Modified Shenlingbaizhu decoction reduces intestinal adenoma formation in adenomatous polyposis coli multiple intestinal neoplasia mice by suppression of hypoxia-inducible factor 1α-induced CD4+CD25+forkhead box P3 regulatory T cells.

OBJECTIVE: To test the hypothesis that modified Shenlingbaizhu decoction (MSD) attenuates the formation of intestinal adenomas by regulating activation of CD4+CD25+ forkhead box P3 (FoxP3) regulatory T cells (Tregs) by downregulation of hypoxia-inducible factor 1α (HIF-1α). METHODS: Chemical fingerprints of ginsenoside Rb1, ginsenoside Rc, paeoniflorin, and dioscin in standard extractions were used as material bases of MSD. Adenomatous polyposis coli multiple intestinal neoplasia (ApcMin/+) mice, which harbor a mutation in adenomatous polyposis coli, were used to host intestinal adenomas. Peripheral blood and spleen Tregs were analyzed by flow cytometry. Protein expression was analyzed by immunohistochemistry and Western blotting. RESULTS: The number and size of intestinal adenomas were significantly reduced by MSD treatment. Mucosal thickening and the spleen size were also substantially decreased by MSD. The carcinogenesis process in ApcMin/+ mice resembled that of human colorectal cancer. Molecular markers of neoplasms, such as ß-catenin, cyclooxygenase-2, proliferating cell nuclear antigen, and p53, were substantially ameliorated by MSD treatment. Moreover, MSD downregulated peripheral and spleen CD4+CD25+FoxP3+ Tregs and reduced in situ expression of CD4, CD25, and FoxP3 in intestinal adenomas. MSD also suppressed HIF-1α expression in the intestinal adenomas, and HIF-1α inhibition decreased expression of FoxP3 in Jurkat T cells under hypoxic conditions. CONCLUSION: MSD is a valid prescription to control the formation of intestinal adenomas in ApcMin/+ mice. It exerts anti-cancer effects partially through suppression of HIF-1α that induced activation of CD4+CD25+FoxP3+ Tregs in vivo and in vitro.

Laparoscopic hepatectomy for colorectal liver metastases located in all segments of the liver.

PURPOSE: Laparoscopic hepatectomy is not a well-established treatment modality for colorectal liver metastases. Moreover, most reports have been limited to tumors in the anterolateral segments (segments 2, 3, 4b, 5, and 6). In this study we evaluated the short- and long-term outcomes after laparoscopic hepatectomy for colorectal liver metastases located in all segments, including tumors located in the posterosuperior segments (segments 1, 4a, 7, and 8). METHODS: This retrospective study included 102 patients who underwent laparoscopic hepatectomy for colorectal liver metastases with radical intent between January 2009 and January 2016. The patients were divided into two groups (anterolateral and posterosuperior group) according to tumor location. The clinical and follow-up data of the two groups were reviewed. RESULTS: There was no 30-day postoperative mortality. Most of the postoperative 30-day complications were classified as minor complications (Clavien-Dindo classification). There was no difference in clinicopathologic characteristics between the two groups. Although posterosuperior group patients had significantly longer operative time (p=0.008) and postoperative hospital stay duration (p=0.041), as well as a greater blood loss (p=0.012), there was no significant difference in the rate and severity of postoperative complications (p=0.314 and 1.000 respectively). During a median follow-up of 41 months, the 5-year overall survival (OS) (p=0.449), and disease-free survival (DFS) (p=0.370) showed no significant difference between the two groups. CONCLUSIONS: Laparoscopic hepatectomy for colorectal liver metastases located in all segments of the liver can be safely performed in selected patients, with acceptable postoperative morbidity and oncologic results.

Laparoscopic hepatectomy for colorectal liver metastases located in all segments of the liver.

PURPOSE: Laparoscopic hepatectomy is not a well-established treatment modality for colorectal liver metastases. Moreover, most reports have been limited to tumors in the anterolateral segments (segments 2, 3, 4b, 5, and 6). We evaluated the short- and long-term outcomes after laparoscopic hepatectomy for colorectal liver metastases located in all segments, including tumors located in the posterosuperior segments (segments 1, 4a, 7, and 8). METHODS: TThis retrospective study included 102 patients who underwent laparoscopic hepatectomy for colorectal liver metastases with radical intent between January 2009 and January 2016. The patients were divided into two groups (anterolateral and posterosuperior group) according to tumor location. The clinical and follow-up data of the two groups were retrospectively reviewed. RESULTS: There was no 30-day postoperative mortality. Most of the postoperative 30-day complications were classified as minor complications (Clavien-Dindo classification). There was no difference in clinicopathologic characteristics between the two groups. Although posterosuperior group patients had significantly longer operative time (p=0.008) and postoperative hospital stay duration (p=0.041), as well as a greater blood loss (p=0.012), there was no significant difference in rate and severity of postoperative complications (p=0.314 and 1.000 respectively). During a median follow-up period of 41 months, the 5-year overall survival (OS) (p=0.449), and disease-free survival (DFS) (p=0.370) was no significant difference between the two groups. CONCLUSIONS: Laparoscopic hepatectomy for colorectal liver metastases located in all segments of the liver can be safely performed in selected patients, with acceptable postoperative morbidity and oncologic results.

[Mechanism of colon cancer cell apoptosis induced by telocinobufagin: role of oxidative stress and apoptosis pathway].

OBJECTIVE: To investigate the effects of telocinobufagin on viability and apoptosis of colorectal cancer (CRC) cells and explore the mechanism of telocinobufagin-induced apoptosis. METHODS: MTT assay was performed to detect the viability of CRC cells exposed to telocinobufagin. Nuclear staining with Hoechst 33342 and flow cytometry were used to analyze the cell death of CRC cells. Expressions of proteins related with cell apoptosis and oxidative stress were determined with Western blotting. RESULTS: Telocinobufagin decreased the viability of CRC cells in a time- and dose-dependent manner. The presence of karyopycnosis and apoptotic bodies together with the results of flow cytometry suggested that telocinobufagin induced cell apoptosis to cause cell death. Western blotting showed that telocinobufagin exposure of the cells resulted in upregulated p53 and Bax protein expressions and promoted cleavage of caspase 9 and PARP. Telocinobufagin induced phosphorylation of Bad and PARP cleavage, and suppressed phosphorylation of IKBα and TAK1 and expression of survivin in the cells. CONCLUSION: Telocinobufagin can decrease the viability of CRC cells by inducing cell apoptosis, which involves p53-mediated Bax activation and inhibition of the IAP pathway.