A yang-promoting Chinese herbal suppository preparation enhances the antioxidant status of red cells in male human subjects

In the 16-week pilot study, the effect of a Yang-promoting Chinese herbal suppository preparation (VI-28) on the red cell antioxidant status was examined in 31 healthy male subjects aged 41-66 years old. VI-28 treatment for 12 weeks (one suppository (0.3 g) daily for week 1-4; one every 2 days for week 5-8; one every 3 days for week 9-12) produced a time/dose-dependent alteration in red cell antioxidant status. The VI-28-induced change is characterized by a slight depletion in cellular reduced glutathione (GSH) level and a decrease in susceptibility to peroxide-induced lipid peroxidation as well as increases in catalase (CAT) and Cu-Zn-superoxide dismutase (SOD) activities. While a reversal trend of change was observed in cellular GSH level, the susceptibility to lipid peroxidation as well as the CAT activity after the cessation of treatment for 4 weeks, the SOD activity exhibited a protracted increase. The results indicate that VI-28 treatment enhances red cell antioxidant status in male subjects. The beneficial effect of VI-28 treatment on red cells may re fl ect a corresponding change in antioxidant status of peripheral tissues.     

A population-based study of colorectal cancer test use: results from the 2001 California Health Interview Survey

BACKGROUND: Recent research has supported the use of colorectal cancer (CRC) tests to reduce disease incidence, morbidity, and mortality. A new health survey has provided an opportunity to examine the use of these tests in California's ethnically diverse population. The authors used the 2001 California Health Interview Survey (CHIS 2001) to evaluate 1) rates of CRC test use, 2) predictors of the receipt of tests, and 3) reasons for nonuse of CRC tests. METHODS: The CHIS 2001 is a random-digit dial telephone survey that was conducted in California. Responses were analyzed from 22,343 adults age >/= 50 years. CRC test use was defined as receipt of a fecal occult blood test in the past year and/or receipt of an endoscopic examination in the past 5 years. RESULTS: Nearly 54% of California adults reported receipt of a recent CRC test. Insurance coverage and having a usual source of care were the most important predictors of CRC testing. Latinos age < 65 years were less likely to be tested than whites (relative risk [RR], 0.84; 95% confidence interval [95% CI], 0.77-0.92). Men were more likely to be tested than women, an effect that was greater among individuals age 50-64 years (RR, 1.28; 95% CI, 1.23-1.32) than among individuals age >/= 65 years (RR, 1.19; 95% CI, 1.15-1.23). Women were more likely than men to say that their physician did not inform them the test was needed and that CRC tests were painful or embarrassing. CONCLUSIONS: Results of the current study indicate a need for physicians to recommend CRC testing to their patients. Assuring that all individuals have both health insurance and a usual source of care would help address gaps in the receipt of CRC tests.     

Gene therapy with secretory leukoprotease inhibitor promoter-controlled replication-competent adenovirus for non-small cell lung cancer

Secretory leukoprotease inhibitor (SLPI) is highly expressed in almost all non-small cell lung cancers (NSCLCs), but not in the majority of other tumor types. In an attempt to create a specific gene therapy for NSCLC, we constructed AdSLPI.E1AdB, an adenovirus vector with a double expression cassette consisting of E1A driven by the SLPI promoter gene followed by E1B-19K under the control of the cytomegalovirus (CMV) promoter that can selectively replicate only in NSCLC cells. Infection with AdSLPI.E1AdB yielded E1A protein expression and adenovirus replication resulting in a >100-fold increase of the virus titers only in SLPI-producing NSCLC cells (A549, H358, and HS24 cells). In contrast, neither E1A protein nor replication was detected in non-SLPI-producing HepG2 cells. Treatment with AdSLPI.E1AdB significantly inhibited the proliferation of NSCLC cells in vitro in a dose-dependent manner, whereas the cell growth of HepG2 or normal human bronchial epithelial cells was not affected by AdSLPI.E1AdB infection. Direct injection of AdSLPI.E1AdB into A549 and H358 tumors in nude mice resulted in a marked reduction in tumor growth compared with controls (A549, 57%, P < 0.02; H358, 67%, P < 0.03). Histological examination revealed the replication of AdSLPI.E1AdB and strong induction of necrosis and apoptosis. In addition, we evaluated the combination of AdSLPI.E1AdB and AdCMV.NK4 encoding NK4 protein, which has strong antiangiogenic activity. E1A expressed by AdSLPI.E1AdB trans-acts on the replication of AdCMV.NK4 and thus increases the expression of NK4. Injection of these two vectors into H358 tumors resulted in a more striking reduction of tumor growth compared with single injection of each vector. These results suggest that AdSLPI.E1AdB could provide a selective therapeutic modality for NSCLC and that the combination of AdSLPI.E1AdB and AdCMV.NK4 may be a more effective gene therapy for NSCLC.     

Estrogen enhances angiogenesis through a pathway involving platelet-activating factor-mediated nuclear factor-kappaB activation

In this study, we investigated the molecular events involved in estrogen-induced angiogenesis. Treatment of the human endometrial adenocarcinoma cells, HEC-1A, with estrogen up-regulated mRNA expression and protein synthesis of various angiogenic factors such as tumor necrosis factor-alpha, interleukin-1, basic fibroblast growth factor, and vascular endothelial growth factor. The estrogen-dependent induction of the expression was blocked by the platelet-activating factor (PAF) antagonists, WEB 2170. Estrogen treatment caused the activation of nuclear factor (NF)-kappaB in HEC-1A cells and was also blocked by PAF antagonist. Inhibitors of NF-kappaB activation inhibited estrogen-induced mRNA expression and protein synthesis of the angiogenic factors. Estrogen led to a pronounced angiogenesis as assessed by a mouse Matrigel model in vivo and endothelial cell sprouting in vitro. PAF antagonists or NF-kappaB inhibitors significantly inhibited this estrogen-dependent angiogenesis. Estrogen caused phospholipase A2 (PLA2) gene and protein expression. Estrogen-induced vascular endothelial growth factor mRNA expression and sprouting were significantly inhibited by PLA2 inhibitors, suggesting PLA2 expression is the upstream pathway in the estrogen-induced angiogenesis. Taken together, these results suggest that estrogen induces the production of angiogenic factors via a mechanism involving PAF-mediated NF-kappaB activation.     

Fine mapping of the 11q22-23 tumor suppressive region and involvement of TSLC1 in nasopharyngeal carcinoma

Previous studies transferring an intact chromosome 11 into HONE1 cells demonstrated the functional significance of chromosome regions, 11q13 and 11q22-23, in nasopharyngeal carcinoma (NPC) development. In our study the 11q22-23 region was comprehensively re-investigated by detailed microsatellite and single nucleotide polymorphism genotyping and by fluorescence in situ hybridization to map precisely the regions containing tumor suppressive activity. We observed 3 chromosomal intervals within 11q22-23 that were commonly lost in the tumor segregants derived from HONE1/chromosome 11 hybrids. One critical region of 0.36 Mb was mapped near the marker D11S2000 and a second 0.44 Mb region was located around the markers D11S1300 and D11S1391. In a third region high allelic loss was also observed at marker D11S4484, where a newly cloned tumor suppressor gene, TSLC1 (tumor suppressor in lung cancer 1), is located. The gene expression analysis showed absence or low expression levels of TSLC1 mRNA in 4 highly tumorigenic NPC cell lines. In addition, the methylation study results show that the TSLC1 promoter region was hypermethylated in all 4 NPC cell lines and re-expression of the gene occurs in HONE1 cells after 5-aza-2'-deoxycytidine treatment. Hence, the mode of silencing of this candidate TSG in NPC may be attributed to promoter hypermethylation. We have obtained functional evidence for multiple critical tumor suppressive regions in 11q22-23 by fine deletion mapping and for inactivation of TSLC1 being one of these candidate TSGs in NPC development.     

Rationale for radiotherapy as a treatment modality in gastric mucosa-associated lymphoid tissue lymphoma

PURPOSE: To provide a rationale for the use of local radiotherapy (RT) for the treatment of low-grade mucosa-associated lymphoid tissue lymphoma of the stomach (MLS). In addition, the clinicopathologic characteristics were analyzed. METHODS AND MATERIALS: The data of 72 patients with MLS, who underwent radical surgery between 1991 and 2001, were retrospectively reviewed. The depth of invasion into the gastric wall and the pattern of lymph node spread according to pathologic grade were analyzed. RESULTS: The patient age range was 24-77 years (median, 51 years). Of the 72 patients, 45 (62.5%) had low-grade and 27 (37.5%) had high-grade MLS; 44 (61%) had Stage I and 28 (39%) Stage II. The tumors were confined to the mucosa or submucosa in 43 patients (58.9%). Sixty-seven percent of low-grade tumors and 48% of high-grade tumors were confined to the mucosa and submucosa. Lymph node involvement was identified in 24.4% of the low-grade MLS patients and 63.0% of the high-grade MLS patients. In the low-grade group, lymph node involvement was limited to the perigastric lymph nodes in all cases except for one. One patient with tumor infiltration beyond the serosa had extensive lymph node involvement into the paraaortic and omental lymph nodes. CONCLUSION: Local RT to the stomach and regional lymphatics can be applied preferably instead of gastrectomy in patients with low-grade MLS who are negative for Helicobacter pylori or are refractory to anti-H. pylori therapy. The timing of RT and the exclusion criteria for RT should be determined in the future.     

Primary pulmonary non-Hodgkin's lymphoma

BACKGROUND: Primary pulmonary non-Hodgkin's lymphoma is a very rare neoplasm. It is represented most commonly by marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type. Although there have been a few reviews of this lymphoma, clinical features, diagnostic procedure, optimal management and prognostic factors have not been well defined. METHODS: We reviewed the medical records of 24 patients who were pathologically and clinically diagnosed as primary pulmonary lymphoma between September 1995 and June 2003. RESULTS: There were 13 patients with MALT lymphoma and two with MALT lymphoma accompanied by large B-cell lymphoma, seven with diffuse large B-cell lymphoma and two with anaplastic large cell lymphoma. Half the patients were asymptomatic at presentation; 46% had respiratory symptoms and 16.7% had B-symptoms. Initial radiological findings were variable including nodules, masses, infiltrates or consolidation. The majority of patients (66.7%) needed surgical approaches (open thoracotomy or video-assisted thoracoscopy) for definite diagnosis. Bronchoscopy was performed in 83%, but only 30% showed a diagnostic yield. The 13 patients with MALT lymphoma were treated with a variety of modalities such as observation, surgery and single or combination chemotherapy, and combination chemotherapy was administered to 11 patients with non-MALT lymphoma regardless of surgery. The overall survival rate at 3 years for all 24 patients was 86% with a median follow-up of 32 months. CONCLUSION: Although this entity of lymphoma appears to have a good prognosis, further clinical experience and long-term follow-up are needed to identify prognostic factors.     

Complete response in an elderly patient with advanced gastric cancer treated with TS-1

The patient was an 89-year-old woman whose complaints were anorexia and weight loss. As a result of various examinations, she was diagnosed with advanced gastric cancer, Borrmann 3. TS-1 was administered at 75 mg/day for two weeks followed by one-week discontinvation during hospitalization; This course was then repeated after discharge. Anorexia and weight loss improved after two weeks, and complete response (CR) was obtained after 10 months of treatment. No cancer cells were confirmed by endoscopic biopsy. During this period no severe toxicities occurred. This TS-1 administration schedule appears to be a feasible and effective therapy for elderly patients with advanced gastric cancer.     

Transgenic mouse model for breast cancer: induction of breast cancer in novel oncogene HCCR-2 transgenic mice

Transgenic mice containing novel oncogene HCCR-2 were generated to analyse the phenotype and to characterize the role of HCCR-2 in cellular events. Mice transgenic for HCCR-2 developed breast cancers and metastasis. The level of p53 in HCCR-2 transgenic mice was elevated in most tissues including breast, brain, heart, lung, liver, stomach, kidney, spleen, and lymph node. We examined whether stabilized p53 is functional in HCCR-2 transgenic mice. Defective induction of p53 responsive genes including p21WAF1, MDM2, and bax indicates that stabilized p53 in HCCR-2 transgenic mice exists in an inactive form. These results suggest that HCCR-2 represents an oncoprotein that is related to breast cancer development and regulation of the p53 tumor suppressor.     

A sustained response to low dose interferon-alpha in a case of refractory pure red cell aplasia

Acquired pure red cell aplasia (PRCA) may be the result of a cellular or humoral autoimmune process. One proposed mechanism is the destruction of erythroid progenitors by self-reactive, cytotoxic T cells or natural killer (NK) cells. These cells normally express MHC class I receptors (KIR) which inhibit cytotoxicity when the target cell expresses the HLA class I antigen(s) they bind. Therefore, loss of these antigens on maturing erythroid progenitors may render them susceptible to destruction by the pathogenic cells. Interferon-alpha (INF-alpha) increases HLA class I expression on hematopoietic precursor cells. Therefore, we initiated a trial of INF-alpha in a patient with refractory PRCA. Following treatment, he developed transfusion independence, and a sustained normal hematocrit. Analysis of bone marrow erythroid cells revealed an increase in expression of HLA class I molecules. INF-alpha should be used in a controlled trial in patients with PRCA to determine its activity and mechanism of action.