Several essential oils possess pharmacological effects. Among the various constituents of essential oils, 1, 8-cineole has been shown to possess pharmacological effects such as anti-bacterial and anti-inflammatory effects. The effect of 1, 8-cineole on human colorectal cancer cells, however, has not reported previously. In this study, we have investigated the anti-proliferative effect of 1, 8-cineole on human colon cancer cell lines HCT116 and RKO by WST-8 and BrdU assays. The cytotoxicity of 1, 8-cineole was investigated by LDH activity and TUNEL staining. The mechanism of apoptosis by 1, 8-cineole was determined by western blot analyses. In in vivo study, RKO cells were injected into the SCID mice and the effect of 1, 8-cineole was investigated. Specific induction of apoptosis, not necrosis, was observed in human colon cancer cell lines HCT116 and RKO by 1, 8-cineole. The treatment with 1, 8-cineole was associated with inactivation of survivin and Akt and activation of p38. These molecules induced cleaved PARP and caspase-3, finally causing apoptosis. In xenotransplanted SCID mice, the 1, 8-cineole group showed significantly inhibited tumor progression compared to the control group. These results indicated 1, 8-cineole suppressed human colorectal cancer proliferation by inducing apoptosis. Based on these studies 1, 8-cineole would be an effective strategy to treat colorectal cancer.
Fatty acid synthase is highly expressed in many types of human cancers. Cerulenin, a natural inhibitor of fatty acid synthase, induced apoptosis in the human colon cancer cell lines HCT116 and RKO. Oxaliplatin also induced cell death in these cell lines. Cerulenin treatment was associated with reduced levels of phosphorylated Akt, activation of p38 and induced caspase-3 cleavage and finally caused apoptosis. Oxaliplatin induced activation of the p53-p21 pathway and p38. In combination with cerulenin and oxaliplatin, activation of the p53-p21 pathway and p38 occurred in a smaller concentration and finally induced caspase-3 cleavage in a smaller concentration of cerulenin and oxaliplatin. In xenotransplanted SCID mice, the cerulenin + oxaliplatin group significantly inhibited tumor progression compared to the control, cerulenin and oxaliplatin groups. Based on these studies, inhibiting fatty acid synthase would be an effective strategy to treat unresectable colorectal cancer tumors in combination with oxaliplatin. Fatty acid synthase inhibitor would be one of the best counterparts of oxaliplatin, which reduces the dose and side-effects of oxaliplatin and would make it possible to endure the chemotherapy over a longer period.
PurposeSerotonin (5-hydroxytryptamine [5-HT])3 receptor antagonists are effective for the treatment of diarrhea-predominant irritable bowel syndrome (IBS-D), in which exaggerated intestinal/colonic hypermotility is often observed. Recent studies have suggested that the motility disorder, especially spastic hypermotility, seen in the neorectum following sphincter-preserving operations for rectal cancer may be the basis of the postoperative defecatory malfunction seen in these patients. We investigated the efficacy of 5-HT3 receptor antagonists in patients suffering from severe low anterior resection syndrome.Patients and methodsA total of 25 male patients with complaints of uncontrollable urgency or fecal incontinence following sphincter-preserving operations were enrolled in this study. Defecatory status, assessed on the basis of incontinence score (0–20), urgency grade (0–3), and number of toilet visits per day, was evaluated using a questionnaire before and 1 month after the administration of the 5-HT3 antagonist ramosetron.ResultsAll the parameters assessed improved significantly after taking ramosetron for 1 month. The effect was more prominent in cases whose anastomotic line was lower, ie, inside the anal canal. Defecatory function was better in patients who commenced ramosetron therapy within 6 months postoperatively, as compared to those who were not prescribed ramosetron for more than 7 months postoperatively.ConclusionThese results suggest that 5-HT3 antagonists are effective for the treatment of low anterior resection syndrome, as in diarrhea-predominant irritable bowel syndrome. The improvement in symptoms is not merely time dependent, but it is related to treatment with 5-HT3 antagonists.
Liquid biopsy is a non-invasive tool to examine the genetic profile of tumors by identification of mutated circulating tumor DNA (ctDNA), which is often analyzed by next generation sequencing (NGS) or droplet digital PCR (ddPCR) assay. We first examined the ctDNA mutation in pre-operative plasma samples obtained from 154 colorectal cancer (CRC) and 46 gastric cancer (GC) patients, using the NGS-based panel assay. The overall detection rate of mutated ctDNA was 72.0% (144 of 200 patients), and the panel-based screening identified 207 and 47 mutations from CRC and GC patients, respectively. The ddPCR analysis was then performed on postoperative samples of 77 patients, and detection of mutated ctDNA was earlier than imaging-based diagnosis in all of 6 patients who showed the tumor recurrences after surgery. Our data also revealed that patients with positive post-operation ctDNA level showed significant shorter recurrence-free survival compared to the patients with negative ctDNA level (HR 14.9; 95% CI, 0.7-313.5; p < 0.0001). These findings suggested that screening of mutated ctDNA by liquid biopsy aids in identifying the patients at high risk of post-operative recurrence, and serial screening of ctDNA would allow to monitor the response after treatment and/or early detection of tumor recurrence.
Hiatal hernias after total gastrectomy for advanced gastric cancer are very rare. We review a case of a 44-year-old male who presented with dyspnea and chest pain 2 days after total gastrectomy, lower esophagectomy, and splenectomy with retrocolic Roux-en-Y reconstruction approached by a left thoracoabdominal incision for gastric cancer at the cardia. Plain and cross-sectional imaging identified a large hiatal hernia protruding into the right thorax containing left-sided transverse colon and small intestine. Our patient underwent a laparotomy, and after hernia reduction the hiatal defect was repaired by direct suturing. He experienced anastomotic leakage and right pyothorax, but recovered. The potential cause is discussed here and the published literature on this rare complication is reviewed briefly.
in order to visualize restricted diffusion, the present study developed a novel method called 'apparent diffusion coefficient (ADC) subtraction method (ASM)' and compared it with diffusion kurtosis imaging (DKI). The diffusion-weighted images of physiological saline, in addtion to bio-phatoms of low cell density and the highest cell density were obtained using two sequences with different effective diffusion times. Then, the calculated ADC values were subtracted. The mean values and standard deviations (SD) of the ADC values of physiological saline, low cell density and the highest cell density phantoms were 2.95±0.08x10-3 , 1.90±0.35x10-3 and 0.79±0.05x10-3 mm 2 /sec, respectively. The mean kurtosis values and SD of DKI were 0.04±0.01, 0.44±0.13 and 1.27±0.03, respectively. The ASM and SD values were 0.25±0.20x10 4 , 0.51±0.41x10 4 and 4.80±4.51x10 4 (sec/mm 2) 2 , respectively. Using bio-phantoms, the present study demonstrated that DKI exhibits restricted diffusion in the extracellular space. Similarly, ASM may reflect the extent of restricted diffusion in the extracellular space.
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