Apoptosis and production of TNF-alpha by tumor-associated inflammatory cells in histological grade III breast cancer.
ABSTRACT Tumor necrosis factor alpha (TNF-alpha) is a cytokine that acts as an important mediator of the apoptotic process that also demonstrates selective citotoxicity against malignant breast tumor cells. In the present study, the presence of apoptotic tumor cells and the synthesis of TNF-alpha by inflammatory cells were investigated in tissue samples from grade III invasive breast cancer with long-term follow-up. In situ detection of tumor apoptotic cells was investigated by direct immuno-peroxidase of digoxigenin-labeled genomic DNA. The production of TNF-alpha and tumor cell proliferation were investigated by immunohistochemical procedures. Our data demonstrated that patients with a clinical history of cancer recurrence and metastasis presented a lower number of cancerous apoptotic cells, higher tumor proliferation rates, and lower TNF-alpha expression rates by inflammatory cells than what is observed among patients diagnosed with the same histopathological breast cancer type but in the absence of tumor recurrence and metastasis.
Article: Cellular profile of the peritumoral inflammatory infiltrate in squamous cells carcinoma of oral mucosa: Correlation with the expression of Ki67 and histologic grading.[show abstract] [hide abstract]
ABSTRACT: Squamous cells carcinoma is the most important malignant tumor with primary site in the oral cavity and, given the great exposure of mucosa and lips to the etiologic factors of this neoplasm, its incidence is high. Investigation of the prognostic determinants is significant for the expectations of treatment proposal and cure of the patient. The local immune response represented by peritumoral inflammatory infiltrate is a possible prognostic factor. In this study, oral mucosa samples of squamous cells carcinoma were analyzed, separated according to their histological classification as well as the phenotypical profile of the cells comprising the peritumoral inflammatory infiltrate was investigated by immunohistochemical method, in addiction, the cell proliferation index via protein Ki67 expression was determinated. The T lymphocytes made up most of this inflammatory infiltrate, and among these cells, there was a predominance of T CD8 lymphocytes relative to the T CD4 lymphocytes. The B lymhocytes were the second most visualized leucocyte cell type followed by macrophages and neutrophils. The immunohistochemical assessment of Ki-67 positive cells revealed a greater expression of this protein in samples of undifferentiated squamous cells carcinoma. The results suggest that the cellular immune response is the main defense mechanism in squamous cells carcinoma of oral mucosa, expressed by the large number of T lymphocytes and macrophages, and that the greatest intensity of local response may be associated with the best prognosis.BMC Oral Health 10/2008; 8:25.
Article: NAD(P)H:quinone oxidoreductase 1 NQO1*2 genotype (P187S) is a strong prognostic and predictive factor in breast cancer.[show abstract] [hide abstract]
ABSTRACT: NQO1 guards against oxidative stress and carcinogenesis and stabilizes p53. We find that a homozygous common missense variant (NQO1(*)2, rs1800566(T), NM_000903.2:c.558C>T) that disables NQO1 strongly predicts poor survival among two independent series of women with breast cancer (P = 0.002, N = 1,005; P = 0.005, N = 1,162), an effect particularly evident after anthracycline-based adjuvant chemotherapy with epirubicin (P = 7.52 x 10(-6)) and in p53-aberrant tumors (P = 6.15 x 10(-5)). Survival after metastasis was reduced among NQO1(*)2 homozygotes, further implicating NQO1 deficiency in cancer progression and treatment resistance. Consistently, response to epirubicin was impaired in NQO1(*)2-homozygous breast carcinoma cells in vitro, reflecting both p53-linked and p53-independent roles of NQO1. We propose a model of defective anthracycline response in NQO1-deficient breast tumors, along with increased genomic instability promoted by elevated reactive oxygen species (ROS), and suggest that the NQO1 genotype is a prognostic and predictive marker for breast cancer.Nature Genetics 08/2008; 40(7):844-53. · 35.53 Impact Factor