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BACKGROUND: To compare the association between prostate-specific antigen (PSA) levels and prostate cancer-specific mortality (PCSM), and the effectiveness of local treatment in patients with high-grade and low-grade prostate cancer (PCa). METHODS: This retrospective cohort study enrolled patients diagnosed with clinically localized PCa (cT1-4N0M0) from January 2010 to December 2020 in the Surveillance, Epidemiology and End Results (SEER) database. Fine-Gray competing risk regression analysis was conducted to generate cumulative incidence plots and estimate the hazards ratio (HR) and 95% confidence interval (95% CI) of PCSM. Multivariable restricted cubic spline (RCS) analysis was used to examine the non-linear associations of continuous values of PSA levels with PCSM. Inverse probability of treatment weighting (IPTW) was employed to minimize imbalances in baseline characteristics between different local treatment cohorts. RESULTS: A total of 392083 eligible patients were included in the study, including 327659 low-grade (Gleason score [GS]≤7) PCa and 64424 high-grade (GS≥8) PCa. In multivariate Fine-Gray competing risk regression analysis, using PSA levels of 4.1-10.0 ng/ml as the reference, the adjusted HR among high-grade patients with PSA levels ≤2.5 ng/ml, 2.6-4.0 ng/ml, 10.1-20.0 ng/ml and >20.0 ng/ml were 1.988 (95% CI=1.677-2.358), 1.411 (95% CI=1.194-1.668), 1.472 (95% CI=1.351-1.603) and 2.506 (95% CI=2.318-2.709), respectively. Among low-grade PCa, the adjusted HR were 0.985 (95% CI=0.800-1.213), 0.727 (95% CI=0.602-0.877), 1.844 (95% CI=1.679-2.026) and 3.574 (95% CI=3.220-3.966), respectively. Multivariable-adjusted RCS analysis showed a U/J-shaped distribution relationship between PSA levels and PCSM in high-grade PCa, while there was a positive association between PSA levels and PCSM in low-grade PCa. As for local treatment effectiveness, radiation therapy (RT) provided better control of PCSM compared to radical prostatectomy (RP) and RP+RT in high-grade PCa, while RP provided better control of PCSM compared to RT and RP+RT in low-grade PCa. CONCLUSION: Low PSA level (≤2.5 ng/ml) is significantly associated with very high risk of PCSM in high-grade localized PCa but not in low-grade localized PCa. High-grade localized PCa patients benefit more from RT in terms of PCSM control, while low-grade localized PCa patients benefit more from RP. High-grade localized PCa with low PSA level may be a unique subgroup that could benefit from novel risk stratification strategies in PCa, which requires further studies to investigate the potential of developing novel therapeutic strategies, prognostic tools, and clinical management approaches.
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BACKGROUND: The B7 protein family is one of the most important immune checkpoint proteins. Gastric cancer (GC) is the fourth most common cause of cancer-related mortality worldwide and shows a significant correlation with the B7 family in tumorigenesis and progression. Helicobacter pylori infection is the most important risk factor promoting the progression of gastric precancerous lesions and GC, which also affects the expression of B7 family members. We aimed to systematically summarize and review current studies on the expression and function of B7 family members during H. pylori infection in precancerous gastric lesions and GC. MATERIALS AND METHODS: PubMed was searched for the relationship between B7 family, H. pylori and gastric carcinogenesis until April 5, 2023. Different permutation and combination of the search terms, including "H. pylori," "Helicobacter pylori," "B7," "gastric cancer," and "gastric precancerous lesions," all the different names of specific B7 molecules, and the names of signaling pathways were used. Literature related to our research topic was selected and summarized. RESULTS: The B7 family participates in gastric carcinogenesis through certain immune signaling pathways by binding to their receptors and exhibiting co-inhibitory or co-stimulatory effects. Targeting the B7 family members with mAbs may be a promising therapeutic strategy for treating gastric diseases. CONCLUSIONS: A thorough understanding of the role of B7 molecules during H. pylori infection and GC progression is helpful for the treatment and prevention of GC and the prediction of H. pylori infection outcomes, providing evidence for H. pylori eradication.
Assuntos
Infecções por Helicobacter , Helicobacter pylori , Lesões Pré-Cancerosas , Neoplasias Gástricas , Humanos , Infecções por Helicobacter/tratamento farmacológico , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Carcinogênese/genética , Carcinogênese/patologia , Lesões Pré-Cancerosas/patologia , Antígenos B7/farmacologia , Mucosa Gástrica/patologiaRESUMO
Paclitaxel is one of the most effective chemotherapy drugs for breast cancer worldwide but 2030% patients show primary resistance to the drug. Screening and identification of markers that facilitate effective and rapid prediction of sensitivity to paclitaxel is therefore an urgent medical requirement. In the present study, G protein signaling modulator 2 (GPSM2) mRNA levels were significantly associated with taxane sensitivity in experiments based on the Gene Expression Omnibus (GEO) online database. Immunohistochemical analysis consistently revealed a significant association of GPSM2 protein levels with paclitaxel sensitivity in breast cancer patients. Knockdown of GPSM2 reduced the sensitivity of breast cancer cells to paclitaxel via regulation of the cell cycle. Animal experiments further corroborated our in vitro findings. These results suggest that GPSM2 plays an important role in breast cancer resistance, supporting its utility as a potential target for improving drug susceptibility in patients as well as a marker of paclitaxel sensitivity.
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Neoplasias da Mama/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Paclitaxel/administração & dosagem , Idoso , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Hidrocarbonetos Aromáticos com Pontes/administração & dosagem , Hidrocarbonetos Aromáticos com Pontes/efeitos adversos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Humanos , Células MCF-7 , Camundongos , Pessoa de Meia-Idade , Paclitaxel/efeitos adversos , RNA Mensageiro/genética , Taxoides/administração & dosagem , Taxoides/efeitos adversos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Neoadjuvant chemotherapy (NAC) is the major preoperative treatment of breast cancer (BC) with negative human epidermal growth factor receptor 2 (HER2), and the efficacy of NAC and the optimization of regimen are under intensive research. The current study aimed to define the predictive biomarkers for paclitaxel (PTX) response in NAC of HER2-negative BC. Data from GSE25065, GSE26065, GSE41998, as well as drug sensitivity data of breast and ovarian cancer cell line from NCI60, were used. Through logistic regression, COX regression, and correlation analysis with bootstrapping, we found that four genes (CDK8, FAM64A, MARC2, and OCEL1) were associated with drug sensitivity of PTX. The four gene "≥3" model had the best classification accuracy. Subgroup analysis found that the model performed well in the hormone receptor positive, HER2-negative subgroup and did not perform well in the triple-negative subgroup. Decision curve analysis showed that the model could enhance the predictive effect of clinical features. Subsequent gene set enrichment analysis, network analysis showed that these genes may be related to the cell cycle, mitosis and other pathways. The current study demonstrated the promising potential of the novel four-gene signature as a predictive biomarker for pathological complete response of HER2-negative BC patients and indicated the drug sensitivity of PTX.
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Neoplasias da Mama/tratamento farmacológico , Terapia Neoadjuvante/métodos , Paclitaxel/uso terapêutico , Receptor ErbB-2/metabolismo , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/genética , Linhagem Celular Tumoral , Feminino , Humanos , Modelos Logísticos , Mitose/efeitos dos fármacos , Mitose/genética , Análise Multivariada , Modelos de Riscos Proporcionais , Receptor ErbB-2/genética , Resultado do TratamentoRESUMO
Fas has been reported to play an important role in apoptosis; however, Fas-mediated autophagy and its mechanism are still unclear. Here, we found that Fas agonistic antibody CH11-induced autophagy in HeLa cells, and inhibition of autophagy by 3-MA increased CH11-induced apoptosis. A Fas antagonistic antibody (UB2) suppressed both CH11-induced autophagy and apoptosis. In addition, the CH11-induced autophagy was blocked by JNK inhibitor (SP600125), but it was not affected by caspase 8 inhibitor (Z-IETD); whereas the CH11-induced apoptosis was increased by SP600125, and it was suppressed by Z-IETD. Further experiments confirmed that JNK was activated by CH11 dose-dependently, and the activation was suppressed when autophagy was blocked by 3-MA. Together, our results suggest that JNK, but not caspase 8, involves in Fas-mediated CH11-induced autophagy in HeLa cells, and this autophagy plays a protective role in CH11-induced cell death.