Cell to cell interaction in clusters enhances thermosensitivity in HT29 human colon cancer cells.

BACKGROUND/AIMS: Tumor cells at high density are considered to be resistant to hyperthermia. Our objective in this study was to investigate hyperthermia sensitivity of clusters, cancer cell aggregation, compared with that of monolayer cells. METHODOLOGY: Colon carcinoma cells HT29 were cultured on poly 2-hydroxyethyl methacrylate-coated dishes for 7 days and the clusters were selected by a 40µm pore filter. To detect the cell reproductive potential, a colony formation assay was performed in HT29 cells from a monolayer and from clusters after exposure to cis-diamino-dichloroplatinum, fluorouracil and/or hyperthermia. Western blotting was used to analyze the induction of heat shock protein expression by hyperthermia. RESULTS: Histological findings of the clusters less than 400µm in diameter showed dividing cells and no secondary central necrosis. Cluster cells were more sensitive to hyperthermia than monolayer cells (p<0.0001). However, cluster formation induced cis-diamino-dichloroplatinum resistance (p<0.0001). The enhancement of hyperthermia sensitivity in clusters was not observed when the cells were heated after dispersion to single cells (p<0.0001). No difference of heat-induced HSP70/72 and HSP27 expression between cluster cells and monolayer cells was found. CONCLUSIONS: Cluster formation induced hyperthermia sensitivity, and cell-to-cell interaction in the clusters might enhance hyperthermia sensitivity.

Effectiveness of intraperitoneal hyperthermo-chemotherapy for malignant peritoneal mesothelioma and estimation of its effect by repeated FDG-PET: a case report.

Malignant peritoneal mesothelioma is a rare neoplasm derived from the peritoneum of the abdominal cavity. Here, we report on a case of malignant peritoneal mesothelioma that expanded aggressively after initial surgery, followed by successful treatment with cytoreductive surgery, intra-abdominal hyperthermo-chemotherapy, to allow the patient to perform daily activities with reduced symptoms. The therapeutic effects were monitored by FDG-PET/CT. The patient, a 55-year-old female, was referred to our hospital with a diagnosis of pelvic tumor. Laparotomy and cytoreductive surgery revealed the diagnosis of malignant mesothelioma. The tumor progressed rapidly in the abdominal cavity, so cytoreduction and intra-abdominal hyperthermo-chemotherapy were performed as strong local therapies. In addition, monthly hyperthermo-chemotherapy was performed. The patient lived for 21 months after the first surgery. Severe bowel obstruction and malignant ascites did not appear. Cancerous pain was controllable throughout this portion of her life. In conclusion, we experienced a case of malignant peritoneal mesothelioma and treated it with hyperthermo-chemotherapy. This treatment helped the patient to maintain daily activities throughout the remainder of her life. Thus, hyperthermo-chemotherapy can be considered an option in the treatment of malignant peritoneal mesothelioma.

[Endocrine cell carcinoma (atypical carcinoid) of the ileocecal region adjacent to an adenocarcinoma].

An 86-year-old woman was admitted because of right lower abdominal pain. A 7 by 6 cm tumor palpable in the right lower quadrant was poorly mobile. Abdominal CT scan showed a huge tumor with a strong enhancement effect. Barium enema and colonoscopic examination revealed a submucosal tumor located from the cecum to the ascending colon on the oral side. An undifferentiated adenocarcinoma was suspected after examination of the biopsy specimen, right hemicolectomy was performed. The tumor invaded the retroperitoneal membrane. Histological examination showed a very atypical carcinoid tumor with central necrosis invading the veins. Pathohistologically, the huge tumor was diagnosed as endocrine cell carcinoma or atypical carcinoid. Furthermore, an elevated lesion, 2.5 cm in size, was revealed in the cecum closed to the huge tumor. Histological examination showed that the polypoid lesion was early moderately differentiated adenocarcinoma. There was no transition between the two tumors. The patient was discharged, but died of local recurrence 9 months after the surgery. Endocrine cell carcinoma of the large bowel is rare, in particular of the ileocecal region. Endocrine cell carcinoma of the ileocecal region adjacent to an adenocarcinoma without transition had not been reported previously in Japan.