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Farnesyltransferase inhibitors (FTIs) suppress tumor aggressiveness in several malignancies by inhibiting Ras signaling. However, treatment of cells with a low dose of the FTI tipifarnib suppresses the expression of hypoxia‐inducible factor‐1α (HIF‐1α) and results in antitumor effects without inhibiting the Ras pathway. Although we previously reported that elevated HIF‐1α expression is associated with an aggressive phenotype in gastric cancer (GC), little is known about the antitumor effects of FTIs on GC. In this study, we examined the relationship between the antitumor effects of low‐dose tipifarnib and HIF‐1α expression in GC cells. Under normoxic conditions, HIF‐1α was expressed only in MKN45 and KATOIII cells. The inhibitory effect of tipifarnib on HIF‐1α was observed in HIF‐1α‐positive cells. Low‐dose tipifarnib had antitumor effects only on HIF‐1α‐positive cells both in vitro and in vivo. Furthermore, low‐dose tipifarnib inactivated ras homolog enriched in brain (Rheb)/mammalian target of rapamycin (mTOR) signaling and decreased intracellular reactive oxygen species (ROS) levels in HIF‐1α‐positive GC cells. Our results that the antitumor effects of low‐dose tipifarnib are at least partially mediated through suppression of mTOR signaling and HIF‐1α expression via inhibition of Rheb farnesylation and reduction in ROS levels. These findings suggest that low‐dose tipifarnib may be capable of exerting an antitumor effect that is dependent on HIF‐1α expression in GC cells. Tipifarnib may have potential as a novel therapeutic agent for HIF‐1α‐expressing GC exhibiting an aggressive phenotype., Low‐dose tipifarnib has antitumor effects on gastric cancer (GC) cells via suppression of mammalian target of rapamycin signaling and reactive oxygen species production. The effects of tipifarnib depend on hypoxia‐inducible factor‐1α (HIF‐1α) expression status. HIF‐1α expression is associated with cancer aggressiveness in GC. Tipifarnib may represent a novel therapeutic agent for GC exhibiting an aggressive phenotype.

Anastomotic leakage (AL) is one of the most serious complications after laparoscopic low anterior resection (LALAR) for rectal cancer. The aim of the present study was to investigate the risk factors for AL after LALAR.A retrospective study was conducted of 103 patients who underwent LALAR in a single institute between October 2008 and January 2018. Univariate and multivariate analyses were performed to determine the clinicopathological factors associated with AL.The overall incidence of AL was 9.7% (10/103). After anastomosis using the double-stapling technique, a transanal tube was placed in 88 patients (85.4%). A diverting stoma was created in 26 patients (25.2%). The univariate analysis showed that a younger age (P = 0.014), higher stage (P = 0.048), deeper depth of tumor invasion (P = 0.028), larger tumor circumference (P = 0.024), longer operation time (P = 0.015), and early postoperative diarrhea (P = 0.002) were associated with AL. The multivariate logistic regression analysis revealed early postoperative diarrhea (odds ratio [OR] 16.513, 95% confidence interval [CI] 2.393-113.971, P = 0.004) a younger age (10-year increments; OR 0.351, 95% CI 0.147-0.839, P = 0.019), operative time (10-min increments; OR 1.089, 95% CI 1.012-1.172, P = 0.022), and higher stage (OR 10.605, 95% CI 1.279-87.919, P = 0.029) were independent risk factors for AL CONCLUSION: Our findings suggest that tumor progression accompanied by a high stage, long operative time, and insufficient bowel preparation and early postoperative diarrhea due to a large tumor circumference may be risk factors of AL after LALAR for rectal cancer.

Highlights • The effectiveness of a transanal decompression tube to prevent anastomotic leakage after rectal surgery is widely accepted. • A rare complication of colonic perforation due to a transanal decompression tube may occurred. • The relationship between the tip of the transanal decompression tube, the intestine and the sacrum might be important., Introduction The effectiveness of transanal decompression tube (TDT) to prevent anastomotic leakage after rectal surgery has been widely accepted in recent years. However, a rare complication of intestinal perforation due to TDT has been also reported. Presentation of case A 88-year-old woman underwent laparoscopic low anterior resection for rectal cancer. An abdominal drainage tube adjacent to the colorectal anastomosis and a TDT were placed. The patient experienced abdominal pain, nausea and elevated inflammatory markers on postoperative day 6. Enema and computed tomography demonstrated colonic perforation due to the TDT, and emergency laparotomy was performed. Perforation of the anterior sigmoid colon located at the proximal side of the colorectal anastomosis was seen, and the TDT was exposed to the abdominal cavity. Therefore, primary closure of the perforation site, peritoneal lavage, drainage tube placement and transverse colostomy was performed. Discussion In our case, TDT seemed to compress the anterior wall of the colon and lead to perforation. The looseness of the remaining oral intestinal tract depressed in the pelvis was compressed by the TDT. Conclusion TDTs should be very carefully placed to avoid complication. The length and looseness of the oral intestine and the relationship between the TDT to be inserted might be important.

Gastric metastasis from breast cancer is clinically diagnosed rarely. The present study described an interesting and valuable case of gastric metastasis from breast cancer, which showed repeated changes of the molecular subtype with an impact on the choice of treatment. A 42-year-old woman underwent mastectomy with axillary lymph node dissection for an invasive lobular carcinoma of the left breast. The patient received gastroscopy due to an epigastric pain during the adjuvant chemotherapy. The endoscopic examination revealed an erosive lesion at the posterior wall of the gastric body. The gastric lesion was immunohistochemically diagnosed as a metastatic disease from the breast cancer. The patient initially received hormone therapy, according to the subtype of the primary and the metastatic diseases. The gastric lesion initially disappeared; however, a relapsed lesion transformed into luminal human epidermal growth factor receptor 2 type from luminal type. Subsequently, the metastatic lesions underwent repeated subtype changing, which created difficultly when deciding the treatment strategy. The molecular profile of breast cancer can change during the treatment, resulting in the treatment resistance observed in certain cases. Therefore, the optimal treatment must be selected, according to the changed subtype.

Patients with scirrhous gastric cancer (SGC) frequently develop peritoneal dissemination, which leads to poor prognosis. The secreted protein angiopoietin-like-4 (ANGPTL4), which is induced by hypoxia, exerts diverse effects on cancer progression. Here, we aimed to determine the biological function of ANGPTL4 in SGC cells under hypoxia. ANGPTL4 levels were higher in SGC cells under hypoxia than in other types of gastric cancer cells. Hypoxia-induced ANGPTL4 mRNA expression was regulated by hypoxia-inducible factor-1α (HIF-1α). Under hypoxic conditions, monolayer cultures of ANGPTL4 knockdown (KD) 58As9 SGC (58As9-KD) cells were arrested in the G1 phase of the cell cycle through downregulation of c-Myc and upregulation of p27, in contrast to control 58As9-SC cells. Moreover, the ability of 58As9-KD xenografts to form tumours in nude mice was strongly suppressed. When 58As9-KD cells were cultured in suspension, hypoxia strongly increased their susceptibility to anoikis through suppression of the FAK/Src/PI3K-Akt/ERK pro-survival pathway, followed by activation of the apoptotic factors caspases-3, -8 and -9. The development of peritoneal dissemination by 58As9-KD cells was completely inhibited compared with that by 58As9-SC cells. In conclusion, ANGPTL4 is uniquely induced by hypoxia in cultured SGC cells and is essential for tumour growth and resistance to anoikis through different mechanisms.