RESUMO
Numerous nanoparticles have been utilized to deliver Fe2+ for tumor ferroptosis therapy, which can be readily converted to Fe3+via Fenton reactions to generate hydroxyl radical (â¢OH). However, the ferroptosis therapeutic efficacy of large tumors is limited due to the slow conversion of Fe3+ to Fe2+via Fenton reactions. Herein, a strategy of intratumor Fe3+/2+ cyclic catalysis is proposed for ferroptosis therapy of large tumors, which was realized based on our newly developed hollow mesoporous iron sesquioxide nanoparticle (HMISN). Cisplatin (CDDP) and Gd-poly(acrylic acid) macrochelates (GP) were loaded into the hollow core of HMISN, whose surface was modified by laccase (LAC). Fe3+, CDDP, GP, and LAC can be gradually released from CDDP@GP@HMISN@LAC in the acidic tumor microenvironment. The intratumor O2 can be catalyzed into superoxide anion (O2â¢-) by LAC, and the intratumor NADPH oxidases can be activated by CDDP to generate O2â¢-. The O2â¢- can react with Fe3+ to generate Fe2+, and raise H2O2 level via the superoxide dismutase. The generated Fe2+ and H2O2 can be fast converted into Fe3+ and â¢OH via Fenton reactions. The cyclic catalysis of intratumor Fe3+/2+ initiated by CDDP@GP@HMISN@LAC can be used for ferroptosis therapy of large tumors.
Assuntos
Ferroptose , Ferro , Ferroptose/efeitos dos fármacos , Animais , Catálise , Humanos , Ferro/química , Linhagem Celular Tumoral , Nanopartículas/química , Porosidade , Camundongos , Cisplatino/química , Cisplatino/uso terapêutico , Neoplasias/tratamento farmacológico , Antineoplásicos/uso terapêutico , Antineoplásicos/química , Camundongos Endogâmicos BALB C , Peróxido de Hidrogênio/química , Microambiente Tumoral/efeitos dos fármacos , Camundongos Nus , FemininoRESUMO
BACKGROUND: The transcription factor NRF2 plays a significant role in regulating genes that protect cells from oxidative damage. O-GlcNAc modification, a type of posttranslational modification, is crucial for cellular response to stress. Although the involvement of both NRF2 and O-GlcNAc in maintaining cellular redox balance and promoting cancer malignancy has been demonstrated, the potential mechanisms remain elusive. METHODS: The immunoblotting, luciferase reporter, ROS assay, co-immunoprecipitation, and immunofluorescence was used to detect the effects of global cellular O-GlcNAcylation on NRF2. Mass spectrometry was utilised to map the O-GlcNAcylation sites on NRF2, which was validated by site-specific mutagenesis and O-GlcNAc enzymatic labelling. Human lung cancer samples were employed to verify the association between O-GlcNAc and NRF2. Subsequently, the impact of NRF2 O-GlcNAcylation in lung cancer malignancy and cisplatin resistance were evaluated in vitro and in vivo. RESULTS: NRF2 is O-GlcNAcylated at Ser103 residue, which hinders its binding to KEAP1 and thus enhances its stability, nuclear localisation, and transcription activity. Oxidative stress and cisplatin can elevate the phosphorylation of OGT at Thr444 through the activation of AMPK kinase, leading to enhanced binding of OGT to NRF2 and subsequent elevation of NRF2 O-GlcNAcylation. Both in cellular and xenograft mouse models, O-GlcNAcylation of NRF2 at Ser103 promotes the malignancy of lung cancer. In human lung cancer tissue samples, there was a significant increase in global O-GlcNAcylation, and elevated levels of NRF2 and its O-GlcNAcylation compared to paired adjacent normal tissues. Chemotherapy promotes NRF2 O-GlcNAcylation, which in turn decreases cellular ROS levels and drives lung cancer cell survival. CONCLUSION: Our findings indicate that OGT O-GlcNAcylates NRF2 at Ser103, and this modification plays a role in cellular antioxidant, lung cancer malignancy, and cisplatin resistance.
Assuntos
Cisplatino , Resistencia a Medicamentos Antineoplásicos , Neoplasias Pulmonares , Fator 2 Relacionado a NF-E2 , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Humanos , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Animais , Camundongos , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Camundongos NusAssuntos
Cisplatino , Peptídeos e Proteínas de Sinalização Intercelular , Progranulinas , Neoplasias da Bexiga Urinária , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/genética , Humanos , Progranulinas/metabolismo , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Resistencia a Medicamentos AntineoplásicosRESUMO
BACKGROUND: Lung cancer, particularly non-small cell lung cancer (NSCLC), remains a significant cause of cancer-related mortality, with drug resistance posing a substantial obstacle to effective therapy. LncRNAs have emerged as pivotal regulators of NSCLC progression, suggesting potential targets for cancer diagnosis and treatment. Therefore, identifying new lncRNAs as therapeutic targets and comprehending their underlying regulatory mechanisms are crucial for treating NSCLC. MATERIALS AND METHODS: RNA-sequencing data from 149 lung adenocarcinoma (LUAD) patients, including 130 responders and 19 nonresponders to primary treatment, were analyzed to identify the most effective lncRNAs. The effects and regulatory pathways of the selected lncRNAs on NSCLC and cisplatin resistance were investigated. RESULTS: Glioblastoma-downregulated RNA (GLIDR) was the most effective lncRNA in nonresponsive NSCLC patients undergoing primary treatment, and it was highly expressed in NSCLC patients and those with cisplatin-resistant NSCLC. Reducing GLIDR expression enhanced cisplatin sensitivity in resistant NSCLC and decreased the malignant characteristics of NSCLC. Moreover, bioinformatic analysis and luciferase assays revealed that microRNA-342-5p (miR-342-5p) directly targets GLIDR. MiR-342-5p overexpression inhibited NSCLC cell proliferation, migration, and invasion, whereas miR-342-5p inhibition promoted NSCLC malignancy, which was rescued by suppressing GLIDR. Peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PPARGC1A) was identified as a downstream target of miR-342-5p. PPARGC1A inhibition increased cisplatin sensitivity in resistant NSCLC. Moreover, PPARGC1A inhibition suppresses NSCLC malignancy, whereas PPARGC1A overexpression promoted it. Furthermore, GLIDR overexpression was found to counteract the inhibitory effects of miR-342-5p on PPARGC1A, and increased PPARGC1A expression reversed the inhibition of NSCLC malignancies caused by decreased GLIDR. CONCLUSIONS: GLIDR is a prognostic marker for cisplatin treatment in NSCLC and a therapeutic target in cisplatin-resistant NSCLC. GLIDR promotes NSCLC progression by sponging miR-342-5p to regulate PPARGC1A expression and regulates cisplatin resistance through the miR-342-5p/PPARGC1A axis, underscoring its potential as a therapeutic target in cisplatin-resistant NSCLC.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Proliferação de Células , Cisplatino , Resistencia a Medicamentos Antineoplásicos , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares , MicroRNAs , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , RNA Longo não Codificante , Humanos , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , MicroRNAs/genética , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , RNA Longo não Codificante/genética , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Feminino , Masculino , Animais , Camundongos , Movimento Celular/genética , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Pessoa de Meia-IdadeRESUMO
Ovarian cancer is an extremely malignant gynaecological tumour with a poor patient prognosis and is often associated with chemoresistance. Thus, exploring new therapeutic approaches to improving tumour chemosensitivity is important. The expression of transcription elongation factor B polypeptide 2 (TCEB2) gene is reportedly upregulated in ovarian cancer tumour tissues with acquired resistance, but the specific mechanism involved in tumour resistance remains unclear. In this study, we found that TCEB2 was abnormally highly expressed in cisplatin-resistant tumour tissues and cells. TCEB2 silencing also inhibited the growth and glycolysis of SKOV-3/cisplatin (DDP) and A2780/DDP cells. We further incubated human umbilical vein endothelial cells (HUVECs) with culture supernatants from cisplatin-resistant cells having TCEB2 knockdown. Results revealed that the migration, invasion, and angiogenesis of HUVECs were significantly inhibited. Online bioinformatics analysis revealed that the hypoxia-inducible factor-1A (HIF-1A) protein may bind to TCEB2, and TCEB2 silencing inhibited SKOV-3/DDP cell growth and glycolysis by downregulating HIF1A expression. Similarly, TCEB2 promoted HUVEC migration, invasion, and angiogenesis by upregulating HIF1A expression. In vivo experiments showed that TCEB2 silencing enhanced the sensitivity of ovarian cancer nude mice to cisplatin and that TCEB2 knockdown inhibited the glycolysis and angiogenesis of tumour cells. Our findings can serve as a reference for treating chemoresistant ovarian cancer.
Assuntos
Cisplatino , Resistencia a Medicamentos Antineoplásicos , Glicólise , Subunidade alfa do Fator 1 Induzível por Hipóxia , Neovascularização Patológica , Neoplasias Ovarianas , Transdução de Sinais , Humanos , Feminino , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Animais , Neovascularização Patológica/metabolismo , Neovascularização Patológica/genética , Camundongos , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Camundongos Nus , Células Endoteliais da Veia Umbilical Humana/metabolismo , Movimento Celular , Proliferação de Células , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Ensaios Antitumorais Modelo de Xenoenxerto , AngiogêneseRESUMO
BACKGROUND: Cisplatin (CDDP) remains a key agent in the treatment of muscle-infiltrating bladder carcinoma (MIBC). However, a proportion of MIBC patients do not respond to chemotherapy, which may be caused by the increased repair of CDDP-induced DNA damage. The purpose of this study was to explore the prognostic value of proteins involved in nucleotide excision repair (NER) and translesion DNA synthesis (TLS) in MIBC patients. METHODS: This is a retrospective analysis of 86 MIBC patients. The XPA, XPF, XPG, ERCC1, POLI, POLH and REV3L proteins were stained in primary bladder tumors and their levels were analyzed both in the total cohort and in a subgroup with metastatic urothelial carcinoma (mUC) that received gemcitabine and CDDP as a first-line therapy. Both cohorts were divided by percentage of cancer cells stained positive for each protein into subgroups with high and low expression. In the same manner, the combined expression of NER (XPA + ERCC1 + XPF + XPG) and TLS (POLI + POLH + REV3L), as the whole pathways, was analyzed. RESULTS: Mortality was 89.5% at the median follow-up of 120.2 months. In the total cohort, patients with tumors stained positive for XPA, XPG and POLI had significantly worse overall survival (OS) compared to those with negative staining [hazard ratio (HR) = 0.60, 0.62 and 0.53, respectively]. Both XPG and POLI were independent prognostic factors in multivariate analyses (MVA). In addition, an increase in NER and TLS pathway expression was significantly associated with worse OS in the total cohort (HR = 0.54 and 0.60, respectively). In the mUC subgroup, high POLI expression was associated with significant deterioration of OS (HR = 0.56) in univariate analyses, and its independent prognostic value was shown in MVA. CONCLUSIONS: Our study showed significant correlations between the tumor expression of XPG and POLI, as well as NER and TLS as the whole pathways, and inferior OS. Hence, they could constitute prognostic biomarkers and potentially promising therapeutic targets in MIBC. However, a prospective trial is required for further validation, thereby overcoming the limitations of this study.
Assuntos
Reparo do DNA , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo , Masculino , Feminino , Idoso , Prognóstico , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Cisplatino/uso terapêutico , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Adulto , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Endonucleases/metabolismo , Endonucleases/genética , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Reparo por Excisão , Síntese de DNA TranslesãoRESUMO
OBJECTIVES: This qualitative study explored patients' experiences and perceptions of the SCOPE2 trial. SCOPE2 examined radiotherapy dose escalation in patients with inoperable oesophageal cancer treated with definitive chemoradiotherapy (dCRT). SETTING: Recruitment at five clinical sites in England and Wales, UK. PARTICIPANTS: SCOPE2 trial participants were invited to take part in interviews from across five clinical sites. Participants self-selected to take part in up to three interviews across four different time points: baseline (before treatment) and at 2-3 months, 3-6 months or 6 months+ after baseline. There were five female and five male interview participants. INTERVENTIONS: Participants were randomised to standard dose dCRT prescribed carboplatin/paclitaxel or cisplatin/capecitabine, or an escalated dose dCRT prescribed carboplatin/paclitaxel or cisplatin/capecitabine. METHODS: This qualitative study used semistructured longitudinal interviews to explore the impact of treatment on patient outlook and quality of life and the impact of the COVID-19 pandemic. Interview data were thematically analysed. RESULTS: 10 patients participated in 16 longitudinal interviews. Three participants were accompanied by companions. Participants experienced side-effects from radiotherapy and chemotherapy including nausea, throat pain, difficulties eating and regaining appetite, thrombosis and fatigue, although most of these symptoms gradually improved. Participants required more ongoing information and support regarding treatment side-effects and cancer status in order to improve their overall quality of life. Best practice examples involved key contacts providing practical advice and signposting support. CONCLUSION: Participants of the SCOPE2 trial reported short and longer-term side-effects from chemoradiotherapy, but these usually lessened over time. Participants attempted to be positive about their survival prospects by readjusting their expectations, priorities and lifestyles. Providing patients with ongoing opportunities to discuss detailed and timely information regarding treatment side-effects, aftercare and cancer status could improve the overall health and well-being of patients during oesophageal cancer trials and pathways. TRIAL REGISTRATION NUMBER: NCT02741856; ISRCTN: 97125464.
Assuntos
Quimiorradioterapia , Neoplasias Esofágicas , Paclitaxel , Pesquisa Qualitativa , Qualidade de Vida , Humanos , Masculino , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/psicologia , Feminino , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Pessoa de Meia-Idade , Idoso , Paclitaxel/uso terapêutico , Paclitaxel/administração & dosagem , COVID-19 , Cisplatino/uso terapêutico , Cisplatino/efeitos adversos , Cisplatino/administração & dosagem , Carboplatina/uso terapêutico , Carboplatina/administração & dosagem , Inglaterra , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina/uso terapêutico , Capecitabina/administração & dosagem , SARS-CoV-2 , País de GalesRESUMO
BACKGROUND: In a randomized phase II/III trial (JCOG1008), weekly cisplatin (40 mg/m2) was non-inferior to 3-weekly cisplatin (100 mg/m2) for postoperative high-risk head and neck cancer. We investigated how acute kidney injury (AKI), a major dose-limiting toxicity effect of cisplatin, affects overall survival (OS). METHODS: We analyzed 251 patients from JCOG1008 receiving chemoradiotherapy. AKI was defined based on AKI Network criteria (serum creatinine increase of ≥0.3 mg/dL or ≥1.5-fold [≥ stage I]) within 30 days after completing chemoradiotherapy. OS in the two arms was compared according to AKI development using the log-rank test. RESULTS: The total incidence of AKI was lower in the weekly arm than in the 3-weekly arm (38/122 [31.1%] vs. 56/129 [43.4%]). Additionally, stage II/III AKI occurred less frequently in the weekly arm than in the 3-weekly arm (8/122 [6.6%] vs. 19/129 [14.7%]). Cisplatin doses were similar in the weekly arm for patients with and without AKI (median, 238.6 mg/m2 vs. 239.2 mg/m2; p = 0.94), but lower in the 3-weekly arm for those who developed AKI (median, 276.3 mg/m2 vs. 297.4 mg/m2; p = 0.007). In the weekly arm, there was no difference in OS between patients with and without AKI (hazard ratio [HR], 1.06; 95% confidence interval [CI], 0.53 to 2.10). However, in the 3-weekly arm, patients with AKI had poorer OS than those without AKI (HR, 1.83; 95% CI, 1.04 to 3.21). CONCLUSIONS: In this supplementary analysis of JCOG1008 data, AKI impacted the OS of patients with head and neck cancer undergoing postoperative chemoradiotherapy in the 3-weekly arm but not in the weekly arm. Our results further endorse the utilization of weekly cisplatin at 40 mg/m2 in this setting.
Assuntos
Injúria Renal Aguda , Quimiorradioterapia , Cisplatino , Neoplasias de Cabeça e Pescoço , Humanos , Cisplatino/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/uso terapêutico , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/etiologia , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias de Cabeça e Pescoço/terapia , Neoplasias de Cabeça e Pescoço/mortalidade , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Idoso , Adulto , Antineoplásicos/efeitos adversos , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêuticoRESUMO
PURPOSE: Cisplatin-based combination chemotherapy (CHT) is standard of care in metastatic urothelial cancer (mUC); however, no predictive molecular biomarkers are available for clinical use. The aim of this study was to investigate the impact of molecular subtypes in relation to treatment response and survival in patients with mUC treated with first-line CHT. PATIENTS AND METHODS: Molecular subtype classification according to the Lund Taxonomy (LundTax) was performed by tumor transcriptomic profiling and immunostaining in a retrospective cohort. Molecular subtypes were investigated in relation to the primary end point overall response rate (ORR) and secondary end points progression-free survival (PFS) and overall survival (OS). Differential gene expression and association to treatment response were explored. RESULTS: Ninety-five patients with mUC were classified into urothelial-like (Uro, 43%), genomically unstable (GU, 26%), basal squamous-like (Ba/Sq, 20%), mesenchymal-like (Mes-like, 8%), and small cell neuroendocrine-like (Sc/NE, 3%) subtypes. Patients with Mes-like tumors had lower ORR (14%) compared with Uro (70%), GU (77%), Ba/Sq (75%), and Sc/NE (67%; odds ratio, 0.06 [95% CI, 0.01 to 0.54], P = .012). Furthermore, patients with Mes-like tumors had significantly shorter PFS (hazard ratio [HR], 5.18 [95% CI, 2.28 to 11.76], P < .001) and OS (HR, 3.19 [95% CI, 1.45 to 7.03], P = .004). Patients with Uro and GU showed the longest survival. In responders, an enrichment of downregulated stromal- and immune-related genes was seen. Downregulation of interferon-induced transmembrane protein 2 was associated with increased ORR and improved OS. CONCLUSION: This study identifies different CHT responses by LundTax molecular subtypes in patients with mUC, where the Mes-like subtype was associated with lower response rate and shorter survival.
Assuntos
Cisplatino , Humanos , Masculino , Cisplatino/uso terapêutico , Feminino , Idoso , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Urológicas/tratamento farmacológico , Neoplasias Urológicas/patologia , Neoplasias Urológicas/genética , Antineoplásicos/uso terapêutico , Idoso de 80 Anos ou mais , Adulto , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/mortalidade , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/genética , Carcinoma de Células de Transição/secundário , Carcinoma de Células de Transição/mortalidadeRESUMO
Cisplatin-based chemotherapy is the mainstay in the treatment of germ cell tumors (GCTs). Glutathione S-transferases (GSTs) are polymorphic enzymes that catalyze the glutathione conjugation of alkylating agents, platinum compounds, and free radicals formed by chemotherapy and are thus implicated in developing treatment resistance. This study aimed to assess the expression level of GST mu 1 (GSTM1) and its association with treatment outcomes in patients with GCT. This translational study included tumor specimens from 207 patients with newly diagnosed GCTs, as well as cisplatin-sensitive GCT cell line xenografts and their resistant variants for all histological variants of GCTs. GSTM1 expression was detected by reverse transcription-quantitative PCR and immunohistochemistry using monoclonal antibodies, scored by the multiplicative quickscore (QS) method. GSTM1 expression was correlated with patient/tumor characteristics and treatment outcomes. The highest GSTM1 expression was observed in seminoma, followed by choriocarcinoma, embryonal carcinoma, and yolk sac tumor, while the lowest was observed in teratoma (p<0.0001). There was no association between GSTM1 expression in tumor tissue and patient/tumor characteristics. The low GSTM1 expression was associated with significantly better relapse-free survival compared with high GSTM1 (HR=0.50, 95% CI 0.23-1.09, p=0.03) but not overall survival (HR=0.61, 95% CI 0.24-1.54, p=0.22). Multivariate analysis showed that the prognostic value of GSTM1 was independent of the International Germ Cell Cancer Collaborative Group (IGCCCG) score. These data revealed the prognostic value of GSTM1 in GCTs, with a high GSTM1 expression associated with worse outcomes, suggesting that GSTM1 could be responsible, in part, for treatment resistance in GCTs.
Assuntos
Glutationa Transferase , Neoplasias Embrionárias de Células Germinativas , Humanos , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Embrionárias de Células Germinativas/metabolismo , Neoplasias Embrionárias de Células Germinativas/mortalidade , Glutationa Transferase/metabolismo , Glutationa Transferase/genética , Masculino , Adulto , Cisplatino/uso terapêutico , Resultado do Tratamento , Adulto Jovem , Pessoa de Meia-Idade , Resistencia a Medicamentos Antineoplásicos , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/patologia , Neoplasias Testiculares/metabolismo , Neoplasias Testiculares/mortalidade , Adolescente , Animais , Feminino , Prognóstico , Linhagem Celular Tumoral , CamundongosRESUMO
PURPOSE: To evaluate the long-term efficacy and safety of GP and TPF sequential chemotherapy regimens in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC). METHODS: From 2005 to 2016, a total of 408 LA-NPC patients treated with GP or TPF sequential chemoradiotherapy were retrospectively included. Propensity Score Matching (PSM) was employed to balance the baseline variables. Survival outcomes and acute toxicities were compared between both groups. RESULTS: A total of 230 patients were selected by 1:1 PSM. At a median follow-up of 91 months, no significant differences were observed between the matched GP and TPF groups regarding 5-year overall survival, progression-free survival, distant metastasis-free survival, and locoregionally relapse-free survival (83.4% vs. 83.4%, P = 0.796; 75.6% vs. 68.6%, P = 0.301; 86.7% vs. 81.1%, P = 0.096; and 87.4% vs. 87.2%, P = 0.721). Notable disparities in adverse effects were identified, with higher incidences of grade 3/4 thrombocytopenia in the GP group while grade 3/4 leukopenia and neutropenia in the TPF group. Though not recorded in our cohort, combined with the FAERS database, thrombotic adverse reactions are a concern for the GP regimen, while the TPF regimen requires vigilance for life-threatening adverse reactions such as septic shock, acute respiratory distress syndrome, and laryngeal edema. CONCLUSION: No significant difference in long-term outcomes was observed between the GP and TPF sequential chemotherapy regimens for LA-NPC. Differences in adverse effects should be noted when choosing the regimen.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Quimiorradioterapia , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Pontuação de Propensão , Humanos , Masculino , Feminino , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/tratamento farmacológico , Pessoa de Meia-Idade , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/mortalidade , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Adulto , Idoso , Resultado do Tratamento , Cisplatino/administração & dosagem , Cisplatino/uso terapêutico , Cisplatino/efeitos adversos , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Gencitabina , Seguimentos , Compostos OrganoplatínicosRESUMO
Objective: Nivolumab, recently proven in a phase 3 clinical trial (CheckMate 901) to enhance survival when combined with gemcitabine-cisplatin for advanced urothelial carcinoma. This study aimed to assess its cost-effectiveness against gemcitabine-cisplatin alone, from US and Chinese payers' perspectives. Methods: A partitioned survival model was established to assess the life-years, quality-adjusted life-years (QALYs), lifetime costs, and incremental cost-effectiveness ratios (ICERs) of nivolumab plus gemcitabine-cisplatin versus gemcitabine-cisplatin alone as first-line treatment for advanced urothelial carcinoma. Univariate, two-way, and probabilistic sensitivity analyses were conducted to assess the model's robustness. Additionally, subgroup analyses were performed. Results: Nivolumab plus gemcitabine-cisplatin and gemcitabine-cisplatin achieved survival benefits of 4.238 life-years and 2.979 life-years for patients with advanced urothelial carcinoma, respectively. Compared with gemcitabine-cisplatin, nivolumab plus gemcitabine-cisplatin resulted in ICERs of $116,856/QALY in the US and $51,997/QALY in China. The probabilities of achieving cost-effectiveness at the current willingness-to-pay thresholds were 77.5% in the US and 16.5% in China. Cost-effectiveness could be reached if the price of nivolumab were reduced to $920.87/100mg in China. Subgroup analyses indicated that the combination had the highest probability of cost-effectiveness in patients under 65 or with an Eastern Cooperative Oncology Group (ECOG) performance-status score of 0 in the US and China. Conclusion: Nivolumab plus gemcitabine-cisplatin first-line treatment for advanced urothelial carcinoma results in longer life expectancy than gemcitabine-cisplatin, but is not cost-effective in China at current price. However, cost-effectiveness is likely to be achieved in most patient subgroups in the US.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Cisplatino , Análise Custo-Benefício , Desoxicitidina , Gencitabina , Nivolumabe , Humanos , Cisplatino/economia , Cisplatino/administração & dosagem , Cisplatino/uso terapêutico , Desoxicitidina/análogos & derivados , Desoxicitidina/economia , Desoxicitidina/administração & dosagem , Desoxicitidina/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/economia , Nivolumabe/economia , Nivolumabe/administração & dosagem , Nivolumabe/uso terapêutico , China , Estados Unidos , Masculino , Anos de Vida Ajustados por Qualidade de Vida , Feminino , Pessoa de Meia-Idade , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/economia , Neoplasias Urológicas/tratamento farmacológico , Neoplasias Urológicas/mortalidade , Neoplasias Urológicas/economia , IdosoRESUMO
MORC family CW-type zinc finger 2 (MORC2) is a newly identified chromatin remodeling protein, and has been proposed as a prognostic biomarker associated with survival in some types of human cancer, but the role of MORC2 in cervical cancer remains unknown. Here, we investigated the role of MORC2 expression in predicting the survival outcomes of locally advanced cervical cancer patients treated with cisplatin-based concurrent chemoradiotherapy (CCRT). In this retrospectively study, we detected MORC2 immunohistochemical expression on 55 biopsies from patients who underwent CCRT. The association between the MORC2 expression and various clinicopathological characteristics were analyzed, as were association between MORC2 expression and locoregional failure and progression-free survival (PFS) of cervical cancer patients. MORC2 expression was positively associated with pelvic node metastasis and locoregional failure. Higher MORC2 expression was a significant indicator of worse PFS. Our results suggest that MORC2 expression may be a prognostic indicator in patients with locally advanced cervical cancer undergoing CCRT.
Assuntos
Quimiorradioterapia , Intervalo Livre de Progressão , Neoplasias do Colo do Útero , Humanos , Neoplasias do Colo do Útero/terapia , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/metabolismo , Feminino , Quimiorradioterapia/métodos , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Biomarcadores Tumorais/metabolismo , Prognóstico , Idoso , Cisplatino/uso terapêutico , Fatores de Transcrição/metabolismoRESUMO
BACKGROUND: Previous studies have demonstrated that the glycolytic enzyme phosphoglycerate kinase 1 (PGK1) can promote tumor development. This study sought to investigate the specific role of PGK1 in bladder cancer (BLCA). METHODS: Public databases and immunohistochemistry assays were utilized to analyze the expression of PGK1 in BLCA and its prognostic significance. Cell proliferation was assessed through CCK-8 and colony formation assays, while the level of metastasis was evaluated using transwell migration experiments. Additionally, IC50 experiments were conducted to assess the impact of PGK1 on cisplatin sensitivity. RESULTS: The mRNA and protein expression levels of PGK1 were significantly upregulated in BLCA. Cox proportional hazards model analysis revealed that PGK1 and T stage were independent prognostic factors for BLCA patients. Both CCK-8 and colony assays demonstrated that PGK1 promotes proliferation. Furthermore, a positive correlation was observed between PGK1 and Ki67, a proliferation index. Transwell migration assays confirmed the ability of PGK1 to enhance metastasis. Finally, PGK1 increased the IC50 associated with cisplatin treatment in BLCA. CONCLUSION: Collectively, these findings suggest that PGK1 may hold clinical value in predicting BLCA prognosis and improving the outcomes of this patient population.
Assuntos
Movimento Celular , Proliferação de Células , Cisplatino , Fosfoglicerato Quinase , Neoplasias da Bexiga Urinária , Humanos , Fosfoglicerato Quinase/metabolismo , Fosfoglicerato Quinase/genética , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/tratamento farmacológico , Prognóstico , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Masculino , Linhagem Celular Tumoral , Feminino , Pessoa de Meia-Idade , Regulação Neoplásica da Expressão Gênica , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , IdosoRESUMO
Background and Objectives: Cisplatin is a chemotherapeutic drug that is frequently used with hyperthermic intraperitoneal chemotherapy (HIPEC). Cisplatin-induced gonadotoxicity leads to a depletion of the ovarian reserve, causing premature ovarian insufficiency. This study aimed to investigate the impact of hyperthermia on cisplatin-induced ovarian toxicity and to determine whether sevoflurane or desflurane could be a more appropriate choice of anesthetic for reducing ovarian toxicity in HIPEC procedures. Materials and Methods: A total of 24 New Zealand rabbits were randomly divided into 4 groups as follows: Group H: HIPEC (cisplatin 7 mg/kg), Group HS: HIPEC (cisplatin 7 mg/kg) + 3% sevoflurane (2 h), Group HD: HIPEC (cisplatin 7 mg/kg) + 6% desflurane (2 h), and Group C: Control (Saline). Two catheters were placed in the abdominal cavity, the upper and lower quadrants. The perfusate was heated to 42 °C and given intraperitoneally for 90 min at a rate of 4 mL/min by catheters. Ovarian tissues were collected for Hematoxylin and Eosin staining and immunohistochemical analysis. Results: The primary follicle number was significantly decreased in Group H and HD compared to the C group (p < 0.05). Bax expression was high in Group H, according to all groups (p < 0.0001). Bax expression significantly decreased after sevoflurane, compared to group H (p = 0.012). The bcl-2 expression decreased in all groups compared to the C group. Bcl-2 expression was increased with sevoflurane compared to the H group (p = 0.001). Caspase 3 and p53 expression increased in all groups compared to the C group. p53 expression was decreased with sevoflurane and desflurane compared to the H group (p = 0.002, p = 0.008, respectively). Conclusions: The application of cisplatin with the intraoperative HIPEC method caused ovarian damage. According to our results, sevoflurane anesthesia could be a better option in mitigating cell death I the n ovarian reserve (follicle count) and apoptosis in the HIPEC procedures. We think that our findings should be supported by large series of clinical and experimental studies.
Assuntos
Cisplatino , Quimioterapia Intraperitoneal Hipertérmica , Ovário , Sevoflurano , Animais , Feminino , Coelhos , Quimioterapia Intraperitoneal Hipertérmica/métodos , Ovário/efeitos dos fármacos , Cisplatino/uso terapêutico , Cisplatino/farmacologia , Sevoflurano/farmacologia , Anestésicos Inalatórios , Desflurano/administração & dosagem , Antineoplásicos/uso terapêutico , Antineoplásicos/efeitos adversos , Distribuição AleatóriaRESUMO
BACKGROUND: Herbal medicine combined with nanotechnology offers an alternative to the increasing burden of surgery and/or chemotherapy, the main therapeutics of oral carcinoma. Phytosomes are nano-vesicular systems formed by the interaction between phospholipids and phyto-active components via hydrogen bonding, exhibiting superior efficacy over pure phytocomponents in drug delivery. METHODS: Tetrahydrocurcumin (THC)-phytosomes were prepared by thin film hydration method. After characterization, in vitro cytotoxicity, antiproliferative capacity, antioxidant potential and full apoptotic workup were paneled on oral squamous cell carcinoma (SCC4) in comparison with native THC-solution and cisplatin (3.58 µg/mL intravenous injection), as positive controls. In addition, we tested the three medications on normal oral keratinocytes and gingival fibroblasts to attest to their tissue-selectivity. RESULTS: Successful preparation of THC-phytosomes using 1:1 molar ratio of THC to phospholipid exhibited significantly increased aqueous solubility, good colloidal properties, and complete drug release after one hour. On SCC4 cells, THC-phytosomes, at their dose-/time-dependency at ~ 60.06 µg/mL escalated cell percentages in the S-phase with 32.5 ± 6.22% increase, as well as a startling 29.69 ± 2.3% increase in apoptotic population. Depletion of the cell colonies survival to 0.29 ± 0.1% together with restraining the migratory rate by -6.4 ± 6.8% validated THC-phytosomes' antiproliferative capacity. Comparatively, the corresponding results of THC-solution and cisplatin revealed 12.9 ± 0.9% and 25.8 ± 1.1% for apoptosis and 0.9 ± 0.1% and 0.7 ± 0.08% for colony survival fraction, respectively. Furthermore, the nanoformulation exhibited the strongest immuno-positivity to caspase-3, which positively correlated with intense mitochondrial fluorescence by Mitotracker Red, suggesting its implication in the mitochondrial pathway of apoptosis, a finding further explained by the enormously high Bax and caspase-8 expression by RT-qPCR. Finally, the THC groups showed the lowest oxidative stress index, marking their highest free radical-scavenging potential among the test groups. CONCLUSIONS: THC-phytosomes are depicted to be an efficient nanoformulation that enhanced the anticancer efficacy over the free drug counterpart and the conventional chemotherapeutic. Additionally, being selective to cancer cells and less cytotoxic to normal cells makes THC-phytosomes a potential candidate for tissue-targeted therapy.
Assuntos
Apoptose , Carcinoma de Células Escamosas , Curcumina , Neoplasias Bucais , Humanos , Curcumina/farmacologia , Curcumina/análogos & derivados , Curcumina/uso terapêutico , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/patologia , Apoptose/efeitos dos fármacos , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Antioxidantes/farmacologia , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Fibroblastos/efeitos dos fármacos , Antineoplásicos/farmacologia , Queratinócitos/efeitos dos fármacos , Progressão da Doença , Fosfolipídeos/química , Fosfolipídeos/farmacologia , FitossomasRESUMO
BACKGROUND: The poor overall survival of osteosarcoma (OS) underscores the need to explore new therapeutic avenues. Tumor necrosis rate (TNR) after neoadjuvant chemotherapy predicts prognosis. AIMS: The study was to investigate safety and activity of neoadjuvant chemotherapy with camrelizumab (a humanized antibody against PD-1) in patients with resectable OS. MATERIALS & METHODS: We conducted a prospective, single-arm, exploratory phase II trial in OS patients. Eligible patients received camrelizumab combined with doxorubicin or liposomal doxorubicin, cisplatin, methotrexate, ifosfamide with mesna. Surgery was performed 12-14 days after neoadjuvant therapy and adjuvant therapy starting 2-3 weeks postoperatively. The primary endpoint was the rate of good tumor necrosis (TNR ≥90%) after neoadjuvant therapy, and the secondary outcomes were safety, 2-year progression free survival and 2-year overall survival. RESULTS: Seventy-five patients were recruited to the study. Subsequently, 64 patients completed neoadjuvant therapy and underwent surgery. Thirty-one patients (48.4%) have a good TNR to neoadjuvant therapy. With a median follow-up of 22.4 months (range 2.2-44.9 months), the estimated 2-year PFS was 69.6% and the estimated 2-year overall survival was 89.4%. Grade 3 or 4 treatment-related adverse events were noticed in 62.7% of the patients. Frequent grade 3 or 4 adverse events were decreased platelet count (45.3%), decreased white blood cell count (36%). No immune-related serious adverse events were observed. DISCUSSION: Our study had limitations. First, it was limited by its non-randomized design. Besides, stromal tumor-infiltrating lymphocytes was comprehensively analyzed in this study. CONCLUSIONS: This study demonstrated that amrelizumab combined with adriamycin, cisplatin, methotrexate, and ifosfamide in the neoadjuvant treatment of resectable OS was safe and tolerable. This combined therapeutic strategy may not increase TNR, but the long-term survival benefit remains to be followed up.
Assuntos
Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Cisplatino , Doxorrubicina , Ifosfamida , Metotrexato , Terapia Neoadjuvante , Osteossarcoma , Humanos , Feminino , Osteossarcoma/tratamento farmacológico , Osteossarcoma/mortalidade , Osteossarcoma/terapia , Osteossarcoma/cirurgia , Masculino , Metotrexato/administração & dosagem , Metotrexato/uso terapêutico , Ifosfamida/administração & dosagem , Ifosfamida/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Terapia Neoadjuvante/métodos , Cisplatino/administração & dosagem , Cisplatino/uso terapêutico , Adulto , Estudos Prospectivos , Adulto Jovem , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Adolescente , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Neoplasias Ósseas/terapia , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: Overall treatment time (OTT) is an important index for local control in patients with locally advanced| cervical cancer treated with definitive chemoradiation (External Beam Radiation Therapy (EBRT), Brachytherapy (BT) and concomittant chemotherapy). This study aimed to evaluate the efficiency and safety of reducing OTT by shortening the brachytherapy duration to one week in the intervention group copared to three weeks in the control group. METHOD: The study was a non-randomized open-label phase II clinical trial, carried out on 49 cervical cancer patients (26 in intervention grouop and 23 in control group) who received EBRT concomitant with Cisplatin, followed by brachytherap in order to deliver 60 Gy equivalent total doses in 2-Gy fractions (EQD2) to Intermediate Risk-Clinical Tumor Volume (IR-CTV) and 85-90 Gy EQD2 to High Risk-Clinical Tumor Volume (HR-CTV). In the intervention group, all brachytherapy sessions were performed in 1 week, while for the control group, it was administrated in 3 consecutive weeks. The participants were followed (Minimum follow up time was 6 month and median follow up time was 10 month) to assess response and toxicity of the treatment. RESULTS: Overall, more than 95% of study participants had a complete response and more than 4.0% reported partial response, and no treatment failure was observed. The complete response in intervention and control groups was 96.1% and 95.6%, respectively (P value > 0.05). There was no difference in acute toxicity between the two groups. CONCLUSION: considering that short course brachytherapy was non inferior to conventional course from point of Response Rate and Side Effects during follow up time; so this strategy can be considered as an option for reducing the OTT which can at least cause decreasing the costs. Studies with larger sample size and phase 3 are recommended.
Assuntos
Braquiterapia , Neoplasias do Colo do Útero , Humanos , Feminino , Braquiterapia/métodos , Braquiterapia/efeitos adversos , Neoplasias do Colo do Útero/radioterapia , Neoplasias do Colo do Útero/patologia , Pessoa de Meia-Idade , Seguimentos , Adulto , Prognóstico , Cisplatino/uso terapêutico , Estudos de Casos e Controles , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/patologia , Quimiorradioterapia , Dosagem Radioterapêutica , Adenocarcinoma/radioterapia , Adenocarcinoma/patologia , IdosoRESUMO
BACKGROUND: Pembrolizumab plus cisplatin and 5-fluorouracil administered as first-line therapy for advanced esophageal cancer patients has shown a better objective response and survival than conventional chemotherapy with less severe hematological adverse events. The safety and efficacy of this regimen were evaluated in patients with T4b esophageal squamous cell carcinoma (ESCC). METHODS: Eight consecutive patients with T4b ESCC received this regimen according to KEYNOTE-590 as induction, and they were evaluated after 1-3 courses. The programmed death-ligand 1 (PD-L1) combined positive score (CPS) was also evaluated before chemotherapy. Efficacy for the primary lesion was evaluated by our original formula for the tumor reduction rate. RESULTS: The numbers of patients with partial response (PR), stable disease, and progressive disease (PD) were 5, 1, and 2, respectively. The tumor reduction rate ranged from 69 to 87% in PR patients, and all PR patients had relief from T4b. Two patients underwent conversion surgery with R0 resection. PD-L1 CPS was over 90 in 2 PR patients, but under 10 in 2 other PR patients. PD-L1 CPS was under 10 in PD patients. One patient had hyperprogression, resulting in an esophago-pulmonary fistula. Greater than grade 3 adverse events were bleeding gastric ulcer in one patient (12.5%), neutropenia without G-CSF in 3 patients (37.5%), and hypopotassemia in 1 patient (12.5%). No patient had febrile neutropenia. CONCLUSIONS: Marked tumor reduction was confirmed in 62.5% of patients with pembrolizumab plus cisplatin and 5-fluorouracil with less adverse events. This regimen could be administered as induction chemotherapy for patients with T4b ESCC.
Assuntos
Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Cisplatino , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Fluoruracila , Humanos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Cisplatino/uso terapêutico , Fluoruracila/administração & dosagem , Fluoruracila/uso terapêutico , Fluoruracila/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Masculino , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/patologia , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Pessoa de Meia-Idade , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Idoso , Antígeno B7-H1 , Resultado do Tratamento , Estadiamento de Neoplasias , Progressão da DoençaRESUMO
OBJECTIVE: Aim: To analyze the results of treatment of patients with oropharyngeal carcinoma. PATIENTS AND METHODS: Materials and Methods: 276 patients with oropharyngeal carcinoma were treated in 2008-2021. Neoadjuvant chemotherapy consisted of three to six cycles: paclitaxel 175 mg/m2 and carboplatin 350 mg/m2 (or cisplatin 100 mg/m2) on the first day. The interval between cycles was 21 days. After the cycles, all patients were prescribed a course of radiation therapy in a total focal dose (TFD) of 65 Gy. The outcome of treatment was assessed by the degree of tumor regression according to RECIST criteria one month after the end of combination treatment. Statistical processing was performed using STATISTICA 6.1 software (StatSoftInc). RESULTS: Results: The three- and five-year survival rates of the examined patients with oropharyngeal carcinoma after treatment were 40.8% respectively (95% CI 33.7 - 47.9) and 27.0%, (95% CI 20.6 - 33, 4) with a median survival of 36 months with 95% CI (35.5 - 40.2). Processing was performed using STATISTICA 6.1 software (StatSoftInc). CONCLUSION: Сonclusions: Analysis of treatment of patients with oropharyngeal carcinoma with predominance of squamous cell carcinoma (90.6%), localized primarily in the palatine tonsil (73.2%), with the most common stages T3N1M0 (30.1%) and T3N1M0 %), with regional metastases to the lymph nodes of the neck (89.9%), showed that the effectiveness of treatment of patients is quite high, because in most of the examined in the short term after combined treatment there was complete or partial regression of the tumor (91.7%), no progression of the oncological process was detected in any of them.