We examined mRNA expression and internal tandem duplication of the Fms-like tyrosine kinase 3 (FLT3) gene in haematological malignancies by reverse transcriptase-polymerase chain reaction (RT-PCR) and genomic PCR followed by sequencing. By RT-PCR, expression of FLT3 was detected in 45/74 (61%) leukaemia cell lines and the frequency of expression of FLT3 was significantly higher in undifferentiated type (B-precursor acute lymphoblastic leukaemia; ALL) than in differentiated type cell lines (B-ALL) (P = 0.0076). Using the genomic PCR method, 194 fresh samples including 87 acute myeloid leukaemias, 60 ALLs, 32 myelodysplastic syndromes (MDSs) and 15 juvenile chronic myelogenous leukaemias (JCMLs) were examined. Tandem duplication was found in 12 (13.8%) AMLs and two (3.3%) ALLs. Sequence analyses of the 14 samples with the duplication revealed that eight showed a simple tandem duplication and six a tandem duplication with insertion. Most of these tandem duplications occurred within exon 11, and two duplications occurred from exon 11 to intron 11 and exon 12. No tandem duplications of FLT3 gene were detected in MDS or JCML. The frequency of tandem duplication of FLT3 gene in childhood AML was lower than that in adult AML so far reported. All of the 12 AML patients with the duplication died within 47 months after diagnosis, whereas two ALL patients with the duplication have survived 44 and 72 months, respectively. These two ALL patients expressed both lymphoid and myeloid antigens and were considered to have biphenotypic leukaemia. These results suggest that tandem duplication is involved in ALL in addition to AML, but not in childhood MDS or JCML, and that childhood AML patients with the tandem duplication have a poor prognosis.

Abstract. Epithelial ovarian cancer (EOC) is the leading cause of death in women with gynecological malignancies. Among EOC, clear cell carcinoma (CCC) and endometrioid adenocarcinoma (EAC) differ from the other histological types with respect to their clinical characteristics and carcinogenesis. Both tumor types are often associated with endometriosis. EAC is recently reported to be characterized by K-RAS activation and PTEN dysfunction. However, the molecular changes in CCC remain largely unknown. The aim of this review is to summarize the current knowledge on the molecular mechanisms involved in CCC tumorigenesis. The present article reviews the English language literature for biological, pathogenetic and pathophysiological studies on endometriosis-associated CCC of the ovary. Several recent studies of loss of heterozygosity (LOH), allelic loss, comparative genomic hybridization, mutation, methylation status, microarray gene-expression profiling and proteomics are discussed in the context of CCC biology. Retrograde menstruation or ovarian hemorrhage carries highly prooxidant factors, such as heme and iron, into the peritoneal cavity or ovarian endometrioma. A histologically normal ectopic endometrium bears genetic damages caused by irondependent oxidative stress. DNA damage or LOH caused by oxidative stress is a critical factor in the carcinogenic process. LOH studies have implicated the involvement of specific chromosomal regions (5q, 6q, 9p, 10q, 11q, 17q and 22q). Furthermore, the PTEN and APC (early event), p53, polo-like kinases, Emi1 and K-RAS (late event) genes may be involved in CCC carcinogenesis. The molecular pathology of CCC is heterogeneous and involves various putative precursor lesions and multiple pathways of development, possibly via genetic alteration by oxidative stress. the candidate tumor suppressor genes 7. Microsatellite instability in CCC 8. Genes specifically up-regulated in CCC 9. Clear cell adenofibroma-CCC sequence 10. Iron, oxidative stress and carcinogenesis 11. Conclusions IntroductionEpithelial ovarian cancer (EOC) is the leading cause of death in women with gynecological malignancies worldwide. The majority of patients present with stage III and IV disease, for which the 5-year survival rates are less than 20%. Most of the patients with EOC present with advanced disease that is not cured by surgery. Ninety per cent of EOC are derived from epithelium within inclusion cysts or from the ovarian surface epithelium and these neoplasms are classified into serous, mucinous, endometrioid adenocarcinoma (EAC), clear cell carcinoma (CCC) and other types (1).Molecular genetic alterations play a key role in carcinogenesis (1). High-grade serous carcinoma arises in a de novo fashion and is characterized by p53 mutations and BRCA1 and/or BRCA2 dysfunction. In contrast, low-grade serous carcinomas are characterized by activation of the RAS-RAF signaling pathway secondary to mutations in KRAS and BRAF in an adenoma-borderline tumor-carcinoma sequence. Similarly, mucinous carcinomas have also ...

These results suggest that post-prandial lipid metabolism is impaired in subjects with intra-abdominal visceral fat accumulation, irrespective of BMI, leading to the development and progression of coronary atherosclerosis.

Autoimmune enteropathy (AIE) is a rare disorder characterized by intractable diarrhoea and antienterocyte autoantibody. In this study, we detected a 75-kD autoantigen which distributed through the whole intestine and the kidney, as assessed by Western blot analysis using sera from two unrelated cases of AIE associated with nephropathy. Our results suggest that the detection of the autoantibody against the 75-kD antigen has a diagnostic value in AIE and that the autoimmune reaction against the 75-kD antigen may be implicated in the development of intestinal and renal tissue damage in this rare disorder.

ELM-TACE is safe and effective treatment for unresectable HCC and is associated with low frequency of postembolization syndrome and minimal damage to the hepatic artery.