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OBJECTIVE: Racial disparities have been well characterized and African American (AA) patients have 30% lower 5-year survival rates than European Americans (EAs) for head and neck squamous carcinoma (HNSCC). This poorer survival can be attributed to a myriad of different factors. The purpose of this study was to characterize AA-EA similarities and differences in sociodemographic, lifestyle, clinical, and psychosocial characteristics in HNSCC patients near the time of surgery. METHODS: Setting: Single tertiary care center. Participants: Thirty-nine newly diagnosed, untreated HNSCC patients (n = 24 EAs,n = 15 AAs) who were to undergo surgery were recruited. Study Design: Cross-sectional study Sociodemographic, lifestyle factors, and disease factors (cancer site, AJCC clinical and pathologic stage, and HPV status)were assessed. Risk factors, leisure time, quality of life and social support were also assessed using validated questionnaires. Exposures: EA and AA patients were similar in the majority of sociodemographic factors assessed. AAs had a higher trend toward pathologically later stage disease compared to EAs and significantly increased time to treatment. RESULTS: EA and AA patients were similar in the majority of sociodemographic factors assessed. AAs had a higher trend toward pathologically later stage disease compared to EAs. AAs also had significantly increased time to treatment (P = 0.05). The majority of AA patients (62%) had later stage pathologic disease. AA were less likely to complete high school or college (P = 0.01) than their EA counterparts. Additionally, AAs were more likely to report having a gap in health insurance during the past decade (37% vs. 15%). CONCLUSIONS: This preliminary study demonstrates a similar profile of demographics, clinical and psychosocial characteristics preoperatively for AAs and EAs. Key differences were AAs tending to have later pathologic stage disease, educational status, delays in treatment initiation, and gaps in health insurance.
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PURPOSE: TRAIL, an endogenous protein involved in immunosurveillance and a novel drug in clinical trials, is of particular interest as cancer therapy because it can induce apoptosis in cancer cells but not in normal cells. Since some cancers develop resistance to TRAIL, safe and effective methods of TRAIL sensitization are of clinical interest. We explored how chemotherapy and oxidative stress affect TRAIL sensitivity and expression of proteins in the apoptotic pathway. MATERIALS AND METHODS: Sensitivity to TRAIL was assessed in viability assays. Apoptosis was measured by caspase-3/7 activity and/or nuclear condensation using Hoechst staining. Western blotting was used to determine cleavage, phosphorylation or alterations in protein expression. RESULTS: TRAIL decreased the viability of 5637 but not of J82 or T24 bladder carcinoma cells (ATCC(R)). Chemotherapy with doxorubicin or cisplatin (Ben Venue Laboratories, Bedford, Ohio) decreased the expression of the anti-apoptotic protein cFLIP(S) and increased caspase-8 cleavage, reversing TRAIL resistance in T24 cells. Specific targeting of cFLIP(S) by siRNA was insufficient for sensitization to TRAIL in T24 cells. However, chemotherapy mediated TRAIL sensitization was mimicked by low concentrations of H(2)O(2), which resulted in the phosphorylation of translation EF2 and decreased the expression of several short half-life, anti-apoptotic proteins, including FLIP(S), XIAP and survivin. CONCLUSIONS: Inducing oxidative stress by low H(2)O(2) concentrations may reverse TRAIL resistance. This warrants the further exploration of H(2)O(2) as an adjuvant intravesical treatment to lower the apoptotic threshold of bladder cancer cells.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/fisiologia , Estresse Oxidativo/fisiologia , Ligante Indutor de Apoptose Relacionado a TNF/fisiologia , Neoplasias da Bexiga Urinária/fisiopatologia , Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD/fisiologia , Linhagem Celular Tumoral , Regulação para Baixo , Humanos , Transdução de SinaisRESUMO
OBJECTIVES: (1) Identify all cases of myoepithelial carcinoma of the major salivary glands from the National Cancer Data Base (NCDB). (2) Analyze the effect of grade, stage, and regional nodal metastasis on survival in myoepithelial carcinoma of the major salivary glands. STUDY DESIGN: Retrospective review of NCDB. SETTING: Multicenter data pooled from 1998 to 2012 in the NCDB. METHODS: We identified all reported cases of myoepithelial carcinomas of the major salivary glands from the United States from 1998 to 2012 in the NCDB. Clinical parameters were then examined and analyzed for predictors of survival. RESULTS: A total of 473 cases of myoepithelial carcinoma were identified. Of the reported cases, 38.1% were low grade; 26.7%, intermediate grade; and 35.2%, high grade. When presenting stage was examined, 24.4% were stage I; 30.6%, stage II; 22.5%, stage III; 12.2%, stage IVa; 3.0%, stage IVb; and 4.1%, stage IVc. At presentation, 18.7% of patients had regional nodal disease, and 4.5% had distant metastases. The 3- and 5-year survival rates were 73% and 64%, respectively. The presence of nodal disease significantly reduced mean survival time versus those without (64 vs 108 months, P < .001), as did high-grade disease compared with low grade (67 vs 114 months, P < .001) and stage III/IV compared with stage I/II disease (61 vs 118 months, P < .001). CONCLUSIONS: The presence of regional nodal disease, high-grade disease, and advanced stage are predictors of lower survival in myoepithelial carcinoma. Further studies based on types of treatment are warranted.
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Mioepitelioma/epidemiologia , Neoplasias das Glândulas Salivares/epidemiologia , Idoso , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Mioepitelioma/patologia , Gradação de Tumores , Prognóstico , Estudos Retrospectivos , Neoplasias das Glândulas Salivares/patologia , Taxa de Sobrevida , Estados Unidos/epidemiologiaRESUMO
OBJECTIVE: (1) To identify predictors of nodal disease in parotid malignancies using various clinical and pathologic variables. (2) To examine the effect of nodal disease on overall survival (OS) in parotid cancers STUDY DESIGN: Retrospective database review. SETTING: National Cancer Data Base (1998-2012). SUBJECTS AND METHODS: We identified all cases of primary parotid malignancies in the United States between 1998 and 2012 in the National Cancer Data Base. Eight histopathologies, constituting >80% of all cases, were examined for nodal metastasis and survival. RESULTS: We identified 22,653 cases of primary parotid cancer. Eight major histologies were studied, with mucoepidermoid carcinoma (31%), acinic cell carcinoma (18%), adenocarcinoma (14%), and adenoid cystic carcinoma (9%) being most common. Regional nodal disease incidence was 24.4% overall and varied by histopathology. Salivary ductal carcinoma had the highest incidence of both nodal metastasis and occult lymph node metastasis. Overall, N0 patients lived significantly longer than N+ (5-year OS, 79% vs 40%; P < .001). Low-grade disease had significantly better survival than high-grade (5-year OS, 88% vs 69%; P < .001). Occult nodal disease was found in 10.2% and varied by histopathology. CONCLUSION: Regional lymph node metastasis significantly decreases survival in many parotid malignancies. High-grade cancers had higher incidences of regional disease than did low grade. Adenocarcinoma had the highest mortality when regional disease was present. Incidence of occult disease varied by histology, but incidence was <10% for all low-grade disease. High T stage and grade are significant independent predictors of nodal disease for most histopathologies.