Biomedical subjects

M Sowa

Publications and source records attributed to M Sowa.

176 records · Page 10Linked to original sources

PubMedDate not supplied

Cyclin D1 overexpression and prognosis in colorectal adenocarcinoma.

Recently, it has been reported that cyclin D1 plays a major role in oncogenesis in various cancers; however, there have been few studies on the association of cyclin D1 overexpression and prognosis of patients with malignant tumors. We evaluated the prognostic significance of cyclin D1 overexpression in colorectal adenocarcinoma. One hundred twenty-three specimens resected from patients with colorectal adenocarcinomas were investigated by staining with a monoclonal antibody against cyclin D1. As a result, both overall survival and disease-free survival were significantly poorer in the patients with tumors strongly positive for cyclin D1 than in those with cyclin-D1-negative or weakly positive tumors. The 5-year survival rate of the patients with tumors strongly positive for cyclin D1 was 53.3%, while the 5-year survival rates of patients with cyclin-D1-negative and weakly positive tumors were 96.2 and 78.8%, respectively. Moreover, multivariate analysis indicated that cyclin D1 overexpression is an independent predictor of disease recurrence in our patients. In conclusion, cyclin D1 overexpression may be useful as a predictor of disease recurrence in colorectal adenocarcinoma.

Adenocarcinoma↗

PubMedDate not supplied

Predictive value of Bcl-2 and Bax protein expression for chemotherapeutic effect in gastric cancer. A pilot study.

We investigated tissue staining for Bcl-2 and Bax proteins, which regulate apoptosis, as indicators of chemotherapeutic effect in patients with gastric cancer. In 23 patients with gastric carcinoma biopsy specimens were obtained endoscopically prior to chemotherapy and stained immunohistochemically with anti-Bcl-2 and anti-Bax antibodies. Patients then were treated with continuous infusion of 5-FU and cisplatin. No correlation was seen between chemotherapeutic effect and Bcl-2 or Bax alone. However, among the Bax-positive cases, the patients with Bcl-2-positive tumors were significantly more chemoresistant (p = 0.036) and had worse prognoses (p = 0.008) than Bcl-2-negative cases. Therefore, immunohistochemical staining for Bcl-2 protein may predict chemotherapeutic efficacy or guide specific therapeutic choices in treating Bax-positive tumors.

Aged↗

PubMedDate not supplied

Expression of p53 and vascular endothelial growth factor associated with tumor angiogenesis and prognosis in gastric cancer.

Recently, it has been reported that p53 tumor suppressor gene plays an important role in controlling tumor angiogenesis by regulating expression of vascular endothelial growth factor (VEGF), which is a well-characterized angiogenic inducer. In this study, we investigated these antigens' expression together with microvessel density, and investigated their clinical importance. One hundred twenty specimens resected from patients with gastric carcinoma were investigated using immunohistochemical methods. p53 and VEGF expression was observed in 42 and 35% tumors, respectively. p53 and VEGF staining status was coincided in 72% tumors, and a significant correlation was found between p53 and VEGF status. The microvessel density, determined by immunostaining for factor VIII-related antigen, was significantly higher in p53-positive or VEGF-positive tumors. According to prognosis, patients with p53-positive tumors had significantly worse survival than those with p53-negative tumors. There was also a significant worse survival in the patients with VEGF-positive tumors than those with VEGF-negative tumors. Moreover, the 5-year survival rate was lowest in the patients with p53-positive and VEGF-positive tumors, while it was highest in the patients with p53-negative and VEGF-negative tumors. In conclusion, both p53 and VEGF significantly correlated with tumor vascularity and prognosis in patients with gastric carcinoma.

Adult↗

PubMedDate not supplied

Association of tumor cell proliferation with lymph node metastasis in early gastric cancer.

Recently, many studies have reported on the relationship between malignant potential of neoplasms and cell proliferation. Proliferating cell nuclear antigen (PCNA) is an auxiliary protein of DNA polymerase delta and is considered to correlate with the cell's proliferative state. In this study, we investigated the correlation between tumor cell proliferation and nodal status of early gastric carcinoma. One hundred two endoscopically biopsied specimens from patients with early gastric carcinoma prior to operation were investigated by an immunohistochemical study, using anti-PCNA monoclonal antibody. Correlation of PCNA labeling index (percentage of positive cells per over 500 tumor cells) with nodal status were studied. PCNA labeling index in patients with lymph node metastasis was significantly higher in those without metastasis. Moreover, multivariate analysis indicated that PCNA labeling index is an independent significant factor for lymph node metastasis. As a result of this study, PCNA labeling index was suggested to be effective as one of the predictors of lymph node metastasis.

Adult↗

PubMedDate not supplied

Elevation in putrescine level and spermidine/spermine N1-acetyltransferase activity coincide with tumor development in 1, 2-dimethylhydrazine-induced rat colon.

Spermidine/spermine N1-acetyltransferase (SSAT), rate-limiting enzyme of polyamine interconversion, has been demonstrated to play an important role in malignant transformation of cells. We examined the involvement of altered polyamine metabolism in the colonic carcinogenesis, using 1,2-dimethylhydrazine (DMH)-induced rat colon tumor model. Following findings were obtained: i) Ornithine decarboxylase demonstrated high activity from the early phase in colon mucosa, and increased significantly in tumors. ii) Spermidine and spermine levels gradually elevated in DMH-treated mucosa, while putrescine increased significantly in tumor tissues. iii) SSAT activity increased gradually in DMH-treated colon mucosa, which preceded elevation of tissue putrescine level, and coincided with tumor development. In conclusion, elevation of putrescine level and induction of SSAT activity are suggested to have a close association in colonic carcinogenesis.

1,2-Dimethylhydrazine↗

PubMedDate not supplied

Telomerase activity in thyroid tumors.

We quantified telomerase activities in thyroid tumors by a telomeric-repeat-amplification-protocol-based assay in an attempt to determine its clinical significance. Telomerase activity was detected in 10 of 18 (55.6%) malignant tumors, but in none of the four benign lesions, and the level of telomerase activity correlated significantly with the progression of the clinical stages. High activity was determined in 4 (80%) of 5 metastatic lesions in the lymph nodes. Five (45.5%) of 11 non-tumoral specimens from malignant cases showed telomerase activity, while none of the four from benign cases did. In conclusion, the determination of telomerase activity might be useful in determining the existence and progression of thyroid cancer.

Adult↗

PubMedDate not supplied

Intrahepatic interleukin-2 with chemotherapy for unresectable liver metastases: a randomized multicenter trial.

BACKGROUND/AIMS: A pilot study of Interleukin-2 (IL-2) with chemotherapy for unresectable colorectal liver metastases revealed a favorable response rate (76%). This prospective, randomized, multicenter study was conducted to evaluate the efficacy of this treatment protocol. METHODOLOGY: Over a period of 32 months, 46 patients with unresectable liver metastases were randomly assigned to 1 of 3 treatment groups: group A: chemotherapy alone, group B: chemotherapy plus high-dose, intermittent IL-2 (2.1 x 10(6) U twice weekly) or group C: chemotherapy plus low-dose, continuous IL-2 (7 x 10(5) U daily). Treatment continued for 4 weeks in the hospital and on an outpatient basis according to the clinical response. No crossover between treatment arms was permitted. RESULTS: IL-2 combined with chemotherapy produced a higher complete and partial response rate of 40% in group A, 60% in group B, and 78% in group C. Toxicity related to IL-2 included fever, chills, malaise, and eosinophilia. CONCLUSIONS: Hepatic arterial infusion of chemotherapy plus IL-2 resulted in an increased tumor response when compared with chemotherapy alone. To confirm the efficacy of this treatment protocol, we have started a large-scale, randomized, multi-institution trial.

Adult↗

PubMedDate not supplied

Complications of total gastrectomy for gastric cancer--with special reference to anastomotic failure.

We have reviewed the data on patients totally gastrectomized for gastric cancer during a 12 year period at our hospital. Our findings are summarized, as follows: 1. Advanced cases (stage III, IV) accounted for 85.4% (276/323) of them. Combined resection of other organs was performed on 87.6% of them. Twelve percent of the patients had peritoneal dissemination of P2 or higher grade and 5.9% hepatic metastases of H1 or higher grade. 2. Roux-en Y anastomosis was the most frequent (83.3%) reconstructive procedure. There were a total of 124 episodes of postoperative complications in 76 cases (23.5%). The lung and liver were often involved. Twenty-four cases (7.4%) suffered from postoperative anastomotic failure, which developed commonly at the site of oesophago-jejunostomy. Major leakage from this portion was the cause of death in 62.5% of the cases. The mortality rate was not notably different between the groups subjected to different reconstructive procedures or between the autosuture group (using an EEA stapler) and the hand suture group. The incidence of death due to the surgical intervention was 1.9%. 4. The 5-year survival after total gastrectomy was 25.2%, which was not necessarily satisfactory. However, it was significantly higher in the curative resection group than in the non-curative resection group (40.2% vs 3.3%).

Anastomosis, Roux-en-Y↗

PubMedDate not supplied

Gastric carcinoma in young adults in Japan.

Forty-nine cases of young adults with carcinoma of the stomach were reviewed. The occurrence of this tumor had a percentage rate of 2.7 of the total of 1767 Japanese patients with stomach carcinoma, with a male to female ratio of 1.0:0.88. The most common complaint observed was epigastric pain (45.7%). In the majority of patients, the period from the onset of symptoms to the time of diagnosis was over two years (49%). Thirty-nine out of 49 patients had resection of the stomach and a consequent operation was curative in 55.1% of them. The overall 5-year survival rate was 26.8%. However, the 5-year survival rate for the curative operation was 42.6% particularly in early gastric carcinoma without any serosal invasion and no patients died from carcinoma of the stomach. These results indicate that early diagnosis is very important to improve the curing rate of this disease in young adults.

Adolescent↗

PubMedDate not supplied

Early stage carcinoma of the gastric remnant in Japan.

In recent years, the number of reported cases of early stage cancer of the remnant stomach has been on a gradual increase thanks to the improvement in diagnostic techniques and also to increasing dealings with cancer of the remnant stomach. In this study we reviewed 124 cases of early stage cancer of the remnant stomach which were reported in Japan by the end of 1990, including the 6 cases which we encountered ourselves, during the 11 years starting from 1980. Their average age was 57 years, with a range from 22 to 78 years. The male-to-female ratio was 2:7. There were 63 asymptomatic cases (61%). This fact suggests that periodical examinations are essential after the first operation on the stomach. Out of the 124 cases, 86 cases operated on for benign lesions (benign group) and the remaining 38 cases for malignant lesions (malignant group) for the first time. The average time between the first and the second surgery was 19.7 years in the benign group and 7.8 years in the malignant group. The initial surgery was performed mainly by Billroth II resection. The frequency of tumor development was higher in the nonsutured portion than in the anastomosed portion of the remnant stomach. Protuberant type lesions and differentiated carcinomas were prevalent according to the classification by gross type and histology, respectively. However, the anastomosed portion was most often involved in the subgroup of patients in whom lesions were detected more than 10 years after Billroth II resection for benign lesions.

Adult↗

PubMedDate not supplied

Ornithine decarboxylase activity in the mucosa of gastric remnant following gastric surgery.

Ornithine decarboxylase (ODC) activity and polyamine levels in mucosal specimens obtained by endoscopic biopsy from the stomal portion and greater curvature of the gastric remnant mucosa taken from 181 patients were determined and compared with the histopathological findings. The results obtained can be summarized as follows. (a) The ODC activity was significantly higher in the stomal portion [455 +/- 340 (mean +/- SD)] of the gastric remnant than in the greater curvature (148 +/- 107). The ODC activity of the stomal portion was significantly higher following a Billroth's II method (599 +/- 417) than following any other operative method that consists of a Billroth's I method (327 +/- 172) and a Roux-en Y (341 +/- 191). (b) The levels of total polyamine, putrescine, spermidine, and spermine were also significantly higher in the stomal portion of the gastric remnant than in the greater curvature. There were no significant differences in the stomal tissue level of any of these substances among operative procedures used. (c) Histopathological changes consisting of glandular dilatation and an irregular glandular structure were detected more frequently in the stomal mucosal specimens, especially following a Billroth's II method. In summary, the present findings suggest that the measurement of ODC activity may thus be considered as one method of estimating the risk of carcinogenesis.

Adult↗

PubMedDate not supplied

Tranilast (N-(3,4-dimethoxycinnamoyl) anthranilic acid) down-regulates the growth of scirrhous gastric cancer.

BACKGROUND: Fibroblasts have been reported to play an important role in the proliferation of scirrhous gastric cancer cells. It would be an effective cancer therapy to reduce the cancer-stimulating activity of fibroblasts. The aim of the present investigation was to define the efficacy of Tranilast (N-(3,4-dimethoxycinnamoyl) anthranilic acid), a drug used clinically for the treatment of excessive proliferation of fibroblasts, on the growth of scirrhous gastric carcinoma both in vitro and in vivo. MATERIALS AND METHOD: The human scirrhous gastric cancer cell line, OCUM-2M, and the human gastric fibroblasts, NF-8, were used. OCUM-2M cells on the upper well and NF-8 cells in the lower well were co-incubated with Tranilast at the required concentrations in vitro. The in vivo effect of Tranilast was examined by measuring the size and the apoptotic index of coinoculated tumor by OCUM-2M cells and NF-8 cells. RESULTS: The proliferation of OCUM-2M cells was significantly stimulated by co-culture with NF-8 cells. Tranilast significantly suppressed the proliferation of NF-8 cells and subsequently decreased the growth of OCUM-2M cells in vitro. Furthermore, Tranilast depressed gastric carcinoma growth and induced cancer cell apoptosis through its effect in blocking the growth-interactions between fibroblasts and scimbous gastric cancer cells in vivo. CONCLUSION: Tranilast is a useful drug to reduce the proliferation of scirrhous gastric carcinoma.

Adenocarcinoma, Scirrhous↗

PubMedDate not supplied

An experimental study of hepatic resection using an in situ hypothermic perfusion technique.

BACKGROUND/AIMS: Recently, along with the progression of hepatic surgery, the in situ hypothermic perfusion technique has been used for major hepatic resection. The aim of this study was to elucidate the utility of the hypothermic perfusion technique in hepatic resection. METHODOLOGY: Two experimental models: a Total Vascular Occlusion group (TVO) and a Total Vascular Occlusion under Hypothermic Perfusion group (HP) were utilized using adult mongrel dogs. An approximately 40-45% hepatic resection was performed under total vascular occlusion with a systemic and portal shunt. In the HP group, the liver was perfused through the portal vein with lactated ringer's solution at 4 degrees C. In the TVO group, hepatic resection was done without perfusion. RESULTS: Serum AST and ALT levels after reperfusion were significantly increased in the TVO group. From the change of serum hyaluronic acid and xanthine oxidase activity, sinusoidal endothelial cell function was maintained in HP more than in TVO. The mean arterial pressure, portal venous pressure and portal venous blood flow were maintained in HP after reperfusion. Examination of vascular permeability using monastral blue showed that vascular permeability of the small intestine, lung and liver was clearly increased in TVO. Chemiluminescense intensity of the hepatic venous blood after reperfusion gradually increased only in TVO. In addition, the chemiluminescense intensity of the hepatic venous blood congested in the liver increased markedly as vascular occlusion continued in TVO. The hepatic venous blood serum congested in the liver induced morphological changes in the human umbilical vein endothelial cells and increased their permeability. The SDS-PAGE of the hepatic venous blood serum congested in the liver revealed several proteins between 37 and 42 KD. CONCLUSION: The hypothermic perfusion technique in hepatic resection may be very useful in preserving the hepatocytes and sinusoidal endothelial cells and in maintaining stability of the systemic or hepatic circulation after reperfusion because of the cooling of the liver and the washing out of congested blood in the liver.

Animals↗

PubMedDate not supplied

The antiproliferative effect of HGF on hepatoma cells involves induction of apoptosis with increase in intracellular polyamine concentration levels.

Hepatocyte growth factor (HGF) induced apoptosis and decreased the DNA synthesis in Hep G2 cells. In the HGF group interleukin-1 converting enzyme, ornithine decarboxylase (ODC) activity and intracellular polyamine concentrations were increased compared to those of the control group. Administration of the ODC inhibitor decreased polyamine concentration, and inhibited apoptotic changes in the cells. These changes were reversed by exogenous addition of polyamine. These findings suggest that one of the mechanisms by which HGF exerts its antiproliferative effect is induction of apoptosis and that increase in intracellular polyamine concentration may be one of the triggers of cell death.

Apoptosis↗