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J Kaganoi

Publications and source records attributed to J Kaganoi.

18 recordsLinked to original sources
PubMed2006

Significance of nerve growth factor overexpression and its autocrine loop in oesophageal squamous cell carcinoma.

Nerve growth factor (NGF) is overexpressed not only in nervous system, but also in several types of cancers. However, the role of NGF in oesophageal squamous cell carcinoma (OESCC) remains unclear. Here, we show the first evidence of NGF-TrkA autocrine loop and clinical significance of NGF overexpression in OESCC. Immunohistochemical study of 109 OESCC specimens revealed that NGF overexpression, found in 63 out of 109 patients (57.8%), was associated with lymph node metastasis, distant metastasis, higher TNM stage, poorer tumour differentiation, and poorer survival. NGF overexpression was also associated with strong expression of TrkA and negative expression of low-affinity neurotrophin receptor (p75NTR). Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) of 19 surgical specimens showed upregulation of NGF mRNA in 17 out of 19 (89%) patients. All five OESCC cell lines tested in vitro secreted detectable NGF in enzyme-linked immunosorbent assay, and expressed TrkA and p75NTR on RT-PCR and Western blot. The motility of HSA/c, one of the OESCC cell lines overexpressing NGF, was significantly decreased by either neutralising anti-NGF antibody, an inhibitor of TrkA, or NGF-small interfering RNA in transwell migration assay. Our findings suggest that NGF is of potential interest not only as a prognostic factor, but also as a novel therapeutic target in OESCC.

Adult↗
PubMed2004

Detection of circulating oesophageal squamous cancer cells in peripheral blood and its impact on prognosis.

BACKGROUND: Many studies have attempted to detect cancer cells using the reverse transcription-polymerase chain reaction (RT-PCR) for specific mRNAs. None has examined the correlation between the presence of circulating oesophageal cancer cells in peripheral blood and long-term outcome. METHODS: Blood samples were obtained on admission, and before, during and after operation from 70 patients with squamous oesophageal cancer who had complete clinicopathological records and who underwent curative oesophagectomy between June 1997 and June 2000. RT-PCR for mRNA encoding squamous cell carcinoma antigen (SCCA mRNA) was used to detect oesophageal cancer cells in peripheral blood. RESULTS: Twenty-three patients (33 per cent) were positive for SCCA mRNA on admission and 17 of these patients developed recurrent disease. SCCA mRNA on admission correlated with the depth of tumour invasion (P < 0.001) and with venous invasion (P < 0.001). Eleven of 24 patients with a positive intraoperative result were positive for SCCA mRNA only during operation, of whom seven also developed recurrence. CONCLUSION: RT-PCR for SCCA mRNA can detect oesophageal cancer cells in peripheral blood. The presence of such cells in blood samples obtained on admission or during operation is a useful predictor of outcome in patients with oesophageal squamous cell carcinoma.

Aged↗
PubMed2003

Growth inhibition through activation of peroxisome proliferator-activated receptor gamma in human oesophageal squamous cell carcinoma.

Peroxisome proliferator-activated receptor gamma (PPARgamma) heterodimerises with retinoid X receptor alpha (RXRalpha) and is thought to be a novel therapeutic target for human malignancies. We evaluated the ability of troglitazone (TRO) alone or in combination with 9-cis retinoic acid (9CRA), ligands of PPARgamma and RXRalpha, respectively, to inhibit the growth of oesophageal squamous cell carcinoma (OSCC). All 10 tested OSCC cell lines of a KYSE series expressed PPARgamma and RXRalpha at both the mRNA and protein levels. In four tested cell lines, TRO inhibited growth, and a synergistic effect was observed with simultaneous 9CRA application. In KYSE 270 cells, a luciferase reporter assay showed that the simultaneous application of TRO and 9CRA to the cells increased the relative luciferase activity approximately 20-fold compared with the controls without TRO or 9CRA application. In this cell line, flow cytometry demonstrated that combined treatment with TRO and 9CRA greatly increased the sub-G1 phase, and Hoechst 33342/propidium iodide (PI) staining showed that apoptotic cell death was mainly induced through ligand treatment. In addition, implanted tumours in nude mice showed significant inhibition of tumour growth when treated with TRO. These results suggest that the PPARgamma/RXRalpha heterodimer may be a new therapeutic target for OSCC.

Alitretinoin↗
PubMed2003

Validity of intraoperative pathological diagnosis of paratracheal lymph node as a strategy for selection of patients for cervical lymph node dissection during esophagectomy.

The aim of this paper is to examine whether intraoperative examination of paratracheal nodes can indicate cervical node dissection and whether this approach is valid. From 1988 to 1997, 76 patients with thoracic esophageal squamous cell carcinoma received esophagectomies with and without cervical lymph node (LN) dissection based on the results of intraoperative pathological diagnosis from selective checking of paratracheal LN. We retrospectively examined the outcomes for the patients and the micro metastasis in the dissected lymph node using cytokeratin staining. Three of the seven patients with cervical LN dissection were detected as having cervical LN metastasis by postoperative hematoxylin-eosin or cytokeratin staining. Five (7%) of the 69 patients without cervical LN dissection had cervical LN recurrence after the operation. Four of the seven patients who were diagnosed as having metastasis or micro metastasis in paratracheal LN by postoperative examination had cervical LN recurrence after the operation. In conclusion, the esophagectomy with and without cervical LN dissection for thoracic esophageal squamous cell carcinoma based on the results of intraoperative pathological diagnosis from selective checking of paratracheal LN was not fully acceptable. The reliability of intraoperative pathological diagnosis of selective checking may improve by increasing the number of checked LN and the detection of micro metastasis.

Aged↗
PubMed2001

Gene expression profiling in human esophageal cancers using cDNA microarray.

Human esophageal cancer cell lines and human esophageal cancer tissues were profiled on cDNA microarrays. In esophageal cancer cell lines, KYAE and OE-33 (adenocarcinomas) were distinguished from KYSE series (squamous cell carcinomas). Although SK-GT-4 and TE7 were derived from adenocarcinomas, they had a comparatively similar expression profile to the KYSE series. A set of genes whose expression commonly either increased or decreased in cancer cell lines was identified. Genes that were characteristically expressed in KYAE and OE-33 were also identified. The gene expression profiles of cancer tissues (CTs) were remarkably different from those of the cancer cell lines (CCLs). Notable differences between CCLs and CTs were observed in matrix metalloproteinases, plasminogen activator, collagens, paxillin, and thrombospondin 2, etc., whose expression was not increased in CCLs but increased in CTs. Twenty-three genes were extracted to categorize patients according to their prognoses, and clustering analyses, using these genes, were performed successfully.

Adenocarcinoma↗
PubMed2001

Suppression of N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumorigenesis in F344 rats by JTE-522, a selective COX-2 inhibitor.

Recent studies have demonstrated that overexpression of cyclooxygenase-2 (COX-2) and elevation of COX-2-mediated synthesis of prostaglandin E(2) (PGE(2)) were observed in various cancers including esophageal cancer, but their roles in carcinogenesis of the esophagi still remain unclear. To address the issue, we observed the reduction of N:-nitrosomethylbenzylamine (NMBA)-induced tumorigenesis in rat esophagi via JTE-522 (4-[4-cyclohexyl-2-methyloxazol-5-yl]-2-fluorobenzenesulfonamide), a selective COX-2 inhibitor. In this study, 54 F344 male rats were divided into nine groups; JTE-522 (3, 9 and 30 mg/kg) was administered orally. We also examined the effects of JTE-522 on COX-2 mRNA and synthesis of PGE(2). In the group in which JTE-522 was administered intermittently at a daily dose of 30 mg/kg, the number of NMBA-induced esophageal tumors per rat significantly reduced, to 62% (P< 0.05), but the size of the tumors was not significantly inhibited. In the group in which JTE-522 was administered continuously five times weekly for 24 weeks at a daily dose of 9 mg/kg, both the number and size of tumors significantly reduced, to 29 and 44%, respectively (P<0.05). Furthermore, JTE-522 suppressed not only tumor formation but also developing carcinomas (P<0.0021) [corrected]. In this study, treatment with NMBA alone resulted in an approximately 5-fold rise in expression of COX-2 mRNA detected by semi-quantitative RT-PCR analysis and an approximately 7-fold increase in the production of PGE(2) measured by ELISA compared with the normal esophageal mucosa. The up-regulated COX-2 expression did not decrease with the treatment of JTE-522 at the 3, 9 and 30 mg/kg doses; however, the increased levels of PGE(2) synthesis were significantly decreased by administering JTE-522 (P<0.01). Our study suggests that COX-2-mediated PGE(2) is important in NMBA-induced esophageal tumorigenesis in rats, and therefore may be a promising chemotherapeutic target for the prevention and treatment of esophageal cancer, especially with selective COX-2 inhibitors.

Animals↗
PubMed2001

Expression of angiogenic factors and apoptotic factors in leiomyosarcoma and leiomyoma.

Angiogenesis is essential for tumor growth and metastasis. Some angiogenic factors, such as vascular endothelial growth factor (VEGF), platelet-derived endothelial cell growth factor (PD-ECGF), transforming growth factor-alpha (TGF-alpha) and basic fibroblast growth factor (bFGF) are involved in increased angiogenic activity and disease progression in many carcinomas. However, there is little information regarding the association between angiogenic factors and leiomyosarcoma. Although there are abundant vessels in the sarcoma which enable it to easily receive nutrition and medicinal components, chemotherapy cannot effectively treat leiomyosarcoma. This means the resistance to anticancer drugs in leiomyosarcoma is very strong. However, the resistant mechanism is still unclear. In this study, expressions of VEGF, PD-ECGF, TGF-alpha, bFGF, intratumoral microvessel density (IMVD), and p53, Bcl-2 and Bax were examined by immunohistochemistry in 30 patients with leiomyosarcoma and 21 patients with leiomyoma. With regard to angiogenesis, PD-ECGF and TGF-alpha were closely associated with an increase in IMVD (p=0.012, 0.0196, respectively), and VEGF and PD-ECGF were significantly expressed in leiomyosarcoma compared with leiomyoma (p=0.041, 0.041, respectively). Although p53 expression in leiomyosarcoma was significantly higher than in leiomyoma (p=0.016), the frequency of p53 positivity was not so high (47%). On the other hand, the ratio of Bcl-2/Bax in leiomyosarcoma was significantly higher than that in leiomyoma (p=0.033). The findings of this study suggest that in leiomyosarcoma, angiogenic factors, such as PD-ECGF, VEGF and TGF-alpha expression may be involved in tumor angiogenesis, and the frequently high ratio of Bcl-2/Bax and expression of p53 gene mutation might be related to chemoresistance mechanism.

Angiogenesis Inducing Agents↗
PubMed2000

Detection of lymph node metastasis of oesophageal cancer by RT-nested PCR for SCC antigen gene mRNA.

With recent development in molecular biology, reverse transcriptase polymerase chain reaction (RT-PCR) has been applied to detect occult lymph node metastasis, but there have been few reports concerning oesophageal cancer. The objective of this study is to investigate the usefulness of the squamous cell carcinoma (SCC) antigen gene as a marker with RT-nested PCR to detect occult lymph node metastases of oesophageal cancer. The SCC antigen has been widely used as a serum tumour marker and was reported as a target gene to detect tumour cells in peripheral blood in cervical cancer. In this study, 620 lymph nodes from 14 oesophageal cancer patients were analysed. The results of RT-nested PCR were compared with that of pathological and immunohistochemical examinations. In the test of sensitivity, the RT-nested PCR detected 10(1) of SCC antigen producing cells in 10(7) peripheral blood mononucleocytes and was not found in 43 control lymph nodes. The pathological examination, immunohistochemical examination and the RT-nested PCR detected 36, 45 and 65 nodes respectively. The RT-nested PCR detected statistically more lymph nodes than the pathological or immunohistochemical examination. The sensitivity and specificity seem higher in squamous cell carcinoma cases. The SCC antigen gene is one of the more useful markers for RT-nested PCR to detect occult lymph node metastases of oesophageal cancer.

Antigens, Neoplasm↗
PubMed2000

PTEN/MMAC1 expression in esophageal squamous cell carcinomas.

The PTEN/MMAC1 gene at 10q23.3 is a novel tumor suppressor gene candidate. Various kinds of tumors have mutations in this gene. However, in some cancers PTEN/MMAC1 gene may be inactivated by mechanisms other than gene deletion and mutation, including promoter methylation or translational modification. The aim of this study was to determine whether there are abnormalities in the expression of PTEN/MMAC1 gene in esophageal cancer. Reverse transcription polymerase chain reaction and western blot were used to examine PTEN/MMAC1 expression in human esophageal squamous cell lines and normal cultured esophageal epithelial cells. Immunohistochemical staining was carried out to detect PTEN/MMAC1 expression in surgically resected esophageal squamous cell carcinomas and normal esophageal epithelium. All 30 esophageal cancer cell lines (KYSE series) and normal cultured esophageal epithelial cells expressed PTEN/MMAC1 mRNA. Western blot analysis confirmed that all the cell lines expressed PTEN/MMAC1 protein and there was no difference in expression level. Immunohistochemical study showed that the PTEN/MMAC1 protein was localized dominantly in the cytoplasm and strongly stained in all 42 surgically resected esophageal squamous cell carcinomas and normal esophageal epithelium. PTEN/MMAC1 is rarely associated with esophageal squamous cell carcinoma carcinogenesis.

Carcinoma, Squamous Cell↗
PubMed2000

Rapid and prominent up-regulation of high-affinity receptor for immunoglobulin G (Fc gamma RI) by cross-linking of beta 2 integrins on polymorphonuclear leukocytes.

Receptors for the Fc region (FcR) of immunoglobulin (Ig)G play essential roles in effector functions of polymorphonuclear leukocytes (PMNs) including the antibody-mediated clearance of microbes. In contrast to the constitutive expression of the low-affinity receptors for IgG (Fc gamma RII [CD32] and Fc gamma RIII [CD16]), the high-affinity receptor Fc gamma RI (CD64) is barely detectable on unactivated PMNs. CD64 expression is induced in a slow kinetic manner by interferon (IFN)-gamma and granulocyte colony-stimulating factor (G-CSF) after 12 to 24 hours of exposure to these agents. We found that the cross-linking of CD11b as well as of CD18 induced comparable rapid increases in CD64 expression on the surface of PMNs, occurring within 15 minutes of exposure. Cross-linking of neither CD11a nor CD11c induced CD64 expression. In contrast to slow induction by IFN-gamma and G-CSF, the integrin-induced rapid CD64 expression did not require RNA synthesis. Genistein, herbimycin A, and 1,2-bis(o-aminophenoxy)ethan-N,N-N',N'-tetraacetic acid blocked the immediate expression of CD64 in a dose-dependent manner, suggesting that the signal is mediated through calcium mobilization and protein tyrosine kinase(s). Such rapid modulation of the high-affinity Fc gamma RI receptor by integrin cross-linking may reflect the requirement for rapid up-regulation of PMN effector functions, after interaction with endothelial cells, platelets or bacteria.

CD11 Antigens↗
PubMed1998

Spontaneous perforation of the rectum with possible stercoral etiology: report of a case and review of the literature.

Stercoral perforation of the colon or rectum is a rare cause of acute abdomen, with fewer than 70 cases documented in the literature. We report herein the case of a 60-year-old man who presented with anuria and epigastric pain with physical signs of peritonitis. An abdominal X-ray showed bilateral subphrenic free air accumulation, and an emergency laparotomy subsequently revealed perforation of the rectum, suggestive of a stercoral cause, which was treated by simple closure after debridement. Following an uneventful postoperative course, he was discharged from the hospital 3 weeks after his operation and is now doing well without having suffered any further gastrointestinal problems. The clinical features, diagnosis, and treatment of the disease are reviewed following the presentation of this case. Surgeons should be aware of the possibility of this fatal disease, despite its rare incidence. Furthermore, it is important to recognize the condition at an early stage because it has a significantly high mortality if not treated early. Conversely, the surgical outcome is satisfactory provided surgery is performed in due time.

Debridement↗
PubMed1998

The incidence of colorectal cancer during pregnancy in Japan: report of two cases and review of Japanese cases.

Colorectal cancer during pregnancy is very rare. We report two additional cases of rectal carcinoma. A 34-year-old woman with an obstructive adenocarcinoma of the rectal region was diagnosed at labor. A 35-year-old woman with an adenocarcinoma of the rectal region was diagnosed at 32 weeks of gestation and underwent a cesarean section and rectal resection at 35 weeks of gestation. A retrospective review of the Japanese literature was performed to identify patients who appeared to have primary colorectal cancer during pregnancy. Thirty-six patients with colon cancer (75.0%), 10 (20.8%) with rectal cancer, and two (4.2%) of unknown sites have been reported in Japanese series. The average age of the mother was 32.2 years. The calculated incidence of colorectal cancer among Japanese pregnant women was one case per 502,316 live births during the years between 1986 through 1995. Although the majority of colorectal cancers diagnosed during pregnancy are rectal carcinomas, the patients in Japan were predominantly complicated by colon cancer. The fetal risk seems small, because there were no cases of colorectal cancer metastatic to the products of conception.

Adenocarcinoma↗
PubMed1998

Effects of closed-system drain in surgery: focus on methicillin-resistant Staphylococcus aureus.

OBJECTIVE: The emergence of methicillin-resistant Staphylococcus aureus (MRSA) has made a strong impact on the strategy of peri-operative antibiotic prophylaxis, since MRSA has become one of the most common causative organisms of nosocomial infection in recent years. In this study, we conducted a bacteriological evaluation of surgical drains before and after introducing strategies to decrease MRSA infection rates. DESIGN AND PATIENTS: Between January 1987 and December 1994, we performed a total of 2, 755 surgical operations on inpatients, including 1,635 major and 1, 120 minor operations. Almost all surgical drains were examined bacteriologically when they were removed. The number of drains examined was 460 +/- 47 (mean +/- SEM) per year. Since the increased incidence of MRSA infection, we started exclusively using a closed drainage system and first-generation cephalosporins in 1991. The strategy was evaluated by comparing the positive rates of drain cultures, changes in bacteriological features, and incidence of MRSA infection for the 4-year periods before and after 1991. RESULTS: The positive rate of bacteria in the drains decreased significantly (p < 0.01) from 25 +/- 2 to 16 +/- 1%. Bacteriologically, the positive rate of Staphylococcus spp. decreased significantly (p < 0.05) from 7 +/- 2 to 3 +/- 0.3%. Positive rates of MRSA decreased significantly (p < 0.05) from 2.1 +/- 0.3 to 1.3 +/- 0.3%. Streptococcus declined dramatically from 3.0 +/- 0.3 to 0.3 +/- 0.1%. Of gram-negative strains, Pseudomonas and Escherichia coli were most often isolated. They showed no significant difference in positive rates between the terms. CONCLUSION: A closed drainage system and thorough use of the first-generation cephalosporins for prophylaxis were effective in decreasing positive bacterial culture of drains and reducing the incidence of MRSA on drains after surgery.

Adult↗
PubMed1997

Postsurgical sequential methotrexate, fluorouracil, and leucovorin for advanced colorectal carcinoma: a preliminary study.

BACKGROUND AND OBJECTIVES: The present study compared the effects of sequential methotrexate and fluorouracil followed by leucovorin rescue (MFL), as an adjuvant chemotherapy versus a combination of tegafur (UFT) and mitomycin C (MMC), on patient survival and recurrence after surgery for colorectal carcinoma. METHODS: Between January 1990 and December 1995, a total of 46 patients with advanced colorectal cancer were treated postsurgically by adjuvant chemotherapy using MFL or UFT-MMC. Surgical treatment was performed according to standardized procedures for radical resection of colorectal cancer. The patients were stratified into two groups after surgery. The MFL regimen consisted of MTX (100 mg/m2) and 5-FU (600 mg/m2) at hour 24, followed by leucovorin rescue. The UFT-MMC regimen consisted of MMC (12 mg/m2) intraoperatively and MMC (6 mg/m2) ever other week after surgery for 2 months and oral UFT (375 mg/m2/day), a combination of tegafur and uracil in a molar ratio of 1:4, was continued for 3 years or longer depending on the patients tolerance. RESULTS: The overall survival rates after surgery was significantly (P < 0.05) higher in the MFL than the UFT-MMC group. Recurrence rates were significantly lower in the MFL than the UFT-MMC Group, especially for liver recurrence. Disease-free survival was significantly (P < 0.05) higher in the MFL than the UFT-MMC group. CONCLUSIONS: The present results demonstrated the superiority of MFL therapy for improving postsurgical survival in patients with advanced colorectal cancer, in particular for those patients with a high risk of recurrence following potential curative resection.

Aged↗
PubMed1992

[A case report of serous cystadenoma located in pancreatic tail].

Cystadenomas of the pancreas are relatively rare compared to pseudocysts. There are two types of cystadenoma of the pancreas; mucinous and serous. Serous cystadenomas of the pancreas are very rare. We experienced a serous cystadenoma located in pancreatic tail. The patient was male, forty-one years old, and was free from any subjective symptom. The pancreatic cyst was found by abdominal ultrasonography and was difficult to differentiate serous or mucinous by computed tomography or celiac angiography preoperatively. We performed distal pancreatectomy and the cyst was revealed to be serous cystadenoma pathologically.

Adult↗
PubMedDate not supplied

Progression of esophageal carcinoma by loss of EGF-STAT1 pathway.

PURPOSE: In only a very limited number of cultured cell lines, epidermal growth factor (EGF), a potent mitogen for many kinds of cells, was shown to activate STAT1 (signal transducer and activator of transcription 1) protein, which can transmit signals that cause cell growth arrest and apoptosis. The purpose of this work is to elucidate the physiologic and/or pathological significance of this EGF-STAT1 pathway. MATERIALS AND METHODS: A series of cultured cell lines that had been established from surgical specimens of esophageal squamous cell carcinoma was studied for the existence of the EGF-STAT1 pathway. Normal esophageal squamous epithelial cells either explanted from non-neoplastic portions of surgically removed human esophageal tissue or in bovine esophageal epithelium in situ were examined as well. RESULTS: EGF treatment leads to a strong growth arrest in three of the 30 esophageal squamous cell carcinoma cell lines. STAT1 was found to be activated by EGF in the three cell lines but not in the others. EGF can also activate STAT1 in cultured normal esophageal squamous epithelial cells. STAT1 is at the activated state in the basal cell layer of the bovine esophageal epithelium. Notably, patients who had harbored the cancer cells with the EGF-STAT1 pathway had a dramatically better prognosis. DISCUSSION: The EGF-STAT1 pathway may be intrinsic to esophageal epithelial lineage of cells and is lost in a considerable fraction of the carcinomas. This loss appears to cause a significantly more malignant clinical course. These findings may point out a critical step in the progression of esophageal cancer and could lead to the development of useful clinical applications.

Blotting, Northern↗
PubMedDate not supplied

Surgical risks of acute cholecystitis in elderly.

BACKGROUND/AIMS: For the elderly patient, an emergency biliary procedure carries a higher risk than an elective operation. Recently introduced advances in ultrasonography and critical care medicine have affected the clinical risks of surgery for acute cholecystitis in the elderly. This study evaluated the clinical risks of open cholecystectomy for the elderly with acute cholecystitis. MATERIALS AND METHODS: During a 10 year period (1985-1994), a total of 145 patients were diagnosed with acute cholecystitis and underwent cholecystectomy. According to their age, the patients were divided into 3 groups (Group A < 59 years of age; Group B between 60-69 years of age; Group C > 70 years of age). The characteristics and the surgical risk factors in open cholecystectomy for the elderly with acute cholecystitis were evaluated. RESULTS: The rate of acalculous cholecystitis and choledochal stones were significantly (p < 0.05) high in Group C. Septic complication, gangrenous changes, and positive bile culture were also increased parallel to the increase in age. A noteworthy finding was an incidental carcinoma found in a case in group B and in 3 cases in group C. Hospital stay was significantly longer in Group C than in the other groups due to pre-operative complications and post-operative morbidity. CONCLUSION: With respect to increase in elderly patients with acute cholecystitis who present more frequent gangrenous changes and carcinomatous changes as well as high rate of septic complication, successful treatment of these patients is increased when early surgery can be performed on the basis of accurate and prompt diagnosis using imaging modalities and meticulous peri-operative management.

Acute Disease↗