Search

Background: Oral mucositis (OM) is an acute debilitating side effects of chemoradiotherapy (CRT) in head and neck cancer (HNC) patients. Salivary biomarkers are noninvasive and aid in early diagnosis and disease prevention. Objective: This study analyzed Bcl-2, Mcl-1, and Bax as potential biomarkers in CRT-induced OM in HNC patients. Methods: Forty-six HNC patients receiving CRT with OM were evaluated using WHO grading. Two time points were observed for saliva sample collection: Day 0 (prior to CRT) and Day 30 (CRT with OM) and from 46 healthy volunteers. Using an enzyme-linked immunosorbent assay (ELISA), levels of Bcl-2, Mcl-1, and Bax were measured. Oral mucositis progression was analyzed using Friedman’s test, and statistical significance between means of different salivary marker was determined using the ANOVA test. Results: From Day 0 to Day 30, grades of OM were statistically significant (P < 0.05). Apoptotic biomarkers showed statistically significant higher expression of proapoptotic regulator Bax and lower expressions of antiapoptotic markers Bcl-2 and Mcl-1 on Day 30 (severe OM) compared to Day 0 and healthy controls (P < 0.0001). Conclusion: Our research showcased Bax, Bcl-2, and Mcl-1 as early predictive indicators of OM, and targeted drugs should be developed against these to prevent onset and severity of oral mucositis that improves patients quality of life.

BCL‐2, a member of the BCL‐2 protein family, is an antiapoptotic factor that regulates the intrinsic pathway of apoptosis. Due to its aberrant activity, it is frequently implicated in haematopoietic cancers and represents an attractive target for the development of therapeutics that antagonize its activity. A selective BCL‐2 inhibitor, venetoclax, was approved for treating chronic lymphocytic leukaemia, acute myeloid leukemia, and other haematologic malignancies, validating BCL‐2 as an anticancer target. Since then, alternative therapeutic approaches to modulate the activity of BCL‐2 have been explored, such as antibody‐drug conjugates and proteolysis‐targeting chimeras. Despite numerous research groups focusing on developing degraders of BCL‐2 family member proteins, selective BCL‐2 PROTACs remain elusive, as disclosed compounds only show dual BCL‐xL/BCL‐2 degradation. Herein, we report our efforts to develop BCL‐2 degraders by incorporating two BCL‐2 binding moieties into chimeric compounds that aim to hijack one of three E3 ligases: CRBN, VHL, and IAPs. Even though our project did not result in obtaining a potent and selective BCL‐2 PROTAC, our research will aid in understanding the narrow chemical space of BCL‐2 degraders. [ABSTRACT FROM AUTHOR]

This study's primary goal is to perform density functional theory and molecular docking simulation to determine decanal's structural stability and biological activity against proteins allied to breast cancer in order to validate its anti‐cancer potential. Initially, the drug‐likeness features of decanal was predicted and the outcomes confirmed that it is non‐toxic and follows Lipinski's rule. Through basis set 6‐311++G (d, p), the structural optimization was performed and molecular geometry was investigated. The FT‐IR and UV–Visible spectroscopic analysis was theoretically performed and validated via experimental analysis. The reactive surface of decanal was further investigated using a calculated molecular electrostatic potential surface. The molecular structural stability and bio‐reactivity of decanal was determined by using the HOMO‐LUMO energies and energy gap calculated is 6.215 eV. The charge distribution among the atoms of decanal was ascertained through the analysis of Mulliken and natural population distribution. To look at the decanal molecule's topological properties, electron localization function and localized orbital locator were used. The decanal's weak interactions were investigated via reduced density gradient assessment. The docking evaluation was performed against the proteins involved in breast cancer and the highest binding ability was calculated against the protein Bcl‐2 with the score of −6.5 kcal/mol. These theoretical findings will pave a way to understand the decanal's structural stability, reactivity and breast cancer inhibitory property and can be used as a drug candidate against tumor after in vitro and clinical evaluation. [ABSTRACT FROM AUTHOR]

Anal cancer is uncommon, comprising 2.2% of gastrointestinal cancers. Squamous cell carcinoma (SCC) is the most common; while perianal basal cell carcinoma (BCC) is rare, representing only 0.2% of anorectal malignancies. BCC, associated with sun exposure and immunosuppression, often resembles benign conditions and manifests as perianal ulcers or masses. Histologically, BCC exhibits basaloid tumor cells with distinct patterns. Despite its rarity, accurate diagnosis is crucial. We expose a case study of a 59-year-old male, previously healthy, that presented with hematochezia and perianal pain, leading to a diagnosis of lower gastrointestinal bleeding. Colonoscopy was needed, and a biopsy revealed an ulcerated, indurated lesion involving the left lateral hemorrhoidal bundle, diagnosed as pigmented basaloid carcinoma. Microscopic examination showed malignant nests of cells with peripheral nuclear palisading, melanocytes, and melanin pigment. Immunohistochemistry confirmed positivity for p63, CK5/6, and BCL2. Respect the treatment, due to the involvement of the anal sphincteric muscle, radiotherapy was chosen. [ABSTRACT FROM AUTHOR]

The high expression of anti‐apoptotic Bcl‐2 protein in cancer cells can confer resistance to apoptosis, allowing cells to evade cell death signals and continue proliferating. Therefore, Bcl‐2 has become a crucial target for cancer therapy. In this work, we looked for new drugs targeting Bcl‐2 that can induce apoptosis in cancer cells and improve treatment effectiveness like chemotherapy. In silico approaches, such as molecular docking, were used to identify potential new drugs by screening the Enamine collection (HLL‐460) against two conformations of the Bcl‐2 protein obtained by molecular dynamics (MD) simulations. Molecular docking was focused on two specific sites of Bcl‐2; the binding groove and the flexible loop domain (FLD), which play an essential role in regulating the apoptotic process. Compounds with docking scores less than those of the reference drugs (Venetoclax and Taxol) were selected. They were analyzed by PASS online, which predicted putative anti‐cancer properties for ten compounds; of these, three candidates targeted binding groove, five to FLD, and two can bind to both sites; these compounds were selected and analyzed. The drug‐like properties of the ten compounds passed Lipinski's rules, their pharmacokinetic profiles were excellent, safe, and had potential anti‐neoplastic activity. [ABSTRACT FROM AUTHOR]

Background: Factors such as exercises training and taking antioxidant supplements can moderate or increase apoptosis. Therefore, this present study aimed to the effect of endurance training and vitamin C consumption in the conditions of air pollution on the expression of apoptotic proteins BAX and Bcl-2 in the brain of male Wistar rats. Materials and Methods: In this experimental study, 30 Wistar rats were randomly divided into five groups: 1) polluted air control, 2) supplement, 3) training, 4) training+supplement, and 5) healthy air control .Rats trained in polluted air were maintained in a special chamber to simulate polluted air and performed endurance training protocol .Vitamin C supplement groups received the supplement at a dose of 20 mg/kg. Data analysis was done through One-Way-ANOVA and Tukey's post-hoc tests in SPSS version 26 software. Results: There is a significant difference in BAX and BCL-2 protein gene expression between the groups (P≤0.0001). This significant difference was the increase in BAX protein expression in the training+supplement group as well as the healthy air control group compared to other groups (P≤0.05). In the training and supplement groups were seen a decrease in BCL-2 protein expression compared to the control group (polluted and healthy) (P≤0.05). Conclusion: Considering the increase in BAX and decrease in BCL-2 expression, it is possible that training in polluted air can lead to cell damage related to apoptosis. Also, the use of vitamin C supplement alone or together with training cannot modulate the apoptosis of brain cells.

The Bcl-2 protein has a vital function in controlling the programmed cell doom of mitochondria. If programmed cell death signals are obstructed, an imbalance between cell survival and death will occur, which is a significant reason for cancer. Therefore, the Bcl-2 protein was identified as a possible therapeutic target for carcinoma treatment. Herein, the Natural Products Atlas (NPAtlas) compounds were virtually screened, seeking potent inhibitors towards the Bcl-2 protein. The performance of AutoDock Vina software to predict the docking score and pose of the investigated compounds was first validated according to the available experimental data. Based on the validated AutoDock Vina parameters, the NPAtlas database was filtered against the Bcl-2 protein. The natural compounds with docking scores less than that of the venetoclax (calc. −10.6 kcal/mol) were submitted to MD simulations, followed by MM-GBSA binding energy calculations. According to MM-GBSA//200 ns MD simulations, saquayamycin F (NPA002200) demonstrated promising binding affinity with a ΔGbinding value of −53.9 kcal/mol towards the Bcl-2 protein when compared to venetoclax (ΔGbinding = −50.6 kcal/mol). The energetical and structural analyses showed a great constancy of the saquayamycin F inside the Bcl-2 protein active site. Moreover, the ADMET and drug-likeness features of the saquayamycin F were anticipated, indicating its good oral bioavailability. According to in silico computations, saquayamycin F is proposed to be used as a therapeutic agent against the wild-type Bcl-2 protein and warrants further experimental assays. [ABSTRACT FROM AUTHOR]

Cancer cells are resistant to apoptosis and this is one of the most obvious symptoms of cancer in humans. One of the most exciting strategies for treating cancer is to design regulators that increase cell death and stop cell growth. Members of the BCL‐2 family of proteins play an important role in the regulation of apoptosis. In this study, an attempt was made to improve the performance of one of the anticancer drugs by designing new analogs of venetoclax (VNT). For this purpose, molecular docking studies were performed to determine the best binding state of VNT and its newly designed derivatives at the protein‐binding site to estimate the binding energy. The best analog in terms of free energy was VNT‐12 with the lowest energy (−12.15 kcal/mol). Finally, to investigate the inhibitory effect of the compounds on BCL‐2 protein, molecular dynamics simulation was used, and by performing the relevant analyses during the simulation, it was observed that the newly designed ligand had better performance in inhibiting BCL‐2 protein compared to VNT. Significance statement: This article introduces new derivatives of venetoclax (VNT) and compares their performance. Some of these derivatives have far better performance on the inhibition of BCL‐2 protein than the original drug. After calculating and comparing the free binding energy of these structures, VNT‐12, having a negative binding energy of −12.15 kcal/mol, an inhibitory constant of 1.24 nM, and 15 hydrophobic bonds, was identified as the most stable BCL‐2 protein inhibitor. [ABSTRACT FROM AUTHOR]

The BCL-2 inhibitor venetoclax is currently approved for treatment of hematologic diseases and is widely used either as monotherapy or in combination strategies. It has produced promising results in the treatment of refractory or relapsed (R/R) and aged malignant hematologic diseases. However, with clinical use, resistance to venetoclax has emerged. We review the mechanism of reduced dependence on BCL-2 mediated by the upregulation of antiapoptotic proteins other than BCL-2, such as MCL-1 and BCL-XL, which is the primary mechanism of venetoclax resistance, and find that this mechanism is achieved through different pathways in different hematologic diseases. Additionally, this paper also summarizes the current investigations of the mechanisms of venetoclax resistance in terms of altered cellular metabolism, changes in the mitochondrial structure, altered or modified BCL-2 binding domains, and some other aspects; this article also reviews relevant strategies to address these resistance mechanisms. [ABSTRACT FROM AUTHOR]

In this article, we discover and demonstrate the way of immunohistochemical identification of extravillous cytotrophoblast in the structures of the uteroplacental area and myometrium, which can be used to study the uteroplacental form of placental insufficiency, in the morphogenesis of which the key reason is a violation of the gestational changes of the spiral arteries of the uterus.

Flavonoids have been reported to have therapeutic potential for spinal cord injury. Hawthorn leaves have abundant content and species of total flavonoids, and studies of the effects of the total flavonoids of hawthorn leaves on spinal cord injury have not been published in or outside China. Therefore, Sprague-Dawley rats were used to establish a spinal cord injury model by Allen's method. Rats were intraperitoneally injected with 0.2 mL of different concentrations of total flavonoids of hawthorn leaves (5, 10, and 20 mg/kg) after spinal cord injury. Injections were administered once every 6 hours, three times a day, for 14 days. After treatment with various concentrations of total flavonoids of hawthorn leaves, the Basso, Beattie, and Bresnahan scores and histological staining indicated decreases in the lesion cavity and number of apoptotic cells of the injured spinal cord tissue; the morphological arrangement of the myelin sheath and nerve cells tended to be regular; and the Nissl bodies in neurons increased. The Basso, Beattie, and Bresnahan scores of treated spinal cord injury rats were increased. Western blot assays showed that the expression levels of pro-apoptotic Bax and cleaved caspase-3 were decreased, but the expression level of the anti-apoptotic Bcl-2 protein was increased. The improvement of the above physiological indicators showed a dose-dependent relationship with the concentration of total flavonoids of hawthorn leaves. The above findings confirm that total flavonoids of hawthorn leaves can reduce apoptosis and exert neuroprotective effects to promote the recovery of the motor function of rats with spinal cord injury. This study was approved by the Ethics Committee of the Guangxi Medical University of China (approval No. 201810042) in October 2018.

The Bcl-2 protein has a vital function in controlling the programmed cell doom of mitochondria. If programmed cell death signals are obstructed, an imbalance between cell survival and death will occur, which is a significant reason for cancer. Therefore, the Bcl-2 protein was identified as a possible therapeutic target for carcinoma treatment. Herein, the Natural Products Atlas (NPAtlas) compounds were virtually screened, seeking potent inhibitors towards the Bcl-2 protein. The performance of AutoDock Vina software to predict the docking score and pose of the investigated compounds was first validated according to the available experimental data. Based on the validated AutoDock Vina parameters, the NPAtlas database was filtered against the Bcl-2 protein. The natural compounds with docking scores less than that of the venetoclax (calc. −10.6 kcal/mol) were submitted to MD simulations, followed by MM-GBSA binding energy calculations. According to MM-GBSA//200 ns MD simulations, saquayamycin F (NPA002200) demonstrated promising binding affinity with a ΔGbinding value of −53.9 kcal/mol towards the Bcl-2 protein when compared to venetoclax (ΔGbinding = −50.6 kcal/mol). The energetical and structural analyses showed a great constancy of the saquayamycin F inside the Bcl-2 protein active site. Moreover, the ADMET and drug-likeness features of the saquayamycin F were anticipated, indicating its good oral bioavailability. According to in silico computations, saquayamycin F is proposed to be used as a therapeutic agent against the wild-type Bcl-2 protein and warrants further experimental assays.

Objective To observe the effects of methyltransferase-like 3 ( METTL3) gene on the expression levels of tumor proteins c-Myc, EGFR, and Bcl-2 in the prostate cancer cell lines PC-3 and DU145 and to investigate the mechanism. Methods We used RNA interference technology to synthesize METTL3 siRNA-1400 and negative siRNA. We divided PC-3 cells into the blank control group, negative control group, and experimental group, and also divided the DU145 cells into the blank control group, negative control group, and experimental group. The cells in the blank control group were not treated, the cells in the negative control group were transfected with negative control siRNA, and the cells in the experimental group were transfected with METL3 siRNA-1400, respectively. Western blotting was used to detect the expression of tumor proteins c-Myc, EGFR and Bcl-2 in each group. The m6A modification level of RNA in each group was detected by Dolt blotting. Results Western blotting showed that the protein levels of c-Myc, EGFR and Bcl-2 in the experimental groups were significantly lower than those in the blank control groups and negative control groups in the PC-3 and DU145 cells (all P < 0. 01). The m6A modification levels of RNA in the experimental groups were significantly lower than those in the blank control groups and negative control groups in the PC-3 and DU145 cells (all P < 0. 01). Conclusion Silencing METTL3 gene in prostate cancer PC-3 and DU145 cells inhibits the expression of c-Myc, EGFR and Bcl-2, and the underlying mechanism may be related to the involvement of METTL3 in m6A modification of RNA. [ABSTRACT FROM AUTHOR]

Seizures in puppies often present a diagnostic challenge in terms of identifying and treating the underlying cause. Dog breeds with mutations of the MDR1-gene are known to show adverse reactions to certain drugs, yet metabolic imbalance exacerbated by physiologically immature organs and other contributing pathologies require consideration before arriving at a diagnosis. This study analysed the brains of two male, 5-week-old Australian Shepherd siblings that died after displaying severe neurological symptoms upon administration of MilproVet® to treat severe intestinal helminth infection. Despite the initial symptoms being similar, their case histories varied in terms of the symptom duration, access to supportive therapy and post-mortem interval. Histopathology and immunohistochemistry were used to obtain more information about the phase of the pathological processes in the brain, employing protein markers associated with acute hypoxic damage (β-amyloid precursor protein/APP) and apoptosis (diacylglycerolkinase-ζ/DGK-ζ, apoptotic protease activating factor 1/Apaf1, and B-cell lymphoma related protein 2/Bcl-2). The results seem to reflect the course of the animals’ clinical deterioration, implicating that the hypoxic damage to the brains was incompatible with life, and suggesting the usefulness of the mentioned immunohistochemical markers in clarifying the cause of death in animals with acute neurological deficits. [ABSTRACT FROM AUTHOR]

Rats were divided into six groups: sham/control, Dl-3-n-butylphthalide, P1 (low phenytoin, 100 mg/kg), P2 (high phenytoin, 200 mg/kg), NP1 (Dl-3-n-butylphthalide 80 mg/kg, phenytoin 100 mg/kg), NP2 (Dl-3-n-butylphthalide 80 mg/kg, phenytoin 200 mg/kg). Hematoxylin/eosin and Nissl staining showed that, compared to the sham/control group, the Dl-3-n-butylphthalide group had no obvious hippocampal and cerebellar neuron loss, but there was a significant neuron loss in the P1 and P2 groups (P P P P P

Leukemia is a group of cancer caused by the abnormal proliferation and differentiation of hematopoietic stem cells. Efforts geared toward effective therapeutic strategies with minimal side effects are underway. Peptides derived from natural resources have recently gained special attention as alternative chemotherapeutic agents due to their minimal adverse effects. In the present study, the aim was to isolate peptides from garlic (Allium sativum) and investigate their anticancer activity against leukemic cell lines. The protein extract of A. sativum was pepsin‐digested to obtain protein hydrolysate followed by sequential purification methods. A novel anticancer peptide, VKLRSLLCS (VS‐9), was identified and characterized by mass spectrometric analysis. The peptide was demonstrated to significantly inhibit the cell proliferation of MOLT‐4 and K562 leukemic cell lines while exhibiting minimal inhibition against normal PBMC. Particularly, VS‐9 could induce apoptosis and upregulate mRNA levels of caspase 3, caspase 8, caspase 9, and Bax while downregulating Bcl‐2, Bcl‐xL, and Bcl‐w. Molecular docking of VS‐9 with the anti‐apoptotic Bcl‐2 protein family suggested that VS‐9 could bind the binding groove of the BH3 domain on target proteins. Protein–peptide interaction analysis by affinity chromatography and LC‐MS/MS further showed that VS‐9 could bind Bcl‐2 proteins. Results suggest VS‐9 as a potential garlic‐derived novel anticancer peptide possessing apoptosis‐inducing properties against leukemic cell lines via anti‐apoptotic Bcl‐2 protein family. [ABSTRACT FROM AUTHOR]

The aim of our present study was to assess the effects of Kanglaite injection on apoptosis and expression of apoptosis-related factors Bcl-2 and Bax protein and the activities of Caspase-3 and Caspase-8 in colon cancer SW480 cells were studied. Compared with the control group without medication, the proliferation inhibition rate of cells processed with Kanglaite injection (10, 20 and 40 µL/mL) significantly increased (p <0.05), the apoptosis rate increased (p <0.05), the expression of Bcl-2 protein decreased (p <0.05), the expression of Bax protein significantly increased (p <0.05), and the activity of Caspase-3 and Caspase-8 increased (p <0.05) in a dose-dependent manner. Hence, this can be concluded that Kanglaite injection can effectively inhibit the proliferation and induce apoptosis of SW480 cells, which may be correlated with the inhibition of Bcl-2 expression, the promotion of Bax expression and the enhancement of caspase activity. [ABSTRACT FROM AUTHOR]

Apoptosis, programmed cell death pathway, is a vital physiological mechanism that ensures cellular homeostasis and overall cellular well-being. In the context of cancer, where evasion of apoptosis is a hallmark, the overexpression of anti-apoptotic proteins like Bcl2, Bcl-xL and Mcl-1 has been documented. Consequently, these proteins have emerged as promising targets for therapeutic interventions. The BCL-2 protein family is central to apoptosis and plays a significant importance in determining cellular fate serving as a critical determinant in this biological process. This review offers a comprehensive exploration of the BCL-2 protein family, emphasizing its dual nature. Specifically, certain members of this family promote cell survival (known as anti-apoptotic proteins), while others are involved in facilitating cell death (referred to as pro-apoptotic and BH3-only proteins). The potential of directly targeting these proteins is examined, particularly due to their involvement in conferring resistance to traditional cancer therapies. The effectiveness of such targeting strategies is also discussed, considering the tumor's propensity for anti-apoptotic pathways. Furthermore, the review highlights emerging research on combination therapies, where BCL-2 inhibitors are used synergistically with other treatments to enhance therapeutic outcomes. By understanding and manipulating the BCL-2 family and its associated pathways, we open doors to innovative and more effective cancer treatments, offering hope for resistant and aggressive cases.

A database of 300 compounds was virtually screened and docked against Bcl-2 protein; the stability of the best-formed complex was evaluated through Molecular dynamics, the top ten compounds with the best in-silico complexation affinities were synthesized, and their In-vitro cytotoxic activity was examined. Thiazolidinone (4e) and isoxazoline (4a-d) were evaluated in-silico . For further evaluation and examination, we designed and synthesized from naturally occurring (R)-carvone and characterized it via spectroscopic analysis, as well as tested for their anticancer activities towards human cancer cell lines such as HT-1080 (fibrosarcome cancer), MCF-7 and MDA-MB-231 (breast cancer) and A-549 (lung cancer) by using MTT method with Doxorubicin as standard drug. Among them, compound 4d showed the most promising anticancer activity against HT-1080, A-549, MCF-7, and MDA-MB-231 cell lines with IC50 values of 15.59 ± 3.21 µM; 18.32 ± 2.73 µM; 17.28 ± 0.33 µM and 19.27 ± 2.73 µM respectively.Communicated by Ramaswamy H. Sarma.

B cell lymphoma 2 (BCL-2) family proteins play an important role in intrinsic apoptosis. Overexpression of BCL-2 proteins in acute myeloid leukemia can circumvent resistance to apoptosis and chemotherapy. Considering this effect, the exploration of anti-apoptotic BCL-2 inhibitors is considered to have tremendous potential for the discovery of novel pharmacological modulators in cancer. This review outlines the impact of BCL-2 family proteins on intrinsic apoptosis and the development of acute myeloid leukemia (AML). Furthermore, we will also review the new combination therapy with venetoclax that overcomes resistance to venetoclax and discuss biomarkers of treatment response identified in early-phase clinical trials.

Introdution: The research has been indicated that reactive oxygen species induced the apoptosis of cardiomyocytes. However, this mechanism has been unclear. The aim of this study was to investigate the effects of concurrent training on some of the heart apoptosis variables (BAX,BCL-2) following by the injection of different H2O2 dose in Wistar rat males. Methods: 50 male rats were randomly assigned to 5 groups with 10 rats in which group. Groups included: group (1): control group (C), group (2, 3): injection of 1 and 2ml H2O2, group (4,5): exercise and injection of 1and 2 ml H2O2. Exercise groups have been run on treadmill for four days during 8 weeks at moderate intensity. 24 hr after the last exercise and in anesthetic state all rats have been knockouted to determine bax and bcl2 proteins ratio. For measuring the BAX and BCL-2 proteins were used by ELISA technic and total protein were determined by brad ford technic. Data were analyzed by SPSS 17, one ways ANOVA was used to analysis of data at the level of p≤0/05. Results: The results have been indicated that after two month continues training no significant difference in BAX, BCL-2 proteins and BAX/BCL2 ratio in exercise and H2O2 groups in compared by control groups. Conclusion: based on the result of this study if the 8-week continues training has been followed by H2O2 injection with both of one and two ml H2O2 concentration, it may not have induced apoptosis cardio myocyte in rats. And it may adjusted the synthesis and degradation myocardial

B cell lymphoma 2 (BCL-2) family proteins play an important role in intrinsic apoptosis. Overexpression of BCL-2 proteins in acute myeloid leukemia can circumvent resistance to apoptosis and chemotherapy. Considering this effect, the exploration of anti-apoptotic BCL-2 inhibitors is considered to have tremendous potential for the discovery of novel pharmacological modulators in cancer. This review outlines the impact of BCL-2 family proteins on intrinsic apoptosis and the development of acute myeloid leukemia (AML). Furthermore, we will also review the new combination therapy with venetoclax that overcomes resistance to venetoclax and discuss biomarkers of treatment response identified in early-phase clinical trials. [ABSTRACT FROM AUTHOR]

The antineoplastic properties of an antioxidant, sodium 2-carboxy-2-(N-acetylamino)-3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate, are studied on an ascites tumor, Sarcoma 37, and on a solid tumor, Lewis carcinoma. A full suppression of Sarcoma 37 and an intensification of apoptosis (a decrease in the level of Bcl-2 antiapoptotic protein) in the cells of Lewis carcinoma are observed for intraperitoneal injection of the preparation. The structure of the complexes of sodium 2-carboxy-2-(N-acetylamino)-3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate with peptides is calculated using quantum chemistry. Quantitative data are obtained which characterize the intra- and intermolecular interactions of the above components in nanoassociates. [ABSTRACT FROM AUTHOR]

To investigate effects of different doses of atorvastatin on serum lipids, cardiomyocyte apoptosis and related genes in rats with myocardial infarction. 60 SD rats were randomized into control group (n = 12) and modeling group (n = 48). The models were established by ligation of left anterior descending (LAD) in rats. 5wk later, the rates after successful modeling were divided into modeling group (n = 12) and treatment group (n = 36), and treatment group was equally divided into low dose group (20 mg/kg atorvastatin daily), medium does group (40 mg/kg atorvastatin daily) and high does group (80 mg/kg atorvastatin daily). After administration, the ratio of heart weight (HW) to body weight (BW) was calculated (HW/BW). Contents of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and moderate – high density lipoprotein cholesterol (HDL-C) in serum of rats were measured. Apoptosis index of rat cardiomyocytes was detected with TUNEL method. Expression levels of Caspase-3, Bax, and Bcl-2 proteins in each group were detected by Western blot. Compared with control group, heart surface of modeling group was rough, and weight of model group was significantly higher than that of control group, low, medium and high dose groups after 9 weeks of modeling (P < 0.05). TC, TG, and LDL-C in modeling group were significantly higher than those in control group (P < 0.05), HDL-C was significantly lower than those in control group (P < 0.05). Changes in blood lipid-related indicators could be improved after administration, and the higher the dose, the better the improvement effect. Apoptosis index of cardiomyocytes in modeling group, the low, medium and high dose group was significantly higher than that in control group (P < 0.05), but apoptosis of cardiomyocytes was significantly reduced in atorvastatin group at different doses. The higher the dose, the more obvious the reduction effect. The expressions of Caspase-3, Bax, and Bcl-2 proteins in modeling group, low, medium and high dose groups were significantly higher than those in control group (P < 0.05), but administration group significantly reduced apoptosis of myocardial cells, and the higher the dose, the more significant the reduction effect. Atorvastatin can reduce TC, TG and LDL-C levels and increase HDL-C level in blood lipids, inhibit expressions of Caspase-3 and Bax and raise expression of Bcl-2 protein so as to inhibit cardiac hypertrophy, reduce cardiomyocyte apoptosis, restore myocardial function and improve myocardial infarction symptoms. [ABSTRACT FROM AUTHOR]

Bcl-2 protein (B-cell lymphoma 2) is one of the proteins in the Bcl-2 protein family that are anti apoptotic and encoded by the BCL-2 gene. This protein controls the permeability of the outer membrane of the mitochondria, which plays a role in the release of cytochrome c and several other proteins that contribute to cell death. Bcl-2 protein plays a role in regulating cell death and regulating the balance between new and old cells. Several studies showed that changes in the structure and function of Bcl-2 play a role in cell apoptosis disorders, producing cancer cells. High expression of Bcl-2 protein is seen in lung, breast, lymph node and brain cancers. Analysis of Bcl-2 protein expression at the molecular level in cancer cell is needed to determine the expression level of this protein. This study aims to produce the Bcl-2 primer for qPCR method that specifically identifies the target gene, and can be used to see the BCL-2 gene expression level in cells. A BCL-2 sequence was obtained from the National Center for Biotechnology Information (NCBI). The next process is further analysis with Primer-BLAST (NCBI). Some primer candidates are produced and undergo another selection based on several criteria. Finally, one pair of potential primers was obtained for the reaction of qPCR to BCL-2. Primer specificity was tested with Basic Local Alignment Tools (BLAST) tools and result in specific primer for human BCL-2 gene. Annealing temperature optimization shows that the primer can react optimally at 59°C. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is the second most common cancer in men. The indolent course of the disease makes the treatment choice a challenge for physicians and patients. In this study, a minimally invasive method was used to evaluate the potential of molecular markers in identifying patients with aggressive disease. Cell-free plasma samples from 60 PCa patients collected before radical prostatectomy were used to evaluate the levels of expression of eight genes (AMACR , BCL2 , NKX3-1 , GOLM1 , OR51E2 , PCA3 , SIM2 and TRPM8) by quantitative real-time PCR. Overexpression of A MACR , GOLM1 , TRPM8 and NKX3-1 genes was significantly associated with aggressive disease characteristics, including extracapsular extension, tumor stage and vesicular seminal invasion. A trio of genes (GOLM1 , NKX3-1 and TRPM8) was able to identify high-risk PCa cases (85% of sensitivity and 58% of specificity), yielding a better overall performance compared with the biopsy Gleason score and prostate-specific antigen, routinely used in the clinical practice. Although more studies are required, these circulating markers have the potential to be used as an additional test to improve the diagnosis and treatment decision of high-risk PCa patients. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Acupuncture & Tuina Science is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

It was shown by immunoblotting that the introduction of an antitumor antioxidant, sodium 2-carboxy-2-(N-acetylamino)-3-(3,5-di-tert-butyl-4-hydrophenyl)propanoate (anphen sodium), into a suspension of Lewis carcinoma cells induces a sharp decrease in the contents of the monomer and homodimer of the anti-apoptotic Bcl-2 protein. According to fluorescence analysis, the number of apoptotic cells sharply increased 1 h after exposure to anphen sodium; preliminary addition of 5 μmol L-1 of hydrogen peroxide increased the cell membrane permeability of anphen sodium and the number of apoptotic cells. The onset of apoptosis detected using fluorophores is comparable in time with the start of the decline of the Bcl-2 level. It was assumed that the mechanism of action of anphen sodium may include the interaction of the agent with the hydrophobic (BH3) domain of Bcl-2 family proteins. [ABSTRACT FROM AUTHOR]

The anti-apoptotic protein B-Cell Lymphoma 2 (Bcl-2) is a key target for the development of anti-cancer agents, as its overexpression can render cancer cells resistant to chemotherapeutic treatments. The current study has systematically evaluated a library of FDA-approved drugs for Bcl-2 inhibition using a drug repurposing strategy via in vitro, biophysical, and in-silico techniques. In vitro anticancer activity was performed, followed by apoptosis assay. The selected compounds were subjected to Saturation Transfer Difference Nuclear Magnetic Resonance (STD-NMR) spectroscopy, molecular docking, and molecular dynamic simulation for ligand-protein interactions. In the initial screening, seventy-five (75) drugs were evaluated against the HL-60 (human blood promyelocytic leukemia) cancer cell line. Among them, paroxetine HCl, carvedilol, clomipramine HCl, and clomifene citrate showed significant anti-proliferative activity (IC 50 = 9.733 ± 0.524, 11.940 ± 0.079, 12.376 ± 1.242, and 6.155 ± 0.363 μM, respectively), in comparison to the reference drug venetoclax (IC 50 = 7.086 ± 0.041 μM). This indicated that the test drugs have comparable IC 50 values to the standard drug. Furthermore, the drugs were able to induce apoptosis in HL-60 cells. These drugs showed interactions with Bcl-2 protein in STD-NMR analysis. Docking and MD simulation studies further supported the interaction of these drugs with Bcl-2 protein, mainly via hydrophobic contacts leading to stable drug-Bcl-2 complexes. This study, identifies paroxetine HCl, carvedilol, clomipramine HCl, and clomifene citrate as significant Bcl-2 inhibitors and needs further pre-clinical and clinical studies for potential anti-cancer agents' evaluation. [Display omitted] [ABSTRACT FROM AUTHOR]

Seizures in puppies often present a diagnostic challenge in terms of identifying and treating the underlying cause. Dog breeds with mutations of the MDR1-gene are known to show adverse reactions to certain drugs, yet metabolic imbalance exacerbated by physiologically immature organs and other contributing pathologies require consideration before arriving at a diagnosis. This study analysed the brains of two male, 5-week-old Australian Shepherd siblings that died after displaying severe neurological symptoms upon administration of MilproVet® to treat severe intestinal helminth infection. Despite the initial symptoms being similar, their case histories varied in terms of the symptom duration, access to supportive therapy and post-mortem interval. Histopathology and immunohistochemistry were used to obtain more information about the phase of the pathological processes in the brain, employing protein markers associated with acute hypoxic damage (β-amyloid precursor protein/APP) and apoptosis (diacylglycerolkinase-ζ/DGK-ζ, apoptotic protease activating factor 1/Apaf1, and B-cell lymphoma related protein 2/Bcl-2). The results seem to reflect the course of the animals’ clinical deterioration, implicating that the hypoxic damage to the brains was incompatible with life, and suggesting the usefulness of the mentioned immunohistochemical markers in clarifying the cause of death in animals with acute neurological deficits.

Introduction: Stomach cancer is one of the most common cancers worldwide. Bcl-2 and p53 appear to be important biomarkers in patients with stomach cancer. In this study, we investigated the expression of Bcl-2 and p53 proteins and its association with clinicopathological factors in 67 Iranian stomach cancer patients over a 5-year period (2010-2015). Material and Methods: In this cross sectional study, the expression of the Bcl-2 and p53 protein was determined using immunohistochemistry, and the pathological features of tumors were evaluated. Results: The expression of Bcl-2 and p53 proteins was detected in 47% and 48% of the patients, respectively. Of the 67 patients, 39 patients had intestinal-type gastric adenocarcinoma, and 57 patients had grade І and ΙΙ. There was a statistically significant association between Bcl-2 and p53 expressions (P=0.04). Conclusions: There is an association between Bcl-2 and p53 protein expressions in patients with stomach cancer. Bcl-2 and p53 protein expressions are more frequent in high-grade tumors. Bcl-2 and p53 expression might play an important role in the early development and phenotypic differentiation of gastric carcinomas, but not so in tumor progression.

Breast cancer (BC) accounts for 30% of all diagnosed cases of cancer in women and remains a leading cause of cancer-related deaths among women worldwide. The current study looks for a protein from the anti-apoptotic/pro-survival BCL-2 family whose overexpression reduces survivability in BC patients and a potential inhibitor for the protein. We found BCL-2A1/BFL1 protein with high expression linked to low survivability in BC. The protein shows prognosis in 8 out of 29 categories, whereas no other family member manifests this property. Out of 7379 compounds, three small molecules (CHEMBL9509, CHEMBL2104550 and CHEMBL3545011) form an H-bond with BCL-2A1/BFL1 protein's unique residue Cys55. Of the three small molecules, we found CHEMBL9509 (Silibinin) to be a potent inhibitor. The compound forms a stable H-bond with the residue Cys55 with the lowest binding energy compared to the other two compounds. It remains stable in the BH3 binding region for more than 100 ns, whereas the other two detach from the region. Additionally, the compound is found to be better than Venetoclax and Nematoclax. We firmly believe in the compound CHEMBL9509 potency to halt BC's progression by inhibiting the BCL-2A1/BFL1 protein, increasing patients' survivability.Communicated by Ramaswamy H. Sarma.

Mimusops elengi L. belonging to the Sapotaceae family is used in various folk systems of medicine in South and Southeast Asia. This study aims to identify the potential constituents responsible for anticancer activity of M. elengi flowers. The EtOAc fraction of M. elengi flowers methanolic extract possessed cytotoxicity and gave an intensive apoptotic response on human leukemia HL-60 cells. A new dipeptide N2-methylaurantiamide acetate was isolated from the fraction along with two peptide derivatives and four phenolic compounds. Among the peptide constituents, N2-methylaurantiamide acetate showed significant inhibition of cell proliferation and possible induction of apoptotic cell death. Molecular docking analysis demonstrated that N2-methylaurantiamide acetate could fit tightly into the BH3-binding groove of anti-apoptotic protein Bcl-2. Our results provide further compelling evidence and enhance the ethnopharmacological value of M. elengi. [ABSTRACT FROM AUTHOR]

Bone marrow cell leukemia protein Mcl-1 is an important member of the anti-apoptotic protein in the Bcl-2 family protein, and has high expression in many kinds of malignant tumor(acute cell leukemia, multiple myeloma, etc), resulting in drug resistance to traditional chemotherapeutic agents and Bcl-2 inhibitors. As an important target for the research and development of antitumor drugs, Mcl-1 is increasingly concerned by the researchers. Great progress has been made in the research of new Mcl-1 inhibitors and joint inhibitors. This article will make a more in-depth analysis of the structure and function of Mcl-1 protein and related inhibitors, and results of the study will be of great significance for the treatment of cancer. [ABSTRACT FROM AUTHOR]

Background: Cystic lesions with odontogenic epithelial origin and similar clinicoradiographic appearance, show different clinical behaviors. Objective: To compare some factors related to cell proliferation and escape from apoptosis in epithelium covering two groups of odontogenic cystic lesions with different clinical behaviors. Methods: In this cross-sectional study 11 paraffin-embedded samples were selected of each lesions radicular cyst, dentigerous cyst, odontogenic keratocyst, and unicystic ameloblastoma. The sample underwent immunohistochemical staining for investigating the expression of ki-67 antigen and bcl-2 protein. Data analyzed with SPSS17 software and Kruskal–Wallis and chi-square statistical tests. Findings: Most of ki-67 positive cells were observed in parabasal layer of odontogenic keratocyst [35.50±26.29%; P=0.001]. The average of ki-67-LI was more in parabasal layer of aggressive group (26.80±37.79%) compared to non-aggressive group (4.04±3.38%), was not being statistically significant. The highest average of bcl-2-LI was 95±6.70% in basal layer of odontogenic keratocyst (P=0.001). In all layers, the average of bcl-2-LI was more in aggressive lesions compared to non-aggressive ones and the highest amount was found in basal layer (72.45±3.94×10%) which was statistically significant (P=0.001). Conclusion: According to the results of this study, more expression of the markers related to escape from apoptosis in aggressive lesions group compared to non-aggressive group, suggests that escape from apoptosis had a more critical role in aggressive behavior of odontogenic cystic lesions.

Aim: This study was aimed at evaluating the anti-apoptotic effects of Bcl-2 protein in cryopreserved buffalo bull sperm. Materials and Methods: A total 10 ejaculates from two buffalo bulls (5 each) were collected using artificial vagina method, and semen was evaluated using a standard protocol. Semen was extended by Tris egg yolk extender supplemented with Bcl-2 protein at 5, 10, and 15 μM. Semen was cryopreserved at ultra-low temperature using traditional vapor freezing method. Prefreeze and post-thaw semen samples were evaluated for percent motility, viability, hypo-osmotic swelling test (HOST) reactive sperms; status of mitochondrial membrane activity and status of sperm phospholipase A1 and phospholipase A2 activity. Results: There were no significant effects of Bcl-2 protein supplementation on pre-freeze sperm quality. Percent motility and active mitochondria in post-thaw Bcl-2 supplemented and control groups were also similar. However, viable sperms were significantly (p

Objective: The aim of this study was to enlighten both the testicular histology and the genetic aspects of the apoptotic process. Thus an experimental study was designed with a model of unilateral vasectomy. Methods: Twenty-two adult male rats were used and 4 main groups were formed. The first (A), the second (B), the third (C), and the fourth group (D) consisted of 4, 4, 4 and 10 rats respectively. Rats in group A had sham operation while rats in other groups (B, C, D) underwent left vasectomy operation including binding of ductus deferens with a 3/0 silk and cutting a minimum of 1 cm part while preserving the vascular structure under 9x magnification. Rats undergoing unilateral vasectomy were sacrificed at the 1st, 2nd and 8th weeks and their testicular structure and proapoptotic gene proteins were compared with that of the control group undergoing sham operation. Results: We found that vasectomy gradually caused destruction and both ipsilateral and contralateral testicles were affected showing initial apoptosis. Conclusion: The procedure causes destruction in the testicular structure by causing bilateral intratubular germ cell necrosis, unilateral obstruction, increase in the tubular pressure and processes that are aggravated by some probable autoimmune reactions.

Background: Keratocystic odontogenic tumor (KCOT) is a developmental odontogenic cyst on which various investigations have been focused due to its biological activities, high tendency to recur and different growth mechanisms in comparison with other cystic lesions. Previous studies have shown different biological and proliferative activities for the lining epithelium of KCOT. The aim of this study was immunohistochemical evaluation of Bcl-2 and epidermal growth factor receptor (EGFR) expression in KCOT compared with dentigerous cyst and ameloblastoma. Materials and Methods: Formalin-fixed and paraffin-embedded tissue sections of 16 cases of KCOT, 16 cases of dentigerous cyst and 16 cases of ameloblastoma were immunohistochemically analyzed to determine Bcl-2 and EGFR proteins′ expression. Biotin-Stereotavidin method was used. It was observed by two oral pathologists separately, and the data were analyzed by Mann-Whitney and Kruskul-Wallis. P < 0.05 was considered as significant. Results: Regardless of staining intensity, all cases of ameloblastoma and KCOT except dentigerous cases were positively stained for Bcl-2. Expression of Bcl-2 was higher in the peripheral layer of ameloblastoma and basal layer of KCOT. Furthermore, all cases of ameloblastoma and dentigerous cysts except KCOT samples were positively stained for EGFR. Expression of EGFR was higher in the peripheral layer of ameloblastoma and basal layer of dentigerous cysts. Conclusion: According to the expression of - Bcl-2 in ameloblastoma and KCOT, and no expression of EGFR in KCOT, it can be concluded that the biological activity and growth mechanisms of KCOT are different compared with other cystic lesions. However, the aggressive potential of KCOT is not as severe as that of a neoplasm such as ameloblastoma.

Schizophrenia is one of the most severe psychiatric diseases the etiology of which remains unknown. Among the many factors involved in the pathophysiology of schizophrenia, a role of apoptosis has also been hypothesized. Bcl-2 protein is a potent inhibitor of apoptosis, showing in addition neurotrophic activity in the central nervous system. Since the expression of Bcl-2 protein is increased in several neurodegenerative diseases and schizophrenia shows some of the features of a limited neurodegenerative disorder, it has been hypothesized that Bcl-2 protein expression is altered in schizophrenia. In order to test this hypothesis, Bcl-2 protein was determined in the sera from 30 patients with schizophrenia and from 30 age- and gender-matched healthy subjects using the ELISA method. Although the mean serum Bcl-2 protein concentration was lower in patients with schizophrenia than in healthy volunteers, there was not any significant difference between the patient (0.276 ± 0.07 ng/mL) and control (0.332 ± 0.22 ng/mL) values. No significant difference was found between males and females either. Similar Bcl-2 concentrations were obtained in the group showing almost equally positive and negative symptoms (0.275 ± 0.068 ng/mL), in the group with a relative predominance of positive symptoms (0.283 ± 0.082 ng/mL) and in the group with a relative predominance of negative symptoms (0.275 ± 0.074 ng/mL). Serum Bcl-2 protein concentration in patients treated with first generation antipsychotics was 0.301 ± 0.075 ng/mL, and it was significantly higher compared to the values in patients receiving second generation antipsychotics (0.233 ± 0.052 ng/mL, p <0.05). There was not any significant correlation between serum Bcl-2 concentration and heredity, onset of the disease, number of psychotic episodes and duration of psychosis. To date and to the best of our knowledge, this has been the first demonstration of Bcl-2 concentration in the sera of patients with schizophrenia, showing significantly different values between the patients treated with typical and those treated with atypical antipsychotics. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the effect of astragalus polysaccharides (APSs), active constituents of astragalus, in the treatment of hepatocellular carcinoma (HCC) and their potential as a promising candidate for future anticancer drug development. Astragalus polysaccharide was administered at different doses to HCC H22-bearing mice to investigate their antitumor effects. Results revealed that APS inhibited the growth of H22 cells with a tumor inhibition rate in the APS 400 mg.kg-1 group of 59.01%. Astragalus polysaccharides significantly increased the spleen and thymus indexes, and also the interleukin (IL) 2, IL-6, and tumor necrosis factor a cytokine concentration in serum, indicating that APS influences immune-regulating properties involved in antitumor activity. In addition, APS increased Bax protein expression and decreased Bcl-2 protein expression; these proteins are apoptosis-regulating factors responsible for cell death or survival. Further development and exploration of APS may enable it to become an effective clinical agent for liver cancer therapy. [ABSTRACT FROM AUTHOR]

The potential of Raman micro spectroscopy as an in vitro, non-invasive tool for clinical applications has been demonstrated in recent years, specifically for cancer research. To further illustrate its potential as a high content and label free technique, it is important to show its capability to elucidate drug mechanisms of action and cellular resistances. In this study, cytotoxicity assays were employed to establish the toxicity profiles for 24 hr exposure of lung cancer cell lines, A549 and Calu-1, to the commercially available drug, doxorubicin (DOX). Raman spectroscopy, coupled with Confocal Laser Scanning Microscopy and Flow Cytometry, was used to track the DOX mechanism of action, at a subcellular level, and to study the mechanisms of cellular resistance to DOX. Biomarkers related to the drug mechanism of action and cellular resistance to apoptosis, namely reactive oxygen species (ROS) and bcl-2 protein expression, respectively, were also measured and correlated to Raman spectral profiles. Calu-1 cells are shown to exhibit spectroscopic signatures of both direct DNA damage due to intercalation in the nucleus and indirect damage due to oxidative stress in the cytoplasm, whereas the A549 cell line only exhibits signatures of the former mechanism of action. [ABSTRACT FROM AUTHOR]

Background: Solid ameloblastoma (SAB) is an invasive tumor which infiltrates adjacent normal tissues. Adenomatoid odontogenic tumor is a noninvasive tumor and never infiltrates surrounding normal tissues. The purpose of this study was to determine the biological behavior of these two epithelial odontogenic neoplasm by detecting Ki-67 and Bcl-2, which are mitotic and anti apoptotic markers respectively. Materials and Methods: In this analytical retrospective study, 16 samples of SAB and 16 samples of adenomatoid odontogenic tumor were selected. The samples were deparafinized and antigens were retrieved. Immunohistochemistry technique was applied for evaluation of these two markers. Monoclonal antibodies MIB1 and Bcl-2 were used to detect Ki-67 and Bcl-2 protein respectively, then the labeling index (LI) was calculated for both markers according to cellular staining. Data were analyzed by "t" test, (P

Background and Objectives: The product of bcl-2 gene, bcl-2 protein, an anti-apoptotic protein, is known to be over-expressed in potentially malignant disorders and squamous cell carcinoma (SCC) of the oral cavity. The aim of this study is to compare the topographical aspect and degree of bcl-2 over-expression in potentially malignant disorders including leukoplakia, oral submucous fibrosis (OSMF), and oral lichen planus (OLP), with that of the oral squamous cell carcinoma (OSCC), and to determine whether bcl-2 protein can be considered as a tumor marker. Materials and Methods : A group of 60 histo-pathologically diagnosed, formalin-fixed, paraffin embedded tissue samples was included in the study. The study group was further subdivided into four groups: Group I, consisting of oral leukoplakia; Group II, OSMF; Group III, OLP and Group IV, OSCC. These samples were collected from Government Dental College, Bangalore, and then subjected to immunohistochemical (IHC) staining using indirect immunoenzyme labeled streptavidin biotin (LSAB) method. Results : Out of 30 cases of OSCC: 11 (36.7%) cases showed greater supra-basal keratinocyte staining; 15 (50%) cases showed greater number of positive cells in the basal cell layer, with relatively less number of supra-basal cells showing positive staining; and, rest of the 4 (13.3%) cases did not show convincing staining. Among the total 30 cases of potentially malignant disorders: 10 each of leukoplakia, OSMF and OLP, 2 (20%), 2 (20%), 4 (40%) of the cases showed greater supra-basal cell layer positive staining and 8 (80%), 6 (60%), 6 (60%) of them showed greater basal cell staining, respectively. Two cases of OSMF did not show convincing staining. In the cases that were bcl-2 positive: 2 (6.67%) of the OSCC, 3 (30%) of leukoplakia, 2 (20%) of OSMF and 1 (10%) of OLP, showed more than 50% of the cells positive. 25-50% cells were positive in 21 (70%) of OSCC, 6 (60%) of leukoplakia, 4 (40%) of OSMF and 6 (60%) of OLP cases. 10-25% of cells were positive in 4 (13.3%) of OSCC, 1(10%) of leukoplakia, 2 (20%) of OSMF and 3 (30%) of OLP cases. Less than 10% of cells were positive in 3 (10%) of OSCC and 2 (20%) of OSMF cases. Clinical Significance and Conclusion : As definite number of cases showed bcl-2 over expression in our study, the role of bcl-2 in the development and progression of oral neoplasia needs further investigation along with other oncogenes.