Association of Uba6-Specific-E2 (USE1) With Lung Tumorigenesis

Background: The UBA6-specific E2 conjugating enzyme 1 (USE1) ubiquitin enzyme cascade is a poorly characterized arm of the ubiquitin-proteasome system. We investigated whether the UBA6-USE1 enzyme cascade plays a role in lung cancer tumorigenesis.

Methods: USE1 expression was assessed in tumor-normal paired samples from 106 lung cancer patients by immunoblot. USE1 was stably overexpressed and knocked down in lung cancer cell lines to evaluate cell proliferation, colony formation, and invasion. Xenograft models were used to determine the effects of USE1 on tumor growth (n = 7). Proteomics analysis was used to identify proteins interacting with USE1. The USE1 gene was sequenced in lung cancer patients, and missense mutations of USE1 were generated to evaluate its function. All statistical tests were two-sided.

Results: USE1 proteins were frequently overexpressed in lung cancer patients (92.5%) Stable overexpression of USE1 increased cell proliferation (P = .002), migration (P < .001), and invasion (P < .001), whereas knockdown of USE1 reduced cell proliferation (P < .001), migration (P = .003), and invasion in lung cancer cells and xenograft models (P < .001). USE1 was found to have a conserved D-box domain, and the level of the protein was regulated by the anaphase-promoting complex. Several missense mutations in USE1 identified in patients prolong the stability of the protein.

Conclusions: USE1 proteins are frequently overexpressed in lung cancer, and missense mutations in USE1 prolong the half-life of the protein, promoting tumor formation. Our findings reveal novel roles for USE1 in lung cancer and the possible use of USE1 as a novel biomarker and therapeutic target for lung cancer treatment.

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Financial Hardships Experienced by Cancer Survivors: A Systematic Review

Background: With rising cancer care costs, including high-priced cancer drugs, financial hardship is increasingly documented among cancer survivors in the United States; research findings have not been synthesized.

Methods: We conducted a systematic review of articles published between 1990 and 2015 describing the financial hardship experienced by cancer survivors using PubMed, Embase, Scopus, and CINAHL databases. We categorized measures of financial hardship into: material conditions (eg, out-of-pocket costs, productivity loss, medical debt, or bankruptcy), psychological responses (eg, distress or worry), and coping behaviors (eg, skipped medications). We abstracted findings and conducted a qualitative synthesis.

Results: Among 676 studies identified, 45 met the inclusion criteria and were incorporated in the review. The majority of the studies (82%, n = 37) reported financial hardship as a material condition measure; others reported psychological (7%, n = 3) and behavioral measures (16%, n = 7). Financial hardship measures were heterogeneous within each broad category, and the prevalence of financial hardship varied by the measure used and population studied. Mean annual productivity loss ranged from $380 to $8236, 12% to 62% of survivors reported being in debt because of their treatment, 47% to 49% of survivors reported experiencing some form of financial distress, and 4% to 45% of survivors did not adhere to recommended prescription medication because of cost.

Conclusions: Financial hardship is common among cancer survivors, although we found substantial heterogeneity in its prevalence. Our findings highlight the need for consistent use of definitions, terms, and measures to determine the best intervention targets and inform intervention development in order to prevent and minimize the impact of financial hardship experienced by cancer survivors.

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The Association of Dyslipidemia With Chronic Lymphocytic Leukemia: A Population-Based Study

Background: Metabolic syndrome (MetS) is a risk factor for development of cancer. Because aberrant lipid metabolism is a pathogenic feature of chronic lymphocytic leukemia (CLL), our objective was to determine if CLL patients have a higher prevalence of MetS preceding diagnosis and to determine the impact of lipid-lowering medications on survival.

Methods: We conducted a population-based case-control study in Ontario, Canada, using administrative databases of adults age 66 years and older to compare the prevalence of MetS preceding CLL with age- and sex-matched control subjects. Logistic regression was used to study the association between MetS and its components to CLL. The Kaplan-Meier method and Cox Regression were used to investigate survival. All statistical tests were two-sided.

Results: We identified 2124 persons with CLL and 7935 control subjects from January 1, 2000, to December 31, 2005, with follow-up until March 31, 2014, three years from the date of last contact with the health care system, or death. The mean age was 75.6 years, 20.2% had diabetes, 35.8% had hypertension, and 17.6% had dyslipidemia. In multivariable analysis, dyslipidemia (odds ratio [OR] = 1.26, 95% confidence interval [CI] = 1.11 to 1.44, P < .001) and hypertension (OR = 1.12, 95% CI = 1.01 to 1.25, P = .03) were associated with the development of CLL, whereas MetS and diabetes were not. Lipid-lowering medication was associated with a statistically significant improved survival in patients with CLL (HR = 0.53, 95% CI = 0.47 to 0.61, P < .001).

Conclusions: We demonstrate a higher prevalence of dyslipidemia preceding a diagnosis of CLL compared with control subjects, supporting preclinical data. Lipid-lowering medications appear to confer a survival advantage in CLL. Prospective studies are needed to confirm these results and test their potential as therapeutic applications.

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Urinary Cadmium and Breast Cancer: A Prospective Danish Cohort Study

Background: Cadmium is a human lung carcinogen, and recent evidence suggests it may play a role in hormone-related cancers because of its estrogenic activity. Case-control studies consistently show higher cadmium concentrations in urine from women diagnosed with breast cancer compared with control women. Our aim was to investigate the association between urinary cadmium and breast cancer in a prospective design.

Methods: We conducted a case-cohort study using the population-based Danish Diet Cancer and Health Cohort. Women age 50 to 64 years were recruited in 1993–1997 and provided urine for analysis. We identified 900 incident case patients in the Danish Cancer Registry and compared with 898 individuals in a subcohort. Urine samples collected at enrollment into the cohort were analyzed for cadmium and creatinine. We estimated incidence rate ratios (IRRs) for breast cancer in Cox proportional hazards models with age as time axis and calculated 95% confidence intervals (CIs).

Results: The linear analysis showed no association between urinary cadmium and risk for breast cancer (IRR = 1.00, 95% CI = 0.81 to 1.24 per ng Cd/mL urine). The categorical analyses showed a slightly higher risk for breast cancer for the second (IRR = 1.10, 95% CI = 0.86 to 1.42) and third (IRR = 1.14, 95% CI = 0.83 to 1.55) exposure tertiles compared with the lowest tertile. Results were similar in analyses of breast cancer subtypes defined by estrogen and progesterone receptor status and by histology, and analyses stratified by years from baseline to diagnosis.

Conclusions: This large prospective study showed no association between urinary concentration of cadmium and subsequent risk for development of postmenopausal breast cancer.

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RETRACTED ARTICLE: The Impact of Breast Cancer on Women’s Everyday Life in Eastern India

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Breast Cancer Knowledge Among Male High School Students in Saudi Arabia

Abstract

Breast cancer (BC) accounts for 24 % of all women cancer cases diagnosed in Saudi Arabia each year. Awareness is extremely important in combating this disease. This study was undertaken to assess male high school students' response to BC. This cross-sectional survey was performed on male high school students across schools in Jeddah. A questionnaire gathered data on respondent demographics, beliefs about BC, BC risk factors, early screening methods, and role of men in BC. Statistical analysis was done using SPSS 20. A total of 824 students participated, with an average age of 17.0 years. There was more than 50 % agreement that early detection of BC enhances the chances of recovery, that BC is treatable, and that clinical breast examination and breastfeeding provide protection from BC. Around half the survey population thought that BC was fatal and contagious. Fewer than 50 % thought that BC was inherited and related to smoking, consumption of contraceptive pills, repeated exposure to radiation, obesity, and wearing a bra and that breast tumors were all malignant and spread to different parts of the body. Others knew that mammograms should be performed periodically. A high percentage persuaded their relatives to have mammograms and provided them with psychological support. Knowledge of BC among male high school students in Saudi Arabia is still limited, and, therefore, programs and activities need to be established to increase awareness among high school students.

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Understanding the Stress Management Needs and Preferences of Latinas Undergoing Chemotherapy

Abstract

This exploratory study provides insights into everyday realities, concerns, and cultural perspectives of Latinas undergoing chemotherapy, and elicits information on stress management and information needs. Informed by a community-based participatory research approach using qualitative methods, we conducted ten interviews with providers, and two focus groups (n = 13) and 20 in-depth interviews with Latinas recently diagnosed with breast cancer. Providers and Latina patients acknowledged multiple physical and emotional stressors associated with cancer treatment, viewed a positive aspect of the cancer experience to include connection with God and enhanced spirituality, saw family as a motivating factor for recovery, and expressed a need to draw on existing coping strategies. Findings show considerable overlap between providers and Latina cancer patients' perceptions of stressors during chemotherapy. However, a few notable differences in perceptions of stress management needs during this treatment period emerged. While Latina cancer patients mentioned similar social/structural stressors (e.g., economic problems, lack of information) they tended to emphasize more of the interpersonal stressors related to family communication and relationships (e.g., providing and caring for family, distance from family), and intrapersonal stressors such as fear, changes in physical appearance, and side effects of chemotherapy. Our study illustrates the importance of including multiple perspectives. The information gained by including both providers and patient perspectives yielded a more complete understanding of the stress management needs of Latinas undergoing chemotherapy. Findings suggest that stress management educational interventions should aim to develop self-care skills, be culturally relevant and language-specific, and build upon stress-reducing strategies Latinas may already employ.

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Issue Information – TOC – Masthead

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Adherence to prevention guidelines may lower cancer risk

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Diagnosis: Overload

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“Project EASE” to follow E-cigarette smokers

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RETRACTED ARTICLE: The Impact of Breast Cancer on Women’s Everyday Life in Eastern India

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Breast Cancer Knowledge Among Male High School Students in Saudi Arabia

Abstract

Breast cancer (BC) accounts for 24 % of all women cancer cases diagnosed in Saudi Arabia each year. Awareness is extremely important in combating this disease. This study was undertaken to assess male high school students' response to BC. This cross-sectional survey was performed on male high school students across schools in Jeddah. A questionnaire gathered data on respondent demographics, beliefs about BC, BC risk factors, early screening methods, and role of men in BC. Statistical analysis was done using SPSS 20. A total of 824 students participated, with an average age of 17.0 years. There was more than 50 % agreement that early detection of BC enhances the chances of recovery, that BC is treatable, and that clinical breast examination and breastfeeding provide protection from BC. Around half the survey population thought that BC was fatal and contagious. Fewer than 50 % thought that BC was inherited and related to smoking, consumption of contraceptive pills, repeated exposure to radiation, obesity, and wearing a bra and that breast tumors were all malignant and spread to different parts of the body. Others knew that mammograms should be performed periodically. A high percentage persuaded their relatives to have mammograms and provided them with psychological support. Knowledge of BC among male high school students in Saudi Arabia is still limited, and, therefore, programs and activities need to be established to increase awareness among high school students.

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Understanding the Stress Management Needs and Preferences of Latinas Undergoing Chemotherapy

Abstract

This exploratory study provides insights into everyday realities, concerns, and cultural perspectives of Latinas undergoing chemotherapy, and elicits information on stress management and information needs. Informed by a community-based participatory research approach using qualitative methods, we conducted ten interviews with providers, and two focus groups (n = 13) and 20 in-depth interviews with Latinas recently diagnosed with breast cancer. Providers and Latina patients acknowledged multiple physical and emotional stressors associated with cancer treatment, viewed a positive aspect of the cancer experience to include connection with God and enhanced spirituality, saw family as a motivating factor for recovery, and expressed a need to draw on existing coping strategies. Findings show considerable overlap between providers and Latina cancer patients' perceptions of stressors during chemotherapy. However, a few notable differences in perceptions of stress management needs during this treatment period emerged. While Latina cancer patients mentioned similar social/structural stressors (e.g., economic problems, lack of information) they tended to emphasize more of the interpersonal stressors related to family communication and relationships (e.g., providing and caring for family, distance from family), and intrapersonal stressors such as fear, changes in physical appearance, and side effects of chemotherapy. Our study illustrates the importance of including multiple perspectives. The information gained by including both providers and patient perspectives yielded a more complete understanding of the stress management needs of Latinas undergoing chemotherapy. Findings suggest that stress management educational interventions should aim to develop self-care skills, be culturally relevant and language-specific, and build upon stress-reducing strategies Latinas may already employ.

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Issue Information – TOC – Masthead

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Adherence to prevention guidelines may lower cancer risk

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Diagnosis: Overload

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“Project EASE” to follow E-cigarette smokers

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Case 32-2016: A 20-Year-Old Man with Gynecomastia

Presentation of Case. Dr. Laura E. Dichtel (Endocrinology): A 20-year-old man was evaluated at this hospital because of gynecomastia. The patient came to the hospital for a routine annual examination to establish adult care. He reported a 3-year history of bilateral breast enlargement, with no…

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Inconceivable Hypokalemia: A Case Report of Acute Severe Barium Chloride Poisoning

Barium is a heavy divalent alkaline earth metal that has been known as a muscle poison. Barium can cause human toxicity, which may lead to significant hypokalemia and have serious consequences. This paper reports a case of unprecedented barium intoxication in which the patient, who suffered from depression, swallowed at least 3.0 g barium chloride to commit suicide. On admission, the patient presented with nausea, vomiting, stomach burning feeling, dizziness, and weakness. Emergency biochemical testing showed that the patient was suffering from severe hypokalemia (K+ 1.7 mmol/L). His electrocardiogram (ECG) prompted atrioventricular blocking, ventricular tachycardia, prolongation of PR interval, ST segment depression with U waves, and T wave inversion. Intravenous potassium supplements were given immediately to correct hypokalemia and regular monitoring of vital signs and fluid balance was arranged. After all-out rescue of our hospital personnel, the condition of the patient is currently stable and he is gradually recovering. This case exemplifies the weaknesses of the management of toxic substances and the lack of mental health education for young people. We hope to get more attention for the supervision of toxic substances and the healthy development of young people.

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A Rare Case of an Irreducible Patella Dislocation

Reports of irreducible patellar dislocations are exceedingly sparse throughout the literature. Obvious radiographic or physical exam findings including fracture or inversion of the patella are often present to explain the block to reduction. Not described previously in the literature is the instance of an irreducible patella dislocation in the setting of innocuous appearing injury imaging. We present a case of a healthy thirty-two-year-old female who sustained an irreducible lateral patella dislocation while participating in a dance aerobics class. Closed means of reduction were unsuccessful, necessitating open reduction. Intraoperative findings suggest incarceration of a nondisplaced fracture and a chondral defect as the block to reduction. Following open reduction, the patient has had no further episodes of pain or instability related to the patella at one-year follow-up. Irreducible patellar dislocations are exceedingly rare injuries, where associated osseous or chondral lesions may necessitate open reduction despite innocuous appearing initial imaging. A high index of suspicion to proceed with open reduction may limit repeated attempts at closed reduction and further injury.

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Adalimumab Induced or Provoked MS in Patient with Autoimmune Uveitis: A Case Report and Review of the Literature

Anti-tumor necrosis factor α (anti-TNF-α) agents have been widely used in the field of autoimmune diseases and have proved decisive efficacy and relative safety. Data concerning their adverse effects has been lately describing central nervous system (CNS) demyelination process at escalating basis. Case Presentation. A 23-year-old male with autoimmune uveitis and a family history of multiple sclerosis (MS) developed two neurological attacks, after Adalimumab infusion, simultaneously with several cerebral lesions on magnetic resonance imaging (MRI). Hence the diagnosis of Adalimumab induced MS was suspected. Conclusion. This case is reported to tell physicians to be cautious when using anti-TNF-α in patients with family history of MS and to reconsider the risk of MS in patients with autoimmune diseases.

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Bowel Ischemia from Heat Stroke: A Rare Presentation of an Uncommon Complication

A healthy 27-year-old female presented to the hospital after she collapsed an hour into her first marathon run on a hot humid day. On presentation, she was hyperthermic, encephalopathic, tachycardic, and hypotensive. On admission, she was found to have lactic acidosis, rhabdomyolysis, and acute kidney injury and was treated with cold normal saline and cooling blankets. She subsequently started having abdominal pain and bloody bowel movements. Computed tomography of the abdomen revealed ascending colon thickening. Furthermore, her lab findings showed transaminitis and elevated coagulation parameters. Due to the acute hypotensive state from the heat stroke, patient had developed bowel ischemia, ischemic hepatitis, and disseminated intravascular coagulation, all of which are uncommon complications of heat stroke. She was managed aggressively with intravenous fluid hydration with resolution of her symptoms over the course of 4 days. In addition to the uncommon complications, early presentation of this bowel ischemia despite adequate hydration in such a healthy individual is another unique aspect of the case.

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Mitochondrial Disorder Aggravated by Metoprolol

Beta-adrenergic blocking agents or beta-blockers are a class of medications used to treat cardiac arrhythmias and systemic hypertension. In therapeutic dosages, they have known adverse outcomes that can include muscular fatigue and cramping, dizziness, and dyspnea. In patients with mitochondrial disease, these effects can be amplified. Previous case reports have been published in the adult population; however, their impact in pediatric patients has not been reported. We describe a pediatric patient with a mitochondrial disorder who developed respiratory distress after metoprolol was prescribed for hypertension. As the patient improved with discontinuation of medication and no alternative etiology was found for symptoms, we surmise that administration of metoprolol aggravated his mitochondrial dysfunction, thus worsening underlying chest wall weakness.

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Cancer: fundamentals behind pH targeting and the double-edged approach

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Personalized treatment in advanced ALK-positive non-small cell lung cancer: from bench to clinical practice

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Prognostic impact of body mass index stratified by smoking status in patients with esophageal squamous cell carcinoma

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Cancers, Vol. 8, Pages 96: Modulation of the Anti-Tumor Efficacy of Photodynamic Therapy by Nitric Oxide

Nitric oxide (NO) produced by nitric oxide synthase (NOS) enzymes is a free radical molecule involved in a wide variety of normophysiologic and pathophysiologic processes. Included in the latter category are cancer promotion, progression, and resistance to therapeutic intervention. Animal tumor photodynamic therapy (PDT) studies several years ago revealed that endogenous NO can reduce PDT efficacy and that NOS inhibitors can alleviate this. Until relatively recently, little else was known about this anti-PDT effect of NO, including: (a) the underlying mechanisms; (b) type(s) of NOS involved; and (c) whether active NO was generated in vascular cells, tumor cells, or both. In addressing these questions for various cancer cell lines exposed to PDT-like conditions, the author's group has made several novel findings, including: (i) exogenous NO can scavenge lipid-derived free radicals arising from photostress, thereby protecting cells from membrane-damaging chain peroxidation; (ii) cancer cells can upregulate inducible NOS (iNOS) after a PDT-like challenge and the resulting NO can signal for resistance to photokilling; (iii) photostress-surviving cells with elevated iNOS/NO proliferate and migrate/invade more aggressively; and (iv) NO produced by photostress-targeted cells can induce greater aggressiveness in non-targeted bystander cells. In this article, the author briefly discusses these various means by which NO can interfere with PDT and how this may be mitigated by use of NOS inhibitors as PDT adjuvants.

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Cancers, Vol. 8, Pages 96: Modulation of the Anti-Tumor Efficacy of Photodynamic Therapy by Nitric Oxide

Nitric oxide (NO) produced by nitric oxide synthase (NOS) enzymes is a free radical molecule involved in a wide variety of normophysiologic and pathophysiologic processes. Included in the latter category are cancer promotion, progression, and resistance to therapeutic intervention. Animal tumor photodynamic therapy (PDT) studies several years ago revealed that endogenous NO can reduce PDT efficacy and that NOS inhibitors can alleviate this. Until relatively recently, little else was known about this anti-PDT effect of NO, including: (a) the underlying mechanisms; (b) type(s) of NOS involved; and (c) whether active NO was generated in vascular cells, tumor cells, or both. In addressing these questions for various cancer cell lines exposed to PDT-like conditions, the author's group has made several novel findings, including: (i) exogenous NO can scavenge lipid-derived free radicals arising from photostress, thereby protecting cells from membrane-damaging chain peroxidation; (ii) cancer cells can upregulate inducible NOS (iNOS) after a PDT-like challenge and the resulting NO can signal for resistance to photokilling; (iii) photostress-surviving cells with elevated iNOS/NO proliferate and migrate/invade more aggressively; and (iv) NO produced by photostress-targeted cells can induce greater aggressiveness in non-targeted bystander cells. In this article, the author briefly discusses these various means by which NO can interfere with PDT and how this may be mitigated by use of NOS inhibitors as PDT adjuvants.

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Antitumor activity of recombinant RGD-IFN-[alpha]2a-core fusion protein in vitro.

Interferon (IFN) regulates immune responses and antitumor activity. Arginine-glycine-aspartic acid (RGD) peptides can specifically bind to integrin [alpha]v[beta]3, a transmembrane receptor that is highly expressed on the surface of various cancer cells. In this study, we expressed recombinant RGD-IFN-[alpha]2a-core fusion proteins and assessed their antitumor activity in vitro. Two RGD-IFN-[alpha]2a-core fusion proteins and a negative control protein were expressed in vitro. These two RGD-IFN-[alpha]2a-core fusion proteins could bind the tumor cell surface specifically and did not bind to normal cells. RGD-IFN-[alpha]2a-core fusion protein treatment of tumor cells significantly reduced cell viability and induced apoptosis in a dose-dependent manner. At the 'mRNA' level, both proteins could upregulate CASP3 expression. These data indicate that both laboratory-engineered RGD-IFN-[alpha]2a-core fusion proteins could bind the surface of tumor cells and induce apoptosis in vitro. Further studies will investigate the in-vivo antitumor activities of the RGD-IFN-[alpha]2a-core fusion proteins. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://ift.tt/1hexVwJ Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Antitumor activity of recombinant RGD-IFN-[alpha]2a-core fusion protein in vitro.

Interferon (IFN) regulates immune responses and antitumor activity. Arginine-glycine-aspartic acid (RGD) peptides can specifically bind to integrin [alpha]v[beta]3, a transmembrane receptor that is highly expressed on the surface of various cancer cells. In this study, we expressed recombinant RGD-IFN-[alpha]2a-core fusion proteins and assessed their antitumor activity in vitro. Two RGD-IFN-[alpha]2a-core fusion proteins and a negative control protein were expressed in vitro. These two RGD-IFN-[alpha]2a-core fusion proteins could bind the tumor cell surface specifically and did not bind to normal cells. RGD-IFN-[alpha]2a-core fusion protein treatment of tumor cells significantly reduced cell viability and induced apoptosis in a dose-dependent manner. At the 'mRNA' level, both proteins could upregulate CASP3 expression. These data indicate that both laboratory-engineered RGD-IFN-[alpha]2a-core fusion proteins could bind the surface of tumor cells and induce apoptosis in vitro. Further studies will investigate the in-vivo antitumor activities of the RGD-IFN-[alpha]2a-core fusion proteins. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://ift.tt/1hexVwJ Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Wnt5b-associated exosomes promote cancer cell migration and proliferation

Summary

Wnt5b, a member of the same family of proteins as Wnt5a of which overexpression is associated with cancer aggressiveness, is suggested to be involved in cancer progression, however details remain unclarified. We analyzed biochemical properties of purified Wnt5b and the mode of secretion of Wnt5b by cancer cells. Wnt5b was glycosylated at three asparagine residues and lipidated at one serine residue, and these post-translational modifications of Wnt5b are essential for secretion. Purified Wnt5b showed Dvl2 phosphorylation and Rac activation abilities to a similar extent as Wnt5a. In cultured-cell conditioned medium Wnt5b was detected in supernatant or precipitation fractions that were separated by centrifugation at 100,000 × g. In PANC-1 pancreatic cancer cells 55% of secreted endogenous Wnt5b was associated with exosomes. Exosomes from wild-type PANC-1 cells, but not those from Wnt5b-knockout PANC-1 cells, activated Wnt5b signaling in CHO cells and stimulated migration and proliferation of A549 lung adenocarcinoma cells, suggesting that endogenous, Wnt5b-associated exosomes are active. The exosomes were taken up by CHO cells and immunoelectron microscopy revealed that Wnt5b is indeed associated with exosomes. In Caco-2 colon cancer cells, most Wnt5b was recovered in precipitation fractions when Wnt5b was ectopically expressed (Caco-2/Wnt5b cells). Knockdown of TSG101, an exosome marker, decreased the secretion of Wnt5b-associated exosomes from Caco-2/Wnt5b cells and inhibited Wnt5b-dependent cell proliferation. Exosomes secreted from Caco-2/Wnt5b cells stimulated migration and proliferation of A549 cells. These results suggest that Wnt5b-associated exosomes promote cancer cell migration and proliferation in a paracrine manner.

This article is protected by copyright. All rights reserved.

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Celecoxib and 2,5-dimethylcelecoxib inhibit intestinal cancer growth by suppressing the Wnt/β-catenin signaling pathway

Summary

We previously reported that celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, strongly inhibited human colon cancer cell proliferation by suppressing the Wnt/β-catenin signaling pathway. 2,5-Dimethylcelecoxib (DM-celecoxib), a celecoxib analogue, which does not inhibit COX-2, has also been reported to have an anti-tumor effect. In the present study, we elucidated whether DM-celecoxib inhibits intestinal cancer growth, and its underlying mechanism of action. First, we compared the effect of DM-celecoxib with that of celecoxib on the human colon cancer cell lines HCT-116 and DLD-1. DM-celecoxib suppressed cell proliferation and inhibited TCF7L2 expression with almost same strength as celecoxib. DM-celecoxib also inhibited the TCF-dependent transcription activity and suppressed the expression of Wnt/β-catenin target gene products cyclin D1 and survivin. Subsequently, we compared the in vivo effects of celecoxib and DM-celecoxib using the Mutyh^-/- mouse model, in which oxidative stress induces multiple intestinal carcinomas. Serum concentrations of orally administered celecoxib and DM-celecoxib elevated to the levels enough to suppress cancer cell proliferation. Repeated administration of celecoxib and DM-celecoxib markedly reduced the number and size of the carcinomas without exhibiting toxicity. These results suggest that the central mechanism for the anti-cancer effect of celecoxib derivatives is the suppression of the Wnt/β-catenin signaling pathway but not the inhibition of COX-2, and that DM-celecoxib might be might be a better lead compound candidate than celecoxib for the development of novel anti-cancer drugs.

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Changes in the tumor microenvironment during lymphatic metastasis of lung squamous cell carcinoma

Abstract

Metastasis and growth in neoplastic lesions requires the multi-step regulation of microenvironmental factors. We aimed to elucidate the microenvironmental changes in the process of lymphatic metastasis of lung squamous cell carcinoma. We examined the morphological characteristics of 102 cases of Primary Tumor (PT), 50 of intralymphatic tumor (ILT), 51 of lymph node (LN) micrometastasis (LN-Mic; less than 2 mm in size) and 82 of LN macrometastasis (LN-Mac; greater than 10 mm in size). Afterwards we evaluated the expression of nine molecules (EGFR, FGFR2, CD44, ALDH1, Podoplanin, E-cadherin, S100A4, geminin and ezrin) in matched PT, ILT, LN-Mic and LN-Mac from 23 of these cases. The number of smooth muscle actin α-positive fibroblasts, CD34-positive microvessels and CD204-positive macrophages were also examined. As a result, the mitotic index of tumor cells was significantly lower in ILT and LN-Mic than PT and LN-Mac (p<0.001). Moreover stromal reaction in ILT and LN-Mic was less prominent than in PT and LN-Mac (p<0.001). Immunohistochemical study revealed that EGFR expression level and frequency of geminin positive cells in ILT and LN-Mic were significantly lower than in PT and LN-Mac (p<0.05). The number of stromal cells indicated by staining of CD34, CD204 and smooth muscle actin α in ILT and LN-Mic also was significantly lower than in PT and LN-Mac (p<0.05). In lung squamous cell carcinoma, drastic microenvironmental changes (e.g., growth factor receptor expression and proliferative capacity of tumor cells and structural changes in stromal cells) occur during both the process of lymphatic permeation and the progression into macrometastases.

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Wnt5b-associated exosomes promote cancer cell migration and proliferation

Summary

Wnt5b, a member of the same family of proteins as Wnt5a of which overexpression is associated with cancer aggressiveness, is suggested to be involved in cancer progression, however details remain unclarified. We analyzed biochemical properties of purified Wnt5b and the mode of secretion of Wnt5b by cancer cells. Wnt5b was glycosylated at three asparagine residues and lipidated at one serine residue, and these post-translational modifications of Wnt5b are essential for secretion. Purified Wnt5b showed Dvl2 phosphorylation and Rac activation abilities to a similar extent as Wnt5a. In cultured-cell conditioned medium Wnt5b was detected in supernatant or precipitation fractions that were separated by centrifugation at 100,000 × g. In PANC-1 pancreatic cancer cells 55% of secreted endogenous Wnt5b was associated with exosomes. Exosomes from wild-type PANC-1 cells, but not those from Wnt5b-knockout PANC-1 cells, activated Wnt5b signaling in CHO cells and stimulated migration and proliferation of A549 lung adenocarcinoma cells, suggesting that endogenous, Wnt5b-associated exosomes are active. The exosomes were taken up by CHO cells and immunoelectron microscopy revealed that Wnt5b is indeed associated with exosomes. In Caco-2 colon cancer cells, most Wnt5b was recovered in precipitation fractions when Wnt5b was ectopically expressed (Caco-2/Wnt5b cells). Knockdown of TSG101, an exosome marker, decreased the secretion of Wnt5b-associated exosomes from Caco-2/Wnt5b cells and inhibited Wnt5b-dependent cell proliferation. Exosomes secreted from Caco-2/Wnt5b cells stimulated migration and proliferation of A549 cells. These results suggest that Wnt5b-associated exosomes promote cancer cell migration and proliferation in a paracrine manner.

This article is protected by copyright. All rights reserved.

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Celecoxib and 2,5-dimethylcelecoxib inhibit intestinal cancer growth by suppressing the Wnt/β-catenin signaling pathway

Summary

We previously reported that celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, strongly inhibited human colon cancer cell proliferation by suppressing the Wnt/β-catenin signaling pathway. 2,5-Dimethylcelecoxib (DM-celecoxib), a celecoxib analogue, which does not inhibit COX-2, has also been reported to have an anti-tumor effect. In the present study, we elucidated whether DM-celecoxib inhibits intestinal cancer growth, and its underlying mechanism of action. First, we compared the effect of DM-celecoxib with that of celecoxib on the human colon cancer cell lines HCT-116 and DLD-1. DM-celecoxib suppressed cell proliferation and inhibited TCF7L2 expression with almost same strength as celecoxib. DM-celecoxib also inhibited the TCF-dependent transcription activity and suppressed the expression of Wnt/β-catenin target gene products cyclin D1 and survivin. Subsequently, we compared the in vivo effects of celecoxib and DM-celecoxib using the Mutyh^-/- mouse model, in which oxidative stress induces multiple intestinal carcinomas. Serum concentrations of orally administered celecoxib and DM-celecoxib elevated to the levels enough to suppress cancer cell proliferation. Repeated administration of celecoxib and DM-celecoxib markedly reduced the number and size of the carcinomas without exhibiting toxicity. These results suggest that the central mechanism for the anti-cancer effect of celecoxib derivatives is the suppression of the Wnt/β-catenin signaling pathway but not the inhibition of COX-2, and that DM-celecoxib might be might be a better lead compound candidate than celecoxib for the development of novel anti-cancer drugs.

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Changes in the tumor microenvironment during lymphatic metastasis of lung squamous cell carcinoma

Abstract

Metastasis and growth in neoplastic lesions requires the multi-step regulation of microenvironmental factors. We aimed to elucidate the microenvironmental changes in the process of lymphatic metastasis of lung squamous cell carcinoma. We examined the morphological characteristics of 102 cases of Primary Tumor (PT), 50 of intralymphatic tumor (ILT), 51 of lymph node (LN) micrometastasis (LN-Mic; less than 2 mm in size) and 82 of LN macrometastasis (LN-Mac; greater than 10 mm in size). Afterwards we evaluated the expression of nine molecules (EGFR, FGFR2, CD44, ALDH1, Podoplanin, E-cadherin, S100A4, geminin and ezrin) in matched PT, ILT, LN-Mic and LN-Mac from 23 of these cases. The number of smooth muscle actin α-positive fibroblasts, CD34-positive microvessels and CD204-positive macrophages were also examined. As a result, the mitotic index of tumor cells was significantly lower in ILT and LN-Mic than PT and LN-Mac (p<0.001). Moreover stromal reaction in ILT and LN-Mic was less prominent than in PT and LN-Mac (p<0.001). Immunohistochemical study revealed that EGFR expression level and frequency of geminin positive cells in ILT and LN-Mic were significantly lower than in PT and LN-Mac (p<0.05). The number of stromal cells indicated by staining of CD34, CD204 and smooth muscle actin α in ILT and LN-Mic also was significantly lower than in PT and LN-Mac (p<0.05). In lung squamous cell carcinoma, drastic microenvironmental changes (e.g., growth factor receptor expression and proliferative capacity of tumor cells and structural changes in stromal cells) occur during both the process of lymphatic permeation and the progression into macrometastases.

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Procalcitonin and cytokine profiles in engraftment syndrome in pediatric stem cell transplantation

Abstract

Background

Diagnosis of engraftment syndrome (ES) following allogeneic hematopoietic stem cell transplantation (HSCT) can be a challenge due to the systemic presentation and alternative etiologies. With a goal of establishing biomarkers to more accurately distinguish ES, we prospectively analyzed levels of cytokines during HSCT.

Procedures

We performed a prospective study of children ≤21 years who underwent allogeneic HSCT. Blood samples for interleukin (IL)-6, IL-8, IL-10, IL-1b, IL-12p70, interferon-γ, tumor necrosis factor alpha (TNF-α) and procalcitonin were obtained from each subject prior to conditioning, at day 0, and then biweekly through engraftment and at days 30, 60 and 100. Patients were evaluated for ES, infection and acute graft-versus-host disease. Cytokines were analyzed by values at engraftment, and also compared to pre-conditioning and day 0 values to evaluate for change from baseline.

Results

A total of 30 subjects (median age: 7 years, min.–max.: 1–21 years) were enrolled of whom 5 had ES. Characterization of the cytokine profile revealed differences between day 0 from pre-HSCT, with a trend towards differences in IL-10, IL-12p70, interferon-γ and TNF-α at the time of ES. For IL8 and procalcitonin, there was evidence that the absolute difference (or fold change) between engraftment and pre-conditioning or day 0 differed according to ES. In particular, procalcitonin increased from baseline (15.1 median fold increase in ES+ versus 2.31 median fold increase in ES−, P = 0.0006, median difference: 13.8, 95% confidence interval: 6.33, 65.6).

Conclusions

Our data provide one of the first prospective studies evaluating cytokines in pediatric allogeneic HSCT and suggest that elevated procalcitonin may serve as a biomarker for ES. Further studies to evaluate this finding are warranted.

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Improving outcome of acute lymphoblastic leukemia with a simplified protocol: report from a tertiary care center in north India

Abstract

Background

The outcome of malignancies in low- and middle-income countries (LMICs) is hampered owing to numerous factors. Current protocols are complex, demanding supportive care, often not optimally available. We de-escalated the UKALL 2003 protocol to improve the outcome of acute lymphoblastic leukemia (ALL) at our center.

Methods

In 2007–2009, children were treated as per the UKALL 2003 protocol (protocol 1). In 2010 and 2011, a modified version of the UKALL 2003 (protocol 2) was followed.

Results

Three hundred and seventy-four children aged 5.71+3.1 (1–13) years were treated. Remission was achieved in 335 of the 338 who completed induction. Treatment-related mortality decreased significantly with the modified protocol (P ≤ 0.001). Relapses were similar with both protocols. Protocol used, regimen, counts at diagnosis, weight for age, gender, education of parents and occupation of caregiver were associated with the outcome of death (P < 0.05). On Cox proportional hazard analysis, patients on protocol 1, female gender and weight ≤5th centile had a greater hazard of dying (0.46 [P < 0.0001]; 1.5 [P = 0.04] and 1.64 [P = 0.01]). The 3 years overall survival (OS) with protocols 1 and 2 was 54.8% (95% CI 47.4–61.7%) and 73.9% (95% CI 66–79%) (P < 0.001), respectively. The event-free survival with protocols 1 and 2 was 50.8% (95% CI 43–57%) and 65.7% (95% CI 58–72%) (P < 0.001), respectively.

Conclusions

A steady improvement in survival has been observed at our center to a 3-year present OS of 73.9% with reduction in treatment intensity. The way forward for LMICs is to formulate rational treatment protocols at par with resources.

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Measuring primary tumor response in neuroblastoma: More than using a ruler

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Comparative retrospective study on the modalities of biopsying peripheral neuroblastic tumors: a report from the Italian Pediatric Surgical Oncology Group (GICOP)

Abstract

Background

Peripheral neuroblastic tumors are the most common extracranial solid neoplasms in children. Early and adequate tissue sampling may speed up the diagnostic process and ensure a prompt start of optimal treatment whenever needed. Different biopsy techniques have been described. The purpose of this multi-center study is to evaluate the accuracy and safety of the various examined techniques and to determine whether a preferential procedure exists.

Methods

All children who underwent a biopsy, from January 2010 to December 2014, as a result of being diagnosed with a peripheral neuroblastic tumor, were retrospectively reviewed. Data collected included patients' demographics, clinical presentation, intraoperative technical details, postoperative parameters, complications, and histology reports. The Mann–Whitney U and Fisher's exact tests were used for statistical analysis.

Results

The cohort included 100 patients, 32 of whom underwent an incisional biopsy (performed through open or minimally invasive access) (Group A), and the remaining 68 underwent multiple needle-core biopsies (either imaging-guided or laparoscopy/thoracoscopy-assisted) (Group B). Comparing the two groups revealed that Group A patients had a higher rate of complications, a greater need for postoperative analgesia, and required red blood cell transfusion more often. Overall adequacy rate was 94%, without significant differences between the two groups (100% vs. 91.2% for Group A and Group B, respectively, P = 0.0933).

Conclusions

Both incision and needle-core biopsying methods provided sub-optimal to optimal sampling adequacy rates in children affected by peripheral neuroblastic tumors. However, the former method was associated with a higher risk of both intraoperative and postoperative complications compared with the latter.

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Procalcitonin and cytokine profiles in engraftment syndrome in pediatric stem cell transplantation

Abstract

Background

Diagnosis of engraftment syndrome (ES) following allogeneic hematopoietic stem cell transplantation (HSCT) can be a challenge due to the systemic presentation and alternative etiologies. With a goal of establishing biomarkers to more accurately distinguish ES, we prospectively analyzed levels of cytokines during HSCT.

Procedures

We performed a prospective study of children ≤21 years who underwent allogeneic HSCT. Blood samples for interleukin (IL)-6, IL-8, IL-10, IL-1b, IL-12p70, interferon-γ, tumor necrosis factor alpha (TNF-α) and procalcitonin were obtained from each subject prior to conditioning, at day 0, and then biweekly through engraftment and at days 30, 60 and 100. Patients were evaluated for ES, infection and acute graft-versus-host disease. Cytokines were analyzed by values at engraftment, and also compared to pre-conditioning and day 0 values to evaluate for change from baseline.

Results

A total of 30 subjects (median age: 7 years, min.–max.: 1–21 years) were enrolled of whom 5 had ES. Characterization of the cytokine profile revealed differences between day 0 from pre-HSCT, with a trend towards differences in IL-10, IL-12p70, interferon-γ and TNF-α at the time of ES. For IL8 and procalcitonin, there was evidence that the absolute difference (or fold change) between engraftment and pre-conditioning or day 0 differed according to ES. In particular, procalcitonin increased from baseline (15.1 median fold increase in ES+ versus 2.31 median fold increase in ES−, P = 0.0006, median difference: 13.8, 95% confidence interval: 6.33, 65.6).

Conclusions

Our data provide one of the first prospective studies evaluating cytokines in pediatric allogeneic HSCT and suggest that elevated procalcitonin may serve as a biomarker for ES. Further studies to evaluate this finding are warranted.

http://ift.tt/2dCeMLz

Improving outcome of acute lymphoblastic leukemia with a simplified protocol: report from a tertiary care center in north India

Abstract

Background

The outcome of malignancies in low- and middle-income countries (LMICs) is hampered owing to numerous factors. Current protocols are complex, demanding supportive care, often not optimally available. We de-escalated the UKALL 2003 protocol to improve the outcome of acute lymphoblastic leukemia (ALL) at our center.

Methods

In 2007–2009, children were treated as per the UKALL 2003 protocol (protocol 1). In 2010 and 2011, a modified version of the UKALL 2003 (protocol 2) was followed.

Results

Three hundred and seventy-four children aged 5.71+3.1 (1–13) years were treated. Remission was achieved in 335 of the 338 who completed induction. Treatment-related mortality decreased significantly with the modified protocol (P ≤ 0.001). Relapses were similar with both protocols. Protocol used, regimen, counts at diagnosis, weight for age, gender, education of parents and occupation of caregiver were associated with the outcome of death (P < 0.05). On Cox proportional hazard analysis, patients on protocol 1, female gender and weight ≤5th centile had a greater hazard of dying (0.46 [P < 0.0001]; 1.5 [P = 0.04] and 1.64 [P = 0.01]). The 3 years overall survival (OS) with protocols 1 and 2 was 54.8% (95% CI 47.4–61.7%) and 73.9% (95% CI 66–79%) (P < 0.001), respectively. The event-free survival with protocols 1 and 2 was 50.8% (95% CI 43–57%) and 65.7% (95% CI 58–72%) (P < 0.001), respectively.

Conclusions

A steady improvement in survival has been observed at our center to a 3-year present OS of 73.9% with reduction in treatment intensity. The way forward for LMICs is to formulate rational treatment protocols at par with resources.

http://ift.tt/2evg9ZM

Measuring primary tumor response in neuroblastoma: More than using a ruler

http://ift.tt/2dCavI0

Comparative retrospective study on the modalities of biopsying peripheral neuroblastic tumors: a report from the Italian Pediatric Surgical Oncology Group (GICOP)

Abstract

Background

Peripheral neuroblastic tumors are the most common extracranial solid neoplasms in children. Early and adequate tissue sampling may speed up the diagnostic process and ensure a prompt start of optimal treatment whenever needed. Different biopsy techniques have been described. The purpose of this multi-center study is to evaluate the accuracy and safety of the various examined techniques and to determine whether a preferential procedure exists.

Methods

All children who underwent a biopsy, from January 2010 to December 2014, as a result of being diagnosed with a peripheral neuroblastic tumor, were retrospectively reviewed. Data collected included patients' demographics, clinical presentation, intraoperative technical details, postoperative parameters, complications, and histology reports. The Mann–Whitney U and Fisher's exact tests were used for statistical analysis.

Results

The cohort included 100 patients, 32 of whom underwent an incisional biopsy (performed through open or minimally invasive access) (Group A), and the remaining 68 underwent multiple needle-core biopsies (either imaging-guided or laparoscopy/thoracoscopy-assisted) (Group B). Comparing the two groups revealed that Group A patients had a higher rate of complications, a greater need for postoperative analgesia, and required red blood cell transfusion more often. Overall adequacy rate was 94%, without significant differences between the two groups (100% vs. 91.2% for Group A and Group B, respectively, P = 0.0933).

Conclusions

Both incision and needle-core biopsying methods provided sub-optimal to optimal sampling adequacy rates in children affected by peripheral neuroblastic tumors. However, the former method was associated with a higher risk of both intraoperative and postoperative complications compared with the latter.

http://ift.tt/2evc3RB

Immunophenotypic and prognostic analysis of PAX8 and TTF-1 expressions in neuroendocrine carcinomas of thymic origin: A comparative study with their pulmonary counterparts

Objectives

To investigate the immunoreactivity of TTF-1 and PAX8 in neuroendocrine carcinoma of thymic (TNEC) and pulmonary origins (PNEC), and whether their immunophenotyping could be used to distinguish between NEC of the two sites, as well as prognosis of patients with TNEC.

Methods

Twenty-two cases of TNEC and 20 cases of PNEC were selected for immunohistochemical analysis using PAX8 and TTF-1. Clinical data and follow-up information were obtained for survival analyses.

Results

TTF-1 immunoreactivity was seen in 19 PNEC cases (95%) and 13 TNEC cases (59.1%). PAX8 was negative in all pulmonary tumors while positive in 19 thymic cases (86.4%). TTF-1 positivity was associated with high sensitivity but low specificity for PNEC, and adding PAX8 negativity significantly increased the specificity. PAX8 positivity alone showed essentially 100% specificity and 86.4% sensitivity for TNEC. Survival analysis showed lung metastasis as a significant prognostic factor in TNEC.

Conclusion

Our study demonstrated that TTF-1/PAX8 immunophenotyping may be helpful for differential diagnosis of NECs of pulmonary and thymic origins. TTF-1+/PAX8− immunophenotyping showed high specificity for PNECs, while PAX8+ alone showed a good diagnostic accuracy for TNEC. Lung metastasis was a predictive factor that associated with survival of TNEC patients. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.

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Patient-centered outcomes to decide treatment strategy for patients with low rectal cancer

Background

For patients with low-lying rectal cancer, the feasibility of anus-preserving surgery in combination with neoadjuvant chemoradiotherapy (NACRT) has been not well established from the perspective of patient-centered outcomes.

Methods

We investigated 278 patients with low-lying rectal adenocarcinoma from 2005 to 2012. We compared their symptoms and QOL scores of patients who underwent anus-preserving surgery with (n = 88) and without (n = 143) NACRT according to the Wexner scale, EORTC QLQ C-30, CR29, and the modified fecal incontinence quality life scale (mFIQL). Furthermore, to assess the rationale for intersphincteric resection (ISR) with NACRT, we also compared QOL of patients who underwent ISR with NACRT (n = 31) and abdominoperineal resection (APR, n = 47).

Results

The adjusted mean differences of the Wexner score estimates of the patients who underwent ISR and very low anterior resection (VLAR) with or without NACRT were 5.29 (P = 0.004) and 2.67 (P = 0.009), respectively. No significant difference was observed in the QOL scores of two treatment groups. Furthermore, there were no significant differences in the QOL or function scores of patients who underwent ISR with NACRT and APR.

Conclusion

The incontinence was significantly worse in patients who receive NACRT. However, there were no significant differences in their QOL or function scores. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.

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Immunophenotypic and prognostic analysis of PAX8 and TTF-1 expressions in neuroendocrine carcinomas of thymic origin: A comparative study with their pulmonary counterparts

Objectives

To investigate the immunoreactivity of TTF-1 and PAX8 in neuroendocrine carcinoma of thymic (TNEC) and pulmonary origins (PNEC), and whether their immunophenotyping could be used to distinguish between NEC of the two sites, as well as prognosis of patients with TNEC.

Methods

Twenty-two cases of TNEC and 20 cases of PNEC were selected for immunohistochemical analysis using PAX8 and TTF-1. Clinical data and follow-up information were obtained for survival analyses.

Results

TTF-1 immunoreactivity was seen in 19 PNEC cases (95%) and 13 TNEC cases (59.1%). PAX8 was negative in all pulmonary tumors while positive in 19 thymic cases (86.4%). TTF-1 positivity was associated with high sensitivity but low specificity for PNEC, and adding PAX8 negativity significantly increased the specificity. PAX8 positivity alone showed essentially 100% specificity and 86.4% sensitivity for TNEC. Survival analysis showed lung metastasis as a significant prognostic factor in TNEC.

Conclusion

Our study demonstrated that TTF-1/PAX8 immunophenotyping may be helpful for differential diagnosis of NECs of pulmonary and thymic origins. TTF-1+/PAX8− immunophenotyping showed high specificity for PNECs, while PAX8+ alone showed a good diagnostic accuracy for TNEC. Lung metastasis was a predictive factor that associated with survival of TNEC patients. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.

http://ift.tt/2euUqkS

Patient-centered outcomes to decide treatment strategy for patients with low rectal cancer

Background

For patients with low-lying rectal cancer, the feasibility of anus-preserving surgery in combination with neoadjuvant chemoradiotherapy (NACRT) has been not well established from the perspective of patient-centered outcomes.

Methods

We investigated 278 patients with low-lying rectal adenocarcinoma from 2005 to 2012. We compared their symptoms and QOL scores of patients who underwent anus-preserving surgery with (n = 88) and without (n = 143) NACRT according to the Wexner scale, EORTC QLQ C-30, CR29, and the modified fecal incontinence quality life scale (mFIQL). Furthermore, to assess the rationale for intersphincteric resection (ISR) with NACRT, we also compared QOL of patients who underwent ISR with NACRT (n = 31) and abdominoperineal resection (APR, n = 47).

Results

The adjusted mean differences of the Wexner score estimates of the patients who underwent ISR and very low anterior resection (VLAR) with or without NACRT were 5.29 (P = 0.004) and 2.67 (P = 0.009), respectively. No significant difference was observed in the QOL scores of two treatment groups. Furthermore, there were no significant differences in the QOL or function scores of patients who underwent ISR with NACRT and APR.

Conclusion

The incontinence was significantly worse in patients who receive NACRT. However, there were no significant differences in their QOL or function scores. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.

http://ift.tt/2dBZ7M5

Synergistic suppression effect on tumor growth of ovarian cancer by combining cisplatin with a manganese superoxide dismutase-armed oncolytic adenovirus

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