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1.
Clin Transl Gastroenterol ; 15(6): e1, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38742743

RESUMO

INTRODUCTION: We designed a race-conscious study to assess the presence of Helicobacter pylori v irulence factor cagA in a retrospective cohort of patients with active H. pylori infection. METHODS: We compared cagA status by race in gastric tissue samples from 473 patients diagnosed with active H. pylori infection from 2015 to 2019. RESULTS: H. pylori + Black patients were 2 times more likely to be cagA + than H. pylori + White patients (82% vs 36%, P < .0001). DISCUSSION: Presence of cagA is common among endoscopy patients with active H. pylori infection; appropriate testing and treatment of H. pylori can both reduce gastric cancer risk and address health disparities.


Assuntos
Antígenos de Bactérias , Proteínas de Bactérias , Infecções por Helicobacter , Helicobacter pylori , Fatores de Virulência , Humanos , Helicobacter pylori/isolamento & purificação , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/microbiologia , Antígenos de Bactérias/análise , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Prevalência , Fatores de Virulência/análise , Adulto , Idoso , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/epidemiologia , População Branca/estatística & dados numéricos , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Negro ou Afro-Americano/estatística & dados numéricos
2.
Clin Genitourin Cancer ; 22(3): 102080, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38653037

RESUMO

BACKGROUND: There is currently limited literature assessing the real-world treatment patterns and clinical outcomes of patients with metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair (HRR) mutations. METHODS: Medical charts were abstracted for mCRPC patients with ≥ 1 of 12 HRR somatic gene alterations treated at US oncology centers participating in the American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange. Treatment patterns and clinical outcomes were assessed from the initiation of first-line or later (1L+) mCRPC therapy received on or after July 1, 2014. RESULTS: Among 138 patients included in the study, the most common somatic HRR mutations were CDK12 (47.8%), BRCA2 (22.5%), and ATM (21.0%). Novel hormonal therapy and taxane chemotherapy were most commonly used in 1L; taxane use increased in later lines. Median overall survival (95% confidence interval [CI]) was 36.3 (30.7-47.8) months from initiation of 1L therapy and decreased for subsequent lines. Similarly, there was a trend of decreasing progression-free survival and prostate-specific antigen response from 1L to 4L+ therapy. CONCLUSIONS: Treatment patterns identified in this study were similar to those among patients with mCRPC regardless of tumor HRR mutation status in the literature.


Assuntos
Proteína BRCA2 , Mutação , Neoplasias de Próstata Resistentes à Castração , Reparo de DNA por Recombinação , Humanos , Masculino , Idoso , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia , Proteína BRCA2/genética , Pessoa de Meia-Idade , Proteínas Mutadas de Ataxia Telangiectasia/genética , Taxoides/uso terapêutico , Taxoides/administração & dosagem , Quinases Ciclina-Dependentes/genética , Resultado do Tratamento , Idoso de 80 Anos ou mais , Antígeno Prostático Específico/sangue , Hidrocarbonetos Aromáticos com Pontes/uso terapêutico , Hidrocarbonetos Aromáticos com Pontes/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos Retrospectivos , Metástase Neoplásica
3.
NPJ Precis Oncol ; 8(1): 124, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38822082

RESUMO

Acquired resistance remains a major challenge for therapies targeting oncogene activated pathways. KRAS is the most frequently mutated oncogene in human cancers, yet strategies targeting its downstream signaling kinases have failed to produce durable treatment responses. Here, we developed multiple models of acquired resistance to dual-mechanism ERK/MAPK inhibitors across KRAS-mutant pancreatic, colorectal, and lung cancers, and then probed the long-term events enabling survival against this class of drugs. These studies revealed that resistance emerges secondary to large-scale transcriptional adaptations that are diverse and cell line-specific. Transcriptional reprogramming extends beyond the well-established early response, and instead represents a dynamic, evolved process that is refined to attain a stably resistant phenotype. Mechanistic and translational studies reveal that resistance to dual-mechanism ERK/MAPK inhibition is broadly susceptible to manipulation of the epigenetic machinery, and that Mediator kinase, in particular, can be co-targeted at a bottleneck point to prevent diverse, cell line-specific resistance programs.

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