The role of protein kinase CK2 in cyclosporine-induced nephropathy in rats.

OBJECTIVES: Protein kinase casein kinase II (PKCK2) has multiple, overlapping roles in induction of apoptosis. Apoptosis can be a common pathway of renal injury caused by a nephrotoxic drug or an injury. We evaluated the role of PKCK2 in cyclosporine (CsA)-induced nephropathy in rats by inhibiting PKCK2 with emodin. METHODS: Male Sprague-Dawley rats fed a low-sodium diet were divided into four treatment groups: control (0.9% saline injection), CsA (15 mg/kg/d subcutaneously), CsA + emodin (CsA plus emodin 20 mg/kg/d subcutaneously), and emodin only. The expression levels of apoptosis-associated factors and of PKCK2 were examined by Western blot analysis. RESULTS: Overexpression of PKCK2 noted with CsA treatment was prevented by emodin, a low-molecular-weight PKCK2 inhibitor, which dampend drug-induced up-regulation phosphorylated p53 and activation of caspases 3, 7, and 8. In addition, emodin prevented increased Bax/Bcl-2 ratio induced by CsA. Emodin prevented up-regulation of PKCK2 by CsA treatment, suggesting that its apoptotic-preventing activity was mediated via PKCK2. CONCLUSIONS: Our findings indicated that PKCK2 may play a role in apoptotic injury associated with CsA-induced nephropathy in rats.

Cancer survival in Busan, Republic of Korea, 1996-2001.

The Busan cancer registry was established in 1996; cancer registration is done by passive and active methods. The registry contributed survival data for 48 cancer sites or types registered during 1996-2001. Follow-up information has been gleaned predominantly by passive methods with median follow-up ranging between 1-57 months for various cancers. The proportion with histologically verified diagnosis for different cancers ranged between 20-100%; death certificates only (DCOs) comprised 0-53%; 47-100% of total registered cases were included for survival analysis. The top-ranking cancers on 5-year age-standardized relative survival rates were penis (94%), thyroid (91%), non-melanoma skin (89%), placenta (86%), breast (76%), Hodgkin lymphoma (75%) and testis (72%). Five-year relative survival by age group showed a decreasing trend with increasing age groups for cancers of the nasopharynx, gall bladder, lung, bone, soft tissue, breast, cervix, corpus uteri, thyroid, multiple myeloma, lymphoid leukaemia and myeloid leukaemia or was fluctuating for other cancers.

Atypical radiological features of a leiomyosarcoma that arose from the ovarian vein and mimicked a vascular tumour.

Leiomyosarcomas of the ovarian vein are extremely rare tumours. Most tumours are hypervascular and typically have a large avascular centre of necrosis. We experienced a case of a retroperitoneal leiomyosarcoma that arose from the ovarian vein with marked vascular proliferation and dilatation within the tumour. To the best of our knowledge, this is the first case report of a retroperitoneal leiomyosarcoma with an atypical vascular structure in the clinical literature.

Molecular detection of cervical intraepithelial neoplasia and cervical carcinoma by microsatellite analysis of Papanicolaou smears.

Carcinoma of the uterine cervix is one of the most common malignancies worldwide, yet it is clearly preventable by population screening. The Papanicolaou (Pap) smear has proved to be the most successful test for the detection of precancerous lesions and is largely responsible for the reduction of cervical cancer mortality and morbidity rates. However, the Pap smear is not perfect; false-negative results of various rates are reported. To improve the diagnostic efficacy of cervical cytology, we performed microsatellite analysis on paired Pap smear samples from cervical lesions. Nine microsatellite markers were chosen from chromosomal regions commonly displaying loss of heterozygostity (LOH) in cervical cancer and those displaying microsatellite instability (MI) in other squamous cell cancer. Microsatellite alterations were detected in 16/21 (76%) Pap smear DNA samples including 11 of 13 (85%) smears from invasive squamous cell carcinomas (SCCs) and 5 of 8 (63%) from squamous intraepithelial lesions (SILs). Microsatellite alterations detected in the Pap smear DNA were identical to those identified in seven paired primary tumors available for analysis. Moreover, this molecular approach detected genetic alterations in two cases apparently negative by cytologic examination. None (0/25) of the control patients displayed microsatellite alterations in paired Pap smears. Microsatellite analysis of cervical cytologic samples may provide a complementary method to analyze suspicious but not diagnostic cytologic samples further.

Promoter hypermethylation of multiple genes in carcinoma of the uterine cervix.

Promoter hypermethylation is an important pathway for the repression of gene transcription in cancer. We investigated promoter hypermethylation of six genes, p16, APC, HIC-1, death-associated protein kinase (DAPK), O(6)-methylguanine-DNA-methyltransferase (MGMT), and E-cadherin, in uterine cervical carcinoma from 53 patients including 31 cases of squamous cell carcinoma (SCC) and 22 cases of adenocarcinoma (AC). Aberrant methylation of at least one of these genes was detected in 79% (42 of 53) of cases including 71% (22 of 31) of SCC and 91% (20 of 22) of AC cases. No aberrant methylation was detected in normal cervical tissue from 24 control hysterectomy specimens. There was no correlation between promoter hypermethylation at any gene and the presence of human papillomavirus-16 or -18 E7 DNA. In AC cases, promoter hypermethylation of the APC and HIC-1 genes was detected at a statistically significant higher frequency than in the SCC cases (APC, 60% versus 13%, P < 0.001; HIC-1, 63% versus 32%, P < 0.03). Conversely, promoter hypermethylation of p16 and DAPK was more common in SCC cases than in AC cases. Our results suggest that promoter hypermethylation is a frequent epigenetic event in cervical carcinoma. The pattern of gene promoter hypermethylation is distinctly different between AC and SCC. The absence of these epigenetic alterations in normal cervical tissue suggests that they may also be valuable as cancer markers.