Surprisingly, in vivo assessment of these same cell lines as xenotransplants showed their decreased growth. 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]. Along these lines, reduction of IAP levels can potentially re-sensitize cells to apoptosis. Pan S.T., Li Z.L., He Z.X., Qiu J.X., Zhou S.F. In spite of promising pre-clinical results, further clinical trials evaluating the anticancer activity of Smac mimetics/IAP antagonists as a monotherapy failed to provide a homogeneous pattern of response. In this regard, it should be noted that the evaluation of the Smac mimetic JP1202 on NSCLC cell line described TNF- independent pathways as being responsible for cell death induced by the treatment. 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. Recently developed Smac mimetics counteract IAP activity and show promise in the re-sensitization to apoptosis in cancer cells. Smac mimetics are thus developed in an effort to decrease IAPs levels observed in cancers and other diseases in which their expression is dysregulated. The users of Scimago Journal & Country Rank have the possibility to dialogue through comments linked to a specific journal. Moore A.S., Alonzo T.A., Gerbing R.B., Lange B.J., Heerema N.A., Franklin J., Raimondi S.C., Hirsch B.A., Gamis A.S., Meshinchi S. BIRC5 (survivin) splice variant expression correlates with refractory disease and poor outcome in pediatric acute myeloid leukemia: A report from the Childrens Oncology Group. Inclusion in an NLM database does not imply endorsement of, or agreement with, For instance, it can polyubiquitylate caspase-9, when ectopically expressed in vitro [37,38,39]. National Library of Medicine Srinivasula S.M., Ashwell J.D. The impact score (IS) 2021 of Apoptosis : an international journal on programmed cell death is 4.91, which is computed in 2022 as per its definition. Yang Q.-H., Du C. Smac/DIABLO selectively reduces the levels of c-IAP1 and c-IAP2 but not that of XIAP and livin in HeLa cells. An apoptosis-inhibiting baculovirus gene with a zinc finger-like motif. Sl. Hanahan D., Weinberg R.A. Hallmarks of cancer: The next generation. Cancers showing no response to, or no expression of, TNF-, have been observed to be resistant to Smac mimetics treatment in some circumstances. [68] achieved sensitization of CLL cells to chemotherapy by modulating the expression of XIAP, among other antiapoptotic proteins, with microRNAs shown to be downregulated in p53 wild-type patients from a Chinese cohort [68]. [126], showed that the effect of LCL161 on vincristine-induced neuroblastoma apoptosis was independent of NF-B and TNF- [126]. XIAP, cIAP-1 and cIAP-2 have RING (Really Interesting New Gene) domains. 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]. [83], did not find a correlation with DFS or OS [83]. 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. High levels of apoptotic cells overwhelm the proper recognition and removal system of these cells. Researchers assessed this compound effectiveness as a single agent in more than 100 human cancer cell lines, although only 15% of the cell lines were responsive to the treatment, MDA-MB-231 breast and SK-OV-3 ovarian cancer lines demonstrated high levels of cell death. However, there is evidence pointing towards a possible relationship between ER stress and Smac mimetics effectivity that cannot be ignored by future evaluations. All types of documents are considered, including citable and non citable documents. Collins R.J., Verschuer L.A., Harmon B.V., Prentice R.L., Pope J.H., Kerr J.F. The human IAP family is composed of eight members: NAIP, cIAP1, cIAP2, XIAP, Survivin, Bruce/Apollon, ML-IAP/Livin and ILP-2, although XIAP, cIAP1 and cIAP2 are the most extensively studied [7,8,9,10]. Xenograft models indicated similar results, where the combination therapy worked better than any of the two as single agents. Many cancers demonstrate evasion of apoptosis enhancing cell survival [1]. However, in contrast to acute leukemias, which develop much faster, it is harder to cure. Abbreviations: NF-B (nuclear factor kappa-light-chain-enhancer of activated B cells), TNF- (tumor necrosis factor-), RIPK (Receptor-interacting serine/threonine-protein kinase), TRADD (TNF Receptor Associated Death Domain), TRAF (TNF Receptor Associated Factor), cIAP (cellular-Inhibitor of Apoptosis Protein), LUBAC (Linear Ubiquitination Assembly Complex), IKK (IB Kinase), NIK (NF-B-inducing kinase), Ub (ubiquitin). On the other hand, an interesting thing was found in triple-negative breast cancer with a specific gene signature characterized by positive expression of TNF- [111]. Traditional cancer chemotherapies are frequently based on the induction of apoptosis in cancerous cells. Tchoghandjian A., Soubran A., Tabouret E., Colin C., Denicola E., Jiguet-Jiglaire C., El-Battari A., Villard C., Baeza-Kallee N., Figarella-Branger D. Inhibitor of apoptosis protein expression in glioblastomas and their in vitro and in vivo targeting by SMAC mimetic GDC-0152. Survival was improved and correlated with XIAP downregulation [141]. Cells | An Open Access Journal from MDPI Positive expression of survivin have significant association with worse OS, High expression is observed in high-invasive breast cancer cells compared to, Lower expression was observed compared to healthy tissue. Abstract for KLF2 reduces dexamethasone-induced injury to growth plate chondrocytes by inhibiting the Runx2-mediated PI3K/AKT and ERK . Furthermore, it demonstrated efficacy in mice models of carboplatin-resistant ovarian cancer in combination with carboplatin, which is currently the first line of treatment, despite eventual relapse. Roy N., Mahadevan M.S., McLean M., Shutter G., Yaraghi Z., Farahani R., Baird S., Besner-Johnston A., Lefebvre C., Kang X. - Article ID 9078475. Prognostic value of survivin expression in breast cancer patients: A meta-analysis. Chen K.-F., Lin J.-P., Shiau C.-W., Tai W.-T., Liu C.-Y., Yu H.-C., Chen P.-J., Cheng A.-L. Inhibition of Bcl-2 improves effect of LCL161, a SMAC mimetic, in hepatocellular carcinoma cells. This interesting association with immune activity will be further explored below. Consequently, combination approaches have been evaluated. 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. Table 1 summarizes the IAPs and cancer. Working Session on Improving Predictive Modeling of Mycotoxin Risk for Africa Held at the 3rd ASM2022 on 7 September 2022, in Stellenbosch, South . American Journal of Biochemistry and Biotechnology, 18 (3), 308-318. https://doi.org/10.3844/ajbbsp.2022.308.318 GDC-0512, LCL16, SM-406/AT-406, Birinapant or ASTX660 stand out as promising compounds in current clinical evaluation. Hao Y., Sekine K., Kawabata A., Nakamura H., Ishioka T., Ohata H., Katayama R., Hashimoto C., Zhang X., Noda T. Apollon ubiquitinates SMAC and caspase-9, and has an essential cytoprotection function. Toxins | An Open Access Journal from MDPI However, there is limited information regarding the contribution of both mechanisms to actual increases in IAP expression in specific cancer types. For instance, NSCLC cell lines were sensitized to chemotherapy by the SM JP1201 even when TNF- expression was not high [125]. (2023) Editorial: Emerging researchers in frontiers in pharmacology: obstetric and pediatric pharmacology 2022. The location of both cIAP-1 and cIAP-2 was assessed by Ponnelle et al. LncRNA RPSAP52 promotes cell proliferation and inhibits cell apoptosis It is based on the idea that 'all citations are not created equal'. We explored the dose-dependent anti-tumor response of melatonin against cervical cancer cell lines, HeLa (HPV-18 positive) and SiHa (HPV-16 positive). Given that in some cancers, Smac is downregulated along with its inherent IAP inhibitory structural properties, peptides mimicking its activity have been developed. Further down the pathway, IAPs have critical roles on caspase inhibition, setting an inhibitory threshold for these enzymes. cIAP2 supports viability of mice lacking cIAP1 and XIAP. Li L., Thomas R.M., Suzuki H., De Brabander J.K., Wang X., Harran P.G. Different signals leading to NF-B formation combined with different dimer combinations account for the modulation of the different NF-B transcriptional programs. Initial testing (stage 1) of LCL161, a SMAC mimetic, by the Pediatric Preclinical Testing Program. Zhang et al. [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]. Together, a constitutive ER stress that promotes upregulation of IAPs could, at least in part, explain the loss of apoptotic capability. Furthermore, the current state of combination therapy involving Smac mimetics with traditional agents as well as with immunotherapy, will be reviewed. The P681R mutation in the spike protein, which is . It measures the scientific influence of the average article in a journal, it expresses how central to the global scientific discussion an average article of the journal is. The site is secure. The structure of the BIR3 domain of cIAP1 in complex with the N-terminal peptides of SMAC and caspase-9. 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 Bardia A., Parton M., Kmmel S., Estvez L.G., Huang C.-S., Corts J., Ruiz-Borrego M., Telli M.L., Martin-Martorell P., Lpez R. Paclitaxel with inhibitor of apoptosis antagonist, LCL161, for localized triple-negative breast cancer, prospectively stratified by gene signature in a biomarker-driven neoadjuvant trial. Vince J.E., Wong W.W.-L., Khan N., Feltham R., Chau D., Ahmed A.U., Benetatos C.A., Chunduru S.K., Condon S.M., McKinlay M. IAP antagonists target cIAP1 to induce TNF-dependent apoptosis. Da Huang (Rhei Radix et . On the other hand, second mitochondrial-derived activator of caspases (Smac), the second mitochondrial-derived activator of caspases, also known as DIABLO, is a mitochondrial protein released to the cytosol upon apoptotic stimuli that antagonizes IAPs endogenously, leading to the activation of caspases and the promotion of programmed cell death in normal conditions [17]. Evolution of the total number of citations and journal's self-citations received by a journal's published documents during the three previous years. IKK then phosphorylates NF-kB1, targeting it for proteasomal degradation. GDC-0152, is described as a pan-IAP antagonist because it has high affinities for cIAP-1, c-IAP2, XIAP-BIR3 and livin [104]. Journal Citation Score*:1.29 Updated List of Journal Impact Factor 2022 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. Instead, NAIP displays a nucleotide-binding oligomerization domain (NOD), which, together with the BIR domains, allows its participation in the inflammasome assembly in cooperation with NLRC4. In terms of IAPs, overexpression in cancerous tissues has been generally observed in comparison to normal tissues. On the other hand, livin negative patients presented longer survivals but only in the APL group. The authors were therefore prevented from giving a more concrete opinion about the role of TNF- in TNBC. Upregulation of survivin in G2/M cells and inhibition of caspase 9 activity enhances resistance in staurosporine-induced apoptosis. Background: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is known to be associated with poor prognosis after cardiovascular events. Apoptosis-inducing factor (AIF) is a mitochondrial flavoprotein which mediates staurosporine (STS) - induced cell death. Likewise, models of multiple myeloma and mammary tumors obtained very high percentages for durable care rates [145]. Abbreviations, ER stress, endoplasmic reticulum stress; IAPs, inhibitor apoptosis proteins; UPR, unfolded protein response. Apoptosis: A Review of Programmed Cell Death - PMC Purroy N., Abrisqueta P., Carabia J., Carpio C., Calpe E., Palacio C., Castellv J., Crespo M., Bosch F. Targeting the proliferative and chemoresistant compartment in chronic lymphocytic leukemia by inhibiting survivin protein. Apoptosis : an international journal on programmed cell death 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. [74] in contrast to what was observed for XIAP, while Takeuchi et al. Together with the causal SMN gene, NAIP was proposed to cause or contribute to SMA pathogenesis, which included dysregulated motor neuron apoptosis [24]. 31 Dec 2022. Promising results were observed when evaluated in combination with paclitaxel; although toxicity was highlighted as an important and limiting factor in the therapeutical scope. Overall, this supports the evaluation of combination therapy in cancers, in which no therapeutic approach has provided positive results on its own. Frontiers | Apoptosis in megakaryocytes: Safeguard and threat for Abbreviations: TNF- (Tumor Necrosis Factor-), TNFR (Tumor Necrosis Factor Receptor), cIAP (cellular- Inhibitor of Apoptosis Protein), RIPK (Receptor-interacting serine/threonine-protein kinase), FADD (Fas-associated protein with death domain), TRAF (TNF receptor associated factor), NIK (NF-B-inducing kinase), NF-B (nuclear factor kappa-light-chain-enhancer of activated B cells). Research Paper LncRNA RPSAP52 promotes cell proliferation and inhibits cell apoptosis via modulating miR-665/STAT3 in gastric cancer Chao He , Yuanyuan Liu , Jinhou Li , Xiao Zheng , Jianwei Liang , Gang Cui & show all Pages 8699-8711 | Received 07 Jan 2022, Accepted 14 Mar 2022, Published online: 24 Mar 2022 Download citation A phase I/II trial of Debio in combination with cisplatin in patients with locally advanced squamous cell carcinoma of the head and neck provided encouraging results including high OS, CR and PFS rates [140]. 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. Name Thank you for visiting nature.com. At the same time, the lack of said cIAPs would allow the NF-B alternative pathway to produce further TNF-, which would feed an autocrine cycle leading to cell death (Figure 3). 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. Gaither A., Porter D., Yao Y., Borawski J., Yang G., Donovan J., Sage D., Slisz J., Tran M., Straub C. A Smac mimetic rescue screen reveals roles for inhibitor of apoptosis proteins in tumor necrosis factor- signaling. 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. Consistent with its cell cycle-dependent expression, survivin is translocated from the cytoplasm to the nucleus during the G2/M phase. Modulation of molecules such as tumor necrosis factor- (TNF-) present in the tumor microenvironment have been suggested to contribute to putative therapeutic efficacy of IAP inhibition, although published results do not show this consistently underlining the complex interaction between IAPs and cancer. Weissman A.M. Indeed, the avoidance of programmed cell death is a characteristic hallmark in cancers. E3 ligase activity from IAPs RING domain allow the addition of Ub residues onto proteins involved in these signaling cascades. In the early 2000s, two studies found a correlation between lower levels of XIAP protein with longer survival [48,49]. Livin and survivin levels were recently analyzed in two AML subtypes, acute promyelocytic (APL) and non-promyelocytic (non-APL). Ubiquitin protein ligase activity of IAPs and their degradation in proteasomes in response to apoptotic stimuli. As a library, NLM provides access to scientific literature. Antiacne and Anti-Inflammatory Effects of Phenolic Compounds from Quercus acutissima Carruth. 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. Again, such differences between in vivo and in vitro results were attributed to higher expression of TNF in the tumors microenvironment [112]. In the meantime, to ensure continued support, we are displaying the site without styles [71] who found that, although the proteins were present in both nucleus and cytoplasm, cIAP-1 was most frequently expressed in the nucleus (85%) and cIAP-2 in the cytoplasm (82%) in CRC samples [71]. 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. Cekay M.J., Roesler S., Frank T., Knuth A.-K., Eckhardt I., Fulda S. Smac mimetics and type II interferon synergistically induce necroptosis in various cancer cell lines. Matzinger O., Viertl D., Tsoutsou P., Kadi L., Rigotti S., Zanna C., Wiedemann N., Vozenin M.-C., Vuagniaux G., Bourhis J. Schematic representation of the IAP family members structure. Translational and posttranslational regulation of XIAP by eIF2 and ATF4 promotes ER stressinduced cell death during the unfolded protein response. It might be worth studying the nature of Smac mimetics resistance. Zhang Q., Lenardo M.J., Baltimore D. 30 years of NF-B: A blossoming of relevance to human pathobiology. Apoptosis : an international journal on programmed cell death Greer R.M., Peyton M., Larsen J.E., Girard L., Xie Y., Gazdar A.F., Harran P., Wang L., Brekken R.A., Wang X. SMAC Mimetic (JP1201) Sensitizes NonSmall Cell Lung Cancers to Multiple Chemotherapy Agents in an IAP-Dependent but TNF-Independent Manner. While these findings agree with those of Makhlouf et al. Apoptosis (Qualify) Latest Impact Factor IF 2021-2022 | Trend Binding to both the catalytic pocket and the IBM results in an effective dock and inhibition of the effector caspases. Weisberg E., Ray A., Barrett R., Nelson E., Christie A., Porter D., Straub C., Zawel L., Daley J.F., Lazo-Kallanian S. Smac mimetics: Implications for enhancement of targeted therapies in leukemia. Although XIAP showed strong correlations with c-IAP1 and c-IAP2 and the latter two with each other, no correlation with survivin was observed. However, Smac/DIABLO is a large protein that can have significant off target effects when delivered to patients at clinical levels. [51], analyzed pro- and anti-apoptotic gene expression in AML patients, documenting a three-gene, (including BIRC3 (c-IAP2), expression signature associated with poor overall survival (OS) [51]. BV6 and Birinapant are both capable of inducing TNF-induced cell death. Finally, other pathways leading to apoptosis, such as that derived from endoplasmic reticulum (ER) stress induction, appear to be, in part, modulated by the presence of IAPs too. 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 . Additionally, Grzybowska et al. [83], found higher cytoplasmic expression compared to normal tissues, while nuclear expression showed no difference [83]. Very limited antitumor activity was hinted at, rather than observed, through the degradation of cIAP-1 [114]. [60] and later confirmed by Ismail et al. In 2007, Hess et al. Although it is mostly a curable disease, when detected at early stages, when symptoms arise, cancer may already have advanced. ASTX660, a novel non-peptidomimetic antagonist of cIAP1/2 and XIAP, potently induces TNF-dependent apoptosis in cancer cell lines and inhibits tumor growth. Consecutive BIR domains are suggested to increase affinity to their ligand and their binding properties are conserved in those molecules that harbor more than one [27]. However, the underlying molecular mechanism is not known. In several cancer types, members of this protein family are overexpressed while their natural antagonist (Smac) appears to be downregulated, contributing to the acquisition of resistance to traditional therapy. Although it is synthesized as a much longer precursor, in its mature form, it is composed of 184 amino acids. According to Eckelman et al. Furthermore, as in other malignancies, Smac/DIABLO protein was observed to be lowered in breast cancer samples compared to control [89]. Mita M.M., LoRusso P.M., Papadopoulos K.P., Gordon M.S., Mita A.C., Ferraldeschi R., Keer H., Oganesian A., Su X.Y., Jueliger S. A phase I study of ASTX660, an antagonist of inhibitors of apoptosis proteins, in adults with advanced cancers or lymphoma. It is not only the inhibition of apoptosis, but also how these proteins interact with immune cells, that create a complex and fairly opaque mode of action and therefore make it difficult to predict Smac mimetics therapy outcomes. 5-year Impact Factor* (2021):7.915 Ma Y., Hendershot L.M. Therefore, in cells are deficient for cIAPs, the classical NF-B pathway is proapoptotic, halting the expression of target genes, including IAPs or inflammatory cytokines. Recently, some investigations have reinforced the fact that these cell death pathways (apoptosis, pyroptosis, and necroptosis) could interact with each other [21]. Melatonin induces apoptosis and cell cycle arrest in For instance, LCL161 has been suggested to require the TNF- pathway and TNF- production to promote apoptosis [117]. Childhood AML was recently defined as a significantly different disease from adult AML at the genetic level [54]. Bertheloot D., Latz E., Franklin B.S. As for their anti-apoptotic activities, survivin and livin contain one BIR domain that interacts with both caspase-3 and -7, regarding the former, and with caspase-3, -7 and -9, respectively [15]. Crystallogr. Lower Smac/DIABLO protein levels also correlated with progressive disease. The set of journals have been ranked according to their SJR and divided into four equal groups, four quartiles. XIAP and survivin expression was observed to be increased in advanced cancer. Pluta et al., [80] evaluated XIAP, cIAP1, cIAP2 and survivin expression in breast cancer samples at diagnosis. SJR:2.497. For example, immune checkpoint inhibitors (ICIs) have already succeeded in stimulating T cell responses against tumors. 8600 Rockville Pike It would not be surprising to find that Smac mimetics resistance is not, at least in part, promoted by ER stress induction of IAPs overexpression, such that previously established doses of Smac mimetics might not be sufficient to overcome inhibition of apoptosis. Clancy-Thompson E., Ali L., Bruck P.T., Exley M.A., Blumberg R.S., Dranoff G., Dougan M., Dougan S.K. official website and that any information you provide is encrypted [76] described the Akt signaling pathway as an important cascade through which XIAP appeared to be upregulated in C-Met overexpressing CRC cells [76]. Expression and prognostic significance of IAP-family genes in human cancers and myeloid leukemias. Caspase 9 inhibition takes place when the BIR3 domain binds to the homodimerization surface of the cysteine protease, interfering with the production of a catalytic pocket [31]. Structural and biochemical basis of apoptotic activation by Smac/DIABLO. Oncogenesis seeks to encompass the breadth of the molecular biology of malignant change, and topics of particular interest include: The 2022journal citation metrics forOncogenesisare as follows: 2-year Impact Factor* (2021):6.524 External citations are calculated by subtracting the number of self-citations from the total number of citations received by the journals documents. Allensworth J.L., Aird K.M., Aldrich A.J., Batinic-Haberle I., Devi G.R. Debio 1143 is capable of synergizing with taxanes, among other agents, against lung adenocarcinoma cells, even reducing the tumor volume in mice xenografts [139]. Netherlands 1. The gene for neuronal apoptosis inhibitory protein is partially deleted in individuals with spinal muscular atrophy. In addition to direct function as caspase inhibition, the IAP family modulates apoptotic events modulating the signaling cascade of NF-B pathways leading to cell survival. [87], suggested that the disagreement observed between different studies could have an origin in the subcellular localization of survivin [87]. SMAC-Mimetic BV-6 Sensitizes Therapeutic Agents-Induced Apoptosis in AML Cells. 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]. Pluta P., Cebula-Obrzut B., Ehemann V., Pluta A., Wierzbowska A., Piekarski J., Bilski A., Nejc D., Kordek R., Robak T. Correlation of Smac/DIABLO protein expression with the clinico-pathological features of breast cancer patients. Total Citations in 2020 and 2021 = 500. To obtain A Review of the Current Impact of Inhibitors of Apoptosis Proteins and 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. A later study, by Pluta et al. High expression of livin has been associated with highly-invasive breast cancer cells in opposition to a lower expression in non-invasive cells [13]. Licensee MDPI, Basel, Switzerland. Furthermore, recent evidence demonstrating new immune-modulatory functions of IAPs, in both innate and adaptive immunity, opens new doors in terms of therapeutic opportunities. Journal Information | Oncogene - Nature Also, a significant correlation between higher levels of XIAP and tumor differentiation, venous invasion and Dukes staging was found. 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. In this regard, the process can be regulated both directly on caspases, through the blockage of substrate entry and ubiquitin-dependent mechanisms, or in an indirect manner through the regulation of nuclear factor kappa-light-chain-enhancer of activated B cell (NF-B) canonical and non-canonical signaling cascades [12]. In the absence of IAPs, complex II is formed. Oncogenesis is a peer-reviewed open access online journal that publishes articles exploring mechanistic insight and molecular basis of cancer and related phenomena. Ultimately, a picture of multifactorial IAP overexpression and acquisition of resistance emerges. P.C. Tanaka K., Iwamoto S., Gon G., Nohara T., Iwamoto M., Tanigawa N. Expression of survivin and its relationship to loss of apoptosis in breast carcinomas. Debio 1143/AT-406 was firstly described in 2011 shown to mimic AVPIs binding to BIR3. 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. [80], observed associations between shorter PFS and XIAP protein expression [80,82]. In addition, possible reasons for their modest effects, shall be presented incorporating new findings which may contribute to understanding of this phenomenon.
apoptosis impact factor 2022