Hiroki Morita

MicroRNA-7 expression in colorectal cancer is associated with poor prognosis and regulates cetuximab sensitivity via EGFR regulation

MicroRNA-7 (miR-7) has been reported to be a tumor suppressor in all malignancies including colorectal cancer (CRC). However, its significance for CRC clinical outcomes has not yet been explored. The potential for miR-7 to act as a tumor suppressor by coordinately regulating the epidermal growth factor receptor (EGFR) signaling pathway at several levels was examined. We investigated the tumor inhibitory effect of miR-7 in CRC, with particular focus on the relationship between miR-7 and the EGFR pathway. Quantitative reverse transcription-PCR was used to evaluate miR-7 expression in 105 CRC cases to determine the clinicopathologic significance of this miRNA. The regulation of EGFR by miR-7 was examined with miR-7 precursor-transfected cells. Furthermore, we investigated whether miR-7 suppresses proliferation of CRC cells in combination with cetuximab, a monoclonal antibody against EGFR. Multivariate analysis indicated that low miR-7 expression was an independent prognostic factor for poor survival (P = 0.0430). In vitro assays showed that EGFR and RAF-1 are direct targets of miR-7, which potently suppressed the proliferation of CRC cells, and, interestingly, that the growth inhibitory effect of each of these was enhanced by cetuximab. miR-7 is a meaningful prognostic marker. Furthermore, these data indicate that miR-7 precursor, alone or in combination with cetuximab, may be useful in therapy against CRC.

Rikkunshito, a traditional Japanese medicine, suppresses cisplatin-induced anorexia in humans

Background The aim of this study was to investigate the effects of Rikkunshito on ghrelin secretion and on cisplatin-induced anorexia in humans. Methods The study was performed as a crossover design, and ten unresectable or relapsed gastric cancer patients were randomly divided into two groups. Group A (n = 5) was started on Rikkunshito (2.5 g three times daily, orally) from the first course of chemotherapy and followed by a second course without Rikkunshito. A treatment with reversed order was performed for Group B (n = 5). All patients received combined chemotherapy with S-1 plus cisplatin. The primary endpoint was the amount of oral intake, and the categories of scales of anorexia, nausea, and vomiting; secondary endpoints included the plasma concentration of acylated ghrelin. Results In the Rikkunshito-on period, no decrease of the plasma concentration of acylated ghrelin induced by cisplatin was observed. The average oral intake in the Rikkunshito-on period was significantly larger than that in the Rikkunshito-off period, and the grade of anorexia was significantly lower in the Rikkunshito-on period than in the Rikkunshito-off period. Conclusion Rikkunshito appeared to prevent anorexia induced by cisplatin, resulting in effective prophylactic administration of chemotherapy with cisplatin, and patients could continue their treatments on schedule.

Interdigestive migrating contractions are coregulated by ghrelin and motilin in conscious dogs

During fasting, gastrointestinal (GI) motility is characterized by cyclical motor contractions. These contractions have been referred to as interdigestive migrating contractions (IMCs). In dogs and humans, IMCs are known to be regulated by motilin. However, in rats and mice, IMCs are regulated by ghrelin. It is not clear how these peptides influence each other in vivo. The aim of the present study was to investigate the relationship between ghrelin and motilin in conscious dogs. Twenty healthy beagles were used in this study. Force transducers were implanted in the stomach, duodenum, and jejunum to monitor GI motility. Subsequent GI motility was recorded and quantified by calculating the motility index. In examination 1, blood samples were collected in the interdigestive state, and levels of plasma ghrelin and motilin were measured. Plasma motilin peaks were observed during every gastric phase III, and plasma ghrelin peaks occurred in nearly every early phase I. Plasma motilin and ghrelin levels increased and decreased cyclically with the interdigestive states. In examination 2, saline or canine ghrelin was administered intravenously during phase II and phase III. After injection of ghrelin, plasma motilin levels were measured. Ghrelin injection during phases II and III inhibited phase III contractions and decreased plasma motilin levels. In examination 3, ghrelin was infused in the presence of the growth hormone secretagogue receptors antagonist [D-Lys3]-GHRP-6. Continuous ghrelin infusion suppressed motilin release, an effect abrogated by the infusion of [D-Lys3]-GHRP-6. Examination 4 was performed to evaluate the plasma ghrelin response to motilin administration. Motilin infusion immediately decreased ghrelin levels. In this study, we demonstrated that motilin and ghrelin cooperatively control the function of gastric IMCs in conscious dogs. Our findings suggest that ghrelin regulates the function and release of motilin and that motilin may also regulate ghrelin.

Serum Albumin Is Superior to Prealbumin for Predicting Short-Term Recurrence in Patients with Operable Colorectal Cancer

The relationship between preoperative prealbumin and cancer survival has not been fully elucidated. The purpose of this study was to examine the relationship between preoperative nutritional conditions, including prealbumin and albumin concentrations, and the risk of recurrence in cases with operable colorectal carcinoma. One hundred fifty-eight patients who underwent elective colorectal resection were analyzed in this study. Of the eligible cases, 56 (35.4%) had decreased serum prealbumin and 15 (9.5%) had decreased serum albumin preoperatively. Among 158 cases in this study, 18 (11.4%) had disease recurrence. In the univariate analysis, the depth of tumor invasion, lymph node metastasis, lymphovascular invasion, serum albumin, prealbumin, and carcinoembryonic antigen were the factors significantly associated with disease recurrence. Multivariate analysis demonstrated that only serum albumin was a predictor of the recurrence; however, serum prealbumin lost its significance on multivariate analysis. Time to tumor recurrence by Kaplan-Meier curves significantly differed among patients with low serum albumin and prealbumin level. Our results suggest that prealbumin and albumin may be sensitive indicators of the risk of recurrent disease; however, low serum albumin levels are more useful than prealbumin in predicting short-term disease recurrence in operable colorectal cancer.

The association of VEGF-C expression with tumor lymphatic vessel density and lymph node metastasis in patients with gastric cancer and gastrointestinal stromal tumor.

BACKGROUND/AIMS Although tumors metastasize to lymph nodes via the lymphatics, the importance of vascular endothelial growth factor-C (VEGF-C) expression in mediating the process has not been well elucidated. We investigated the correlation between VEGF-C expression and lymphatic vessel density (LVD) and node metastasis in cases with gastric cancer and gastrointestinal stromal tumor (GIST). METHODOLOGY Immunohistochemistry, VEGF-C expression and LVD were performed in 41 patients with gastric cancer invading the muscularis propria and 19 patients with GIST. The clinicopathological features of these cases were compared. RESULTS In gastric cancer, VEGF-C expression was significantly associated with tumor LVD and lymph node metastasis. In GIST, none of these patients had lymph node metastasis and VEGF-C expression was not detected. The LVD was significantly higher in the cases with gastric cancer than in those with GIST. In gastric cancer, LVD was increased more in patients with positive lymph nodes than in those with negative lymph nodes. CONCLUSIONS These results indicate that the expression of VEGF-C is associated with tumor LVD and lymph node metastasis, suggesting that VEGF-C plays a critical role in node metastasis via lymphangiogenesis. The clinical observation that GIST rarely metastasizes to the lymph nodes may depend on the lack of VEGF-C expression.

Benefit of oral feeding as early as one day after elective surgery for colorectal cancer: oral feeding on first versus second postoperative day.

The optimal timing of early oral intake after surgery has not been fully established. The objective of this study was to compare early oral intake at postoperative day 1 after resection of colorectal cancer with that of day 2 to identify the optimal timing for resumption of oral intake in such patients. Consecutive patients with colorectal cancer who underwent elective colorectal resection were separated into two groups. Sixty-two patients began a liquid diet on the first postoperative day (POD1 group) and 58 patients began on POD2 (POD2 group) and advanced to a regular diet within the next 24 hours as tolerated. As for gastrointestinal recovery, the first passage of flatus was experienced, on average, on postoperative day 3.1 ± 1.0 in the POD2 group and on day 2.3 ± 0.7 in the POD1 group. The first defecation was also significantly earlier in patients in the POD1 group than those in the POD2 group (POD 3.2 ± 1.2 versus 4.2 ± 1.4, respectively). No statistical difference was found between the two groups in terms of postoperative complications. Our results suggest that very early feeding on POD1 after colorectal resection is safe and feasible and that induced a quicker recovery of postoperative gastrointestinal movement in patients.

Effects of 5-HT2B, 5-HT3 and 5-HT4 receptor antagonists on gastrointestinal motor activity in dogs

AIM To study the effects of 5-hydroxytryptamine (5-HT) receptor antagonists on normal colonic motor activity in conscious dogs. METHODS Colonic motor activity was recorded using a strain gauge force transducer in 5 dogs before and after 5-HT2B, 5-HT3 and 5-HT4 receptor antagonist administration. The force transducers were implanted on the serosal surfaces of the gastric antrum, terminal ileum, ileocecal sphincter and colon. Test materials or vehicle alone was administered as an intravenous bolus injection during a quiescent period of the whole colon in the interdigestive state. The effects of these receptor antagonists on normal gastrointestinal motor activity were analyzed. RESULTS 5-HT2B, 5-HT3 and 5-HT4 receptor antagonists had no contractile effect on the fasting canine terminal ileum. The 5-HT3 and 5-HT4 receptor antagonists inhibited phase III of the interdigestive motor complex of the antrum and significantly inhibited colonic motor activity. In the proximal colon, the inhibitory effect was dose dependent. Dose dependency, however, was not observed in the distal colon. The 5-HT2B receptor antagonist had no contractile effect on normal colonic motor activity. CONCLUSION The 5-HT3 and 5-HT4 receptor antagonists inhibited normal colonic motor activity. The 5-HT2B receptor antagonist had no contractile effect on normal colonic motor activity.

Adenoma of the nipple projecting out of the nipple: curative resection without excision of the nipple

BackgroundAdenoma of the nipple is a rare breast tumor that is often mistaken clinically for Paget’s disease and misinterpreted pathologically as invasive ductal carcinoma.Case reportWe report herein a distinctive case of adenoma of the nipple projecting out of the nipple. In the current case, we were able to perform curative resection through a periareolar incision similar to a microdochectomy without excision of the nipple. The diagnosis of adenoma of the nipple was confirmed histopathologically.ConclusionAlthough the tumor was found on top of the nipple, curative tumor resection without excision of the nipple was possible and the nipple was completely preserved. Adenoma of the nipple is a benign tumor, and thus the diagnosis of adenoma of the nipple must be confirmed so that unnecessary surgery can be avoided.

FDG-PET/CT of schwannomas arising in the brachial plexus mimicking lymph node metastasis: report of two cases

BackgroundSchwannoma is a tumor that develops on peripheral nerves or spinal roots. Although any part of the body can be affected, axillar and supraclavicular lesions are unusual for schwannoma. We report two cases of schwannoma arising in the brachial plexus, which were detected by 18F-fluorodeoxyglucose positron emission tomography and computed tomography (FDG-PET/CT).Case 1A 75-year-old Japanese woman showed high FDG accumulation in a subclavicular or axillary lesion found by FDG-PET/CT. Axillar-subclavicular lymph node metastasis was suspected and surgical excision was performed. Histological evaluation revealed schwannoma.Case 2A 75-year-old Japanese woman was diagnosed with suspected primary lung cancer with brain metastases. She showed high FDG uptake at a subclavicular or axillary lesion found by FDG-PET/CT. Surgical excision was performed to arrive at a definitive diagnosis. The mass was located at the trunk of the brachial plexus and was identified as a schwannoma.ConclusionAlthough schwannoma within an axillar or subclavicular lesion is relatively rare, brachial plexus schwannoma should be considered in the diagnosis of masses detected by FDG-PET/CT.

A Rare Case of Anterior Chest Wall Schwannoma Masquerading as a Breast Tumor

A schwannoma is a tumor that develops on peripheral nerves or spinal roots. Although any part of the body can be affected, the breast is a quite unusual site for schwannomas. We report herein a case of schwannoma presenting as a breast tumor. In the current case, the tumor showed both clinically and mammographically as a well-defined breast mass. Of interest, sonographically, the well-defined mass appeared to be located in subcutaneous tissue, not in breast parenchyma, and this finding was confirmed histopathologically. These findings indicate the possibility that a schwannoma arising from subcutaneous breast tissue can show exophytic growth to the breast and appear as a breast tumor. In other words, our case implies the possible presence of a “pseudo” breast schwannoma.