Molecular profiling readily distinguishes between benign and malignant thyroid tumors with excellent sensitivity and specificity. Elucidated genes may provide insight into the molecular pathogenesis of thyroid cancer. Gene profiling may significantly enhance the evaluation of thyroid nodules in the future.
Activation of telomerase represents an early step in carcinogenesis. Increased telomerase expression in malignant thyroid tumors suggests that inactivation of telomerase may represent a potential chemotherapeutic target. The purpose of this study was to inhibit the protein component of telomerase, hTERT, in a human thyroid cancer cell line in vitro and in vivo using an antisense strategy. A 235-bp fragment of hTERT cDNA was subcloned, and sense and antisense hTERT expression vectors were constructed. These vectors were transfected into a human thyroid carcinoma cell line (FRO). Tumorigenic potential was determined by cellular growth assay, rate of apoptosis, anchorage-independent growth, and tumor growth in a nude mouse model. Significant down-regulation of hTERT expression was seen in the antisense transfected cells, compared with control and those transfected with the sense vector. A decrease in telomerase activity by TRAP assay was observed in the antisense hTERT cells but not in cells transfected with the sense hTERT construct. Inhibition of cell growth was observed after approximately 20 population doublings in the antisense-hTERT clones and was associated with an increase in the rate of apoptosis and a change in cellular morphology. Moreover, anchorage-independent growth was reduced in vitro, and tumor growth rate was diminished in vivo in the antisense hTERT clones. Inhibition of telomerase activity with antisense hTERT in human thyroid cancer cells is achievable and may represent a novel target to inhibit tumor growth.
Human RCC inhibits the host antitumor immune response by promoting PGE(2) production and Th2 cytokines in PBMC. Selective inhibition of COX-2 may have a role in abrogating this effect.
The American Cancer Society has recommended monthly breast self-examinations (BSEs) to aid in the early detection of breast cancer. Compliance with BSE recommendations has been shown to be decreased in certain ethnic groups. This investigation evaluates relevant variables involved in BSE compliance in an urban breast cancer screening center. A survey over a 1-year period (June 1996-June 1997) was given to all patients on their initial visit to the Breast Health Center at Tulane University Medical Center. Demographic and socioeconomic factors associated with the compliance of BSE were explored. The overall rate of BSE was relatively high at 80%. There was no difference between ethnic groups in rates of BSE (Caucasians 21% versus African Americans 20%). Statistically significant variables associated with BSE noncompliance were high school education (did not complete high school 16% versus completed high school 33%; p < 0.0004), employment status (employed 16% versus unemployed 31%; p < 0.0004), and marital status (married 15% versus single/divorced 22%; p < 0.05). While the majority of women in our study practiced BSE and ethnicity did not predict BSE, several socioeconomic factors were predictive of BSE compliance. Efforts to increase community outreach to lower socioeconomic patients as well as efforts to ensure proficient BSE techniques by patients may help detect early breast cancer.
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