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apoptotic pathways as a therapeutic target for colorectal cancer treatment

World Journal of Gastrointestinal Oncology 2016年第8期8卷 583-591页

作者： Aman M Abraha Ezra B Ketema Department of Medical Biochemistry College of Health Sciences Mekelle University

Colorectal cancer is the second leading cause of death from cancer among adults. The disease begins as a benign adenomatous polyp, which develops into an advanced adenoma with high-grade dysplasia and then progresses to an invasive cancer. Appropriate apoptotic signaling is fundamentally important to preserve a healthy balance between cell death and cell survival and in maintaining genome integrity. Evasion of apoptotic pathway has been established as a prominent hallmark of several cancers. During colorectal cancer development, the balance between the rates of cell growth and apoptosis that maintains intestinal epithelial cell homeostasis gets progressively disturbed. Evidences are increasingly available to support the hypothesis that failure of apoptosis may be an important factor in the evolution of colorectal cancer and its poor response to chemotherapy and radiation. The other reason for targeting apoptotic pathway in the treatment of cancer is based on the observation that this process is deregulated in cancer cells but not in normal cells. As a result, colorectal cancer therapies designed to stimulate apoptosis in target cells would play a critical role in controlling its development and progression. A better understanding of the apoptotic signaling pathways, and the mechanisms by which cancer cells evade apoptotic death might lead to effective therapeutic strategies to inhibit cancer cell proliferation with minimal toxicity and high responses to chemotherapy. In this review, we analyzed the current understanding and future promises of apoptotic pathways as a therapeutic target in colorectal cancer treatment.

关键词： Colorectal cancer apoptotic pathways Drug resistance Colorectal cancer therapies Apoptosis

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Regulation of apoptotic signal transduction pathways by the heat shock proteins

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Science China(Life Sciences) 2004年第2期47卷 107-114页

作者： LI Zhengyu1, ZHAO Xia1 & WEI Yuquan2 1. Department of Gynecology and Obstetrics, West China Second Hospital of Sichuan University, Chengdu 610041, China 2. Key Laboratory of Biotherapy of Human Diseases of Ministry of Education, West China Hospital of Sichuan university, Chengdu 610041, China Department of Gynecology and Obstetrics West China Second Hospital of Sichuan University Chengdu China Key Laboratory of Biotherapy of Human Diseases of Ministry of Education West China Hospital of Sichuan university Chengdu China

The study about apoptotic signal transductions has become a project to reveal the molecular mechanisms of apoptosis. Heat shock proteins (hsps), which play an important role in cell growth and apoptosis, have attracted great attentions. A lot of researches have showed there is a hsps superfamily including hsp90, hsp70, hsp60 and hsp27, etc., which regulates the bio-logical behaviors of cells, particularly apoptotic signal transduction in Fas pathway, JNK/SAPK pathway and caspases pathway at different levels, partly by the function of molecular chaperone.

关键词： heat shock protein, apoptotic signal transduction, molecular chaperone, caspases.

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

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World Journal of Gastroenterology 2017年第27期23卷 5018-5033页

作者： Qi Huang Shu Li Pu Cheng Mei Deng Xin He Zhen Wang Cheng-Hui Yang Xiao-Ying Zhao Jian Huang Department of Surgical Oncology the Second Affiliated HospitalZhejiang University School of MedicineZhejiang University Department of Hematology Second Affiliated HospitalZhejiang University School of Medicine

AIM To systematically evaluate the prognostic-predictive capability of Bcl-2 in colorectal cancer(CRC).METHODS A systematic literature search was conducted using Pub Med,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 *** A 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 withprognosis(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. CONCLUSION Bcl-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.

关键词： Bcl-2 Colorectal cancer Meta-analysis Prognostic apoptotic

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Methanolic extract of Clausena excavata promotes wound healing via antiinflammatory and anti-apoptotic activities

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Asian Pacific Journal of Tropical Biomedicine 2020年第5期10卷 232-238页

作者： Shaymaa Fadhel Abbas Albaayit Abdullah Rasedee Noorlidah Abdullah Yusuf Abba Department of Biology College of ScienceUniversity of BaghdadBaghdad-Iraq Department of Veterinary Laboratory Diagnosis Faculty of Veterinary MedicineUniversiti Putra Malaysia43400SerdangSelangorMalaysia Institute of Biological Sciences Faculty of ScienceUniversity of Malaya50603 Kuala LumpurMalaysia Department of Veterinary Pathology and Microbiology Faculty of Veterinary MedicineUniversiti Putra Malaysia43400 SerdangSelangorMalaysia

Objective: To investigate the anti-inflammatory properties of methanolic extract of Clausena excavata in lipopolysaccharide(LPS)-activated macrophages(J774 A.1) and the effect on skin wound in a rat model through determining cytokine levels and gene expressions. Methods: The effects of methanolic extract of Clausena excavata on in vitro viability and TNF-α, IL-6, IL-10, and nitric oxide release by LPS-activated J774 A.1 cells were determined. In addition, relative expressions of BAX, BCL-2 and COX-2 genes were examined in healed wounds of rats. Results: The methanolic extract of Clausena excavata was not toxic to J774 A.1 cells at the highest dose of 400 μg/m L. It decreased levels of TNF-α and IL-6, while increasing IL-10 level in LPSactivated J774 A.1 cells and in the healed wounds of rats. The methanolic extract of Clausena excavata also inhibited nitric oxide production in LPS-activated J774 A.1 cells. The BAX and COX-2 genes were downregulated while the BCL-2 gene was upregulated in the healed wound of rats. Conclusions: The methanolic extract of Clausena excavata promotes wound healing via its anti-inflammatory and anti-apoptotic activities.

关键词： Clausena excavata leaves Anti-inflammatory cytokines Cytotoxicity apoptotic genes

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Pro-apoptotic and anti-proliferative effects of Physalis angulata leaf extract on retinoblastoma cells

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International Journal of Ophthalmology(English edition) 2019年第9期12卷 1402-1407页

作者： Marsha Dechastra Chairissy Lely Retno Wulandari Hidayat Sujuti Department of Ophthalmology Faculty of Medicine Brawijaya University

AIM: To investigate the effect of Physalis angulata leaf extract on apoptotic and proliferation of retinoblastoma cells. Despite several previous studies evidencing the anticancer potential of Physalis angulata;however, certain study that proves its benefits in retinoblastoma cancer cells has been ***: This study utilizes an in-vitro experimental study by applying Y79 human retinoblastoma cell line culture obtained from the American Type Culture Collection(ATCC;10801 University Boulevard Manassas, VA 20110, USA). The cell was divided into 4 groups. Group I was the control group without the administration of Physalis angulata leaf extract. Whereas, group II, II and IV are engaged with 25, 50, and 100 μg/mL of Physalis angulata leaf extract respectively. After a 24 h incubation, an examination with microtetrazolium(MTT) cell proliferation assay and Annexin V apoptosis detection was conducted. Statistical analysis was performed with the Tukey ***: Physalis angulata leaf extract improved apoptosis and significantly reduced the number of living cells in retinoblastoma cells, along with the increase in the given dose. Based on the Tukey test, a significant difference was found in the treatment group at 50 μg/mL(P=0.025) and 100 μg/mL(P=0.001) in the measurement of apoptosis. Proliferation measurements also indicated a significant decrease in the number of living cells in the 50μg/m L treatment group(P=0.004), and in the 100 μg/mL treatment group(P=0.000). Meanwhile, a dose of 25 μg/mL indicated insignificant difference in the two measurements. Improved apoptosis and decreased number of living cells occured at a dose of 100 μg/mL. Decreased number of living cells(in the measurement of proliferation) was due to the inhibited proliferation or improved ***: Physalis angulata leaf extract improve apoptosis in retinoblastoma cell culture, requiring further research to inhibit proliferation.

关键词： Physalis angulata apoptotic proliferation retinoblastoma cells

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Colorectal cancer and adjacent normal mucosa differ in apoptotic and inflammatory protein expression

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Engineered Regeneration 2021年第1期2卷 279-287页

作者： Xiaojing Sun Zhonghua Xue Aqeela Yasin Yingkun He Yaru Chai Jingan Li Kun Zhang School of Materials Science and Engineering&Henan Key Laboratory of Advanced Magnesium Alloy&Key Laboratory of Materials Processing and Mold Technology(Ministry of Education) Zhengzhou UniversityZhengzhou 450001China Department of Cerebrovascular Disease Zhengzhou University People’s HospitalHenan Provincial Neurointerventional Engineering Research CenterHenan International Joint Laboratory of Cerebrovascular Disease and Henan Engineering Research Center of Cerebrovascular InterventionZhengzhou 450003China School of Life Science Zhengzhou UniversityZhengzhou 450001China

Colorectal cancer usually refers to the occurrence of the appendix,rectum or colon and other parts of the ma-lignant tumor in the large intestine mucosa and glands,is also one of the most common malignant tumors in *** recent years,studies have shown that chronic inflammation is the"initiator"of *** plays a causal role in the early formation of tumors by regulating the initiation and promotion of tumor genesis and development through a series of inflammatory *** plays a causal role in the early for-mation of tumors by regulating the initiation and promotion of tumor genesis and development through a series of inflammatory *** latter part of this review describes the role of several important inflammatory factors:tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and transforming growth factor-β(TGF-β)in col-orectal *** normal mucosa,inflammatory factors play an important role in the immune response of the ***,when a large number of inflammatory factors accumulate,they will cause pathological damage to the body,trigger inflammation and even deteriorate into *** levels of most inflammatory factors were low in healthy controls,but were elevated in colorectal cancer ***,we review the relationship be-tween apoptosis,inflammation and cancer,and analyze the difference in the expression of inflammatory proteins in colorectal cancer and its adjacent mucosa.

关键词： Colorectal cancer apoptotic Genetic mutations Chronic inflammation Inflammatory cytokines

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S100b protects IMR-32 cells against Ab(1-42) induced neurotoxicity via modulation of apoptotic genes expression

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Advances in Alzheimer's Disease 2013年第3期2卷 99-108页

作者： M. Elisabetta Clementi Beatrice Sampaolese Doriana Triggiani Antonio Tiezzi Bruno Giardina 1CNR-ICRM Institute of Chimica del Riconoscimento Molecolare Department for Innovation in Biological Agro-food and Forest Systems (DIBAF) Tuscia University Viterbo Italy Institute of Biochemistry and Clinical Biochemistry Catholic University School of Medicine Rome Italy

Amyloid beta (1-42) peptide is considered responsible for the formation of senile plaques that accumulate in the brain of patients with Alzheimer’s disease (AD). In the past years considerable attention has been focused on identifying new protective substances that prevent or almost retard the appearance of amyloid beta (1-42)-related neurotoxic effects. In this study, human neuroblastoma cells (IMR-32) was used as system model to evaluate the protective role of S100b, a neurotrophic factor and neuronal survival protein, that is highly expressed by reactive astrocytes in close vicinity of beta-amyloid deposits, against amyloid beta (1-42)-dependent toxicity. Our results show that at nanomolar concentrations, S100b protects cells against Aβmediated cytotoxicity, as assessed by MTS vitality test. The protective mechanism seems to be related to the effect on bcl-2 (an anti-apoptotic gene) expression, which is highly down-regulated by amyloid beta (1-42) treatment, while resulted more expressed in the presence of S100b. On the contrary, Bax, a proapoptotic gene, resulted down-regulated by the treatment with S100 compared with the results obtained in the presence of amyloid beta (1-42) peptide. However, at micromolar doses, S100b is toxic for IMR-32 cells and its toxicity adds to that of the Aβpeptide, suggesting that additional molecular mechanisms may be involved in theneurotoxic process.

关键词： S100b Neurodegeneration Oxidate Methionine apoptotic Genes Expression

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Evaluating the Importance of apoptotic Index, Mitotic Index and Turnover Index in Premalignant and Malignant Lesions of Cervix

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Open Journal of Pathology 2015年第2期5卷 29-37页

作者： Subhash Bhardwaj Farooq Ahmed Wani Department of Pathology Government Medical College Jammu India Department of Pathology Aljouf College of Medicine Sakaka KSA

Aim: To evaluate the premalignant and malignant lesions of the uterine cervix on light microscopy for apoptosis. To calculate and correlate the apoptotic index (AI), mitotic index (MI) and turnover index of the lesions. Materials and methods: A 2-year retrospective (November 2007 to October 2009) and 1-year prospective study (November 2009 to October 2010). A total of 95 cases of premalignant and malignant lesions of cervix were studied. The hematoxylin-eosin stained slides were screened for apoptosis under oil immersion lens. apoptotic index (AI) was calculated as the number of apoptotic cells and apoptotic bodies, expressed as percentage of total no. of tumour cells counted in each case. Mitotic index (MI) was calculated by counting mitosis among 1000 tumour cells. Turnover index (TOI) was obtained by adding MI and AI, i.e., (TOI = MI + AI). After calculating, all these indices were correlated with different grades of the cervical lesions. Results: Premalignant lesions were divided into four subgroups. On statistical analysis, it was found that the difference in the apoptotic indices and turnover indices in all the four subgroups was not statistically significant. However for mitotic indices, significant statistical difference was found in Subgroup II (mild dysplasia vs. moderate dysplasia) with a p value of 0.03 and in subgroup IV (squamous metaplasia vs. moderate/severe dysplasia) with a p value of 0.0005. Within the malignant group, we compared well differentiated with less well differentiated subgroup. Statistical analysis revealed a significant difference in TOI between the two subgroups of malignant tumours (p = 0.04). Statistical comparison between premalignant and malignant group of lesions showed a highly significant difference between the AI, MI and TOI with p value of 0.0001. Conclusion: We conclude that proliferative and apoptotic indices are useful in distinguishing between benign and malignant lesions of the cervix. Proliferative activity of a lesion

关键词： Apoptosis apoptotic Index Mitosis Cervical Carcinoma

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Diarrhea and Hypokalemic Rhabdomyolysis Due to apoptotic Colitis as the Initial Manifestation of Common-Variable Immunodeficiency in an Adolescent

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Open Journal of Pediatrics 2014年第2期4卷 129-134页

作者： David Green Nina Dave Hua Liu Charu Subramony Michael J. Nowicki Department of Pathology University of Mississippi Medical Center Jackson USA Division of Pediatric Allergy-Immunology University of Mississippi Medical Center Jackson USA Division of Pediatric Gastroenterology University of Mississippi Medical Center Jackson USA School of Medicine University of Mississippi Medical Center Jackson USA

We present the case of an adolescent who presented with rhabdomyolysis due to severe hypokalemia arising from chronic diarrhea. Initial evaluation for celiac disease, known to present in this manner, was negative. Further evaluation with colonoscopy showed a normal appearing colon but biopsies showed a significant number of apoptotic cells in the mucosal crypts supporting a diagnosis of apoptotic colitis. Investigation into the cause of apoptotic colitis resulted in a diagnosis of common variable immune deficiency due to a defect in the inducible T-cell costimulator (ICOS) gene. Physicians should be aware of this uncommon condition and the importance of mucosal biopsy despite the presence of normal appearing mucosa.

关键词： apoptotic Colitis Common-Variable Immune Deficiency Hypokalemia Rhabdomyolysis

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Alteration of apoptotic Gene Expression and Reproductive Parameters through Thymus vulgaris Administration Following Paclitaxel-Induced Testopathy in Mice

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Reproductive and Developmental Medicine 2020年第4期4卷 219-227页

作者： Roshankhah Shiva Hassanzadeh GholamReza Faramarzi Azita Salahshoor Mohammad Reza Department of Anatomical Sciences Medical SchoolKermanshah University of Medical SciencesKermanshahIran Department of Anatomical Sciences Medical SchoolTehran University of Medical SciencesTehranIran

Objective:Paclitaxel(PAC)is a chemotherapy drug and has an active role in the treatment of lung,breast,and ovarian cancers;however,its use causes increased levels of free radicals,leading to severe and irreversible organ *** vulgaris is a species of flowering plant that contains various antioxidant chemical *** study aimed to investigate the effect of *** on PAC-induced oxidative damage in mice testis and sperm ***:In this study,40 BALB/c mice were divided into five groups:normal control(NC);positive control(20 mg/kg of PAC);and three treatment groups(4.5,9,and 18 mg/kg doses of *** extract+20 mg/kg PAC).Treatments were administered intraperitoneally daily for 50 ***,the levels of serum luteinizing hormone(LH),follicle-stimulating hormone(FSH),and testosterone were measured using immunoassay *** stereological features and sperm parameters were also *** parameters were measured using nitrite oxide(NO)and perioxidation levels and ferric-reducing ability of plasma *** expressions of p53,caspase-3,Bax,and Bcl-2 were measured through real-time quantitative polymerase chain ***:***+PAC treatments at all doses significantly increased all parameters in NC and three treatment groups compared with the positive control group(20 mg/kg of PAC)(P<0.05),except the LH,FSH,and NO levels,which were ***,significantly downregulated levels of p53,caspase-3,and Bax genes and upregulated levels of Bcl-2 gene expression were noted in NC and three treatment groups in comparison with the positive control group(P<0.05).Conclusions:*** administration attenuates the toxic effects of PAC on male reproductive parameters.

关键词： apoptotic Paclitaxel Reproductive Testopathy Thymus vulgaris

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