Seiichi Ishii

Introduction of antisense CD44s cDNA down‐regulates expression of overall CD44 isoforms and inhibits tumor growth and metastasis in highly metastatic colon carcinoma cells

We created antisense CD44 transfectants using LS174T, a colon adenocarcinoma cell line and assessed the effects of overall CD44 down‐regulation on colorectal tumor growth and metastasis. The expression of antisense CD44s (the standard form of CD44) cDNA markedly inhibited the overall expression of CD44 variants. In vitro studies showed a significantly reduced ability of the stable antisense transfectants (LS174TAS1 and LS174TAS2) to bind hyaluronate and osteopontin, ligands for CD44. These cells developed tumors more slowly than controls (parental LS174T and mock transfectants) when the cells were subcutaneously injected into SCID mice. However, in vitro proliferation assays demonstrated no significant difference between the antisense transfectants and the controls on a hyaluronate‐coated surface, suggesting the participation of ligands other than hyaluronate in tumor growth in vivo. Intrasplenic injection of parental LS174T cells produced colonies in the liver in 10 of 11 mice, whereas mice injected with the antisense transfectants were completely free of metastasis. In peritoneal dissemination, the weight of nodules and amount of ascites were significantly reduced in LS174TAS1 and AS2 compared with the controls. In vitro adhesion assays between the transfectants or controls and human peritoneal mesothelial cells revealed that the binding of LS174T cells to mesothelial cells was partly mediated by CD44‐hyaluronate interaction. These data suggest that CD44‐hyaluronate interaction plays a crucial role in peritoneal dissemination in colorectal carcinoma. The results of our study demonstrate the possible application of antisense CD44s to the treatment of colorectal carcinoma. Int. J. Cancer 91:67–75, 2001.

Outcomes after Pylorus-preserving Gastrectomy for Early Gastric Cancer: A Prospective Multicenter Trial

The aim of the present study was to compare in a prospective, multicenter trial the results early and late after pylorus-preserving gastrectomy (PPG) versus conventional distal gastrectomy (CDG) with Billroth I anastomosis for early gastric cancer. Eighty-one patients with early gastric cancer were randomized and then underwent either PPG or CDG. Duration of operation, intraoperative blood loss, days until removal of the nasogastric tube, days until start of oral intake, and decrease in body weight were studied as parameters for outcomes early after the surgery. Late results were studied in patients followed for longer than 3 years. Change in body weight, status of oral intake, symptoms suggesting early dumping syndrome, and overall satisfaction were addressed in the questionnaire. The presence of gallstones was examined with ultrasonography. There were no differences in early results between PPG and CDG. The incidence of early dumping syndrome was lower in PPG (8%) than in CDG (33%). Other late results including the incidence of gallstones were not different between the 2 groups. These results indicate that PPG is as safe as CDG and has an advantage in terms of early dumping syndrome.

Allelic loss of the NF1 gene in anal malignant melanoma in a patient with neurofibromatosis type 1

Abstract A 64-year-old man with neurofibromatosis type 1 (NF1) developed a primary malignant melanoma of the anus. Genetic analysis of the resected tumor confirmed loss of heterozygosity (LOH) of the NF1 gene. Anorectal malignant melanoma in NF1 is extremely rare, and genetic studies of the NF1 gene in such patients have not been reported. The allelic loss detected in the present patient supports the previously raised idea that NF1 can function as a tumor suppressor gene in the development of malignant melanoma in patients with NF1.

CD44H participates in the intrahepatic growth of murine colon 26 adenocarcinoma cells.

The purpose of this study was to determine if CD44, a metastasis‐associated cell adhesion molecule, is involved in the hepatic colonization by murine colon 26 adenocarcinoma cells. Indirect membrane immunofluorescence and FACS analysis showed strong expressions of CD44 and integrin β1 on colon 26 cells. Injection of 1×105 colon 26 cells into the superior mesenteric vein of syngeneic BALB/c mice produced macroscopic hepatic nodules in 92% (22/24) of the mice 14 days after inoculation. When colon 26 cells were pretreated with an anti‐CD44 monoclonal antibody (mAb), IM7, only 30% (3/10) of the mice produced minute nodules in the liver on day 14 (P<0.001), though IM7 did not inhibit growth of the cells in vitro. Pretreatment of colon 26 cells with an anti‐integrin β1 mAb did not significantly block the hepatic metastasis. Histologically, microcolonies of tumor cells were detected in all of the livers on day 14 including the IM7‐pretreatment mice that were free of gross nodules. However, percentages of tumor‐occupied areas in the liver were consistently lower in IM7‐pretreatment mice than in control mice (0.82% vs. 5.0% on day 14; P<0.005). Reverse transcription‐polymerase chain reaction (RT‐PCR) amplification of mRNA revealed that colon 26 cells and splenocytes only expressed the hematopoietic isoform of CD44 (CD44H), which had no insertion of variant exons, while normal colonocytes expressed possible variant isoforms. These data suggest that malignant transformation of murine colonic epithelium altered the expression pattern of CD44 isoforms and that CD44H participates in the intrahepatic growth of colon 26 cells.

Cytogenetic abnormality 46,XX,add(21)(q11.2) in a patient with follicular dendritic cell sarcoma

The case of a patient with follicular dendritic cell (FDC) sarcoma with chromosomal aberration add(21)(q11.2) is described. Cytogenetic studies showed the karyotype 46,XX,add(21)(q11.2)[3]/46,XX[17], although the encoded protein involved was not clarified. The abnormal pattern was quite simple, and different from a previous report. The clinical course of the FDC sarcoma in this case has been indolent, as for most FDC sarcoma patients. Although this patient suffered from breast carcinoma 6 years after the onset of FDC sarcoma, the carcinoma showed different histological and phenotypic profiles.

Successful treatment of intraoperative heart failure caused by ampulla cardiomyopathy by intra-aortic balloon pumping and percutaneous cardiopulmonary support : Report of a case

An 82-year-old woman underwent total gastrectomy for advanced gastric cancer with invasion to the lower esophagus. Her blood pressure dropped alarmingly during the operation, which was performed via the transabdominal and left-side transthoracic approach. Using echocardiography, we diagnosed intraoperative-oneset reversible heart failure caused by ampulla cardiomyopathy. Because the infusion of catecholamines is associated with secondary heart failure, we gave her calcium antagonists and nicorandil, then started intra-aortic balloon pumping (IABP) and the percutaneous cardiopulmonary support system (PCPS). On postoperative day (POD) 7, the IABP and PCPS were removed and on POD 12, she was extubated successfully. The patient was discharged on POD 54 and has remained well. The factors predisposing her to ampulla cardiomyopathy were left-side thoracotomy, hypoxia caused by one-lung ventilation, and the infusion of high-dose catecholamines. Prompt diagnosis and timely treatment of the heart failure with IABP and PCPS prevented any further complications.

An unusual case of abdominal pain

In March 2003, the patient exhibited severe right lower abdominal pain. This 71 year old man was also suffering with severe …