Cd20 Expression and Effects on Outcome of Relapsed/Refractory Diffuse Large B Cell Lymphoma after Treatment with Rituximab

Introduction: Down regulation of CD20 expression has been reported in diffuse large B cell lymphoma (DLBCL)).Therefore, it is important to determine whether chemotherapy with rituximab induces CD20 down regulation and effectssurvival. Objectives: To determine the incidence of down regulation of CD20 expression in relapsed DLBCL aftertreatment with rituximab and to compare outcomes and assess pattern of relapse between CD20 negative and CD20positive cases. Methodology: We retrospectively reviewed patients with relapsed DLBCL who received rituximab inthe first line setting at Aga Khan University Hospital between January 2007 and December 2014. Data were recordedon predesigned questionnaires, with variables including demographics, details regarding date of diagnosis and relapse,histology, staging, international prognostic index, treatment and outcomes at initial diagnosis and at relapse. The Chisquare test was applied to determine statistical significance between categorical variables. Survival curves were generatedby the Kaplan–Meier method. Results: A total of 54 patients with relapsed DLBCL were included in our study, 38 (70%) males and 16(30%) females. Some 23 (43%) patients were at stage IV at the time of diagnosis and 34 (63%) had Bsymptoms. The most frequent R-IPI at diagnosis was II in 24 (44%) patients. Only 6 (11%) did not show CD20 expressionon re-biopsy for relapsed/refractory disease, 2 with CD20 negative DLBCL responding to second line chemotherapy.A complete response after salvage chemotherapy was noted in 16 (29.6%) cases with relapsed/refractory DLBCL.Seven (13%) patients underwent an autologous bone marrow transplant as consolidation after second line treatment.Median overall survival was 18 months in CD20 positive vs. 13 months in CD20 negative patients. Conclusion: Thisstudy demonstrated that a small percentage of patients treated with rituximab lose their CD20 expression at the timeof relapse. However, it is unclear whether this is associated with an inferior outcome.     

Disease Characteristics,Clinical Management,and Outcomes of Young Patients With Colon Cancer: A Population-based Study

Introduction

The incidence of colorectal cancer in young patients has been increasing. We evaluated whether the disease characteristics, management, and outcomes of patients with colon cancer differ among patients aged ≤ 40 years compared with those of older patients.

Non-coding RNAs in photoaging-related mechanisms: a new paradigm in skin health

Biogerontology - The aging of skin is a biological process affected by environmental or genetic factors. Exposure to ultraviolet (UV) radiation is the main environmental factor causing skin aging....     

Increased peripheral blood mitochondrial DNA in type 2 diabetic patients with nephropathy

We report that mitochondrial DNA (MtDNA) copy numbers are increased in peripheral blood of patients with diabetic nephropathy (DN). Using qPCR for quantitation, we found a 2–4-fold significant increase (p < 0.05) in the mean MtDNA values in DN patients vs. healthy controls and diabetics without nephropathy. Increased MtDNA in DN could contribute to increased oxidative stress.     

Cytoplasmic β‐catenin accumulation is a good prognostic marker in upper and lower gastrointestinal adenocarcinomas

Norwood M G A, Bailey N, Nanji M, Gillies R S, Nicholson A, Ubhi S, Darnton J J, Steyn R S, Womack C, Hughes A, Hemingway D, Harrison R, Waters R & Jankowski J A
(2010) Histopathology 57, 101–111
Cytoplasmic β‐catenin accumulation is a good prognostic marker in upper and lower gastrointestinal adenocarcinomas Aims: β‐Catenin is an important molecule in cancer biology. Membranous β‐catenin enhances cellular differentiation and inhibits invasion by its action on E‐cadherin. The aim was to ascertain whether the cellular expression of these molecules in colorectal and oesophageal cancer specimens is associated with survival in patients with gastrointestinal cancer. Methods and results: Tumour samples from 149 patients undergoing resection for colorectal adenocarcinoma and 147 patients undergoing resection for oesophageal adenocarcinoma were retrospectively analysed using immunohistochemical techniques to assess β‐catenin expression. Increasing β‐catenin expression in the cytoplasm was associated with improved survival for colorectal cancer cases on both univariate (P = 0.003) and multivariate (P = 0.01) analysis. In addition, increased expression in the most recent cohort of oesophageal adenocarcinoma patients was associated with improved TNM staging (P = 0.007). Membrane expression was weakly associated with survival in colorectal cancer on univariate analysis (P = 0.09), but not on multivariate analysis (P = 0.21). Complete absence of β‐catenin expression at all three sites was associated with reduced 5‐year survival in colorectal cancer. Conclusions: This is one of the largest prognostic studies of β‐catenin in gastrointestinal adenocarcinoma. It shows that low levels of cytoplasmic β‐catenin expression are associated with reduced survival in patients with colorectal cancer as well as worse TNM staging in oesophageal adenocarcinoma (a recognized surrogate end‐point for survival). We believe this is the first time that this has been reported. This finding should be tested prospectively in oncological trials to validate whether the presence of cytoplasmic β‐catenin could be used as a prognostic marker for less aggressive disease.     

Effect of Dietary Fat on Ito Cell Activation by Chronic Ethanol Intake: A Long-Term Serial Morphometric Study on Alcohol-Fed and Control Rats

We studied the effects of long-term ethanol ingestion and dietary fat on Ito cell activation morphometrically in rats. Sixteen pairs of Wistar male rats were divided into two groups, one fed tallow and the other fed corn oil as the source of dietary fat. Each group of rats were pair-fed a nutritional adequate liquid diet containing either corn oil (CF) or tallow (TF) as fat as well as protein and carbohydrate. Half of each group received ethanol, the rest were pair-fed isocaloric amounts of dextrose via an implanted gastric tube for up to 5 months. Morphometric analysis of the change in fat and rough endoplasmic reticulum (RER) of Ito cells was performed on electron micrographs obtained from monthly biopsies including baseline. Ito cell activation was assessed by a decrease in the ratio of fat/RER in Ito cells. The ratio of fat/RER in Ito cells of alcoholic rats fed the CF diet (CFA) gradually decreased. The ratio was found to be lower than in the pair-fed control rats (CFC) at 5 months of feeding. CFA: 1.74 +/- 0.57, vs. 7.46 +/- 2.05, respectively, p less than 0.05, mean +/- SE). Ito cell fat also significantly decreased at 5 months of feeding (p less than 0.05). The fat/RER ratio in CFA significantly decreased only subsequent to the development of fatty change, necrosis, and inflammation followed by fibrosis of the liver. In contrast, the TFA rats did not show a significant decrease in the fat/RER ratio in the Ito cells throughout the study, while TFC rats showed an increase in the fat/RER ratio.(ABSTRACT TRUNCATED AT 250 WORDS)     

Apoptosis and Bcl-2 Protein Expression in Experimental Alcoholic Liver Disease in the Rat

We used the intragastric feeding rat model to investigate the relationship between severity of alcoholic liver injury, apoptosis, bcl-2 protein expression, and lipid peroxidation. Rats were fed ethanol with different dietary fats (saturated fat, corn oil, and fish oil) for a 1-month period. Apoptosis was evaluated using an immunohistochemical method, and flow cytometry. Bcl-2 protein concentrations in liver were evaluated by Western blot analysis and lipid peroxidation by measurement of conjugated diems. Pathological changes (fatty liver, necrosis, and inflammation) were present in com oil-ethanol and fish oil-ethanol groups only. The highest number of apoptotic cells were seen in the group of rats exhibiting her Injury. The fish oil-ethanol-fed group had the highest concentrations of bcl-2 protein; this protein was localized in the bile duct epithelial and inflammatory cells. A significant correlation was seem between bcl-2 protein assessed densitometrically and the number of inflammatory cells/mm² ( r = 0.78, p < 0.02) and conjugated diene levels ( r = 0.82, p < 0.01). Increased numbers of apoptotic cells were seen in rats developing ethanol-induced pathological liver injury. Increased bcl-2 protein concentrations are associated with the presence of inflammatory cells and lipid peroxidation.     

Community and Family Perspectives on Addressing Overweight in Urban, African-American Youth

Objective To assess weight-related beliefs and concerns of overweight urban, African-American children, their parents, and community leaders before developing a family-based intervention to reduce childhood overweight and diabetes risk. Design We conducted 13 focus groups with overweight children and their parents and eight semistructured interviews with community leaders. Participants and Setting Focus group participants (N = 67) from Chicago’s South Side were recruited through flyers in community sites. Interview participants (N = 9) were recruited to sample perspectives from health, fitness, education, civics, and faith leaders. Results Community leaders felt awareness was higher for acute health conditions than for obesity. Parents were concerned about their children’s health, but felt stressed by competing priorities and constrained by lack of knowledge, parenting skills, time, and financial resources. Parents defined overweight in functional terms, whereas children relied upon physical appearances. Children perceived negative social consequences of overweight. Parents and children expressed interest in family-based interventions to improve nutrition and physical activity and offered suggestions for making programs interesting. Conclusions This study provides insights into the perspectives of urban, African-American overweight children, their parents, and community leaders regarding nutrition and physical activity. The specific beliefs of these respondents can become potential leverage points in interventions. Electronic supplementary material The online version of this article (doi: ) contains supplementary material, which is available to authorized users.