Human papillomavirus (HPV) type 58 has been found to be prevalent among Chinese patients with cervical cancer. This study examined the oncogenic risk of HPV58 variants in Hong Kong, a southern part of China. Altogether, 1924 women were studied: 42.8% with a normal cervix, 16.2% with cervical intraepithelial neoplasia (CIN) I, 12.7% with CIN II, 20.8% with CIN III, and 7.6% with invasive cervical cancer (ICC). The overall prevalence of HPV58 was 11.4% (220) and increased statistically significantly with the severity of neoplasia (P(trend)<.001, chi(2) test for trend). Among HPV58-positive women, the occurrence of E7 632C-->T (T20I) and E7 760G-->A (G63S) variants (T20I/G63S) showed a positive trend of association with the severity of neoplasia (P(trend)<.001, chi(2) test for trend). HPV58 variants carrying these two substitutions showed an odds ratio (OR) for ICC of 26.79 (95% confidence interval = 10.14 to 74.72), and this OR was 6.9-fold higher than the ORs of variants without these substitutions. Patients with CIN III or ICC who were also infected with T20I/G63S variants had a statistically significant younger age at diagnosis than those infected with other variants (median age = 37 years versus 48 years; P =.038, two-sided Mann-Whitney U test). Thus, HPV58 variants carrying E7 T20I/G63S substitutions may be associated with an increased risk for cervical cancer.

Intravenous leiomyomatosis is a rare smooth muscle tumor. We report two cases of intravenous leiomyomatosis that grew along different routes of the venous system into the inferior vena cava and the right atrium. The different route of extension makes a difference in the ease of excision of tumor masses. Using MEDLINE together with the references in each publication, we identified all cases of intracardiac leiomyomatosis reported in the English literature in the period between 1980 and 2003 and performed a brief review on this potentially lethal disease entity.

Key words: human papillomavirus infection; cervical cancer, epidemiology; ChinaThere is strong epidemiologic evidence indicating that human papillomavirus (HPV) plays a central role in the etiology of cervical cancer. [1][2][3][4] The women positive for HPV DNA have a risk of developing cervical cancer 15-50 times higher than those without HPV DNA. 1,2,4,5 Although HPV infection is common among young women, only a small minority go on to develop cervical cancer. This situation was reviewed by a group of researchers, who concluded that viral persistence of oncogenic HPV appears to be crucial for the development of cervical cancer. 6 Indeed, HPV-16, -18, -31 and -33 have been officially declared to be oncogenic by the World Health Organization (WHO). 7 The International Biological Study on Cervical Cancer (IBSCC) study group revealed that on average 92.9% of the tumors contained HPV DNA, with a range of 75-100%. 8 Although this international survey included 10 of the 18 regions of the world and provided the most extensive global view of HPV in cervical cancer, there were no data from China, 1 of the largest populations in the world. Furthermore, there are few published data from a well-designed study using a quality-controlled method on the prevalence of either HPV infection or HPV genotypes in cervical cancers in China.We conducted a multicenter study of HPV infection in cervical cancer by selecting 5 geographic regions of China: Shanghai (Eastern China), Guangzhou (Southern China), Sichuan (Western China), Beijing (Northern China) and Hong Kong (Specific Administration Region). MATERIAL AND METHODS PatientsCervical cancer specimens were collected from each of the 5 regions in China, including Shanghai, Guangzhou, Sichuan, Beijing and Hong Kong. Each of the 5 settings (Tumor Hospital, Shanghai Medical University in Shanghai, Tumor Hospital, Sun Yat-sen University of Medical Sciences in Guangzhou, Second Hospital, West China Medical University in Sichuan, Tumor Hospital, Chinese Academy of Medical Sciences in Beijing, and Prince of Wales Hospital, The Chinese University of Hong Kong in Hong Kong) was responsible for collecting 150 or more tumor specimens consecutively from the year 1997 to 1999. Patients from Hong Kong were prospectively recruited with informed consent, and all specimens were freshly frozen. Those specimens collected in other parts of China were paraffin-embedded and retrieved retrospectively from the pathology files in those reference centers. Ethical approvals were obtained from each of the ethical review boards of the respective institutes. Histology reviewAll histologic slides submitted were reviewed by 1 of the investigators (M.K.M.C.) to reestablish the histologic type and

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Overexpression of BMI1 correlates with cancer development, progression, and therapy failure; however, the underlying molecular mechanisms remain to be fully elucidated. Using the C666-1 nasopharyngeal cancer (NPC) model, the role of BMI1 in mediating response of NPC cells to radiation therapy (RT) was investigated. The results showed a novel radioresistance function for BMI1 in NPC, wherein BMI1 depletion sensitized NPC cells to RT. Cell cycle analysis and transmission electron microscopy (TEM) showed apoptosis as the major mode of cell death, and the mitochondria as a primary targeted cellular organelle. Genomewide microarray and pathway analyses revealed that the P53 pathway is a critical mediator of this process. Cotransfection with siP53 rescued C666-1 cells from cytotoxicity upon BMI1 depletion and RT, thereby corroborating the role for P53. Pretreatment with the antioxidant, Trolox, inhibited apoptosis, indicating that production of reactive oxygen species (ROS) is also mediating cytotoxicity. In vivo, BMI1 depletion combined with RT abrogated tumor-forming capacity in SCID mice, showing the relevance of this process in a more complex tumor environment. Hence, we show a novel role for BMI1 in conferring radioresistance in cancer cells through the downregulation of p53-mediated apoptosis. These results suggest a potential strategy of BMI1 depletion combined with RT for tumors wherein BMI1 appears to be driving disease progression.

Nasopharyngeal carcinoma (NPC) is a common cancer among ethnic Cantonese living in Hong Kong and southern China. It is closely associated with Epstein-Barr virus (EBV) infection. Unfortunately, there are very few representative xenografts and cell lines established from NPC available for investigation. Most of the NPC xenografts established have been passaged in immune deficient animals for over 20 years and may not be representative of the original NPC in patients. For in vitro NPC cell lines, there is only one cell line which retains the EBV genomes. Other NPC cell lines have all lost their EBV episomes. Furthermore, many of these NPC cell lines are found to be contaminated with genetic components from HeLa cells (HPV16 genome) which raised issues on their origins and limited their uses as NPC cells. There is great urgency in establishment new NPC cell lines both in vivo and in vitro for various research investigations and for the study of pathogenic role of EBV infection in NPC. We have carried out continuous efforts since 2010 to attempt establishment of new NPC xenografts and cell lines from surgical and biopsies NPC tissues. NPC tissues from resected recurrent NPC and biopsies from primary NPC were explanted to subrenal capsular sites and maintained for four months to one year to observe for growth of new NPC xenografts. Attempts to establish new NPC celles were also carried out. At present, we have successfully established 3 NPC xenografts (Xeno 23, Xeno 32, Xeno 47) which could be passages at subcutaneously sites and one in vitro NPC cells (NPC43) which harbors EBV genomes. The growth properties and genetic alterations of these newly established NPC cell lines have been characterized. Novel genetic alterations and growth signaling pathways were observed in these newly established NPC cell lines and may represent driver mutations and signaling pathways essential for progression of NPC. Profiling of EBV gene expression of these newly established NPC cell lines revealed predominant latent EBV infection and expression of EBV-encoded mRNA from the BART transcripts which are characteristic of EBV infection in NPC. The establishment of new NPC cells will contribute to investigate the pathogenesis of NPC and its intimate relationship with EBV infection. Funding acknowledgement: University Grant Council (HK) grants (AoE NPC (AoE/M-06/08); TBRS (T12-401/13R); GRF); University of Hong Kong (CRCG and SRT cancer) Citation Format: WT Lin, L Xia, Dan Dan Wen, CM Tsang, KW Lo, ML Lung, George Sai-Wah Tsao. Establishment and characterization of xenografts and cell lines trom nasopharyngeal carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 632.

Both p16 and p15, encoded by the genes located on chromosome 9p21, are inhibitors of cyclin-dependent kinases (CDK4/6) and the upstream regulators of Rb function. In hematopoietic malignancies, deletion of p16/p15 locus has been shown to be highly specific to lymphoid, and more particularly from B-lineage malignancies except multiple myeloma (MM). To investigate whether these genes are inactivated by deletions, mutations, and hypermethylation of the 5′ CpG islands, we examined 12 MM patients by Southern hybridization and polymerase chain reaction–single-strand conformation polymorphism (PCR-SSCP) analysis. No deletions nor mutations of the p16 and p15 genes were found. However, hypermethylation was observed in 75% for p16 and 67% for p15 in our group of MM patients. Such high frequencies of involvement of these genes in MM make them hitherto the most common genetic abnormalities in this disease. Concomitant hypermethylation, uncommon thus far in the literature of the study of these genes, is a rather common phenomenon, occurring in 67% of our patient group. Moreover, hypermethylation of p16/p15 was associated with blastic disease and concomitant hypermethylation of both genes may be pathogenetically related to plasmacytoma development. These results indicate that these genes are important in MM pathogenesis. Here we report, for the first time in the literature, the high incidences of p16 and p15 alterations in MM, not by homozygous deletions or mutations, but solely by hypermethylation of the 5′ CpG islands, which may be a specific mechanism in this disease.