Otto Warburg observed that cancerous cells prefer fermentative instead of oxidative metabolism of glucose, although the former is in theory less efficient Since Warburg's pioneering works, special attention has been given to this difference in cell metabolism The Warburg effect has been implicated in cell transformation, immortalization, and proliferation during tumorigenesis Cancer cells display enhanced glycolytic activity, which is correlated with high proliferation, and thus, glycolysis appears to be an excellent candidate to target cancer cells Nevertheless, little attention has been given to noncancerous cells that exhibit a "Warburg-like" metabolism with slight, but perhaps crucial, alterations that may provide new directions to develop new and effective anticancer therapies Within the testis, the somatic Sertoli cell (SC) presents several common metabolic features analogous to cancer cells, and a clear "Warburg-like" metabolism Nevertheless, SCs actively proliferate only during a specific time period, ceasing to divide in most species after puberty, when they become terminally differentiated The special metabolic features of SC, as well as progression from the immature but proliferative state, to the mature nonproliferative state, where a high glycolytic activity is maintained, make these cells unique and a good model to discuss new perspectives on the Warburg effect Herein we provide new insight on how the somatic SC may be a source of new and exciting information concerning the Warburg effect and cell proliferation

/pdf/the-warburg-effect-revisited-lesson-from-the-sertoli-cell-2lfg6zpo2t.pdf

The Warburg Effect Revisited—Lesson from the Sertoli Cell

Purpose Many anticancer drugs induce apoptosis in malignant cells, and resistance to apoptosis could lead to suboptimal or no therapeutic benefit. Two cytoplasmic proteins, B-cell lymphoma protein 2 (Bcl-2)-associated X (Bax) and Bcl-2, act as a promoter and an inhibitor of apoptosis, respectively. Both Bax and Bcl-2 as well as their ratio have been regarded as prognostic markers in various cancers. However, conflicting results have been reported. A clear understanding of apoptosis has also become crucial due to reports about anti-Bcl-2 chemotherapy. We explored the relationship of Bax and Bcl-2 gene expression and their ratio with the therapeutic response in acute myeloid leukemia (AML) patients. Patients and methods Bone marrow and/or blood samples from 90 AML patients treated with cytarabine and daunorubicin were included. Expression of Bax and Bcl-2 was determined through real-time polymerase chain reaction by using ΔΔCt method of relative expression. Results Bax and Bcl-2 expression among marrow and blood samples correlated with each other (rs=0.5, p<0.01). Although bone marrow expression of Bax and Bcl-2 tended to remain higher among responders (median 1.01 and 0.29, respectively) as compared to non-responders (median 0.66 and 0.24, respectively), the difference failed to reach statistical significance (U=784.5 and 733; p=0.68 and 0.28, respectively). Conversely, Bax/Bcl-2 ratio was higher among poor responders (median 3.07 vs 1.78), though again failed to reach statistical significance (U=698.5, p=0.07). Conclusion Expression of Bax and Bcl-2 does not differ significantly among AML patients treated with cytarabine and daunorubicin in terms of remission, relapse, resistance, overall survival, and disease-free survival, thus questioning the utility of emerging anti-Bcl-2 therapy.

/pdf/bax-bcl-2-and-bax-bcl-2-as-prognostic-markers-in-acute-1gv7urszk8.pdf

Bax, Bcl-2, and Bax/Bcl-2 as prognostic markers in acute myeloid leukemia: are we ready for Bcl-2-directed therapy?

Pancreatic cancer (PC) is a great health burden to patients owing to its poor overall survival rate. Long noncoding RNAs (lncRNAs) interact with microRNAs (miRs) to participate in tumorigenesis. Therefore, we aim to uncover the role and related mechanism of LINC00473 in PC through the modulation of miR-195-5p and programmed death-ligand 1 (PD-L1). Increased LINC00473 and PD-L1 but declined miR-195-5p were determined in PC tissues and cell lines, and it was found that LINC00473 mainly situated in the cytoplasm. Also, miR-195-5p was verified to bind with both LINC00473 and PD-L1. Next, with the aim to examine the ability of LINC00473, miR-195-5p, and PD-L1 on the PC progression, the expression of LINC00473, miR-195-5p and PD-L1 were altered with mimics, inhibitors, overexpression vectors or siRNAs in PC cells and cocultured CD8+ T cells. It was demonstrated that LINC00473 sponged miR-195-5p to upregulate PD-L1 expression. More important, the obtained results revealed that LINC00473 silencing or miR-195-5p upregulation elevated the expression of Bcl-2 associated X protein (Bax), interferon (IFN)-γ, and interleukin (IL)-4 but reduced the expression of B-cell lymphoma-2 (Bcl-2), matrix metalloproteinase (MMP)-2, MMP-9, and IL-10, thus inducing the enhancement of the apoptosis as along with the inhibition of proliferation, invasion, and migration of the PC cells. LINC00473 silencing or miR-195-5p elevation activated the CD8+ T cells. Taken together, LINC00473 silencing blocked the PC progression through enhancing miR-195-5p-targeted downregulation of PD-L1. This finding offers new therapeutic options for treating this devastating disease.

Long noncoding RNA LINC00473 drives the progression of pancreatic cancer via upregulating programmed death-ligand 1 by sponging microRNA-195-5p.

Effects of probiotics Lactobacillus plantarum 16 and Paenibacillus polymyxa 10 on intestinal barrier function, antioxidative capacity, apoptosis, immune response, and biochemical parameters in broilers.

Anticancer activities of fatty acids and their heterocyclic derivatives.

Background: Bax and Bcl-2 are the major members of Bcl-2 family whose play a key role in tumor progression or inhibition of intrinsic apoptotic pathway triggered by mitochondrial dysfunction. Therefore, the balance between pro- and anti-apoptotic members of this family can determine the cellular fate. Methods: In this study, the relative level of mRNA expression of Bax and Bcl-2 genes was determined using RNA extraction, cDNA synthesis and RT-qPCR technique from 22 tumoral tissues and adjacent non-tumoral tissues from adenocarcinoma colorectal cancer. Results: The potential prognostic and predictive significance of Bax and Bcl-2 gene expression and Bax/Bcl-2 ratio were demonstrated in colorectal cancer. The significant correlation between qPCR data and different clinicopathologic parameters of colorectal carcinoma, including age, gender, tumor size, tumor stage, tumor location, and tumor differentiation was also examined. Interestingly, no significant correlation was seen between Bax and Bcl-2 expressions and clinicopathological parameters of colorectal cancer. However, Bax/Bcl-2 ratio was statistically correlated with age and tumor location. Patients with age above 50 showed decreased levels of Bax/Bcl-2 ratio. Moreover, the Bax/Bcl-2 ratio was significantly lower in tumors resected from colon compared to sigmoid colon, rectosigmoid and rectum tumors. Conclusion: This study indicates a significant correlation between age and tumor location with Bax/Bcl-2 expression ratio, suggesting predictive value as a potential molecular marker of colorectal cancer. Iran. Biomed. J. 19 (2): 69-75, 2015

/pdf/is-bax-bcl-2-ratio-considered-as-a-prognostic-marker-with-2amukk7lrs.pdf

Is Bax/Bcl-2 Ratio Considered as a Prognostic Marker with Age and Tumor Location in Colorectal Cancer?

Background
Breast cancer is one of the most common cancers among women throughout the world. Therefore, established cell lines are widely used as in vitro experimental models in cancer research.

/pdf/establishment-and-characterization-of-two-human-breast-15eiitoz5i.pdf

Establishment and characterization of two human breast carcinoma cell lines by spontaneous immortalization: Discordance between Estrogen, Progesterone and HER2/neu receptors of breast carcinoma tissues with derived cell lines

Gastric cancer is the fourth most common cancer and the second leading cause of cancer death worldwide. Although the global incidence of gastric cancer has been decreased dramatically in recent decades, north and northwest of Iran have the highest incidence rate of gastric cancer. Whilst the surgical procedures for gastric cancer have been improved, there is no cure for that. The intestinal type of GC results from pre-neoplastic conditions including atrophic gastritis, intestinal metaplasia and dysplasia. Trefoil Factors Family proteins (TFFs) are small and stable molecules secreted by the mammalian gastrointestinal tract. TFFs constitute a family of three peptides (TFF1, TFF2and TFF3) that are widely expressed in a tissue specific manner in the gastrointestinal tract. Variable TFFs expression in gastric cancer and pre-neoplastic lesions has been found. TFF1 has a tumor suppressor activity and inhibits tumorogenesis in gastric cancer. Its expression decreases in gastritis, gastric atrophy, dysplasia, intestinal metaplasia and gastric cancer.TFF2 has a protective effect on gastrointestinal epithelium. As a prognostic factor, TFF2 expression decreases in gastric ulcer, chronic atrophic gastritis and gastric cancer. TFF3 is considered as an oncogenic factor in gastric tissues. Whilst the normal gastric tissues don’t express TFF3, it increases in intestinal metaplasia. Therefore, more studies are necessary to clarify the role of TFFs in GC and pre-neoplastic conditions. This review has focused on elucidating the important role of TFFs in gastric cancer and pre-neoplastic lesions.

Trefoil Factor Family in Pre-neoplastic Lesions and Gastric Cancer

Hairy cell leukemia being defined as a mature B-cell lymphoma shows unique clinicopathological, immunophenotype, and genetic alteration features among another mature B-cell malignancy. Although lymphocytes with hairy appearance and co-expression of CD25, CD11c and CD103 markers on B-cells are compatible with hairy cell leukemia, there are some difficulties in differential diagnosis between HCL with its variant and splenic marginal zone lymphoma. The presence of kinase-activating BRAF V600E mutation in classical HCL clone and in no other mature B-cell lymphomas/ leukemia has implication in differential diagnosis. In this study, we evaluated BRAF V600E mutation detection of H&E stained peripheral blood smears by Sanger sequencing method in patients with classical HCL and findings related to morphology and immunophenotype. Peripheral smear review indicated a subpopulation of atypical lymphocytes with villous cytoplasmic projections. By flow cytometry analysis, B-cells represented immunophenotype of CD19+ CD20(bright)+ CD11c+ CD25+ CD103+. Sanger sequencing demonstrated that presence of BRAF V600E mutation in 86.6% (13/15) of analyzed HCL DNA. Hence, gain-of-function mutation of BRAF V600E is detectable in DNA of peripheral blood smear of patients with classical HCL that were evaluated by immunophenotyping. In conclusion, DNA from peripheral blood smear can be used to identify BRAF V600E mutation using Sanger sequencing method in samples with at least 10% HCL clone as supplementary approach to aid in the diagnosis of classical HCL.

Narges Jafarzadeh

Papers

Is Bax/Bcl-2 Ratio Considered as a Prognostic Marker with Age and Tumor Location in Colorectal Cancer?

Establishment and characterization of two human breast carcinoma cell lines by spontaneous immortalization: Discordance between Estrogen, Progesterone and HER2/neu receptors of breast carcinoma tissues with derived cell lines

Trefoil Factor Family in Pre-neoplastic Lesions and Gastric Cancer

Correlation of BRAF V600E Mutation in Peripheral Blood Smears of Hairy Cell Leukemia with Morphology and Immunophenotyping