RESUMO
Desmoplastic Small Round Cell Tumor (DSRCT) is a rare and an aggressive malignancy with poor outcome. This tumor can co-express epithelial, neural, and mesenchymal markers. The molecular hallmark of DSRCT is the EWS-WT1 fusion protein. Despite the diversities in treatment modality, the best results have been seen with radical surgery and adjuvant or neoadjuvant chemotherapy.
Assuntos
Neoplasias Abdominais/terapia , Tumor Desmoplásico de Pequenas Células Redondas/terapia , Neoplasias Abdominais/genética , Neoplasias Abdominais/mortalidade , Neoplasias Abdominais/patologia , Anticorpos Monoclonais/uso terapêutico , Quimioterapia Adjuvante , Quimioterapia do Câncer por Perfusão Regional , Tumor Desmoplásico de Pequenas Células Redondas/genética , Tumor Desmoplásico de Pequenas Células Redondas/mortalidade , Tumor Desmoplásico de Pequenas Células Redondas/patologia , Humanos , Hipertermia Induzida , Imuno-Histoquímica , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Proteínas de Fusão Oncogênica/genética , Radioterapia Adjuvante , Tomografia Computadorizada por Raios X , Translocação GenéticaRESUMO
Nuclear Factor-kappaB (NF-kappaB) activation and COX-2 overexpression have been reported in head and neck cancer, but the relationship between these proteins remains to be investigated. To determine the relationship between NF-kappaB and COX-2 in Smokeless Tobacco (ST) associated oral tumorigenesis, we performed immunohistochemistry in serial sections from 107 OSCCs, 78 oral precancerous lesions (OPLs) (58 hyperplasias, 20 dysplasias) and 15 histologically normal oral tissues and correlated with clinicopathological data. Significant increase in NF-kappaB and COX-2 immunopositivity was observed from normal oral mucosa to OPLs to OSCCs (p = 0.009 and p = 0.002 respectively). Upregulation of NF-kappaB and COX-2 was observed as early as in hyperplasia [p = 0.006; OR = 6.1 and p = 0.003; OR = 7.6, respectively]. Expression of both proteins was found to be significantly associated in OPLs (p = 0.000; OR = 12.6) and OSCCs (p = 0.001; OR = 4.0). Intriguingly, khaini consumption correlated with NF-kappaB immunopositivity in OPLs (p = 0.05, OR = 3.8) and OSCCs (p = 0.01, OR = 3.4) and with COX-2 expression in OPLs (p = 0.03; OR = 4.3). In vitro experimental system of ST associated oral carcinogenesis was used to demonstrate ST (khaini) and NNK mediated activation of NF-kappaB and COX-2, supporting the clinical data. In conclusion, this study demonstrates correlation between over expression of NF-kappaB and COX-2 in early precancerous stages of development of oral cancer and sustained elevation down the tumorigenic pathway, underscoring their potential as targets for early intervention. In vitro studies demonstrated that NNK may be one of the carcinogenic components of ST (khaini) inducing activation of NF-kappaB and COX-2 in oral precancer and cancer cells, suggesting plausible role in ST-induced oral carcinogenesis.
Assuntos
Carcinoma de Células Escamosas/patologia , Ciclo-Oxigenase 2/biossíntese , Proteínas de Membrana/biossíntese , Neoplasias Bucais/patologia , NF-kappa B/biossíntese , Lesões Pré-Cancerosas/patologia , Adulto , Idoso , Western Blotting , Carcinoma de Células Escamosas/etiologia , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular Tumoral , Distribuição de Qui-Quadrado , Citoplasma/efeitos dos fármacos , Citoplasma/metabolismo , Relação Dose-Resposta a Droga , Feminino , Humanos , Imuno-Histoquímica , Masculino , Microscopia Confocal , Pessoa de Meia-Idade , Neoplasias Bucais/etiologia , Neoplasias Bucais/metabolismo , NF-kappa B/metabolismo , Nitrosaminas/farmacologia , Oligonucleotídeos/genética , Oligonucleotídeos/metabolismo , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Lesões Pré-Cancerosas/etiologia , Lesões Pré-Cancerosas/metabolismo , Ligação Proteica/efeitos dos fármacos , Fatores de Tempo , Tabaco sem Fumaça/efeitos adversos , Tabaco sem Fumaça/químicaRESUMO
BACKGROUND AND OBJECTIVES: Locally advanced breast cancer (LABC) remains a major problem in developing countries. While trials utilizing neo-adjuvant chemotherapy demonstrate superior survival rates compared to historic controls, randomized studies evaluating the precise role of neo-adjuvant chemotherapy in LABC are lacking. In the present trial, neo-adjuvant chemotherapy was compared against adjuvant chemotherapy to assess survival advantage in operable T4b N0-2 M0 breast cancer. METHODS: A total of 101 women with operable LABC (T4b N0-2 M0) were randomized. In arm A, 50 patients received 3 cycles of CEF chemotherapy before and 3 cycles following surgery. In arm B, 51 patients had primary surgery followed by 6 cycles of CEF chemotherapy. In both arms, loco-regional radiotherapy was given after completion of CEF. RESULTS: The response of primary tumor to neo-adjuvant chemotherapy was 66%, complete response (CR) 14% and partial response (PR) 52%. Clinical nodal response occurred in 95% of node positive patients. Only two (4%) patients had pathologic CR both in tumor and axilla. There was a significant (P = 0.02) increase in incidence of pathologically negative nodes in arm A. At a median follow up of 25 months, there was no significant difference in overall and disease free survival (DFS) in both arms (P = 0.42 and 0.18). Patients showing a response to neo-adjuvant chemotherapy had better DFS (P = 0.04) compared to those who had no response. CONCLUSIONS: Early results of the study indicate no survival benefit with the inclusion of neo-adjuvant chemotherapy in LABC (T4b N0-2 M0). Neo-adjuvant chemotherapy resulted in significant down staging; good responders had a better DFS compared to those who did not respond.