Apoptotic cell death is a highly regulated process, which plays a crucial role in many biological events. The aim of the present research was to investigate the expression of the apoptosis related genes BCL2 and BAX in Hep-2 and HL60 cells. Apoptosis was induced in these cell lines during treatment with etoposide. The expression levels of BCL2 and BAX genes were measured after 6 h and 12 h of treatment by quantitative real-time RT-PCR. In Hep-2 cells the expression level of BCL2 significantly increased both 6 h and 12 h of treatment, whereas expression level of BAX didn't change. In HL-60 cells the expression level of BCL2 decreased after 6 h of treatment and expression of BAX increased both 6 h and 12 h of treatment with etoposide. Those findings show distinct reactions of Hep-2 and HL-60 cells to etoposide treatment and different upregulation or downregulation of apoptosis-related genes BCL2 and BAX.

• MeSH
• antitumorózní látky fytogenní farmakologie   MeSH
• apoptóza účinky léků   genetika   MeSH
• etoposid farmakologie   MeSH
• geny bcl-2 genetika   MeSH
• HL-60 buňky MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• protein X asociovaný s bcl-2 genetika   MeSH
• regulace genové exprese u nádorů účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antitumorózní látky fytogenní MeSH
• etoposid MeSH
• protein X asociovaný s bcl-2 MeSH

BACKGROUND: Breast cancer (BC), the most frequent malignancy in women worldwide, is currently diagnosed in about 1.4 million female patients annually. Approximately 10-20% of BC is represented by triple negative breast cancer (TNBC) which is aggressive, the prognosis is poor and patients cannot benefit from targeted treatment based on hormonal or HER2 receptors. For this reason, search for markers that can predict the efficacy of chemotherapy in TNBC is a priority. METHODS AND RESULTS: This review focuses on BCL2 protein as a prognostic marker in TNBC and its potential as a predictor of sensitivity to chemotherapy. CONCLUSION: BCL2 protein expression is a positive prognostic factor in BC. Better survival of patients with BCL2 positivity (BCL2+) has been explained by the correlation with estrogen receptor positive (ER+) status. BCL2+ is however not simply a surrogate marker for ER+. Moreover, BCL2 protein expression is also a positive prognostic marker in the TNBC subgroup. We and others show, that low BCL2 expression was associated with good outcome of TNBC patients treated with both adjuvant and neoadjuvant anthracycline-based chemotherapy. On the other hand, recent studies have shown that a subset of TNBC patients may benefit from the classical adjuvant CMF (cyclophosphamide, methotrexate, 5-fluorouracil) regimen. Given the heterogeneity of TNBC there is an urgent need to find and validate the sensitivity predictors to these regimens making them usable in clinical practice. BCL2 enrichment has been described in the mesenchymal stem-like (MSL) TNBC subgroup.

• MeSH
• lidé MeSH
• nádorové biomarkery genetika   metabolismus   MeSH
• protokoly antitumorózní kombinované chemoterapie terapeutické užití   MeSH
• protoonkogenní proteiny c-bcl-2 genetika   metabolismus   MeSH
• triple-negativní karcinom prsu farmakoterapie   genetika   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• BCL2 protein, human MeSH Prohlížeč
• nádorové biomarkery MeSH
• protoonkogenní proteiny c-bcl-2 MeSH

PURPOSE: To investigate the roles of BCL2, MCL1, and BCL-XL in the survival of diffuse large B-cell lymphoma (DLBCL). EXPERIMENTAL DESIGNS: Immunohistochemical analysis of 105 primary DLBCL samples, and Western blot analysis of 18 DLBCL cell lines for the expression of BCL2, MCL1, and BCL-XL. Pharmacologic targeting of BCL2, MCL1, and BCL-XL with ABT-199, homoharringtonine (HHT), and ABT-737. Analysis of DLBCL clones with manipulated expressions of BCL2, MCL1, and BCL-XL. Immunoprecipitation of MCL1 complexes in selected DLBCL cell lines. Experimental therapy aimed at inhibition of BCL2 and MCL1 using ABT-199 and HHT, single agent, or in combination, in vitro and in vivo on primary cell-based murine xenograft models of DLBCL. RESULTS: By the pharmacologic targeting of BCL2, MCL1, and BCL-XL, we demonstrated that DLBCL can be divided into BCL2-dependent and MCL1-dependent subgroups with a less pronounced role left for BCL-XL. Derived DLBCL clones with manipulated expressions of BCL2, MCL1, and BCL-XL, as well as the immunoprecipitation experiments, which analyzed MCL1 protein complexes, confirmed these findings at the molecular level. We demonstrated that concurrent inhibition of BCL2 and MCL1 with ABT-199 and HHT induced significant synthetic lethality in most BCL2-expressing DLBCL cell lines. The marked cytotoxic synergy between ABT-199 and HHT was also confirmed in vivo using primary cell-based murine xenograft models of DLBCL. CONCLUSIONS: As homoharringtonine is a clinically approved antileukemia drug, and ABT-199 is in advanced phases of diverse clinical trials, our data might have direct implications for novel concepts of early clinical trials in patients with aggressive DLBCL.

• MeSH
• apoptóza účinky léků   MeSH
• bicyklické sloučeniny heterocyklické aplikace a dávkování   MeSH
• bifenylové sloučeniny aplikace a dávkování   MeSH
• difúzní velkobuněčný B-lymfom klasifikace   farmakoterapie   genetika   patologie   MeSH
• harringtoniny aplikace a dávkování   MeSH
• homoharringtonin MeSH
• lidé MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nitrofenoly aplikace a dávkování   MeSH
• piperaziny aplikace a dávkování   MeSH
• proliferace buněk účinky léků   MeSH
• protein bcl-X biosyntéza   MeSH
• protein MCL-1 biosyntéza   genetika   MeSH
• protoonkogenní proteiny c-bcl-2 biosyntéza   genetika   MeSH
• regulace genové exprese u nádorů účinky léků   MeSH
• sulfonamidy aplikace a dávkování   MeSH
• xenogenní modely - testy antitumorózní aktivity MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• ABT-737 MeSH Prohlížeč
• BCL2L1 protein, human MeSH Prohlížeč
• bicyklické sloučeniny heterocyklické MeSH
• bifenylové sloučeniny MeSH
• harringtoniny MeSH
• homoharringtonin MeSH
• MCL1 protein, human MeSH Prohlížeč
• nitrofenoly MeSH
• piperaziny MeSH
• protein bcl-X MeSH
• protein MCL-1 MeSH
• protoonkogenní proteiny c-bcl-2 MeSH
• sulfonamidy MeSH
• venetoclax MeSH Prohlížeč

We studied the relationship between DNA damage, DNA repair rates and messenger RNA (mRNA) expression levels of cell cycle genes TP53, p21(CDKN1A), BCL2 and BAX in a group of 71 styrene-exposed workers and 51 control individuals. The exposure was assessed by measuring the concentration of styrene at workplace and in blood. Parameters of DNA damage [measured as single-strand breaks (SSBs) and endonuclease III-sensitive sites], γ-irradiation-specific DNA repair rates and mRNA levels of studied genes were analyzed in peripheral blood lymphocytes. The workers were divided into low (<50 mg/m³) and high (>50 mg/m³) styrene exposure groups. We found negative correlations between mRNA expression of TP53, BCL2, BAX and styrene exposure (P < 0.001 for all parameters). In contrast, p21(CDKN1A) mRNA expression significantly increased with increasing styrene exposure (P = 0.001). SSBs and endonuclease III-sensitive sites increased with increasing mRNA levels of TP53 (P < 0.001 for both) and BCL2 (P = 0.038, P = 0.002, respectively), whereas the same parameters decreased with increasing mRNA levels of p21(CDKN1A) (P < 0.001, P = 0.007, respectively). γ-Irradiation-specific DNA repair rates increased with p21(CDKN1A) mRNA levels up to the low exposure level (P = 0.044). Our study suggests a possible relationship between styrene exposure, DNA damage and transcript levels of key cell cycle genes.

• MeSH
• CDC geny účinky léků   MeSH
• dospělí MeSH
• exprese genu účinky léků   MeSH
• inhibitor p21 cyklin-dependentní kinasy účinky léků   genetika   MeSH
• lidé MeSH
• messenger RNA analýza   MeSH
• nádorový supresorový protein p53 účinky léků   genetika   MeSH
• oprava DNA účinky léků   MeSH
• polymerázová řetězová reakce MeSH
• poškození DNA účinky léků   MeSH
• pracovní expozice škodlivé účinky   MeSH
• protein X asociovaný s bcl-2 účinky léků   genetika   MeSH
• protoonkogenní proteiny c-bcl-2 účinky léků   genetika   MeSH
• styren škodlivé účinky   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• CDKN1A protein, human MeSH Prohlížeč
• inhibitor p21 cyklin-dependentní kinasy MeSH
• messenger RNA MeSH
• nádorový supresorový protein p53 MeSH
• protein X asociovaný s bcl-2 MeSH
• protoonkogenní proteiny c-bcl-2 MeSH
• styren MeSH

Venetoclax (VEN), a B-cell lymphoma 2 (BCL2) inhibitor, has a promising single-agent activity in mantle cell lymphoma (MCL), acute lymphoblastic leukemia (ALL), and large BCLs, but remissions were generally short, which call for rational drug combinations. Using a panel of 21 lymphoma and leukemia cell lines and 28 primary samples, we demonstrated strong synergy between VEN and A1155463, a BCL-XL inhibitor. Immunoprecipitation experiments and studies on clones with knockout of expression or transgenic expression of BCL-XL confirmed its key role in mediating inherent and acquired VEN resistance. Of note, the VEN and A1155463 combination was synthetically lethal even in the cell lines with lack of expression of the proapoptotic BCL2L11/BIM and in the derived clones with genetic knockout of BCL2L11/BIM. This is clinically important because BCL2L11/BIM deletion, downregulation, or sequestration results in VEN resistance. Immunoprecipitation experiments further suggested that the proapoptotic effector BAX belongs to principal mediators of the VEN and A1155463 mode of action in the BIM-deficient cells. Lastly, the efficacy of the new proapoptotic combination was confirmed in vivo on a panel of 9 patient-derived lymphoma xenografts models including MCL (n = 3), B-ALL (n = 2), T-ALL (n = 1), and diffuse large BCL (n = 3). Because continuous inhibition of BCL-XL causes thrombocytopenia, we proposed and tested an interrupted 4 days on/3 days off treatment regimen, which retained the desired antitumor synergy with manageable platelet toxicity. The proposed VEN and A1155463 combination represents an innovative chemotherapy-free regimen with significant preclinical activity across diverse BCL2+ hematologic malignancies irrespective of the BCL2L11/BIM status.

• MeSH
• antitumorózní látky farmakologie   terapeutické užití   MeSH
• apoptóza účinky léků   MeSH
• benzothiazoly MeSH
• bicyklické sloučeniny heterocyklické * farmakologie   terapeutické užití   MeSH
• chemorezistence * MeSH
• isochinoliny MeSH
• lidé MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• protein bcl-X * metabolismus   antagonisté a inhibitory   MeSH
• protein BCL2L11 * metabolismus   genetika   MeSH
• protoonkogenní proteiny c-bcl-2 metabolismus   antagonisté a inhibitory   MeSH
• sulfonamidy * farmakologie   terapeutické užití   MeSH
• synergismus léků MeSH
• xenogenní modely - testy antitumorózní aktivity MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• A-1155463 MeSH Prohlížeč
• antitumorózní látky MeSH
• BCL2L1 protein, human MeSH Prohlížeč
• benzothiazoly MeSH
• bicyklické sloučeniny heterocyklické * MeSH
• isochinoliny MeSH
• protein bcl-X * MeSH
• protein BCL2L11 * MeSH
• protoonkogenní proteiny c-bcl-2 MeSH
• sulfonamidy * MeSH
• venetoclax MeSH Prohlížeč

INTRODUCTION: The prognostic value of B-cell lymphoma 2 (BCL2) expression in de novo diffuse large B-cell lymphoma (DLBCL) treated with immunochemotherapy is of interest to define a target patient population for clinical development of BCL2 inhibitors. We aimed to develop a reproducible immunohistochemistry algorithm and assay to determine BCL2 protein expression and assess the prognostic value of BCL2 in newly diagnosed DLBCL cohorts. PATIENTS AND METHODS: The prospectively defined algorithm incorporated BCL2 staining intensity and percentage of BCL2-positive cells. Functionally relevant cutoffs were based on the sensitivity of lymphoma cell lines to venetoclax. This assay was highly reproducible across laboratories. The prognostic impact of BCL2 expression was assessed in DLBCL patients from the phase 3 MAIN (n = 230) and GOYA (n = 366) trials, and a population-based registry (n = 310). RESULTS: Approximately 50% of tumors were BCL2 positive, with a higher frequency in high International Prognostic Index (IPI) and activated B-cell-like DLBCL subgroups. BCL2 expression was associated with poorer progression-free survival in the MAIN study (hazard ratio [HR], 1.66; 95% confidence interval [CI], 0.81-3.40; multivariate Cox regression adjusted for IPI and cell of origin). This trend was confirmed in the GOYA and registry cohorts in adjusted multivariate analyses (GOYA: HR, 1.72; 95% CI, 1.05-2.82; registry: HR, 1.89; 95% CI, 1.29-2.78). Patients with BCL2 immunohistochemistry-positive and IPI-high disease had the poorest prognosis: 3-year progression-free survival rates were 51% (GOYA) and 37% (registry). CONCLUSION: Findings support use of our BCL2 immunohistochemistry scoring system and assay to select patients with BCL2-positive tumors for future studies.

• Klíčová slova
• ABC DLBCL subtype, Biomarkers, Cell of origin, GCB DLBCL subtype, Immunohistochemistry,
• MeSH
• chemorezistence genetika   MeSH
• difúzní velkobuněčný B-lymfom farmakoterapie   genetika   mortalita   patologie   MeSH
• doba přežití bez progrese choroby MeSH
• dospělí MeSH
• Kaplanův-Meierův odhad MeSH
• klinické zkoušky, fáze III jako téma MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• multicentrické studie jako téma MeSH
• nádorové biomarkery analýza   genetika   MeSH
• prognóza MeSH
• protokoly antitumorózní kombinované chemoterapie farmakologie   terapeutické užití   MeSH
• protoonkogenní proteiny c-bcl-2 analýza   genetika   MeSH
• randomizované kontrolované studie jako téma MeSH
• registrace statistika a číselné údaje   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• BCL2 protein, human MeSH Prohlížeč
• nádorové biomarkery MeSH
• protoonkogenní proteiny c-bcl-2 MeSH

Synovial sarcoma (SS) is a highly aggressive soft tissue sarcoma that causes death in more than half of the affected patients. An immunohistochemical and molecular study of the BCL2, MKI67, and CCND1 genes (expressing the BCL2, KI-67, and cyclin D1 proteins, respectively) was performed to determine the expression profiles in correlation with mRNA levels, and to assess the possible utility of these genes as a potential target for the treatment. Cyclin D1 staining was identified in 18 of 30 cases (60%), and CCND1 mRNA was overexpressed in 15 of 32 cases (47%). KI-67 nuclear immunoreactivity was found in 14 of 29 cases (48%), and MKI67 mRNA was overexpressed in 12 of 32 cases (37.5%). The high level of MKI67 mRNA was observed predominantly in monophasic SS. BCL2, a negative regulator of apoptosis, was expressed in all 32 cases. The intensity of the BCL2 protein expression correlated well with the mRNA level (P<0.0001). The high level of BCL2 mRNA correlated with a high level of CCND1 mRNA, but not with MKI67 mRNA level. Despite advances in therapy of sarcomas, the prognosis of patients with SS remains unfavorable, and a search for an improved therapy approach remains necessary. The strong immunopositivity of BCL2 in SS correlates well with a high level of BCL2 mRNA. Treatment with antisense BCL2 (G3139) may therefore represent an appropriate alternative therapy for patients with BCL2-positive synovial sarcomas.

• MeSH
• analýza rozptylu MeSH
• antigen Ki-67 genetika   metabolismus   MeSH
• buněčné jádro chemie   metabolismus   MeSH
• cyklin D1 genetika   metabolismus   MeSH
• dítě MeSH
• dospělí MeSH
• imunohistochemie MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• messenger RNA analýza   genetika   MeSH
• mladiství MeSH
• nádory měkkých tkání genetika   metabolismus   MeSH
• neparametrická statistika MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• předškolní dítě MeSH
• protoonkogenní proteiny c-bcl-2 genetika   metabolismus   MeSH
• RNA nádorová analýza   MeSH
• senioři MeSH
• synoviom genetika   metabolismus   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigen Ki-67 MeSH
• CCND1 protein, human MeSH Prohlížeč
• cyklin D1 MeSH
• messenger RNA MeSH
• protoonkogenní proteiny c-bcl-2 MeSH
• RNA nádorová MeSH

The pro-survival MCL1 protein is overexpressed in many cancers, including B-cell non-Hodgkin lymphomas (B-NHL). S63845 is a highly specific inhibitor of MCL1. We analyzed mechanisms of sensitivity/resistance to S63845 in preclinical models of diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma. Annexin V-based cytotoxic assays, Western blot analysis, protein co-immunoprecipitation, and cell clones with manipulated expression of BCL2 family proteins were used to analyze mechanisms of sensitivity to S63845. Experimental in vivo therapy with S63845 and/or venetoclax was performed using patient-derived xenografts (PDX) of treatment-refractory B-NHL. A subset of DLBCL and majority of Burkitt lymphoma cell lines were sensitive to S63845. The level of BCL2 protein expression was the major determinant of resistance to S63845: BCL2 serves as a buffer for pro-apoptotic proteins released from MCL1 upon exposure to S63845. While BCL2-negative lymphomas were effectively eliminated by single-agent S63845, its combination with venetoclax was synthetically lethal in BCL2-positive PDX models. Concerning MCL1, both, the level of MCL1 protein expression, and its occupational status represent key factors mediating sensitivity to S63845. In contrast to MCL1-BIM/BAK1 complexes that prime lymphoma cells for S63845-mediated apoptosis, MCL1-NOXA complexes are associated with S63845 resistance. In conclusion, MCL1 represents a critical survival molecule for most Burkitt lymphomas and a subset of BCL2-negative DLBCLs. The level of BCL2 and MCL1 expression and occupational status of MCL1 belong to the key modulators of sensitivity/resistance to S63845. Co-treatment with venetoclax can overcome BCL2-mediated resistance to S63845, and enhance efficacy of MCL1 inhibitors in BCL2-positive aggressive B-NHL.

• MeSH
• apoptóza MeSH
• Burkittův lymfom genetika   mortalita   MeSH
• difúzní velkobuněčný B-lymfom genetika   mortalita   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• protein MCL-1 metabolismus   MeSH
• protoonkogenní proteiny c-bcl-2 metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• BCL2 protein, human MeSH Prohlížeč
• MCL1 protein, human MeSH Prohlížeč
• protein MCL-1 MeSH
• protoonkogenní proteiny c-bcl-2 MeSH

BACKGROUND: Mantle cell lymphoma (MCL) is a chronically relapsing malignancy with deregulated cell cycle progression. We analyzed efficacy, mode of action, and predictive markers of susceptibility to palbociclib, an approved CDK 4/6 inhibitor, and its combination with venetoclax, a BCL2 inhibitor. METHODS: A panel of nine MCL cell lines were used for in vitro experiments. Four patient derived xenografts (PDX) obtained from patients with chemotherapy and ibrutinib-refractory MCL were used for in vivo proof-of-concept studies. Changes of the mitochondrial membrane potential, energy-metabolic pathways, AKT activity, and pro-apoptotic priming of MCL cells were evaluated by JC-1 staining, Seahorse XF analyser, genetically encoded fluorescent AKT reporter, and BH3 profiling, respectively. MCL clones with gene knockout or transgenic (over)expression of CDKN2A, MYC, CDK4, and RB1 were used to estimate impact of these aberrations on sensitivity to palbociclib, and venetoclax. RESULTS: Co-targeting MCL cells with palbociclib and venetoclax induced cytotoxic synergy in vitro and in vivo. Molecular mechanisms responsible for the observed synthetic lethality comprised palbociclib-mediated downregulation of anti-apoptotic MCL1, increased levels of proapoptotic BIM bound on both BCL2, and BCL-XL and increased pro-apoptotic priming of MCL cells mediated by BCL2-independent mechanisms, predominantly palbociclib-triggered metabolic and mitochondrial stress. Loss of RB1 resulted in palbociclib resistance, while deletion of CDKN2A or overexpression of CDK4, and MYC genes did not change sensitivity to palbociclib. CONCLUSIONS: Our data strongly support investigation of the chemotherapy-free palbociclib and venetoclax combination as an innovative treatment strategy for post-ibrutinib MCL patients without RB1 deletion.

• Klíčová slova
• BCL2, Cyclin-dependent kinase (CDK) inhibitors, Mantle cell lymphoma (MCL), Palbociclib, RB1, Venetoclax,
• Publikační typ
• dopisy MeSH

Neither targeted therapies nor predictors for chemotherapy sensitivity are available for triple-negative breast cancer (TNBC). Our study included 187 patients with TNBC, 164 of whom were treated with anthracycline-based adjuvant chemotherapy. Eleven molecular biomarkers were analyzed. BCL2, epidermal growth factor receptor (EGFR), MYC, TOP2A, and Ki-67 protein expression was evaluated by immunohistochemistry. The status of the EGFR, MYC, and TOP2A genes and chromosomes 7, 8, and 17 was assessed using fluorescence in situ hybridization. High BCL2 expression predicted poor relapse-free survival (RFS) in patients treated with anthracycline-based adjuvant chemotherapy (p = 0.035), poor breast cancer-specific survival (BCSS) (p = 0.048), and a trend to poor overall survival (OS) (p = 0.085). High levels of BCL2 expression predicted poor OS in basal-like (BL) TNBC patients treated with adjuvant anthracycline-based regimens (log-rank p = 0.033, hazard ratio (HR) 3.04, 95 % confidence interval (CI) 1.04-8.91) and a trend to poor RFS (log-rank p = 0.079) and poor BCSS (log-rank p = 0.056). Multivariate analysis showed that BCL2 status, tumor size, and nodal status all had independent predictive significance for RFS (p = 0.005, p = 0.091, p = 0.003, respectively; likelihood ratio test for the whole model, p = 0.003), BCSS (p = 0.012, p = 0.077, p = 0.01, respectively; likelihood ratio test for the whole model, p = 0.016), and OS (p = 0.008, p = 0.004, p = 0.004, respectively; likelihood ratio test for the whole model, p = 0.0006). Similarly, multivariate analysis for BL TNBC showed BCL2, tumor size, and nodal status all had independent predictive significance for RFS (likelihood ratio test for the whole model, p = 0.00125), BCSS (p = 0.00035), and OS (p = 0.00063). High EGFR expression was associated with poor BCSS (p = 0.039) in patients treated with anthracycline-based adjuvant chemotherapy. Patients who underwent anthracycline-based adjuvant chemotherapy and exhibited CMYC amplification had a trend to worse BCSS (p = 0.066). In conclusion, high BCL2 expression is a significant independent predictor of poor outcome in TNBC patients treated with anthracycline-based adjuvant chemotherapy, and this is the first study showing the BCL2 prediction in BL TNBC. BCL2 expression analysis could facilitate decision making on adjuvant treatment in TNBC patients.

• MeSH
• adjuvantní chemoterapie MeSH
• antracykliny aplikace a dávkování   MeSH
• dospělí MeSH
• erbB receptory biosyntéza   genetika   MeSH
• Kaplanův-Meierův odhad MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru farmakoterapie   genetika   patologie   MeSH
• přežití po terapii bez příznaků nemoci MeSH
• protoonkogenní proteiny c-bcl-2 biosyntéza   genetika   MeSH
• senioři MeSH
• triple-negativní karcinom prsu farmakoterapie   genetika   patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antracykliny MeSH
• EGFR protein, human MeSH Prohlížeč
• erbB receptory MeSH
• protoonkogenní proteiny c-bcl-2 MeSH