<span class="paragraphSection"><div class="boxTitle">Abstract</div>It has been proven that there is no survival advantage of surgery in clinical N2 non-small-cell lung cancer rather than chemoradiotherapy. Several decades ago, the results of thoracic radiotherapy for Clinical Stage III non-small-cell lung cancer were poor, and long-term survival rate was only 6%. Recent advances in combined therapy (radiotherapy and chemotherapy) have improved median survival to 15–20 months. In the Japanese registry of lung cancer surgery, the number of patients with Clinical Stage IIIA has decreased over the last decade because of the poor results of surgery alone for Clinical Stage III non-small-cell lung cancer. In contrast, survival of patients with Clinical Stage III non-small-cell lung cancer treated with surgery has improved gradually. This can be mainly attributed to the following: first, well-selected patients are treated with surgery; second, improved diagnostic imaging has produced a 'Will Rogers phenomenon'. Similarly, concurrent chemoradiotherapy has also further improved and in recent clinical trials, the median survival time was 28–40 months. Unfortunately, recent randomized trials comparing induction chemotherapy followed by surgery, or induction chemoradiotherapy followed by surgery with chemoradiotherapy showed no significant survival advantage of surgery. Until appropriate patient selection for surgery can be shown in randomized control trials, chemoradiotherapy is the mainstream treatment for clinical N2 non-small-cell lung cancer in clinical practice.</span>
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Cancer Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Παρασκευή 18 Νοεμβρίου 2016
Role of surgery in clinical N2 non-small-cell lung cancer: a pro and con debate; the ‘con’ viewpoint
A prediction model of survival for patients with bone metastasis from uterine corpus cancer
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objective</div>The aim of the study was to establish a predictive model of survival period after bone metastasis from endometrial cancer.<div class="boxTitle">Methods</div>A total of 28 patients with bone metastasis from uterine corpus cancer were included in the study. Data at the time of bone metastasis diagnosis, which included presence of extraskeletal metastasis, performance status, history of any previous radiation/chemotherapy and the number of bone metastases, were collected. Survival data were analyzed using Kaplan–Meier methods and Cox proportional hazard models.<div class="boxTitle">Results</div>The most common site of bone metastasis was the pelvis (50.0%), followed by lumbar spine (32.1%), thoracic spine (25.0%) and rib bone (17.9%). The median survival period after bone metastasis was 25 weeks. The overall rate of survival after bone metastasis of the entire cohort was 75.0% at 13 weeks, 46.4% at 26 weeks and 42.9% at 52 weeks. Performance status of 3–4 was confirmed as an independent prognostic factor (Hazard ratio, 3.5; 95% confidence interval, 1.41–8.70) and multiple bone metastases tended to be associated with poor prognosis (Hazard ratio, 2.4; 95% confidence interval, 0.95–5.97). A prognostic score was calculated by adding up the number of these two factors. The 26-week survival rates after bone metastasis were 88.9% for those with a score of 0, 45.5% for those with a score of 1 and 0% for those with a score of 2 (<span style="font-style:italic;">P </span>= 0.0006).<div class="boxTitle">Conclusions</div>This scoring system can be used to determine the optimal treatment for patients with bone metastasis from endometrial cancer.</span>
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Prognostic significance of vascular invasion in intermediate-grade subtype of lung adenocarcinoma
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>Although the recent reclassification of histological subtypes of lung adenocarcinoma reflects disease prognosis better, the prognosis of papillary and acinar-predominant adenocarcinoma, which are highly prevalent, is heterogeneity. The present study aimed to identify the prognostic indicators for papillary and acinar-predominant adenocarcinoma.<div class="boxTitle">Methods</div>This retrospective study included 315 consecutive patients with completely resected pathological N0 lung adenocarcinoma tumors ≤3 cm from two institutions. Tumors were classified according to histologically predominant subtypes as low-grade (adenocarcinoma <span style="font-style:italic;">in situ</span>, minimally invasive adenocarcinoma or lepidic predominant), intermediate-grade (papillary or acinar predominant) or high-grade (solid or micropapillary predominant). Prognostic factors in intermediate-grade group were assessed among clinicopathological factors of age, gender, surgical procedure, tumor size, pleural, lymphatic and vascular invasion using Cox proportion hazards analyses.<div class="boxTitle">Results</div>There were 174 patients in the low-grade group, 109 in the intermediate-grade group and 32 in the high-grade group. The 3-year recurrence-free survival rates were 98.1%, 86.3% and 74.8% for these groups, respectively (<span style="font-style:italic;">P</span> < 0.001). In the intermediate-grade group, the presence of vascular invasion was an independent prognostic factor on multivariate Cox regression analysis of recurrence-free survival (hazard ratio, 3.48; 95% confidence interval, 1.26–9.57, <span style="font-style:italic;">P</span> = 0.01). Classification of intermediate-grade group based on vascular invasion revealed a clear division into favorable and unfavorable prognostic subgroups.<div class="boxTitle">Conclusions</div>Consideration of the vascular invasion status in addition to the predominant subtype could provide a more accurate assessment of malignant aggressiveness and prognosis of patients with early-stage lung adenocarcinoma.</span>
http://ift.tt/2g32PwE
Clinical significance of adding 3 Tesla MRI to the algorithm for decision making on neurovascular bundle preservation in radical prostatectomy
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>The aim of this study was to evaluate the additional benefit of 3 Tesla magnetic resonance imaging for neurovascular bundle preservation in radical prostatectomy.<div class="boxTitle">Methods</div>We retrospectively evaluated patients who underwent 3 T magnetic resonance imaging followed by radical prostatectomy from April 2010 through February 2014 in our university. A total of 50 patients (100 prostate sides) were included in the study. The algorithm previously we described and magnetic resonance imaging findings were considered for the decision on neurovascular bundle preservation. A tumor adjacent to the neurovascular bundle or with extracapsular extension of a posterolateral lesion of the prostate on magnetic resonance imaging was considered a contraindication for nerve-sparing radical prostatectomy. Two experienced radiologists evaluated the magnetic resonance imaging findings. Patients who received neoadjuvant hormonal therapy were excluded. All patients underwent ultrasound-guided prostate biopsy with at least 10 cores.<div class="boxTitle">Results</div>Overall, 60 of the 100 neurovascular bundles were preserved according to an algorithm that consisted of the clinical stage, prostate specific antigen, Gleason score and a positive biopsy core in the apex of the prostate. Considering magnetic resonance imaging findings together with the algorithm, six neurovascular bundles were not preserved. The accuracy of predicting a positive surgical margin only by the algorithm was 56 of 60 neurovascular bundle (93.3%). When adding magnetic resonance imaging, the accuracy was 50 of 54 neurovascular bundle (92.3%).<div class="boxTitle">Conclusions</div>3 T magnetic resonance imaging provided no additional benefit to our algorithm for neurovascular bundle preservation.</span>
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The clinical presentation and favorable prognosis of patients with isolated metachronous brain metastasis from germ cell tumors
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objective</div>We conducted the present study to elucidate the clinical presentation, treatment outcomes and risk factors for the development of metachronous brain metastasis at a single progressive disease site, the so-called isolated brain metastasis, in patients with testicular germ cell tumors.<div class="boxTitle">Methods</div>To identify metachronous brain metastasis in a timely manner, brain imaging was performed when the re-elevation of tumor markers was observed during chemotherapy, even in patients who were free from central nervous system symptoms. The medical records of 147 patients with metastatic germ cell tumors who were treated between 1991 and 2015 were retrospectively reviewed.<div class="boxTitle">Results</div>Eight (5.4%) of the 147 patients presented synchronous brain metastasis. Of these, five patients suffered from metachronous brain metastasis relapse. An additional nine patients developed metachronous brain metastasis during or after chemotherapy. Ten of the 14 patients with metachronous brain metastasis did not have central nervous system symptoms. Eight (57%) patients had isolated brain metastasis. Ten patients underwent multimodal treatments, predominantly chemotherapy and radiotherapy. The 3-year overall survival of all 14 patients was 34.6%, but that of the patients with isolated brain metastasis was high as 66.7%. The development of metachronous brain metastasis was associated with a choriocarcinoma element at the primary site and an human chorionic gonadotropin level of >50 000 IU/L and brain metastasis at the initial diagnosis.<div class="boxTitle">Conclusions</div>In our series, we identified isolated brain metastasis in 57% of the metachronous brain metastasis patients. The monitoring of tumor markers and appropriate brain imaging are mandatory for the diagnosis of isolated brain relapse, which is associated with a higher rate of long-term survival.</span>
http://ift.tt/2fc03rt
Guidelines for parenteral fluid management for terminal cancer patients
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Background</div>Japan's first guidelines for parenteral fluid management for terminal cancer patients were issued in 2006. These guidelines focused on the fluid levels to administer to patients with a remaining life expectancy of 1–2 months. However, recent refinement of the concept of cachexia is prompting caregivers worldwide to rethink parenteral fluid management for terminal cancer patients.<div class="boxTitle">Objective</div>Our objective was to develop guidelines for parenteral fluid management for terminal cancer patients with a remaining life expectancy of 1 month, a point when cachexia generally begins to severely adversely affect the body.<div class="boxTitle">Methods</div>The Japanese Society for Palliative Medicine appointed a Guidelines Working Practitioner Group consisting of a multidisciplinary team of specialists. In response to 26 clinical questions on parenteral fluid management for terminal cancer patients, the Working Group used the Delphi method to reach consensus on the recommendability and evidence level of 89 relevant manuscripts identified through a systematic literature review. The Working Group then had an outside committee reviews the draft guidelines validity before authoring the final version.<div class="boxTitle">Results</div>The resulting clinically aligned guidelines contain specific recommendations (25 recommendations on physical suffering/remaining life expectancy, 10 nursing-related recommendations and 4 ethical recommendations) assessed using the Delphi method and by an outside committee.<div class="boxTitle">Conclusions</div>Japanese Society for Palliative Medicine released a revised edition of the Guidelines for Parenteral Fluid Management for Terminal Cancer Patients, which are based on medical evidence and consider the pathologic features of cachexia. We recommend that caregivers carefully evaluate the clinical usefulness of the guidelines.</span>
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Role of surgery in clinical N2 non-small-cell lung cancer: a pro and con debate; the ‘con’ viewpoint
<span class="paragraphSection"><div class="boxTitle">Abstract</div>It has been proven that there is no survival advantage of surgery in clinical N2 non-small-cell lung cancer rather than chemoradiotherapy. Several decades ago, the results of thoracic radiotherapy for Clinical Stage III non-small-cell lung cancer were poor, and long-term survival rate was only 6%. Recent advances in combined therapy (radiotherapy and chemotherapy) have improved median survival to 15–20 months. In the Japanese registry of lung cancer surgery, the number of patients with Clinical Stage IIIA has decreased over the last decade because of the poor results of surgery alone for Clinical Stage III non-small-cell lung cancer. In contrast, survival of patients with Clinical Stage III non-small-cell lung cancer treated with surgery has improved gradually. This can be mainly attributed to the following: first, well-selected patients are treated with surgery; second, improved diagnostic imaging has produced a 'Will Rogers phenomenon'. Similarly, concurrent chemoradiotherapy has also further improved and in recent clinical trials, the median survival time was 28–40 months. Unfortunately, recent randomized trials comparing induction chemotherapy followed by surgery, or induction chemoradiotherapy followed by surgery with chemoradiotherapy showed no significant survival advantage of surgery. Until appropriate patient selection for surgery can be shown in randomized control trials, chemoradiotherapy is the mainstream treatment for clinical N2 non-small-cell lung cancer in clinical practice.</span>
http://ift.tt/2g32das
Key predictive factors for efficacy of axitinib in first-line metastatic renal cell carcinoma: subgroup analysis in Japanese patients from a randomized, double-blind phase II study
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Clinical significance of adding 3 Tesla MRI to the algorithm for decision making on neurovascular bundle preservation in radical prostatectomy
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>The aim of this study was to evaluate the additional benefit of 3 Tesla magnetic resonance imaging for neurovascular bundle preservation in radical prostatectomy.<div class="boxTitle">Methods</div>We retrospectively evaluated patients who underwent 3 T magnetic resonance imaging followed by radical prostatectomy from April 2010 through February 2014 in our university. A total of 50 patients (100 prostate sides) were included in the study. The algorithm previously we described and magnetic resonance imaging findings were considered for the decision on neurovascular bundle preservation. A tumor adjacent to the neurovascular bundle or with extracapsular extension of a posterolateral lesion of the prostate on magnetic resonance imaging was considered a contraindication for nerve-sparing radical prostatectomy. Two experienced radiologists evaluated the magnetic resonance imaging findings. Patients who received neoadjuvant hormonal therapy were excluded. All patients underwent ultrasound-guided prostate biopsy with at least 10 cores.<div class="boxTitle">Results</div>Overall, 60 of the 100 neurovascular bundles were preserved according to an algorithm that consisted of the clinical stage, prostate specific antigen, Gleason score and a positive biopsy core in the apex of the prostate. Considering magnetic resonance imaging findings together with the algorithm, six neurovascular bundles were not preserved. The accuracy of predicting a positive surgical margin only by the algorithm was 56 of 60 neurovascular bundle (93.3%). When adding magnetic resonance imaging, the accuracy was 50 of 54 neurovascular bundle (92.3%).<div class="boxTitle">Conclusions</div>3 T magnetic resonance imaging provided no additional benefit to our algorithm for neurovascular bundle preservation.</span>
http://ift.tt/2g2Z2j0
The current state of stomach cancer surgery in the world
<span class="paragraphSection"><div class="boxTitle">Abstract</div>The incidence of gastric cancer and the number of gastric cancer patients that a surgeon treats annually are so vastly different between countries and regions that it is not easy to define which type of gastric cancer surgery should be considered the global standard. Nevertheless, a consensus that D2 dissection is the most appropriate way to treat resectable advanced gastric cancer has arguably been reached after long-term follow-up and flexible interpretation of the Dutch D1 versus D2 trial and evidence from the Japan Clinical Oncology Group 9501 study which denied survival benefit of more extensive lymphadenectomy. After the Japan Clinical Oncology Group 9501 trial, surgeons gradually lost interest in attempting to improve survival through extended resection and instead began to expend greater resources on establishing and standardizing the technique of minimally invasive surgery and proving its oncological non-inferiority compared with the conventional approach. Laparoscopic distal gastrectomy has become an option in daily clinical practice in the Far East, and more demanding procedures such as laparoscopic total gastrectomy and laparoscopic surgery for advanced gastric cancer are currently being explored in clinical trials from the viewpoint of both safety and oncological feasibility. In addition, the high proportion of early-stage cancer in the Far East prompted surgeons to develop limited surgery such as proximal gastrectomy and pylorus-preserving gastrectomy, which warrant further evaluation regarding benefits in terms of postoperative nutritional state and/or quality of life measurements to convince the rest of the world.</span>
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Guidelines for parenteral fluid management for terminal cancer patients
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Background</div>Japan's first guidelines for parenteral fluid management for terminal cancer patients were issued in 2006. These guidelines focused on the fluid levels to administer to patients with a remaining life expectancy of 1–2 months. However, recent refinement of the concept of cachexia is prompting caregivers worldwide to rethink parenteral fluid management for terminal cancer patients.<div class="boxTitle">Objective</div>Our objective was to develop guidelines for parenteral fluid management for terminal cancer patients with a remaining life expectancy of 1 month, a point when cachexia generally begins to severely adversely affect the body.<div class="boxTitle">Methods</div>The Japanese Society for Palliative Medicine appointed a Guidelines Working Practitioner Group consisting of a multidisciplinary team of specialists. In response to 26 clinical questions on parenteral fluid management for terminal cancer patients, the Working Group used the Delphi method to reach consensus on the recommendability and evidence level of 89 relevant manuscripts identified through a systematic literature review. The Working Group then had an outside committee reviews the draft guidelines validity before authoring the final version.<div class="boxTitle">Results</div>The resulting clinically aligned guidelines contain specific recommendations (25 recommendations on physical suffering/remaining life expectancy, 10 nursing-related recommendations and 4 ethical recommendations) assessed using the Delphi method and by an outside committee.<div class="boxTitle">Conclusions</div>Japanese Society for Palliative Medicine released a revised edition of the Guidelines for Parenteral Fluid Management for Terminal Cancer Patients, which are based on medical evidence and consider the pathologic features of cachexia. We recommend that caregivers carefully evaluate the clinical usefulness of the guidelines.</span>
http://ift.tt/2fc43YN
Single Nucleotide Polymorphisms within MicroRNAs, MicroRNA Targets, and MicroRNA Biogenesis Genes and Their Impact on Colorectal Cancer Survival
Abstract
We have shown that single nucleotide polymorphisms (SNPs) in microRNA (miRNA) genes, miRNA target genes, and miRNA biogenesis genes minimally contribute to colon cancer risk. It is possible that these SNPs alter survival. We analyzed 565 SNPs in or adjacent to microRNAs, target genes, or biogenesis genes, using 1115 cases and 1173 controls; 837 cases had survival information. We tested SNPs for associations with colorectal cancer (CRC) survival using a Cox proportional hazard model adjusting for age, study center, gender, AJCC disease stage, and MSI tumor status. Multiple comparison adjustments were made using the step-down Bonferroni correction. SNPs associated with survival (Praw < 0.05) also were assessed with messenger RNA (mRNA). Seven of the 565 SNPs analyzed were associated significantly with CRC survival after adjustment for multiple comparisons. Six of these increased risk of dying, and one, rs12140 (ADAMTS1) decreased risk of dying from CRC (HRR=0.44, 95% CI (0.24, 0.83; PHolm=0.011). Six SNPs altered colon cancer risk and five were associated with altered mRNA expression across genotypes. One SNP, rs2059691 (PRKRA), was associated with increased mRNA expression and worse survival, and one SNP, rs6598964 (LIN28A), decreased risk of developing colon cancer (OR=0.77 95% CI (0.61, 0.98)) and increased risk of dying from CRC (HRR=2.26 95% CI (1.52, 3.36). PHolm=0.003). The few SNPs associated with CRC survival, colon cancer risk, or with mRNA expression, resided in genes that influence metastasis and angiogenesis. This article is protected by copyright. All rights reserved.
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Key predictive factors for efficacy of axitinib in first-line metastatic renal cell carcinoma: subgroup analysis in Japanese patients from a randomized, double-blind phase II study
http://ift.tt/2g2VEV8
The current state of stomach cancer surgery in the world
<span class="paragraphSection"><div class="boxTitle">Abstract</div>The incidence of gastric cancer and the number of gastric cancer patients that a surgeon treats annually are so vastly different between countries and regions that it is not easy to define which type of gastric cancer surgery should be considered the global standard. Nevertheless, a consensus that D2 dissection is the most appropriate way to treat resectable advanced gastric cancer has arguably been reached after long-term follow-up and flexible interpretation of the Dutch D1 versus D2 trial and evidence from the Japan Clinical Oncology Group 9501 study which denied survival benefit of more extensive lymphadenectomy. After the Japan Clinical Oncology Group 9501 trial, surgeons gradually lost interest in attempting to improve survival through extended resection and instead began to expend greater resources on establishing and standardizing the technique of minimally invasive surgery and proving its oncological non-inferiority compared with the conventional approach. Laparoscopic distal gastrectomy has become an option in daily clinical practice in the Far East, and more demanding procedures such as laparoscopic total gastrectomy and laparoscopic surgery for advanced gastric cancer are currently being explored in clinical trials from the viewpoint of both safety and oncological feasibility. In addition, the high proportion of early-stage cancer in the Far East prompted surgeons to develop limited surgery such as proximal gastrectomy and pylorus-preserving gastrectomy, which warrant further evaluation regarding benefits in terms of postoperative nutritional state and/or quality of life measurements to convince the rest of the world.</span>
http://ift.tt/2g2YIR9
Single Nucleotide Polymorphisms within MicroRNAs, MicroRNA Targets, and MicroRNA Biogenesis Genes and Their Impact on Colorectal Cancer Survival
Abstract
We have shown that single nucleotide polymorphisms (SNPs) in microRNA (miRNA) genes, miRNA target genes, and miRNA biogenesis genes minimally contribute to colon cancer risk. It is possible that these SNPs alter survival. We analyzed 565 SNPs in or adjacent to microRNAs, target genes, or biogenesis genes, using 1115 cases and 1173 controls; 837 cases had survival information. We tested SNPs for associations with colorectal cancer (CRC) survival using a Cox proportional hazard model adjusting for age, study center, gender, AJCC disease stage, and MSI tumor status. Multiple comparison adjustments were made using the step-down Bonferroni correction. SNPs associated with survival (Praw < 0.05) also were assessed with messenger RNA (mRNA). Seven of the 565 SNPs analyzed were associated significantly with CRC survival after adjustment for multiple comparisons. Six of these increased risk of dying, and one, rs12140 (ADAMTS1) decreased risk of dying from CRC (HRR=0.44, 95% CI (0.24, 0.83; PHolm=0.011). Six SNPs altered colon cancer risk and five were associated with altered mRNA expression across genotypes. One SNP, rs2059691 (PRKRA), was associated with increased mRNA expression and worse survival, and one SNP, rs6598964 (LIN28A), decreased risk of developing colon cancer (OR=0.77 95% CI (0.61, 0.98)) and increased risk of dying from CRC (HRR=2.26 95% CI (1.52, 3.36). PHolm=0.003). The few SNPs associated with CRC survival, colon cancer risk, or with mRNA expression, resided in genes that influence metastasis and angiogenesis. This article is protected by copyright. All rights reserved.
http://ift.tt/2go2YPu
Regulation of autophagy by Ca 2+
Abstract
Autophagy is an evolutionarily conserved lysosomal catabolic process used as an internal engine in response to nutrient starvation or metabolic stress. A number of protein complexes and an intricate network of stress signaling cascades impinge on the regulation of autophagy; the mammalian target of rapamycin serves as a canonical player. Ca2+, as a major intracellular second messenger, regulates multiple physiological and pathological functions. Although significant information is already well-established about the role of Ca2+ in apoptosis, its role in autophagy has been recently determined and is poorly understood. Intracellular Ca2+ positively and negatively affects autophagy. In this review, evidence for both views and the interplay of Ca2+ between autophagy and apoptosis induction are discussed. The available data revealed the bidirectional role of Ca2+ in the regulation of autophagy. Moreover, the data also indicated that this role probably depends on the context of time, space, Ca2+ source, and cell state, thus either preventing or enhancing autophagy.
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Issue Contents
Source:Cancer/Radiothérapie, Volume 20, Issue 8
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Editorial Board
Source:Cancer/Radiothérapie, Volume 20, Issue 8
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Issue Contents
Source:Cancer/Radiothérapie, Volume 20, Issue 8
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Editorial Board
Source:Cancer/Radiothérapie, Volume 20, Issue 8
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Deubiquitination and Stabilization of PD-L1 by CSN5
Publication date: Available online 17 November 2016
Source:Cancer Cell
Author(s): Seung-Oe Lim, Chia-Wei Li, Weiya Xia, Jong-Ho Cha, Li-Chuan Chan, Yun Wu, Shih-Shin Chang, Wan-Chi Lin, Jung-Mao Hsu, Yi-Hsin Hsu, Taewan Kim, Wei-Chao Chang, Jennifer L. Hsu, Hirohito Yamaguchi, Qingqing Ding, Yan Wang, Yi Yang, Chung-Hsuan Chen, Aysegul A. Sahin, Dihua Yu, Gabriel N. Hortobagyi, Mien-Chie Hung
Pro-inflammatory cytokines produced in the tumor microenvironment lead to eradication of anti-tumor immunity and enhanced tumor cell survival. In the current study, we identified tumor necrosis factor alpha (TNF-α) as a major factor triggering cancer cell immunosuppression against T cell surveillance via stabilization of programmed cell death-ligand 1 (PD-L1). We demonstrated that COP9 signalosome 5 (CSN5), induced by NF-κB p65, is required for TNF-α-mediated PD-L1 stabilization in cancer cells. CSN5 inhibits the ubiquitination and degradation of PD-L1. Inhibition of CSN5 by curcumin diminished cancer cell PD-L1 expression and sensitized cancer cells to anti-CTLA4 therapy.
Graphical abstract
Teaser
Lim et al. show that inflammation increases PD-L1 expression in tumors through TNF-α-mediated activation of NF-κB, leading to transactivation of CSN5. CSN5 reduces PD-L1 ubiquitination and stabilizes it. Inhibition of CSN5 cooperates with anti-CTLA4 to enhance anti-tumor T cell function and reduce tumor growth.http://ift.tt/2gnDTEz
Inhibition of the Glycolytic Activator PFKFB3 in Endothelium Induces Tumor Vessel Normalization, Impairs Metastasis, and Improves Chemotherapy
Publication date: Available online 17 November 2016
Source:Cancer Cell
Author(s): Anna Rita Cantelmo, Lena-Christin Conradi, Aleksandra Brajic, Jermaine Goveia, Joanna Kalucka, Andreas Pircher, Pallavi Chaturvedi, Johanna Hol, Bernard Thienpont, Laure-Anne Teuwen, Sandra Schoors, Bram Boeckx, Joris Vriens, Anna Kuchnio, Koen Veys, Bert Cruys, Lise Finotto, Lucas Treps, Tor Espen Stav-Noraas, Francesco Bifari, Peter Stapor, Ilaria Decimo, Kim Kampen, Katrien De Bock, Guttorm Haraldsen, Luc Schoonjans, Ton Rabelink, Guy Eelen, Bart Ghesquière, Jalees Rehman, Diether Lambrechts, Asrar B. Malik, Mieke Dewerchin, Peter Carmeliet
Abnormal tumor vessels promote metastasis and impair chemotherapy. Hence, tumor vessel normalization (TVN) is emerging as an anti-cancer treatment. Here, we show that tumor endothelial cells (ECs) have a hyper-glycolytic metabolism, shunting intermediates to nucleotide synthesis. EC haplo-deficiency or blockade of the glycolytic activator PFKFB3 did not affect tumor growth, but reduced cancer cell invasion, intravasation, and metastasis by normalizing tumor vessels, which improved vessel maturation and perfusion. Mechanistically, PFKFB3 inhibition tightened the vascular barrier by reducing VE-cadherin endocytosis in ECs, and rendering pericytes more quiescent and adhesive (via upregulation of N-cadherin) through glycolysis reduction; it also lowered the expression of cancer cell adhesion molecules in ECs by decreasing NF-κB signaling. PFKFB3-blockade treatment also improved chemotherapy of primary and metastatic tumors.
Graphical abstract
Teaser
Cantelmo et al. show that tumor endothelial cells have hyperglycolytic metabolism. Inactivation of the glycolytic activator PFKFB3 normalizes tumor vessels and improves vessel perfusion via tightening the vascular barrier, which reduces cancer cell intravasation and metastasis and improves chemotherapy response.http://ift.tt/2gnzeCx
Deubiquitination and Stabilization of PD-L1 by CSN5
Publication date: Available online 17 November 2016
Source:Cancer Cell
Author(s): Seung-Oe Lim, Chia-Wei Li, Weiya Xia, Jong-Ho Cha, Li-Chuan Chan, Yun Wu, Shih-Shin Chang, Wan-Chi Lin, Jung-Mao Hsu, Yi-Hsin Hsu, Taewan Kim, Wei-Chao Chang, Jennifer L. Hsu, Hirohito Yamaguchi, Qingqing Ding, Yan Wang, Yi Yang, Chung-Hsuan Chen, Aysegul A. Sahin, Dihua Yu, Gabriel N. Hortobagyi, Mien-Chie Hung
Pro-inflammatory cytokines produced in the tumor microenvironment lead to eradication of anti-tumor immunity and enhanced tumor cell survival. In the current study, we identified tumor necrosis factor alpha (TNF-α) as a major factor triggering cancer cell immunosuppression against T cell surveillance via stabilization of programmed cell death-ligand 1 (PD-L1). We demonstrated that COP9 signalosome 5 (CSN5), induced by NF-κB p65, is required for TNF-α-mediated PD-L1 stabilization in cancer cells. CSN5 inhibits the ubiquitination and degradation of PD-L1. Inhibition of CSN5 by curcumin diminished cancer cell PD-L1 expression and sensitized cancer cells to anti-CTLA4 therapy.
Graphical abstract
Teaser
Lim et al. show that inflammation increases PD-L1 expression in tumors through TNF-α-mediated activation of NF-κB, leading to transactivation of CSN5. CSN5 reduces PD-L1 ubiquitination and stabilizes it. Inhibition of CSN5 cooperates with anti-CTLA4 to enhance anti-tumor T cell function and reduce tumor growth.from Cancer via ola Kala on Inoreader http://ift.tt/2gnDTEz
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Inhibition of the Glycolytic Activator PFKFB3 in Endothelium Induces Tumor Vessel Normalization, Impairs Metastasis, and Improves Chemotherapy
Publication date: Available online 17 November 2016
Source:Cancer Cell
Author(s): Anna Rita Cantelmo, Lena-Christin Conradi, Aleksandra Brajic, Jermaine Goveia, Joanna Kalucka, Andreas Pircher, Pallavi Chaturvedi, Johanna Hol, Bernard Thienpont, Laure-Anne Teuwen, Sandra Schoors, Bram Boeckx, Joris Vriens, Anna Kuchnio, Koen Veys, Bert Cruys, Lise Finotto, Lucas Treps, Tor Espen Stav-Noraas, Francesco Bifari, Peter Stapor, Ilaria Decimo, Kim Kampen, Katrien De Bock, Guttorm Haraldsen, Luc Schoonjans, Ton Rabelink, Guy Eelen, Bart Ghesquière, Jalees Rehman, Diether Lambrechts, Asrar B. Malik, Mieke Dewerchin, Peter Carmeliet
Abnormal tumor vessels promote metastasis and impair chemotherapy. Hence, tumor vessel normalization (TVN) is emerging as an anti-cancer treatment. Here, we show that tumor endothelial cells (ECs) have a hyper-glycolytic metabolism, shunting intermediates to nucleotide synthesis. EC haplo-deficiency or blockade of the glycolytic activator PFKFB3 did not affect tumor growth, but reduced cancer cell invasion, intravasation, and metastasis by normalizing tumor vessels, which improved vessel maturation and perfusion. Mechanistically, PFKFB3 inhibition tightened the vascular barrier by reducing VE-cadherin endocytosis in ECs, and rendering pericytes more quiescent and adhesive (via upregulation of N-cadherin) through glycolysis reduction; it also lowered the expression of cancer cell adhesion molecules in ECs by decreasing NF-κB signaling. PFKFB3-blockade treatment also improved chemotherapy of primary and metastatic tumors.
Graphical abstract
Teaser
Cantelmo et al. show that tumor endothelial cells have hyperglycolytic metabolism. Inactivation of the glycolytic activator PFKFB3 normalizes tumor vessels and improves vessel perfusion via tightening the vascular barrier, which reduces cancer cell intravasation and metastasis and improves chemotherapy response.from Cancer via ola Kala on Inoreader http://ift.tt/2gnzeCx
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Trends in cardiac mortality in women with ductal carcinoma in situ
Abstract
Purpose
In certain ductal carcinoma in situ (DCIS) subpopulations, there is no consensus regarding whether to postoperatively irradiate; decisions are often made based on potential risk of cardiac toxicities. Given the utility of Surveillance, Epidemiology, and End Results (SEER) data for studying cardiac mortality in invasive disease, this is the first such study specific for DCIS patients, evaluating trends in cardiac mortality after left-sided radiotherapy (RT).
Methods
The SEER database was queried for patients with DCIS that received RT and had known unilaterality. The central design of this study was to compare cardiac-specific mortality (CSM) between left- and right-sided DCIS patients as stratifying for "older" RT (1973–1982) versus more "modern" RT (1983–1992 or 1993–2002). Survival analysis was performed using Kaplan–Meier methodology and multivariate Cox regression modeling for factors associated with overall survival (OS) and CSS.
Results
Left- and right-sided patients were demographically balanced. CSM was worse for left-sided patients with DCIS diagnosed in 1973–1982 [hazard ratio (HR) 1.295; 95% confidence interval (CI) 1.182–1.420], but not in 1983–1992 (HR 1.022; 95% CI 0.949–1.100) or in 1993–2002 (HR 0.989; 95% CI 0.935–1.046)]. On multivariate analysis, laterality was not associated with OS in either decade. However, left-sided laterality was independently associated with CSM during the 1973–1982 time period, but not the more recent time periods. Examining temporal patterns in the 1973–1982 cohort, cardiac mortality was significantly increased during 10–19 and ≥20 years after diagnosis, but there was no significant increase in cardiac mortality for patients diagnosed up to 10 years after diagnosis.
Conclusions
In the largest such DCIS series to date, left-sided RT was an independent risk factor for increased cardiac mortality from 1973 to 1982, but not after 1983. Using modern RT techniques and maintaining low heart doses, RT may not induce excess CSM in the DCIS population.
http://ift.tt/2gnuo8n
Heterogeneity of colorectal cancer risk by tumour characteristics: Large prospective study of UK women
ABSTRACT
Associations between behavioural and other personal factors and colorectal cancer risk have been reported to vary by tumour characteristics, but evidence is inconsistent. In a large UK-based prospective study we examined associations of 14 postulated risk factors with colorectal cancer risk overall, and across 3 anatomical sites and 4 morphological subtypes. Among 1.3 million women, 18,518 incident colorectal cancers were identified during 13.8 (SD 3.4) years follow-up via record linkage to national cancer registry data. Cox regression yielded adjusted relative risks. Statistical significance was assessed using correction for multiple testing. Overall, colorectal cancer risk was significantly associated with height, body mass index (BMI), smoking, alcohol intake, physical activity, parity and menopausal hormone therapy use. For smoking there was substantial heterogeneity across morphological types; relative risks around 2 or greater were seen in current smokers both for signet ring cell and for neuroendocrine tumours. Obese women were also at higher risk for signet ring cell tumours. For adenocarcinomas, the large majority of colorectal cancers in the cohort, all risk factor associations were weak. There was little or no heterogeneity in risk between tumours of the right colon, left colon and rectum for any of the 14 factors examined. These epidemiological findings complement an emerging picture from molecular studies of possible different developmental pathways for different tumour types. This article is protected by copyright. All rights reserved.
http://ift.tt/2g3RFcg
Effects of Statins on Cancer Mortality and Progression: A Systematic Review and Meta-analysis of 95 Cohorts Including 1111407 Individuals
ABSTRACT
Statins have been implicated in the regulation of cell proliferation, apoptosis and tumor progression in cancer patients and statin use at the time of cancer diagnosis has been reported to be associated with reduced cancer risk and improved survival, irrespective of concomitant anti-cancer therapy. A systematic literature search of relevant databases through May 2015 was conducted to identify studies assessing the prognostic impact of statin use on prognostic outcomes in cancer patients. Literature search identified 95 cohort studies that met the inclusion criteria. A meta-analysis of 55 articles showed that statin use was significantly associated with decreased risk of all-cause mortality (HR 0.70, 95% Cl 0.66 to 0.74) compared with non-users. The observed pooled estimates were retained for cancer-specific mortality (HR 0.60, 95% Cl 0.47 to 0.77), progression-free survival (HR 0.67, 95% Cl 0.56 to 0.81), recurrence-free survial (HR 0.74, 95% Cl 0.65 to 0.83) and disease-free survival (HR 0.53, 95% Cl 0.40 to 0.72). These associations almost remained consistent across those outcomes when stratified by publication type, tumour location, study design, sample size, initiation of statins, disease stage, research country, follow-up duration or research hospital involved. Subgroup analyses according to initiation of statins showed postdiagnosis statin users (HR 0.65, 95% Cl 0.54 to 0.79) gained significantly more recurrence-free survival benefit than prediagnosis statin users (HR 0.86, 95% Cl 0.77 to 0.96) (P for interaction=0.018). Statin therapy has potential survival benefit for patients with malignancy. Further large-scale prospective studies emphasising survival outcomes of individual cancer type are strongly encouraged. This article is protected by copyright. All rights reserved.
http://ift.tt/2gqr39j
Heterogeneity of colorectal cancer risk by tumour characteristics: Large prospective study of UK women
ABSTRACT
Associations between behavioural and other personal factors and colorectal cancer risk have been reported to vary by tumour characteristics, but evidence is inconsistent. In a large UK-based prospective study we examined associations of 14 postulated risk factors with colorectal cancer risk overall, and across 3 anatomical sites and 4 morphological subtypes. Among 1.3 million women, 18,518 incident colorectal cancers were identified during 13.8 (SD 3.4) years follow-up via record linkage to national cancer registry data. Cox regression yielded adjusted relative risks. Statistical significance was assessed using correction for multiple testing. Overall, colorectal cancer risk was significantly associated with height, body mass index (BMI), smoking, alcohol intake, physical activity, parity and menopausal hormone therapy use. For smoking there was substantial heterogeneity across morphological types; relative risks around 2 or greater were seen in current smokers both for signet ring cell and for neuroendocrine tumours. Obese women were also at higher risk for signet ring cell tumours. For adenocarcinomas, the large majority of colorectal cancers in the cohort, all risk factor associations were weak. There was little or no heterogeneity in risk between tumours of the right colon, left colon and rectum for any of the 14 factors examined. These epidemiological findings complement an emerging picture from molecular studies of possible different developmental pathways for different tumour types. This article is protected by copyright. All rights reserved.
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Effects of Statins on Cancer Mortality and Progression: A Systematic Review and Meta-analysis of 95 Cohorts Including 1111407 Individuals
ABSTRACT
Statins have been implicated in the regulation of cell proliferation, apoptosis and tumor progression in cancer patients and statin use at the time of cancer diagnosis has been reported to be associated with reduced cancer risk and improved survival, irrespective of concomitant anti-cancer therapy. A systematic literature search of relevant databases through May 2015 was conducted to identify studies assessing the prognostic impact of statin use on prognostic outcomes in cancer patients. Literature search identified 95 cohort studies that met the inclusion criteria. A meta-analysis of 55 articles showed that statin use was significantly associated with decreased risk of all-cause mortality (HR 0.70, 95% Cl 0.66 to 0.74) compared with non-users. The observed pooled estimates were retained for cancer-specific mortality (HR 0.60, 95% Cl 0.47 to 0.77), progression-free survival (HR 0.67, 95% Cl 0.56 to 0.81), recurrence-free survial (HR 0.74, 95% Cl 0.65 to 0.83) and disease-free survival (HR 0.53, 95% Cl 0.40 to 0.72). These associations almost remained consistent across those outcomes when stratified by publication type, tumour location, study design, sample size, initiation of statins, disease stage, research country, follow-up duration or research hospital involved. Subgroup analyses according to initiation of statins showed postdiagnosis statin users (HR 0.65, 95% Cl 0.54 to 0.79) gained significantly more recurrence-free survival benefit than prediagnosis statin users (HR 0.86, 95% Cl 0.77 to 0.96) (P for interaction=0.018). Statin therapy has potential survival benefit for patients with malignancy. Further large-scale prospective studies emphasising survival outcomes of individual cancer type are strongly encouraged. This article is protected by copyright. All rights reserved.
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Detection of pancoronavirus using PCR in Camelus dromedarius in Iran (first report)
Abstract
Coronaviride is a colossal family of viruses that cause a variety of diseases in humans and other animals. As of late, a novel coronavirus, not anterior-optically discerned in humans, has been identified in a denizen of the Middle East. There is growing evidence that the Camelus dromedarius is host species for the virus and plays an important role of a source of human infection. Along these lines, the authors decided to detect coronaviruses in dromedary camels in two high-risk areas of Iran by employing an reverse transcription polymerase chain reaction (RT-PCR) assay. In the present study, nasal swab specimens were collected from 98 camels (C. dromedarius) traditionally reared in southeast and northwest of Iran. The detection of pancoronavirus was carried out, using RT-PCR. Pancoronavirus RNA was observed in seven cases among 98 nasal swab samples. Among these, 4 positive samples belonged to Azerbaijan province located in northwest of Iran and 3 positive samples were taken from southeast of Iran. The results of this study contribute to raising the hypothesis to the extent of transmission and risk factors for human infection and public health in Iran.
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Comparing hematological coagulation and biochemical parameters of healthy dogs living at below and above sea levels
Abstract
There is limited information in the literature about the effect of altitude on the variability of hematological, coagulation, and biochemical parameters in healthy dogs. The main aim of this research is to evaluate and compare hematological, coagulation, and selected biochemical parameters of apparently healthy dogs living below and above sea level. Hematological coagulation and selected biochemical parameters were compared between 21 apparently healthy middle-aged dogs living at 180 to 260 m below sea level and 1012 to 1160 m above sea level. The mean values of WBC, MCV, MCH, granulocytes, AST, BUN, sodium, and prothrombin time were significantly lower in dogs living below sea level (low altitude) while mean values of lymphocytes and monocytes were higher when compared with dogs living above sea level. Significant differences were found in a set of hematological coagulation and biochemical parameters of dogs living at different altitudes. This is the first study to compare such parameters below and above sea level in healthy dogs. The findings are preliminary and potentially can pave the road for further research regarding altitude effect. Furthermore, it highlighted the effect of altitude on the variability of hematological, coagulation, and biochemical parameters in healthy dogs.
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Examining the Impact of Rehospitalization on Healthcare Cost of Myocardial Infarction Patients in Beijing: A Retrospective Observational Study
Abstract
Introduction
To examine the impact of rehospitalization on the healthcare expenditure of myocardial infarction (MI) patients in Beijing.
Methods
Retrospective data of MI patients were retrieved from the Beijing Medical Insurance Database, an administrative database of social medical reimbursement activities for the urban population in Beijing, China. Ten percent of patients diagnosed with MI from January 1 to December 31, 2012 were randomly selected and their first hospitalization was considered as the index event. Their hospital utilization after the index event was extracted till September 30, 2013. Rehospitalization was defined as an event of hospital admission due to the same diagnosis and with a time interval of at least 14 days from the most recent admission. The healthcare cost of patients was analyzed, including inpatient cost and outpatient cost. Patients' demographic characteristics, co-morbidities, and length of hospital stay were also collected from the database.
Results
Of the 1235 MI patients identified, 335 (mean age of 66.14 ± 15.04 years; 84.18% males) had rehospitalization. The rate of MI recurrence was 27.13%. The annual healthcare expense was significantly higher for MI patients with rehospitalization compared to MI patients without rehospitalization (99,920.43 ± 84,113.52 CNY vs. 58,877.89 ± 93,942.90 CNY; P < 0.001). The significant positive predictors of incurring healthcare expenditure were male gender, age 45 years old or more, length of stay at first hospital admission, whether having rehospitalization (yes/no), co-morbidity (heart failure and diabetes), and admission to a tertiary hospital at first hospital admission.
Conclusion
There was a high risk of MI recurrence for patients in Beijing. The annual healthcare cost of MI patients with rehospitalization was significantly higher than MI patients without rehospitalization. Male patients of 45 years old or more with heart failure and diabetes are likely to incur higher healthcare expenditure.
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Unproven Therapies for Diabetes and Their Implications
Abstract
Diabetes is a chronic disease and is one of the leading causes of morbidity and mortality worldwide. Being an ancient disease, many individuals follow complementary and alternative medicinal (CAM) therapies for either the cure or prevention of the disease. The popularity of these practices among the general public is in no way a testimony to their safety and efficacy. Due to the possibility of undesirable interactions with conventional medicines, it is imperative that patients are asked about CAM use during patient assessment. Patient- and physician-targeted awareness programs on various aspects of CAM use must be initiated to create a better understanding of evidence-based use of these practices. In addition, there should be guidelines in place based on clinical trial outcomes, and stricter regulations need to be enforced on CAM practices to ensure their safety and effectiveness.
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Examining the Impact of Rehospitalization on Healthcare Cost of Myocardial Infarction Patients in Beijing: A Retrospective Observational Study
Abstract
Introduction
To examine the impact of rehospitalization on the healthcare expenditure of myocardial infarction (MI) patients in Beijing.
Methods
Retrospective data of MI patients were retrieved from the Beijing Medical Insurance Database, an administrative database of social medical reimbursement activities for the urban population in Beijing, China. Ten percent of patients diagnosed with MI from January 1 to December 31, 2012 were randomly selected and their first hospitalization was considered as the index event. Their hospital utilization after the index event was extracted till September 30, 2013. Rehospitalization was defined as an event of hospital admission due to the same diagnosis and with a time interval of at least 14 days from the most recent admission. The healthcare cost of patients was analyzed, including inpatient cost and outpatient cost. Patients' demographic characteristics, co-morbidities, and length of hospital stay were also collected from the database.
Results
Of the 1235 MI patients identified, 335 (mean age of 66.14 ± 15.04 years; 84.18% males) had rehospitalization. The rate of MI recurrence was 27.13%. The annual healthcare expense was significantly higher for MI patients with rehospitalization compared to MI patients without rehospitalization (99,920.43 ± 84,113.52 CNY vs. 58,877.89 ± 93,942.90 CNY; P < 0.001). The significant positive predictors of incurring healthcare expenditure were male gender, age 45 years old or more, length of stay at first hospital admission, whether having rehospitalization (yes/no), co-morbidity (heart failure and diabetes), and admission to a tertiary hospital at first hospital admission.
Conclusion
There was a high risk of MI recurrence for patients in Beijing. The annual healthcare cost of MI patients with rehospitalization was significantly higher than MI patients without rehospitalization. Male patients of 45 years old or more with heart failure and diabetes are likely to incur higher healthcare expenditure.
http://ift.tt/2fM5ZWl
Unproven Therapies for Diabetes and Their Implications
Abstract
Diabetes is a chronic disease and is one of the leading causes of morbidity and mortality worldwide. Being an ancient disease, many individuals follow complementary and alternative medicinal (CAM) therapies for either the cure or prevention of the disease. The popularity of these practices among the general public is in no way a testimony to their safety and efficacy. Due to the possibility of undesirable interactions with conventional medicines, it is imperative that patients are asked about CAM use during patient assessment. Patient- and physician-targeted awareness programs on various aspects of CAM use must be initiated to create a better understanding of evidence-based use of these practices. In addition, there should be guidelines in place based on clinical trial outcomes, and stricter regulations need to be enforced on CAM practices to ensure their safety and effectiveness.
http://ift.tt/2g3y7Hh
Challenges in the use of immunotherapy in metastatic melanoma
A 65-year-old man with metastatic melanoma was started on immunotherapy, switched to alternative targeted therapy and developed disseminated intravascular coagulation. This case underscores the complexity of interpreting and managing side effects of novel therapies in cancer care, identification of progression versus pseudoprogression and challenges in sequencing treatments in metastatic melanoma.
http://ift.tt/2g2gcgC
Oral and gastrointestinal symptomatic metastases as initial presentation of lung cancer
Metastasis to the tongue, duodenum or pancreas from primary lung cancer is uncommon. Primary lung cancer presenting with symptoms related to metastases at these sites, at initial presentation is extremely rare. We report a 45-year-old man with disseminated lung malignancy who presented with dyspepsia, melena, symptoms due to anaemia and swelling in the tongue. Oral examination revealed a hard submucosal anterior tongue lesion. Biopsies from the tongue lesion and the duodenal ulcer seen on upper gastrointestinal endoscopy were suggestive of metastasis from lung primary. CT revealed lung primary with disseminated metastasis to lung, liver, adrenals, kidneys, head and body of pancreas, duodenum and intra-abdominal lymph nodes. The patient was treated with palliative chemotherapy. The unusual presentation and diagnostic details are discussed.
http://ift.tt/2fbjsJ1
Bacteraemia due to Parvimonas micra, a commensal pathogen, in a patient with an oesophageal tumour
A man aged 53 years was admitted to our hospital due to general malaise, fever and chills for the past 24 hours. He had a history of chronic alcoholic liver disease. The blood tests showed leucocytosis with neutrophilia, lactic acidosis and acute-phase reactants. The blood cultures were positive for Parvimonas micra, an anaerobic pathogen which is part of the flora of the oral cavity. There was no evidence of abscess formation in either the examination or the imaging tests, but in the work-up that followed, a gastroscopy showed a stenotic oesophageal mass that turned out to be an invasive squamous cell carcinoma.
http://ift.tt/2fblw3D
Targeted intraoperative radiotherapy tumour bed boost during breast-conserving surgery after neoadjuvant chemotherapy
Abstract
Introduction
The use of targeted intraoperative radiotherapy (TARGIT-IORT) as a tumour bed boost during breast-conserving surgery (BCS) for breast cancer has been reported since 1998. We present its use in patients undergoing breast conservation following neoadjuvant therapy (NACT).
Method
In this retrospective study involving 116 patients after NACT we compared outcomes of 61 patients who received a tumour bed boost with IORT during lumpectomy versus 55 patients treated in the previous 13 months with external (EBRT) boost. All patients received whole breast radiotherapy. Local recurrence-free survival (LRFS), disease-free survival (DFS), distant disease-free survival (DDFS), breast cancer mortality (BCM), non-breast cancer mortality (NBCM) and overall mortality (OS) were compared.
Results
Median follow up was 49 months. The differences in LRFS, DFS and BCM were not statistically significant. The 5‑year Kaplan–Meier estimate of OS was significantly better by 15% with IORT: IORT 2 events (96.7%, 95%CI 87.5–99.2), EBRT 9 events (81.7%, 95%CI 67.6–90.1), hazard ratio (HR) 0.19 (0.04–0.87), log rank p = 0.016, mainly due to a reduction of 10.1% in NBCM: IORT 100%, EBRT 89.9% (77.3–95.7), HR (not calculable), log rank p = 0.015. The DDFS was as follows: IORT 3 events (95.1%, 85.5–98.4), EBRT 12 events (69.0%, 49.1–82.4), HR 0.23 (0.06–0.80), log rank p = 0.012.
Conclusion
IORT during lumpectomy after neoadjuvant chemotherapy as a tumour bed boost appears to give results that are not worse than external beam radiotherapy boost. These data give further support to the inclusion of such patients in the TARGIT-B (boost) randomised trial that is testing whether IORT boost is superior to EBRT boost.
http://ift.tt/2fCMotZ
Expression of Par3 polarity protein correlates with poor prognosis in ovarian cancer
Abstract
Background
Previous studies have shown that the cell polarity protein partitioning defective 3 (Par3) plays an essential role in the formation of tight junctions and definition of apical-basal polarity. Aberrant function of this protein has been reported to be involved in epithelial–mesenchymal transition (EMT) and cancer invasion. The aim of this study was to examine the functional mechanism of Par3 in ovarian cancer.
Methods
First, we investigated the association between Par3 expression level and survival of 50 ovarian cancer patients. Next, we conducted an in vitro analysis of ovarian cancer cell lines, focusing on the cell line JHOC5, to investigate Par3 function. To investigate the function of Par3 in invasion, the IL-6/STAT3 pathway was analyzed upon Par3 knockdown with siRNA. The effect of siRNA treatment was assessed by qPCR, ELISA, and western blotting. Invasiveness and cell proliferation following treatment with siRNA against Par3 were investigated using Matrigel chamber, wound healing, and cell proliferation assays.
Results
Expression array data for ovarian cancer patient samples revealed low Par3 expression was significantly associated with good prognosis. Univariate analysis of clinicopathological factors revealed significant association between high Par3 levels and peritoneal dissemination at the time of diagnosis. Knockdown of Par3 in JHOC5 cells suppressed cell invasiveness, migration, and cell proliferation with deregulation of IL-6/STAT3 activity.
Conclusion
Taken together, these results suggest that Par3 expression is likely involved in ovarian cancer progression, especially in peritoneal metastasis. The underlying mechanism may be that Par3 modulates IL-6 /STAT3 signaling. Here, we propose that the expression of Par3 in ovarian cancer may control disease outcome.
http://ift.tt/2g28HWT
Salinomycin inhibits metastatic colorectal cancer growth and interferes with Wnt/β-catenin signaling in CD133 + human colorectal cancer cells
Abstract
Background
The polyether antibiotic Salinomycin (Sal) is regarded as an inhibitor of cancer stem cells. Its effectiveness on human colorectal cancer (CRC) cells in vitro has been demonstrated before. The aim of this study was to establish a murine model to investigate the effectiveness of Sal in vivo. Furthermore, we investigated the impact of Sal on Wnt/β-catenin signaling in human CD133+ CRC cells.
Methods
The two murine CRC cell lines MC38 and CT26 were used to analyze the impact of Sal on tumor cell proliferation, viability, migration, cell cycle progression and cell death in vitro. For in vivo studies, CT26 cells were injected into syngeneic BALB/c mice to initiate (i) subcutaneous, (ii) orthotopic, or (iii) metastatic CRC growth. Sal was administered daily, 5-Fluoruracil served as a control. For mechanistic studies, the CD133+and CD133- subpopulations of human CRC cells were separated by flow cytometry and separately exposed to increasing concentrations of Sal. The impact on Wnt/β-catenin signaling was determined by Western blotting and quantitative PCR.
Results
Sal markedly impaired tumor cell viability, proliferation and migration, and induced necrotic cell death in vitro. CRC growth in vivo was likewise inhibited upon Sal treatment. Interference with Wnt signaling and reduced expression of the Wnt target genes Fibronectin and Lgr5 indicates a novel molecular mechanism, mediating anti-tumoral effects of Sal in CRC.
Conclusion
Sal effectively impairs CRC growth in vivo. Furthermore, Sal acts as an inhibitor of Wnt/β-catenin signaling. Thus, Salinomycin represents a promising candidate for clinical CRC treatment.
http://ift.tt/2fbca80
NUT midline carcinoma mimicking a germ cell tumor: a case report
Abstract
Background
NUT midline carcinoma (NMC) is a rare and highly aggressive malignancy. Although more information on NMC has been recently accumulating in the literature, most oncologists and pathologists remain unfamiliar with the clinical and pathologic features of this disease. The clinical features of NMC sometimes mimic those of other malignancies, and NMC can therefore be overlooked if the diagnosis is not suspected. We present the case of a young male with NMC arising in the mediastinum with elevated serum alpha-fetoprotein levels suggestive of an extragonadal nonseminomatous germ-cell tumor.
Case presentation
A 28-year-old Japanese male presented with cough and left-sided chest pain for 6 weeks. The patient had a mediastinal tumor with metastases to the right lung, lymph nodes, and bones at initial presentation. Nonseminomatous germ cell tumor was suspected due to the young age, location of the tumors, and elevated serum alpha-fetoprotein. However, biopsy confirmed the diagnosis of NMC with immunohistochemistry. The tumor briefly responded to cytotoxic chemotherapy but subsequently progressed and became refractory to the chemotherapy regimen. External beam radiotherapy was administered with dramatic shrinkage of the tumor and a metabolic response on 18-fluoro-2-deoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scan. However, the patient died 4.5 months after the diagnosis of NMC.
Conclusions
Serum levels of alpha-fetoprotein may be elevated in patients with NMC. Regardless of the level of tumor markers, immunohistochemistry for NUT should be performed in cases of poorly differentiated carcinomas without glandular differentiation arising in the midline structures. 18F-FDG PET/CT is useful for staging and assessing responses to therapy.
http://ift.tt/2g27Oxt
Expression of Par3 polarity protein correlates with poor prognosis in ovarian cancer
Abstract
Background
Previous studies have shown that the cell polarity protein partitioning defective 3 (Par3) plays an essential role in the formation of tight junctions and definition of apical-basal polarity. Aberrant function of this protein has been reported to be involved in epithelial–mesenchymal transition (EMT) and cancer invasion. The aim of this study was to examine the functional mechanism of Par3 in ovarian cancer.
Methods
First, we investigated the association between Par3 expression level and survival of 50 ovarian cancer patients. Next, we conducted an in vitro analysis of ovarian cancer cell lines, focusing on the cell line JHOC5, to investigate Par3 function. To investigate the function of Par3 in invasion, the IL-6/STAT3 pathway was analyzed upon Par3 knockdown with siRNA. The effect of siRNA treatment was assessed by qPCR, ELISA, and western blotting. Invasiveness and cell proliferation following treatment with siRNA against Par3 were investigated using Matrigel chamber, wound healing, and cell proliferation assays.
Results
Expression array data for ovarian cancer patient samples revealed low Par3 expression was significantly associated with good prognosis. Univariate analysis of clinicopathological factors revealed significant association between high Par3 levels and peritoneal dissemination at the time of diagnosis. Knockdown of Par3 in JHOC5 cells suppressed cell invasiveness, migration, and cell proliferation with deregulation of IL-6/STAT3 activity.
Conclusion
Taken together, these results suggest that Par3 expression is likely involved in ovarian cancer progression, especially in peritoneal metastasis. The underlying mechanism may be that Par3 modulates IL-6 /STAT3 signaling. Here, we propose that the expression of Par3 in ovarian cancer may control disease outcome.
from Cancer via ola Kala on Inoreader http://ift.tt/2g28HWT
via IFTTT
Salinomycin inhibits metastatic colorectal cancer growth and interferes with Wnt/β-catenin signaling in CD133 + human colorectal cancer cells
Abstract
Background
The polyether antibiotic Salinomycin (Sal) is regarded as an inhibitor of cancer stem cells. Its effectiveness on human colorectal cancer (CRC) cells in vitro has been demonstrated before. The aim of this study was to establish a murine model to investigate the effectiveness of Sal in vivo. Furthermore, we investigated the impact of Sal on Wnt/β-catenin signaling in human CD133+ CRC cells.
Methods
The two murine CRC cell lines MC38 and CT26 were used to analyze the impact of Sal on tumor cell proliferation, viability, migration, cell cycle progression and cell death in vitro. For in vivo studies, CT26 cells were injected into syngeneic BALB/c mice to initiate (i) subcutaneous, (ii) orthotopic, or (iii) metastatic CRC growth. Sal was administered daily, 5-Fluoruracil served as a control. For mechanistic studies, the CD133+and CD133- subpopulations of human CRC cells were separated by flow cytometry and separately exposed to increasing concentrations of Sal. The impact on Wnt/β-catenin signaling was determined by Western blotting and quantitative PCR.
Results
Sal markedly impaired tumor cell viability, proliferation and migration, and induced necrotic cell death in vitro. CRC growth in vivo was likewise inhibited upon Sal treatment. Interference with Wnt signaling and reduced expression of the Wnt target genes Fibronectin and Lgr5 indicates a novel molecular mechanism, mediating anti-tumoral effects of Sal in CRC.
Conclusion
Sal effectively impairs CRC growth in vivo. Furthermore, Sal acts as an inhibitor of Wnt/β-catenin signaling. Thus, Salinomycin represents a promising candidate for clinical CRC treatment.
from Cancer via ola Kala on Inoreader http://ift.tt/2fbca80
via IFTTT
NUT midline carcinoma mimicking a germ cell tumor: a case report
Abstract
Background
NUT midline carcinoma (NMC) is a rare and highly aggressive malignancy. Although more information on NMC has been recently accumulating in the literature, most oncologists and pathologists remain unfamiliar with the clinical and pathologic features of this disease. The clinical features of NMC sometimes mimic those of other malignancies, and NMC can therefore be overlooked if the diagnosis is not suspected. We present the case of a young male with NMC arising in the mediastinum with elevated serum alpha-fetoprotein levels suggestive of an extragonadal nonseminomatous germ-cell tumor.
Case presentation
A 28-year-old Japanese male presented with cough and left-sided chest pain for 6 weeks. The patient had a mediastinal tumor with metastases to the right lung, lymph nodes, and bones at initial presentation. Nonseminomatous germ cell tumor was suspected due to the young age, location of the tumors, and elevated serum alpha-fetoprotein. However, biopsy confirmed the diagnosis of NMC with immunohistochemistry. The tumor briefly responded to cytotoxic chemotherapy but subsequently progressed and became refractory to the chemotherapy regimen. External beam radiotherapy was administered with dramatic shrinkage of the tumor and a metabolic response on 18-fluoro-2-deoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scan. However, the patient died 4.5 months after the diagnosis of NMC.
Conclusions
Serum levels of alpha-fetoprotein may be elevated in patients with NMC. Regardless of the level of tumor markers, immunohistochemistry for NUT should be performed in cases of poorly differentiated carcinomas without glandular differentiation arising in the midline structures. 18F-FDG PET/CT is useful for staging and assessing responses to therapy.
from Cancer via ola Kala on Inoreader http://ift.tt/2g27Oxt
via IFTTT