250 and 500 mg/kg produced a significant (p < 0.05) reduction of anxiety-like behavior in mice and results are comparable to standard anxiolytic drug diazepam.
https://ift.tt/2qHtqr1
Indian Ginseng (Withania somnifera) supplementation ameliorates oxidative stress and mitochondrial dysfunctions in experimental model of stroke
Abstract
Stroke is an increasingly prevalent clinical condition and second leading cause of death globally. The present study evaluated the therapeutic potential of Indian Ginseng, also known as Withania somnifera (WS), supplementation on middle cerebral artery occlusion (MCAO) induced mitochondrial dysfunctions in experimental model of ischemic stroke. Stroke was induced in animals by occluding the middle cerebral artery, followed by reperfusion injury. Ischemia reperfusion injury resulted in increased oxidative stress indicated by increased reactive oxygen species and protein carbonyl levels; compromised antioxidant system; in terms of reduced superoxide dismutase and catalase activity, along with reduction in GSH levels and the redox ratio, impaired mitochondrial functions and enhanced expression of apoptosis markers. Ischemia reperfusion injury induced mitochondrial dysfunctions in terms of (i) reduced activity of the mitochondrial respiratory chain enzymes, (ii) reduced histochemical staining of complex-II and IV, (iii) reduced in-gel activity of mitochondrial complex-I to V, (iv) mitochondrial structural changes in terms of increased mitochondrial swelling, reduced mitochondrial membrane potential and ultrastructural changes. Additionally, an increase in the activity of caspase-3 and caspase-9 was also observed, along with altered expression of apoptotic proteins Bcl-2 and Bax in MCAO animals. MCAO animals also showed significant impairment in cognitive functions assessed using Y maze test. WS pre-supplementation, on the other hand ameliorated MCAO induced oxidative stress, mitochondrial dysfunctions, apoptosis and cognitive impairments. The results show protective effect of WS pre-supplementation in ischemic stroke and are suggestive of its potential application in stroke management.
https://ift.tt/2J9ECTN
Unique barriers to well‐being for pathology residents and how to address them
Cancer Cytopathology, EarlyView.
https://ift.tt/2vsMDl3
Analysis of histologic follow‐up and risk of malignancy for salivary gland neoplasm of uncertain malignant potential proposed by the milan system for reporting salivary gland cytopathology
Cancer Cytopathology, EarlyView.
https://ift.tt/2HzPywW
Study of platelet activation markers and plasma cytokines in sickle cell disease patients during vaso-occlusive pain crises
Abstract
The present study was designed to examine platelet function during the sickle cell disease (SCD) vaso-occlusive pain crisis (VOC) in comparison with steady-state SCD patients and healthy controls. Platelets were immunophenotyped using different activation CD markers in a group of 34 patients with SCD. Among those SCD patients, 19 patients were admitted to our hospital for symptoms of VOC pain crises. Fifteen patients of SCD were studied in parallel during asymptomatic steady state (SS) of their disease. Fifteen healthy control volunteers were immunophenotyped in parallel. In addition, all patients and healthy control plasma were assayed for levels of the inflammatory cytokines which are IL-8, TGF-β1, and TNF-α. Our results confirmed the strong expression of activation markers CD40, CD41a, CD42a, CD61, CD62p, CD36, CD49f, and CD59 on platelets from patients studied during VOC pain episodes (P ˂ 0.005). However, both the steady-state SCD patients and normal healthy controls did not show increased expression of any of these markers on their platelets. In addition, the mean levels of IL-8 in the plasma of VOC-SCD patients were statistically significant superior to IL-8 mean values of normal control plasma (P = 0.008). These results suggest over activation of platelets in SCD patients during VOC pain episodes compared to SCD steady state or normal controls. Alongside, we found significant increase of plasma IL-8 levels during VOC pain crises. These findings indicate over activation of platelets, together with over production of IL-8 during VOC pain crises in SCD patients.
https://ift.tt/2JVIAAR
Patient views and correlates of radiotherapy omission in a population‐based sample of older women with favorable‐prognosis breast cancer
Cancer, EarlyView.
from Cancer via ola Kala on Inoreader https://ift.tt/2HfokZm
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Development and validation of algorithms to differentiate ductal carcinoma in situ from invasive breast cancer within administrative claims data
Cancer, EarlyView.
from Cancer via ola Kala on Inoreader https://ift.tt/2HzX2jF
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Patient views and correlates of radiotherapy omission in a population‐based sample of older women with favorable‐prognosis breast cancer
Cancer, EarlyView.
https://ift.tt/2HfokZm
Development and validation of algorithms to differentiate ductal carcinoma in situ from invasive breast cancer within administrative claims data
Cancer, EarlyView.
https://ift.tt/2HzX2jF
Stereotactic body radiotherapy for castration-sensitive prostate cancer bone oligometastases
Abstract
To evaluate outcome in patients treated with stereotactic body radiotherapy (SBRT) on bone oligometastases from castration-sensitive prostate cancer after primary treatment. We retrospectively collected data of patients with less than five lesions at time of SBRT and hormone-naïve disease at the first extra-regional localization, treated between 03/2012 and 11/2016. Prostate-specific antigen (PSA) was measured every 3 months after SBRT. Imaging was performed in case of progression. Survival analysis was performed with Kaplan–Meier (log-rank test) approach. Fifty-five patients were treated on 77 bone oligometastases. Median age, initial PSA and pre-SBRT PSA were 72 years, 9.12 and 3.5 ng/mL, respectively. Twenty-five patients (45%) received SBRT alone while the remaining 30 patients (55%) received concomitant ADT. Median follow-up was 24.6 months (range 3.0–67.2 months). No acute or late toxicity of grade > 1 was reported. Clinical progression was observed in 38 (69%) patients. 1-year biochemical progression-free survival (b-PFS), clinical progression-free survival (c-PFS), prostate-specific survival (PCSS) and local control (LC) rates were 51, 56, 100 and 83%, respectively. Comparing patients treated with SBRT alone and with concomitant ADT, no significant differences were found for those outcomes. SBRT is safe and allows high 1-year LC rate (83%) with low toxicity profile. No significant improvement in outcomes was registered with the addition of ADT to SBRT.
from Cancer via ola Kala on Inoreader https://ift.tt/2vrMQVq
via IFTTT
Stereotactic body radiotherapy for castration-sensitive prostate cancer bone oligometastases
Abstract
To evaluate outcome in patients treated with stereotactic body radiotherapy (SBRT) on bone oligometastases from castration-sensitive prostate cancer after primary treatment. We retrospectively collected data of patients with less than five lesions at time of SBRT and hormone-naïve disease at the first extra-regional localization, treated between 03/2012 and 11/2016. Prostate-specific antigen (PSA) was measured every 3 months after SBRT. Imaging was performed in case of progression. Survival analysis was performed with Kaplan–Meier (log-rank test) approach. Fifty-five patients were treated on 77 bone oligometastases. Median age, initial PSA and pre-SBRT PSA were 72 years, 9.12 and 3.5 ng/mL, respectively. Twenty-five patients (45%) received SBRT alone while the remaining 30 patients (55%) received concomitant ADT. Median follow-up was 24.6 months (range 3.0–67.2 months). No acute or late toxicity of grade > 1 was reported. Clinical progression was observed in 38 (69%) patients. 1-year biochemical progression-free survival (b-PFS), clinical progression-free survival (c-PFS), prostate-specific survival (PCSS) and local control (LC) rates were 51, 56, 100 and 83%, respectively. Comparing patients treated with SBRT alone and with concomitant ADT, no significant differences were found for those outcomes. SBRT is safe and allows high 1-year LC rate (83%) with low toxicity profile. No significant improvement in outcomes was registered with the addition of ADT to SBRT.
https://ift.tt/2vrMQVq
Dietary patterns and prostate cancer risk in Japanese: the Japan Public Health Center-based Prospective Study (JPHC Study)
Abstract
Purpose
The development of prostate cancer may be impacted by environmental factors, including diet. The aim of this study was to evaluate the association between dietary patterns and risk of prostate cancer in a large prospective cohort study among Japanese men.
Methods
A total of 43,469 men who participated in the Japan Public Health Center-based Prospective Study were followed from 1995 to 1998 to the end of 2012, during which 1,156 cases of prostate cancer were newly identified. Dietary intake was assessed using a validated food frequency questionnaire in the 5-year follow-up survey.
Results
Three major dietary patterns were derived using exploratory factors analysis: prudent, westernized, and traditional dietary patterns. The westernized dietary pattern was associated with a higher risk of total prostate cancer (HR: 1.22; 95% CI 1.00–1.49; p trend = 0.021), localized cancer (HR: 1.24; 95% CI 0.97–1.57; p trend = 0.045), and advanced cancer (HR: 1.23; 95% CI 0.82–1.84; p trend = 0.233). The prudent dietary pattern was associated with a lower risk of total and localized prostate cancer, with respective multivariable HRs for the highest and lowest quintiles of 0.71 (95% CI 0.50–1.02; p trend = 0.037) and 0.63 (95% CI 0.38–1.03; p trend = 0.048) among subjects detected by subjective symptoms. No association was found between the traditional dietary pattern and prostate cancer risk among our subjects.
Conclusion
Our results suggest that a western-style diet may lead to a higher risk of prostate cancer in the total population, whereas the prudent diet contributes to a lower risk among subjects detected by subjective symptoms.
https://ift.tt/2JUe8qI
Hormone replacement therapy, mammographic density, and breast cancer risk: a cohort study
Abstract
Purpose
Hormone replacement therapy (HRT) use increases breast cancer risk and mammographic density (MD). We examine whether MD mediates or modifies the association of HRT with the breast cancer.
Methods
For the 4,501 participants in the Danish diet, cancer and health cohort (1993–1997) who attended mammographic screening in Copenhagen (1993–2001), MD (mixed/dense or fatty) was assessed at the first screening after cohort entry. HRT use was assessed by questionnaire and breast cancer diagnoses until 2012 obtained from the Danish cancer registry. The associations of HRT with MD and with breast cancer were analyzed separately using Cox's regression. Mediation analyses were used to estimate proportion [with 95% confidence intervals (CI)] of an association between HRT and breast cancer mediated by MD.
Results
2,444 (54.3%) women had mixed/dense breasts, 229 (5.4%) developed breast cancer, and 35.9% were current HRT users at enrollment. Compared to never users, current HRT use was statistically significantly associated with having mixed/dense breasts (relative risk and 95% CI 1.24; 1.14–1.35), and higher risk of breast cancer (hazard ratio 1.87; 1.40–2.48). Association between current HRT use and breast cancer risk was partially mediated by MD (percent mediated = 10%; 95% CI 4–22%). The current HRT use-related breast cancer risk was higher in women with mixed/dense (1.94; 1.37–3.87) than fatty (1.37; 0.80–2.35) breasts (p value for interaction = 0.15).
Conclusions
MD partially mediates some of the association between HRT and breast cancer risk. The association between HRT and breast cancer seems to be stronger in women with dense breasts.
https://ift.tt/2J2Fp9m
Self-reported dietary flavonoid intake and serum markers of inflammation: the multiethnic cohort
Abstract
Purpose
To examine if dietary intake of foods rich in flavonoids, which have been shown to be inversely associated with chronic diseases, is associated with inflammatory processes.
Methods
This analysis includes controls of case–control studies nested within the Multiethnic Cohort (MEC) who completed a validated food frequency questionnaire at cohort entry. Biomarkers were assessed in blood donated during follow-up (mean = 9.6 years). We used multivariate linear regression adjusted for potential confounders to estimate associations between intake of flavanones, flavonols, and isoflavones and levels of adiponectin, leptin, C-reactive protein, interleukin (IL)-1β, IL-6, IL-10, and tumor necrosis factor-α.
Results
Among the 1,287 participants, the respective median intakes of flavanones, flavonols, and isoflavones were 26.5, 12.4, and 1.3 mg/day at cohort entry. With the exception of flavanone intake, which was statistically significantly inversely associated with adiponectin (p = 0.01) and IL-6 concentrations (p = 0.01), none of the examined flavonoids was related with levels of adipokines or inflammatory markers. Heterogeneity by ethnicity was only observed for flavonol intake and IL-10 (pinteraction = 0.04) and may be the result of multiple testing. These null findings were confirmed in a subset of participants who completed a second dietary history within 2.6 years of blood draw.
Conclusion
The current results do not support a consistent association between dietary intake of flavonoids and markers of inflammatory processes.
https://ift.tt/2EXstyV
Dietary patterns and prostate cancer risk in Japanese: the Japan Public Health Center-based Prospective Study (JPHC Study)
Abstract
Purpose
The development of prostate cancer may be impacted by environmental factors, including diet. The aim of this study was to evaluate the association between dietary patterns and risk of prostate cancer in a large prospective cohort study among Japanese men.
Methods
A total of 43,469 men who participated in the Japan Public Health Center-based Prospective Study were followed from 1995 to 1998 to the end of 2012, during which 1,156 cases of prostate cancer were newly identified. Dietary intake was assessed using a validated food frequency questionnaire in the 5-year follow-up survey.
Results
Three major dietary patterns were derived using exploratory factors analysis: prudent, westernized, and traditional dietary patterns. The westernized dietary pattern was associated with a higher risk of total prostate cancer (HR: 1.22; 95% CI 1.00–1.49; p trend = 0.021), localized cancer (HR: 1.24; 95% CI 0.97–1.57; p trend = 0.045), and advanced cancer (HR: 1.23; 95% CI 0.82–1.84; p trend = 0.233). The prudent dietary pattern was associated with a lower risk of total and localized prostate cancer, with respective multivariable HRs for the highest and lowest quintiles of 0.71 (95% CI 0.50–1.02; p trend = 0.037) and 0.63 (95% CI 0.38–1.03; p trend = 0.048) among subjects detected by subjective symptoms. No association was found between the traditional dietary pattern and prostate cancer risk among our subjects.
Conclusion
Our results suggest that a western-style diet may lead to a higher risk of prostate cancer in the total population, whereas the prudent diet contributes to a lower risk among subjects detected by subjective symptoms.
from Cancer via ola Kala on Inoreader https://ift.tt/2JUe8qI
via IFTTT
Hormone replacement therapy, mammographic density, and breast cancer risk: a cohort study
Abstract
Purpose
Hormone replacement therapy (HRT) use increases breast cancer risk and mammographic density (MD). We examine whether MD mediates or modifies the association of HRT with the breast cancer.
Methods
For the 4,501 participants in the Danish diet, cancer and health cohort (1993–1997) who attended mammographic screening in Copenhagen (1993–2001), MD (mixed/dense or fatty) was assessed at the first screening after cohort entry. HRT use was assessed by questionnaire and breast cancer diagnoses until 2012 obtained from the Danish cancer registry. The associations of HRT with MD and with breast cancer were analyzed separately using Cox's regression. Mediation analyses were used to estimate proportion [with 95% confidence intervals (CI)] of an association between HRT and breast cancer mediated by MD.
Results
2,444 (54.3%) women had mixed/dense breasts, 229 (5.4%) developed breast cancer, and 35.9% were current HRT users at enrollment. Compared to never users, current HRT use was statistically significantly associated with having mixed/dense breasts (relative risk and 95% CI 1.24; 1.14–1.35), and higher risk of breast cancer (hazard ratio 1.87; 1.40–2.48). Association between current HRT use and breast cancer risk was partially mediated by MD (percent mediated = 10%; 95% CI 4–22%). The current HRT use-related breast cancer risk was higher in women with mixed/dense (1.94; 1.37–3.87) than fatty (1.37; 0.80–2.35) breasts (p value for interaction = 0.15).
Conclusions
MD partially mediates some of the association between HRT and breast cancer risk. The association between HRT and breast cancer seems to be stronger in women with dense breasts.
from Cancer via ola Kala on Inoreader https://ift.tt/2J2Fp9m
via IFTTT
Self-reported dietary flavonoid intake and serum markers of inflammation: the multiethnic cohort
Abstract
Purpose
To examine if dietary intake of foods rich in flavonoids, which have been shown to be inversely associated with chronic diseases, is associated with inflammatory processes.
Methods
This analysis includes controls of case–control studies nested within the Multiethnic Cohort (MEC) who completed a validated food frequency questionnaire at cohort entry. Biomarkers were assessed in blood donated during follow-up (mean = 9.6 years). We used multivariate linear regression adjusted for potential confounders to estimate associations between intake of flavanones, flavonols, and isoflavones and levels of adiponectin, leptin, C-reactive protein, interleukin (IL)-1β, IL-6, IL-10, and tumor necrosis factor-α.
Results
Among the 1,287 participants, the respective median intakes of flavanones, flavonols, and isoflavones were 26.5, 12.4, and 1.3 mg/day at cohort entry. With the exception of flavanone intake, which was statistically significantly inversely associated with adiponectin (p = 0.01) and IL-6 concentrations (p = 0.01), none of the examined flavonoids was related with levels of adipokines or inflammatory markers. Heterogeneity by ethnicity was only observed for flavonol intake and IL-10 (pinteraction = 0.04) and may be the result of multiple testing. These null findings were confirmed in a subset of participants who completed a second dietary history within 2.6 years of blood draw.
Conclusion
The current results do not support a consistent association between dietary intake of flavonoids and markers of inflammatory processes.
from Cancer via ola Kala on Inoreader https://ift.tt/2EXstyV
via IFTTT
Laparoscopic paraaortic surgical staging in locally advanced cervical cancer: a single-center experience
Abstract
Background
One aim of this study was to assess the efficacy and safety of laparoscopic paraaortic lymphadenectomy for paraaortic lymph node staging in locally advanced cervical carcinoma. The second aim was to identify prognostic factors in the evolution of this disease and to evaluate how the results of the surgery modify the oncological treatment of patients.
Materials and methods
We analyzed 59 patients diagnosed with locally advanced cervical cancer International Federation of Gynecology and Obstetrics stage IB2–IVA who underwent laparoscopic paraaortic lymphadenectomy at our hospital between 2009 and 2015. Depending on the results of the paraaortic lymphadenectomy, treatment consisted of pelvic- or extended-field chemoradiotherapy.
Results
The mean age at diagnosis was 52.3 years. The median operative time was 180 min. The mean hospital stay was 1.7 days. The mean number of paraaortic lymph nodes excised was 16.4. Eight patients (13.5%) had positive paraaortic lymph nodes. Thirteen patients (22%) underwent surgery via the transperitoneal route, and 46 (78%) underwent surgery via the retroperitoneal route. The sensitivity and specificity of computerized axial tomography (CT) scanning for detecting paraaortic lymph node involvement was 75 and 86%, respectively. The statistically significant prognostic factors that affected survival were surgical paraaortic lymph node involvement, radiological pelvic lymph node involvement, and radiological tumor size as assessed with nuclear magnetic resonance. The rate of serious complications was 1.7%.
Conclusions
Pretherapeutic laparoscopic paraaortic lymphadenectomy for locally advanced cervical carcinoma allows the adaption of radiotherapy fields to avoid false-positive and false-negative imaging results.
https://ift.tt/2qHhZPT
Prognostic value of Ki-67 according to age in patients with triple-negative breast cancer
Abstract
Purpose
The prognostic value of Ki-67 in triple-negative breast cancer (TNBC) is yet unclear because the cut-off points employed differ widely and its predictive effect may vary according to age. The purpose of this study was to analyze the role of Ki-67 among patients with TNBC, and determine the optimal Ki-67 cut-off point to demonstrate its prognostic relevance associated with patient age and treatment strategy.
Methods/patients
201 consecutive patients treated for primary TNBC from 1999 to 2014 were analyzed. Clinicopathological characteristics and outcomes were compared between patients treated with neoadjuvant or adjuvant chemotherapy. We used time-dependent receiver operating characteristic (ROC) curve and time-dependent area under the ROC curve (AUC) to evaluate the discriminative ability of Ki-67 at 3 and 5 years of follow-up. A Ki-67 cut-off point that maximized sensibility and specificity was established. Interaction effect between age and Ki-67 on disease-free survival (DFS) and overall survival (OS) was evaluated by stratified analysis.
Results
According to the coordinates of the ROC curves, the best cut-off point for Ki-67 was 60% (high/low). In the whole group, there was not a statistically significant association between Ki-67 and OS and DFS, using a cut-off point of 60%. In multivariate analysis (COX proportional hazards regression), for DFS high Ki-67 (> 60%) was a poor prognostic factor in patients > 40 years old and a better prognostic factor among the patients < 40 years old.
Conclusion
Prognostic value of Ki-67 in TNBC, using a cut-off point of 60%, may vary depending on age.
https://ift.tt/2vsBQY0
Laparoscopic paraaortic surgical staging in locally advanced cervical cancer: a single-center experience
Abstract
Background
One aim of this study was to assess the efficacy and safety of laparoscopic paraaortic lymphadenectomy for paraaortic lymph node staging in locally advanced cervical carcinoma. The second aim was to identify prognostic factors in the evolution of this disease and to evaluate how the results of the surgery modify the oncological treatment of patients.
Materials and methods
We analyzed 59 patients diagnosed with locally advanced cervical cancer International Federation of Gynecology and Obstetrics stage IB2–IVA who underwent laparoscopic paraaortic lymphadenectomy at our hospital between 2009 and 2015. Depending on the results of the paraaortic lymphadenectomy, treatment consisted of pelvic- or extended-field chemoradiotherapy.
Results
The mean age at diagnosis was 52.3 years. The median operative time was 180 min. The mean hospital stay was 1.7 days. The mean number of paraaortic lymph nodes excised was 16.4. Eight patients (13.5%) had positive paraaortic lymph nodes. Thirteen patients (22%) underwent surgery via the transperitoneal route, and 46 (78%) underwent surgery via the retroperitoneal route. The sensitivity and specificity of computerized axial tomography (CT) scanning for detecting paraaortic lymph node involvement was 75 and 86%, respectively. The statistically significant prognostic factors that affected survival were surgical paraaortic lymph node involvement, radiological pelvic lymph node involvement, and radiological tumor size as assessed with nuclear magnetic resonance. The rate of serious complications was 1.7%.
Conclusions
Pretherapeutic laparoscopic paraaortic lymphadenectomy for locally advanced cervical carcinoma allows the adaption of radiotherapy fields to avoid false-positive and false-negative imaging results.
from Cancer via ola Kala on Inoreader https://ift.tt/2qHhZPT
via IFTTT
Prognostic value of Ki-67 according to age in patients with triple-negative breast cancer
Abstract
Purpose
The prognostic value of Ki-67 in triple-negative breast cancer (TNBC) is yet unclear because the cut-off points employed differ widely and its predictive effect may vary according to age. The purpose of this study was to analyze the role of Ki-67 among patients with TNBC, and determine the optimal Ki-67 cut-off point to demonstrate its prognostic relevance associated with patient age and treatment strategy.
Methods/patients
201 consecutive patients treated for primary TNBC from 1999 to 2014 were analyzed. Clinicopathological characteristics and outcomes were compared between patients treated with neoadjuvant or adjuvant chemotherapy. We used time-dependent receiver operating characteristic (ROC) curve and time-dependent area under the ROC curve (AUC) to evaluate the discriminative ability of Ki-67 at 3 and 5 years of follow-up. A Ki-67 cut-off point that maximized sensibility and specificity was established. Interaction effect between age and Ki-67 on disease-free survival (DFS) and overall survival (OS) was evaluated by stratified analysis.
Results
According to the coordinates of the ROC curves, the best cut-off point for Ki-67 was 60% (high/low). In the whole group, there was not a statistically significant association between Ki-67 and OS and DFS, using a cut-off point of 60%. In multivariate analysis (COX proportional hazards regression), for DFS high Ki-67 (> 60%) was a poor prognostic factor in patients > 40 years old and a better prognostic factor among the patients < 40 years old.
Conclusion
Prognostic value of Ki-67 in TNBC, using a cut-off point of 60%, may vary depending on age.
from Cancer via ola Kala on Inoreader https://ift.tt/2vsBQY0
via IFTTT
Ambient benzene at the residence and risk for subtypes of childhood leukemia, lymphoma and CNS tumor
International Journal of Cancer, EarlyView.
from Cancer via ola Kala on Inoreader https://ift.tt/2qI84ch
via IFTTT
Ambient benzene at the residence and risk for subtypes of childhood leukemia, lymphoma and CNS tumor
International Journal of Cancer, EarlyView.
https://ift.tt/2qI84ch
Laparoscopic paraaortic surgical staging in locally advanced cervical cancer: a single-center experience
Abstract
Background
One aim of this study was to assess the efficacy and safety of laparoscopic paraaortic lymphadenectomy for paraaortic lymph node staging in locally advanced cervical carcinoma. The second aim was to identify prognostic factors in the evolution of this disease and to evaluate how the results of the surgery modify the oncological treatment of patients.
Materials and methods
We analyzed 59 patients diagnosed with locally advanced cervical cancer International Federation of Gynecology and Obstetrics stage IB2–IVA who underwent laparoscopic paraaortic lymphadenectomy at our hospital between 2009 and 2015. Depending on the results of the paraaortic lymphadenectomy, treatment consisted of pelvic- or extended-field chemoradiotherapy.
Results
The mean age at diagnosis was 52.3 years. The median operative time was 180 min. The mean hospital stay was 1.7 days. The mean number of paraaortic lymph nodes excised was 16.4. Eight patients (13.5%) had positive paraaortic lymph nodes. Thirteen patients (22%) underwent surgery via the transperitoneal route, and 46 (78%) underwent surgery via the retroperitoneal route. The sensitivity and specificity of computerized axial tomography (CT) scanning for detecting paraaortic lymph node involvement was 75 and 86%, respectively. The statistically significant prognostic factors that affected survival were surgical paraaortic lymph node involvement, radiological pelvic lymph node involvement, and radiological tumor size as assessed with nuclear magnetic resonance. The rate of serious complications was 1.7%.
Conclusions
Pretherapeutic laparoscopic paraaortic lymphadenectomy for locally advanced cervical carcinoma allows the adaption of radiotherapy fields to avoid false-positive and false-negative imaging results.
from Cancer via ola Kala on Inoreader https://ift.tt/2qHhZPT
via IFTTT
Prognostic value of Ki-67 according to age in patients with triple-negative breast cancer
Abstract
Purpose
The prognostic value of Ki-67 in triple-negative breast cancer (TNBC) is yet unclear because the cut-off points employed differ widely and its predictive effect may vary according to age. The purpose of this study was to analyze the role of Ki-67 among patients with TNBC, and determine the optimal Ki-67 cut-off point to demonstrate its prognostic relevance associated with patient age and treatment strategy.
Methods/patients
201 consecutive patients treated for primary TNBC from 1999 to 2014 were analyzed. Clinicopathological characteristics and outcomes were compared between patients treated with neoadjuvant or adjuvant chemotherapy. We used time-dependent receiver operating characteristic (ROC) curve and time-dependent area under the ROC curve (AUC) to evaluate the discriminative ability of Ki-67 at 3 and 5 years of follow-up. A Ki-67 cut-off point that maximized sensibility and specificity was established. Interaction effect between age and Ki-67 on disease-free survival (DFS) and overall survival (OS) was evaluated by stratified analysis.
Results
According to the coordinates of the ROC curves, the best cut-off point for Ki-67 was 60% (high/low). In the whole group, there was not a statistically significant association between Ki-67 and OS and DFS, using a cut-off point of 60%. In multivariate analysis (COX proportional hazards regression), for DFS high Ki-67 (> 60%) was a poor prognostic factor in patients > 40 years old and a better prognostic factor among the patients < 40 years old.
Conclusion
Prognostic value of Ki-67 in TNBC, using a cut-off point of 60%, may vary depending on age.
from Cancer via ola Kala on Inoreader https://ift.tt/2vsBQY0
via IFTTT
Laparoscopic paraaortic surgical staging in locally advanced cervical cancer: a single-center experience
Abstract
Background
One aim of this study was to assess the efficacy and safety of laparoscopic paraaortic lymphadenectomy for paraaortic lymph node staging in locally advanced cervical carcinoma. The second aim was to identify prognostic factors in the evolution of this disease and to evaluate how the results of the surgery modify the oncological treatment of patients.
Materials and methods
We analyzed 59 patients diagnosed with locally advanced cervical cancer International Federation of Gynecology and Obstetrics stage IB2–IVA who underwent laparoscopic paraaortic lymphadenectomy at our hospital between 2009 and 2015. Depending on the results of the paraaortic lymphadenectomy, treatment consisted of pelvic- or extended-field chemoradiotherapy.
Results
The mean age at diagnosis was 52.3 years. The median operative time was 180 min. The mean hospital stay was 1.7 days. The mean number of paraaortic lymph nodes excised was 16.4. Eight patients (13.5%) had positive paraaortic lymph nodes. Thirteen patients (22%) underwent surgery via the transperitoneal route, and 46 (78%) underwent surgery via the retroperitoneal route. The sensitivity and specificity of computerized axial tomography (CT) scanning for detecting paraaortic lymph node involvement was 75 and 86%, respectively. The statistically significant prognostic factors that affected survival were surgical paraaortic lymph node involvement, radiological pelvic lymph node involvement, and radiological tumor size as assessed with nuclear magnetic resonance. The rate of serious complications was 1.7%.
Conclusions
Pretherapeutic laparoscopic paraaortic lymphadenectomy for locally advanced cervical carcinoma allows the adaption of radiotherapy fields to avoid false-positive and false-negative imaging results.
https://ift.tt/2qHhZPT
Prognostic value of Ki-67 according to age in patients with triple-negative breast cancer
Abstract
Purpose
The prognostic value of Ki-67 in triple-negative breast cancer (TNBC) is yet unclear because the cut-off points employed differ widely and its predictive effect may vary according to age. The purpose of this study was to analyze the role of Ki-67 among patients with TNBC, and determine the optimal Ki-67 cut-off point to demonstrate its prognostic relevance associated with patient age and treatment strategy.
Methods/patients
201 consecutive patients treated for primary TNBC from 1999 to 2014 were analyzed. Clinicopathological characteristics and outcomes were compared between patients treated with neoadjuvant or adjuvant chemotherapy. We used time-dependent receiver operating characteristic (ROC) curve and time-dependent area under the ROC curve (AUC) to evaluate the discriminative ability of Ki-67 at 3 and 5 years of follow-up. A Ki-67 cut-off point that maximized sensibility and specificity was established. Interaction effect between age and Ki-67 on disease-free survival (DFS) and overall survival (OS) was evaluated by stratified analysis.
Results
According to the coordinates of the ROC curves, the best cut-off point for Ki-67 was 60% (high/low). In the whole group, there was not a statistically significant association between Ki-67 and OS and DFS, using a cut-off point of 60%. In multivariate analysis (COX proportional hazards regression), for DFS high Ki-67 (> 60%) was a poor prognostic factor in patients > 40 years old and a better prognostic factor among the patients < 40 years old.
Conclusion
Prognostic value of Ki-67 in TNBC, using a cut-off point of 60%, may vary depending on age.
https://ift.tt/2vsBQY0
Prognostic value of systemic inflammatory markers in ovarian Cancer: a PRISMA-compliant meta-analysis and systematic review
Abstract
Background
The prognostic effect of elevated systemic inflammatory markers, including neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR), remains controversial in cancer patients. This meta-analysis was conducted to evaluate the predictive values of these markers for prognoses in ovarian cancer patients.
Methods
Potentially relevant publications in PubMed, ISI Web of Science, and EBSCO were searched. Pooled hazard ratios (HRs) and corresponding 95% confidence intervals (95% CIs) for overall survival (OS) and progression-free survival (PFS) were determined using a fixed or random effects model.
Results
Ten studies involving 2919 patients were included in this meta-analysis. In multivariate analysis, the group with higher NLR had worse OS (HR = 1.34, 95% CI = 1.16-1.54) and shorter PFS (HR = 1.36, 95% CI = 1.17-1.57) than the control group. Furthermore, PLR values higher than the cut-off were associated with not only poorer OS (HR = 1.97, 95% CI = 1.61-2.40) but also more unfavorable PFS (HR = 1.79, 95% CI = 1.46-2.20). Univariate analysis also indicated the same results. Additionally, subgroup analysis showed that when the cut-off values for NLR and PLR were higher, their predictive effects became stronger.
Conclusion
This comprehensive meta-analysis suggested that the values of inflammatory markers such as NLR and PLR were associated with ovarian cancer survival. Therefore, inflammatory markers can potentially serve as prognostic biomarkers.
https://ift.tt/2HtZUyn
Predictive values of upper gastrointestinal cancer alarm symptoms in the general population: a nationwide cohort study
Abstract
Background
Survival rates for upper gastrointestinal (GI) cancer are poor since many are diagnosed at advanced stages. Fast track endoscopy has been introduced to prompt diagnosis for patients with alarm symptoms that could be indicative of upper GI cancer. However, these symptoms may represent benign conditions and little is known about the predictive values of alarm symptoms of upper GI cancer in the general population.
Methods
The study is a nationwide cohort study of 60,562 individuals aged 45 years or above randomly selected from the Danish general population. Participants were invited to complete a survey comprising of questions on several symptom experiences, including alarm symptoms for upper GI cancer within the past four weeks. The participants were asked about specific symptoms (repeated vomiting, difficulty swallowing, signs of upper GI bleeding or persistent and recent-onset abdominal pain) and non-specific symptoms (nausea, weight loss, loss of appetite, feeling unwell and tiredness).
We obtained information on upper GI cancer diagnosed in a 12-month period after completing the questionnaire from the Danish Cancer Registry. We calculated positive predictive values and positive likelihood ratios for the association between alarm symptom and subsequent upper GI cancer.
Results
A total of 33,040 individuals above 45 years completed the questionnaire, yielding a response rate of 54.6%. Respondents were fairly respresentative of the study sample. During the follow-up period, 18 people were diagnosed with upper GI cancer. The number of incident cancers was similar among eligible non-respondents. Two thirds of the respondents with an upper GI malignancy had experienced one or more alarm symptoms.
The positive predictive value for being diagnosed with upper GI cancer after reporting a least one alarm symptom was 0.1% (95% CI:0.0–0.1%). The positive likelihood ratio was 4.4 for specific alarm symptoms and 1.1 for non-specific alarm symptoms.
Conclusions
We found that positive predictive values of alarm symptoms of upper GI cancer experienced in the general population are low. It is important knowledge that despite denoted alarm symptoms even patients with specific alarm symptoms of upper GI cancer have a low risk of being diagnosed with upper GI cancer.
https://ift.tt/2vqS0Rx
Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) for the treatment of malignant mesothelioma
Abstract
Background
Patients with recurrent malignant epithelioid mesothelioma (MM) after surgery and standard chemotherapy with cisplatin and pemetrexed have limited treatment options.
Methods
We performed a retrospective cohort study of patients with recurrent MM undergoing Pressurized IntraPeritoneal/Thoracal Aerosol Chemotherapy (PIPAC/PITAC) with doxorubicin 1.5 mg/m2 and cisplatin 7.5 mg/m2. Data were retrospectively collected in a prospective registry of patients undergoing PIPAC/PITAC. Study outcomes were microscopic tumor regression grade (TRG), survival and adverse events (v4.0 CTCAE).
Results
A total of 29 patients (m/f = 17/12) with MM with a mean age of 62.4 (range: 42 to 84) years were analyzed. A total of 74 PIPAC and 5 PITAC procedures were performed. The mean number of PIPAC applications was 2.5 (range: 0 to 10) per patient. Twenty patients (69%) had > 2 PIPAC procedure and were eligible for TRG analysis. TRG 1 to 4 was observed in 75% (15/20) of patients. Major regression (TRG 3) or complete regression (TRG 4) was observed in 20% and 10%, respectively. PIPAC induced significant tumor regression in 51.7% (15/29) of patients with a cumulative effect after repetitive PIPACs (PIPAC #1 vs. PIPAC #2: p = 0.001; PIPAC #1 vs. PIPAC #3: p = 0.001; PIPAC #1 vs. PIPAC #4: p = 0.001). Postoperative CTCAE grade 4 complications were observed in two patients (6.9%) who had cytoreductive surgery (CC2) and intraoperative PIPAC. One patient (3.4%) died due to postoperative kidney insufficiency. After a follow up of 14.4 (95% CI: 8.1 to 20.7) months after the last PIPAC/PITAC application, median overall survival was 26.6 (95% CI: 9.5 to 43.7) months (from the first application).
Conclusion
After prior abdominal surgery and systemic chemotherapy, repetitive PIPAC applications are feasible and safe for patients with end-stage MM. Furthermore, PIPAC induces significant histological regression of malignant mesothelioma in the majority of patients. PITAC is feasible, but its safety and efficacy to control malignant pleural effusion remain unclear.
https://ift.tt/2qIBKGT
Salivary extracellular vesicle-associated miRNAs as potential biomarkers in oral squamous cell carcinoma
Abstract
Background
Several studies in the past have investigated the expression of micro RNAs (miRNAs) in saliva as potential biomarkers. Since miRNAs associated with extracellular vesicles (EVs) are known to be protected from enzymatic degradation, we evaluated whether salivary EVs from patients with oral squamous cell carcinoma (OSCC) were enriched with specific subsets of miRNAs.
Methods
OSCC patients and controls were matched with regards to age, gender and risk factors. Total RNA was extracted from salivary EVs and the differential expression of miRNAs was evaluated by qRT-PCR array and qRT-PCR. The discrimination power of up-regulated miRNAs as biomarkers in OSCC patients versus controls was evaluated by the Receiver Operating Characteristic (ROC) curves.
Results
A preliminary qRT-PCR array was performed on samples from 5 OSCC patients and 5 healthy controls whereby a subset of miRNAs were identified that were differentially expressed. On the basis of these results, a cohort of additional 16 patients and 6 controls were analyzed to further confirm the miRNAs that were up-regulated or selectively expressed in the previous pilot study. The following miRNAs: miR-302b-3p and miR-517b-3p were expressed only in EVs from OSCC patients and miR-512-3p and miR-412-3p were up-regulated in salivary EVs from OSCC patients compared to controls with the ROC curve showing a good discrimination power for OSCC diagnosis. The Kyoto Encyclopedia of Gene and Genomes (KEGG) pathway analysis suggested the possible involvement of the miRNAs identified in pathways activated in OSCC.
Conclusions
In this work, we suggest that salivary EVs isolated by a simple charge-based precipitation technique can be exploited as a non-invasive source of miRNAs for OSCC diagnosis. Moreover, we have identified a subset of miRNAs selectively enriched in EVs of OSCC patients that could be potential biomarkers.
https://ift.tt/2vrTVpb
Improving quality of life through the routine use of the patient concerns inventory for head and neck cancer patients: a cluster preference randomized controlled trial
Abstract
Background
The consequences of treatment for Head and Neck cancer (HNC) patients has profound detrimental impacts such as impaired QOL, emotional distress, delayed recovery and frequent use of healthcare. The aim of this trial is to determine if the routine use of the Patients Concerns Inventory (PCI) package in review clinics during the first year following treatment can improve overall quality of life, reduce the social-emotional impact of cancer and reduce levels of distress. Furthermore, we aim to describe the economic costs and benefits of using the PCI.
Methods
This will be a cluster preference randomised control trial with consultants either 'using' or 'not using' the PCI package at clinic. It will involve two centres Leeds and Liverpool. 416 eligible patients from at least 10 consultant clusters are required to show a clinically meaningful difference in the primary outcome. The primary outcome is the percentage of participants with less than good overall quality of life at the final one-year clinic as measured by the University of Washington QOL questionnaire version 4 (UWQOLv4). Secondary outcomes at one-year are the mean social-emotional subscale (UWQOLv4) score, Distress Thermometer (DT) score ≥ 4, and key health economic measures (QALY-EQ-5D-5 L; CSRI).
Discussion
This trial will provide knowledge on the effectiveness of a consultation intervention package based around the PCI used at routine follow-up clinics following treatment of head and neck cancer with curative intent. If this intervention is (cost) effective for patients, the next step will be to promote wider use of this approach as standard care in clinical practice.
Trial registration
32,382. Clinical Trials Identifier, NCT03086629. Protocol: Version 3.0, 1st July 2017.
https://ift.tt/2HAEMGP
Small cell and non small cell lung cancer form metastasis on cellular 4D lung model
Abstract
Background
Metastasis is the main cause of death for lung cancer patients. The ex vivo 4D acellular lung model has been shown to mimic this metastatic process. However, the main concern is the model's lack of cellular components of the tumor's microenvironment. In this study, we aim to determine if the intact lung microenvironment will still allow lung cancer metastasis to form.
Methods
We harvested a heart-lung block from a rat and placed it in a bioreactor after cannulating the pulmonary artery, trachea and tying the right main bronchus for 10–15 days without any tumor cells as a control group or with NSCLC (A549, H1299 or H460), SCLC (H69, H446 or SHP77) or breast cancer cell lines (MCF7 or MDAMB231) through the trachea. We performed lobectomy, H&E staining and IHC for human mitochondria to determine the primary tumor's growth and formation of metastatic lesions. In addition, we isolated circulating tumor cells (CTC) from the model seeded with GFP tagged cells.
Results
In the control group, no gross tumor nodules were found, H&E staining showed hyperplastic cells and IHC showed no staining for human mitochondria. All of the models seeded with cancer cell lines formed gross primary tumor nodules that had microscopic characteristics of human cancer cells on H&E staining with IHC showing staining for human mitochondria. CTC were isolated for those cells labeled with GFP and they were viable in culture. Finally, all cell lines formed metastatic lesions with cells stained for human mitochondria.
Conclusion
The cellular ex vivo 4D model shows that human cancer cells can form a primary tumor, CTC and metastatic lesions in an intact cellular environment. This study suggests that the natural matrix scaffold is the only necessary component to drive metastatic progression and that cellular components play a role in modulating tumor progression.
https://ift.tt/2J4idaG
Prognostic value of systemic inflammatory markers in ovarian Cancer: a PRISMA-compliant meta-analysis and systematic review
Abstract
Background
The prognostic effect of elevated systemic inflammatory markers, including neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR), remains controversial in cancer patients. This meta-analysis was conducted to evaluate the predictive values of these markers for prognoses in ovarian cancer patients.
Methods
Potentially relevant publications in PubMed, ISI Web of Science, and EBSCO were searched. Pooled hazard ratios (HRs) and corresponding 95% confidence intervals (95% CIs) for overall survival (OS) and progression-free survival (PFS) were determined using a fixed or random effects model.
Results
Ten studies involving 2919 patients were included in this meta-analysis. In multivariate analysis, the group with higher NLR had worse OS (HR = 1.34, 95% CI = 1.16-1.54) and shorter PFS (HR = 1.36, 95% CI = 1.17-1.57) than the control group. Furthermore, PLR values higher than the cut-off were associated with not only poorer OS (HR = 1.97, 95% CI = 1.61-2.40) but also more unfavorable PFS (HR = 1.79, 95% CI = 1.46-2.20). Univariate analysis also indicated the same results. Additionally, subgroup analysis showed that when the cut-off values for NLR and PLR were higher, their predictive effects became stronger.
Conclusion
This comprehensive meta-analysis suggested that the values of inflammatory markers such as NLR and PLR were associated with ovarian cancer survival. Therefore, inflammatory markers can potentially serve as prognostic biomarkers.
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Predictive values of upper gastrointestinal cancer alarm symptoms in the general population: a nationwide cohort study
Abstract
Background
Survival rates for upper gastrointestinal (GI) cancer are poor since many are diagnosed at advanced stages. Fast track endoscopy has been introduced to prompt diagnosis for patients with alarm symptoms that could be indicative of upper GI cancer. However, these symptoms may represent benign conditions and little is known about the predictive values of alarm symptoms of upper GI cancer in the general population.
Methods
The study is a nationwide cohort study of 60,562 individuals aged 45 years or above randomly selected from the Danish general population. Participants were invited to complete a survey comprising of questions on several symptom experiences, including alarm symptoms for upper GI cancer within the past four weeks. The participants were asked about specific symptoms (repeated vomiting, difficulty swallowing, signs of upper GI bleeding or persistent and recent-onset abdominal pain) and non-specific symptoms (nausea, weight loss, loss of appetite, feeling unwell and tiredness).
We obtained information on upper GI cancer diagnosed in a 12-month period after completing the questionnaire from the Danish Cancer Registry. We calculated positive predictive values and positive likelihood ratios for the association between alarm symptom and subsequent upper GI cancer.
Results
A total of 33,040 individuals above 45 years completed the questionnaire, yielding a response rate of 54.6%. Respondents were fairly respresentative of the study sample. During the follow-up period, 18 people were diagnosed with upper GI cancer. The number of incident cancers was similar among eligible non-respondents. Two thirds of the respondents with an upper GI malignancy had experienced one or more alarm symptoms.
The positive predictive value for being diagnosed with upper GI cancer after reporting a least one alarm symptom was 0.1% (95% CI:0.0–0.1%). The positive likelihood ratio was 4.4 for specific alarm symptoms and 1.1 for non-specific alarm symptoms.
Conclusions
We found that positive predictive values of alarm symptoms of upper GI cancer experienced in the general population are low. It is important knowledge that despite denoted alarm symptoms even patients with specific alarm symptoms of upper GI cancer have a low risk of being diagnosed with upper GI cancer.
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Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) for the treatment of malignant mesothelioma
Abstract
Background
Patients with recurrent malignant epithelioid mesothelioma (MM) after surgery and standard chemotherapy with cisplatin and pemetrexed have limited treatment options.
Methods
We performed a retrospective cohort study of patients with recurrent MM undergoing Pressurized IntraPeritoneal/Thoracal Aerosol Chemotherapy (PIPAC/PITAC) with doxorubicin 1.5 mg/m2 and cisplatin 7.5 mg/m2. Data were retrospectively collected in a prospective registry of patients undergoing PIPAC/PITAC. Study outcomes were microscopic tumor regression grade (TRG), survival and adverse events (v4.0 CTCAE).
Results
A total of 29 patients (m/f = 17/12) with MM with a mean age of 62.4 (range: 42 to 84) years were analyzed. A total of 74 PIPAC and 5 PITAC procedures were performed. The mean number of PIPAC applications was 2.5 (range: 0 to 10) per patient. Twenty patients (69%) had > 2 PIPAC procedure and were eligible for TRG analysis. TRG 1 to 4 was observed in 75% (15/20) of patients. Major regression (TRG 3) or complete regression (TRG 4) was observed in 20% and 10%, respectively. PIPAC induced significant tumor regression in 51.7% (15/29) of patients with a cumulative effect after repetitive PIPACs (PIPAC #1 vs. PIPAC #2: p = 0.001; PIPAC #1 vs. PIPAC #3: p = 0.001; PIPAC #1 vs. PIPAC #4: p = 0.001). Postoperative CTCAE grade 4 complications were observed in two patients (6.9%) who had cytoreductive surgery (CC2) and intraoperative PIPAC. One patient (3.4%) died due to postoperative kidney insufficiency. After a follow up of 14.4 (95% CI: 8.1 to 20.7) months after the last PIPAC/PITAC application, median overall survival was 26.6 (95% CI: 9.5 to 43.7) months (from the first application).
Conclusion
After prior abdominal surgery and systemic chemotherapy, repetitive PIPAC applications are feasible and safe for patients with end-stage MM. Furthermore, PIPAC induces significant histological regression of malignant mesothelioma in the majority of patients. PITAC is feasible, but its safety and efficacy to control malignant pleural effusion remain unclear.
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Salivary extracellular vesicle-associated miRNAs as potential biomarkers in oral squamous cell carcinoma
Abstract
Background
Several studies in the past have investigated the expression of micro RNAs (miRNAs) in saliva as potential biomarkers. Since miRNAs associated with extracellular vesicles (EVs) are known to be protected from enzymatic degradation, we evaluated whether salivary EVs from patients with oral squamous cell carcinoma (OSCC) were enriched with specific subsets of miRNAs.
Methods
OSCC patients and controls were matched with regards to age, gender and risk factors. Total RNA was extracted from salivary EVs and the differential expression of miRNAs was evaluated by qRT-PCR array and qRT-PCR. The discrimination power of up-regulated miRNAs as biomarkers in OSCC patients versus controls was evaluated by the Receiver Operating Characteristic (ROC) curves.
Results
A preliminary qRT-PCR array was performed on samples from 5 OSCC patients and 5 healthy controls whereby a subset of miRNAs were identified that were differentially expressed. On the basis of these results, a cohort of additional 16 patients and 6 controls were analyzed to further confirm the miRNAs that were up-regulated or selectively expressed in the previous pilot study. The following miRNAs: miR-302b-3p and miR-517b-3p were expressed only in EVs from OSCC patients and miR-512-3p and miR-412-3p were up-regulated in salivary EVs from OSCC patients compared to controls with the ROC curve showing a good discrimination power for OSCC diagnosis. The Kyoto Encyclopedia of Gene and Genomes (KEGG) pathway analysis suggested the possible involvement of the miRNAs identified in pathways activated in OSCC.
Conclusions
In this work, we suggest that salivary EVs isolated by a simple charge-based precipitation technique can be exploited as a non-invasive source of miRNAs for OSCC diagnosis. Moreover, we have identified a subset of miRNAs selectively enriched in EVs of OSCC patients that could be potential biomarkers.
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Improving quality of life through the routine use of the patient concerns inventory for head and neck cancer patients: a cluster preference randomized controlled trial
Abstract
Background
The consequences of treatment for Head and Neck cancer (HNC) patients has profound detrimental impacts such as impaired QOL, emotional distress, delayed recovery and frequent use of healthcare. The aim of this trial is to determine if the routine use of the Patients Concerns Inventory (PCI) package in review clinics during the first year following treatment can improve overall quality of life, reduce the social-emotional impact of cancer and reduce levels of distress. Furthermore, we aim to describe the economic costs and benefits of using the PCI.
Methods
This will be a cluster preference randomised control trial with consultants either 'using' or 'not using' the PCI package at clinic. It will involve two centres Leeds and Liverpool. 416 eligible patients from at least 10 consultant clusters are required to show a clinically meaningful difference in the primary outcome. The primary outcome is the percentage of participants with less than good overall quality of life at the final one-year clinic as measured by the University of Washington QOL questionnaire version 4 (UWQOLv4). Secondary outcomes at one-year are the mean social-emotional subscale (UWQOLv4) score, Distress Thermometer (DT) score ≥ 4, and key health economic measures (QALY-EQ-5D-5 L; CSRI).
Discussion
This trial will provide knowledge on the effectiveness of a consultation intervention package based around the PCI used at routine follow-up clinics following treatment of head and neck cancer with curative intent. If this intervention is (cost) effective for patients, the next step will be to promote wider use of this approach as standard care in clinical practice.
Trial registration
32,382. Clinical Trials Identifier, NCT03086629. Protocol: Version 3.0, 1st July 2017.
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Small cell and non small cell lung cancer form metastasis on cellular 4D lung model
Abstract
Background
Metastasis is the main cause of death for lung cancer patients. The ex vivo 4D acellular lung model has been shown to mimic this metastatic process. However, the main concern is the model's lack of cellular components of the tumor's microenvironment. In this study, we aim to determine if the intact lung microenvironment will still allow lung cancer metastasis to form.
Methods
We harvested a heart-lung block from a rat and placed it in a bioreactor after cannulating the pulmonary artery, trachea and tying the right main bronchus for 10–15 days without any tumor cells as a control group or with NSCLC (A549, H1299 or H460), SCLC (H69, H446 or SHP77) or breast cancer cell lines (MCF7 or MDAMB231) through the trachea. We performed lobectomy, H&E staining and IHC for human mitochondria to determine the primary tumor's growth and formation of metastatic lesions. In addition, we isolated circulating tumor cells (CTC) from the model seeded with GFP tagged cells.
Results
In the control group, no gross tumor nodules were found, H&E staining showed hyperplastic cells and IHC showed no staining for human mitochondria. All of the models seeded with cancer cell lines formed gross primary tumor nodules that had microscopic characteristics of human cancer cells on H&E staining with IHC showing staining for human mitochondria. CTC were isolated for those cells labeled with GFP and they were viable in culture. Finally, all cell lines formed metastatic lesions with cells stained for human mitochondria.
Conclusion
The cellular ex vivo 4D model shows that human cancer cells can form a primary tumor, CTC and metastatic lesions in an intact cellular environment. This study suggests that the natural matrix scaffold is the only necessary component to drive metastatic progression and that cellular components play a role in modulating tumor progression.
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A novel method for demonstrating cold agglutinin disease: a case report
Cold agglutinin disease is a rare disorder characterized by an autoimmune hemolytic anemia occurring at low temperatures. Physical examination findings, often limited to acrocyanosis, are combined with a therm...
https://ift.tt/2HHIcVM
The CXCL5/CXCR2 axis contributes to the epithelial-mesenchymal transition of nasopharyngeal carcinoma cells by activating ERK/GSK-3β/snail signalling
Distant metastasis is the major cause of treatment failure in patients with nasopharyngeal carcinoma (NPC). Although several biomarkers correlate with metastasis and prognosis, the molecular mechanisms of NPC ...
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Cancers, Vol. 10, Pages 123: Innovative Diagnostic Methods for Early Prostate Cancer Detection through Urine Analysis: A Review
Cancers, Vol. 10, Pages 123: Innovative Diagnostic Methods for Early Prostate Cancer Detection through Urine Analysis: A Review
Cancers doi: 10.3390/cancers10040123
Authors: Carmen Bax Gianluigi Taverna Lidia Eusebio Selena Sironi Fabio Grizzi Giorgio Guazzoni Laura Capelli
Prostate cancer is the second most common cause of cancer death among men. It is an asymptomatic and slow growing tumour, which starts occurring in young men, but can be detected only around the age of 40–50. Although its long latency period and potential curability make prostate cancer a perfect candidate for screening programs, the current procedure lacks in specificity. Researchers are rising to the challenge of developing innovative tools able of detecting the disease during its early stage that is the most curable. In recent years, the interest in characterisation of biological fluids aimed at the identification of tumour-specific compounds has increased significantly, since cell neoplastic transformation causes metabolic alterations leading to volatile organic compounds release. In the scientific literature, different approaches have been proposed. Many studies focus on the identification of a cancer-characteristic “odour fingerprint” emanated from biological samples through the application of sensorial or senso-instrumental analyses, others suggest a chemical characterisation of biological fluids with the aim of identifying prostate cancer (PCa)-specific biomarkers. This paper focuses on the review of literary studies in the field of prostate cancer diagnosis, in order to provide an overview of innovative methods based on the analysis of urine, thereby comparing them with the traditional diagnostic procedures.
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Cancers, Vol. 10, Pages 123: Innovative Diagnostic Methods for Early Prostate Cancer Detection through Urine Analysis: A Review
Cancers, Vol. 10, Pages 123: Innovative Diagnostic Methods for Early Prostate Cancer Detection through Urine Analysis: A Review
Cancers doi: 10.3390/cancers10040123
Authors: Carmen Bax Gianluigi Taverna Lidia Eusebio Selena Sironi Fabio Grizzi Giorgio Guazzoni Laura Capelli
Prostate cancer is the second most common cause of cancer death among men. It is an asymptomatic and slow growing tumour, which starts occurring in young men, but can be detected only around the age of 40–50. Although its long latency period and potential curability make prostate cancer a perfect candidate for screening programs, the current procedure lacks in specificity. Researchers are rising to the challenge of developing innovative tools able of detecting the disease during its early stage that is the most curable. In recent years, the interest in characterisation of biological fluids aimed at the identification of tumour-specific compounds has increased significantly, since cell neoplastic transformation causes metabolic alterations leading to volatile organic compounds release. In the scientific literature, different approaches have been proposed. Many studies focus on the identification of a cancer-characteristic “odour fingerprint” emanated from biological samples through the application of sensorial or senso-instrumental analyses, others suggest a chemical characterisation of biological fluids with the aim of identifying prostate cancer (PCa)-specific biomarkers. This paper focuses on the review of literary studies in the field of prostate cancer diagnosis, in order to provide an overview of innovative methods based on the analysis of urine, thereby comparing them with the traditional diagnostic procedures.
https://ift.tt/2vx7X99
Regulatory T cells control endothelial chemokine production and migration of T cells into intestinal tumors of APC min/+ mice
Abstract
Tumor-infiltrating lymphocytes are crucial for anti-tumor immunity. We have previously shown that regulatory T cells (Treg) are able to reduce T-cell transendothelial migration in vitro and accumulation of effector T cells in intestinal tumors in vivo. Treg depletion also resulted in increased levels of the chemokines CXCL9 and CXCL10 specifically in the tumors. In this study, we investigated the mechanisms for Treg mediated suppression of T-cell migration into intestinal tumors in the APCmin/+ mouse model. By breeding APCmin/+ mice with DEREG mice, which harbour a high affinity diphtheria toxin receptor under the control of the FOXP3 promoter, we were able to deplete Treg in tumor-bearing mice. Using adoptive transfer experiments, we could document a markedly increased migration of T cells specifically into Treg depleted tumors, and that Treg depletion results in increased production of the CXCR3 ligand CXCL10 from endothelial cells in the tumors. Furthermore, we were able to demonstrate that T cells use CXCR3 to migrate into intestinal tumors. In addition, human colon adenocarcinomas express high levels of mRNA CXCR3 ligands and tumor endothelial cells produce CXCL9 and CXCL10 ex vivo. In conclusion, this study demonstrates that Treg reduce endothelial CXCL10 production, inhibit T-cell migration into tumors and that CXCR3 mediated signalling is crucial for lymphocyte accumulation in intestinal tumors. Thus, immunotherapy aimed at Treg depletion may be effective by increasing not only T effector cell activity, but also their accumulation in tumors.
https://ift.tt/2qDybRs
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