Preferred spoken language mediates differences in neuraxial labor analgesia utilization among racial and ethnic groups.
International journal of obstetric anesthesia
2014; 23 (2): 161-167
Racial and Ethnic Disparities in Obstetrics and Obstetric Anesthesia in the United States
Current Anesthesiology Reports
2013; 3 (4): 292-9
Defining the Molecular Signature of Chemotherapy-Mediated Lung Tumor Phenotype Modulation and Increased Susceptibility to T-Cell Killing
CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS
2012; 27 (1): 23-35
The aims of this study were to assess racial/ethnic disparities for neuraxial labor analgesia utilization and to determine if preferred spoken language mediates the association between race/ethnicity and neuraxial labor analgesia utilization.We performed a retrospective cohort study of 3129 obstetric patients who underwent vaginal delivery at a tertiary care obstetric center. Bivariate analyses and multivariate logistic regression models were used to assess the relationships between race/ethnicity, preferred spoken language and neuraxial labor analgesia.Hispanic ethnicity (adjusted OR 0.77, 95% CI 0.61-0.98) and multiparity (adjusted OR 0.59, 95% CI 0.51-0.69) were independently associated with a reduced likelihood of neuraxial labor analgesia utilization. When preferred spoken language was controlled for, the effect of Hispanic ethnicity was no longer significant (adjusted OR 0.84, 95% CI 0.66-1.08) and only non-English preferred spoken language (adjusted OR 0.82, 95% CI 0.67-0.99) and multiparity (adjusted OR 0.59, 95% CI 0.51-0.69) were associated with a reduced likelihood of neuraxial labor analgesia utilization.This study provides evidence that preferred spoken language mediates the relationship between Hispanic ethnicity and neuraxial labor analgesia utilization.
View details for DOI 10.1016/j.ijoa.2013.09.001
View details for PubMedID 24703871
Prognostic Factors for Survival in Patients Treated With Stereotactic Radiosurgery for Recurrent Brain Metastases After Prior Whole Brain Radiotherapy
International Journal of Radiation Oncology*Biology*Physics
2012; 83 (1): 303-9
Exploitation of differential homeostatic proliferation of T-cell subsets following chemotherapy to enhance the efficacy of vaccine-mediated antitumor responses
CANCER IMMUNOLOGY IMMUNOTHERAPY
2011; 60 (9): 1227-1242
Chemotherapy with platinum doublets, including cisplatin plus vinorelbine, is standard of care for non-small-cell lung cancer. Sublethal exposure to certain chemotherapeutic agents has been demonstrated to alter the phenotype or biology of human tumor cells, rendering them more susceptible to cytotoxic T lymphocyte (CTL)-mediated lysis. The effects of cisplatin/vinorelbine on tumor sensitivity to T-cell cytotoxicity and its molecular mechanisms, however, have not been fully elucidated. We examined the effect of this chemotherapy on growth, cell-surface phenotype, and CTL-mediated lysis of five distinct human lung carcinoma cell lines in vitro and examined the molecular mechanisms associated with enhanced CTL sensitivity. These studies demonstrate that sublethal exposure of human lung tumor cells to the platinum doublet modulates tumor cell phenotype and increases sensitivity to major histocompatibility complex-restricted perforin/granzyme-mediated CTL killing. These studies also demonstrate that exposure to chemotherapy markedly decreased the protein secretion ratio of transforming growth factor-?/interleukin (IL)-8. We examined the gene expression profile of two lung tumor cell lines to identify a shared gene signature in response to sublethal cisplatin/vinorelbine and found coordinate expression of only 16 transcripts, including those for cytokine/chemokine expression and apoptosis such as tumor necrosis factor-?, IL8, CXCL5, and B cell lymphoma-2-like genes (BCL-2). Overall, these results suggest that sublethal exposure to cisplatin/vinorelbine increases sensitivity to perforin/granzyme-mediated CTL killing by modulation of (a) tumor phenotype, (b) cytokine/chemokine milieu, and (c) the proapoptotic/antiapoptotic gene ratio. The data presented here propose a complex mechanism that is distinct from and complementary to that of immunogenic cell death. This molecular signature may be useful in predicting responses to immunotherapy as well as provide the rationale for the potential clinical benefit of the combined use of vaccine with cisplatin/vinorelbine regimens.
View details for DOI 10.1089/cbr.2012.1203
View details for Web of Science ID 000300595200005
View details for PubMedID 22316209
The 5-year survival rate for stage IB-III non-small-cell lung cancer (NSCLC) remains 15%. Surgical resection followed by adjuvant chemotherapy with cisplatin and vinorelbine is one standard-of-care. We sought to determine in a preclinical model whether (a) the combination of cisplatin and vinorelbine could positively modulate components of the immune system independent of antitumor activity, and (b) there were synergistic effects of this drug combination and vaccine immunotherapy. We examined the effect of cisplatin/vinorelbine on gene expression, cell-surface phenotype, and CTL-mediated cytolysis of murine lung carcinoma cells in vitro; we also assessed the effects of cisplatin/vinorelbine on immune subsets and function of Tregs in vivo. Finally, we evaluated the potential synergy between chemotherapy and a recombinant yeast-CEA vaccine in a murine model transgenic for CEA with mice bearing lung tumors. These studies demonstrate that exposure of lung tumor cells to the platinum doublet cisplatin/vinorelbine modulates tumor cell phenotype and increases sensitivity to CTL-mediated cytolysis. These studies also demonstrate that cisplatin/vinorelbine (a) induces sub-myeloablative leucopenia that differentially modulates reconstitution of Treg versus effector T-cell subsets and (b) can be employed synergistically with vaccine, exploiting homeostatic peripheral expansion of T cells. Antitumor studies show for the first time that cisplatin/vinorelbine combined with vaccine increases the survival of mice with established NSCLC. These findings provide the rationale for the potential clinical benefit of the combined use of vaccine with cisplatin/vinorelbine chemotherapy regimens.
View details for DOI 10.1007/s00262-011-1020-8
View details for Web of Science ID 000294215600003
View details for PubMedID 21544650