Kuniyuki Kato

Downregulation of miR-138 is associated with overexpression of human telomerase reverse transcriptase protein in human anaplastic thyroid carcinoma cell lines

Alterations of several microRNA (miRNA) have been linked to cancer development and its biology. To search for unique miRNA that might play a role in the development of anaplastic thyroid carcinoma (ATC), we examined the expression of multiple miRNA and their functional effects on target genes in human thyroid carcinoma cell lines. We quantitatively evaluated the expression of multiple miRNA in 10 ATC and five papillary thyroid carcinoma (PTC) cell lines, as well as primary tumors from 11 thyroid carcinoma patients (three ATC and eight PTC), using the stem‐loop‐mediated reverse transcription real‐time polymerase chain reaction method. We also examined the target gene specificity of unique miRNA that showed differences in expression between ATC and PTC cell lines. One miRNA, miR‐138, was significantly downregulated in ATC cell lines in comparison with PTC (P < 0.01). Eleven miRNA (including miR‐138) potentially targeting the human telomerase reverse transcriptase (hTERT) gene were totally downregulated in both ATC and PTC cell lines in comparison with normal thyroid tissues. A tendency for an inverse correlation between miR‐138 and hTERT protein expression was observed in the thyroid cancer cell lines, although this failed to reach significance (r = –0.392, P = 0.148). We demonstrated that overexpression of miR‐138 induced a reduction in hTERT protein expression, and confirmed target specificity between miR‐138 and the hTERT 3′‐untranslated region by luciferase reporter assay. These results suggest that loss of miR‐138 expression may partially contribute to the gain of hTERT protein expression in ATC, and that further multiple miRNA targeting hTERT mRNA might be involved in the development of thyroid carcinoma. (Cancer Sci 2008; 99: 280–286)

Angiotensin II and epidermal growth factor receptor cross-talk mediated by a disintegrin and metalloprotease accelerates tumor cell proliferation of hepatocellular carcinoma cell lines.

Aim:  The cross‐talk pathway between angiotensin II (AngII) and the epidermal growth factor receptor (EGFR) mediated by epidermal growth factor (EGF)‐like ligands cleaved by a disintegrin and metalloprotease (ADAM) has been elucidated in several cell types. Even though the liver is a representative angiotensinogen‐producing organ, such cross‐talk has never been elucidated in hepatocellular carcinomas (HCCs). We investigated whether AngII exerted a mitogenic effect on HCC cell lines through the AngII–EGFR cross‐talk pathway.

Laparoscopic-assisted proctocolectomy with prolapsing technique for familial adenomatous polyposis.

Purpose: The role of laparoscopic total proctocolectomy (TPC) and ileal pouch-anal anastomosis (IPAA) for familial adenomatous polyposis (FAP) has been controversial, given its technical difficulty of selecting the appropriate distal transection line and achieving safe anastomosis. We herein describe our initial experience with the prolapsing technique for laparoscopic-assisted TPC and IPAA (J-pouch) in the treatment of FAP. Methods: A consecutive series of patients with FAP undergoing laparoscopic-assisted TPC with IPAA were identified from a prospectively collected database between June 2004 and February 2012. Medical records were reviewed for patient demographics, operative outcomes, and follow-up. Results: The surgery was successfully completed in all 6 patients without any conversion to open surgery. The median operating time was 279 minutes (range, 240 to 386 min) and the median blood loss was 17.5 mL (range, 5 to 161 mL). No patient required blood transfusion. The median length of diet resumption and postoperative hospital stay were 7 days (range, 6 to 10 d) and 15 days (range, 13 to 21 d), respectively. A postoperative complication, wound infection, occurred in 1 patient. No anastomotic leakages or small bowel obstructions occurred. At a median follow-up of 59 months (range, 14.2 to 107.5 mo), no carcinoma had developed at the pouch or at the anastomotic site. Sexual function and fertility were unchanged as compared with preoperatively in 2 male patients. None of the patients experienced night-time incontinence or had to use a pad. Conclusions: Our limited experience suggests that this prolapsing technique helps prevent problems with laparoscopic-assisted TPC and IPAA for FAP patients.