Song Z., Yao X., Wu M. Direct interaction between survivin and Smac/DIABLO is essential for the anti-apoptotic activity of survivin during taxol-induced apoptosis. Cheung H., St Jean M., Beug S., Lejmi-Mrad R., LaCasse E., Baird S., Stojdl D., Screaton R., Korneluk R. SMG1 and NIK regulate apoptosis induced by Smac mimetic compounds. MDA-MB231 breast cancer xenograft mouse models benefited from antitumor activity in vivo when GDC-0152 was administered orally as a single agent. Tamm I., Kornblau S.M., Segall H., Krajewski S., Welsh K., Kitada S., Scudiero D.A., Tudor G., Qui Y.H., Monks A. Molecular mechanisms for tumour resistance to chemotherapy. The .gov means its official. Langemann D., Trochimiuk M., Appl B., Hundsdoerfer P., Reinshagen K., Eschenburg G. Sensitization of neuroblastoma for vincristine-induced apoptosis by Smac mimetic LCL161 is attended by G2 cell cycle arrest but is independent of NFB, RIP1 and TNF-. [126], showed that the effect of LCL161 on vincristine-induced neuroblastoma apoptosis was independent of NF-B and TNF- [126]. According to Benetatos et al. However, some cancers can be both responsive and non-responsive to Smac mimetics, irrespective of their TNF- status. Altogether, available data suggest a strong link between IAP-mediated apoptosis inhibition and ER stress induction, although it remains unclear whether the UPR apoptosis program contributes or not (and to what extent) to cell death promoted by Smac mimetics treatment [135]. However, upon substrate binding after recognition of CD40L by CD40, the ligand-receptor complex recruits TRAF3-TRAF2-cIAP for ubiquitylation of TRAF3. Therefore, over time, more and more studies evaluating childhood malignancies as independent diseases have started to appear. We aimed to assess the dynamic changes in TRAIL levels and the relation of TRAIL level to stroke severity, its impact on the short-term outcomes, and its association with markers of cardiac . Anti-Inflamm. Li F., Yin X., Luo X., Li H.-Y., Su X., Wang X.-Y., Chen L., Zheng K., Ren G.-S. Livin promotes progression of breast cancer through induction of epithelialmesenchymal transition and activation of AKT signaling. However, and despite supporting evidence, in other cases, death promoted by administration of Smac mimetics is not dependent on TNF- or NF-kB. The site is secure. IKK then phosphorylates NF-kB1, targeting it for proteasomal degradation. Also, different levels of IAPs expression in distinct patient groups have hinted at a possible involvement in treatment response and have been suggested to possess great potential as prognostic markers. This effect was ascribed to the presence of cytotoxic T cells, and decrease in immunosuppressive CD4+ T cells, and seemed to involve IFNs and TNF- pathways. Therefore, compared to the classical methods targeting viral . Interestingly, XIAP expression was comparable in normal and cancerous tissues in both young and older patients [70]. Clancy-Thompson E., Ali L., Bruck P.T., Exley M.A., Blumberg R.S., Dranoff G., Dougan M., Dougan S.K. In addition to BIR domains, this function as an inhibitor of apoptosis is supported by the presence of various other domains which are not conserved among the different family members. [83], did not find a correlation with DFS or OS [83]. Importantly, and given the recent evidence of IAPs role in the immune system, different immunotherapeutic approaches have been suggested to potentially benefit from Smac mimetics co-treatment. 5-year Impact Factor* (2021):7.915 Pyroptosis is characterized by diminution of plasma membrane integrity and induced by activation of so-called inflammasome sensors, such as the Nod-like receptor (NLR) family, the Pyrin receptor, and DNA receptor Absent in Melanoma 2 [21,22], and necroptosis, which is a complementary type of regulated cell death, mimicking features of necrosis and apoptosis [23]. Houghton P.J., Kang M.H., Reynolds C.P., Morton C.L., Kolb E.A., Gorlick R., Keir S.T., Carol H., Lock R., Maris J.M. Rebucci M., Michiels C. Molecular aspects of cancer cell resistance to chemotherapy. 31 Dec 2022. During the last decades, the Unfolded Protein Response (UPR) to ER stress has been systematically studied and associated with cancer pathogenesis [131]. Shin S., Sung B.-J., Cho Y.-S., Kim H.-J., Ha N.-C., Hwang J.-I., Chung C.-W., Jung Y.-K., Oh B.-H. An anti-apoptotic protein human survivin is a direct inhibitor of caspase-3 and-7. Regulation of inflammasome activity. Karasawa H., Miura K., Fujibuchi W., Ishida K., Kaneko N., Kinouchi M., Okabe M., Ando T., Murata Y., Sasaki H. Down-regulation of cIAP2 enhances 5-FU sensitivity through the apoptotic pathway in human colon cancer cells. You are using a browser version with limited support for CSS. Kearney C.J., Lalaoui N., Freeman A.J., Ramsbottom K.M., Silke J., Oliaro J. PD-L1 and IAPs co-operate to protect tumors from cytotoxic lymphocyte-derived TNF. Only three of the members (RelA, RelB and c-Rel) are produced in their mature forms, while the other two (NF-kB1 and NF-kB2) require a proteolytic cleavage of the precursors C-terminal portion. Dysregulated apoptosis is often observed in other pathological conditions, such as neurodegenerative disorders (Alzheimers Disease, motor system disorders, stroke and many others) or autoimmune diseases (type I diabetes, multiple sclerosis, rheumatoid arthritis and more) [3,4]. Beug S.T., Beauregard C.E., Healy C., Sanda T., St-Jean M., Chabot J., Walker D.E., Mohan A., Earl N., Lun X. Smac mimetics synergize with immune checkpoint inhibitors to promote tumour immunity against glioblastoma. It aims to stimulate research on the basis of mechanisms of apoptosis and on its role in various human disease processes including: cancer, autoimmune disease, viral infection, AIDS, cardiovascular disease, neurodegenerative disorders, osteoporosis and ageing. In glioblastomas, livin is correlated with worse PFS and OS rates. Cytoplasmic localization correlated to HER-2 expression status, and mutant-type (P53) status, and was considered to be a prognostic biomarker for basal-like breast cancer. Therefore, its use in combination with other therapies was proposed as a follow-up. Impact Factor of the Journal in 2022 = 500/100 = 5. Allensworth J.L., Aird K.M., Aldrich A.J., Batinic-Haberle I., Devi G.R. Indeed, the avoidance of programmed cell death is a characteristic hallmark in cancers. Mattson M.P. Dimeric Smac/DIABLO interacts with BIR2 and BIR3 IAP domains, ultimately leading to proteolytic cleavage and activation of procaspase-3 and procaspase-9, and the induction of caspase-3 enzymatic activity [97]. Introduction. [50], and Pluta et al. Chandele A., Prasad V., Jagtap J.C., Shukla R., Shastry P.R. Heard K.N., Bertrand M.J., Barker P.A. Evolution of the number of published documents. Yun Qian, Bo Tang, Hao . Careers, Unable to load your collection due to an error. Review of the Current Impact of Inhibitors of Apoptosis Proteins and Their Repression in Cancer. In turn, given CLL cells fail to engage apoptotic programs in vivo although not in vitro, as observed by Collin et al. Two kinds of BIR-containing protein-inhibitors of apoptosis, or required for mitosis. Despite the classical definition of CLL as a non-proliferative disease, some studies have paid attention to the proliferative nature of CLL cells found in pseudo-follicles formed in lymphoid organs [64]. Further down the pathway, IAPs have critical roles on caspase inhibition, setting an inhibitory threshold for these enzymes. Survivin and cyclin E2 genes expression in a cohort of Egyptian acute leukemia patients: Clinical importance and future prospects. Apoptosis has since been recognized and accepted as a distinctive and important mode of "programmed" cell death, which involves the genetically determined elimination of cells. National Library of Medicine Initial testing (stage 1) of LCL161, a SMAC mimetic, by the Pediatric Preclinical Testing Program. Abstract for KLF2 reduces dexamethasone-induced injury to growth plate chondrocytes by inhibiting the Runx2-mediated PI3K/AKT and ERK . 2-year Impact Factor* (2021): 12.073 5-year Impact Factor . Caspase-3 and -7 are blocked, as the linker region between the BIR1 and BIR2 domains of XIAP bind to the catalytic site of the cysteine proteases, preventing substrate entry. The nomenclature, length, and domains of the different proteins are shown. Nuclear Factor Erythroid-2-Related Factor 2 (Nrf2) Signalling Pathway Once ubiquitylated, these components recruit LUBAC, TAK1-TAB2-TAB3 and IKK-IKK-IKK. The impact factor is calculated by dividing the number of times the articles are cited in the last two years by the total number of publications in those two years. Wei Y., Fan T., Yu M. Inhibitor of apoptosis proteins and apoptosis. All types of documents are considered, including citable and non citable documents. Although it is synthesized as a much longer precursor, in its mature form, it is composed of 184 amino acids. However, there is limited information regarding the contribution of both mechanisms to actual increases in IAP expression in specific cancer types. NF-B (p50p65) translocates to the nucleus and transcribes survival and inflammation-related genes. Evolution of the total number of citations and journal's self-citations received by a journal's published documents during the three previous years. In this work, IAP structure, function, and role in cancer will be addressed, as well as anticancer therapies based on their inhibition to promote apoptosis. Schematic representation of the IAP family members structure. In 2007, Hess et al. Cancers showing no response to, or no expression of, TNF-, have been observed to be resistant to Smac mimetics treatment in some circumstances. This, again, pointed to the well-established complex nature of IAPs biology, emphasized by the fact that the inhibition of apoptosis seems to be only one of this class of proteins many functions. For instance, NSCLC cell lines were sensitized to chemotherapy by the SM JP1201 even when TNF- expression was not high [125]. C-IAP1 and cIAP2 have been found to be overexpressed in osteosarcoma, and XIAPs expression levels were high in esophageal, ovarian and pancreatic cancers [92,93]. Melatonin, a neurohormone has been documented as a promising therapeutic molecule for cervical cancer. The authors declare no conflict of interest. X-Linked inhibitor of apoptosis protein expression level in colorectal cancer is regulated by hepatocyte growth factor/C-met pathway via Akt signaling. Table of Contents 2022 | Evidence-Based Complementary and Pluta A., Wierzbowska A., Cebula-Obrzut B., Pluta P., Stpka K., Szmigielska-Kapon A., Grzybowska-Izydorczyk O., Czemerska M., Smolewski P., Wrzesien-Kus A. Prognostic value of inhibitor of apoptosis protein family expression in patients with acute myeloid leukemia. IAPs participate in the inhibition of apoptosis through several mechanisms allowing their involvement in both extrinsic and intrinsic apoptotic programs. Yang Y., Fang S., Jensen J.P., Weissman A.M., Ashwell J.D. ASTX660 antagonizes cIAP-1, ciap-2 and XIAP through binding to BIR3. . Apoptosis (Qualify) Latest Impact Factor IF 2021-2022| Trend, Prediction, Ranking & Analysis - Academic Accelerator Forum Toolbox Journal Matcher Manuscript Generator Research Trend Ranking Conference Ranking Country Ranking Institution Ranking Journal Ranking Scholar Ranking Database Conference Database Here, the development and effectiveness of the most clinically relevant Smac mimetics during pre-clinical experimentation will be described, as well as the results that preliminary investigation in the clinical contexts. In this regard, later experiments showed viability in XIAP and cIAP1 null mice, with a marked upregulation of cIAP2 observed in double knockouts [33]. Total Number of Publications in 2020 and 2021 = 100. Accessibility Universities and research institutions in Netherlands Lecis D., De Cesare M., Perego P., Conti A., Corna E., Drago C., Seneci P., Walczak H., Colombo M., Delia D. Smac mimetics induce inflammation and necrotic tumour cell death by modulating macrophage activity. The development of compounds that mimic the action of Smac showed promise in the re-sensitization of the cell suicide defense mechanism in cancer cells, particularly in combination with other treatments. These results pointed out the potential benefits of using ICIs together with Smac mimetics as a way of increasing TNF-production, while forcing the TNFR pathway towards a caspase-8 dependent death. Indeed, according to Yabal et al. Song J., Su H., Zhou Y.Y., Guo L.L. As a result, new therapies targeting IAPs expression have been designed to re-sensitize cancerous cells to apoptosis. As outlined above, cIAPs have important roles in the regulation of the signaling cascade following the binding of TNF- to its receptor. It aims to stimulate both research on the basis of mechanisms of apoptosis and on its role in various human disease processes including: cancer, autoimmune disease, viral infection, AIDS, cardiovascular disease, neurodegenerative disorders, osteoporosis and ageing. The two main signaling cascades that activate NF-B can be classified either as classical (canonical) or alternative (non-canonical) pathways. On their own, immunotherapy approaches can show impressive efficacy. Journal Information | Oncogene - Nature Clinical significance of Smac/DIABLO expression in colorectal cancer. The structure of the BIR3 domain of cIAP1 in complex with the N-terminal peptides of SMAC and caspase-9. This study showed a significant relationship with the PI3K pathway, p-AKT, Ki-67 and PARP. In the early 2000s, two studies found a correlation between lower levels of XIAP protein with longer survival [48,49]. Cuni S., Perez-Aciego P., Perez-Chacon G., Vargas J., Sanchez A., Martin-Saavedra F., Ballester S., Garcia-Marco J., Jorda J., Durantez A. It was assessed in leukemia and hepatocellular carcinoma cell lines inducing cell death. Along these lines, reduction of IAP levels can potentially re-sensitize cells to apoptosis. P.C. cIAP2 supports viability of mice lacking cIAP1 and XIAP. Severe adverse events included anemia, and increased lipase and lymphopenia, which were observed, but only in seven patients. Fulda S., Wick W., Weller M., Debatin K.-M. Smac agonists sensitize for Apo2L/TRAIL-or anticancer drug-induced apoptosis and induce regression of malignant glioma in vivo. Similar results have been obtained when assessing BV-6s and Debbio 1143s efficacies [119,120]. It induces cIAP1 degradation and binds to XIAP and cIAP-2. ISSN 2157-9024 (online). The anti-cancer effect of . Doron B., Abdelhamed S., Butler J.T., Hashmi S.K., Horton T.M., Kurre P. Transmissible ER stress reconfigures the AML bone marrow compartment. This downregulation is also mediated by PERK, which halts global protein translation after activation, and the activation of ATF4. Finally, not only apoptosis but also necrosis is promoted as part of Smac mimetics treatment, unpacking new layers of IAPs relationship with tumoral development/progression. The 2022 journal metrics* for Oncogene are as follows: 2-year Impact Factor* (2021): 8.756 5-year Impact Factor* (2021): 9.273 Immediacy index*: 1.405 Eigenfactor score*: 0.05014 J.P.-D. and A.M. revised the manuscript. Le Tourneau C., Tao Y., Gomez-Roca C., Cristina V., Borcoman E., Deutsch E., Bahleda R., Calugaru V., Modesto A., Rouits E. Phase I Trial of Debio 1143, an Antagonist of Inhibitor of Apoptosis Proteins, Combined with Cisplatin Chemoradiotherapy in Patients with Locally Advanced Squamous Cell Carcinoma of the Head and Neck. However, Smac/DIABLO is a large protein that can have significant off target effects when delivered to patients at clinical levels. Despite these barrier, promising advances are being made. [72] observed higher cIAP-2 expression in stage II CRC with lymph node metastasis [72]. [76] described the Akt signaling pathway as an important cascade through which XIAP appeared to be upregulated in C-Met overexpressing CRC cells [76]. Cai Q., Sun H., Peng Y., Lu J., Nikolovska-Coleska Z., McEachern D., Liu L., Qiu S., Yang C.-Y., Miller R. A potent and orally active antagonist (SM-406/AT-406) of multiple inhibitor of apoptosis proteins (IAPs) in clinical development for cancer treatment. Expression and prognostic significance of IAP-family genes in human cancers and myeloid leukemias. Additionally, Hu et al. Phase I dose-escalation study of LCL161, an oral inhibitor of apoptosis proteins inhibitor, in patients with advanced solid tumors. The latest evidence supporting the role of IAPs in some death-resistant cancers and cancer progression are reviewed next. Grzybowska-Izydorczyk O., Cebula B., Robak T., Smolewski P. Expression and prognostic significance of the inhibitor of apoptosis protein (IAP) family and its antagonists in chronic lymphocytic leukaemia. However, given that current screening methods present specificity, sensitivity and cost limitations, make it has proven difficult to rapidly advance towards personalized and targeted therapies. GDC-0152, is described as a pan-IAP antagonist because it has high affinities for cIAP-1, c-IAP2, XIAP-BIR3 and livin [104]. Smac mimetics are thus developed in an effort to decrease IAPs levels observed in cancers and other diseases in which their expression is dysregulated. Bruce/Apollon can modulate caspase-3, caspase-7 and caspase-9. Hrdinka M., Yabal M. Inhibitor of apoptosis proteins in human health and disease. In turn, IAPs set an inhibitory threshold that caspases must overcome to result in cell death [30]. Dhuriya Y.K., Sharma D. Necroptosis: A regulated inflammatory mode of cell death. The Inhibitor of Apoptosis (IAP) family possesses the ability to inhibit programmed cell death through different mechanisms; additionally, some of its members have emerged as important regulators of the immune response. Apoptosis : an international journal on programmed cell death INKT cells can be stimulated to produce cytokines upon Smac mimetics stimulation [146]. Although XIAP showed strong correlations with c-IAP1 and c-IAP2 and the latter two with each other, no correlation with survivin was observed. Hussain A.R., Siraj A.K., Ahmed M., Bu R., Pratheeshkumar P., Alrashed A.M., Qadri Z., Ajarim D., Al-Dayel F., Beg S. XIAP over-expression is an independent poor prognostic marker in Middle Eastern breast cancer and can be targeted to induce efficient apoptosis. In addition, ER and progesterone receptor-negative hormonal status was observed in to correlate with survivin level [85]. Similarly, Karasawa et al. In order to become active, different members combine to form dimers. It was, Higher expression of XIAP, cIAP1, cIAP2 and survivin was observed in, Modulation of XIAP expression sensitized CLL cells to chemotherapy in, Co-expression of survivin and cIAP1 was related with shorter OS and, Inhibition of survivin sensitized CLL cells to cytotoxic agents and induced. Enhanced fusogenicity and pathogenicity of SARS-CoV-2 Delta P681R Endo T., Abe S., Seidlar H., Nagaoka S., Takemura T., Utsuyama M., Kitagawa M., Hirokawa K. Expression of IAP family proteins in colon cancers from patients with different age groups. Their experiments led to the determination of survivin expression as a potential prognostic factor for ductal breast carcinoma. Taxanes as first-line therapy for advanced non-small cell lung cancer: A systematic review and practice guideline. Upon induction of the intrinsic apoptotic pathway, mitochondria release Smac from their intermembrane space into the cytosol along with cytochrome C [17,94,95]. APOPTOSIS -Impact factor 2022 - 2023 - Journal Impact Score Bartke T., Pohl C., Pyrowolakis G., Jentsch S. Dual role of BRUCE as an antiapoptotic IAP and a chimeric E2/E3 ubiquitin ligase. Firestone B., Conway C., Yang G., Gao H., Porter D., Slisz J., He D., Mosher R., Monahan J., Straub C. Abstract B27: Correlation between TNF and LCL161 anti-tumor activity in patient derived xenograft models of human cancer. Pluta P., Jeziorski A., Cebula-Obrzut A., Wierzbowska A., Piekarski J., Smolewski P. Expression of IAP family proteins and its clinical importance in breast cancer patients. Interestingly, lymph node metastases with low levels of cIAP-2 and TUCAN (CARD8) showed a larger percentage of five-year survival in a 2005 study of IAPs expression [73]. Huang Y., Rich R.L., Myszka D.G., Wu H. Requirement of both the second and third BIR domains for the relief of X-linked inhibitor of apoptosis protein (XIAP)-mediated caspase inhibition by Smac. Chem. [83], found higher cytoplasmic expression compared to normal tissues, while nuclear expression showed no difference [83]. Chesi M., Mirza N.N., Garbitt V.M., Sharik M.E., Dueck A.C., Asmann Y.W., Akhmetzyanova I., Kosiorek H.E., Calcinotto A., Riggs D.L. Oncogenesis (Oncogenesis) Sect. Journal Information | Oncogenesis - Nature Mak D.H., Manton C., Andreeff M., Carter B.Z. Hanahan D., Weinberg R.A. Hallmarks of cancer: The next generation. Apoptosis : an international journal on programmed cell death Federal government websites often end in .gov or .mil. Survival was improved and correlated with XIAP downregulation [141]. Cervical cancer is the most prevalent cancer in females. It might be worth studying the nature of Smac mimetics resistance. No. Apoptotic/necrotic death induced by Smac mimetics and TNF- crucially depends on RIPK1 because RIPK1 deficient MEFs, and cancer cells in which RIPK1 is depleted, are resistant to TNFR1 killing following treatment with Smac mimetics [46,123].
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