Min-Hua Zheng

Heated and humidified CO2 prevents hypothermia, peritoneal injury, and intra-abdominal adhesions during prolonged laparoscopic insufflations.

BACKGROUND Insufflation with standard cold-dry CO(2) during laparoscopic surgery has been shown to predispose patients to hypothermia and peritoneal injury. This study aimed to compare the effect of prolonged cold-dry CO(2) insufflation with heated-humidified CO(2) insufflation (3-5 h) on hypothermia, peritoneal damage, and intra-abdominal adhesion formation in a rat model. MATERIALS AND METHODS A total of 160 Wistar rats were randomized to undergo no insufflation or insufflation with cold-dry CO(2) (21 degrees C, <1% relative humidity) or heated-humidified CO(2) (37 degrees C, 95% relative humidity) for 3, 4, or 5 h. Core body temperature was measured via rectum before and during insufflations. Peritoneal samples were taken at 6, 24, 48, and 96 h after treatments and analyzed with light microscopy and scanning electron microscopy. Intra-abdominal adhesions were evaluated 2 weeks later. RESULTS Core body temperature significantly decreased in the cold-dry group, whereas it was maintained and increased in the heated-humidified group. Scanning electron microscopy and light microscopy studies showed intense peritoneal injury in the cold-dry CO(2) group but significantly less damages in the heated-humidified group. Increased intra-abdominal adhesion formation was observed in the cold-dry CO(2) group, while no adhesions were found in the rats insufflated with heated-humidified CO(2). CONCLUSIONS Heated-humidified CO(2) insufflation results in significantly less hypothermia, less peritoneal damage, and decreased adhesion formation as compared with cold-dry CO(2) insufflation. Heated-humidified CO(2) may be more suitable for insufflation application in prolonged laparoscopic surgery.

P21-activated protein kinase 1 is overexpressed in gastric cancer and induces cancer metastasis

P21-activated protein kinase (Pak1), a main downstream effector of small Rho GTPases, plays an important role in the regulation of cell morphogenesis, motility, mitosis and angiogenesis. However, the role of Pak1 in gastric cancer metastasis remains unclear. Here, we showed that Pak1 is overexpressed in gastric cancer tissues from 74 patients by immunohistochemistry. Overexpression of Pak1 was associated with metastasis and prognosis of gastric cancer. In addition, overexpression of Pak1 increased gastric cancer cell motility and invasion, whereas downregulation of Pak1 expression reduced gastric cancer cell migration and invasion. In further study, data showed that activated Pak1 inhibited stress fiber and focal adhesion complex formation in gastric cancer cells and led to the formation of motile phenotypes. Importantly, activated Pak1 elicited phosphorylation of the ERK and JNK-dependent pathway in gastric cancer cell lines. In conclusion, our results suggest that Pak1 is overexpressed in gastric cancer and plays an important role in the metastasis of gastric cancer. The mechanism by which Pak1 induces cancer metastasis may involve activation of ERK and JNK.

Aberrant expression and demethylation of γ-synuclein in colorectal cancer, correlated with progression of the disease

Recent evidence suggests that γ‐synuclein is abnormally expressed in a high percentage of tumor tissues of diversified cancer types, but rarely expressed in tumor‐matched non‐neoplastic adjacent tissues (NNAT). The molecular mechanism of CpG island demethylation may underlie aberrant γ‐synuclein expression. To fully understand the roles of aberrant γ‐synuclein expression and demethylation in the development of colorectal cancer (CRC), we examined the expression and methylation status of γ‐synuclein in 67 CRC samples, 30 NNAT samples, and five CRC cell lines as well. By using reverse transcription–polymerase chain reaction (RT‐PCR), western blot, and immunohistochemistry analyses, γ‐synuclein expression was detected in both HT‐29 and HCT116 cells, and was much higher in CRC samples than in NNAT samples (P < 0.05). The demethylating agent, 5‐aza‐2¢‐deoxycytidine, can induce re‐expression of γ‐synuclein in COLO205, LoVo, and SW480 cells. Unmethylated γ‐synuclein alleles were detected in HT‐29, HCT116, and LoVo cells by nested methylation‐specific PCR, and the demethylated status of γ‐synuclein was much higher in CRC samples than in NNAT samples by real‐time quantitative methylation‐specific PCR (P < 0.05). The results of genomic bisulfite DNA sequencing further confirmed that the aberrant γ‐synuclein expression in CRC was primarily attributed to the demethylation of CpG island. The protein expression and demethylation status of γ‐synuclein in 67 CRC samples correlated with clinical stage, lymph node involvement, and distant metastasis. These findings suggest an involvement of aberrant γ‐synuclein expression and demethylation in progression of CRC, especially in advanced stages. (Cancer Sci 2008; 99: 1924–1932)

Modulated T‐complex protein 1 ζ and peptidyl‐prolyl cis‐trans isomerase B are two novel indicators for evaluating lymph node metastasis in colorectal cancer: Evidence from proteomics and bioinformatics

Lymph node metastasis (LNM) is an important indicator for systematic therapy, which could increase the survival of colorectal cancer (CRC) patients. However, effective clinical evaluation for LNM is still absent to date. In this study, protein expression profiles of CRC tissues were compared between patients with and without LNM. Based on average expression level, 12 proteins were found to be differentially expressed in the CRC tissues with LNM, whose discrimination reliability was confirmed by PCA. With stepwise linear discriminant analysis, T‐complex protein 1 ζ subunit and peptidyl‐prolyl cis‐trans isomerase B (PPIB) were identified as two main contributors for separating CRC tissues with positive LNM from those negative ones in both original‐grouped and cross‐validated‐grouped cases, which was also supported in subsequent linear support vector machine analysis. In addition, the expression alterations of the two proteins were verified by Western blot and immunohistochemistry. Functional studies also confirmed the role of PPIB in migration and invasion of cancer cells. Taken together, the down‐regulated T‐complex protein 1 ζ subunit and up‐regulated PPIB were identified as two promising indicators for the clinical evaluation of LNM in CRC patients.

Laparoscopic sphincter-preserving surgery for low rectal tumor using prolapsing technique

Introduction: With this study, we aimed to assess the feasibility and outcome of laparoscopy‐assisted low anterior resection with a prolapsing technique for low rectal tumors.