Different effects of polymorphisms of tumor necrosis factor-alpha and interleukin-1 beta on development of peptic ulcer and gastric cancer

BACKGROUND AND AIM: In Western countries, polymorphism of pro-inflammatory cytokine genes is associated with the development of gastric cancer and duodenal ulcer. The aim of this study was to clarify the association of polymorphisms of interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha with susceptibility to peptic ulcer diseases and gastric cancer in Japan. METHODS: The IL-1beta-511/-31 and TNF-alpha-308/-857/-863/-1031 genotypes were determined in Helicobacter pylori-positive patients with gastritis only (n = 164), gastric ulcers (n = 110), duodenal ulcers (n = 94), or gastric cancers (n = 105), and in H. pylori-negative controls (n = 172). RESULTS: Carriage of the alleles TNF-alpha-857 T (odd ratio [OR], 1.826; 95% confidence interval [CI], 1.097-3.039), TNF-alpha-863 A (OR, 1.788; 95% CI, 1.079-2.905) and TNF-alpha-1031 C (OR, 1.912; 95% CI, 1.152-3.171) was associated with increased risk for gastric ulcer development. Carriage of the alleles TNF-alpha-857 T (OR, 1.686; 95% CI, 1.003-2.832), TNF-alpha-863 A (OR, 1.863; 95% CI, 1.118-3.107) and TNF-alpha-1031 C (OR 2.074; 95% CI, 1.244-3.457) was also associated with increased risk of gastric cancer development. There was no relationship between the development of H. pylori-related diseases and polymorphisms of IL-1beta-511/-31 and TNF-alpha-308. The simultaneous carriage of three different high-producer alleles of TNF-alpha-857/-863/-1031 significantly increased the risk of gastric ulcer (OR, 6.57; 95% CI, 2.34-18.40) and gastric cancer (OR, 5.20; 95% CI, 1.83-14.78). CONCLUSIONS: Polymorphisms in TNF-alpha rather than IL-1beta are associated with increased risk for gastric ulcers and gastric cancer in Japan. The simultaneous carriage of more than one high-producer allele of TNF-alpha further increased the risks for gastric ulcer and cancer.     

Postischemic mild hypothermia alleviates hearing loss because of transient ischemia

The effect of postischemic mild hypothermia on the inner ear has not been clarified. In this study, we investigated whether hypothermia after transient ischemia could prevent cochlear damage and its therapeutic time window. Mongolian gerbils were divided into six groups: a sham-operation group, a normothermia group, and four hypothermia groups in which hypothermia was induced 1-7, 1-4, 3-6, and 6-9 h after reperfusion. Animals subjected to postischemic mild hypothermia within 3 h after reperfusion had attenuated hearing loss and inner hair cell loss. The protective effect was greater when hypothermia was induced earlier and had a longer duration. This implies that mild hypothermia after ischemia could have therapeutic effects for inner ear ischemic damage.     

Two cases of stage IV gastric cancer responding to chemotherapy with S-1 or UFT

We report patients with advanced Stage IV gastric cancer responding to chemotherapy with S-1 or UFT. Case 1: The patient was a 59-year-old man with Stage IV gastric cancer because of CY 1. After surgery, chemotherapy with S-1 (100 mg/body/day) was performed for one year and 11 months. At present, 5 years and 5 months after surgery, this patient shows no signs of tumor recurrence. Case 2: The patient was a 68-year-old woman with Stage IV gastric cancer because of P 1. She was treated with 200 mg/day of UFT for one year and 9 months. At present, 5 years after surgery, she shows no signs of tumor recurrence. We considered that the longterm survival of such patients is attributable to chemotherapy with S-1 or UFT. The OPRT activity of the two cases was high, so chemotherapy with S-1 or UFT was thought to be effective for them.     

Dual therapy with high doses of rabeprazole and amoxicillin versus triple therapy with rabeprazole,amoxicillin, and metronidazole as a rescue regimen for <Emphasis Type="Italic">Helicobacter pylori</Emphasis> infection after the standard triple therapy

Backgrounds and Aims Development of safe and effective rescue regimens for eradication failure of Helicobacter pylori infection by standard regimens is an urgent task. We designed the prospective study to compare the efficacy of two rescue regimens after eradication failure by the standard triple therapy. Methods One hundred and thirty-two patients in whom eradication of H. pylori infection failed initial triple therapy with lansoprazole 30 mg b.i.d, amoxicillin 750 mg b.i.d. and clarithromycin 400 mg b.i.d. for 1 week were randomized to either the 1–week triple therapy with rabeprazole 10 mg b.i.d., amoxicillin 750 mg b.i.d., and metronidazole 250 mg b.i.d. (RAM) or the 2–week dual therapy with rabeprazole 10 mg q.i.d. and amoxicillin 500 mg q.i.d. (RA). Eradication of H. pylori was judged by ¹³C-urea breath test 1 month later. Results The intention-to-treat and per-protocol-based eradication rates were 92.4% (95% CI: 83.2–97.5) and 95.3% (95% CI: 86.9–99.0) for the RAM therapy and 90.9% (95% CI: 81.2–96.6) and 93.8% (95% CI: 84.8–98.3), respectively, for the RA therapy (P > 0.2 for both). No clinically recognizable adverse events were observed with either regimen. Conclusion RA as well as RAM therapy are safe and effective rescue regimens for H. pylori infection after eradication failure by the standard triple therapy.     

Oncolytic virus therapy--foreword

We are very pleased and proud to be able to publish this special issue of Current Cancer Drug Targets devoted to oncolytic virus therapy covering basic and clinical research on adenovirus, vaccinia virus, herpes virus, and Newcastle disease virus. In these papers, we welcome the world's top authorities in the field who have generously contributed their latest review articles for exclusive publication in this special issue. Moreover, this issue also includes a range of opinion from government drug organizations. Here we simply wish to bring together the newest knowledge and experience in the field of cutting-edge oncolytic virus therapy for researchers and every kind of cancer therapist. The Foreword presents a historical perspective on the development of oncolytic virus together with the encouraging results of recent clinical trials (e.g., H101 has been tested in clinical trial of nearly 250 patients and approved for human use by the Chinese FDA, while PV701 has been tried in over 110 patients, as described in our special issue).     

RhoB is frequently downregulated in non-small-cell lung cancer and resides in the 2p24 homozygous deletion region of a lung cancer cell line

Identification of a homozygous deletion in cancer cells provides strong evidence for the location of a tumor suppressor gene (TSG). We analyzed the 2p24 homozygous deletion of a non-small-cell lung cancer (NSCLC) cell line, NCI-H2882, and found that the deletion size was 3.7 Mbp. Since RhoB, which has been suggested to be a candidate TSG, was located in this region, we analyzed RhoB for alterations in NSCLC. Although we found no mutations in 48 cell lines including 20 NSCLCs, a loss of heterozygosity (LOH) analysis in 128 primary NSCLCs showed that 25 of 62 informative samples had LOH at the RhoB locus. Northern blot analysis of 28 cell lines (including 15 NSCLCs) indicated that RhoB expression was downregulated in 27. We analyzed RhoB expression in 112 primary NSCLCs with immunohistochemistry and found no or a weak RhoB expression in 33 (42%) of 78 adenocarcinomas, whereas we found it in 29 (94%) of 31 squamous cell carcinomas. No or a weak expression of RhoB was more frequently observed in poorly- or moderately-differentiated adenocarcinomas than in well-differentiated ones (p = 0.0014). Furthermore, no or a weak expression of RhoB indicated a tendency to poor patient prognosis. Although hypermethylation was not found at the promoter region, the RhoB expression in NSCLC cell lines was induced by histone deacetylase inhibition, suggesting that RhoB downregulation may be due to histone modification. The present study demonstrates that RhoB expression is frequently downregulated in NSCLCs by multiple mechanisms, suggesting that RhoB is a candidate TSG for NSCLC.     

Relation of Family History of Cancer and Environmental Factors to the Risk of Colorectal Cancer: A Case-control Study

The relation of a family history of cancer and environmentalfactors to colorectal cancer was investigated in a case-controlstudy conducted from 1992 to 1994 at 10 medical institutionsin Japan using a self-administered questionnaire, and 363 casesof colorectal cancer were compared with 363 controls matchedfor sex and age. A family history of colorectal cancer was positivelyassociated with colon cancer (odds ratio (OR)=2.0, 95% confidenceinterval(Cl)1.03–3.87) and rectal cancer (OR=2.1 Cl 0.94–4.48),but a family history of other cancers did not increase the risk.The proportion of patients with a family history of colorectalcancer within first-degree relatives was 12.4% — appreciablyhigher than figures previously reported in Japan. On the otherhand, the incidence of hereditary non-polyposis colorectal cancerwas 1.4%, and lower than previous estimates. Among dietary factors,a western-style diet significantly increased the risk of bothcolon and rectal cancer (OR = 2.3 Cl 1.30–3.88 and OR=2.1Cl 1.26–3.63, respectively). Consumption of rice was protectiveagainst both colon and rectal cancer(OR=0.5 Cl 0.31–0.82and OR = 0.3 Cl 0.18–0.65, respectively). Animal meat,oily food, fish, vegetables and fruit were shown to affect therisk, but no statistically significant correlation was found.Among other factors, constipation increased the risk of coloncancer (OR= 2.0 Cl 1.02–3.76) and consumption of coffeeraised the risk of rectal cancer (OR =1.7 Cl 1.07–2.82).Our findings suggest that a family history of colorectal canceris an important risk factor for this disease, and does not contradictthe hypothesis that the risk of colorectal cancer in Japan maybe influenced by westernization of lifestyle. However, we wereunable to find conclusive evidence that familial clusteringof this disease is strongly affected by environmental factorsor genetic diseases such as hereditary non-polyposis colorectalcancer.