Cancer Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Κυριακή 4 Δεκεμβρίου 2016
Prognostic impact of MutT homolog-1 expression on esophageal squamous cell carcinoma
Abstract
MutT homolog-1 (MTH1) is a pyrophosphatase that acts on oxidized nucleotides and hydrolyzes 8-oxo-2'-deoxyguanosine triphosphate in deoxynucleoside triphosphate pool to prevent its incorporation into nuclear and mitochondrial DNA, result in reduce cytotoxicity in tumor cells. MTH1 is overexpressed in various cancers and is considered as a therapeutic target. Environmental factors such as cigarette smoking and alcohol consumption are critical risk factors for the development and progression of esophageal squamous cell carcinoma (ESCC), suggesting that oxidative stress contributes to the pathogenesis of ESCC. We examined the expression of MTH1 and the accumulation of 8-oxo-2'-deoxyguanosine (8-oxo-dG) in 84 patients with ESCC who underwent curative resection without neoadjuvant therapy. MTH1 mRNA level was quantified by performing quantitative reverse transcription-PCR. Immunohistochemical analysis of paraffin-embedded cancer tissues was performed to determine MTH1 protein expression and 8-oxo-dG accumulation. MTH1 mRNA expression was higher in cancerous tissues than in the corresponding normal epithelium (P < 0.0001). Immunohistochemical analysis showed that high MTH1 expression was significantly associated with deeper tumor invasion and venous invasion, advanced cancer stage, and poor overall survival (P = 0.0021) and disease-specific survival (P = 0.0013) compared with low MTH1 expression. Furthermore, high MTH1 expression was an independent predictor of poor disease-specific survival (P = 0.0121). In contrast, 8-oxo-dG accumulation was not associated with any clinicopathological factor and poor prognosis. These results suggest that MTH1 overexpression is a predictor of ESCC progression and poor prognosis and that MTH1 can serve as a therapeutic target for treating patients with ESCC.
MTH1 is a pyrophosphatase that hydrolyzes oxidized dNTPs in dNTP pool. This is the first study to show a correlation between MTH1 expression and malignancy of esophageal squamous cell carcinoma (ESCC). The enhanced MTH1 expression strongly correlates with tumor progression and is an independent prognostic factor in ESCC.
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Prognostic impact of MutT homolog-1 expression on esophageal squamous cell carcinoma
Abstract
MutT homolog-1 (MTH1) is a pyrophosphatase that acts on oxidized nucleotides and hydrolyzes 8-oxo-2'-deoxyguanosine triphosphate in deoxynucleoside triphosphate pool to prevent its incorporation into nuclear and mitochondrial DNA, result in reduce cytotoxicity in tumor cells. MTH1 is overexpressed in various cancers and is considered as a therapeutic target. Environmental factors such as cigarette smoking and alcohol consumption are critical risk factors for the development and progression of esophageal squamous cell carcinoma (ESCC), suggesting that oxidative stress contributes to the pathogenesis of ESCC. We examined the expression of MTH1 and the accumulation of 8-oxo-2'-deoxyguanosine (8-oxo-dG) in 84 patients with ESCC who underwent curative resection without neoadjuvant therapy. MTH1 mRNA level was quantified by performing quantitative reverse transcription-PCR. Immunohistochemical analysis of paraffin-embedded cancer tissues was performed to determine MTH1 protein expression and 8-oxo-dG accumulation. MTH1 mRNA expression was higher in cancerous tissues than in the corresponding normal epithelium (P < 0.0001). Immunohistochemical analysis showed that high MTH1 expression was significantly associated with deeper tumor invasion and venous invasion, advanced cancer stage, and poor overall survival (P = 0.0021) and disease-specific survival (P = 0.0013) compared with low MTH1 expression. Furthermore, high MTH1 expression was an independent predictor of poor disease-specific survival (P = 0.0121). In contrast, 8-oxo-dG accumulation was not associated with any clinicopathological factor and poor prognosis. These results suggest that MTH1 overexpression is a predictor of ESCC progression and poor prognosis and that MTH1 can serve as a therapeutic target for treating patients with ESCC.
MTH1 is a pyrophosphatase that hydrolyzes oxidized dNTPs in dNTP pool. This is the first study to show a correlation between MTH1 expression and malignancy of esophageal squamous cell carcinoma (ESCC). The enhanced MTH1 expression strongly correlates with tumor progression and is an independent prognostic factor in ESCC.
http://ift.tt/2gSHU0u
Management of Hot Flashes in Women with Breast Cancer Receiving Ovarian Function Suppression
Source:Cancer Treatment Reviews
Author(s): Roberto A. Leon-Ferre, Neil Majithia, Charles L. Loprinzi
Most breast cancers express estrogen and/or progesterone receptors, allowing the opportunity to use anti-estrogen therapies, which have demonstrated substantial efficacy in both the metastatic and adjuvant settings. Young premenopausal women with early-stage high-risk or with metastatic hormone-receptor positive breast cancer may benefit from ovarian function suppression in addition to anti-estrogen medications. While these endocrine manipulations have successfully improved breast cancer outcomes, they may lead to a significant proportion of women experiencing vasomotor symptoms. While not life-threatening, vasomotor symptoms adversely impact quality of life and can result in early treatment discontinuation. For these reasons, supportive management of this treatment-related toxicity is crucial, and clinicians caring for breast cancer patients and survivors should be familiar with the options available and the data behind them. This manuscript will review the pathophysiology, clinical manifestations, quality of life implications and non-estrogenic management options of vasomotor symptoms for women with breast cancer undergoing estrogen depletion.
http://ift.tt/2grcOg1
Effects and moderators of exercise on quality of life and physical function in patients with cancer: an individual patient data meta-analysis of 34 RCTs.
Source:Cancer Treatment Reviews
Author(s): Laurien M. Buffart, Joeri Kalter, Maike G. Sweegers, Kerry S. Courneya, Robert U. Newton, Neil K. Aaronson, Paul B. Jacobsen, Anne M. May, Daniel A. Galvão, Mai J. Chinapaw, Karen Steindorf, Melinda L. Irwin, Martijn M.Stuiver, Sandi Hayes, Kathleen A. Griffith, Alejandro Lucia, Ilse Mesters, Ellen van Weert, Hans Knoop, Martine M. Goedendorp, Nanette Mutrie, Amanda J. Daley, Alex McConnachie, Martin Bohus, Lene Thorsen, Karl-Heinz Schulz, Camille E. Short, Erica L. James, Ron C. Plotnikoff, Gill Arbane, Martina E. Schmidt, Karin Potthoff, Marc van Beurden, Hester S. Oldenburg, Gabe S. Sonke, Wim H. van Harten, Rachel Garrod, Kathryn H. Schmitz, Kerri M. Winters-Stone, Miranda J. Velthuis, Dennis R. Taaffe, Willem van Mechelen, Marie-José Kersten, Frans Nollet, J. Wenzel Jennifer, Joachim Wiskemann J, I.M. Verdonck-de Leeuw, J. Brug
This individual patient data meta-analysis aimed to evaluate the effects of exercise on quality of life (QoL) and physical function (PF) in patients with cancer, and to identify moderator effects of demographic (age, sex, marital status, education), clinical (body mass index, cancer type, presence of metastasis), intervention-related (intervention timing, delivery mode and duration, and type of control group), and exercise-related (exercise frequency, intensity, type, time) characteristics.Relevant published and unpublished studies were identified in September 2012 via PubMed, EMBASE, PsycINFO, and CINAHL, reference checking and personal communications. Principle investigators of all 69 eligible trials were requested to share IPD from their study. IPD from 34 randomised controlled trials (n=4,519 patients) that evaluated the effects of exercise compared to a usual care, wait-list or attention control group on QoL and PF in adult patients with cancer were retrieved and pooled. Linear mixed-effect models were used to evaluate the effects of the exercise on post-intervention outcome values (z-score) adjusting for baseline values. Moderator effects were studies by testing interactions.Exercise significantly improved QoL (β=0.15, 95%CI=0.10;0.20) and PF (β=0.18,95%CI=0.13;0.23). The effects were not moderated by demographic, clinical or exercise characteristics. Effects on QoL (βdifference_in_effect=0.13, 95%CI=0.03;0.22) and PF (βdifference_in_effect=0.10, 95%CI=0.01;0.20) were significantly larger for supervised than unsupervised interventions.In conclusion, exercise, and particularly supervised exercise, effectively improves QoL and PF in patients with cancer with different demographic and clinical characteristics during and following treatment. Although effect sizes are small, there is consistent empirical evidence to support implementation of exercise as part of cancer care.
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Study Seeks New AML Therapies [News in Brief]
The Leukemia and Lymphoma Society announced the launch of the Beat AML Master Trial, in which several medical centers and biopharmaceutical companies will collaboratively test multiple experimental drugs in patients with the disease who are over age 60 and whose cancer has one of nine genomic signatures.
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PIM1 May Be a Therapeutic Target in Triple-Negative Breast Cancer [Breast Cancer]
Targeting PIM1 induces apoptosis, reduces MYC activity, and upregulates p27 to suppress TNBC growth.
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MET Fusions May Be Druggable Targets in Pediatric Glioblastoma [Glioblastoma]
Structural rearrangements create recurrent MET fusion genes in ~10% of pediatric glioblastomas.
http://ift.tt/2gXhUUQ
DNA Damage Induces the lncRNA DINO to Stabilize p53 [DNA Damage]
The DINO lncRNA is induced by DNA damage and required for the p53-dependent DNA damage response.
http://ift.tt/2gX1hpy
Niraparib Slows Ovarian Cancer Progression [News in Brief]
Results from a phase III trial indicate that maintenance therapy with the PARP inhibitor niraparib is more effective than placebo in slowing the progression of recurrent platinum-sensitive ovarian cancer. Improved progression-free survival was seen regardless of the presence or absence of germline BRCA mutations, or of homologous recombination deficiency; however, patients who had these mutations or defective DNA repair did better.
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FOXK2 Represses Transcription to Suppress Breast Cancer Progression [Transcriptional Regulation]
FOXK2 is a repressor that interacts with various corepressor complexes to target the hypoxic response.
http://ift.tt/2gX1xot
A Genome-Wide Assay for MSI [News in Brief]
A recent study from the University of Washington in Seattle indicates that microsatellite instability, classically associated with colorectal, stomach, and endometrial cancers, is a much more extensive phenotype than previously appreciated. The researchers developed MOSAIC, a method to assess microsatellite instability on a comprehensive, genome-wide scale, and identified tumors positive for this phenotype in 14 of 18 different cancers evaluated.
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Glycosylation Blockade Targets Receptor Tyrosine Kinase-Driven Tumors [Drug Discovery]
Prevention of N-linked glycosylation induces senescence in RTK-dependent tumor cells.
http://ift.tt/2gXea5y
Durable Responses Achieved with AM0010 [News in Brief]
In a phase Ib trial, a combination of the experimental immunotherapy AM0010, a PEGylated form of the recombinant human cytokine IL10, and the anti–PD-1 checkpoint inhibitor pembrolizumab was well tolerated and effective at controlling tumors in some patients with advanced renal cell carcinoma, non–small cell lung cancer, and melanoma.
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Genomic Analysis of Pancreatic Cancers Reveals Punctuated Evolution [Pancreatic Cancer]
Most pancreatic tumors display complex rearrangements linked to mitotic errors and chromothripsis.
http://ift.tt/2gXg3PT
Ceritinib Outperforms Chemo as Second-Line Treatment [News in Brief]
Many oncologists have already adopted ceritinib as a second-line treatment for ALK-positive non–small cell lung cancer in patients who have developed resistance to crizotinib. The results of a randomized trial, presented at the European Society for Medical Oncology 2016 Congress, confirm that ceritinib is an effective option because it increases progression-free survival by 4 months over chemotherapy.
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Copy-Number Changes Can Create Pathogenic Chromatin Domains [Chromatin]
DNA duplications that overlap topologically associated domain (TAD) boundaries can create new TADs.
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Triple Therapy Improves Colorectal Cancer Response [News in Brief]
Findings from a phase I/II study indicate a higher response rate among patients with BRAF-mutant metastatic colorectal cancer treated with an EGFR inhibitor alongside dual, as opposed to single-level, MAPK blockade. Panitumumab combined with trametinib and dabrafenib only modestly increased median progression-free survival, however; a short-lived decrease in responders' BRAF V600E mutant allele fraction and the emergence of RAS mutations may have been contributing factors.
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MCL1 Can Be Targeted to Induce Apoptosis in Multiple Cancer Types [Drug Discovery]
An MCL1 inhibitor, S63845, has antitumor activity in multiple hematologic malignancies in vivo.
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Mortality Similar for Prostate Cancer Therapies [News in Brief]
The UK-based ProtecT trial reports that, after a median of 10 years of follow up, there is no significant difference in prostate cancer–specific mortality between active monitoring, surgery, and radiotherapy. However, the likelihood of developing metastases is more than twice as great with active monitoring compared with treatment.
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Phosphorylation of Histone H2A Promotes Tumorigenesis [Epigenetics]
VRK1-mediated phosphorylation of H2A T120 upregulates CCND1 to promote oncogenic transformation.
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Shedding Light on Fat Dependence in AML [News in Brief]
Scientists have begun unraveling the molecular intricacies that drive the appetite of acute myeloid leukemia for fat. They found that these tumor cells have particularly low levels of PHD3, an enzyme that normally activates ACC2 to repress fatty-acid oxidation. This fuels the cells' metabolic reliance on fat-burning, but also renders them highly susceptible to inhibitors of fatty-acid oxidation.
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SOX2-Induced Lineage Restriction Drives Lung Squamous Cell Carcinoma [Lung Cancer]
SOX2-mediated lineage restriction in different cells of origin promotes LSCC development.
http://ift.tt/2gXf5D1
Targeting Immune Suppression in Cancer [News in Brief]
Researchers have figured out a way to switch the immunosuppressive phenotype of tumor-associated macrophages to one that's immunostimulatory. By inhibiting PI3K in these macrophages, they significantly suppressed tumor growth in mice; when anti–PD-1 therapy was added to PI3K inhibition, complete and sustained tumor eradication was observed in many cases.
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Engineered T Cells Can Drive Custom Immune Cell Responses [Targeted Therapy]
SynNotch T cells can promote antigen-specific delivery of cytokines or antibodies and direct cell fate.
http://ift.tt/2gXdKfx
Study Seeks New AML Therapies [News in Brief]
The Leukemia and Lymphoma Society announced the launch of the Beat AML Master Trial, in which several medical centers and biopharmaceutical companies will collaboratively test multiple experimental drugs in patients with the disease who are over age 60 and whose cancer has one of nine genomic signatures.
http://ift.tt/2gX2QUv
PIM1 May Be a Therapeutic Target in Triple-Negative Breast Cancer [Breast Cancer]
Targeting PIM1 induces apoptosis, reduces MYC activity, and upregulates p27 to suppress TNBC growth.
http://ift.tt/2gXfXrv
The PETALE study: Late adverse effects and biomarkers in childhood acute lymphoblastic leukemia survivors
Abstract
Background
Childhood cancer survivorship issues represent an established public health challenge. Most late adverse effects (LAEs) have been demonstrated to be time and treatment dependent. The PETALE study is a multidisciplinary research project aiming to comprehensively characterize LAEs and identify associated predictive biomarkers in childhood acute lymphoblastic leukemia (cALL) survivors.
Methods
cALL survivors treated at Sainte-Justine University Health Center with Dana-Farber Cancer Institution-ALL protocols 87-01 through 2005-01 were eligible. During Phase I of the study, the participants underwent comprehensive clinical, biologic, and psychosocial investigation targeting metabolic syndrome, cardiotoxicity, bone morbidity, neurocognitive problems, and quality of life issues. Whole-exome sequencing was performed for all participants. Subjects identified with an extreme phenotype during Phase I were recalled for additional testing (Phase II).
Results
Phase I included 246 survivors (recall rate 71.9%). Of those, 85 participants completed Phase II (recall rate 88.5%). Survivors agreeing to participate in Phase I (n = 251) were similar to those who refused (n = 31) in terms of relapse risk profile, radiotherapy exposure, and age at the time of study. Participants, however, tended to be slightly older at diagnosis (6.1 vs. 4.7 years old, P = 0.08), with a higher proportion of female agreeing to participate compared with males (93.2 vs. 86.5%, P = 0.07).
Conclusion
The PETALE study will contribute to comprehensively characterize clinical, psychosocial, biologic, and genomic features of cALL survivors using an integrated approach. Expected outcomes include LAE early detection biomarkers, long-term follow-up guidelines, and recommendations for physicians and health professionals.
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Societal preferences in the treatment of pediatric medulloblastoma: Balancing risk of death and quality of life
Abstract
Purpose
Medulloblastoma is the most prevalent childhood brain cancer. Children with medulloblastoma typically receive a combination of surgery, radiation, and chemotherapy. The survival rate is high but survivors often have sequelae from radiotherapy of the entire developing brain and spinal cord. Ongoing genetic studies have suggested that decreasing the dose of radiation might be possible among children with favorable molecular variants; however, this may result in an increased disease recurrence. As such, there is a need to investigate the nature of trade-offs that individuals are willing to make regarding the treatment of medulloblastoma.
Method
We used best–worst scaling to estimate the importance of attributes affecting the general public's decision making around the treatment of medulloblastoma. After conducting focus groups, we selected three relevant attributes: (1) the accuracy of the genetic test; (2) the probability of serious adverse effects of the treatment(s); and (3) the survival rate. Using the paired method, we applied a conditional logit model to estimate preferences.
Results
In total, 3,006 respondents (51.3% female) with an average age of 43 years answered the questionnaires. All coefficients were statistically significantly different from zero and the attribute levels of adverse effects and the survival rate had the most impact on individuals' stated decision making.
Conclusion
Overall, respondents showed high sensitivity to children experiencing disability particularly in the setting of a good prognosis. However, among children with poor prognostic molecular variants, participants showed tolerance about having a child with mild and partial disability compared to a low rate of survival.
http://ift.tt/2gScGqu
The PETALE study: Late adverse effects and biomarkers in childhood acute lymphoblastic leukemia survivors
Abstract
Background
Childhood cancer survivorship issues represent an established public health challenge. Most late adverse effects (LAEs) have been demonstrated to be time and treatment dependent. The PETALE study is a multidisciplinary research project aiming to comprehensively characterize LAEs and identify associated predictive biomarkers in childhood acute lymphoblastic leukemia (cALL) survivors.
Methods
cALL survivors treated at Sainte-Justine University Health Center with Dana-Farber Cancer Institution-ALL protocols 87-01 through 2005-01 were eligible. During Phase I of the study, the participants underwent comprehensive clinical, biologic, and psychosocial investigation targeting metabolic syndrome, cardiotoxicity, bone morbidity, neurocognitive problems, and quality of life issues. Whole-exome sequencing was performed for all participants. Subjects identified with an extreme phenotype during Phase I were recalled for additional testing (Phase II).
Results
Phase I included 246 survivors (recall rate 71.9%). Of those, 85 participants completed Phase II (recall rate 88.5%). Survivors agreeing to participate in Phase I (n = 251) were similar to those who refused (n = 31) in terms of relapse risk profile, radiotherapy exposure, and age at the time of study. Participants, however, tended to be slightly older at diagnosis (6.1 vs. 4.7 years old, P = 0.08), with a higher proportion of female agreeing to participate compared with males (93.2 vs. 86.5%, P = 0.07).
Conclusion
The PETALE study will contribute to comprehensively characterize clinical, psychosocial, biologic, and genomic features of cALL survivors using an integrated approach. Expected outcomes include LAE early detection biomarkers, long-term follow-up guidelines, and recommendations for physicians and health professionals.
http://ift.tt/2gWNMca
Societal preferences in the treatment of pediatric medulloblastoma: Balancing risk of death and quality of life
Abstract
Purpose
Medulloblastoma is the most prevalent childhood brain cancer. Children with medulloblastoma typically receive a combination of surgery, radiation, and chemotherapy. The survival rate is high but survivors often have sequelae from radiotherapy of the entire developing brain and spinal cord. Ongoing genetic studies have suggested that decreasing the dose of radiation might be possible among children with favorable molecular variants; however, this may result in an increased disease recurrence. As such, there is a need to investigate the nature of trade-offs that individuals are willing to make regarding the treatment of medulloblastoma.
Method
We used best–worst scaling to estimate the importance of attributes affecting the general public's decision making around the treatment of medulloblastoma. After conducting focus groups, we selected three relevant attributes: (1) the accuracy of the genetic test; (2) the probability of serious adverse effects of the treatment(s); and (3) the survival rate. Using the paired method, we applied a conditional logit model to estimate preferences.
Results
In total, 3,006 respondents (51.3% female) with an average age of 43 years answered the questionnaires. All coefficients were statistically significantly different from zero and the attribute levels of adverse effects and the survival rate had the most impact on individuals' stated decision making.
Conclusion
Overall, respondents showed high sensitivity to children experiencing disability particularly in the setting of a good prognosis. However, among children with poor prognostic molecular variants, participants showed tolerance about having a child with mild and partial disability compared to a low rate of survival.
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A novel two-nucleotide deletion in HPS6 affects mepacrine uptake and platelet dense granule secretion in a family with Hermansky–Pudlak syndrome
Summary
Background
Hermansky–Pudlak syndrome (HPS) is a rare autosomal recessive disease characterized by oculocutaneous albinism and platelet dysfunction. We report on a novel HPS6 homozygous frameshift variant (c.1919_1920delTC; p.Val640Glyfs*29) in a nonconsanguineous Caucasian family with two affected siblings (index patients) who presented with oculocutaneous albinism at birth and a mild bleeding phenotype during childhood and adolescence.
Procedure
Genetic analysis was conducted by panel-based next-generation sequencing (NGS) and Sanger sequencing. Platelets of the index patients, their parents, and the unaffected sister were then comprehensively evaluated by luminoaggregometry, whole blood flow cytometry, immunoblotting, immunofluorescence, and transmission electron microscopy.
Results
The homozygous frameshift variant in HPS6 gene detected by panel-based NGS and its segregation in the family was confirmed by Sanger sequencing. Flow cytometric analysis of the patients' platelets revealed a substantially decreased mepacrine uptake and release upon activation with a thrombin receptor agonist. Electron microscopy of resting platelets confirmed diminished dense granule content and enhanced vacuolization. Reduced release of adenosine triphosphate and CD63 neoexposition upon activation indicated not only a lack of dense granule content, but even an impairment of dense granule release.
Conclusions
Our results demonstrate that the novel loss-of-function variant in the HPS6 subunit of biogenesis of lysosome-related organelles complex 2 is pathologic and leads to a reduced platelet dense granules and their release. The findings are compatible with an impaired platelet function and hence an enhanced bleeding risk. In future, a valid genotype–phenotype correlation may translate into best supportive care, especially regarding elective surgery or trauma management.
http://ift.tt/2gS10nC
A novel two-nucleotide deletion in HPS6 affects mepacrine uptake and platelet dense granule secretion in a family with Hermansky–Pudlak syndrome
Summary
Background
Hermansky–Pudlak syndrome (HPS) is a rare autosomal recessive disease characterized by oculocutaneous albinism and platelet dysfunction. We report on a novel HPS6 homozygous frameshift variant (c.1919_1920delTC; p.Val640Glyfs*29) in a nonconsanguineous Caucasian family with two affected siblings (index patients) who presented with oculocutaneous albinism at birth and a mild bleeding phenotype during childhood and adolescence.
Procedure
Genetic analysis was conducted by panel-based next-generation sequencing (NGS) and Sanger sequencing. Platelets of the index patients, their parents, and the unaffected sister were then comprehensively evaluated by luminoaggregometry, whole blood flow cytometry, immunoblotting, immunofluorescence, and transmission electron microscopy.
Results
The homozygous frameshift variant in HPS6 gene detected by panel-based NGS and its segregation in the family was confirmed by Sanger sequencing. Flow cytometric analysis of the patients' platelets revealed a substantially decreased mepacrine uptake and release upon activation with a thrombin receptor agonist. Electron microscopy of resting platelets confirmed diminished dense granule content and enhanced vacuolization. Reduced release of adenosine triphosphate and CD63 neoexposition upon activation indicated not only a lack of dense granule content, but even an impairment of dense granule release.
Conclusions
Our results demonstrate that the novel loss-of-function variant in the HPS6 subunit of biogenesis of lysosome-related organelles complex 2 is pathologic and leads to a reduced platelet dense granules and their release. The findings are compatible with an impaired platelet function and hence an enhanced bleeding risk. In future, a valid genotype–phenotype correlation may translate into best supportive care, especially regarding elective surgery or trauma management.
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Metachronous Synchronous Sternal and Colonic Metastasis with Asymptomatic Colo-colic Fistula from Carcinoma Ovary Rare Presentation of Ovarian Cancer
Abstract
Ovarian cancer is one of the most common gynecological cancers worldwide. It is the third leading cause of cancer among women in India. Metastatic disease to the visceral organs from ovarian cancer occurs as a terminal event in the natural history of the disease. In particular, spread to the bone and large bowel is infrequently described. The risk of distant metastasis increases in a recurrent setting. We describe a case of a 77-year-old lady, who was diagnosed for ovarian carcinoma in 2007 and underwent primary cytoreductive surgery, stage IIIc. She presented to us with asymptomatic rising cancer antigen (CA) 125 levels during follow-up. On evaluation she was found to have sternal and colonic deposits. She underwent left hemicolectomy and biopsy of sternal deposit. Histopathology revealed metastasis from the carcinoma ovary to the colon and sternum. This case report highlights the rare synchronous metastatic disease in a metachronous setting from ovarian carcinoma.
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Metachronous Synchronous Sternal and Colonic Metastasis with Asymptomatic Colo-colic Fistula from Carcinoma Ovary Rare Presentation of Ovarian Cancer
Abstract
Ovarian cancer is one of the most common gynecological cancers worldwide. It is the third leading cause of cancer among women in India. Metastatic disease to the visceral organs from ovarian cancer occurs as a terminal event in the natural history of the disease. In particular, spread to the bone and large bowel is infrequently described. The risk of distant metastasis increases in a recurrent setting. We describe a case of a 77-year-old lady, who was diagnosed for ovarian carcinoma in 2007 and underwent primary cytoreductive surgery, stage IIIc. She presented to us with asymptomatic rising cancer antigen (CA) 125 levels during follow-up. On evaluation she was found to have sternal and colonic deposits. She underwent left hemicolectomy and biopsy of sternal deposit. Histopathology revealed metastasis from the carcinoma ovary to the colon and sternum. This case report highlights the rare synchronous metastatic disease in a metachronous setting from ovarian carcinoma.
http://ift.tt/2h3ue20
Relative costs of anesthesiologist prepared, hospital pharmacy prepared and outsourced anesthesia drugs
Anesthesia drugs can be prepared by anesthesia providers, hospital pharmacies or outsourcing facilities. The decision whether to outsource all or some anesthesia drugs is challenging since the costs associated with different anesthesia drug preparation methods remain poorly described.
http://ift.tt/2gRbFyX
MYD88, CD79B, and CARD11 gene mutations in CD5-positive diffuse large B-cell lymphoma
BACKGROUND
CD5-positive (CD5+) diffuse large B-cell lymphoma (DLBCL) is characterized by frequent central nervous system recurrence and a predominant activated B-cell-like nature. Primary DLBCL in sanctuary sites (DLBCL-SS) also demonstrates these features, and >70% of patients harbor myeloid differentiation primary response 88 (MYD88) (L265P) and CD79B mutations. The objective of the current study was to elucidate a possible relationship between CD5+ DLBCL and DLBCL-SS.
METHODS
MYD88, CD79B, CD79A, and caspase recruitment domain family member 11 (CARD11) mutations were examined in samples from 40 patients with CD5+ DLBCL. Mutation analysis was performed by direct sequencing.
RESULTS
MYD88 and CD79B mutations were detected in 33% (13 patients) and 38% (15 patients), respectively, of the 40 patients with CD5+ DLBCL. Ten patients had these 2 gene mutations, and 1 had a CD79A mutation. One of 2 patients with testicular involvement had both MYD88 and CD79B mutations. The other patient had a MYD88 mutation alone. None of the 31 patients examined was found to have a CARD11 mutation. MYD88 and CD79B mutations were found to be associated with localized disease (P = .038 and P = .003, respectively). Primary extranodal lymphoma was associated with higher frequencies of mutations in MYD88 or both MYD88 and CD79B (P = .008 and P = .014, respectively). There was no significant difference in overall survival based on MYD88 and CD79B mutation status.
CONCLUSIONS
The incidence of MYD88 and CD79B mutations in patients with CD5+ DLBCL is lower than that in patients with DLBCL-SS, suggesting that CD5+ DLBCL is not the same disease as DLBCL-SS in terms of gene mutation status. CARD11 mutations are rare in patients with CD5+ DLBCL. Cancer 2016. © 2016 American Cancer Society.
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MYD88, CD79B, and CARD11 gene mutations in CD5-positive diffuse large B-cell lymphoma
BACKGROUND
CD5-positive (CD5+) diffuse large B-cell lymphoma (DLBCL) is characterized by frequent central nervous system recurrence and a predominant activated B-cell-like nature. Primary DLBCL in sanctuary sites (DLBCL-SS) also demonstrates these features, and >70% of patients harbor myeloid differentiation primary response 88 (MYD88) (L265P) and CD79B mutations. The objective of the current study was to elucidate a possible relationship between CD5+ DLBCL and DLBCL-SS.
METHODS
MYD88, CD79B, CD79A, and caspase recruitment domain family member 11 (CARD11) mutations were examined in samples from 40 patients with CD5+ DLBCL. Mutation analysis was performed by direct sequencing.
RESULTS
MYD88 and CD79B mutations were detected in 33% (13 patients) and 38% (15 patients), respectively, of the 40 patients with CD5+ DLBCL. Ten patients had these 2 gene mutations, and 1 had a CD79A mutation. One of 2 patients with testicular involvement had both MYD88 and CD79B mutations. The other patient had a MYD88 mutation alone. None of the 31 patients examined was found to have a CARD11 mutation. MYD88 and CD79B mutations were found to be associated with localized disease (P = .038 and P = .003, respectively). Primary extranodal lymphoma was associated with higher frequencies of mutations in MYD88 or both MYD88 and CD79B (P = .008 and P = .014, respectively). There was no significant difference in overall survival based on MYD88 and CD79B mutation status.
CONCLUSIONS
The incidence of MYD88 and CD79B mutations in patients with CD5+ DLBCL is lower than that in patients with DLBCL-SS, suggesting that CD5+ DLBCL is not the same disease as DLBCL-SS in terms of gene mutation status. CARD11 mutations are rare in patients with CD5+ DLBCL. Cancer 2016. © 2016 American Cancer Society.
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Recommend Maintenance Therapy with Lenalidomide
Publication date: Available online 3 December 2016
Source:Seminars in Oncology
Author(s): Elisabet E Manasanch
http://ift.tt/2gPlOMk
Treatment of Newly Diagnosed Myeloma: Bortezomib-based Triplet
Publication date: Available online 3 December 2016
Source:Seminars in Oncology
Author(s): Archana M. Rajan, S. Vincent Rajkumar
In this paper we review the options for the treatment of newly diagnosed myeloma in a patient who is a candidate for autologous stem cell transplantation. Bortezomib, lenalidomide, dexamethasone (VRD) has been studied in two randomized trials as first line therapy. In one of these trials, VRD demonstrated improved overall survival compared with lenalidomide plus dexamethasone (Rd). By contrast, phase III data with overall survival differences are not available for other bortezomib containing regimens compared with modern lenalidomide containing regimens. Carfilzomib-lenalidomide-dexamethasone (KRD) is an alternative promising regimen but has only been evaluated in small phase II studies in the frontline setting. More data are needed before this regimen can be recommended to standard risk patients with newly diagnosed myeloma. A phase III trial comparing VRD and KRD is ongoing.
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Corrigendum to ‘Targeting FGFR2 with alofanib (RPT835) shows potent activity in tumour models’ [Eur J Cancer 61 (2016) 20–28]
Source:European Journal of Cancer
Author(s): Ilya Tsimafeyeu, John Ludes-Meyers, Evgenia Stepanova, Frits Daeyaert, Dmitry Khochenkov, Jean-Baptiste Joose, Eliso Solomko, Koen Van Akene, Nina Peretolchina, Wei Yin, Oxana Ryabaya, Mikhail Byakhov, Sergei Tjulandin
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Enthesitis in a 16-Year-Old Boy with M694V Mutation
Introduction. FMF (Familial Mediterranean Fever) is characterized by recurrent attacks of fever and articular pain. Enthesitis is the hallmark of pain in spondyloarthropathy. Literature suggests association of M694V mutation and enthesitis. We report a case of a 16-year-old boy with enthesitis and FMF. Case Presentation. A 16-year-old boy of Turkish origin with a history of FMF presented with localized tenderness of the heel and severe disability. MRI showed an enthesitis of the plantar fascia. Standard treatment of FMF and enthesitis was not successful. After referral to a university hospital and expert opinion of a professor in rheumatology, this enthesitis should be treated as an enthesitis related arthritis. With this treatment, our patient fully recovered 8 months after the onset of the disease symptoms. Conclusion. M694V mutation related enthesitis should be considered in FMF patients with enthesitis. We would suggest treatment for enthesitis related arthritis in similar cases. This is of clinical importance because the treatment is different from treatment of enthesitis or articular pain caused by FMF.
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