Expression of p16 and pKi-67 in cervical preneoplasia and neoplasia

This study was conducted to investigate the expression of p16 and pKi-67 in normal, preneoplasia and neoplasia lesions of the uterine cervix. One hundred and thirty one cervical specimens, consisting of normal cervix (n = 43), cervical intraepithelial neoplasia (CIN) lesions (n = 40) [16 LSIL: CIN 1 and 24 HSIL: 9 CIN 2 and 15 CIN 3] and cervical squamous cell carcinomas (n = 48) [16 SCC I, 17 SCC II, 7 SCC III and 8 SCC IV] were examined immunohistochemically in paraffin sections. All samples of the normal cervix were negative for p16. Immunoreactivity of p16 was observed in 4/ 16 LSIL, 12/24 HSIL and 30/48 SCC. In all p16-positive samples, both nuclear and cytoplasmic staining were observed. High expression of p16 (> 50 % of cell stained) was found in HSIL and SCC. Ki-67 index was significantly (p < 0.05) higher in high-grade squamous intraepithelial lesions (HSIL: CIN 2 & 3) and SCC lesions when compared to normal cervices. The expression of p16 and Ki-67 proliferation profile ( 30 % stained cells) were significantly associated with the grade of lesions (χ2 = 6.832, p = 0.033 and χ2 = 10.952; p = 0.012 respectively). There was no significant relationship demonstrated between p16 positivity and Ki-67 proliferation profile (χ2 = 0.292; p = 0.589). Our results indicated that p16protein may be involved in the carcinogenesis of cervical cancer. However, overexpression of p16 seemed to have no effect on cell proliferation. The expression of p16 and pKi-67 may be useful in cases where it is difficult to make a diagnosis by histology

Positive TPMT genotype-phenotype correlation underscores importance of TPMT genotyping for personalized thiopurine dosing

This study explored TPMT genotype-phenotype correlation in a group of acute lymphoblastic leukemia (ALL) patients to investigate the potential of TPMT genotyping for personalized thiopurine dosing. Genotyping for G238C (TPMT*2), G460A (TPMT*3B) and A719G (TPMT*3C) loci was determined in 89 subjects via PCR, while TPMT activity was measured using HPLC. TPMT*3C was the only mutant allele detected in 4 heterozygous carriers. These patients had significantly lower (23.0 nmol/g Hb/h) TPMT activity compared to wildtype patients (51.0 nmol/g Hb/h) (p = 0.003). Positive correlation between TPMT genotype and phenotype projects the possibility of using TPMT genotyping as a guide prior thiopurine drug administration.

Chlorella vulgaris triggers apoptosis in hepatocarcinogenesis-induced rats*

Chlorella vulgaris (CV) has been reported to have antioxidant and anticancer properties. We evaluated the effect of CV on apoptotic regulator protein expression in liver cancer-induced rats. Male Wistar rats (200~250 g) were divided into eight groups: control group (normal diet), CDE group (choline deficient diet supplemented with ethionine in drinking water to induce hepatocarcinogenesis), CV groups with three different doses of CV (50, 150, and 300 mg/kg body weight), and CDE groups treated with different doses of CV (50, 150, and 300 mg/kg body weight). Rats were sacrificed at various weeks and liver tissues were embedded in paraffin blocks for immunohistochemistry studies. CV, at increasing doses, decreased the expression of anti-apoptotic protein, Bcl-2, but increased the expression of pro-apoptotic protein, caspase 8, in CDE rats, which was correlated with decreased hepatoctyes proliferation and increased apoptosis as determined by bromodeoxy-uridine (BrdU) labeling and terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling (TUNEL) assay, respectively. Our study shows that CV has definite chemopreventive effect by inducing apoptosis via decreasing the expression of Bcl-2 and increasing the expression of caspase 8 in hepatocarcinogenesis-induced rats