Progress of X-linked inhibitor of apoptosis deficiency in hemophagocytic lymphohistiocytosis / 国际儿科学杂志

Hemophagocytic lymphohistiocytosis(HLH)is a systemic hyperinflammation syndrome.XIAP deficiency is an innate immunodeficiency disorder, often combined with HLH, with increased susceptibility to EB virus, mostly in childhood.XIAP deficiency leads to innate immune deficiency, increased apoptosis, and excessive activation of NLRP3 inflammasome, which together lead to impaired clearance of pathogens and excessive release of cytokines, resulting in HLH.The course of HLH in patients with XIAP deficiency is generally mild and the mortality rate is low, but it frequently relapses.In addition to HLH, XIAP deficiency can be combined with some auto-inflammatory disease.Hematopoietic stem cell transplantation is the only curable method and reduced-intensity conditioning is recommended.Some new targeted therapies, such as IFN-γ monoclonal antibodies, IL-18 and IL-6 antagonists may be effective, but the specific efficacy needs more study.

Diallyl disulfide downregulates XIAP through miR-7 to inhibit proliferation, migration and invasion of human gastric cancer SGC7901 cells / 中国药理学通报

Aim To investigate whether diallyl disul¬fide ( DADS) downregulates X-linked inhibitor of ap- optosis protein ( XIAP) through miR-7 , inhibiting the proliferation, migration anrl invasion of gastric eaneer SGC7901 eel Is.Methods Gastric eaneer SGC7901 eell line overexpressing XIAP was established.qRT- PCR and Western blot were used to deteet the effeet of DADS on XIAP expression in overexpressed eells.CCK-8 and plate elone formation assay were used to analyze the effeet of DADS on the proliferation of XIAP overexpressing eells.Wound healing and Transwell ex¬periments were employed to analyze the effeets of DADS on the migration and invasion of XIAP overex¬pressing eells.qRT-PCR was used to deteet the effeet of DADS on the expression of miR-7.Negative regula¬ tion of miR-7 on XIAP was verified by using dual lucif- erase reporter gene assay, qRT-PCR ,anrl Western blot.Results XIAP overexpression enhanced the prolifera¬tion , migration and invasion of SGC7901 cells.DADS downregulated XIAP and inhibited the proliferation, mi¬gration and invasion of XIAP overexpressing cells.DADS upregulated miR-7 expression.miR-7 bound and regulated XIAP 3 'UTR directly.Overexpression of miR-7 decreased XIAP expression,while knockdown of miR-7 increased XIAP expression.Conclusion DADS downregulates XIAP through miR-7 to inhibit SGC7901 cell proliferation, migration and invasion.

Apoptosis (programmed cell death) and its signals - A review / Apoptose, morte celular programada e seus sinais: uma revisão

Abstract Apoptosis is a sequential order of cell death occurring regularly to ensure a homeostatic balance between the rate of cell formation and cell death. However, a misplaced of this balancing function can contribute to an abnormal cell growth / proliferation or autoimmune disorders etc. Apoptosis is therefore said to be crucial from the point of development of an embryo throughout the growth of an organism contributing to the renewal of tissues and also the getting rid of inflammatory cells. This review seeks to elaborate on the recent overview of the mechanism involved in apoptosis, some element and signal contributing to its function and inhibition together with how their malfunction contribute to a number of cancer related cases.

Resumo A apoptose é uma ordem sequencial de morte celular que ocorre regularmente para garantir um equilíbrio homeostático entre a taxa de formação e a morte celular. No entanto, um desequilíbrio dessa função pode contribuir para um crescimento/proliferação celular anormal ou distúrbios autoimunes. A apoptose é, portanto, considerada crucial do ponto de desenvolvimento de um embrião ao longo do crescimento de um organismo que contribui para a renovação dos tecidos e também a eliminação de células inflamatórias. Esta revisão procura elaborar a recente visão geral do mecanismo envolvido na apoptose, alguns elementos e sinais que contribuem para sua função e inibição, além de como o mau funcionamento deles contribui para vários casos relacionados ao câncer.

The mechanism by which Ginkgo biloba extract induces the apoptosis of human laryngeal cancer Hep-2 cells by reducing reactive oxygen species level and activating JNK signaling pathway / 中国基层医药

Objective:To investigate the apoptosis-inducing effect of Ginkgo biloba extract (Ginaton) on human laryngeal cancer Hep-2 cells and the underlying molecular mechanism.Methods:Human laryngeal cancer Hep-2 cells were cultured in vitro and human laryngeal cancer Hep-2 cells in the log phase were treated with Ginaton in time and concentration gradients. The cell counting kit-8 (CCK-8) assay was performed to investigate the inhibitory effects of Ginaton on Hep-2 cells. Flow cytometry was performed to detect apoptosis and determine the level of reactive oxygen species (ROS). Western blot assay was performed to detect apoptosis and signaling pathway-related protein expression. Results:Ginaton inhibited the proliferation of Hep-2 cells in a time-dependent and concentration-dependent manner. Malondialdehyde level decreased gradually in a time-dependent manner, and decreased to 2.98 μmol/g after 24 hours of Ginaton treatment. Superoxide dismutase level increased gradually in a time-dependent manner and increased to 90.35 U/g after 24 hours of Ginaton treatment. ROS level decreased gradually in a time-dependent manner and deceased to 18.7% of the level before treatment after 24 hours of Ginaton treatment. There was no significant difference in ROS level between before and after 24 hours of Ginaton treatment ( F = 14.98, 19.65, 11.47, all P < 0.001). After 3, 6, 12 and 24 hours of Ginaton treatment, the expression of phosphorylated N-terminal protein kinase increased to 1.98, 2.57, 2.91 and 3.28 in a time-dependent manner. There was significant difference in the expression of phosphorylated N-terminal protein kinase between before treatment and after 3, 6, 12 and 24 hours of Ginaton treatment ( F = 16.37, P < 0.001). Conclusion:Ginaton can effectively inhibit the proliferation and induce apoptosis of human laryngeal cancer Hep-2 cells in vitro, which may be related to regulating ROS level and activating JNK signaling pathway.

The Effect of XIAP and Its Application in Tumor / 中国生物化学与分子生物学报

It has been found that X-linked inhibitor of apoptosis (XIAP) is the most characteristic and strongest inhibition of apoptosis proteins. The characteristic structures of XIAP are BIR domain and RING domain, which are important structures for XIAP to play an anti- apoptotic role. A variety of endogenous inhibitory proteins (XAF1, SMAC and OMI) can also inhibit XIAP’s anti-apoptotic effect in different ways. XIAP can directly inhibit the initiation and persistence of apoptosis pathway of caspase. XIAP participates in the death receptor pathway and mitochondrial pathway of inhibiting apoptosis in a variety of ways, such as directly binds to caspases, and activates NF-кB way and other signal pathways, which is essential for regulating the survival and development of tumor cells. XIAP is highly expressed in many kinds of tumor tissues. The high expression of XIAP is closely related to the occurrence and development, drug resistance, treatment and prognosis of tumors. XIAP deletion can significantly reduce the tumorigenicity of tumor cells, and XIAP is the downstream factor of cell apoptosis formed by blocking multiple signal pathways. Therefore, XIAP has become a new target for clinical anticancer drug design. At present, three potential directions of XIAP application in clinical treatment of cancer are small molecule inhibitors, antisense oligonucleotide inhibitors and XIAP gene silencing. This paper will introduce the biological function of XIAP against apoptosis and its role in the occurrence and development, drug resistance, treatment and prognosis of tumor diseases.

A new perspective of triptolide-associated hepatotoxicity: the relevance of NF- B and NF- B-mediated cellular FLICE-inhibitory protein

Previously, we proposed a new perspective of triptolide (TP)-associated hepatotoxicity: liver hypersensitivity upon lipopolysaccharide (LPS) stimulation. However, the mechanisms for TP/LPS-induced hepatotoxicity remained elusive. The present study aimed to clarify the role of LPS in TP/LPS-induced hepatotoxicity and the mechanism by which TP induces liver hypersensitivity upon LPS stimulation. TNF- inhibitor, etanercept, was injected intraperitoneally into mice to investigate whether induction of TNF- by LPS participated in the liver injury induced by TP/LPS co-treatment. Mice and hepatocytes pretreated with TP were stimulated with recombinant TNF- to assess the function of TNF- in TP/LPS co-treatment. Additionally, time-dependent NF-B activation and NF-B-mediated pro-survival signals were measured and . Finally, overexpression of cellular FLICE-inhibitory protein (FLIP), the most potent NF-B-mediated pro-survival protein, was measured and to assess its function in TP/LPS-induced hepatotoxicity. Etanercept counteracted the toxic reactions induced by TP/LPS. TP-treatment sensitized mice and hepatocytes to TNF-, revealing the role of TNF- in TP/LPS-induced hepatotoxicity. Mechanistic studies revealed that TP inhibited NF-B dependent pro-survival signals, especially FLIP, induced by LPS/TNF-. Moreover, overexpression of FLIP alleviated TP/LPS-induced hepatotoxicity and TP/TNF--induced apoptosis . Mice and hepatocytes treated with TP were sensitive to TNF-, which was released from LPS-stimulated immune cells. These and other results show that the TP-induced inhibition of NF-B-dependent transcriptional activity and FLIP production are responsible for liver hypersensitivity.

The role of Survivin as a biomarker and potential prognostic factor for breast cancer

SUMMARY Breast cancer (BC) is one of the primary health problems worldwide. As the most common cancer in women in the world and in Brasil, behind only non-melanoma skin cancer, this neoplasm corresponds to approximately 28% of new cases per year in the country. BC also affects men, although the incidence corresponds to only 1% of total cases. Currently, most of the chemotherapeutic agents used in BC treatment are extremely toxic and cause long-term side effects. There is also a need to obtain earlier diagnoses, more accurate prognoses and make new therapies available that are more selective and effective in order to improve the current scenario. Therefore, this work sought to evaluate the importance of the biomarker survivin (Sur) in relation to BC, through the detailing of the role of Sur as a biomarker, the correlation between this protein and the prognosis of BC patients, and a summary of therapeutic strategies that target Sur for the development of new anticancer therapies.

RESUMO O câncer de mama (CM) é um dos principais problemas de saúde em todo o mundo. Como o câncer mais comum em mulheres no mundo e no Brasil, precedido apenas pelo câncer de pele não melanoma, essa neoplasia corresponde a aproximadamente 28% dos novos casos por ano no país. O CM também afeta homens, embora a incidência corresponda a apenas 1% do total de casos. Atualmente, a maioria dos agentes quimioterápicos utilizados no tratamento do CM são extremamente tóxicos e causam efeitos colaterais a longo prazo. Há também a necessidade de se obterem diagnósticos mais precoces, prognósticos mais precisos e disponibilizar novas terapias seletivas e efetivas, a fim de melhorar o cenário atual. Portanto, este trabalho buscou avaliar a importância do biomarcador Survivina (Sur) em relação ao CM, por meio do detalhamento do papel do Sur como biomarcador, da correlação entre essa proteína com o prognóstico de pacientes com CM e de um resumo do tratamento terapêutico e das estratégias que visam utilizar a Sur para o desenvolvimento de novas terapias anticâncer.

Effect of electroacupuncture on c-IAP1 mRNA and c-lAP2 mRNA in synovial tissues of rats with adjuvant arthritis / 针灸推拿医学（英文版）

Objective:To observe the therapeutic effect of electroacupuncture (EA) at Zusanli (ST 36),Guanyuan (CV 4) and Ashi points on adjuvant arthritis rats,and explore the mechanism of EA treatment of rheumatoid arthritis (RA).Methods:Sixty male rats were randomly divided into a normal group,a model group,a methotrexate group and an EA group,with 15 rats in each group.Rats in the normal group and the model group were routinely raised and did not receive treatment;rats in the methotrexate group received methotrexate at a dose of 0.35 mg/(kg·bw),twice a week for 3 weeks;rats in the EA group received acupuncture at Zusanli (ST 36),Guanyuan (CV 4) and Ashi points,and the bilateral Zusanli (ST 36) and Ashi points were connected to EA apparatus,once a day for 3 weeks.The general status,the swelling degree of the toe,the arthritis index (AI) score,the pathological morphology of the ankle joint,and the mRNA expressions of cellular inhibitor of apoptosis protein (c-IAP) 1 and c-IAP2 in joint synovial tissue cells of the rats in each group were observed.Results:The swelling degree of the toe,AI score and mRNA expressions of c-IAP1 and c-IAP2 in the model group were significantly higher than those in the normal group (all P＜0.05).Compared with the model group,the swelling degree of the toe,AI score and mRNA expressions of c-IAP1 and c-IAP2 in the methotrexate group and the EA group improved (P＜0.01 or P＜0.05);the expressions of c-IAP1 mRNA and c-IAP2 mRNA in rat synovial tissues in the EA group were significantly higher than those in the methotrexate group (P＜0.01).Conclusion:EA alleviates joint swelling in rats with adjuvant arthritis.The mechanism may be related to suppressing mRNA expressions of c-IAP1 and c-IAP2,thus to induce apoptosis of synoviocytes.

Efficacy of phosphocreatine pre-administration on XIAP and Smac in ischemic penumbra of rats with focal cerebral ischemia reperfusion injury

Abstract Purpose: To observe the efficacy of phosphocreatine pre-administration (PCr-PA) on X-linked inhibitor of apoptosis protein (XIAP), the second mitochondia-derived activator of caspase (Smac) and apoptosis in the ischemic penumbra of rats with focal cerebral ischemia-reperfusion injury (CIRI). Methods: A total of 60 healthy male Sprague Dawley (SD) rats were randomly divided into three groups (n=20): group A (the sham operation group), group B <intraperitoneally injected with 20 mg/kg (10 mg/ml) of saline before preparing the ischemia-reperfusion (IR) model>, and group C <intraperitoneally injected with 20 mg/kg (10 mg/ml) of PCr immediately before preparing the IR model>. After 24 h for reperfusion, the neurological function was evaluated and the tissue was sampled to detect expression of XIAP, Smac and caspase-3 positive cells in the ischemic penumbra so as to observe the apoptosis. Results: Compared with group B, neurological deficit scores, numbers of apoptotic cells, expression of Smac,caspase-9 and the numbers of Caspase-3 positive cells were decreased while expression of XIAP were increased in the ischemic penumbra of group C. Conclusions: Phosphocreatine pre-administration may elicit neuroprotective effects in the brain by increasing expression of X-linked inhibitor of apoptosis protein, reducing expression of second mitochondia-derived activator of caspase, and inhibiting the apoptosis in the ischemic penumbra.

X-linked inhibitor of apoptosis deficiency manifested as Crohn's disease: a case report and literature review / 中华儿科杂志

Objective@#To analyze the clinical characteristics of X-linked inhibitor of apoptosis (XIAP) deficient patients with clinical manifestation of Crohn's disease.@*Methods@#Clinical manifestations, laboratory investigations, genetic testing and therapeutic interventions of one case of XIAP deficiency who was admitted to Department of Gastroenterology in Children's Hospital, Zhejiang University School of Medicine in May 2016 were summarized. PubMed and Chinese database for articles published from January 2016 to June 2017 were searched using the key words of'Crohn's disease’and'XIAP’, and the relevant literature was reviewed.@*Results@#The case we reported was a 6-year-1-month-old boy with recurrent bloody stool for 2 months, and abdominal pain with fever for 2 weeks. The patient had a past history of hemophagocytic lymphohistiocytosis (HLH) and epilepsy in the past one year. Complete blood cell count showed mild anemia (Hb108 g/L). The patient had an elevated high-sensitivity C reactive protein (86 mg/L) and erythrocyte sedimentation rate (46 mm/1h) . White blood cells, pus cells and red blood cells were found on routine stool examination. Biochemical panel showed hypoalbuminemia (25.2 g/L) , elevated transaminase (alanine aminotransferase 175 U/L, aspartate transaminase 229 U/L) , hypertriglyceridemia (4.41 mmol/L) , and hyperferritinemia (>1 650.0 μg/L) . Magnetic resonance enterography revealed the intestinal wall thickening and increased enhancement in parts of illeum and colon. Capsule endoscopy revealed multiple ulcers in jejunum. Colonoscopy showed multiple ulcers in colon and the pathological examination revealed chronic inflammation in mucosa of terminal ileum and colon, which was combined with partial necrosis and ulceration. Some phagocytes were seen in bone marrow smears. The patient was given multiple diagnoses, including hemophagocytic lymphohistiocytosis, Crohn's disease, sepsis, epilepsy, severe malnutrition, and hypoproteinemia. The pediatric Crohn's disease activity index (PCDAI) was 37.5. Genetic testing identified a hemizygotic mutation of c.910G>T chrX:123022501 p.G304X in XIAP. The parents had no such mutation. The patient showed response to infliximab with oral intake of mercaptopurine and corticosteroids, and had remission with PCDAI of 0. There were 9 relevant articles (Chinese 0 English 9), which showed 33.3% XIAP deficient patients manifested with inflammatory bowel disease(IBD), who might have other manifestations such as hemophagocytic lymphohistiocytosis or splenomegaly simultaneously or sequentially. Those patients showed poor response to monotherapy.@*Conclusion@#XIAP deficient patients have various clinical manifestations. Genetic testing is important to those male pediatric IBD patients who have the complicated symptoms or little response to standard therapy.

Effects of Acupuncture-rehabilitation Therapy on Neurological Function and Expression of Apoptosis-related Proteins in Ischemic Penumbra of Rats with Cerebral Ischemia / 中国康复理论与实践

@#Objective To investigate the effect of acupuncture-rehabilitation therapy on the neurological function and the expression of cleaved-caspase-8, cleaved-caspase-3 and cellular inhibitor of apoptosis 1 (cIAP1) in ischemic penumbra of rats with cerebral ischemia. Methods A total of 90 male Sprague-Dawley rats were randomly divided into sham group, model group, acupuncture group, rehabilitation group and acupuncture-rehabilitation group. Each group was divided into three days, seven days and 14 days subgroups (n=6). The cerebral ischemia model was established with the modified Koizumi suture method. The sham group and the model group received no treatment. The acupuncture group received cluster needling of scalp acupuncture, the rehabilitation group received treadmill training, and the acupuncture-rehabilitation group received both acupuncture and treadmill training. Three days, seven days and 14 days after modeling, their neurological function was assessed with modified Neurological Severity Score (mNSS) and Rota-rod test, and the expression of cleaved-caspase-8, cleaved-caspase-3 and cIAP1 protein in cerebral ischemic penumbra were detected with Western blotting. Results Compared with the model group, the mNSS scores decreased, the retention time of Rota-rod test increased, the expression of cleaved-caspase-8, cleaved-caspase-3 protein decreased and the expression of cIAP1 protein increased in each treatment group at each time point (P<0.05). Compared with the other two treatment groups, the mNSS scores further decreased, the retention time further increased, the expression of cleaved-caspase-8, cleaved-caspase-3 protein further decreased, and the expression of cIAP1 protein further increased (P<0.05) seven days and 14 days after modeling in the acupuncture-rehabilitation group.Conclusion Acupuncture-rehabilitation therapy can improve the neurological function in rats with cerebral ischemia, that is better than the simple acupuncture or exercise, which may relate to the inhibition of caspase-8 and caspase-3 protein activation, and promotion of cIAP1 protein expression, to inhibit the apoptotic caspases cascade reaction.

Evaluation of survivin immunoexpression in the differentiation of high- and low-grade breast ductal carcinoma in situ / Expressão da proteína survivina em carcinoma ductal in situ de mama de alto e de baixo grau

ABSTRACT Objective To evaluate the expression of survivin protein in low- and high-grade ductal carcinoma in situ. Methods Breast tissue fragments obtained by incisional biopsy and surgical procedures of 37 women with ductal carcinoma in situ of the breast were subdivided into two groups: Group A, composed of women with low-grade ductal carcinoma in situ, and Group B, women with high-grade ductal carcinoma in situ. Survivin protein expression test was performed by immunohistochemistry, using a monoclonal antibody clone I2C4. The criterion to evaluate survivin immunoexpression was based on the percentage of neoplastic cells that presented brown-gold staining. This criterion was positive when the percentage of stained cells was ≥10%. Results The survivin protein was expressed in 22 out of 24 cases of high-grade ductal carcinoma in situ (78%), whereas, in Group A, of low-grade ductal carcinoma in situ (n=13), it was positive in only 6 cases (21.40%; p=0.004). Conclusion The frequency of expression of survivin was significantly higher in the group of patients with high-grade ductal carcinoma in situ compared to those in the low-grade ductal carcinoma in situ group.

RESUMO Objetivo Avaliar a imunoexpressão da proteína survivina nos carcinomas ductais in situ de mama de baixo e de alto graus. Métodos Fragmentos de tecido mamários obtidos por biópsia incisional e procedimentos cirúrgicos de 37 mulheres acometidas por carcinoma ductal in situ de mama foram subdivididos em dois grupos: Grupo A, formado por mulheres com carcinoma ductal in situ de baixo grau; e Grupo B, por mulheres com carcinoma ductal in situ de alto grau. A pesquisa de expressão da proteína survivina foi realizada pela técnica de imuno-histoquímica, utilizando-se anticorpo monoclonal clone I2C4. O critério de avaliação da imunoexpressão da survivina baseou-se na percentagem de células neoplásicas que apresentava coloração castanho-dourada. Considerouse tal critério positivo quando a percentagem de células apresentasse marcação ≥10%. Resultados A proteína survivina apresentou-se expressa em 22 dos 24 casos de carcinoma ductal in situ de alto grau (78%), enquanto no Grupo A, de carcinoma ductal in situ de baixo grau (n=13), apresentou-se positiva em apenas 6 casos (21,40%; p=0,004). Conclusão O índice de frequência de expressão da survivina foi significativamente mais elevado no grupo de pacientes com carcinoma ductal in situ de alto grau, quando comparado às do grupo com carcinoma ductal in situ de baixo grau.

New strategy for antagonizing drug resistance: targeting survivin / 中国药理学通报

Multidrug resistance ( MDR) often leads to failure of cancer chemotherapy. survivin, a member of the inhibitor of apoptosis proteins (IAP) family, is overexpressed in almost all kinds of tumor cells. Importantly, survivin has been identified as one of the most important molecules involved in the regulation of MDR. Therefore, inhibiting the activity of survivin or down-reg-ulating the expression of survivin might be an effective strategy to overcome tumor MDR. In this article, the roles of survivin in-volved in the development of drug resistance and the strategies to overcome drug resistance by targeting survivin are thus re-viewed.

Relationship between iASPP expression with clinicopathological features and prognosis in patients with nasopharyngeal carcinoma / 重庆医学

Objective To investigate the expression change of inhibitory member of the ASPP family(iASPP) and its relationship with clinicopathological features and prognosis in the patients with nasopharyngeal carcinoma(NPC).Methods One hundred and thirty-three cases of nasopharyngeal carcinoma confirmed by pathology in the hospital were selected,at the same time 30 cases of nasopharyngeal chronic mucositis biopsy paraffin blocks previously collected in the pathology department served as the control group.The immunohistochemical staining was used to compare the expression of iASPP protein in the two groups and the relationship between the expression of iASPP with the clinicopathologic characteristics and prognosis in the patients with NPC was analyzed.Results The positive expression of iASPP protein in the nasopharyngeal carcinoma tissue was 72.18％,which was higher than 20.00％ in the control group(P＜0.05);the positive expression of iASPP protein in the nasopharyngeal carcinoma tissue had a certain relationship with the primary tumor range and lymph node metastasis(P＜0.05);92 cases of nasopharyngeal carcinoma were followed up,including 63 cases of iASPP protein positive expression and 29 cases of iASPP protein negative expression,the 5-year survival rate in the patients with iASPP protein positive expression was 71.43％,which in the patients with iASPP protein negative expression was 86.21％,the difference was not statistically significant(P＞0.05).Conclusion The iASPP expression in the nasopharyngeal carcinoma tissue is up-regulated,which is related to the lymph node metastasis and the primary tumor range,but its influence on the patient's prognosis is not significant.

High expression of XIAP and Bcl-2 may inhibit programmed cell death in glioblastomas / Alta expressão de XIAP e Bcl-2 pode inibir morte celular programada em glioblastomas

ABSTRACT Glioblastoma (GBM) is the most malignant glioma and represents 29% of all brain tumors. Tumorigenesis is intimately connected with characteristics acquired in the physiologic pathway of cellular death. Objective: In the present study, the expression of anti-apoptotic (XIAP and Bcl-2) and apoptotic (cytochrome C, caspase 9, APAF-1), caspase 3 and the Smac/DIABLO genes related to the apoptosis pathway were evaluated in 30 samples of glioblastoma. Methods: The gene expression was evaluated in 30 glioblastomas (WHO grade IV) and compared to 10 white matter control samples with real-time PCR. Results and Conclusion: There were higher expressions of XIAP (p = 0.0032) and Bcl-2 (p = 0.0351) in the glioblastoma samples compared to the control samples of normal brain. These results raise the question of whether Bcl-2 and XIAP genes can be responsible for the inhibition of programmed cell death in glioblastomas. Moreover, they provide additional information capable of allowing the development of new target therapy strategies.

RESUMO O glioblastoma (GBM) é o glioma mais maligno e representa 29% de todos os tumores cerebrais. A tumorigênese está intimamente ligada à características adquiridas na via fisiológica de morte celular. Objetivo: Avaliar a expressão de genes anti-apoptóticos (XIAP e Bcl-2) e apoptóticos (citocromo C, a caspase 9, APAF-1), caspase 3 e SMAC/DIABLO, relacionados à apoptose, em 30 amostras de tecido de pacientes com glioblastoma. Métodos: A expressão gênica foi avaliada em trinta glioblastomas e comparada a dez amostras controles de substância branca por PCR em tempo real. Resultados e Conclusão: Houve maior nível de expressão de XIAP (p = 0,0032) e Bcl-2 (p = 0,0351) em comparação com as amostras controle, de cérebro normal. Estes resultados levantam a questão de que os genes Bcl-2 e XIAP podem ser responsáveis pela inibição da morte celular programada em glioblastomas, além disso, proporcionam informação adicional capaz de permitir o desenvolvimento de novas estratégias de terapia alvo.

Apoptosis (programmed cell death) and its signals - A review

Abstract Apoptosis is a sequential order of cell death occurring regularly to ensure a homeostatic balance between the rate of cell formation and cell death. However, a misplaced of this balancing function can contribute to an abnormal cell growth / proliferation or autoimmune disorders etc. Apoptosis is therefore said to be crucial from the point of development of an embryo throughout the growth of an organism contributing to the renewal of tissues and also the getting rid of inflammatory cells. This review seeks to elaborate on the recent overview of the mechanism involved in apoptosis, some element and signal contributing to its function and inhibition together with how their malfunction contribute to a number of cancer related cases.

Resumo A apoptose é uma ordem sequencial de morte celular que ocorre regularmente para garantir um equilíbrio homeostático entre a taxa de formação e a morte celular. No entanto, um desequilíbrio dessa função pode contribuir para um crescimento/proliferação celular anormal ou distúrbios autoimunes. A apoptose é, portanto, considerada crucial do ponto de desenvolvimento de um embrião ao longo do crescimento de um organismo que contribui para a renovação dos tecidos e também a eliminação de células inflamatórias. Esta revisão procura elaborar a recente visão geral do mecanismo envolvido na apoptose, alguns elementos e sinais que contribuem para sua função e inibição, além de como o mau funcionamento deles contribui para vários casos relacionados ao câncer.

Analysis on the expression of Smac and Survivin in precancerous lesions of gastric ulcer / 国际检验医学杂志

Objective To investigate the expression of pro-apoptotic factor (Smac) and Survivin in gastric ulcer tissue.Methods Selected the 80 cases of gastric ulcer patients as the research object in the first people′s hospital of neijiang,in which no precancerous lesions of 40 cases of gastric ulcer (N group),40 cases of precancerous lesions of gastric ulcer(Y group),two groups of patients were Smac mRNA and Survivin mRNA were detected by using PCR method,immunohistochemical SP method of Smac and Survivin in specimens of table detect.Gastric ulcer patients were treated by triple therapy,and the apoptosis index was detected by TUNEL.Results Smac in N group(++) and (+++) in the expression accounted for 82.5％ was higher than that in Y group accounted for 47.5％,Survivin in group N (++) and (+++) in the expression accounted for 15.0％ was significantly lower than Y group accounted for 35.0％;And Smac mRNA in the N group relative expression the amount was significantly higher than that of Y group,while the expression of Survivin mRNA in the N group were significantly lower than Y group;N group the apoptosis index of the triple therapy after treatment than before treatment significantly decreased,the difference was statistically significant(P<0.05).Conclusion The clinical application of Smac and Survivin can be used as an auxiliary diagnostic index for the diagnosis of precancerous lesions in patients with gastric ulcer.Patients with gastric ulcer without precancerous lesion treated by triple therapy which can effectively control the apoptosis index of patients,improve the survival rate of patients.

Treatment of paclitaxel combined with oxaliplatinchemotherapy to the non-small cell lung cancer mouse model / 基础医学与临床

Objective To investigate the therapeutic effect of paclitaxel plus oxaliplatin chemotherapy to the transplanted non-small cell lung cancer of nude mice and the effect to the apoptosis protein expression of PDCD5 and XIAP with mice model.Methods A tumor-bearing mice were randomly divided into blank group, normal saline group, oxaliplatin group, paclitaxel group, paclitaxel plus oxaliplatin group.The gene expression of PDCD5 and XIAP was assayed by real-time quantitative PCR(q-PCR).The apoptosis related PDCD5 and XIAP protein were detected by Western blot.Finally, the tumor weight of each group was measured for statistical analysis.ResultsThe mRNA expression of PDCD5 was highest and the gene expression of XIAP was lowest in paclitaxel plus oxaliplatin group(P<0.01).The expression of PDCD5 protein was highest and the expression of XIAP protein was lowest in paclitaxel plus oxaliplatin group (P<0.01).Finally, compare the tumor weight of each group, paclitaxel plus oxaliplatin group has the least mass(P<0.01).Conclusions Paclitaxel plus oxaliplatin group chemotherapy significantly increases PDCD5 expression and reduce XIAP expression.Meanwhile, paclitaxel plus oxaliplatin chemotherapy can significantly reduce the tumor weight of happened non-small cell lung cancer.

Expression significance of cellular inhibitor of apoptosis proteins 2 in patients with hepatitis B related HCC / 重庆医学

Objective To investigate the significance of cellular inhibitor of apoptosis proteins 2 (cIAP2) expression in the patients with hepatitis B and non-hepatitis B related hepatocellular carcinoma (HCC).Methods The medical record data and tissue samples in the patients with HCC resection operation were collected.Expression of cIAP2 in HCC cancer lesion,adjacent tissues and cancer-distant tissues was detected by immunohistochemical staining and Western blotting.Results In the cancer lesion,paracancerous tissues and cancer-distant tissues of the two groups,the cIAP2 expression amount was decreased in turn.But in the non-hepatitis B related HCC group,the cIAP2 expression in the cancer-distant tissues was significantly lower than that in the HCC cancer lesion and paracancerous tissues,while in the hepatitis B related HCC group,the cIAP2 expression amounts had no significant difference between the caner-distant tissues and paracancerous tissues,while lower than that in the cancer lesion.Conclusion cIAP2 is one of important mechanisms causing hepatic B related HCC and can serve as a therapeutic target point for inhibiting HCC development and eliminating hepatitis B virus.

IAP-1 gene silencing enhanced the radiosensitivity of liver cancer SMMC-7721 cells / 中华肝胆外科杂志

Objective To explore the effect of cellular inhibitor of apoptosis protein1 (cIAP-1) gene on the radiosensitivity of SMMC-7721 cells.Methods We silenced cIAP-1 expressions by the shRNA technology,and then we detected the changes of cell proliferation,cell cycle and cell apoptosis by CCK8 as-say,Western blot,qRT-PCR and flow cytometry after the radiotherapy.Results The cell proliferation rate of liver cancer SMMC-7721 cells at different radiation doses of 1 Gy,4 Gy,7 Gy and 10 Gy was detected.Comparing with control group (pGCsi-H1-control),the cell proliferation in cIAP-1 silencing group (pGCsiH1-shRNA) was significantly reduced at various radiation doses,and the effect was dose-dependent (P ＜ 0.05).G1/G0 phase arrest was observed after radiation (P ＜0.01),and the proportion of cells in S phase was significantly reduced compared with control (P ＜ 0.01).Compared with control group,G1/G0 phase arrest was detected (P ＜ 0.05),and the percentage of cell apoptosis was increased significantly in cIAP-1 silencing group (P ＜ 0.05).Conclusion cIAP-1 silencing can enhance the radiosensitivity of liver cancer cells,and inhibit cell proliferation by promoting the anti-tumor effect of radiation.