No abstract

A fundamental obstacle in cancer gene therapy is the specific targeting of therapy directly to a solid tumor, and no systemic delivery system yet exists. A strain of domestic bacteria, Bifidobacterium longum, which is nonpathogenic and anaerobic, selectively localized to and proliferated in 7,12-dimethylbenz[a]anthracene-induced rat mammary tumors after systemic application. We further ascertained the tumor specificity of genetically engineered, as well as wild-type, Bifidobacterium longum. This is the first demonstration that Bifidobacterium longum can be utilized as a specific gene delivery vector for gene therapy on solid breast tumors.

Standard chemotherapeutic agents and ionizing radiation destroy dividing cells. Because tumor cells divide more rapidly than normal cells, there is a therapeutic index in which damage to the cancer cells is maximized while keeping the toxicity to the normal host cells acceptable. Suicide gene therapy strives to deliver genes to the cancer cells, which convert nontoxic prodrugs into active chemotherapeutic agents. With this strategy, the systemically administered prodrug is converted to the active chemotherapeutic agent only in cancer cells, thereby allowing a maximal therapeutic effect while limiting systemic toxicity. A literature search was conducted using the MEDLINE database from 1990 to 2001 to identify articles related to suicide gene therapy for cancer. A number of suicide gene systems have been identified, including the herpes simplex virus thymidine kinase gene, the cytosine deaminase gene, the varicella-zoster virus thymidine kinase gene, the nitroreductase gene, the Escherichia coli gpt gene, and the E. coli Deo gene. Various vectors, including liposomes, retroviruses, and adenoviruses, have been used to transfer these suicide genes to tumor cells. These strategies have been effective in cell culture experiments, laboratory animals, and some early clinical trials. Advances in tissue- and cell-specific delivery of suicide genes using specific promoters will improve the clinical utility of suicide gene therapy.

Bifidobacterium longum is a nonpathogenic anaerobic bacterium among normal bacterial flora. Recently, it was reported that B. longum accumulated in hypoxic solid tumors. The gene of interest was expressed in transfected B. longum by the shuttle vector pBLES100 in solid tumors. In this report, we constructed pBLES100-S-eCD, which included the cytosine deaminase gene. We confirmed by western blotting that transfected B. longum produced cytosine deaminase. In addition, transfected B. longum produced cytosine deaminase that converted 5-fluorocytosine into 5-fluorouracil. B. longum could be useful for enzyme/pro-drug therapy of hypoxic solid tumors.

The aim of this study was to investigate the characteristics of oesophageal cancer associated with other primary cancers and the survival rate after surgery for the patients with these cancers. Of 202 patients with oesophageal cancer treated in the Second Department of Surgery, Shinshu University School of Medicine between 1981 and 1995, 31 patients (15.3%) had oesophageal cancer associated with other primary cancers. Twenty-one synchronous and 10 metachronous associated cancers were found and 25 of them were resected. Early-stage oesophageal cancer was much more frequent in the associated cases than in the non-associated cases. The stomach was the most frequently associated organ. The numbers of cases with triple and quadruple cancers were three and one, respectively. Three of these cases had intervals of over 6 years between tumours. Three cases with other primary cancers which had intervals of over 7 years after oesophagectomy were found, and two were carcinomas of the reconstructed gastric tube. In the outcome after surgery for oesophageal cancer, there was no difference between the associated and the non-associated cases, and also no difference between the synchronous and metachronous associated cases. Regarding the five-year and 10-year survival rates after surgery for the first cancers, the synchronous cases had a poorer outcome than did the metachronous cases. In conclusion, oesophageal cancer with other primary cancers is not always rare, and its outcome is not poor compared with that of the non-associated cases. These patients may achieve survival by early detection of both lesions and positive treatment. It is important to consider the risk of other primary cancers after oesophagectomy, and the success of the reconstructed gastric tube should be followed by endoscopy.

An artificial endocrine pancreas is a mechanical device that frequently measures blood glucose and adjusts the rate of insulin infusion to maintain normoglycemia. In this study, we evaluated the effect of pancreatic polypeptide (PP) on insulin requirements after total pancreatectomy. However, other endocrine hormones are needed not only to facilitate the effect of insulin, but also to regulate insulin functions in vivo. In this study, the effect of PP infusion on insulin requirements after total pancreatectomy in dogs is examined. After total pancreatectomy, five dogs were supported by artificial endocrine pancreas model STG-22 for 72 h. In a second group of five dogs, both insulin and PP were infused. Mean blood glucose levels and insulin requirements were compared between the two groups. There was no difference in mean plasma glucose levels between the two groups. In all 10 dogs, the mean blood glucose level for 72 h was 110 +/- 4 mg/dL and was tightly controlled between 65 and 190 mg/dL. However, the insulin requirement for the first and second postoperative days in the group treated with PP was significantly less than that of the control group (90.0 +/- 20.8 mU/kg vs. 445.0 +/- 151.9 mU/kg; P < 0.05, and 562.7 +/- 126.5 mU/kg vs. 1007.7 +/- 144.9 mU/kg; P < 0.05, respectively). We conclude that infusion of PP reduces the insulin requirement for the initial 48 h in pancreatectomized dogs treated with an artificial endocrine pancreas.

Introduction:The Suwa Onbashira Festival is held every six years and draws approximately one million spectators from across Japan. Men ride the Onbashira pillars (logs) down steep slopes.At each festival, several people are crushed under the heavy log. During the 2004 festival, for the first time, a medical care system that coordinated a medical team, an emergency medical service, related agencies, and local hospitals was constructed.Objective:The aims of this study were to characterize the spectrum of injuries and illness and to evaluate the medical care system of this festival.Methods:The festival was held 02 April–10 May 2004. The medical records of all of the patients who presented to an on-site medical tent or who were treated at the scene and transported to hospitals over a 12-day period were reviewed.The following items were evaluated: (1) the emergency medical system at the festival; (2) the environmental circumstances; and (3) patient data.Results:All medical usage rates are reported as patients per 10,000 attendees (PPTT). A total 1.8 million spectators attended the festival during the 12-day study period; a total of 237 patients presented to the medical tent (1.32 PPTT), and 63 (27%) were transferred to hospitals (0.35 PPTT). Of the total, 135 (57%) suffered from trauma—two were severely injured with pelvic and cervical spine fractures; and 102 (43%) had medical problems including heat-related illness.Conclusions:Comprehensive medical care is essential for similar mass gatherings. The appropriate triage of patients can lead to efficient medical coverage.

Synchronous gastric tumors associated with esophageal cancer are not rare. When an endoscope cannot pass through the esophagus before surgery, other techniques must be performed to explore the stomach. For these patients, surgical treatment should be adapted positively.