Publication date: January 2018
Source:European Journal of Cancer, Volume 88
Author(s): S. Valpione, G. Gremel, P. Mundra, P. Middlehurst, E. Galvani, M.R. Girotti, R.J. Lee, G. Garner, N. Dhomen, P.C. Lorigan, R. Marais
IntroductionTumour burden is a prognostic biomarker in metastatic melanoma. However, tumour burden is difficult to measure and there are currently no reliable surrogate biomarkers to easily and reliably determine it. The aim of this study was to assess the potential of plasma total cell free DNA as biomarker of tumour burden and prognosis in metastatic melanoma patients.Materials and methodsA prospective biomarker cohort study for total plasma circulating cell-free DNA (cfDNA) concentration was performed in 43 metastatic melanoma patients. For 38 patients, paired blood collections and scan assessments were available before treatment and at first response evaluation. Tumour burden was calculated as the sum of volumes from three-dimensional radiological measurements of all metastatic lesions in individual patients.ResultsBaseline cfDNA concentration correlated with pre-treatment tumour burden (ρ = 0.52, P < 0.001). Baseline cfDNA levels correlated significantly with hazard of death and overall survival, and a cut off value of 89 pg/μl identified two distinct prognostic groups (HR = 2.22 for high cfDNA, P = 0.004). Patients with cfDNA ≥89 pg/μl had shorter OS (10.0 versus 22.7 months, P = 0.009; HR = 2.22 for high cfDNA, P = 0.004) and the significance was maintained when compared with lactic dehydrogenase (LDH) in a multivariate analysis. We also found a correlation between the changes of cfDNA and treatment-related changes in tumour burden (ρ = 0.49, P = 0.002). In addition, the ratio between baseline cfDNA and tumour burden was prognostic (HR = 2.7 for cfDNA/tumour volume ≥8 pg/(μl*cm3), P = 0.024).ConclusionsWe have demonstrated that cfDNA is a surrogate marker of tumour burden in metastatic melanoma patients, and that it is prognostic for overall survival.
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Cancer Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Πέμπτη 23 Νοεμβρίου 2017
Plasma total cell-free DNA (cfDNA) is a surrogate biomarker for tumour burden and a prognostic biomarker for survival in metastatic melanoma patients
Prognostic impact of interval breast cancer detection in women with pT1a N0M0 breast cancer with HER2-positive status: Results from a multicentre population-based cancer registry study
Source:European Journal of Cancer, Volume 88
Author(s): A. Musolino, F. Falcini, A. Sikokis, D. Boggiani, A. Rimanti, B. Pellegrino, E.M. Silini, N. Campanini, E. Barbieri, C. Zamagni, R. Degli Esposti, L. Cortesi, G. Bisagni, L. Cavanna, A. Frassoldati, P. Sgargi, M. Michiara
BackgroundAlthough human epidermal growth factor receptor 2 (HER2) overexpression is associated with poor prognosis, patients (pts) with pT1a N0M0 breast cancers (BCs) have an excellent outcome across all subtypes. Interval cancers (ICs) have poorer survival than screen-detected (SD) tumours, and an association has been reported between ICs and HER2 overexpression. We aimed to determine, in a general population of pT1a N0M0 BCs with known screening status, whether HER2-positive ICs have a poorer outcome than HER2-positive SD cancers.MethodsWe evaluated all incident pT1a N0M0 BCs (n = 874) collected in the Emilia-Romagna region (Italy) from 2003 to 2009 and diagnosed in women aged 50–69. Pts unexposed to screening, with unknown HER2 status and/or treated with adjuvant trastuzumab were excluded from analysis.ResultsSixty-one percent of the BCs were SD, whereas 19% were ICs. BCs with high histologic grade, hormone receptor–negative or HER2-positive status (odds ratio=1.7; 95% confidence interval [CI]: 1.1–2.7) were more likely ICs. Median follow-up was 115 months. The 10-year invasive disease-free survival (iDFS) for HER2-positive ICs was lower than that for HER2-positive SD cancers: 75.0% (95% CI: 55.5%–94.5%) versus 93.8% (95% CI: 86.5%–100%). An interaction between ICs and HER2-positive status was found for poorer iDFS after adjusting for prognostic variables (HR = 5.3; 95% CI: 1.6–16.7).ConclusionsIC detection may identify pts with HER2-positive pT1a N0M0 tumours in whom the rate of recurrence justifies consideration for conventional, anti-HER2, adjuvant treatment.
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Corrigendum to “Loss of tight junction plaque molecules in breast cancer tissues is associated with a poor prognosis in patients with breast cancer” [Eur J Cancer 40 (18) (2004) 2717–2725]
Source:European Journal of Cancer
Author(s): Tracey A. Martin, Gareth Watkins, Robert E. Mansel, Wen G. Jiang
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Overall survival in MERiDiAN, a double-blind placebo-controlled randomised phase III trial evaluating first-line bevacizumab plus paclitaxel for HER2-negative metastatic breast cancer
Source:European Journal of Cancer
Author(s): David Miles, David Cameron, Magalie Hilton, Josep Garcia, Joyce O'Shaughnessy
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Confirmed Ceylon krait (Bungarus ceylonicus) envenoming in Sri Lanka resulting in neuromuscular paralysis: a case report
Ceylon krait (Bungarus ceylonicus) is a venomous elapid snake endemic to Sri Lanka. It inhabits shaded home gardens and forests in the wet zone of Sri Lanka and might creep into houses in the night. Despite frequ...
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Correction to: Long-term patient reported outcomes following radiation therapy for oropharyngeal cancer: cross-sectional assessment of a prospective symptom survey in patients ≥65 years old
In the original publication [1] the name of author Jeremy M. Aymard was spelled wrong. The original article was updated to rectify this error.
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Correction to: Long-term patient reported outcomes following radiation therapy for oropharyngeal cancer: cross-sectional assessment of a prospective symptom survey in patients ≥65 years old
In the original publication [1] the name of author Jeremy M. Aymard was spelled wrong. The original article was updated to rectify this error.
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Personal history of non-melanoma skin cancer diagnosis and death from melanoma in women
Abstract
Melanoma incidence is increasing. We evaluated risk of melanoma death after diagnosis of non-melanoma skin cancer (NMSC).
We followed 77,288 female American nurses from the Nurses' Health Study from 1986 to 2012. We used Cox proportional hazards models to determine the hazard ratio (HR) of lethal and non-lethal melanoma diagnosis and melanoma death, according to personal NMSC history. Among melanoma cases, we examined the HR of melanoma death and the odds ratio (OR) of melanoma with a Breslow thickness ≥ 0.8mm or Clark's level of IV and V according to history of NMSC.
We documented 930 melanoma cases without NMSC history and 615 melanoma cases with NMSC history over 1.8 million person-years. The multivariate-adjusted HR (95% confidence interval) of melanoma death associated with personal history of NMSC was 2.89 (1.85-4.50). Women with history of NMSC were more likely to develop non-lethal melanoma than lethal melanoma (HR (95% CI): 2.31 (2.05–2.60) vs. 1.74 (1.05-2.87)). Among melanoma cases, women with history of NMSC had a non-significant decreased risk of melanoma deaths (0.87 (0.55-1.37)), Breslow thickness ≥0.8mm (0.85 (0.59-1.21)) and Clark's levels IV and V (0.81(0.52-1.24)).
Women with NMSC history were less likely to be diagnosed with a lethal melanoma than a non-lethal melanoma, but overall rate of melanoma diagnosis was increased in both subtypes, leading to the increased risk of subsequent melanoma death. Our findings suggest the continued need for dermatologic screening for patients after NMSC diagnosis, given increased melanoma risk. Early detection among NMSC patients may decrease deaths from subsequent melanoma. This article is protected by copyright. All rights reserved.
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Bevacizumab in Combination with Different Platinum-based Doublets in the First-line Treatment for Advanced Nonsquamous Non-small-cell Lung Cancer: A Network Meta-Analysis
Abstract
Platinum-based doublet chemotherapy with or without bevacizumab is the standard treatment for untreated advanced nonsquamous non-small-cell lung cancer (NS-NSCLC). However, adding bevacizumab to chemotherapies other than paclitaxel-carboplatin is, though widely applied clinically, largely unjustified due to the lack of head-to-head data. We performed a Bayesian network meta-analysis (NMA) to address this important issue. Data of 8548 patients from 18 randomized controlled trials (RCTs) receiving six treatments including taxane-platinum (Taxane-Pt), gemcitabine-platinum (Gem-Pt), pemetrexed-platinum (Pem-Pt), taxane-platinum + bevacizumab (Taxane-Pt+B), gemcitabine-platinum + bevacizumab (Gem-Pt+B) and pemetrexed-platinum + bevacizumab (Pem-Pt+B) were incorporated into the analyses. Direct and indirect evidence of overall survival (OS) and progression-free survival (PFS) were synthesized at the hazard ratio (HR) scale and evidence of objective response rate (ORR) and serious adverse events (SAE) were synthesized at the odds ratio (OR) scale. Taxane-Pt+B showed significant advantages in OS (HR=0.79, P<0.001), PFS (HR=0.54, P<0.001) and ORR (OR=2.7, P<0.001) over Taxane-Pt with comparable tolerability (OR=3.1, P=0.08). Gem-Pt+B showed no OS benefit compared to any other treatment. No significant differences were detected between Pem-Pt+B and Pem-Pt in four outcomes. In terms of the benefit-risk ratio, Pem-Pt and Taxane-Pt+B were ranked the first and second respectively. In conclusion, in the first-line treatment for advanced NS-NSCLC, Taxane-Pt and Gem-Pt are the most and least preferable regimens to be used with bevacizumab, respectively. Adding bevacizumab to Pem-Pt remains unjustified because it fails to improve efficacy or tolerability. In terms of the benefit-risk ratio, Pem-Pt and Taxane-Pt+B are the best and second-best treatment for this population. This article is protected by copyright. All rights reserved.
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Personal history of non-melanoma skin cancer diagnosis and death from melanoma in women
Abstract
Melanoma incidence is increasing. We evaluated risk of melanoma death after diagnosis of non-melanoma skin cancer (NMSC).
We followed 77,288 female American nurses from the Nurses' Health Study from 1986 to 2012. We used Cox proportional hazards models to determine the hazard ratio (HR) of lethal and non-lethal melanoma diagnosis and melanoma death, according to personal NMSC history. Among melanoma cases, we examined the HR of melanoma death and the odds ratio (OR) of melanoma with a Breslow thickness ≥ 0.8mm or Clark's level of IV and V according to history of NMSC.
We documented 930 melanoma cases without NMSC history and 615 melanoma cases with NMSC history over 1.8 million person-years. The multivariate-adjusted HR (95% confidence interval) of melanoma death associated with personal history of NMSC was 2.89 (1.85-4.50). Women with history of NMSC were more likely to develop non-lethal melanoma than lethal melanoma (HR (95% CI): 2.31 (2.05–2.60) vs. 1.74 (1.05-2.87)). Among melanoma cases, women with history of NMSC had a non-significant decreased risk of melanoma deaths (0.87 (0.55-1.37)), Breslow thickness ≥0.8mm (0.85 (0.59-1.21)) and Clark's levels IV and V (0.81(0.52-1.24)).
Women with NMSC history were less likely to be diagnosed with a lethal melanoma than a non-lethal melanoma, but overall rate of melanoma diagnosis was increased in both subtypes, leading to the increased risk of subsequent melanoma death. Our findings suggest the continued need for dermatologic screening for patients after NMSC diagnosis, given increased melanoma risk. Early detection among NMSC patients may decrease deaths from subsequent melanoma. This article is protected by copyright. All rights reserved.
http://ift.tt/2BimKDp
Bevacizumab in Combination with Different Platinum-based Doublets in the First-line Treatment for Advanced Nonsquamous Non-small-cell Lung Cancer: A Network Meta-Analysis
Abstract
Platinum-based doublet chemotherapy with or without bevacizumab is the standard treatment for untreated advanced nonsquamous non-small-cell lung cancer (NS-NSCLC). However, adding bevacizumab to chemotherapies other than paclitaxel-carboplatin is, though widely applied clinically, largely unjustified due to the lack of head-to-head data. We performed a Bayesian network meta-analysis (NMA) to address this important issue. Data of 8548 patients from 18 randomized controlled trials (RCTs) receiving six treatments including taxane-platinum (Taxane-Pt), gemcitabine-platinum (Gem-Pt), pemetrexed-platinum (Pem-Pt), taxane-platinum + bevacizumab (Taxane-Pt+B), gemcitabine-platinum + bevacizumab (Gem-Pt+B) and pemetrexed-platinum + bevacizumab (Pem-Pt+B) were incorporated into the analyses. Direct and indirect evidence of overall survival (OS) and progression-free survival (PFS) were synthesized at the hazard ratio (HR) scale and evidence of objective response rate (ORR) and serious adverse events (SAE) were synthesized at the odds ratio (OR) scale. Taxane-Pt+B showed significant advantages in OS (HR=0.79, P<0.001), PFS (HR=0.54, P<0.001) and ORR (OR=2.7, P<0.001) over Taxane-Pt with comparable tolerability (OR=3.1, P=0.08). Gem-Pt+B showed no OS benefit compared to any other treatment. No significant differences were detected between Pem-Pt+B and Pem-Pt in four outcomes. In terms of the benefit-risk ratio, Pem-Pt and Taxane-Pt+B were ranked the first and second respectively. In conclusion, in the first-line treatment for advanced NS-NSCLC, Taxane-Pt and Gem-Pt are the most and least preferable regimens to be used with bevacizumab, respectively. Adding bevacizumab to Pem-Pt remains unjustified because it fails to improve efficacy or tolerability. In terms of the benefit-risk ratio, Pem-Pt and Taxane-Pt+B are the best and second-best treatment for this population. This article is protected by copyright. All rights reserved.
http://ift.tt/2zi1cVS
Cause-specific mortality in HPV+ and HPV− oropharyngeal cancer patients: insights from a population-based cohort
Abstract
Identifying the causes of death in head and neck cancer patients can optimize follow-up and therapeutic strategies, but studies in oropharyngeal squamous cell carcinoma (OPSCC) patients stratified by HPV status are lacking. We report cause-specific mortality in a population-based cohort of patients with OPSCC. Patients who had been diagnosed with OPSCC (n = 1541) between 2000 and 2014 in eastern Denmark were included in the study. Causes of death were collected through medical files and the Danish National Cause of Death registry. Deaths were grouped as (1) primary oropharyngeal cancer, (2) secondary malignancies, (3) cardiovascular and pulmonary disease, or (4) other/unspecified. The cumulative incidence of death and specific causes of death were determined using risk analysis. At follow-up, 723 (47.5%) patients had died. The median time to and cause of death were determined: oropharyngeal cancer (n = 432; 1.00 year), secondary malignancies (n = 131; 2.37 years), cardiovascular and pulmonary causes (n = 58; 3.48 years), and unspecified causes (n = 102; 3.42 years). HPV/p16 status was the strongest predictor of improved survival across all causes of death. The only cause of death to decrease in incidence over the 2 years after treatment was death from OPSCC. HPV/p16 positivity was an independent factor for improved survival across all causes of death in patients with OPSCC. In addition, both HPV-positive and HPV-negative OPSCC patients faced high 5- and 10-year mortality rates. Implementing secondary screening and prevention strategies for late toxicity and mortality are major goals in managing the treatment of these patients.
Identifying cause of death in oropharyngeal cancer patients may aid in optimizing follow-up and therapeutic strategies, but studies stratified on HPV status is lacking. We report cause-specific mortality in a population-based cohort of oropharyngeal cancer patients from 2000 to 2014.
http://ift.tt/2iKDGuw
Cause-specific mortality in HPV+ and HPV− oropharyngeal cancer patients: insights from a population-based cohort
Abstract
Identifying the causes of death in head and neck cancer patients can optimize follow-up and therapeutic strategies, but studies in oropharyngeal squamous cell carcinoma (OPSCC) patients stratified by HPV status are lacking. We report cause-specific mortality in a population-based cohort of patients with OPSCC. Patients who had been diagnosed with OPSCC (n = 1541) between 2000 and 2014 in eastern Denmark were included in the study. Causes of death were collected through medical files and the Danish National Cause of Death registry. Deaths were grouped as (1) primary oropharyngeal cancer, (2) secondary malignancies, (3) cardiovascular and pulmonary disease, or (4) other/unspecified. The cumulative incidence of death and specific causes of death were determined using risk analysis. At follow-up, 723 (47.5%) patients had died. The median time to and cause of death were determined: oropharyngeal cancer (n = 432; 1.00 year), secondary malignancies (n = 131; 2.37 years), cardiovascular and pulmonary causes (n = 58; 3.48 years), and unspecified causes (n = 102; 3.42 years). HPV/p16 status was the strongest predictor of improved survival across all causes of death. The only cause of death to decrease in incidence over the 2 years after treatment was death from OPSCC. HPV/p16 positivity was an independent factor for improved survival across all causes of death in patients with OPSCC. In addition, both HPV-positive and HPV-negative OPSCC patients faced high 5- and 10-year mortality rates. Implementing secondary screening and prevention strategies for late toxicity and mortality are major goals in managing the treatment of these patients.
Identifying cause of death in oropharyngeal cancer patients may aid in optimizing follow-up and therapeutic strategies, but studies stratified on HPV status is lacking. We report cause-specific mortality in a population-based cohort of oropharyngeal cancer patients from 2000 to 2014.
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Adjuvant breast radiotherapy: How to trade-off cost and effectiveness?
A series of health economic evaluations (HEE) has analysed the efficiency of new fractionation schedules and techniques for adjuvant breast radiotherapy. This overview assembles the available evidence and evaluates to what extent HEE-results can be compared.
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MYC regulation of glutamine–proline regulatory axis is key in luminal B breast cancer
MYC regulation of glutamine–proline regulatory axis is key in luminal B breast cancer
MYC regulation of glutamine–proline regulatory axis is key in luminal B breast cancer, Published online: 23 November 2017; doi:10.1038/bjc.2017.387
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HER2 expression patterns in paired primary and metastatic endometrial cancer lesions
HER2 expression patterns in paired primary and metastatic endometrial cancer lesions
HER2 expression patterns in paired primary and metastatic endometrial cancer lesions, Published online: 23 November 2017; doi:10.1038/bjc.2017.422
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Gemcitabine plus platinum-based chemotherapy for first-line treatment of hepatocholangiocarcinoma: an AGEO French multicentre retrospective study
Gemcitabine plus platinum-based chemotherapy for first-line treatment of hepatocholangiocarcinoma: an AGEO French multicentre retrospective study
Gemcitabine plus platinum-based chemotherapy for first-line treatment of hepatocholangiocarcinoma: an AGEO French multicentre retrospective study, Published online: 23 November 2017; doi:10.1038/bjc.2017.413
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Inflammatory cytokine IL-8/CXCL8 promotes tumour escape from hepatocyte-induced dormancy
Inflammatory cytokine IL-8/CXCL8 promotes tumour escape from hepatocyte-induced dormancy
Inflammatory cytokine IL-8/CXCL8 promotes tumour escape from hepatocyte-induced dormancy, Published online: 23 November 2017; doi:10.1038/bjc.2017.414
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MYC regulation of glutamine–proline regulatory axis is key in luminal B breast cancer
MYC regulation of glutamine–proline regulatory axis is key in luminal B breast cancer
MYC regulation of glutamine–proline regulatory axis is key in luminal B breast cancer, Published online: 23 November 2017; doi:10.1038/bjc.2017.387
MYC regulation of glutamine–proline regulatory axis is key in luminal B breast cancerhttp://ift.tt/2iMQf8P
HER2 expression patterns in paired primary and metastatic endometrial cancer lesions
HER2 expression patterns in paired primary and metastatic endometrial cancer lesions
HER2 expression patterns in paired primary and metastatic endometrial cancer lesions, Published online: 23 November 2017; doi:10.1038/bjc.2017.422
HER2 expression patterns in paired primary and metastatic endometrial cancer lesionshttp://ift.tt/2iL43R6
Gemcitabine plus platinum-based chemotherapy for first-line treatment of hepatocholangiocarcinoma: an AGEO French multicentre retrospective study
Gemcitabine plus platinum-based chemotherapy for first-line treatment of hepatocholangiocarcinoma: an AGEO French multicentre retrospective study
Gemcitabine plus platinum-based chemotherapy for first-line treatment of hepatocholangiocarcinoma: an AGEO French multicentre retrospective study, Published online: 23 November 2017; doi:10.1038/bjc.2017.413
Gemcitabine plus platinum-based chemotherapy for first-line treatment of hepatocholangiocarcinoma: an AGEO French multicentre retrospective studyhttp://ift.tt/2iLHvzx
Inflammatory cytokine IL-8/CXCL8 promotes tumour escape from hepatocyte-induced dormancy
Inflammatory cytokine IL-8/CXCL8 promotes tumour escape from hepatocyte-induced dormancy
Inflammatory cytokine IL-8/CXCL8 promotes tumour escape from hepatocyte-induced dormancy, Published online: 23 November 2017; doi:10.1038/bjc.2017.414
Inflammatory cytokine IL-8/CXCL8 promotes tumour escape from hepatocyte-induced dormancyhttp://ift.tt/2iMkywb
Influence of enhanced recovery after surgery programs on laparoscopy-assisted gastrectomy for gastric cancer: a systematic review and meta-analysis of randomized control trials
Abstract
Background
This meta-analysis is aimed to evaluate the feasibility and safety of enhanced recovery after surgery (ERAS) programs in gastric cancer patients undergoing laparoscopy-assisted gastrectomy (LAG).
Methods
We performed a meta-analysis of randomized control trials involving either enhanced recovery after surgery (ERAS)/fast track surgery (FTS) for patients underwent LAG. EMBASE, Pubmed, Web of science, and Cochrane Library were searched. Primary outcomes included the length of postoperative hospital stay, cost of hospitalization, postoperative complications, and readmission rate.
Results
Five randomized control trials were eligible for analysis. There were 159 cases in FTS group and 156 cases in conventional care group. Compared with conventional care group, FTS group relates to shorter postoperative hospital stay (WMD − 2.16; 95% CI − 3.05 to − 1.26, P < 0.00001), less cost of hospitalization (WMD − 4.72; 95% CI − 6.88 to − 2.55, P < 0.00001), shorter time to first flatus (WMD − 9.72; 95% CI − 13.75 to − 5.81, P < 0.00001), lower level of C-reaction protein on postoperative days 3 or 4 (WMD − 19.66; 95% CI − 28.98 to − 10.34, P < 0.00001), higher level of albumin on postoperative day 4 (WMD 3.45; 95% CI 2.01 to 4.89, P < 0.00001), and postoperative day 7 (WMD 5.63; 95% CI 1.01 to 10.24, P = 0.02). Regarding postoperative complications, no significant differences were observed between FTS group and conventional care group (OR 0.63, 95% CI 0.37 to 1.09, P = 0.10). The readmission rate of FTS group was comparable to conventional care group (WMD 3.14; 95% CI 0.12 to 81.35, P = 0.49).
Conclusions
Among patients undergoing LAG, FTS is associated with shorter postoperative hospital stay, rapid postoperative recovery, and decreased cost without increasing complications or readmission rate. The combined effects of the two methods could further accelerate clinical recovery of gastric cancer patients.
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Influence of enhanced recovery after surgery programs on laparoscopy-assisted gastrectomy for gastric cancer: a systematic review and meta-analysis of randomized control trials
Abstract
Background
This meta-analysis is aimed to evaluate the feasibility and safety of enhanced recovery after surgery (ERAS) programs in gastric cancer patients undergoing laparoscopy-assisted gastrectomy (LAG).
Methods
We performed a meta-analysis of randomized control trials involving either enhanced recovery after surgery (ERAS)/fast track surgery (FTS) for patients underwent LAG. EMBASE, Pubmed, Web of science, and Cochrane Library were searched. Primary outcomes included the length of postoperative hospital stay, cost of hospitalization, postoperative complications, and readmission rate.
Results
Five randomized control trials were eligible for analysis. There were 159 cases in FTS group and 156 cases in conventional care group. Compared with conventional care group, FTS group relates to shorter postoperative hospital stay (WMD − 2.16; 95% CI − 3.05 to − 1.26, P < 0.00001), less cost of hospitalization (WMD − 4.72; 95% CI − 6.88 to − 2.55, P < 0.00001), shorter time to first flatus (WMD − 9.72; 95% CI − 13.75 to − 5.81, P < 0.00001), lower level of C-reaction protein on postoperative days 3 or 4 (WMD − 19.66; 95% CI − 28.98 to − 10.34, P < 0.00001), higher level of albumin on postoperative day 4 (WMD 3.45; 95% CI 2.01 to 4.89, P < 0.00001), and postoperative day 7 (WMD 5.63; 95% CI 1.01 to 10.24, P = 0.02). Regarding postoperative complications, no significant differences were observed between FTS group and conventional care group (OR 0.63, 95% CI 0.37 to 1.09, P = 0.10). The readmission rate of FTS group was comparable to conventional care group (WMD 3.14; 95% CI 0.12 to 81.35, P = 0.49).
Conclusions
Among patients undergoing LAG, FTS is associated with shorter postoperative hospital stay, rapid postoperative recovery, and decreased cost without increasing complications or readmission rate. The combined effects of the two methods could further accelerate clinical recovery of gastric cancer patients.
http://ift.tt/2zw6h1c
Identification of key gene modules and pathways of human breast cancer by co-expression analysis
Abstract
Background
Breast cancer is the most common and aggressive tumor causing injury to women world wide. Although gene expression analysis had been performed previously, systemic co-expression analysis for this cancer is still lacking to date. We attempted to identify the critical modules of breast cancer.
Methods
Co-expression modules were established with the help of WGCNA and the interactions among them were performed by R language. Biological process and pathways analysis of co-expression genes were figured out by GO and KEGG functional enrichment analysis using DAVID dataset.
Results
In this study, expression data of 4,000 genes from 136 samples with breast cancer was used for the establishment of co-expression modules. And nine modules were identified. There was much higher scale independence among different modules by interactions analysis. Moreover, there was an obvious difference in adjacency degree among different modules. The most enriched pathways as immune response and ubiquitin-mediated proteolysis were identified as the most critical modules of breast cancer by GO and KEGG enrichment analysis.
Conclusion
Our result demonstrated that immune response and ubiquitin-mediated proteolysis could serve as prognostic and predictive markers for the occurrence of breast cancer, providing evidence for further analysis in the prognosis and treatment of breast cancer.
http://ift.tt/2i0dDT5
Repurposing Drugs in Oncology (ReDO)—chloroquine and hydroxychloroquine as anti-cancer agents
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Repurposing Drugs in Oncology (ReDO)—chloroquine and hydroxychloroquine as anti-cancer agents
Ciska Verbaanderd, Hannelore Maes, Marco B Schaaf, Vikas P Sukhatme, Pan Pantziarka, Vidula Sukhatme, Patrizia Agostinis and Gauthier Bouche
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Identifying accessible prognostic factors for breast cancer relapse: a case-study on 405 histologically confirmed node-negative patients
Abstract
Background
Histologically, node-negative breast cancer generally have a good prognosis. However, 10 to 30% of the cases present local relapses or metastasis. This group of people has high chances of remission if detected early. The aim of this study is to identify financial affordability for developing countries to adjust treatment.
Methods
We selected 405 patients with histologically confirmed node-negative breast cancer in our institution between January 2001 and December 2003. Patients with metastasis were excluded. The statistical analysis was conducted using SPSS ver. 18 (SPSS, Inc., Chicago, Illinois).
Results
The medial age was 51 years old. The medial tumor size was 35.4 mm. Clinically, 67.2% of the patients were staged cT2 and 63.2%, cN1i. Breast conservation was achieved in 41% of cases. In the histologic examination, the medial size was 30 mm. Grade III tumors were found in 50.1% of patients and positive hormonal receptors in 53.4%. The mean number of lymph nodes was 14. Eight patients had neoadjuvant chemotherapy. Adjuvant locoregional radiation and adjuvant chemotherapy were prescribed respectively in 70.6 and 64.4% of cases. 59.7% had adjuvant hormonal therapy. The follow-up showed 17.7% cases of relapse either locally or in a metastatic way in a mean time of 57.4 months. The disease-free survival at 5 years was 82.1%, and the overall survival for the same period was 91.5%.
The histologic tumor size and the grade and number of lymph node dissected were shown to be influencing the disease-free survival. Radiation therapy and hormone therapy showed improved disease-free survival and overall survival.
Conclusion
Our study found interesting results that may help personalize the treatment especially for patient living in underdeveloped countries, but further studies are needed to evaluate those and more accessible prognostic factors for a more accessible healthcare.
http://ift.tt/2B5qxTt
Identifying accessible prognostic factors for breast cancer relapse: a case-study on 405 histologically confirmed node-negative patients
Abstract
Background
Histologically, node-negative breast cancer generally have a good prognosis. However, 10 to 30% of the cases present local relapses or metastasis. This group of people has high chances of remission if detected early. The aim of this study is to identify financial affordability for developing countries to adjust treatment.
Methods
We selected 405 patients with histologically confirmed node-negative breast cancer in our institution between January 2001 and December 2003. Patients with metastasis were excluded. The statistical analysis was conducted using SPSS ver. 18 (SPSS, Inc., Chicago, Illinois).
Results
The medial age was 51 years old. The medial tumor size was 35.4 mm. Clinically, 67.2% of the patients were staged cT2 and 63.2%, cN1i. Breast conservation was achieved in 41% of cases. In the histologic examination, the medial size was 30 mm. Grade III tumors were found in 50.1% of patients and positive hormonal receptors in 53.4%. The mean number of lymph nodes was 14. Eight patients had neoadjuvant chemotherapy. Adjuvant locoregional radiation and adjuvant chemotherapy were prescribed respectively in 70.6 and 64.4% of cases. 59.7% had adjuvant hormonal therapy. The follow-up showed 17.7% cases of relapse either locally or in a metastatic way in a mean time of 57.4 months. The disease-free survival at 5 years was 82.1%, and the overall survival for the same period was 91.5%.
The histologic tumor size and the grade and number of lymph node dissected were shown to be influencing the disease-free survival. Radiation therapy and hormone therapy showed improved disease-free survival and overall survival.
Conclusion
Our study found interesting results that may help personalize the treatment especially for patient living in underdeveloped countries, but further studies are needed to evaluate those and more accessible prognostic factors for a more accessible healthcare.
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OV21/PETROC: A randomized Gynecologic Cancer Intergroup phase II study of intraperitoneal versus intravenous chemotherapy following neoadjuvant chemotherapy and optimal debulking surgery in epithelial ovarian cancer
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Prevalence and clinical association of gene mutations through Multiplex Mutation Testing in patients with NSCLC: Results from the ETOP Lungscape Project
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OV21/PETROC: A randomized Gynecologic Cancer Intergroup phase II study of intraperitoneal versus intravenous chemotherapy following neoadjuvant chemotherapy and optimal debulking surgery in epithelial ovarian cancer
http://ift.tt/2hYkT1t
Prevalence and clinical association of gene mutations through Multiplex Mutation Testing in patients with NSCLC: Results from the ETOP Lungscape Project
http://ift.tt/2jR8pJK
Unilateral erythaema nodosum: atypical presentation in paediatrics
Description
A previously healthy 12-year-old boy was observed in the emergency department due to pain and erythaema in the left shin for the past 2 weeks. He was discharged with flucloxacilin for cellulitis. One week later, he returned with oedema and erythaema of the left shin, with palpable nodules and purple discolouration (figure 1). The right leg was normal. Oropharyngeal hyperaemia was observed.
Figure 1
Erythaema, oedema and nodules in the left shin.
Complementary study revealed erythrocyte sedimentation rate of 12 mm/hour and antistreptolysin O titre was 985 UI/mL (normal range 0–408 UI/mL). C reactive protein was <2.90 mg/dL; autoimmunity study, infectious serologies (hepatitis B virus and Epstein-Barr virus, EBV, Mycoplasma pneumoniae and Salmonella spp.) rapid strep test and Mantoux test were negative. Ultrasound showed subcutaneous oedema. Biopsy revealed septal panniculitis, compatible with erythaema nodosum (figure 2). He was discharged.
Figure 2
Incisional biopsy....
http://ift.tt/2zeVX9t
ANCA-positive IgA nephropathy without necrotising or crescentic glomerulonephritis: a clinical conundrum
IgA nephropathy, the most prevalent form of primary glomerular disease, usually portends a favourable outcome. Antineutrophil cytoplasmic autoantibodies (ANCAs) have been reported in association with IgA nephropathy in a small subset of patients, mostly presenting with rapidly progressive glomerulonephritis and necrotising crescentic lesions. Herein, we describe a case of IgA nephropathy, positive serum cytoplasmic and perinuclear ANCAs with anti-myeloperoxidase antibody, and preserved renal function without any histological evidence of necrotising or crescentic glomerulonephritis. Based on available mechanistic and clinical data, we opine that such patients could benefit from close monitoring of renal function.
http://ift.tt/2Bh212E
Twist on a classic: vitamin D and hypercalcaemia of malignancy
Malignancy is the most common cause of hypercalcaemia in the inpatient setting. Most cases are caused by tumour production of parathyroid hormone-related protein and osseous metastases. In less than 1% of cases, hypercalcaemia is driven by increased production of 1,25-dihydroxyvitamin D (1,25(OH)2D), a mechanism most commonly seen in haematological malignancies. Here, we describe a woman with metastatic small cell cervical carcinoma who developed hypercalcaemia secondary to paraneoplastic overproduction of 1,25(OH)2D, a finding that, to our knowledge, has not been previously associated with this cancer. We also review the current cases of solid tumours reported to have this mechanism of hypercalcaemia and the evidence behind multiple therapeutic approaches.
http://ift.tt/2zjeMIs
A regressing spindle cell tumour of Reed
Description
Spindle cell tumour of Reed is a benign melanocytic naevus which usually presents as a deeply pigmented mole. It is more commonly found on the lower extremities of young girls. It is an uncommon naevus but its incidence and prevalence are not known. A Reed naevus typically goes through a rapid initial growth phrase before stabilising in size and then regresses over time.1 Awareness of Reed naevus has been demonstrated to be low, even among dermatology doctors.2
The main dermoscopic patterns (when observed under magnification using a dermatoscope) observed are the starburst pattern (50.6% of cases), pattern of dotted vessels (19.3%), globular pattern (17%) and atypical pattern (9.0%).3
Figure 1A illustrates a 7 mmx5 mm symmetrical deeply pigmented plaque on the right knee of a 5-year-old girl. Figure 1B shows the dermatoscopic symmetrical starburst pattern with regular pigment network....
http://ift.tt/2BggkEz
Dental implants in a patient with suspected leucocyte adhesion deficiency
Aggressive periodontitis and premature tooth loss in leucocyte adhesion deficiency (LAD) have adverse functional and psychological consequences on affected individuals. Dental implant rehabilitation might become necessary to overcome the functional and psychological adverse effects of LAD periodontitis, especially in patients with milder forms who are expected to have a relatively normal life expectancy. Outcome of dental implants in patients with LAD has not been previously reported; we describe the dental rehabilitation of a 24-year-old man with clinical features of LAD using endosseous dental implants.
http://ift.tt/2zjeKjO
Multiple hybrid sutures of bucket handle injury on the lateral and medial meniscus of the knee
The objective of the study is to show possibilities of several combinations of suture techniques in a rare bicompartmental bucket handle injury. According to specific injury characteristics, combined suturing techniques were used. The option for different meniscal suture techniques in the two knee compartments allowed the patient, after completing the treatment, to return to his activities with a preserved meniscus. Although meniscectomy continues to be a chosen technique in bucket handle injury, we attempted to show a case of bicompartmental meniscal suture with different techniques. In this, which could be a case of rapid resolution and quick return to activities with bicompartmental meniscectomy, we chose to preserve the menisci with more complex techniques and longer rehabilitation, believing that the preservation of this structure could be extremely valuable in the long term.
http://ift.tt/2zYR3Bf
Eosinophilic myocarditis as a first presentation of eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)
We present the case of a 28-year-old man who presented with chest pain and elevated cardiac biomarkers, with no evidence of acute ischaemia. He had a pronounced eosinophilia, abnormal echocardiographic, cardiac MRI and CT findings. He underwent transbronchial biopsy of carinal lymph nodes and of lung parenchyma. Endomyocardial biopsy yielded an eosinophilic infiltrate. He was treated with high dose glucocorticoids and made a rapid recovery. Testing for FIP1L1-PDGFRA and other BCR-ABL1 mutations was negative. Ultimately, he was diagnosed with eosinophilic granulomatosis with polyangiitis, also known as Churg-Strauss syndrome.
http://ift.tt/2ApYqCm
Dysosmia and dysgeusia associated with duloxetine
Common adverse effects of serotonin–norepinephrine reuptake inhibitors are nausea, dry mouth, dizziness and headache. We describe the case of a patient with dysosmia and subsequent dysgeusia associated with duloxetine. A 68-year-old Japanese woman with a history of type 1 diabetes mellitus, hypertension, insomnia and reflux esophagitis presented to a local hospital with bilateral leg pain; she was treated with duloxetine. However, after 4 weeks, she sensed rotten egg smell, experienced nausea and vomiting and was admitted to our hospital. We diagnosed dysosmia using the T&T olfactometer threshold test and dysgeusia using filter paper disk method. Taste was assessed using electrogustometry. We suspected that dysosmia and dysgeusia were adverse effects of duloxetine. After stopping duloxetine, her symptoms gradually subsided and the above test results improved, despite continuing the other ongoing medication. To the best of our knowledge, this is the first case report of dysosmia and dysgeusia associated with duloxetine.
http://ift.tt/2A2lKFC
Kikuchi-Fujimoto disease: an unusual presentation of meningitis in a returning traveller
A 19-year-old, previously healthy woman developed a pruritic erythematous maculopapular rash on her bilateral palms and wrists, right-sided tender cervical lymphadenopathy and nightly fevers and headaches 5 days after returning from a 1-month trip to Cambodia. She presented 2 weeks after her trip due to ongoing nightly fevers to a maximum of 38.8°C. She was given empiric doxycycline for possible rickettsial disease, though an extensive infectious workup returned without positive findings. Lumbar puncture was performed on hospital day 4, and spinal fluid analysis was consistent with aseptic meningitis. On hospital day 5, core biopsy and fine-needle aspiration were performed on the largest anterior cervical lymph node. Her fever curve gradually improved, and she was discharged on hospital day 6. Results of the lymph node biopsy were finalized 5 days after discharge and were compatible with Kikuchi's lymphadenitis. Symptoms had completely resolved on follow-up with infectious disease and rheumatology.
http://ift.tt/2ArOOa6
False-positive phencyclidine (PCP) on urine drug screen attributed to desvenlafaxine (Pristiq) use
We report a likely false-positive phencyclidine (PCP) result detected with a urine drug screen (UDS) (Medtox, St Paul, Minnesota, USA) in the setting of therapeutic desvenlafaxine (Pristiq) use. Desvenlafaxine (O-desmethylvenlafaxine) is the active metabolite of venlafaxine (Effexor). Prior reports have confirmed venlafaxine use resulting in a false-positive for PCP on a UDS. However, there has been a paucity of reporting of commercially available desvenlafaxine formulations (Pristiq, Khedezla) resulting in false-positives for PCP on a UDS.
http://ift.tt/2A13ufU
Wernickes encephalopathy secondary to gestational hyperthyroidism
Background
Wernicke's encephalopathy is a neurological disorder secondary to the deficiency of vitamin B1 (thiamine). The classic symptoms consist of nystagmus, ophthalmoplegia, ataxia and mental status changes.1 Initially, this was described by Carl Wernicke in 1881 as acute haemorrhagic polioencephalitis.2
Wernicke's encephalopathy is mostly described in association with malnutrition and alcoholism.1 However, it has been increasingly being noted in various other settings. There is also evidence that this may be an underdiagnosed condition as several cases may not manifest the classical triad of symptoms. Prompt diagnosis and treatment are essential as any delay or undertreatment can result in irreversible complications.
We report a case of gestational hyperthyroidism causing Wernicke's encephalopathy. To our knowledge, there have been only four previous cases of gestational hyperthyroidism causing Wernicke's encephalopathy in the literature.3–7
Case presentation...http://ift.tt/2ArOxnA
Muscle fasciculation detected by ECG
A 79-year-old man presented to hospital with scald burns to the perineum after a syncopal episode while in a hot bathtub. Admission ECG was misdiagnosed as possible ventricular fibrillation with high-frequency irregular waveforms in lead V2 at a rate exceeding 1000 cycles per minute, corresponding to intervening skeletal muscle contractions unrelated to the heart. Follow-up ECG showed full resolution of the irregular waveforms. Muscle fasciculations are a benign cause of ECG artefact and can easily be mistaken for serious cardiac arrhythmias. While most muscle fasciculations detected on ECG are benign, in the correct clinical circumstance these waveforms indicate an underlying neuromuscular disorder. The patient underwent surgical skin grafting with no perioperative cardiac complications and no further syncope in hospital.
http://ift.tt/2A19aGv
Schizophrenia and anaesthesia
Administering anaesthesia for elderly patients with chronic schizophrenia has always been a great challenge to anaesthetists. These patients will usually be on multiple antipsychotic drugs for many years and may lead to delayed awakening, cardiovascular instability, arrhythmias and sudden cardiac death during general anaesthesia. This case report is about the perioperative anaesthetic management of an elderly schizophrenic patient undergoing removal of femur implant. This article will explore important drug interactions and available options for a successful anaesthesia.
http://ift.tt/2A13cFQ
Panuveitis simulating ocular Behcets in cases of chronic myelogenous leukaemia in remission
We report two patients with chronic myelogenous leukaemia (CML) in remission phase who developed panuveitis simulating Behcet's disease. A 26-year-old man presented with bilateral panuveitis (hypopyon in the right eye, bilateral anterior segment inflammation, vitritis and retinitis). He was on imatinib for CML which was in remission. He gave a history of recurrent oral ulcers. The panuveitis responded to oral and topical steroids but recurred after the steroids were stopped. His ocular condition again stabilised on restarting oral steroids and azathioprine. The second patient, a 28-year-old man, presented with bilateral anterior segment inflammation, vitritis, exudative retinal detachment and hypopyon in the right eye. He was also on imatinib with the CML being in remission. The uveitis and exudative retinal detachment improved on systemic and topical steroids. The vision of this patient did not improve as optic atrophy ensued. The panuveitis seen in our patients with CML responded favourably to oral steroids/immunosuppressant therapy.
http://ift.tt/2ApkAV0
Rare presentation of cementoblastoma associated with the deciduous maxillary second molar
Cementoblastoma is a benign odontogenic neoplasm accounting for less than 0.69%–8% of all odontogenic tumours and is characterised by the presence of sheets of cementum-like tissue demonstrating large number of reversal lines. It shows an unlimited growth potential and a recurrence rate as high as 37.1%. It most commonly affects the permanent mandibular molars. This paper presents the third reported case of cementoblastoma affecting the deciduous maxillary posterior dentition. A 12-year-old male patient reported to the Department of Oral and Maxillofacial Pathology with a chief complaint of pain and swelling in relation to the deciduous maxillary left second molar.
http://ift.tt/2zYQLKF
Large, extra-abdominal leiomyoma of the round ligament with carneous degeneration
Round ligament tumours represent a rare entity that can present similarly to an incarcerated hernia. Basic understanding and appropriate preoperative management is imperative in order to differentiate between the two diagnoses. Leiomyoma is the most common type of round ligament tumour. It is associated with oestrogen exposure and is more common in the presence of uterine leiomyomas. Here we discuss a 68-year-old woman who presented with a palpable left inguinal mass that progressively grew in size, associated with pelvic pressure and discomfort. On surgical resection, the mass was found to be derived from the round ligament at the entrance of the external inguinal ring. Pathology confirmed a round ligament leiomyoma, measuring 25x9x8.5 cm. This case is the largest round ligament leiomyoma recorded to date and the first to exhibit carneous degeneration. A review of the current literature is also provided.
http://ift.tt/2Are0xt
A case of large right MCA stroke with hyperdense MCA sign in CT imaging
Description
A 76-year-old woman with no significant medical history was brought to the emergency department with complaints of sudden onset of left-sided weakness and facial drooping 1 hour prior to the arrival. On physical examination, patient had profound left-sided neglect and conjugate deviation of the eyes to the right side. Motor examination showed grade 0 power on left upper and lower extremities, and she had 3+ reflexes on the left and 2+ reflexes on the right. Babinski was positive on the left side. She was sent for a CT scan which showed increased density of M1 segment of middle cerebral artery (MCA) with loss of grey white differentiation of MCA territory (figure 1). Alberta Stroke Programme Early CT Score was 8. Patient's initial National Institutes of Health Stroke Scale score was 17 and was immediately given tissue plasminogen activator (TPA) as the family adamantly refused endovascular procedure; however, her post-TPA score was also 17 as...
http://ift.tt/2A1HvFk
Characteristic imaging findings in pulmonary fat embolism syndrome (FES)
Description
A 21-year-old male presented to the hospital following a road accident. He was riding a motorcycle when he flung into a roadside drain. On arrival, his Glasgow Coma Scale was 15/15 and vital signs were stable. On examination, there was tenderness and deformity of the left thigh. The diagnosis of closed comminuted fractures of the left femur was confirmed following plain radiography. Chest radiograph was normal (figure 1). He was admitted and planned for interlocking nail (ILN) insertion at the left femur. Two days after admission, his blood oxygen saturation (SpO2) became low at 92% despite 3 L of oxygen. He was febrile and tachycardic. On day 3, he developed chest pain, palpitations and tachypnoea. Oxygen support was escalated to intubation and mechanical ventilation. Chest radiograph then showed diffuse air space opacities bilaterally (figure 1). CT pulmonary angiogram showed diffuse ground-glass opacities and consolidations in both lung...
http://ift.tt/2AphPDm
The rare occurrence of cutaneous and mucosal lichen planus in HIV infection
Description
A 36-year-old man, a rickshaw driver by profession, who was diagnosed with HIV infection 3 years back, was on regular antiretroviral therapy consisting of zidovudine, lamivudine and nevirapine. He presented with complaints of a pruritic rash on both his legs since 7 months, which started as a single lesion and gradually spread to the current state over the next 6 weeks. Barring his antiretroviral therapy, he did not have any other drug history. He did not consume alcohol, did not chew tobacco and did not smoke. His CD4-positive cell count at the time of presentation was 336/mm3, serology for hepatitis C virus and hepatitis B virus was negative and other laboratory parameters such as complete blood count, liver and renal function tests were normal.
On examination, he had polygonal, planar, purple papules over the anterior aspect of legs (figure 1), and also white lacy lines (with a reticular pattern) in the left buccal mucosa (figure 2), which were suggestive of Wickham striae.
http://ift.tt/2zZYh7U
Tenon patch graft for corneal fistula: a rare entity treated by a simple technique
A 50-year-old patient presented with dull aching pain with some discomfort in his right eye for the past 2 weeks. History revealed the patient had a past episode of infective keratitis managed medically in a local hospital. The last follow-up record suggested a diagnosis of healed keratitis with corneoiridic scar. On examination, the patient had visual acuity of hand movement and a corneoiridic scar of 7x7 mm with an inferotemporal translucent cystic area measuring 3x4 mm in size with underlying uveal tissue visible. Seidel test was found to be positive confirming leakage. For this, a tenon patch over the area of defect along with anterior chamber formation was done. On postoperative day 1, the graft was well attached and anterior chamber was formed with no leak on Seidel test. Intraocular pressure was 16 mm Hg.
http://ift.tt/2ApmXYi
DNA replication stress and cancer chemotherapy
Abstract
DNA replication is one of the fundamental biological processes in which dysregulation can cause genome instability. This instability is one of the hallmarks of cancer and confers genetic diversity during tumorigenesis. Numerous experimental and clinical studies have indicated that most tumors have experienced and overcome the stresses caused by the perturbation of DNA replication, which is also referred to as DNA replication stress (DRS). When we consider therapeutic approaches for tumors, it is important to exploit the differences in DRS between tumor and normal cells. In this review, we introduce the current understanding of DRS in tumors and discuss about the underlying mechanism of cancer therapy from the aspect of DRS.
This article is protected by copyright. All rights reserved.
http://ift.tt/2zwikeC
HOXC13 promotes proliferation of esophageal squamous cell carcinoma via repressing transcription of CASP3
Summary
Esophageal squamous cell carcinoma (ESCC), the dominant subtype of esophageal cancer, is one of the most common digestive tumors worldwide. In this study, we confirmed that HOXC13, a member of the homeobox HOXC gene family, was significantly upregulated in ESCC and its overexpression was associated with poorer clinical characteristics and worse prognosis. Moreover, knockdown of HOXC13 inhibited proliferation and induced apoptosis of ESCC via upregulating CASP3. Chromatin Immunoprecipitation analysis revealed that HOXC13 repressed transcription of CASP3 via directly targeting the promotor region of CASP3. We also found that miR-503 downregulated HOXC13, by directly targeting its 3′UTR, and inhibited proliferation of ESCC. In conclusion, our study demonstrates that HOXC13, which is directly targeted by miR-503, promotes proliferation and inhibits apoptosis of ESCC via repressing transcription of CASP3.
This article is protected by copyright. All rights reserved.
http://ift.tt/2A395C1
Proliferation genes in lung development associated with the prognosis of lung adenocarcinoma but not squamous cell carcinoma
Abstract
There are many similarities between embryonic development and tumorigenesis, and gene expression profiles show that certain correlations exist between the gene signature during development and the clinical phenotypes of different cancers. Our group previously reported the gene expression profiles of human lung development, and the expression of one group of proliferation-related genes (named as PTN1 genes) steadily decreased during lung development. Here, we examined the prognostic value of PTN1 genes in five independent lung adenocarcinoma (ADC) and five lung independent squamous cell carcinoma (SCC) microarray datasets and found that the expression levels of PTN1 genes were associated with survival in lung ADC but not lung SCC. All the lung ADC datasets contained a set of highly correlated genes from PTN1 genes, but the lung SCC datasets had no similar set of genes. We identified 63 unique core genes from the PTN1 genes in the five lung ADC datasets, 17 of these core genes appeared in at least four of the lung ADC datasets, and the 17 corresponding proteins clearly interacted more strongly with each other in lung ADC than in lung SCC. Moreover, 16 of the 17 core genes play major roles in the G2/M phase of the cell cycle. These data indicate that proliferation-related genes in lung development have a significant prognostic value for lung ADC; the synergistic effects of the 17 core genes play an important role in lung ADC prognosis. These genes may have significant clinical implications for the treatment and prognosis of lung ADC.
This article is protected by copyright. All rights reserved.
http://ift.tt/2hKTkoJ
PRIMA-1 induces p53-madiated apoptosis by upregulating Noxa in esophageal squamous cell carcinoma with TP53 missense mutation
Abstract
TP53 is associated with the resistance of cytotoxic treatment and patient prognosis, and the mutation rate of TP53 in esophageal squamous cell carcinoma (ESCC) is extraordinarily high, at over 90%. PRIMA-1 (p53 re-activation and induction of massive apoptosis) has recently been reported to restore the function of mutant TP53; however, its antitumor effect and mechanism in ESCC remain unclear. After evaluating the TP53 mutation status of a panel of eleven ESCC cell lines by Sanger sequencing, we assessed the in vitro effect of PRIMA-1 administration on cells with different p53 status by conducting cell viability and apoptosis assays. The expression levels of proteins in TP53-related pathways were examined by Western blotting, while knockdown studies were conducted to investigate the mechanism underlying PRIMA-1′s function. An ESCC xenograft model was further used to evaluate the therapeutic effect of PRIMA-1 in vivo. PRIMA-1 markedly inhibited cell growth and induced apoptosis by upregulating Noxa expression in ESCC cell lines with TP53 missense mutations, whereas no apoptosis was induced in ESCC with wild type TP53 and TP53 with frameshift and nonsense mutations. Importantly, the knockdown of Noxa cancelled the apoptosis induced by PRIMA treatment in ESCC cell lines with TP53 missense mutations. PRIMA-1 administration, compared with placebo, showed a significant antitumor effect by inducing Noxa in the xenograft model of an ESCC cell line with a TP53 missense mutation. PRIMA-1 exhibits a significant antitumor effect, inducing massive apoptosis through the upregulation of Noxa in ESCC with TP53 missense mutations.
This article is protected by copyright. All rights reserved.
http://ift.tt/2A1PDFy
DNA replication stress and cancer chemotherapy
Abstract
DNA replication is one of the fundamental biological processes in which dysregulation can cause genome instability. This instability is one of the hallmarks of cancer and confers genetic diversity during tumorigenesis. Numerous experimental and clinical studies have indicated that most tumors have experienced and overcome the stresses caused by the perturbation of DNA replication, which is also referred to as DNA replication stress (DRS). When we consider therapeutic approaches for tumors, it is important to exploit the differences in DRS between tumor and normal cells. In this review, we introduce the current understanding of DRS in tumors and discuss about the underlying mechanism of cancer therapy from the aspect of DRS.
This article is protected by copyright. All rights reserved.
from Cancer via ola Kala on Inoreader http://ift.tt/2zwikeC
via IFTTT
HOXC13 promotes proliferation of esophageal squamous cell carcinoma via repressing transcription of CASP3
Summary
Esophageal squamous cell carcinoma (ESCC), the dominant subtype of esophageal cancer, is one of the most common digestive tumors worldwide. In this study, we confirmed that HOXC13, a member of the homeobox HOXC gene family, was significantly upregulated in ESCC and its overexpression was associated with poorer clinical characteristics and worse prognosis. Moreover, knockdown of HOXC13 inhibited proliferation and induced apoptosis of ESCC via upregulating CASP3. Chromatin Immunoprecipitation analysis revealed that HOXC13 repressed transcription of CASP3 via directly targeting the promotor region of CASP3. We also found that miR-503 downregulated HOXC13, by directly targeting its 3′UTR, and inhibited proliferation of ESCC. In conclusion, our study demonstrates that HOXC13, which is directly targeted by miR-503, promotes proliferation and inhibits apoptosis of ESCC via repressing transcription of CASP3.
This article is protected by copyright. All rights reserved.
from Cancer via ola Kala on Inoreader http://ift.tt/2A395C1
via IFTTT
Proliferation genes in lung development associated with the prognosis of lung adenocarcinoma but not squamous cell carcinoma
Abstract
There are many similarities between embryonic development and tumorigenesis, and gene expression profiles show that certain correlations exist between the gene signature during development and the clinical phenotypes of different cancers. Our group previously reported the gene expression profiles of human lung development, and the expression of one group of proliferation-related genes (named as PTN1 genes) steadily decreased during lung development. Here, we examined the prognostic value of PTN1 genes in five independent lung adenocarcinoma (ADC) and five lung independent squamous cell carcinoma (SCC) microarray datasets and found that the expression levels of PTN1 genes were associated with survival in lung ADC but not lung SCC. All the lung ADC datasets contained a set of highly correlated genes from PTN1 genes, but the lung SCC datasets had no similar set of genes. We identified 63 unique core genes from the PTN1 genes in the five lung ADC datasets, 17 of these core genes appeared in at least four of the lung ADC datasets, and the 17 corresponding proteins clearly interacted more strongly with each other in lung ADC than in lung SCC. Moreover, 16 of the 17 core genes play major roles in the G2/M phase of the cell cycle. These data indicate that proliferation-related genes in lung development have a significant prognostic value for lung ADC; the synergistic effects of the 17 core genes play an important role in lung ADC prognosis. These genes may have significant clinical implications for the treatment and prognosis of lung ADC.
This article is protected by copyright. All rights reserved.
from Cancer via ola Kala on Inoreader http://ift.tt/2hKTkoJ
via IFTTT
PRIMA-1 induces p53-madiated apoptosis by upregulating Noxa in esophageal squamous cell carcinoma with TP53 missense mutation
Abstract
TP53 is associated with the resistance of cytotoxic treatment and patient prognosis, and the mutation rate of TP53 in esophageal squamous cell carcinoma (ESCC) is extraordinarily high, at over 90%. PRIMA-1 (p53 re-activation and induction of massive apoptosis) has recently been reported to restore the function of mutant TP53; however, its antitumor effect and mechanism in ESCC remain unclear. After evaluating the TP53 mutation status of a panel of eleven ESCC cell lines by Sanger sequencing, we assessed the in vitro effect of PRIMA-1 administration on cells with different p53 status by conducting cell viability and apoptosis assays. The expression levels of proteins in TP53-related pathways were examined by Western blotting, while knockdown studies were conducted to investigate the mechanism underlying PRIMA-1′s function. An ESCC xenograft model was further used to evaluate the therapeutic effect of PRIMA-1 in vivo. PRIMA-1 markedly inhibited cell growth and induced apoptosis by upregulating Noxa expression in ESCC cell lines with TP53 missense mutations, whereas no apoptosis was induced in ESCC with wild type TP53 and TP53 with frameshift and nonsense mutations. Importantly, the knockdown of Noxa cancelled the apoptosis induced by PRIMA treatment in ESCC cell lines with TP53 missense mutations. PRIMA-1 administration, compared with placebo, showed a significant antitumor effect by inducing Noxa in the xenograft model of an ESCC cell line with a TP53 missense mutation. PRIMA-1 exhibits a significant antitumor effect, inducing massive apoptosis through the upregulation of Noxa in ESCC with TP53 missense mutations.
This article is protected by copyright. All rights reserved.
from Cancer via ola Kala on Inoreader http://ift.tt/2A1PDFy
via IFTTT
Herpes simplex type 1 pneumonitis and acute respiratory distress syndrome in a patient with chronic lymphatic leukemia: a case report
Pulmonary pathogenicity of herpes simplex virus type 1 in patients in intensive care without classic immunosuppression as well as the necessity of antiviral treatment in the case of herpes simplex virus detect...
http://ift.tt/2mTuus6
Genetic Variants in the Platelet-Derived Growth Factor Subunit B Gene Associated with Pancreatic Cancer Risk
Abstract
The PDGF signaling pathway plays important roles in development and progression of human cancers. In this study, we aimed to identify genetic variants of the PDGF pathway genes associated with pancreatic cancer risk in European populations by using three published GWAS datasets, which consisted of 9,381 cases and 7,719 controls. The expression quantitative trait loci (eQTL) analysis was also performed by using data from the 1000 Genomes, TCGA and GTEx projects. As a result, we identified two potential susceptibility loci (rs5757573 and rs6001516) of PDGFB associated with pancreatic cancer risk [odds ratio (OR) = 1.10, 95% confidence interval (CI) = 1.05-1.16, and P = 4.70x10−5 for the rs5757573 C allele and 1.21, 1.11-1.32, and 2.01x10−5 for the rs6001516 T allele]. Haplotype analysis revealed that the C-T haplotype carriers had a significantly increased risk of pancreatic cancer than those carrying the T-C haplotype (OR = 1.23, 95% CI = 1.12-1.34, P =5.00 × 10−6). The multivariate regression model incorporating the number of unfavorable genotypes (NUGs) with age and sex showed that carriers with 1-2 NUGs, particularly among 60-70 age group or males, had an increased risk of pancreatic cancer, compared with those without NUG. Further, the eQTL analysis revealed that both loci were correlated with a decreased mRNA expression level of PDGFB in lymphoblastoid cell lines and pancreatic tumor tissues (P = 0.015 and 0.071, respectively). Our results suggest that genetic variants in PDGFB may play a role in susceptibility to pancreatic cancer. Further population and functional validations of our findings are warranted. This article is protected by copyright. All rights reserved.
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Adipokines and inflammation markers and risk of differentiated thyroid carcinoma: The EPIC study
Abstract
Other than the influence of ionizing radiation and benign thyroid disease, little is known about the risk factors for differentiated thyroid cancer (TC) which is an increasing common cancer worldwide. Consistent evidence shows that body mass is positively associated with TC risk. As excess weight is a state of chronic inflammation, we investigated the relationship between concentrations of leptin, adiponectin, C-reactive protein, interleukin(IL)-6, IL-10 and TNF-α and the risk of TC.
A case-control study was nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study and included 475 first primary incident TC cases (399 women and 76 men) and 1,016 matched cancer-free cohort participants. Biomarkers were measured in serum samples using validated and highly sensitive commercially available immunoassays. Odds ratios (ORs) of TC by levels of each biomarker were estimated using conditional logistic regression models, adjusting for BMI and alcohol consumption.
Adiponectin was inversely associated with TC risk among women (ORT3vs.T1=0.69, 95%CI: 0.49-0.98, Ptrend=0.04) but not among men (ORT3vs.T1=1.36, 95%CI: 0.67-2.76, Ptrend=0.37). Increasing levels of IL-10 were positively associated with TC risk in both genders and significantly so in women (ORT3vs.T1=1.59, 95%CI: 1.13-2.25, Ptrend=0.01) but not in men (ORT3vs.T1=1.78, 95%CI: 0.80-3.98, Ptrend=0.17). Leptin, CRP, IL-6 and TNF-α were not associated with TC risk in either gender.
These results indicate a positive association of TC risk with IL-10 and a negative association with adiponectin that is probably restricted to women. Inflammation may play a role in TC in combination with or independently of excess weight. This article is protected by copyright. All rights reserved.
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The arginine metabolome in Acute Lymphoblastic Leukemia can be targeted by the PEG-recombinant Arginase I BCT-100
Abstract
Arginine is a semi-essential amino acid that plays a key role in cell survival and proliferation in normal and malignant cells. BCT-100, a pegylated recombinant human arginase, can deplete arginine and starve malignant cells of the amino acid. Acute Lymphoblastic Leukemia is the most common cancer of childhood, yet for patients with high risk or relapsed disease prognosis remains poor. We show that BCT-100 is cytotoxic to ALL blasts from patients in vitro by necrosis, and is synergistic in combination with dexamethasone. Against ALL xenografts BCT-100 leads to a reduction in ALL engraftment and a prolongation of survival. ALL blasts express the arginine transporter CAT-1, yet the majority of blasts are arginine auxotrophic due to deficiency in either argininosuccinate synthase (ASS) or ornithine transcarbamylase (OTC). Although endogenous upregulation or retroviral transduced increases in ASS or OTC may promote ALL survival under moderately low arginine conditions, expression of these enzymes cannot prevent BCT-100 cytotoxicity at arginine depleting doses. RNA-sequencing of ALL blasts and supporting stromal cells treated with BCT-100 identifies a number of candidate pathways which are altered in the presence of arginine depletion. Therefore BCT-100 provides a new clinically-relevant therapeutic approach to target arginine metabolism in ALL. This article is protected by copyright. All rights reserved.
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Tumor characteristics and prognosis in women with pregnancy-associated breast cancer
Abstract
There is evidence of poor prognosis in women with pregnancy-associated breast cancer (PABC) diagnosed during pregnancy or within two years of delivery. Using a large, population-based cohort, we examined clinicopathologic features and survival in women with PABC. A cohort of women diagnosed with invasive breast cancer between 1992 and 2009 at ages 15 to 44 years was identified in the Swedish Cancer Register and the Breast Cancer Quality Registers. Dates of childbirths for each woman were retrieved from the Swedish Multi-Generation Register. Age-standardized distributions of tumor stage (TNM), Elston grade and ER/PR/HER2 status were compared between nulliparous women and women with breast cancer during pregnancy and up to 10 years post-delivery. Adjusted hazard ratios for all-cause mortality rates among patients were estimated using Cox regression. We identified 1,661 nulliparous women with breast cancer, 778 women with PABC (97 during pregnancy, 270 within first and 411 within second year post-delivery), and 3,598 during 2-10 years post-delivery. Compared to nulliparous women, women with PABC, and especially women diagnosed 0-12 months after delivery, had more advanced T and N stage, and higher proportions of ER/PR negative, HER2 positive and triple-negative tumors. Increased hazard ratios were observed in women diagnosed within 5 years of delivery after adjustment for age, year, education and region. Following additional adjustment for tumor characteristics, the hazard ratios were attenuated and non-significant. The poorer prognosis observed in women with pregnancy-associated breast cancer appears to be largely explained by more adverse tumor characteristics at diagnosis. This article is protected by copyright. All rights reserved.
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YY1 suppresses proliferation and migration of pancreatic ductal adenocarcinoma by regulating the CDKN3/MdM2/P53/P21 signaling pathway
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the malignant lethal tumors. It has been reported that the transcriptional regulator Yin Yang-1 (YY1) suppressed the invasion and metastasis of PDAC. However, the function of YY1 on proliferation and migration of pancreatic cancer remains to be clarified. In this study, we found that YY1 overexpression or knockdown can inhibit or promote the proliferation and migration of pancreatic cancer cells. Digital gene expression (DGE) sequencing indicates that cyclin-dependent kinase inhibitor 3 (CDKN3) may be the candidate target gene of YY1. Then we found that YY1 can downregulate the expression of CDKN3 by directly binding to the promoter region of CDKN3. Silencing CDKN3 expression could inhibit the ability of cell proliferation and migration, and overexpression of CDKN3 could restore the effects induced by YY1 overexpression in pancreatic cancer cells. The expression levels of YY1 and CDKN3 were negatively correlated in pancreatic cancer tissues and PDAC patients with higher levels of CDKN3 have poor prognosis. Vitro and vivo study show that CDKN3 can form a complex with MdM2-P53, thus leading to inhibiting the expression of P21, which is the target gene of P53, and finally facilitates the cell cycle to promote the proliferation of pancreatic cancer cells. Hence, YY1 can directly regulate the expression of CDKN3 and participate in the cycle of pancreatic cancer cells, which can inhibit the progression of pancreatic cancer. These results reveal that YY1-CDKN3-MDM2/P53-P21 axis is involved in pancreatic tumorigenesis, which may develop new methods for human pancreatic cancer therapy. This article is protected by copyright. All rights reserved.
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Genetic Variants in the Platelet-Derived Growth Factor Subunit B Gene Associated with Pancreatic Cancer Risk
Abstract
The PDGF signaling pathway plays important roles in development and progression of human cancers. In this study, we aimed to identify genetic variants of the PDGF pathway genes associated with pancreatic cancer risk in European populations by using three published GWAS datasets, which consisted of 9,381 cases and 7,719 controls. The expression quantitative trait loci (eQTL) analysis was also performed by using data from the 1000 Genomes, TCGA and GTEx projects. As a result, we identified two potential susceptibility loci (rs5757573 and rs6001516) of PDGFB associated with pancreatic cancer risk [odds ratio (OR) = 1.10, 95% confidence interval (CI) = 1.05-1.16, and P = 4.70x10−5 for the rs5757573 C allele and 1.21, 1.11-1.32, and 2.01x10−5 for the rs6001516 T allele]. Haplotype analysis revealed that the C-T haplotype carriers had a significantly increased risk of pancreatic cancer than those carrying the T-C haplotype (OR = 1.23, 95% CI = 1.12-1.34, P =5.00 × 10−6). The multivariate regression model incorporating the number of unfavorable genotypes (NUGs) with age and sex showed that carriers with 1-2 NUGs, particularly among 60-70 age group or males, had an increased risk of pancreatic cancer, compared with those without NUG. Further, the eQTL analysis revealed that both loci were correlated with a decreased mRNA expression level of PDGFB in lymphoblastoid cell lines and pancreatic tumor tissues (P = 0.015 and 0.071, respectively). Our results suggest that genetic variants in PDGFB may play a role in susceptibility to pancreatic cancer. Further population and functional validations of our findings are warranted. This article is protected by copyright. All rights reserved.
http://ift.tt/2mTfzhS
Adipokines and inflammation markers and risk of differentiated thyroid carcinoma: The EPIC study
Abstract
Other than the influence of ionizing radiation and benign thyroid disease, little is known about the risk factors for differentiated thyroid cancer (TC) which is an increasing common cancer worldwide. Consistent evidence shows that body mass is positively associated with TC risk. As excess weight is a state of chronic inflammation, we investigated the relationship between concentrations of leptin, adiponectin, C-reactive protein, interleukin(IL)-6, IL-10 and TNF-α and the risk of TC.
A case-control study was nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study and included 475 first primary incident TC cases (399 women and 76 men) and 1,016 matched cancer-free cohort participants. Biomarkers were measured in serum samples using validated and highly sensitive commercially available immunoassays. Odds ratios (ORs) of TC by levels of each biomarker were estimated using conditional logistic regression models, adjusting for BMI and alcohol consumption.
Adiponectin was inversely associated with TC risk among women (ORT3vs.T1=0.69, 95%CI: 0.49-0.98, Ptrend=0.04) but not among men (ORT3vs.T1=1.36, 95%CI: 0.67-2.76, Ptrend=0.37). Increasing levels of IL-10 were positively associated with TC risk in both genders and significantly so in women (ORT3vs.T1=1.59, 95%CI: 1.13-2.25, Ptrend=0.01) but not in men (ORT3vs.T1=1.78, 95%CI: 0.80-3.98, Ptrend=0.17). Leptin, CRP, IL-6 and TNF-α were not associated with TC risk in either gender.
These results indicate a positive association of TC risk with IL-10 and a negative association with adiponectin that is probably restricted to women. Inflammation may play a role in TC in combination with or independently of excess weight. This article is protected by copyright. All rights reserved.
http://ift.tt/2zumRP1
The arginine metabolome in Acute Lymphoblastic Leukemia can be targeted by the PEG-recombinant Arginase I BCT-100
Abstract
Arginine is a semi-essential amino acid that plays a key role in cell survival and proliferation in normal and malignant cells. BCT-100, a pegylated recombinant human arginase, can deplete arginine and starve malignant cells of the amino acid. Acute Lymphoblastic Leukemia is the most common cancer of childhood, yet for patients with high risk or relapsed disease prognosis remains poor. We show that BCT-100 is cytotoxic to ALL blasts from patients in vitro by necrosis, and is synergistic in combination with dexamethasone. Against ALL xenografts BCT-100 leads to a reduction in ALL engraftment and a prolongation of survival. ALL blasts express the arginine transporter CAT-1, yet the majority of blasts are arginine auxotrophic due to deficiency in either argininosuccinate synthase (ASS) or ornithine transcarbamylase (OTC). Although endogenous upregulation or retroviral transduced increases in ASS or OTC may promote ALL survival under moderately low arginine conditions, expression of these enzymes cannot prevent BCT-100 cytotoxicity at arginine depleting doses. RNA-sequencing of ALL blasts and supporting stromal cells treated with BCT-100 identifies a number of candidate pathways which are altered in the presence of arginine depletion. Therefore BCT-100 provides a new clinically-relevant therapeutic approach to target arginine metabolism in ALL. This article is protected by copyright. All rights reserved.
http://ift.tt/2mTfrPq
Tumor characteristics and prognosis in women with pregnancy-associated breast cancer
Abstract
There is evidence of poor prognosis in women with pregnancy-associated breast cancer (PABC) diagnosed during pregnancy or within two years of delivery. Using a large, population-based cohort, we examined clinicopathologic features and survival in women with PABC. A cohort of women diagnosed with invasive breast cancer between 1992 and 2009 at ages 15 to 44 years was identified in the Swedish Cancer Register and the Breast Cancer Quality Registers. Dates of childbirths for each woman were retrieved from the Swedish Multi-Generation Register. Age-standardized distributions of tumor stage (TNM), Elston grade and ER/PR/HER2 status were compared between nulliparous women and women with breast cancer during pregnancy and up to 10 years post-delivery. Adjusted hazard ratios for all-cause mortality rates among patients were estimated using Cox regression. We identified 1,661 nulliparous women with breast cancer, 778 women with PABC (97 during pregnancy, 270 within first and 411 within second year post-delivery), and 3,598 during 2-10 years post-delivery. Compared to nulliparous women, women with PABC, and especially women diagnosed 0-12 months after delivery, had more advanced T and N stage, and higher proportions of ER/PR negative, HER2 positive and triple-negative tumors. Increased hazard ratios were observed in women diagnosed within 5 years of delivery after adjustment for age, year, education and region. Following additional adjustment for tumor characteristics, the hazard ratios were attenuated and non-significant. The poorer prognosis observed in women with pregnancy-associated breast cancer appears to be largely explained by more adverse tumor characteristics at diagnosis. This article is protected by copyright. All rights reserved.
http://ift.tt/2zuO3wW
YY1 suppresses proliferation and migration of pancreatic ductal adenocarcinoma by regulating the CDKN3/MdM2/P53/P21 signaling pathway
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the malignant lethal tumors. It has been reported that the transcriptional regulator Yin Yang-1 (YY1) suppressed the invasion and metastasis of PDAC. However, the function of YY1 on proliferation and migration of pancreatic cancer remains to be clarified. In this study, we found that YY1 overexpression or knockdown can inhibit or promote the proliferation and migration of pancreatic cancer cells. Digital gene expression (DGE) sequencing indicates that cyclin-dependent kinase inhibitor 3 (CDKN3) may be the candidate target gene of YY1. Then we found that YY1 can downregulate the expression of CDKN3 by directly binding to the promoter region of CDKN3. Silencing CDKN3 expression could inhibit the ability of cell proliferation and migration, and overexpression of CDKN3 could restore the effects induced by YY1 overexpression in pancreatic cancer cells. The expression levels of YY1 and CDKN3 were negatively correlated in pancreatic cancer tissues and PDAC patients with higher levels of CDKN3 have poor prognosis. Vitro and vivo study show that CDKN3 can form a complex with MdM2-P53, thus leading to inhibiting the expression of P21, which is the target gene of P53, and finally facilitates the cell cycle to promote the proliferation of pancreatic cancer cells. Hence, YY1 can directly regulate the expression of CDKN3 and participate in the cycle of pancreatic cancer cells, which can inhibit the progression of pancreatic cancer. These results reveal that YY1-CDKN3-MDM2/P53-P21 axis is involved in pancreatic tumorigenesis, which may develop new methods for human pancreatic cancer therapy. This article is protected by copyright. All rights reserved.
http://ift.tt/2mTHMVD
Outcomes from ovarian cancer screening in the PLCO trial: Histologic heterogeneity impacts detection, overdiagnosis and survival
Source:European Journal of Cancer, Volume 87
Author(s): Sarah M. Temkin, Eric A. Miller, Goli Samimi, Christine D. Berg, Paul Pinsky, Lori Minasian
AimA mortality benefit from screening for ovarian cancer has never been demonstrated. The aim of this study was to evaluate the screening outcomes for different histologic subtypes of ovarian cancers.MethodsWomen in the screening arm of the Prostate, Lung, Colorectal and Ovarian Screening Trial underwent CA-125 and transvaginal ultrasound annually for 3–5 years. We compared screening test characteristics (including overdiagnosis) and outcomes by tumour type (type II versus other) and study arm (screening versus usual care).ResultsOf 78,215 women randomised, 496 women were diagnosed with ovarian cancer. Of the tumours that were characterised (n = 413; 83%), 74% (n = 305) were type II versus 26% other (n = 108). Among screened patients, 70% of tumours were type II compared to 78% in usual care (p = 0.09). Within the screening arm, 29% of type II tumours were screen detected compared to 54% of the others (p < 0.01). The sensitivity of screening was 65% for type II tumours versus 86% for other types (p = 0.02). 15% of type II screen-detected tumours were stage I/II, compared to 81% of other tumours (p < 0.01). The overdiagnosis rate was lower for type II compared to other tumours (28.2% versus 72.2%; p < 0.01). Ovarian cancer–specific survival was worse for type II tumours compared to others (p < 0.01). Survival was similar for type II (p = 0.74) or other types (p = 0.32) regardless of study arm.ConclusionsTest characteristics of screening for ovarian cancer differed for type II tumours compared to other ovarian tumours. Type II tumours were less likely to be screen diagnosed, early stage at diagnosis or overdiagnosed.
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