HapMap-based study on the association between MPO and GSTP1 gene polymorphisms and lung cancer susceptibility in Chinese Han population.

AIM: Myeloperoxidase (MPO) and glutathione S-transferase pi 1 (GSTP1) are important carcinogen-metabolizing enzymes. The aim of this study was to investigate the association between the common polymorphisms of MPO and GSTP1 genes and lung cancer risk in Chinese Han population. METHODS: A total of 266 subjects with lung cancer and 307 controls without personal history of the disease were recruited in this case control study. The tagSNPs approach was used to assess the common polymorphisms of MOP and GSTP1 genes and lung cancer risk according to the disequilibrium information from the HapMap project. The tagSNP rs7208693 was selected as the polymorphism site for MPO, while the haplotype-tagging SNPs rs1695, rs4891, rs762803 and rs749174 were selected as the polymorphism sites for GSTP1. The gene polymorphisms were confirmed using real-time PCR, cloning and sequencing. RESULTS: The four GSTP1 haplotype-tagging SNPs rs1695, rs4891, rs762803 and rs749174, but not the MPO tagSNP rs7208693, exhibited an association with lung cancer susceptibility in smokers in the overall population and in the studied subgroups. When Phase 2 software was used to reconstruct the haplotype for GSTP1, the haplotype CACA (rs749174+rs1695 + rs762803+rs4891) exhibited an increased risk of lung cancer among smokers (adjust odds ratio 1.53; 95%CI 1.04-2.25, P=0.033). Furthermore, diplotype analyses demonstrated that the significant association between the risk haplotype and lung cancer. The risk haplotypes co-segregated with one or more biologically functional polymorphisms and corresponded to a recessive inheritance model. CONCLUSION: The common polymorphisms of the GSTP1 gene may be the candidates for SNP markers for lung cancer susceptibility in Chinese Han population.

Calpain, Atg5 and Bak play important roles in the crosstalk between apoptosis and autophagy induced by influx of extracellular calcium.

Calcium (Ca(2+)) signals are involved in important checkpoints in cell death pathways and promote both apoptosis and autophagy. However, the relationship between autophagy and apoptosis in response to Ca(2+) level elevation is poorly understood. Here, we provided evidence that the influx of extracellular Ca(2+) triggered by Trichokonin VI (TK VI), an antimicrobial peptide, induced calpain-dependent apoptosis and autophagy in hepatocellular carcinoma (HCC) cells. Remarkably, TK VI preferentially induced apoptosis that was associated with calpain-mediated Bax and Atg5 cleavage, which resulted in the collapse of the mitochondrial membrane potential and cytochrome c release. Interestingly, truncated, but not full-length Atg5, associated with Bcl-xL and promoted the intrinsic pathway. Moreover, TK VI treatment induced reactive oxygen species (ROS) accumulation, an effect in which Bak might play a major role. This accumulation of ROS resulted in the subsequent disposal of damaged mitochondria within autophagosomes via Atg5-mediated and mitochondria-selective autophagy. Both the inhibition of calpain activity and Bax deficiency activated a switch that promoted an enhancement of autophagy. The inhibition of both apoptosis and autophagy significantly attenuated the TK VI cytotoxicity, indicating that the two processes had stimulatory effects during TK VI-meditated cell death. These results suggested that calpain, Bak and Atg5 were molecular links between autophagy and apoptosis and revealed novel aspects of the crosstalk between these two processes. The potential of TK VI is proposed as a promising anticancer agent for its well-characterized activity of Ca(2+) agonist and as a possible novel therapeutic strategy that acts on cancer cell mitochondria.

Oyster (Crassostrea gigas) hydrolysates produced on a plant scale have antitumor activity and immunostimulating effects in BALB/c mice.

Oyster extracts have been reported to have many bioactive peptides. But the function of oyster peptides produced by proteolysis is still unknown. In this study, the oligopeptide-enriched hydrolysates from oyster (Crassostrea gigas) were produced using the protease from Bacillus sp. SM98011 at laboratory level, and scaled up to pilot (100 L) and plant (1,000 L) levels with the same conditions. And the antitumor activity and immunostimulating effects of the oyster hydrolysates in BALB/c mice were investigated. The growth of transplantable sarcoma-S180 was obviously inhibited in a dose-dependent manner in BALB/c mice given the oyster hydrolysates. Mice receiving 0.25, 0.5 and 1 mg/g of body weight by oral gavage had 6.8%, 30.6% and 48% less tumor growth, respectively. Concurrently, the weight coefficients of the thymus and the spleen, the activity of natural killer (NK) cells, the spleen proliferation of lymphocytes and the phagocytic rate of macrophages in S180-bearing mice significantly increased after administration of the oyster hydrolysates. These results demonstrated that oyster hydrolysates produced strong immunostimulating effects in mice, which might result in its antitumor activity. The antitumor and immunostimulating effects of oyster hydrolysates prepared in this study reveal its potential for tumor therapy and as a dietary supplement with immunostimulatory activity.

[Study of gastric function after esophagectomy and cardiectomy with vagus nerve preserved and reconstruction of gastric funds in patients with esophageal and cardiac cancer].

OBJECTIVE: To study the gastric function after esophagectomy and cardiectomy with vagus nerve preserved and reconstruction of gastric funds (VPRG)in patients with esophageal cancer (EC) and cardiac cancer (CC). METHODS: Sixty-eight patients with early or middle staged EC or CC received esophagectomy and cardiectomy with vagus nerve preserved and reconstruction of gastric funds (VPRG),while other 68 patients esophagectomy and cardiectomy with vagus nerve severed and no reconstruction of gastric funds (VSNG) as control. The symptoms,the pressure of the residual esophagus and thoracic stomach, 24-hour pH monitoring, mean basic gastric acid output, gastric emptying time of the intrathoracic stomach,fasting serum gastrin level, fibreoptic endoscopic results were compared before and after operation between the two groups. RESULTS: The patients with VPRG had less symptoms after operation than those with VSNG such as anorexia, belch, reflux, heartburn, nausea, diarrhea, postcibal satiety (P< 0.01). In VPRG group,compared with the results before operation,there were no significant differences in 24-hour pH monitoring,the mean basic gastric acid output, the fasting serum gastrin level,the gastric emptying time of intrathoracic stomach one month and one year after operation (both P > 0.05). The pressure of the residual esophagus above the anastomosis in VPRG group was significantly higher than that in VSNG group (both P< 0.05). Fibreoptic endoscopic examination revealed higher incidences of postoperative atrophic gastritis and reflux esophagitis in VPRG group one month and one year after operation than those in VSNG group (P< 0.01). CONCLUSION: Preservation of the vagus nerve and reconstruction of gastric funds after esophagectomy and cardiectomy for esophageal and cardiac cancer can prevent digestive disorder and improve the life quality of the patients.

[Bronchial and pulmonary arterial sleeve resection and reconstruction in the treatment of central NSCLC].

OBJECTIVE: To evaluate the indications and surgical procedure of bronchial and pulmonary artery sleeve resection for patients with centrally located non-small cell lung cancer, and how to prevent complications. METHODS: From July 1989 to Aug 2000, 32 cases of central NSCLC were treated with bronchial and pulmonary arterial sleeve resection and reconstruction. The results were retrospectively analyzed. RESULTS: The complication rate was 25.0% (8/32), the mortality rate in 30-day postoperation was 6.3% (2/32), the overall 1-, 3- and 5-year survival rate was 82.8% (24/29), 50.0% (11/22) and 33.3% (4/12), respectively. CONCLUSION: Bronchial and pulmonary arterial sleeve resection and reconstruction in the treatment of patients with central NSCLC can not only maximize preservation of functional pulmonary parenchyma and improve patients, quality of life, but also provide an opportunity for those patients with poor pulmonary function to receive surgical resection of the tumor.