Bcl-2 High Expression Research Articles

Cyclooxygenase-2 and Bcl-2 expression in patients with triple-negative breast cancer

Introduction. Triple-negative breast cancer (TNBC) is a rare type of breast cancer associated with lack of expression of estrogen and progesterone receptors and the HER2 protein. It is characterized by a poor outcome and chemotherapy resistance. Cyclooxygenase-2 (COX-2) is a constitutional enzyme responsible for prostaglandin synthesis, present in neoplastic cells and premalignant lesions. The B-cell lymphoma 2 (Bcl-2) protein is considered one of the most potent apoptosis-regulating agents, assuring body homeostasis. Material and methods. The aim of the present study was to evaluate the immunohistochemical (IHC) profile of COX-2 and Bcl-2 expression in patients suffering from TNBC in order to obtain more detailed data on additional factors nega­tively influencing TNBC outcome. The IHC evaluation of COX-2 and Bcl-2 expression among 21 women with diagnosis of TNBC was performed. Results. The most common histological subtype was invasive ductal cancer of no special type. COX-2 was present in all examined samples with moderate to strong expression detected in 20 of 21 cases. There was a positive corre­lation between histological grade (G) and COX-2 expression (p = 0.002). Bcl-2 was present in all examined samples. The analysis showed that tumours presenting highly positive expression of Bcl-2 accounted for the majority of examined cases (57.2%). Conclusions. The achieved results might lead to a conclusion that COX-2 and Bcl-2 high expression in TNBC may be linked to tumour aggressiveness and poor overall survival. However, before their consideration as additional markers to be used in routine histological examinations and breast cancer grading, it will be necessary to undertake further studies.

Efficacy and Safety of Lenalidomide, Rituximab Combined with Second-Line Chemotherapy (R2-chemo) in Patients with Relapsed/Refractory Diffuse Large-B Cell Lymphoma

Objective: Outcome of patients with relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL) remains poor, highlighting the need for novel treatment regimens. Lenalidomide is an immunomodulatory drug that could reverse rituximab refractoriness in lymphoma patients. This study aimed to explore the efficacy and safety of lenalidomide, rituximab combined with second-line chemotherapy (R2-chemo) in patients with r/r DLBCL. Methods: In this study, r/r DLBCL patients received R2-chemo as second-line salvage therapy. The treatment plan was as follows: lenalidomide 10mg/day, day 1-14; rituximab 375mg/m2, day 1; chemo-regimen in combination with R2 as per Investigator's discretion. The overall response rate (ORR), complete remission rate (CR rate), duration of remission (DOR), disease-free survival (PFS) and overall survival (OS) were evaluated. Results: As of Aug 1, 2020, 15 patients with r/r DLBCL were enrolled in this study with median age 65 years (range, 49 to 74 years), and 60% female. 20% (3/15) was transformed DLBCL, 33.3% (5/15) was relapse and 46.7% (7/15) had refractory disease. All received at least 1 prior line of immune-chemotherapy including rituximab, and 1 case was recurrence after autologous hematopoietic stem cell transplantation. 6.7% (1/15) had double-hit lymphoma, 66.7% (10/15) had MYC or BCL-2 high expression by IHC, of whom 26.7% (4/15) had co-expression of the MYC and BCL2. Cell of origin features using the Hans algorithm: 26.7% (4/15) were GCB, and 73.3% (11/15) were non-GCB. The chemo-regimens in combination with R2 were as follows: 5 cases of GEMOX or GCD, 7 cases of DICE or ICE, 2 cases of DHAP, 1 case of CHOPE regimen. As of the cutoff date, 13 cases were evaluable for efficacy. The ORR (CR+PR) was 61.5%, with 53.8% achieving a CR, and the median DOR was 9.7m (range, 2.9 to 23.7m). With a median time to follow-up of 15.3m (95%CI, 12.2 to 18.4m), median PFS and OS had not yet reached. The estimated 2-year PFS and OS rates were 53.8% and 75.2%, respectively. The most common treatment-related adverse event was hematological toxicity, and no treatment-related deaths occurred. Conclusion: The R2 combined with second-line salvage chemotherapy regimen has a significant efficacy in the treatment of patients with r/r DLBCL, and can be well- tolerated with no significant additive toxicities. The efficacy and safety of this regimen and the choice of chemo-regimen as an optimal combination partner for R2 need to be further verified by prospective clinical studies with a larger sample size. Figure Disclosures No relevant conflicts of interest to declare.

Clinical Impact of Ibrutinib with R-CHOP in Untreated Non-GCB DLBCL Co-Expressing BCL2 and MYC Genes in the Phase 3 Phoenix Trial

Clinical Impact of Ibrutinib with R-CHOP in Untreated Non-GCB DLBCL Co-Expressing BCL2 and MYC Genes in the Phase 3 Phoenix Trial

High expression of anti-apoptotic protein Bcl-2 is a good prognostic factor in colorectal cancer: Result of a meta-analysis.

AIMTo systematically evaluate the prognostic-predictive capability of Bcl-2 in colorectal cancer (CRC).METHODSA systematic literature search was conducted using PubMed, Web of Science and EMBASE databases. Any eligible study must meet the following criteria: (1) bcl-2 expression was evaluated in human CRC tissues by immunohistochemistry; (2) assessment of the relationships between bcl-2 expression and overall survival (OS), disease free survival (DFS), recurrent free survival (RFS) or clinic-pathological characteristics of CRC was included; (3) sufficient information was provided to estimate the hazard ratio (HR) or odds ratio and their 95% confidence intervals (CIs); and (4) the study was published in English. The impact of Bcl-2 expression on survival of CRC patients were evaluated through this meta-analysis.RESULTSA total of 40 eligible articles involving 7658 patients were enrolled in our final analysis. We drew the conclusion that Bcl-2 high expression was significantly correlated with favorable OS (pooled HR = 0.69, 95%CI: 0.55-0.87, P = 0.002) and better DFS/RFS (pooled HR = 0.65, 95%CI: 0.50-0.85, P = 0.001). Additionally, the subgroup analysis suggested that Bcl-2 overexpression was significantly associated with prognosis (OS) especially in patients came from Europe and America but not Asian and patients who did not receive any adjuvant therapy before surgery. Finally, our present results indicated that expression of bcl-2 protein was associated with high differentiation grade and A/B Ducks’ stage.CONCLUSIONBcl-2 high expression was significantly correlated with favorable OS and better DFS/RFS. Hence, we propose that Bcl-2 may be a valuable prognostic-predictive marker in CRC.

Retrospective study of clinicopathological characteristics in bronchopulmonary carcinoid

背景与目的支气管肺类癌（bronchopulmonary carcinoid, BPC）占全部肺原发性恶性肿瘤不到2%，相关研究报道较少，本研究拟分析BPC的总体及其两个亚型——典型类癌（typical carcinoid, TC）和不典型类癌（atypical carcinoid, AC）的临床、病理学特点。方法回顾性分析中山大学肿瘤防治中心1994年1月-2009年6月收治的28例BPC的临床资料，调取可再行切片的病理蜡块，重新切片染色及病理玻片会诊，分析BPC的总体及其亚型的临床特征和相关免疫组化指标与预后的关系。结果全部28例患者的总体5年生存率为56%，TC的5年生存率为70%，AC为41%，单因素分析示TNM分期（P=0.037)、有无淋巴结转移（P=0.001）、Ki-67核阳性数是否大于5%（P=0.009）是BPC总体的预后因素。相关性分析示BPC亚型与CD99、Bcl-2及Ki-67的表达具有相关性（P值分别0.017、0.043、0.033）。20例行肺癌根治性手术患者的5年生存率为73%，TC的5年生存率为83%，AC为57%。单因素分析示BPC亚型（P=0.013）、术后有无淋巴结转移（P=0.004)、Ki-67核阳性数是否大于5%（P=0.006）、TNM分期（P=0.047）是行肺癌根治性手术患者的预后因素。肿瘤复发（n=4）与Ki-67核阳性的表达和Bcl-2表达具有相关性（P值分别为0.027、0.045）。结论BPC是预后较好的肺原发性恶性肿瘤，Ki-67、Bcl-2的高表达是提示BPC复发及预后不良的影响因素，TNM分期是影响预后的独立因素，行根治性手术是主要的治疗手段。

Expression of apoptosis markers on peripheral blood lymphocytes from patients with cutaneous T-cell lymphoma during extracorporeal photochemotherapy

The mechanisms of extracorporeal photochemotherapy (ExP) therapeutic activity in cutaneous T-cell lymphomas (CTCLs) are not yet well understood, even though it has been suggested that a major mechanism may be induction of apoptosis. In vitro studies demonstrate that UVA-induced apoptosis is mediated by CD95-Fas expression and inhibited by Bcl-2 up-regulation and that UVA irradiation is able to down-regulate Bcl-2 expression. High-resolution multiparameter flow-cytometric analyses were used to evaluate Bcl-2/CD95-Fas expression on phenotypically identifiable circulating clonal T cells from 7 patients with CTCL (4 with Sézary syndrome and 3 with mycosis fungoides with peripheral involvement) before and during ExP, in an attempt to ascertain whether Bcl-2/CD95-Fas status can be related to the hematologic response. A Bcl-2 normal phenotype before ExP or a normalization in Bcl-2 expression during ExP were related to a better clinical response, whereas a persistent Bcl-2 high expression was a negative prognostic factor. On the other hand, no response was found in patients with a CD95-Fas-negative phenotype, whereas the expression of CD95-Fas was associated with hematologic remission. Although further studies are needed to confirm these preliminary results, this study suggests that Bcl-2 and CD95-Fas expression could be evaluated, together with the other known clinical and immunologic factors, as additional parameters related to clinical response in patients with CTCL undergoing ExP. (J Am Acad Dermatol 2001;44:40-7.)

Intereukin-8 Induces the Accumulation of B-Cell Chronic Lymphocytic Leukemia Cells by Prolonging Survival in an Autocrine Fashion

Several cytokines have been suggested to play a regulatory action on the neoplastic clone of patients with B-cell chronic lymphocytic leukemia (B-CLL) by interfering in the differentiation, proliferation, or death/survival pathways. Interleukin-8 (IL-8) is a chemoattractant protein constitutively expressed at the mRNA level and released by B-CLL cells. In view of the presence of the IL-8 receptor mRNA and of specific IL-8 binding, confirmed also by Scatchard analysis using 125I-IL-8, the study was extended to evaluate the possible regulatory role of this cytokine on B-CLL cells. IL-8 failed to show any in vitro proliferative effect on leukemic B-CLL cells. By contrast, the propidium iodide (PI) staining of the DNA content showed that IL-8 could prolong the survival of resting B-CLL cells in 11 of 16 cases studied. In the remaining 5 cases, 90.6% +/- 4.39% SD of the cells after culture remained viable and IL-8 could exert a significant death protection action after pretreatment with 10(-4) mol/L hydrocortisone, which reduced the percentage of viable B-CLL cells. The dose range of IL-8 capable of inducing the prolonging survival effect is comparable with the levels of IL-8 released constitutively by B-CLL cells, indicating that the death protection action is exerted at physiologic doses. The in vitro rescue from death induced by IL-8 is reflected by an increased expression of bcl-2 mRNA in B-CLL cases incubated in the presence of IL-8. These findings were further confirmed at the protein level, because in B-CLL cells that displayed a bimodal bcl-2 intracytoplasmatic protein expression IL-8 was capable of upmodulating the bcl-2high expression peak. The potential autocrine regulatory action exerted by IL-8 is supported by the evidence that exogenous IL-8 can upregulate IL-8 mRNA in B-CLL cells. These results, together with the demonstration that antibody-mediated neutralization of endogenous IL-8 could induce a significant in vitro reduction in the number of living cells, further support the hypothesis that, in B-CLL, the physiologic doses of IL-8 released constitutively by the leukemic clone may play an autocrine role in the process of cell accumulation characteristic of this disease.