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J Clin Oncol ; 34(10): 1034-42, 2016 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-26598744


BACKGROUND: Lapatinib (L) plus trastuzumab (T) improves outcomes for metastatic human epidermal growth factor 2-positive breast cancer and increases the pathologic complete response in the neoadjuvant setting, but their role as adjuvant therapy remains uncertain. METHODS: In the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization trial, patients with centrally confirmed human epidermal growth factor 2-positive early breast cancer were randomly assigned to 1 year of adjuvant therapy with T, L, their sequence (T→L), or their combination (L+T). The primary end point was disease-free survival (DFS), with 850 events required for 80% power to detect a hazard ratio (HR) of 0.8 for L+T versus T. RESULTS: Between June 2007 and July 2011, 8,381 patients were enrolled. In 2011, due to futility to demonstrate noninferiority of L versus T, the L arm was closed, and patients free of disease were offered adjuvant T. A protocol modification required P ≤ .025 for the two remaining pairwise comparisons. At a protocol-specified analysis with a median follow-up of 4.5 years, a 16% reduction in the DFS hazard rate was observed with L+T compared with T (555 DFS events; HR, 0.84; 97.5% CI, 0.70 to 1.02; P = .048), and a 4% reduction was observed with T→L compared with T (HR, 0.96; 97.5% CI, 0.80 to 1.15; P = .61). L-treated patients experienced more diarrhea, cutaneous rash, and hepatic toxicity compared with T-treated patients. The incidence of cardiac toxicity was low in all treatment arms. CONCLUSION: Adjuvant treatment that includes L did not significantly improve DFS compared with T alone and added toxicity. One year of adjuvant T remains standard of care.

Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Biomarcadores Tumorais/análise , Neoplasias da Mama/tratamento farmacológico , Quinazolinas/administração & dosagem , Quinazolinas/efeitos adversos , Receptor ErbB-2/análise , Trastuzumab/administração & dosagem , Trastuzumab/efeitos adversos , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/química , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Esquema de Medicação , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Lapatinib , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Seleção de Pacientes , Resultado do Tratamento
J Tradit Chin Med ; 35(2): 234-7, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25975059


OBJECTIVE: To observe the effect of lit-moxa stimu- lating acupoint Guanyuan (CV 4) on lactic acid and super-oxide dismutase (SOD) in skeletal muscle after exercise exhaustion. METHODS: Twenty-eight adult male Sprague-Dawley rats were randomly divided into normal control group, exhausted control group, exercise group and moxibustion group using exercise training and mild heating with lit-moxa stick as treatment methods. The exhausted control group, moxibustion group and exercise group received an exhaustive swimming after 20 days of intervention. Swimming exhausted times were recorded. Lactic acid and SOD concentration in soleus muscle were detected and compared between every two groups. RESULTS: The swimming exhausted times of the moxibustion group and the exercise group were significantly increased compare to the exhausted control group (P < 0.05). The lactic acid of the exhausted control group was significantly increased comparing with the normal control group (P < 0.05), and the lactic acid of the moxibustion group and the exercise group were significantly lower than that of the exhausted control group (P < 0.05). The SOD level of the exhausted control group was significantly decreased comparing with the normal control group (P < 0.05), and the SOD level of the moxibustion group and the exercise group were significantly higher than that of the exhausted control group (both, P < 0.05). There was no statistical difference between the moxibustion group and the exercise group. CONCLUSION: With lit moxa stick, heat stimulating acupoint of Guanyuan (CV 4) decreased the levels of lactic acid and SOD in rat's skeletal muscle.

Tolerância ao Exercício , Ácido Láctico/metabolismo , Moxibustão , Músculo Esquelético/metabolismo , Superóxido Dismutase/metabolismo , Pontos de Acupuntura , Animais , Humanos , Masculino , Músculo Esquelético/enzimologia , Ratos , Ratos Sprague-Dawley
Mol Cancer ; 8: 125, 2009 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-20021699


BACKGROUND: One of the major reasons for poor prognosis of pancreatic cancer is its high resistance to currently available chemotherapeutic agents. In recent years, focal adhesion kinase (FAK), a central molecule in extracellular matrix (ECM)/integrin-mediated signaling, has been thought to be a key determinant of chemoresistance in cancer cells. In this study, we aimed to determine the roles of FAK phosphorylation in the intrinsic chemoresistance of pancreatic cancer cell lines. RESULTS: Our results showed that, the level of constitutive phosphorylation of FAK at Tyr397 correlated with the extent of intrinsic resistance to Gemcitabine (Gem) in four pancreatic cancer cell lines. Moreover, in Panc-1 cells, which had high expression of pFAK, specific inhibition of constitutive FAK phosphorylation by either RNAi or FRNK overexpression decreased the phosphorylation of Akt, reduced the levels of survivin expression and Bad phosphorylation at Ser136 and increased Gem-induced cytotoxicity and apoptosis. However, in AsPC-1 cells with a low level of pFAK, neither FAK RNAi nor FRNK overexpression affected Gem-induced cell apoptosis. We further found that laminin (LN) induced FAK and Akt phosphorylation in a time-dependent manner, increased the levels of survivin and pBad (pS136) and decreased Gem-induced cytotoxicity and apoptosis in AsPC-1 cells; Specific inhibition of LN-induced FAK phosphorylation by either FAK RNAi or FRNK overexpression suppressed the effects of LN on AsPC-1 cells. Moreover, inhibition of constitutive FAK phosphorylation in Panc-1 cells and LN-induced FAK phosphorylation in AsPC-1 cells by a novel and more specific FAK phosphorylation inhibitor PF-573,228 showed similar results with those of FAK phosphorylation inhibition by FAK RNAi or FRNK overexpression. CONCLUSIONS: In conclusion, our research demonstrates for the first time that both constitutive and LN-induced FAK phosphorylation contribute to increased intrinsic chemoresistance to Gem in pancreatic cancer cell lines and these effects are partly due to the regulation of Akt and Bad phosphorylation and survivin expression. Development of selective FAK phosphorylation inhibitors may be a promising way to enhance chemosensitivity in pancreatic cancer.

Antimetabólitos Antineoplásicos/farmacologia , Desoxicitidina/análogos & derivados , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Laminina/metabolismo , Neoplasias Pancreáticas/metabolismo , Apoptose , Sequência de Bases , Western Blotting , Linhagem Celular Tumoral , Primers do DNA , Desoxicitidina/farmacologia , Resistencia a Medicamentos Antineoplásicos , Citometria de Fluxo , Imunofluorescência , Humanos , Neoplasias Pancreáticas/enzimologia , Neoplasias Pancreáticas/patologia , Fosforilação , Interferência de RNA
Urology ; 74(2): 364-8, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19362343


OBJECTIVES: To avoid unnecessary lymphadenectomy for renal cell cancer (RCC) in patients with retroperitoneal enlarged lymph nodes (ELNs). METHODS: Frozen section examination (FSE) of ELNs was used to evaluate the lymphatic status. In the present study, 114 patients with RCC underwent FSE of ELNs and concurrent regional lymphadenectomy. The results of FSE were compared with the final histopathologic results of lymphadenectomy. Some clinical tumor characteristics were also considered to improve the evaluation effect of the FSE. Multiple regression analysis was applied to define the independent risk factors for lymphatic metastasis. RESULTS: The final histopathologic results indicated that 36 patients (31.6%) had nodal metastases. In these 36 patients, the FSE of ELNs revealed positive findings in 32 patients and negative findings in 4 patients. The sensitivity, specificity, concordance, and false-negative rate of FSE was 88.9%, 100%, 96.5%, and 11.1%, respectively. Multivariate analysis revealed that distant metastasis and high T stage (T3-T4) were independent risk factors for lymphatic metastasis. When FSE indicated negative results, no nodal metastases were found (64 patients) without these 2 risk factors. CONCLUSIONS: ELNs in patients with RCC do not necessarily indicate metastatic disease, and more than one half of ELNs were benign. FSE of ELNs can be used to evaluate the lymphatic status. Using the findings from FSE and the clinical characteristics of the primary tumor, we can avoid unnecessary lymphadenectomy in patients with retroperitoneal ELNs.

Biópsia , Carcinoma de Células Renais/cirurgia , Secções Congeladas , Neoplasias Renais/cirurgia , Excisão de Linfonodo , Linfonodos/patologia , Nefrectomia , Adulto , Idoso , Carcinoma de Células Renais/secundário , Feminino , Humanos , Neoplasias Renais/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Prognóstico , Espaço Retroperitoneal , Sensibilidade e Especificidade