Loss of expression of tropomyosin-1, a novel class II tumor suppressor that induces anoikis, in primary breast tumors.

Suppression of tropomyosins (TMs), a family of actin-binding, microfilament-associated proteins, is a prominent feature of many transformed cells. Yet it is unclear whether downregulation of TMs occur in human tumors. We have investigated the expression of tropomyosin-1 (TM1) in human breast carcinoma tissues by in situ hybridization and immunofluorescence. TM1 mRNA and protein are readily detectable in normal mammary tissue. In contrast, TM1 expression is abolished in the primary human breast tumors. Expression of other TM isoforms, however, is variable among the tumors. The consistent and profound downregulation of TM1 suggests that TM1 may be a novel and useful biomarker of mammary neoplasms. These data also support the hypothesis that suppression of TM1 expression during the malignant conversion of mammary epithelium as a contributing factor of breast cancer. In support of this hypothesis, we show that the ability to suppress malignant growth properties of breast cancer cells is specific to TM1 isoform. Investigations into the mechanisms of TM1-induced tumor suppression reveal that TM1 induces anoikis (detachment induced apoptosis) in breast cancer cells. Downregulation of TM1 in breast tumors may destabilize microfilament architecture and confer resistance to anoikis, which facilitates survival of neoplastic cells outside the normal microenvironment and promote malignant growth.

Vitamin B(12) and Folate Status in Head and Neck Cancer.

Deficiency of vitamin B(12) and folate is associated with causation of certain precancerous conditions and cancer. The present study was carried out on 56 controls, 167 patients with oral precancerous conditions (OPC) and 214 head and neck cancer patients, to evaluate the plasma vitamin B(12) and folate levels to determine their association with tobacco habits and vegetarianism and several sociodemographic factors. The subjects were interviewed using a health habit and diet questionnaire at the time of blood collection. Simultaneous estimations of plasma vitamin B(12) and folate were done by Dual Count Radioassay. It was found that the habit of tobacco consumption, lower education and low income were among the risk factors. A decrease in the plasma vitamin B(12) and folate levels with respect to tobacco habits, disease progression, and vegetarian diet was also observed. The individuals in the ower quartile for vitamin B(12) and folate were at a higher risk of developing OPC, as compared to those in higher quartiles. Similarly, the patients with OPC in lower quartiles were found to be at a higher risk of developing cancer than their counterparts. There was a significant positive correlation between vitamin B(12) and folate levels in the subjects consuming tobacco, and more so in patients with OPC (r=0.4330, p=0.000). Folate levels were significantly lower in patients with advanced as compared with early disease (ANOVA p=0.006 and Spearman's Rho = -0.211 and p=0.01). The results suggest, potential significance of plasma vitamin B(12) and folate levels in head and neck malignancies which needs to be confirmed by further studies on a large population.

A Study of Various Sociodemographic Factors and Plasma Vitamin Levels in Oral and Pharyngeal Cancer in Gujarat, India.

Present study examined various socio-demographic factors, dietary patterns, habit of tobacco consumption and plasma vitamin levels in 56 healthy individuals, 146 patients with oral precancerous conditions (OPC) and 132 untreated oral and pharyngeal cancer patients. The subjects were interviewed with a detailed health, habit and diet questionnaire. Plasma b-carotene, vitamin-A and vitamin-E levels were determined spectrophotometrically. An increased incidence of OPC was observed in the age group of <30 years which was associated with tobacco chewing. Whereas, incidence of cancer was in the age group of 30-60 years where habit of tobacco smoking was more prevalent. Majorities of the subjects were from rural area, poor, unaware about association of diet with cancer. The body mass index was lower (p=0.045) in patients with OPC and cancer patients as compared to the controls. Plasma b-carotene and vitamin-E levels were lower in patients with OPC (p=0.000 and 0.031, respectively) and untreated cancer patients (p=0.000 and 0.071, respectively) than the controls. ROC curve revealed that plasma vitamin levels have ability to discriminate between controls and cancer patients. Lower plasma b-carotene and vitamin-E levels were observed in tobacco consumers as compared to non-consumers. Odds ratio revealed that controls and patients with OPC having tobacco habit and lower plasma levels of b-carotene were at a higher risk (p<0.05) of developing cancer. Regression study and Analysis of Variance revealed that plasma b-carotene levels were inversely associated (r(2)=0.14, p=0.001 and F=0.000, respectively) with increase in the stage of cancer. The data provide interesting clues of potential role of diet, tobacco habits, socio-demographic status and plasma vitamin levels in etiology of oral and pharyngeal cancer in Gujarat, where no such findings are reported.