No abstract

Islet cell transplantation is one of the most promising therapies for diabetes mellitus (DM). However, the limited availability of purified islets for transplantation and the risk of immunological rejection severely limit its use. In vitro transdifferentiation of autologous bone marrow‐derived mesenchymal stem cells (BMSCs) into insulin‐producing cells (IPCs) could provide an abundant source of cells for this procedure and avoid immunological rejection. Here, we isolated and characterized BMSCs and induced their in vitro differentiation into IPCs. Reverse‐transcription polymerase chain reaction analysis revealed that these IPCs could express Ins1, Ins2, glucagon, glucose transporter 2, and pancreatic duodenal homeobox‐1. Insulin production by the IPCs was confirmed by immunocytochemistry and Western blot analysis. On this basis, donor rats supplying BMSCs were made diabetic by a single intraperitoneal injection of streptozotocin. The IPCs were then autologously transplanted into the duodenal submucosa of diabetic rats. Grafted cells could be visualized in sections after 2, 4, and 8 weeks by immunohistochemical staining for insulin. Furthermore, in the IPC‐implanted group, hyperglycemia was normalized, compared with a persistent increase in glucose levels in the diabetic group and intraperitoneal glucose tolerance test‐induced responses were observed in the IPC‐implanted group. These results on autologous transplantation of IPCs derived from BMSCs into the duodenal wall could offer a novel potential therapeutical protocol for DM. Anat Rec, 292:728–735, 2009. © 2009 Wiley‐Liss, Inc.

BACKGROUNDHepatocellular carcinoma (HCC) with portal venous invasion (PVI) has a very poor prognosis, with a median survival of 3 months and virtually no survival at 1 year. The combination of intraarterial 5‐fluorouracil (FU) and systemic interferon‐α (IFNα) was recently reported to be effective against HCC with PVI, but these were small pilot studies.METHODSOne hundred and sixteen patients with HCC with PVI received IFNα (5,000,000 U intramuscularly on Days 1, 3, and 5 of each week of treatment) and 5‐FU (500 mg into hepatic artery on Days 1‐5 of the first and second week of each 4‐week cycle). The therapy was either terminated at the end of the first cycle in cases with progressive disease, or continued for at least 3 cycles, when responses to treatment were evaluated by Eastern Cooperative Oncology Group criteria. The survival rate was compared with that of historical controls (n = 40).RESULTSNineteen (16%) patients showed complete response and another 42 (36%) showed partial response. Adverse events were limited to nausea and appetite loss. The survival rates at 12 and 24 months among overall patients were 34% and 18%, respectively, in contrast to 15% and 5% among the historical controls. Survival rates at 12 and 24 months were 81% and 59% among complete responders, respectively, and 43% and 18% among partial responders.CONCLUSIONThe combination therapy with 5‐FU and IFN was safe, and substantially improved the survival rate among the complete responders. These results provide a rationale for future randomized controlled trials. Cancer 2006. © 2006 American Cancer Society.

After tumor ablation by ethanol injection, interferon therapy may enhance patient survival in selected patients with chronic hepatitis C.

We evaluated the efficacy and safety of radiofrequency (RF) ablation for hepatocellular carcinoma (HCC) in presumably high-risk locations. Between February 1999 and December 2001, we performed RF ablation on 1,419 nodules in 636 consecutive HCC patients, of which 231 nodules in 207 patients were in high-risk locations, defined as less than 5 mm from a large vessel or an extrahepatic organ. Eighty-one patients had a nodule adjacent to a large vessel, 145 patients had a nodule adjacent to an extrahepatic organ, of whom 19 also had one adjacent to a large vessel. Early complications and local tumor progression were analyzed with regard to the location of each nodule. The mean nodule diameter and average number per patient were 27 mm and 2.3, respectively. Early complications, within 30 days after ablation, occurred in 12 of 207 patients (5.8 %) with a nodule in a high-risk location and in 15 of 429 patients (3.5 %) without (P ‫؍‬ .1776). There was no significant difference in local tumor progression rate between nodules in high-risk locations (1 year: 2.1%, 2 years: 3.1%, 3 years: 3.1%) and those elsewhere (1 year: 0.6%, 2 years: 1.7%, 3 years: 2.5%) (P ‫؍‬ .2745). In conclusion, HCC nodules adjacent to a large vessel or extrahepatic organ were treated with RF ablation without compromising the efficacy of the procedure. However, even though without significant difference, some complications occurred at risky locations and need to be carefully considered.