Alisertib Induces Cell Cycle Arrest, Apoptosis, Autophagy and Suppresses EMT in HT29 and Caco-2 Cells.

Colorectal cancer (CRC) is one of the most common malignancies worldwide with substantial mortality and morbidity. Alisertib (ALS) is a selective Aurora kinase A (AURKA) inhibitor with unclear effect and molecular interactome on CRC. This study aimed to evaluate the molecular interactome and anticancer effect of ALS and explore the underlying mechanisms in HT29 and Caco-2 cells. ALS markedly arrested cells in G2/M phase in both cell lines, accompanied by remarkable alterations in the expression level of key cell cycle regulators. ALS induced apoptosis in HT29 and Caco-2 cells through mitochondrial and death receptor pathways. ALS also induced autophagy in HT29 and Caco-2 cells, with the suppression of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR), but activation of 5' AMP-activated protein kinase (AMPK) signaling pathways. There was a differential modulating effect of ALS on p38 MAPK signaling pathway in both cell lines. Moreover, induction or inhibition of autophagy modulated basal and ALS-induced apoptosis in both cell lines. ALS potently suppressed epithelial to mesenchymal transition (EMT) in HT29 and Caco-2 cells. Collectively, it suggests that induction of cell cycle arrest, promotion of apoptosis and autophagy, and suppression of EMT involving mitochondrial, death receptor, PI3K/Akt/mTOR, p38 MAPK, and AMPK signaling pathways contribute to the cancer cell killing effect of ALS on CRC cells.

[Laparoscopic anterior resection of rectal carcinoma with preservation of the left colonic artery].

OBJECTIVE: To evaluate the feasibility and efficacy of laparoscopic anterior resection of rectal carcinoma with preservation of the left colonic artery. METHODS: From February 2006 to February 2009, 52 patients with rectal carcinoma formerly scheduled for Dixon operation (clinical stage I and II) received laparoscopic Dixon surgery. The inferior mesenteric artery, left colonic artery, sigmoid artery or superior rectal artery, and lymph nodes were dissected through the vasa vasorum approach. The left colonic artery was retained by transecting the inferior mesenteric artery inferior to the left colonic artery. The operative time, intraoperative hemorrhage volume, intraoperative complications, anastomotic tension, number and histopathological features of the dissected lymph nodes surrounding the inferior mesenteric artery, and the rates of local recurrence, lymph node metastasis and anastomotic leakage were analyzed. RESULTS: The operation was successfully completed in all the 52 cases. The operative time ranged from 115 to 320 min with a mean of 150 min. The mean intraoperative hemorrhage was 25 ml (range 15-75 ml). None of the patients had perforation of the rectum, injuries to blood vessel, ureter or adjacent organs, or anastomotic tension. The number of dissected lymph nodes surrounding the inferior mesenteric artery ranged from 4 to 8, with a mean of 6.2. The dissected lymph nodes in the base of the inferior mesenteric artery showed no cancer cell metastasis, while 4 patients had cancer cell metastasis in the lymph nodes surrounding superior rectal artery. None of patients had anastomotic leakage. Local recurrence was found in only 1 case at 7 months after the operation. CONCLUSION: Laparoscopic anterior resection of the rectal carcinoma with preservation of the left colonic artery can be completed in patients with rectal carcinoma planning to receive Dixon operation (clinical stage I or II). This surgical approach preserves more supplying vessels and prevents anastomotic leakage without increasing the anastomotic tension or affecting lymph node dissection surrounding the inferior mesenteric artery.

[Endoscopic and histopathological features of serrated adenoma of large intestine:an analysis of 71 cases].

OBJECTIVE: To explore the endoscopic and histopathological morphology of large intestinal serrated adenomas (SA). METHODS: The endoscopic and pathological data of 71 SA patients, diagnosed in the Digestive Endoscopy Center, Nanfang Hospital from January 2002 to July 2005, were analyzed retrospectively. RESULTS: Forty-seven of the 71 serrated adenomas were protruded (sessile 23, semipedunculated 5, pedunculated 23) and 24 were superficial (flat 16, laterally spreading 8). The mean sizes of the protruded and superficial SA were 10.5 mm and 16.6 mm, respectively, and both of them were frequently located in the sigmoid and rectum. Histopathologically, SA contained tubular glands in 53, tubulovillous glands in 9 and villous glands in 9 cases. Mild dysplasia was found in 47 SAs, moderate dysplasia in 22 SAs, and canceration foci in 2 SAs. The dysplasia of SAs (<10 mm) was significantly better than that of SAs (>or= 10 mm) (P< 0.01). Most IV and III L pit SAs presented villous glands (64%) and tubular glands (68%), respectively. 40% of hyperplastic polyps-like SAs, composed of tubular glands,showed II pit pattern. Atypia in II pit SAs was similar to that in IIIL pit SAs, but was worse than that in IV pit SAs. CONCLUSION: Polyps with II pit pattern possibly are SAs sometimes. SA with the common characters of neoplastic polyps,should be regarded as a new potential precancerous lesion.