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Biomedical subjects

S Majima

Publications and source records attributed to S Majima.

At least 19 recordsLinked to original sources

Multistep renal carcinogenesis as gene expression disease in tumor suppressor TSC2 gene mutant model--genotype, phenotype and environment.

Cancer is an inheritable disorder of somatic cells. Environment and heredity both operate in the origins of human cancer. These environmental and genetic determinants of cancer can be classified into four groups designated "Oncodemes" [1]. Oncodeme 1 is the irreducible "background" level of cancer due to spontaneous mutagenesis. Oncodeme 2 is "environmentally induced" cancer, whose causative agents are chemical carcinogens, radiation and viruses. Oncodeme 3 is basically "environmentally induced" cancer, but there are genetically determined differences among persons, e.g. the activation or inactivation of carcinogenes. Most human cancers are believed to belong to Oncodemes 2 and/or 3 (about 80%), for which the probability of the occurrence of the initial carcinogenic step(s) is increased, although the number of steps is not decreased. Oncodeme 1 would contain the approximately 20% that would remain if "environmentally induced" cancers (Oncodeme 2 and/or 3) were prevented. Lastly, Oncodeme 4 is "hereditary" cancer. Hereditary cancers could prove valuable in elucidating carcinogenesis, even though only a small proportion of cancers belong to this group. Here, we present a unique animal model of Oncodeme 4 for the study of problems in carcinogenesis; e.g. cell stage and tissue/cell-type-specific tumorigenesis, multistep carcinogenesis, species-specific differences in tumorigenesis, modifier gene(s) in renal carcinogenesis and cancer prevention.

Animals↗

A novel gene "Niban" upregulated in renal carcinogenesis: cloning by the cDNA-amplified fragment length polymorphism approach.

A modified AFLP (amplified fragment length polymorphism) method was employed to isolate genes differentially expressed in renal carcinogenesis of Tsc2 gene mutant (Eker) rats. One gene, selected for further investigation, was named "Niban" "second" in Japanese), because it is the second new gene to be found after Erc (expressed in renal carcinoma) in our laboratory. Importantly, "Niban" is well expressed even in small primary rat Eker renal tumors, more than in progressed cell lines, and is also expressed in human renal carcinoma cells, but not in normal human or rat kidneys. Chromosome assignment was to RNO 13 in the rat, and HSA 1. This "Niban" gene is a candidate as a marker for renal tumor, especially early-stage renal carcinogenesis.

Amino Acid Sequence↗

Recent therapeutic strategy for sustained ventricular tachycardia in Japan.

We investigated the therapeutic principles and strategies to treat sustained ventricular tachycardia (SVT) as five leading medical institutions in the Tokyo area and summarized the present situation of SVT treatment in Japan. Catheter ablation (ABL) has been almost established to be effective in idiopathic ventricular tachycardia (IVT) and was used as the last treatment in 60.3% of IVTs in this series. ABL may be the first option of therapy for IVT. In patients with SVT who have underlying cardiac diseases, the last treatment was class I drugs in 8.3%, class III drugs in 34.3%, combination drug therapy in 24.0%, ABL in 33.3%, surgical therapy (SUR) in 7.3%, and implantable cardioverter defibrillator (ICD) in 12.5% (nonpharmacological therapy in combination with other therapy). The use of class I drugs was not common, whereas class III drugs were used more frequently in patients with a low left ventricular ejection fraction. In some patients with reduced cardiac function, a combination of class III drugs and non-pharmacological therapy is appropriate.

Adult↗

Adjuvant chemotherapy for murine neuroblastoma with special reference to cell kinetics of residual tumor after primary tumor removal.

We examined the effect of adjuvant chemotherapy for neuroblastoma (C-1300NB) after surgery, especially on the increase in cells in the DNA synthetic phase in the remaining neuroblastoma from the 6th to 24th postoperative h caused by the reduction of the tumor cell in the tumor-bearing A/J mice. The mice were inoculated with C-1300NB cells in the chest and leg simultaneously, and administered adriamycin (ADM), as a cell cycle phase-specific agent, or cyclophosphamide (CPM), as a cell cycle phase nonspecific agent. The growth rate of chest tumors (residual tumors) in the mice treated with ADM just after amputation of the tumor-bearing leg was significantly lower than that of the other groups (p less than 0.05). 3H-TdR labeling indices of chest tumors in this group decreased more effectively than in the other groups. These results indicate that it is important to administer a cell cycle phase-specific agent rather than a cell cycle phase nonspecific agent during the period of rapid growth of residual tumors after surgery.

Animals↗

Alteration of adenosine deaminase levels in peripheral blood lymphocytes of patients with gastric cancer.

The present study was undertaken to determine the adenosine deaminase (ADA) activity of peripheral lymphocytes in patients with gastric cancer, with respect to the cancer progression, the effect of surgery and/or immunotherapy. The gastric cancer patients showed lower lymphocyte ADA activity than did the normal control. The lymphocyte ADA activity did not decrease with the cancer progression. There was a significant correlation between lymphocyte ADA activity and blastogenesis of lymphocyte by phytohemaglutinin or concanavalin A. Six months following gastrectomy, the lymphocyte ADA activity was increased, as compared with the preoperative value. The ADA activity of patients on post-operative OK-432 showed a greater increase, as compared to that of patients not given this treatment. In conclusion, decreased lymphocyte ADA activity in gastric cancer patients might be due to either the cancer bearing status or to the immunological suppression.

Adenosine Deaminase↗

Evaluation of aortography in assessing the resectability of retroperitoneal neuroblastoma in children.

To assess the resectability of retroperitoneal neuroblastoma and determine the timing of a "second-look" resection of primary tumor on the basis of aortographic findings, 32 abdominal aortographies performed on 26 patients with retroperitoneal neuroblastoma (22 adrenal, 4 paraspinal) were examined retrospectively. Angiographic findings of both displacement of aorta and narrowing of aorta indicate the difficulty of complete removal of the neuroblastoma. These findings were particularly useful in determining the resectability of retroperitoneal neuroblastoma. On the other hand, the absence of angiographic findings of both displacement of main vessels (celiac axis, origin of superior mesenteric artery, or renal arteries) and stretching of main vessels indicate the feasibility of complete removal of retroperitoneal neuroblastoma. On the basis of angiographic findings, the decision to resect the retroperitoneal neuroblastoma could be made in 6 patients, who underwent the "second-look" operation.

Adolescent↗

Experimental study on the growth and proliferation kinetics of residual tumor after surgery in mouse neuroblastoma.

In order to elucidate the proliferation kinetics of residual tumors after surgery, experimental studies were performed, using C-1300NB and A/J mice, tumor-host system. Mice were inoculated with C-1300NB cells in the chest and leg simultaneously, and then divided into three groups. Growth curves of chest tumors (residual tumors) in Group B after amputation of the tumor-bearing leg were significantly steeper than those of both Group A, whose tumor-bearing legs were not amputated, and Group C, whose normal legs were amputated, at the same tumor age. 3H-TdR labeling indices of chest tumors of Group B were significantly higher than those of Group A (P less than 0.05). DNA histograms of the chest tumors of Group A uniformly showed a unimodal distribution with a peak in the 2c range. On the other hand, in Group B the peak of nuclear DNA distribution shifted from the 2c range to the 4c range after amputation of tumor-bearing leg. The results indicated that an increase in cells in the DNA synthetic phase occurred in the remaining neuroblastoma after reducing the volume of tumor in host by amputation of tumor-bearing legs.

Amputation, Surgical↗

Immunohistochemical investigations of gut hormones in the colon of patients with Hirschsprung's disease.

The distributions of gut hormones in the colon of Hirschsprung's disease were investigated by the peroxidase-antiperoxidase (PAP) immunohistochemical method. Three colonic segments (ganglionic, oligoganglionic, and aganglionic) were stained by the unlabeled antibody enzyme method. The immunoreactivity of vasoactive intestinal polypeptide (VIP) was found to be reduced in the oligoganglionic and aganglionic segments. Antisera to substance P and met-enkephalin demonstrated immunoreactive cells and fibers in the ganglionic segment, whereas these cells and fibers were almost completely absent in the oligoganglionic and aganglionic segments. A similar distribution was seen for the mucosal endocrine cells with somatostatin immunoreactivity. Antisera to neurotensin, motilin, bombesin, and cholecystokinin revealed no immunoreactivity in the normal colon or the three segments. The differences in these peptides between normal and impaired colonal segments may be one of the causes of colon constriction in Hirschsprung's disease.

Adult↗

An evaluation of surgical treatment and chemotherapy of advanced neuroblastoma (stage III & IV) with special reference to proliferation kinetics of residual tumors.

Twenty two children with advanced retroperitoneal neuroblastoma and one child with advanced posterior mediastinal neuroblastoma admitted to our clinic were treated as follows. Seven patients (group A) underwent primary resection of tumor immediately after diagnosis. In two patients of this group, the levels of VMA and HVA in urine after surgery decreased to nearly normal (group A-I), while they did not change appreciably in the other 5 patients (group A-II). Seven patients (group B) underwent resection of tumor following complete or partial response to preoperative chemotherapy. Nine patients (group C) did not undergo resection of the tumor except for exploratory laparotomy. Two group A-I patients have survived, free of disease, for 6 months and 12 months after diagnosis. All patients of group A-II died within a year. Residual tumors of 4 patients of this group began to grow explosively just after surgery, although they received persistent postoperative chemotherapy. Four patients of group B survived for more than two years and the two patients of this group who received continuous intra-arterial PGE1 therapy had no postoperative explosive growth of residual tumors. Two patients in group C survived for 20 months and the others died within a year. Primary tumors and metastatic foci responded well to therapy as compared with group A-II, which suggests that presence of primary tumors may inhibit rapid growth of metastatic foci. Resection of primary tumors, therefore, was not always conducive to survival unless residual tumor responded to postoperative chemotherapy.

Adolescent↗

Cancer of the gallbladder in a 9-year-old girl.

Carcinoma of the gallbladder was found in a 9-year-old girl. The patient was transferred to our hospital because of an abdominal mass and right upper quadrant pain. X-ray cholecystography and ultrasonography were performed preoperatively. The ultrasonic scan showed a thickened wall and lack of contractility of the gallbladder. A laparotomy was performed under the diagnosis of chronic cholecystitis. At operation a peanut-sized nodule, in which adeno carcinoma was demonstrated by frozen section, was palpable at the neck of the gallbladder. Cholecystectomy was performed with T-tube drainage and postoperative chemotherapy was administered. The patient has had no evidence of tumour recurrence in 24 months of follow-up.

Adenocarcinoma↗

Comparative studies between liposomes containing muramyl dipeptide and various immunomodulators on activation of mouse peritoneal macrophages and NK cells.

We compared the effects among muramyl dipeptide (MDP), liposome-encapsulated MDP (liposome MDP), bacillus Calmette-Guérin (BCG) and OK-432 on cytotoxic activity of mouse peritoneal macrophages (PM) and natural killer (NK) cells in vitro and in vivo, and their tumor-inhibitory effects against MH134 ascitic tumors in C3H/He mice. The cytotoxicity of PM induced by free MDP was lower than that induced by BCG, but a significantly higher cytotoxicity was induced by liposomes containing MDP and OK-432. The peritoneal NK cells were not activated by MDP, liposome MDP or BCG, but OK-432 profoundly augmented peritoneal NK activity. Growth inhibition of ascitic tumor was not observed in free MDP and BCG intraperitoneally treated mice, but moderate growth inhibition was noted in liposome-MDP-treated mice; and in OK-432-treated mice, marked tumor growth inhibition and prolongation of survival time were observed. These results suggested that OK-432 is more advantageous in controlling malignant tumor growth in vivo than free MDP, liposome MDP or BCG because of its ability to activate both macrophages and NK cells.

Acetylmuramyl-Alanyl-Isoglutamine↗

[The effect of vagotomy on carcinogenesis in the glandular stomach of rats, induced by N-methyl-N'-nitro-N-nitrosoguanidine].

The effect of hydrochlorhydria caused by vagotomy on carcinogenesis in the glandular stomach of male rats was studied. Group A (35 rats): After N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) 80 mg/l solution was orally administered during the first 15 weeks of life, vagotomy was performed. Group B (35 rats): After the oral administration of MNNG 80 mg/l solution during the first 15 weeks of life, laparotomy was done. Group C (10 rats): As the control, vagotomy was undertaken at the 15th week of life. Group D (10 rats): As the control, laparotomy was done at the same time. At the 52nd week, all surviving rats were autopsied, and gastrin cell counts and body weight were ascertained. The incidence of adenocarcinoma was 62% in Group A, 32% in Group B (p less than 0.05) and nil in Group C and D. These results strongly support the view that the hypochlorhydria plays the role of a promoting factor in producing gastric carcinoma.

Adenocarcinoma↗

Eradication of microscopic metastases with intratumoral injection of bacillus Calmette-Guerin.

The studies reported here were designed to examine the effects of intratumoral preoperative administration of Bacillus Calmette-Guerin (BCG) on the cure rates of C3H mice transplanted with MH134 tumor cells and on the metastatic rates in the regional lymph nodes. Furthermore, the morphological findings occurring in the regional lymph nodes were monitored during tumor growth using H-E stain and non-specific esterase staining. The cure rate of the Group treated with BCG intratumoral injection and surgery was significantly higher than that of the Group treated with surgery alone, and in the BCG + surgery group metastatic rates of regional lymph nodes decreased consistently after operation. Moreover, in this group, extensive sinus histiocytosis and marked swelling of the regional nodes were frequently observed. Quantitative studies of the cell kinds using the esterase staining indicated that intratumoral injection of BCG has an effect on the influx of lymphoid cells into the regional nodes, but does not aid specific cell lineage to flow into the regional nodes. In cytostatic assays, it was shown that the regional lymph node cells and spleen cells in the BCG + surgery group always have a greater per cent of inhibition than those in the surgery alone group.

Animals↗

Antireflux mechanism in Nissen fundoplication--an experimental study.

The antireflux mechanism of the Nissen fundoplication was investigated in 15 mongrel dogs by esophageal manometry. Nissen fundoplication increased the lower esophageal resting pressure for 2 weeks after operation; however, by 4 weeks it had decreased to a level which did not differ significantly from the preoperative value. Thus, lower esophageal sphincter (LES) length, unlike LES pressure, was maintained for a long period. These results suggest that restoration of competence at the gastroesophageal junction after Nissen fundoplication depends on an adequate length of LES as well as increased LES pressure. The gastrin-stimulated LES pressure 1, 2 and 4 weeks after operation was significantly higher than the preoperative stimulation pressure. Therefore, it seems that the antireflux mechanism is associated not only with the mechanical aspect of the wrapping but also with creation of a new muscular sphincter substitute that reacts sufficiently to gastrin stimulation.

Animals↗

Immunosuppressive activity of sera from gastric cancer patients.

Sera from 60 gastric cancer patients and 20 patients with benign gastric diseases and 8 healthy controls were tested for inhibitory effects on the humoral response to sheep erythrocytes (SRBC) by the plaque forming cell assay (PFC R.I.) using mouse spleen cells and on the phytohemagglutinin (PHA)-induced blastogenesis of normal mouse spleen cells (PHA S.R.). Gastric cancer patient sera showed a significantly lower PFC R.I. than did sera from benign gastric disease patients and from the healthy controls. However, there was no appreciable interstage difference in the degree of depression. The PHA-induced blastogenesis of normal spleen cells was also decreased in the presence of sera from cancer patients, as compared to that in the presence of sera from benign disease patients and from the healthy controls. The depression progressed with advancing stage of cancer. The PHA S.R. showed significant negative correlations with serum levels of IAP, IS, alpha 1-acid glycoprotein and alpha 1-antitrypsin, but there were no such correlations between PFC R.I. and these glycoproteins in serum. There was also no correlation between the values of the PHA S.R. and the PFC R.I. These results suggest that these two assays may depict immunosuppressive activities operating through entirely different mechanisms.

Animals↗

Comparative study of CEA staining in gastric and colorectal cancer tissues.

Expression of CEA was studied in tissue sections from 140 cases of gastric and 54 cases of colorectal carcinoma by the immunoperoxidase technique. In some cases of gastric cancer, the intensity of CEA staining was compared with the CEA concentration by radioimmunoassay, and the intensity of the CEA staining was related to CEA concentration. CEA was more strongly positive in colorectal carcinomas than in gastric carcinomas. The intensity of the CEA staining was stronger in differentiated gastric and colorectal carcinomas than in anaplastic ones. No relationship was seen between the expression of CEA and the extent of disease in gastric or colorectal carcinoma. The CEA expression was related to the location of tumors in colorectal carcinomas, but not in gastric carcinomas.

Adenocarcinoma↗