RESUMO
BACKGROUND: immune checkpoint inhibitors(ICIs) have shown contradictory results in patients with advanced gastro-oesophageal junction/gastric cancer(GOJ/GC). AIM: to identify specific patient subgroups that would derive survival benefit from ICIs. METHODS: a subgroup meta-analysis of randomised clinical trials(RCTs) was carried out. RESULTS: four phase-III-RCTs were identified with data on the following variables: primary location(Gastric vs GOJ); age(≤ 65 vs >65); gender(male vs female); ECOG PS(0 vs 1); ethnicity (Asian vs non-Asian), histology(intestinal vs diffuse), PD-L1 expression(≥ 1% vs < 1%). PD-L1 positivity was significantly associated with survival benefit from ICIs (HR: 0.82, p 0.047), with a significant interaction between PD-L1 expression and ICI efficacy (interaction HR: 1.41, p 0.02). Numerically, the second most relevant interaction was ICI efficacy and gender, with ICI being more effective in males. CONCLUSION: The PD-L1 positive patient subgroup derives significant survival benefit from ICI in GOJ/GC, however other predictors are eagerly needed to further refine patient selection.
Assuntos
Adenocarcinoma , Neoplasias Gástricas , Adenocarcinoma/tratamento farmacológico , Junção Esofagogástrica , Feminino , Humanos , Inibidores de Checkpoint Imunológico , Masculino , Receptor de Morte Celular Programada 1 , Neoplasias Gástricas/tratamento farmacológicoRESUMO
Excision repair cross-complementation group 1 (ERCC1) is a key component in DNA repair mechanisms and may influence the tumor DNA-targeting effect of the chemotherapeutic agent oxaliplatin. Germline ERCC1 polymorphisms may alter the protein expression and published data on their predictive and prognostic value have so far been contradictory. In the present article we review available evidence on the clinical role and utility of ERCC1 polymorphisms and, in the absence of a 'perfect' trial, what we call the 'sliding doors' trial, we present the data of ERCC1 genotyping in our local patient population. We found a useful predictive value for oxaliplatin-induced risk of anemia.
Assuntos
Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/enzimologia , Proteínas de Ligação a DNA/genética , Endonucleases/genética , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/genética , Reparo do DNA , DNA de Neoplasias/genética , Proteínas de Ligação a DNA/química , Endonucleases/química , Feminino , Humanos , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Polimorfismo de Nucleotídeo Único , Prognóstico , Proteína de Replicação C/química , Proteína de Replicação C/genética , Fatores de Transcrição/química , Fatores de Transcrição/genéticaAssuntos
Clonidina , Hipertensão Renovascular/diagnóstico , Neoplasias das Glândulas Suprarrenais/complicações , Neoplasias das Glândulas Suprarrenais/diagnóstico , Adulto , Reações Falso-Positivas , Feminino , Humanos , Hiperaldosteronismo/complicações , Hiperaldosteronismo/diagnóstico , Hipertensão Renovascular/etiologia , Masculino , Pessoa de Meia-Idade , Feocromocitoma/complicações , Feocromocitoma/diagnóstico , Sensibilidade e EspecificidadeRESUMO
The authors studied the antihypertensive effect and tolerability of a new sustained-release formulation of nifedipine 50 mg once a day, in comparison with nifedipine retard 20 mg twice a day in patients with mild or moderate primary arterial hypertension. Both treatments significantly lowered blood pressure with no difference in daily blood pressure profile. At steady state, the two drugs determined comparable plasma levels of nifedipine as measured immediately before the morning dose. After a 12-month treatment, the new formulation of nifedipine still displayed satisfactory blood pressure control in both supine and standing positions, with no change in tolerability throughout the study. In conclusion, this new sustained-release formulation of nifedipine has similar efficacy and tolerability to conventional treatment with nifedipine retard 20 mg twice a day.
Assuntos
Hipertensão/tratamento farmacológico , Nifedipino/uso terapêutico , Preparações de Ação Retardada , Método Duplo-Cego , Esquema de Medicação , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Nifedipino/administração & dosagem , Nifedipino/sangue , Fatores de TempoRESUMO
The Authors reproduced, experimentally, lesions of oesophageal mucosa on "Wistar" rats, using 1% and 2% solutions of HCl and NaOH. They studied DP modifications and observed that acid solutions produced a complete and persistent DP modification, while alkaline solutions produce DP inversions that diminish few days after the treatment.