Risk of second malignancies in patients with gastric marginal zone lymphomas of mucosa associate lymphoid tissue (MALT)

Background

It is controversial whether patients with gastric marginal zone lymphomas of mucosa associated lymphoid tissue (MALT) have higher risk of second malignancies. The aim of this study was to define the risk of second malignancies in these patients.

Methods

We analyzed prospective follow-up data of 146 consecutive patients with gastric MALT lymphoma treated at Aichi Cancer Center Hospital and compared the incidence of second malignancies with that in the general population. We calculated the standardized incidence ratio (SIR), using age- and sex-specific incidence rates from the Aichi Cancer Registry.

Results

The median follow-up period was 74 months. A total of 27 tumors occurred in 22 patients (15.1 %), including 19 solid tumors. Of these, nine tumors were detected concomitantly with, and 18 tumors following, the diagnosis of gastric MALT lymphoma. Four patients had two second malignancies each. For the entire group, the SIR of an additional malignancy was 3.39 (95 % confidence interval [CI] 2.11–4.66). An increased incidence of solid tumors (SIR 2.91 [1.60–4.22]) and hematologic malignancies (SIR 5.54 [1.70–9.38]) were seen. In addition, there was increased risk for development of second malignancies during follow up (SIR 2.26 [1.21–3.30]). Chemotherapy for treatment of MALT was an independent risk factor for second malignancies (age–sex adjusted hazard ratio 3.98 [1.47–10.79].

Conclusions

Compared with the general population, patients with gastric MALT lymphoma are at increased risk for second malignancies, including gastric cancer.     

Circulating microRNA-203 predicts metastases,early recurrence,and poor prognosis in human gastric cancer

Background

Metastasis is a major cause of death in patients with gastric cancer (GC). MicroRNAs (miRNAs) relating to the epithelial–mesenchymal transition (EMT) control GC progression and metastasis. The aim of this study was to evaluate serum EMT-associated miRNAs for metastatic and prognostic noninvasive biomarkers in GC.

Methods

In the first step of this study (preliminary experiments), we selected candidate miRNAs associated with metastasis by analyzing the expression of the miR-200 family (miR-200a, miR-200b, miR-200c, miR-141, and miR-429) and miR-203 in serum samples from stage I (n = 12) and stage IV (n = 12) GC patients. The second phase involved the independent validation of candidate miRNAs in serum specimens from 130 patients with GC and 22 controls.

Results

Based on the preliminary experiments, miR-203 was selected as the candidate serum miRNA that was most closely associated with metastasis. Validation analysis revealed that serum miR-203 levels were significantly lower in stage IV than stage I–III GC patients. Serum miR-203 expression was significantly lower in GC patients with a higher T stage, vessel invasion, and lymph node, peritoneal, and distant metastases. Low expression of serum miR-203 was significantly associated with poor disease-free and overall survival. Multivariate analysis revealed that low serum miR-203 expression was an independent predictive marker for lymph node, peritoneal, and distant metastases and a poor prognosis in patients with GC.

Conclusions

Serum miR-203 has the potential to serve as a noninvasive biomarker for prognosis and to predict metastasis in patients with GC.

     

Biological measures to minimize the risk of radiotherapy-associated second cancer: A research perspective

Purpose Second cancers are among the most serious sequelae for cancer survivors who receive radiotherapy. This article aims to review current knowledge regarding how the risk of radiotherapy-associated second cancer can be minimized by biological measures and to discuss relevant research needs.

Results The risk of second cancer can be reduced not only by physical measures to decrease the radiation dose to normal tissues but also by biological means that interfere with the critical determinants of radiation-induced carcinogenesis. Requirements for such biological means include the targeting of tumor types relevant to radiotherapy-associated risk, concrete safety and efficacy evidence and feasibility and minimal invasiveness. Mechanistic insights into the process of radiation carcinogenesis provide rational approaches to minimize the risk. Five mechanism-based strategies are proposed herein based on the current state of knowledge. Epidemiological studies on the joint effects of radiation and lifestyle or other factors can provide evidence for factors that modify radiation-associated risks if deliberately controlled.

Conclusions Mechanistic and epidemiological evidence indicates that it is possible to develop interventional measures to minimize the second cancer risk associated with radiotherapy. Research is needed regarding the critical determinants of radiation-induced carcinogenesis available for intervention and joint effects of radiation and controllable factors.     

Chemopreventive Effects of Coumaperine from Pepper on the Initiation Stage of Chemical Hepatocarcinogenesis in the Rat

This study was designed to investigate the chemopreventive action of three natural products, coumaperine, aurapten and an extract from rosemary, against the initiation stage of rat hepatocarcinogenesis. Coumaperine has been isolated from white pepper as a naturally occurring antioxidative agent, but its potential modifying effects on carcinogenesis remain unclear. In experiment 1, a modification of the model developed by Tsuda et al. was applied, with assessment of numbers and areas of induced glutathione S-transferase placental form (GST-P)-positive hepatocellular foci in male F344 rats. Coumaperine, aurapten and the extract from rosemary were administered i.g. at 100 mg/kg/day once daily for 5 days with initiation by diethylnitrosamine (DEN) on day 4 (20 mg/kg, i.p.). Numbers and areas of GST-P-positive foci in each group given test chemicals tended to be decreased as compared to the vehicle control group values, significance being achieved for number with coumaperine. Experiment 2 was planned to investigate the mechanism of the inhibitory effects of coumaperine. Livers at 8 h after initiation by DEN were examined with coumaperine administered at 100 mg/kg/day once daily for 3 days. Proliferating cell nuclear antigen (PCNA)- positive cells tended to be decreased as compared to the vehicle control, but no effects on apoptosis or cytochrome P-450 (CYP) 2E1 expression were apparent. Our results suggest that coumaperine provides protection against initiation of hepatocarcinogenesis, and that this is related to inhibition of cell proliferation.     

Isolation and characterization of a novel human pancreas-specific gene,pancpin, that is down-regulated in pancreatic cancer cells

By means of the differential display method, we isolated a novel human gene that is expressed specifically in pancreas. The cDNA, designated “pancpin,” contained an open reading frame of 1,215 nucleotides encoding a 405 amino acid protein, showing a high degree of similarity to serine protease inhibitors belonging to the serpin superfamily. To investigate its possible role in pancreatic carcinogenesis, we looked for genetic alterations of this gene in pancreatic cancer cell lines and primary pancreatic cancer tissues. Expression of pancpin was barely detectable in any of the four pancreatic cancer cell lines examined, and very weak also in 10 of 13 pancreatic cancer tissues. A somatic missense mutation at codon 221 was found in two of 16 primary pancreatic cancers. These findings indicate that down-regulation of pancpin expression may play a significant role in development or progression of pancreatic cancer. Genes Chromosomes Cancer 22:179–185, 1998. © 1998 Wiley-Liss, Inc.     

Metabolic characteristics and antitumor activity of BOF-A2, a new 5-fluorouracil derivative

A new 5-fluorouracil (5-FU) derivative, BOF-A2 (3-[3-(6-benzoyloxy-3-cyano-2-pyridyloxycarbonyl)benzoyl]-1- ethoxymethyl- 5-fluorouracil), is consisted of EM-FU (1-ethoxymethyl-5-fluorouracil) which is specifically and gradually converted to 5-FU by the drug-metabolizing enzyme of liver microsomes and CNDP (3-cyano-2,6-dihydroxypyridine), a potent inhibitor of 5-FU degradation in the liver. When BOF-A2 was given orally, blood levels of the main metabolites, EM-FU and CNDP, were maintained for a longer time in the tumor-bearing rats, and eventually the blood 5-FU levels were maintained over 12 hours. Moreover, 5-FU levels in the tumor tissue tended to be maintained higher and longer time over 24 hrs. than those in the blood of rats. Antitumor activity of such characterized BOF-A2 was investigated with transplantable tumors in rodents and DMBA-induced breast carcinomas in rats. The ED 50 (the dose for 50% inhibition of tumor growth) value was about 15 to 25 mg/kg against the tumors tested. These result may suggest that BOF-A2 has potent antitumor activity in accordance to the long persistence of 5-FU level in the tumor tissue.