PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 32123008-7 2020 Furthermore, protein stability and cell viability assays using two distinct proteasome inhibitor anticancer drugs, the 20S proteasome inhibitor bortezomib and the ubiquitin-activating enzyme E1 inhibitor TAK-243, show that the upregulation of the NRF3-POMP axis leads to ubiquitin-independent proteolysis of p53 and Rb and to impaired sensitivity to bortezomib but not TAK-243. Bortezomib 350-360 tumor protein p53 Homo sapiens 308-311 34025442-8 2021 Results: In the initial small molecular inhibitor screening in KIT-independent GIST62, we found that bortezomib-mediated inhibition of the ubiquitin-proteasome machinery showed anti-proliferative effects of KIT-independent GIST cells via downregulation of cyclin D1 and induction of p53 and p21. Bortezomib 101-111 tumor protein p53 Homo sapiens 283-286 32798402-0 2020 [Clinical Efficacy and Prognosis of Double-Hit Multiple Myeloma Patients with Deletion P53 Treated with Regimen Based on Bortezomib]. Bortezomib 121-131 tumor protein p53 Homo sapiens 87-90 32798402-1 2020 OBJECTIVE: To investigate the clinical efficacy and prognosis of double-hit multiple myeloma patients with deletion P53 treated with regimen based on bortezomib. Bortezomib 150-160 tumor protein p53 Homo sapiens 116-119 32123008-7 2020 Furthermore, protein stability and cell viability assays using two distinct proteasome inhibitor anticancer drugs, the 20S proteasome inhibitor bortezomib and the ubiquitin-activating enzyme E1 inhibitor TAK-243, show that the upregulation of the NRF3-POMP axis leads to ubiquitin-independent proteolysis of p53 and Rb and to impaired sensitivity to bortezomib but not TAK-243. Bortezomib 144-154 tumor protein p53 Homo sapiens 308-311 32446382-8 2020 These results suggest that co-treatment with bortezomib and kuanoniamine C is a novel therapeutic strategy for the treatment of osteosarcoma that enhances bortezomib-dependent cell death by the downregulation of GRP78, and this combination selectively targets the major cell population of osteosarcoma, which expresses wild-type p53. Bortezomib 45-55 tumor protein p53 Homo sapiens 329-332 29569972-6 2018 Moreover, inhibition TRIM28 expression in B-NHL cells enhanced the sensibility to Bortezomib by regulating p53-mediated apoptosis pathway. Bortezomib 82-92 tumor protein p53 Homo sapiens 107-110 33163985-2 2020 Methods: From our predictive synthetic lethality model used in SL-BioDP, we inferred TP53 mutation lead to potential synergistic drug combination of Bortezomib and Vorinostat. Bortezomib 149-159 tumor protein p53 Homo sapiens 85-89 32235770-8 2020 BTZ inhibited proliferation and induced apoptosis through the accumulation of p53 in three human Myc-ATRT cell lines (PDX-derived tumor cell line Re1-P6, BT-12 and CHLA-266). Bortezomib 0-3 tumor protein p53 Homo sapiens 78-81 31482012-2 2019 In addition to doxorubicin, our results here indicated that camptothecin and bortezomib, which are a topoisomerase 1 poison and a 26 S proteasome inhibitor, respectively, could also induce apoptosis in a p53-dependent manner in prostate cancer. Bortezomib 77-87 tumor protein p53 Homo sapiens 204-207 31482012-5 2019 In contrast, p53-mediated apoptosis from bortezomib-induced stress is transcription-dependent. Bortezomib 41-51 tumor protein p53 Homo sapiens 13-16 31482012-7 2019 We then investigated the p53 ratio of nucleus to cytosol corresponding to low and high dose doxorubicin, camptothecin, or bortezomib treatment. Bortezomib 122-132 tumor protein p53 Homo sapiens 25-28 30936194-1 2019 KRAS G12D-mutant/p53-deficient non-small-cell lung cancer (NSCLC) models are dependent on the NF-kappaB pathway that can be down-regulated by the proteasome inhibitor bortezomib. Bortezomib 167-177 tumor protein p53 Homo sapiens 17-20 30554133-0 2019 In HPV-Positive HNSCC Cells, Functional Restoration of the p53/p21 Pathway by Proteasome Inhibitor Bortezomib Does Not Affect Radio- or Chemosensitivity. Bortezomib 99-109 tumor protein p53 Homo sapiens 59-62 30554133-6 2019 In HPV+ cells, BZM also restored the radiation-induced p53/p21 transactivation. Bortezomib 15-18 tumor protein p53 Homo sapiens 55-58 30365089-3 2019 The mechanistic studies confirmed that the enhancement of Snail1 expression in bortezomib-resistant MMCs directly upregulated transcription of the intracellular MDR1 gene to immediately develop multiple drug resistance mechanisms and inhibited P53 protein expression through the Snail1/hsa-miRNA-22-3p/P53 pathway to inhibit tumor cell apoptosis. Bortezomib 79-89 tumor protein p53 Homo sapiens 244-247 30365089-3 2019 The mechanistic studies confirmed that the enhancement of Snail1 expression in bortezomib-resistant MMCs directly upregulated transcription of the intracellular MDR1 gene to immediately develop multiple drug resistance mechanisms and inhibited P53 protein expression through the Snail1/hsa-miRNA-22-3p/P53 pathway to inhibit tumor cell apoptosis. Bortezomib 79-89 tumor protein p53 Homo sapiens 302-305 29269566-8 2018 Further analysis demonstrated that treatment with Bortezomib sensitized TC cells to Vemurafenib via mitochondrial dysregulation and apoptosis of TC cells, as evidenced by the increase in the expression of p53, Noxa protein, the loss of mitochondrial membrane potential, cytochrome c release and Poly (ADP-ribose) polymerase cleavage. Bortezomib 50-60 tumor protein p53 Homo sapiens 205-208 30214587-5 2018 c-Jun N-terminal kinase/p38-mitogen-activated protein kinase-induced endoplasmic reticulum (ER) stress through serial exposure to celecoxib and bortezomib may have induced the intracellular Ca2+ release, leading to the generation of autophagosomes in p53-expressing HCT-116 cells. Bortezomib 144-154 tumor protein p53 Homo sapiens 251-254 30214587-7 2018 Although p53-/- HCT-116 cells were less sensitive to sequential treatment with celecoxib and bortezomib, co-localization of autophagosomes was detected in the absence of CCAAT-enhancer-binding protein homologous protein expression. Bortezomib 93-103 tumor protein p53 Homo sapiens 9-12 28798402-0 2017 Nutlin-3 enhances the bortezomib sensitivity of p53-defective cancer cells by inducing paraptosis. Bortezomib 22-32 tumor protein p53 Homo sapiens 48-51 28798402-3 2017 In this study, we show that treatment of various p53-defective bortezomib-resistant solid tumor cells with bortezomib plus nutlin-3 induces paraptosis, which is a cell death mode accompanied by dilation of the endoplasmic reticulum (ER) and mitochondria. Bortezomib 63-73 tumor protein p53 Homo sapiens 49-52 28798402-3 2017 In this study, we show that treatment of various p53-defective bortezomib-resistant solid tumor cells with bortezomib plus nutlin-3 induces paraptosis, which is a cell death mode accompanied by dilation of the endoplasmic reticulum (ER) and mitochondria. Bortezomib 107-117 tumor protein p53 Homo sapiens 49-52 27626308-11 2016 Interestingly, GSK2830371 sensitized MCL cells to bortezomib and doxorubicin in p53 wild-type and mutant cells; p38 signaling appeared to be involved in the GSK2830371/bortezomib lethality. Bortezomib 50-60 tumor protein p53 Homo sapiens 80-83 28710427-5 2017 Transient resistance to bortezomib treatment was observed in p53-null cells that was later accompanied by an increase in levels and nuclear translocation of TAp73, an isoform of the p53-homologue p73, as well as induction of apoptosis. Bortezomib 24-34 tumor protein p53 Homo sapiens 61-64 28710427-5 2017 Transient resistance to bortezomib treatment was observed in p53-null cells that was later accompanied by an increase in levels and nuclear translocation of TAp73, an isoform of the p53-homologue p73, as well as induction of apoptosis. Bortezomib 24-34 tumor protein p53 Homo sapiens 182-185 28710427-8 2017 Thus, our results clearly demonstrated that TAp73 served as a substitute for p53 in bortezomib-induced apoptosis in p53-deficient or mutated cells, implicating that TAp73 could be a potential therapeutic target for treatment of CRCs, in particular those lacking functional p53. Bortezomib 84-94 tumor protein p53 Homo sapiens 116-119 28710427-8 2017 Thus, our results clearly demonstrated that TAp73 served as a substitute for p53 in bortezomib-induced apoptosis in p53-deficient or mutated cells, implicating that TAp73 could be a potential therapeutic target for treatment of CRCs, in particular those lacking functional p53. Bortezomib 84-94 tumor protein p53 Homo sapiens 116-119 28679691-0 2017 Metastatic triple-negative breast cancer patient with TP53 tumor mutation experienced 11 months progression-free survival on bortezomib monotherapy without adverse events after ending standard treatments with grade 3 adverse events. Bortezomib 125-135 tumor protein p53 Homo sapiens 54-58 28679691-10 2017 The success of bortezomib may be explained by the previously reported up-regulation of caspase-mediated apoptosis, which is p53-independent. Bortezomib 15-25 tumor protein p53 Homo sapiens 124-127 27903750-3 2017 Inhibition of CRM1, the nuclear export carrier protein, hampered protein export and synergistically enhanced the cytotoxic action of bortezomib on colon cancer cells containing wild-type p53, which underwent G2-M cell-cycle block and apoptosis. Bortezomib 133-143 tumor protein p53 Homo sapiens 187-190 27903750-5 2017 Moreover, knockdown of p53 significantly reduced the synergistic cytotoxic action of bortezomib and KPT330 on p53+/+ HCT116 cells. Bortezomib 85-95 tumor protein p53 Homo sapiens 23-26 27903750-5 2017 Moreover, knockdown of p53 significantly reduced the synergistic cytotoxic action of bortezomib and KPT330 on p53+/+ HCT116 cells. Bortezomib 85-95 tumor protein p53 Homo sapiens 110-113 27903750-7 2017 These results indicate that nuclear p53 is a major mediator in the synergistic antitumor effect of bortezomib and KPT330, and provides a rationale for the use of proteasome inhibitor together with nuclear export blocker in the treatment of colorectal cancer. Bortezomib 99-109 tumor protein p53 Homo sapiens 36-39 27822577-0 2016 Combined bortezomib-based chemotherapy and p53 gene therapy using hollow mesoporous silica nanospheres for p53 mutant non-small cell lung cancer treatment. Bortezomib 9-19 tumor protein p53 Homo sapiens 107-110 27822577-2 2016 Then we found that the tumor-suppressing effect of BTZ or HMSNs-BTZ was compromised in p53 null/mutant NSCLC. Bortezomib 51-54 tumor protein p53 Homo sapiens 87-90 27822577-5 2016 Here, HMSN-based co-delivery of BTZ and the tumor-suppressor gene p53 was developed for p53 signal impaired NSCLC therapy. Bortezomib 32-35 tumor protein p53 Homo sapiens 66-69 27822577-5 2016 Here, HMSN-based co-delivery of BTZ and the tumor-suppressor gene p53 was developed for p53 signal impaired NSCLC therapy. Bortezomib 32-35 tumor protein p53 Homo sapiens 88-91 27822577-7 2016 Live/dead staining assay for treated H1299 cells exhibited wider distribution, and higher dead staining was prominent in the HMSNs-PEI-BTZ-p53 group when compared to that of the HMSNs-BTZ group with equivalent BTZ concentration, which was consistent with accumulated p53 expression. Bortezomib 135-138 tumor protein p53 Homo sapiens 139-142 27822577-7 2016 Live/dead staining assay for treated H1299 cells exhibited wider distribution, and higher dead staining was prominent in the HMSNs-PEI-BTZ-p53 group when compared to that of the HMSNs-BTZ group with equivalent BTZ concentration, which was consistent with accumulated p53 expression. Bortezomib 135-138 tumor protein p53 Homo sapiens 267-270 27822577-9 2016 Western blotting and real time PCR results showed that several p53 downstream genes responded strongly and synergistically to BTZ function and p53 restored expression (accumulation of p21 and bax, activation of caspase 3, down-regulation of Bcl-2, etc.). Bortezomib 126-129 tumor protein p53 Homo sapiens 63-66 27626308-11 2016 Interestingly, GSK2830371 sensitized MCL cells to bortezomib and doxorubicin in p53 wild-type and mutant cells; p38 signaling appeared to be involved in the GSK2830371/bortezomib lethality. Bortezomib 168-178 tumor protein p53 Homo sapiens 80-83 26354682-0 2015 Hypoxia Promotes Synergy between Mitomycin C and Bortezomib through a Coordinated Process of Bcl-xL Phosphorylation and Mitochondrial Translocation of p53. Bortezomib 49-59 tumor protein p53 Homo sapiens 151-154 27123085-7 2016 These results suggest that the 26S proteasome inhibitor bortezomib is more potent, compared with irinotecan and etoposide, in the androgen-insensitive and tumor protein p53-null cell line PC-3. Bortezomib 56-66 tumor protein p53 Homo sapiens 169-172 24632713-3 2014 The present results demonstrate that GO-203 and BTZ synergistically downregulate expression of the p53-inducible regulator of glycolysis and apoptosis (TIGAR), which promotes shunting of glucose-6-phosphate into the pentose phosphate pathway to generate reduced glutathione (GSH). Bortezomib 48-51 tumor protein p53 Homo sapiens 99-102 26378933-4 2015 In vitro analysis revealed a higher resistance to bortezomib possibly due to an altered gene expression profile caused by del(8)(p21) including genes such as TRAIL-R4, CCDC25, RHOBTB2, PTK2B, SCARA3, MYC, BCL2 and TP53. Bortezomib 50-60 tumor protein p53 Homo sapiens 214-218 25530422-6 2015 In the present study, we demonstrate that the proteasome inhibitor Bortezomib strongly inhibits ERalpha and HER2/neu expression, increases expression of cyclin-dependent kinase inhibitors, inhibits expression of multiple genes associated with poor prognosis in ERalpha+ breast cancer patients and induces cell death in ER+ breast cancer cells in both the presence and absence of functional p53. Bortezomib 67-77 tumor protein p53 Homo sapiens 390-393 25530422-7 2015 Although Bortezomib increased the levels of p53 and increased the expression of pro-apoptotic target genes in ERalpha+ breast cancer cells harboring wild-type p53, Bortezomib also exerts anti-tumoral effects on ERalpha+ breast cancer cells through suppression of ERalpha expression and inhibition of PI3K/Akt/mammalian target of rapamycin (mTOR) and ERK signaling independently of functional p53. Bortezomib 9-19 tumor protein p53 Homo sapiens 44-47 26544558-8 2015 Mature miR-3151 level and p53 protein level were detected after HHT or Bortezomib treatment. Bortezomib 71-81 tumor protein p53 Homo sapiens 26-29 24125776-7 2014 Finally, the tumor-suppressing effect of HMSNs-BTZ was enhanced in the presence of wild-type p53 signaling, suggesting a potential enhancement in clinical efficacy with combined p53 gene therapy and BTZ-based chemotherapy. Bortezomib 47-50 tumor protein p53 Homo sapiens 93-96 24485799-4 2014 In this study, we investigate whether combined treatment with romidepsin and bortezomib would induce apoptosis in A549 NSCLC cells by activating cell cycle arrest, enhanced generation of p21 and p53, down-regulation of matrix metalloproteinases (MMPs) 2,9 also altering the acetylation status of histone proteins. Bortezomib 77-87 tumor protein p53 Homo sapiens 195-198 24485799-5 2014 Our data show that combination of romidepsin and bortezomib caused cell cycle arrest at Sub G0-G1 transition, up-regulation of cell cycle protein p21 and tumour suppressor protein p53. Bortezomib 49-59 tumor protein p53 Homo sapiens 180-183 24380881-4 2014 BTZ-treated HTLA-230 cells down-regulated p53 and up-regulated p21, favoring cell survival. Bortezomib 0-3 tumor protein p53 Homo sapiens 42-45 24380881-5 2014 The inhibition of HO-1 activity obtained by Zinc (II) protoprophyrin IX (ZnPPIX) was able to significantly increase the pro-apoptotic effect of BTZ in a p53- and p21-independent way. Bortezomib 144-147 tumor protein p53 Homo sapiens 153-156 24125776-7 2014 Finally, the tumor-suppressing effect of HMSNs-BTZ was enhanced in the presence of wild-type p53 signaling, suggesting a potential enhancement in clinical efficacy with combined p53 gene therapy and BTZ-based chemotherapy. Bortezomib 47-50 tumor protein p53 Homo sapiens 178-181 23635777-6 2013 Btz treatment led to caspase activation and induced DNA damage, as evidenced by the accumulation of phosphorylated gammaH2AX and p53. Bortezomib 0-3 tumor protein p53 Homo sapiens 129-132 23635777-7 2013 The addition of SAHA to Btz treatment was synergistic, as SAHA induced early acetylation of p53 and reduced interaction with its negative regulator MDM2, augmenting the effects of Btz. Bortezomib 24-27 tumor protein p53 Homo sapiens 92-95 23357978-0 2013 Synergistic activity of bortezomib and HDACi in preclinical models of B-cell precursor acute lymphoblastic leukemia via modulation of p53, PI3K/AKT, and NF-kappaB. Bortezomib 24-34 tumor protein p53 Homo sapiens 134-137 23064281-7 2013 In addition, sequential or concomitant treatment of bortezomib and cisplatin stimulated the expression of p53, hScrib and p21 and the stimulation was markedly influenced by the order of drugs in HeLa cells. Bortezomib 52-62 tumor protein p53 Homo sapiens 118-121 23421999-6 2013 Here, we demonstrate that siRNAs targeting the E6/E7 RNA, or treatment with the proteasome inhibitor bortezomib, resulted in upregulation of functional p53 and p53 gene targets in three HPV-positive HNSCC cell lines, but not in HPV-negative HNSCC cells. Bortezomib 101-111 tumor protein p53 Homo sapiens 152-155 23421999-6 2013 Here, we demonstrate that siRNAs targeting the E6/E7 RNA, or treatment with the proteasome inhibitor bortezomib, resulted in upregulation of functional p53 and p53 gene targets in three HPV-positive HNSCC cell lines, but not in HPV-negative HNSCC cells. Bortezomib 101-111 tumor protein p53 Homo sapiens 160-163 23421999-7 2013 Apoptosis induced by E6/E7 siRNA in HPV-positive cells was found to be dependent on p53, while bortezomib-induced cell death was modestly p53-dependent. Bortezomib 95-105 tumor protein p53 Homo sapiens 138-141 22964432-4 2012 We investigated the effects of bortezomib using a panel of six cancer cell lines with variable status of ERalpha or p53 and found that bortezomib inhibited the growth of all cell lines in the same concentration range irrespective of the ERalpha expression or the mutational status of p53. Bortezomib 135-145 tumor protein p53 Homo sapiens 116-119 22964432-4 2012 We investigated the effects of bortezomib using a panel of six cancer cell lines with variable status of ERalpha or p53 and found that bortezomib inhibited the growth of all cell lines in the same concentration range irrespective of the ERalpha expression or the mutational status of p53. Bortezomib 135-145 tumor protein p53 Homo sapiens 284-287 22324515-7 2012 Bad, p53, p21 and p27 were downregulated by neuropeptides in PC-3, and these effects were reversed with the addition of bortezomib. Bortezomib 120-130 tumor protein p53 Homo sapiens 5-8 23226303-8 2012 Mechanistic studies of apoptotic pathways indicated that bortezomib induced activation of p53 and Bax, as well as cleavage of caspases and poly-ADP-ribose polymerase (PARP) in exposed chondrocytes. Bortezomib 57-67 tumor protein p53 Homo sapiens 90-93 22559167-7 2012 The effects of rapamycin and/or bortezomib on the mRNA expression levels of p53, p27, p21 and Bcl-2 family in HCCLM3 cells were evaluated by RT-PCR. Bortezomib 32-42 tumor protein p53 Homo sapiens 76-79 21297663-6 2011 As a result, in the presence of Myc, miR-34a inhibited p53-dependent bortezomib-induced apoptosis as efficiently as anti-p53 small interfering RNA. Bortezomib 69-79 tumor protein p53 Homo sapiens 55-58 21532991-4 2011 Here we show that siRNA-mediated silencing of p53 is sufficient to completely abrogate hypersensitivity not only to Cisplatin but also to non-genotoxic inducers of p53 such as the Mdm2 antagonist Nutlin-3 and the proteasome inhibitor Bortezomib. Bortezomib 234-244 tumor protein p53 Homo sapiens 46-49 21459798-7 2011 Knockdown of Bid, Noxa, or p53 significantly delays the kinetic of bortezomib- and TRAIL-induced apoptosis, whereas it does not confer long-term protection. Bortezomib 67-77 tumor protein p53 Homo sapiens 27-30 21454483-9 2011 Furthermore, we show that the MDM2 inhibitor Nutlin cooperates with the proteasome inhibitor Bortezomib by stimulating p53 DNA binding and transcriptional activity, providing a rationale for combination therapy using proteasome and MDM2 inhibitors. Bortezomib 93-103 tumor protein p53 Homo sapiens 119-122 21459798-5 2011 In addition, bortezomib increases expression of p53 and Noxa. Bortezomib 13-23 tumor protein p53 Homo sapiens 48-51 21139584-8 2011 Treatment with a combination of GUT-70 and bortezomib or doxorubicin had synergistic antiproliferative effects in MCL cells that were independent of p53 status. Bortezomib 43-53 tumor protein p53 Homo sapiens 149-152 20850924-3 2010 In the bortezomib sensitive wild-type TP53 MCL cells, the Nutlin-3/bortezomib combination caused G0/G1 cell cycle arrest followed by the increase in apoptosis induction. Bortezomib 67-77 tumor protein p53 Homo sapiens 38-42 21224072-4 2011 We found that well-known proteasome inhibitors such as MG132 and bortezomib, as well as the recently discovered proteasome inhibitor thiostrepton, induced p53-independent apoptosis in human cancer cell lines that correlated with p53-independent induction of proapoptotic Noxa but not Puma protein. Bortezomib 65-75 tumor protein p53 Homo sapiens 155-158 21224072-4 2011 We found that well-known proteasome inhibitors such as MG132 and bortezomib, as well as the recently discovered proteasome inhibitor thiostrepton, induced p53-independent apoptosis in human cancer cell lines that correlated with p53-independent induction of proapoptotic Noxa but not Puma protein. Bortezomib 65-75 tumor protein p53 Homo sapiens 229-232 21273177-2 2011 In preclinical non-small-cell lung cancer (NSCLC) models, p53-dependent growth arrest after bortezomib treatment resulted in reduced cytotoxicity if bortezomib preceded docetaxel. Bortezomib 92-102 tumor protein p53 Homo sapiens 58-61 21273177-2 2011 In preclinical non-small-cell lung cancer (NSCLC) models, p53-dependent growth arrest after bortezomib treatment resulted in reduced cytotoxicity if bortezomib preceded docetaxel. Bortezomib 149-159 tumor protein p53 Homo sapiens 58-61 20850924-0 2010 MDM2 antagonist Nutlin-3 enhances bortezomib-mediated mitochondrial apoptosis in TP53-mutated mantle cell lymphoma. Bortezomib 34-44 tumor protein p53 Homo sapiens 81-85 20006625-10 2010 Results of FAK promoter activity and ChIP assays in A549 and H1299 cells indicated that bortezomib suppressed FAK activity through a p53-independent pathway. Bortezomib 88-98 tumor protein p53 Homo sapiens 133-136 20850924-2 2010 In the mutant TP53 MCL cells which are intrinsically resistant to bortezomib, the combination of Nutlin-3/bortezomib synergistically induced cytotoxicity through the mitochondrial apoptotic pathway mediated by transcription-independent upregulation of NOXA, sequestration of MCL-1, activation of BAX, BAK, caspase-9 and -3. Bortezomib 106-116 tumor protein p53 Homo sapiens 14-18 20850924-3 2010 In the bortezomib sensitive wild-type TP53 MCL cells, the Nutlin-3/bortezomib combination caused G0/G1 cell cycle arrest followed by the increase in apoptosis induction. Bortezomib 7-17 tumor protein p53 Homo sapiens 38-42 20460535-5 2010 We causally linked bortezomib-induced cell death to the accumulation of ASF1B, Myc, ODC1, Noxa, BNIP3, Gadd45alpha, p-SMC1A, SREBF1, and p53. Bortezomib 19-29 tumor protein p53 Homo sapiens 137-140 20096120-0 2010 Cancer cell sensitivity to bortezomib is associated with survivin expression and p53 status but not cancer cell types. Bortezomib 27-37 tumor protein p53 Homo sapiens 81-84 20096120-5 2010 RESULTS: We found that cancer cells with wild type p53 show a low level expression of survivin and are sensitive to treatment with bortezomib, while cancer cells with a mutant or null p53 show a high level expression of survivin and are resistant to bortezomib-mediated apoptosis induction. Bortezomib 131-141 tumor protein p53 Homo sapiens 51-54 20096120-9 2010 CONCLUSIONS: Our findings, for the first time, unify the current inconsistent findings for bortezomib treatment and survivin expression, and linked the effect of bortezomib on survivin expression, apoptosis induction and bortezomib resistance in the relationship with p53 status, which is independent of cancer cell types. Bortezomib 162-172 tumor protein p53 Homo sapiens 268-271 20096120-5 2010 RESULTS: We found that cancer cells with wild type p53 show a low level expression of survivin and are sensitive to treatment with bortezomib, while cancer cells with a mutant or null p53 show a high level expression of survivin and are resistant to bortezomib-mediated apoptosis induction. Bortezomib 250-260 tumor protein p53 Homo sapiens 51-54 20096120-7 2010 We further noted that modulation of survivin expression by bortezomib is dependent on p53 status but independent of cancer cell types. Bortezomib 59-69 tumor protein p53 Homo sapiens 86-89 20096120-9 2010 CONCLUSIONS: Our findings, for the first time, unify the current inconsistent findings for bortezomib treatment and survivin expression, and linked the effect of bortezomib on survivin expression, apoptosis induction and bortezomib resistance in the relationship with p53 status, which is independent of cancer cell types. Bortezomib 162-172 tumor protein p53 Homo sapiens 268-271 19934289-0 2009 Interactions of the Hdm2/p53 and proteasome pathways may enhance the antitumor activity of bortezomib. Bortezomib 91-101 tumor protein p53 Homo sapiens 25-28 19934289-8 2009 CONCLUSIONS: This differential response of MM versus epithelial carcinomas to combination of nutlin-3 with bortezomib sheds new light on the role of p53 in bortezomib-induced apoptosis. Bortezomib 156-166 tumor protein p53 Homo sapiens 149-152 19608275-7 2010 The enhanced cytotoxicity of ATO+bortezomib was associated with augmented STAT3 inhibition and JNK activation, up-regulation of Bim, p21, p27, p53 as well as down-regulation of Bcl-2. Bortezomib 33-43 tumor protein p53 Homo sapiens 143-146 19934289-8 2009 CONCLUSIONS: This differential response of MM versus epithelial carcinomas to combination of nutlin-3 with bortezomib sheds new light on the role of p53 in bortezomib-induced apoptosis. Bortezomib 107-117 tumor protein p53 Homo sapiens 149-152 19661301-0 2009 Inhibition of proteasome activity by bortezomib in renal cancer cells is p53 dependent and VHL independent. Bortezomib 37-47 tumor protein p53 Homo sapiens 73-76 19661301-7 2009 Stable down-regulation of p53 expression by siRNA led to attenuation of bortezomib effects, survivin down-regulation and p21 induction, suggesting that cellular effects are p53-dependent. Bortezomib 72-82 tumor protein p53 Homo sapiens 26-29 19549370-6 2009 The expression of NF-kappaB mRNA and p53 mRNA decreased after treatment with bortezomib. Bortezomib 77-87 tumor protein p53 Homo sapiens 37-40 19661301-7 2009 Stable down-regulation of p53 expression by siRNA led to attenuation of bortezomib effects, survivin down-regulation and p21 induction, suggesting that cellular effects are p53-dependent. Bortezomib 72-82 tumor protein p53 Homo sapiens 173-176 19661301-8 2009 CONCLUSION: These results demonstrate that the antiproliferative effects of bortezomib in CCRCC cells are VHL independent and dependent on pathways regulated by p53. Bortezomib 76-86 tumor protein p53 Homo sapiens 161-164 19549370-8 2009 NF-kappaB and p53 gene are supposed to participate in the bortezomib induced apoptosis of Raji cells. Bortezomib 58-68 tumor protein p53 Homo sapiens 14-17 19188164-8 2009 The combination of Nutlin-3 with doxorubicin or bortezomib was synergistic in wt-TP53 MCL cells. Bortezomib 48-58 tumor protein p53 Homo sapiens 81-85 19068089-5 2009 In addition, among the members of the BH3-only family, upregulation of Noxa was consistently seen at both the transcriptional and protein levels in a p53-independent manner after exposure to bortezomib. Bortezomib 191-201 tumor protein p53 Homo sapiens 150-153 19147762-7 2009 Treatment of cervical cancer cells with bortezomib elevated the level of p53 but not hDlg, hScribble or hMAGI. Bortezomib 40-50 tumor protein p53 Homo sapiens 73-76 18790767-3 2008 Mechanistically, bortezomib induced a G2-M-phase cell cycle arrest and p53-independent apoptosis associated with caspase cleavage and Noxa induction. Bortezomib 17-27 tumor protein p53 Homo sapiens 71-74 17363600-0 2007 The proteasome inhibitor bortezomib acts independently of p53 and induces cell death via apoptosis and mitotic catastrophe in B-cell lymphoma cell lines. Bortezomib 25-35 tumor protein p53 Homo sapiens 58-61 17096161-3 2007 We also tested whether bortezomib interactions with cytarabine and anthracyclines are affected by p53, because proteasome inhibition stabilizes p53 and may thus cause cell cycle arrest. Bortezomib 23-33 tumor protein p53 Homo sapiens 98-101 17235352-1 2007 In this report, the effects of a combined treatment with the proteasome inhibitor bortezomib and either a recombinant adeno-associated virus type 2 (rAAV-2)-mediated p53 gene transfer or chemotherapeutic agents, docetaxel and pemetrexed, were tested on p53 positive and p53negative non-small cell lung cancer (NSCLC) cell lines. Bortezomib 82-92 tumor protein p53 Homo sapiens 253-256 17235352-2 2007 The combination of bortezomib and rAAV-p53 led to a significant synergistic inhibition of cell growth between 62-82% depending on the p53 status of the cell line and drug concentration. Bortezomib 19-29 tumor protein p53 Homo sapiens 134-137 17235352-4 2007 Enhanced cell toxicity was associated with a 5.3-14.4-fold increase of the apoptotic rate and intracellular p53 level up to 50.4% following vector-mediated p53 restoration and bortezomib treatment. Bortezomib 176-186 tumor protein p53 Homo sapiens 108-111 17910628-6 2007 Bortezomib/PXD101 treatment markedly triggered reactive oxygen species (ROS) generation that was accompanied by p53, H2A.X and p38-mitogen-activated protein kinase phosphorylation. Bortezomib 0-10 tumor protein p53 Homo sapiens 112-115 17363600-3 2007 Bortezomib induced a time- and concentration-dependent reduction in cell viability in five lymphoma cell lines, with EC(50) values ranging from 6 nmol/L (DHL-7 cells) to 25 nmol/L (DHL-4 cells) after 72 h. Bortezomib cytotoxicity was independent of p53 function, as all cell lines exhibited mutations by sequence analysis. Bortezomib 0-10 tumor protein p53 Homo sapiens 249-252 16849420-8 2006 Bortezomib inhibited NF-kappaB activity; increased p53, p21, and jun expression; and induced caspase-dependent apoptosis. Bortezomib 0-10 tumor protein p53 Homo sapiens 51-54 16091363-9 2005 More importantly, small interfering RNA knockdown of ASPP2/(53BP2L) levels attenuated bortezomib-induced apoptosis, and this effect was greater in wild-type p53 cells. Bortezomib 86-96 tumor protein p53 Homo sapiens 157-160 16166592-0 2006 The proteasome inhibitor bortezomib induces apoptosis in mantle-cell lymphoma through generation of ROS and Noxa activation independent of p53 status. Bortezomib 25-35 tumor protein p53 Homo sapiens 139-142 16382051-4 2005 Colon cancer cell lines lacking p53 or Bax were sensitized by bortezomib, suggesting that neither p53 nor Bax levels were crucial for sensitization. Bortezomib 62-72 tumor protein p53 Homo sapiens 32-35 16178003-3 2005 Proteasome inhibition with bortezomib has specifically promoted apoptosis of tumor cells through the stabilization of p53, p21, p27, Bax, and IkappaBalpha, resulting in nuclear factor kappaB inhibition. Bortezomib 27-37 tumor protein p53 Homo sapiens 118-121 15929791-4 2005 Exposure to bortezomib has been shown to stabilize p21, p27, and p53, as well as the proapoptotic Bid and Bax proteins, caveolin-1, and inhibitor kappaB-alpha, which prevents activation of nuclear factor kappaB-induced cell survival pathways. Bortezomib 12-22 tumor protein p53 Homo sapiens 65-68 15830705-0 2005 Intracellular inhibitory effects of Velcade correlate with morphoproteomic expression of phosphorylated-nuclear factor-kappaB and p53 in breast cancer cell lines. Bortezomib 36-43 tumor protein p53 Homo sapiens 130-133 15830705-1 2005 Velcade, a proteasome inhibitor, has been shown to inhibit DNA binding activity of nuclear factor-kappaB (NF-kappaB) and to stabilize p53 in vitro. Bortezomib 0-7 tumor protein p53 Homo sapiens 134-137 15830705-9 2005 Velcade treatment resulted in cleaved caspase-3 expression in MDA-231 cells and in the overexpression of p53 and p21WAF1 in all 3 cell lines, as evaluated using Western blotting. Bortezomib 0-7 tumor protein p53 Homo sapiens 105-108 15830705-10 2005 In summary, morphoproteomic analysis of p-NF-kappaB and p53 can be correlated with the inhibitory effect of Velcade in vitro. Bortezomib 108-115 tumor protein p53 Homo sapiens 56-59 15016328-4 2004 In this study, we found that PS-341 induced growth arrest and apoptosis of androgen-dependent human prostate cancer LNCaP cells in conjunction with markedly up-regulated levels of p21(waf1) and p53. Bortezomib 29-35 tumor protein p53 Homo sapiens 194-197 15464472-13 2004 Combined gemcitabine and bortezomib enhanced p21 and p53 expression and induced S-phase and G2/M cell-cycle arrests, respectively. Bortezomib 25-35 tumor protein p53 Homo sapiens 53-56 15052205-11 2004 The proteins p21 and p53 were stabilized after treatment with bortezomib, correlating with a G(2)/M cell-cycle arrest. Bortezomib 62-72 tumor protein p53 Homo sapiens 21-24 15662128-5 2005 Apoptosis induced by Bortezomib was associated with inhibition of the classical and alternative NF-kappaB pathways, upregulation of p53, p21 and p27 and activation of caspase cascade. Bortezomib 21-31 tumor protein p53 Homo sapiens 132-135 15638966-3 2004 Bortezomib targets pathways relevant to tumor progression and therapy resistance and can directly modulate expression of cyclins, p27kip1, p53, nuclear factor-kB, Bcl-2, and Bax. Bortezomib 0-10 tumor protein p53 Homo sapiens 139-142 14965369-5 2004 Interestingly, when the JNK/c-Jun/AP-1 signal pathway was disrupted by the JNK inhibitor SP600125, the ability of PS-341 to inhibit the growth of NSCLC cells and to up-regulate the levels of p21(waf1) in these cells was blunted, but the expression of p53 was sustained at a high level, suggesting that the JNK/c-Jun/AP-1 signal pathway might mediate the anti-lung cancer effects of PS-341, with p21(waf1) playing the central role. Bortezomib 114-120 tumor protein p53 Homo sapiens 251-254 14688479-5 2003 In this study, we investigated the role of p53 and its downstream targets in bortezomib-induced apoptosis in HCT116 human colon cancer cells. Bortezomib 77-87 tumor protein p53 Homo sapiens 43-46 14612532-5 2003 Nonetheless, bortezomib stimulated p53 translocation to the nucleus (not mitochondria) and enhanced p53 DNA binding, accumulation of p53-dependent transcripts, and activation of a p53-responsive reporter gene. Bortezomib 13-23 tumor protein p53 Homo sapiens 100-103 14612532-6 2003 Furthermore, stable LNCaP-Pro5 transfectants of LNCaP-Pro5 expressing the p53 inhibitor human papillomavirus-E6 displayed reduced bortezomib-induced p53 activation and cell death. Bortezomib 130-140 tumor protein p53 Homo sapiens 74-77 14612532-6 2003 Furthermore, stable LNCaP-Pro5 transfectants of LNCaP-Pro5 expressing the p53 inhibitor human papillomavirus-E6 displayed reduced bortezomib-induced p53 activation and cell death. Bortezomib 130-140 tumor protein p53 Homo sapiens 149-152 14612532-7 2003 Together, our data demonstrate that bortezomib stimulates p53 activation via a novel mechanism. Bortezomib 36-46 tumor protein p53 Homo sapiens 58-61 14965369-3 2004 In this study, we found that PS-341 induced growth arrest and apoptosis of NCI-H520 and -H460 non-small cell lung cancer (NSCLC) cells in conjunction with markedly up-regulated levels of p21(waf1) and p53, and down-regulation of bcl-2 protein in these cells. Bortezomib 29-35 tumor protein p53 Homo sapiens 201-204 14612532-0 2003 The proteasome inhibitor bortezomib stabilizes a novel active form of p53 in human LNCaP-Pro5 prostate cancer cells. Bortezomib 25-35 tumor protein p53 Homo sapiens 70-73 14612532-4 2003 Bortezomib induced strong stabilization of p53, but it did not promote phosphorylation on serines 15 and 20, and p53 remained bound to its inhibitor, mdm2. Bortezomib 0-10 tumor protein p53 Homo sapiens 43-46 14612532-5 2003 Nonetheless, bortezomib stimulated p53 translocation to the nucleus (not mitochondria) and enhanced p53 DNA binding, accumulation of p53-dependent transcripts, and activation of a p53-responsive reporter gene. Bortezomib 13-23 tumor protein p53 Homo sapiens 35-38 14612532-5 2003 Nonetheless, bortezomib stimulated p53 translocation to the nucleus (not mitochondria) and enhanced p53 DNA binding, accumulation of p53-dependent transcripts, and activation of a p53-responsive reporter gene. Bortezomib 13-23 tumor protein p53 Homo sapiens 100-103 14612532-5 2003 Nonetheless, bortezomib stimulated p53 translocation to the nucleus (not mitochondria) and enhanced p53 DNA binding, accumulation of p53-dependent transcripts, and activation of a p53-responsive reporter gene. Bortezomib 13-23 tumor protein p53 Homo sapiens 100-103 14688479-6 2003 We demonstrated that bortezomib induced p53, and activated its downstream genes p21, PUMA and Bax in a p53-dependent fashion. Bortezomib 21-31 tumor protein p53 Homo sapiens 40-43 14688479-6 2003 We demonstrated that bortezomib induced p53, and activated its downstream genes p21, PUMA and Bax in a p53-dependent fashion. Bortezomib 21-31 tumor protein p53 Homo sapiens 103-106 14688479-11 2003 These results indicate that p53 downstream targets can collectively modulate apoptotic response to bortezomib and other proteasome inhibitors. Bortezomib 99-109 tumor protein p53 Homo sapiens 28-31 14513055-6 2003 L-NAC also opposed bortezomib/HA14-1-mediated JNK activation, upregulation of p53 and Bax, and release of cytochrome c and Smac/DIABLO. Bortezomib 19-29 tumor protein p53 Homo sapiens 78-81 12631620-9 2003 CONCLUSIONS: Our data suggest that the PS-341-induced G(2)-M-phase arrest may be associated with the inhibition of degradation of cell cycle regulators and that the up-regulation of p21(cip/waf-1) expression may be via p53-dependent and/or -independent pathways. Bortezomib 39-45 tumor protein p53 Homo sapiens 219-222 12821677-11 2003 The transient transfection of wild type p53 in p53 null H358 cells caused stimulation of the bortezomib-induced apoptosis but failed to enhance ROS generation and Delta psi m increase. Bortezomib 93-103 tumor protein p53 Homo sapiens 40-43 12821677-11 2003 The transient transfection of wild type p53 in p53 null H358 cells caused stimulation of the bortezomib-induced apoptosis but failed to enhance ROS generation and Delta psi m increase. Bortezomib 93-103 tumor protein p53 Homo sapiens 47-50 12393500-4 2003 We here demonstrate molecular mechanisms whereby PS-341 mediates anti-MM activity by inducing p53 and MDM2 protein expression; inducing the phosphorylation (Ser15) of p53 protein; activating c-Jun NH(2)-terminal kinase (JNK), caspase-8, and caspase-3; and cleaving the DNA protein kinase catalytic subunit, ATM, and MDM2. Bortezomib 49-55 tumor protein p53 Homo sapiens 94-97 12393500-4 2003 We here demonstrate molecular mechanisms whereby PS-341 mediates anti-MM activity by inducing p53 and MDM2 protein expression; inducing the phosphorylation (Ser15) of p53 protein; activating c-Jun NH(2)-terminal kinase (JNK), caspase-8, and caspase-3; and cleaving the DNA protein kinase catalytic subunit, ATM, and MDM2. Bortezomib 49-55 tumor protein p53 Homo sapiens 167-170 11306489-3 2001 In this study, we demonstrate that the proteasome inhibitor PS-341 directly inhibits proliferation and induces apoptosis of human MM cell lines and freshly isolated patient MM cells; inhibits mitogen-activated protein kinase growth signaling in MM cells; induces apoptosis despite induction of p21 and p27 in both p53 wild-type and p53 mutant MM cells; overcomes drug resistance; adds to the anti-MM activity of dexamethasone; and overcomes the resistance to apoptosis in MM cells conferred by interleukin-6. Bortezomib 60-66 tumor protein p53 Homo sapiens 314-317 11740818-6 2001 PS-341 inhibits p44/42 mitogen-activated protein kinase (MAPK) growth signaling triggered by IL-6 and induces apoptosis, despite induction of p21 and p27, in p53 wild-type and p53 mutant MM cells. Bortezomib 0-6 tumor protein p53 Homo sapiens 158-161 11740818-6 2001 PS-341 inhibits p44/42 mitogen-activated protein kinase (MAPK) growth signaling triggered by IL-6 and induces apoptosis, despite induction of p21 and p27, in p53 wild-type and p53 mutant MM cells. Bortezomib 0-6 tumor protein p53 Homo sapiens 176-179 11306489-3 2001 In this study, we demonstrate that the proteasome inhibitor PS-341 directly inhibits proliferation and induces apoptosis of human MM cell lines and freshly isolated patient MM cells; inhibits mitogen-activated protein kinase growth signaling in MM cells; induces apoptosis despite induction of p21 and p27 in both p53 wild-type and p53 mutant MM cells; overcomes drug resistance; adds to the anti-MM activity of dexamethasone; and overcomes the resistance to apoptosis in MM cells conferred by interleukin-6. Bortezomib 60-66 tumor protein p53 Homo sapiens 332-335 34589431-0 2021 Four and a Half LIM Domains Protein 2 Mediates Bortezomib-Induced Osteogenic Differentiation of Mesenchymal Stem Cells in Multiple Myeloma Through p53 Signaling and beta-Catenin Nuclear Enrichment. Bortezomib 47-57 tumor protein p53 Homo sapiens 147-150 34608124-3 2021 In contrast, bortezomib and paclitaxel could drive U2OS or MG63 toward apoptosis effectively, suggesting that apoptosis induced by bortezomib or paclitaxel is p53-independent. Bortezomib 13-23 tumor protein p53 Homo sapiens 159-162 34608124-3 2021 In contrast, bortezomib and paclitaxel could drive U2OS or MG63 toward apoptosis effectively, suggesting that apoptosis induced by bortezomib or paclitaxel is p53-independent. Bortezomib 131-141 tumor protein p53 Homo sapiens 159-162 34589431-12 2021 In conclusion, FHL2 is critical for Bzb-induced osteoblast differentiation of MM-MSCs and promotes the osteogenesis, through p53 signaling and beta-catenin activation. Bortezomib 36-39 tumor protein p53 Homo sapiens 125-128 35088582-6 2022 In contrast, delivery of wild type p53 and suppression of NEK2 in TP53-/- MM cell lines inhibit tumor formation and enhance the effect of Bortezomib against MM. Bortezomib 138-148 tumor protein p53 Homo sapiens 35-38 35088582-6 2022 In contrast, delivery of wild type p53 and suppression of NEK2 in TP53-/- MM cell lines inhibit tumor formation and enhance the effect of Bortezomib against MM. Bortezomib 138-148 tumor protein p53 Homo sapiens 66-70 35071005-6 2021 Third, treatments that specifically affect HPV+ cancer cells by targeting the viral enzymes E6/E7 which are responsible for the breakdown of p53 such as Ad-E6/E7-As and bortezomib. Bortezomib 169-179 tumor protein p53 Homo sapiens 141-144