Survivin and cIAP-2 expression were distinctive in elderly groups with CRC compared to younger patients, which suggested age-related differences in CRC. Indeed, Bv6 was found to synergize with IFN- in the promotion of necroptosis in a TNF- independent manner [18]. FOIA The radiosensitizing activity of the SMAC-mimetic, Debio 1143, is TNF-mediated in head and neck squamous cell carcinoma. 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. The purpose is to have a forum in which general doubts about the processes of publication in the journal, experiences and other issues derived from the publication of papers are resolved. In parallel, different studies have demonstrated that ER stress can both induce and reduce the expression of IAPs. IAPs auto-ubiquitylate when Smac/DIABLO induces their RING domains E3 activity. Impact Factor 4.677 by WOS Ranking 2257 by WOS Apoptosis : an international journal on programmed cell death SJR, SJR Impact Factor and H Index H Index 115 SJR 1.318 Scopus Impact Factor 4.905 Visit the Nature Research journals metrics page for a description of these metrics. Cells | An Open Access Journal from MDPI The authors were therefore prevented from giving a more concrete opinion about the role of TNF- in TNBC. Hurwitz H.I., Smith D.C., Pitot H.C., Brill J.M., Chugh R., Rouits E., Rubin J., Strickler J., Vuagniaux G., Sorensen J.M. Adverse effects were evident for higher doses and comprised headaches, nausea, vomiting and Bells palsy in 2 of the 3 patients receiving the highest dose. [56] and El-Mesallamy et al. Therefore, compared to the classical methods targeting viral . Although XIAP showed strong correlations with c-IAP1 and c-IAP2 and the latter two with each other, no correlation with survivin was observed. Birinapant (TL32711), a bivalent SMAC mimetic, targets TRAF2-associated cIAPs, abrogates TNF-induced NF-B activation, and is active in patient-derived xenograft models. However, there is evidence pointing towards a possible relationship between ER stress and Smac mimetics effectivity that cannot be ignored by future evaluations. However, a third study showed no correlation between the levels of XIAP protein expression and survival was found [50]. Livin and survivin levels were recently analyzed in two AML subtypes, acute promyelocytic (APL) and non-promyelocytic (non-APL). Furthermore, the current state of combination therapy involving Smac mimetics with traditional agents as well as with immunotherapy, will be reviewed. [80], who observed XIAP, cIAP1, cIAP2 and survivin expression in breast cancer samples at diagnosis, its effect on survival could not be confirmed [80]. Internet Explorer). The Inhibitor of Apoptosis (IAP) family of proteins has emerged as a potential pharmacological target in cancer. Exploring mechanistic insight and molecular basis of cancer and related phenomena. Cancers 2022, 14, 1671 2 of 25 1. In addition to E3 ligase activity targeting other proteins for degradation, the three IAPs also share autodegradative capacity [34]. Although the stable response was observed in 19% of patients, no objective response was observed. For instance, LCL161 has been suggested to require the TNF- pathway and TNF- production to promote apoptosis [117]. [75] showed XIAP staining with immunocytochemistry in the cytoplasm of CRC cells [75]. Suppression of apoptosis in mammalian cells by NAIP and a related family of IAP genes. Oncogenesis is a peer-reviewed open access online journal that publishes articles exploring mechanistic insight and molecular basis of cancer and related phenomena. Evidence of Birinapants efficacy has been modest but promising. Lack of tumoral TNF- production and sensitivity was identified as a possible cause for the low efficacy obtained. Both direct and indirect activity on caspases or the modulation of survival pathways, such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-B), have been implicated in mediating its effects. Updated List of Journal Impact Factor 2022 ASTX660 antagonizes cIAP-1, ciap-2 and XIAP through binding to BIR3. However, due to higher discontinuation provoked by AEs in the TNF- negative TNBC patient group, lower efficacy observed could be attributed to either the consequent lower paclitaxel exposure or their TNF- status [111]. [87], suggested that the disagreement observed between different studies could have an origin in the subcellular localization of survivin [87]. Guoan et al. In addition, in some cancers, ER stress has been identified as responsible for the acquisition of resistance to chemotherapeutic agents. Alteration in structure, expression, or even epigenetic regulation of genes, such as TP53 or BCL2 and the caspase-family of genes (or their products) leading to a dysregulated apoptotic process, are classically involved in this hallmark of cancer [2]. Therefore, its use in combination with other therapies was proposed as a follow-up. Silke J., Vaux D.L. Ismail E.A.R., Mahmoud H.M., Tawfik L.M., Habashy D.M., Adly A.A.M., El-Sherif N.H., Abdelwahab M.A. Additionally, data obtained from mRNA levels must be assessed and compared to those of protein in both adult and child populations in order to validate these IAPs as prognostic factors. The use of viral vectors and the induction of parallel pathways have been considered. Oncogenesis (Oncogenesis) Moreover, a trial assessing its efficacy on advanced ovarian, fallopian tube and peritoneal cancer had to be canceled early due to lack of clinical benefit ({"type":"clinical-trial","attrs":{"text":"NCT01681368","term_id":"NCT01681368"}}NCT01681368). The AVPI fragment, the minimal fragment conserving Smacs inhibitory activity, has been systematically modified to optimize its pharmacological properties [103]. A sustained activation of PI3K/NF- B pathway is critical for the survival of chronic lymphocytic leukemia B cells. On the other hand, livin negative patients presented longer survivals but only in the APL group. Ma Y., Hendershot L.M. For topics on particular articles, maintain the dialogue through the usual channels with your editor. [76] described the Akt signaling pathway as an important cascade through which XIAP appeared to be upregulated in C-Met overexpressing CRC cells [76]. Endo K., Kohnoe S., Watanabe A., Tashiro H., Sakata H., Morita M., Kakeji Y., Maehara Y. [62], it becomes apparent that the tumor microenvironment might have a role in these differences [62]. The role of the unfolded protein response in tumour development: Friend or foe? 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. As caspase inhibitors, IAPs can reportedly either block substrate entry or add ubiquitin (Ub) chains on caspases targeting them for proteasomal degradation. [128], XIAP protein might be involved in RIP1 and RIP3 ubiquitylation in the necrosome but, instead of promoting it, they regulate it, since deletion of XIAP renders elevated RIP1 ubiquitylation [128]. The overexpression of apollon was correlated with an unfavorable prognosis in pediatric patients, a finding first observed by Sung et al. Different signals leading to NF-B formation combined with different dimer combinations account for the modulation of the different NF-B transcriptional programs. (2023) Editorial: Emerging researchers in frontiers in pharmacology: obstetric and pediatric pharmacology 2022. Apoptosis Impact Factor IF 2022|2021|2020 - BioxBio This way explain normal phenotypes in mice deficient for these proteins [20]. For example, this is the case with NSCLC, where paclitaxel only shows modest efficacy and data is limited [136]. Additionally, the maximum tolerated dose (MTD) was determined at 1800 mg when higher doses provoked symptoms of cytokine release syndrome (CRS) in 6% of the patients: vomiting, fatigue, nausea and anorexia. Collins R.J., Verschuer L.A., Harmon B.V., Prentice R.L., Pope J.H., Kerr J.F. This downregulation is also mediated by PERK, which halts global protein translation after activation, and the activation of ATF4. In fact, different IAPs seem to play important roles in the correct function of the immune system. J.P.-D. and A.M. revised the manuscript. Expression of cIAP-2 was higher in node-positive breast cancer, although cIAP-1 levels did not correlate with clinicopathological features of this malignancy. Spontaneous programmed death (apoptosis) of B-chronic lymphocytic leukaemia cells following their culture in vitro. We explored the dose-dependent anti-tumor response of melatonin against cervical cancer cell lines, HeLa (HPV-18 positive) and SiHa (HPV-16 positive). A phase I study on solid tumors revealed good tolerability but poor efficacy [110]. 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]. In 2007, Hess et al. Journal Information | Cell Death & Differentiation Yun Qian, Bo Tang, Hao . However, under physiological conditions, IAPs are not enough to evade apoptosis, since the accumulation of apoptotic signals rapidly decides the cells fate. In glioblastomas, livin is correlated with worse PFS and OS rates. [13], described the role of livin in cancer cell migration and invasion by means of the activation of Akt signaling and the induction of EMT in vitro and in vivo [13]. Netherlands [82], reported differential subcellular expressions in breast cancer samples when cytoplasmic XIAP was observed in all the studied cases but nuclear staining in only 43% [82]. This might be of particular interest in the context of TNF- non-responsive cancers. and F.A.-M. designed the work. Ibrahim L., Aladle D., Mansour A., Hammad A., Al Wakeel A.A., Abd El-Hameed S.A. Therefore, over time, more and more studies evaluating childhood malignancies as independent diseases have started to appear. During the last decades, the Unfolded Protein Response (UPR) to ER stress has been systematically studied and associated with cancer pathogenesis [131]. Lee K.-H., Lee S., Lee H.-M., Back S.-C., Cho S.-B., Lee J.-H. Inhibitors of apoptosis proteins expression and their prognostic significance in colorectal carcinoma. Smac mimetics are thus developed in an effort to decrease IAPs levels observed in cancers and other diseases in which their expression is dysregulated. However, and despite supporting evidence, in other cases, death promoted by administration of Smac mimetics is not dependent on TNF- or NF-kB. Tamm I., Richter S., Oltersdorf D., Creutzig U., Harbott J., Scholz F., Karawajew L., Ludwig W.-D., Wuchter C. High expression levels of x-linked inhibitor of apoptosis protein and survivin correlate with poor overall survival in childhood de novo acute myeloid leukemia. Xenograft models indicated similar results, where the combination therapy worked better than any of the two as single agents. Combination therapy of Smac mimetics with ICIs have provided good results in pre-clinical models. 1Research and Advances in Molecular and Cellular Immunology, Center of Biomedical Research, University of Granada, Armilla, 18016 Granada, Spain; moc.liamg@orartecireip, 2Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, 18071 Granada, Spain, 3Childrens Hospital of Eastern Ontario Research Institute, Ottawa, ON K1H 8L1, Canada; ac.no.oehc@eiznekcam, 4Instituto de Investigacin Biosanitaria IBS.GRANADA, Complejo Hospitalario Universitario de Granada, 18014 Granada, Spain, 5Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada, 6Institute of Nutrition and Food Technology Jos Mataix, Biomedical Research Center, University of Granada, Armilla, 18016 Granada, Spain, 7Department of Cell Biology, School of Sciences, University of Granada, 18071 Granada, Spain. Many molecular mechanisms can be involved in resistance to chemotherapeutics, amongst which the evasion of apoptosis is frequently observed. Altered molecular pathways documented in CRC have delineated a large number of potential biomarkers. Through this web page, researchers can check the impact factor, total citation, journal quartile and journal aim & scope. 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. Growing evidence indicates that CLL proliferative cells might be responsible for disease relapse after treatment, so any approach targeting said microenvironment could mean a complete clear out of malignant cells [66]. It is based on the idea that 'all citations are not created equal'. Universities and research institutions in Netherlands Flygare J.A., Beresini M., Budha N., Chan H., Chan I.T., Cheeti S., Cohen F., Deshayes K., Doerner K., Eckhardt S.G. Langdon C.G., Wiedemann N., Held M.A., Mamillapalli R., Iyidogan P., Theodosakis N., Platt J.T., Levy F., Vuagniaux G., Wang S. SMAC mimetic Debio 1143 synergizes with taxanes, topoisomerase inhibitors and bromodomain inhibitors to impede growth of lung adenocarcinoma cells. Additionally, a recent clinical trial is currently recruiting participants to evaluate ASTX660s safety and efficacy in patients with refractory or relapsing T-cell lymphoma ({"type":"clinical-trial","attrs":{"text":"NCT04362007","term_id":"NCT04362007"}}NCT04362007). Studies evaluating the role of different IAPs in AM have revealed heterogeneous patient profiles while analyses of IAPs expression have failed to provide strong evidence that establishes IAPs as potent individual prognostic markers. ISSN 2157-9024 (online). [63] found the co-expression of survivin and cIAP1to be a negative prognostic factor, since patients presenting it showed shorter OS [63]. [142], when PD-L1 expression seemed to inhibit TNF- production in cytotoxic lymphocytes, avoiding a possible paracrine interaction with tumoral cells and the subsequent TNF-mediated cell death [142]. Mak D.H., Manton C., Andreeff M., Carter B.Z. The inhibition of cIAPs alters NF-B pathways. oxidative stress (hsp60 and hsp70), apoptosis (hid, grim, and reaper), and DNA . Abstract for KLF2 reduces dexamethasone-induced injury to growth plate chondrocytes by inhibiting the Runx2-mediated PI3K/AKT and ERK . This research received no external funding. Guoan X., Xiaomin W., Hanning W., Kaiyun C., Hao L. Expression of X-linked inhibitor of apoptosis protein in human colorectal cancer and its correlation with prognosis. CLL is a heterogeneous disease characterized by the accumulation of monoclonal mature CD5+ B cells in lymphoid organs, bone marrow and peripheral blood. Takeuchi et al. 8600 Rockville Pike [81], observed an increase in XIAP expression in higher grades of ductal invasive breast carcinoma and ductal breast carcinoma in situ [81]. IAPs: Whats in a name? Similarly, Karasawa et al. Knockout experiments in mice suggested overlapping activities of both cIAP1 and cIAP2, with cIAP1 having more biological impact. Birinapant has been assayed with several chemotherapeutics due to its good tolerability. Smac, also known as DIABLO (Direct IAP Binding protein with Low pI), is a mitochondrial protein encoded in the nuclear genome. The NF-B canonical pathway is classically activated upon stimulation of TNFR1, IL-1E1, TLRs, BCR or TCR. 07 Nov 2022. Bertheloot D., Latz E., Franklin B.S.
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