Search PubMed⌕ Search

Biomedical subjects

H Baba

Publications and source records attributed to H Baba.

At least 595 records · Page 33Linked to original sources

Effect of DN-1417 on photosensitivity and cortically kindled seizure in Senegalese baboons, Papio papio.

The effect of DN-1417, a thyrotropin-releasing hormone (TRH) analogue, on photosensitivity and cortically kindled seizures was examined in seven Senegalese baboons (Papio papio). Intravenous (i.v.) administration of 2 mg/kg had no effect on either photosensitivity or cortically kindled seizures. When this agent was administered intracisternally, both the photomyoclonic response and cortically kindled seizures were suppressed for 4-5 days. A study of the transcallosal response also showed a long-lasting attenuation of the early positive wave (P1) amplitude (peak latency, 5-10 ms) elicited by a single stimulus after cisternal injection of DN-1417. These findings are consistent with the assumption that endogenous TRH is involved in suppression of epileptic seizures.

Animals↗

Predictive value of preoperative carcinoembryonic antigen levels for the prognosis of patients with well-differentiated gastric cancer. A multivariate analysis.

Serum carcinoembryonic antigen (CEA) levels were determined preoperatively in 221 patients with well-differentiated gastric cancer. The mean preoperative serum CEA level was 15.9 +/- 88.5 ng/ml (1.0-1,133.0 ng/ml) for all patients, and the incidence of an elevated CEA (> 5 ng/ml) was 11.8% (26/221). The CEA-positive patients had larger tumors, a more prominent serosal invasion, more frequent lymphatic and vascular involvement, less expansive tumor growth and higher rates of lymph node and hepatic metastases than did the CEA-negative patients. Thus, the CEA-positive patients had a more advanced stage of disease, and 61.5% underwent noncurative resection (vs. 11.3% in CEA-negative patients). The survival rate of the CEA-positive patients was lower than that of the CEA-negative ones (p < 0.01). As the multivariate analysis revealed the preoperative CEA level to be an independent prognostic factor for survival, an assay for this antigen prior to surgery is to be recommended.

Adenocarcinoma↗

Hydralazine combined with hyperthermia enhances the effects of carboquone.

Carboquone (CQ) and hyperthermia (HT) are capable of preferentially killing oxygen-deficient cells, both in vitro and in vivo. We examined effects of the combination of CQ and HT on an in vitro hypoxic system and on murine solid tumors using hydralazine (HYD), a vasoactive agent. Under in vitro hypoxic conditions, the combined cytotoxicity of CQ and HT (43 degrees C, for 1 h) was enhanced and the enhancement ratio (ER) for the IC90 of CQ was 21.4-, 9.4-, and 2.6-fold compared to that for CQ alone, CQ under hypoxic condition, and CQ plus HT under aerated cells, respectively. Five mg/kg i.p. HYD reduced the level of tumor blood flow in mice to about 20% of constant level and this reduction persisted for 1 h. In mice bearing B16 melanoma tumors, HYD enhanced tumor susceptibility of the combined therapy of CQ and HT. The ER which was a comparison of tumor growth time in the control group, was 2.3, 3.6 for the two combination groups of 1, 2 mg/kg i.p. CQ, HT (43 degrees C for 20 min), and 5 mg/kg i.p. HYD, respectively. Thus, hyperthermochemotherapy using CQ combined with HYD, seems to selectively attack a solid tumor.

Animals↗

Analysis of 390 patients surviving 10 years or longer after curative resection for gastric cancer.

We analyzed clinicopathological features and prognosis of 390 Japanese patients with gastric cancer who survived 10 years or longer after curative resection. All of the patients were treated in our clinics. One hundred and ninety-one of these patients had early gastric cancer and the other 199 had advanced gastric cancer. The mean age was 53.5 years and the male to female ratio was 2:1. The upper one-third of the stomach was less commonly involved and a partial gastrectomy was most often done. Lymph node metastasis was present in 28.7% and extensive lymph node dissection (R2 or R3) was done in 92.5% of the cases. Nine patients died with a recurrence of gastric cancer and 20 patients died with a malignancy in other organs. Curative resection with extensive lymph node dissection and, when required, combined resection of the neighboring organs does improve the survival rate for patients with either early or advanced gastric cancer. An annual follow-up examination to rule out recurrences or malignancies in other organs is to be recommended.

Adult↗

Hyperthermia enhances the cytotoxicity against hypoxic cells of RP-170, a new 2-nitroimidazole nucleoside hypoxic cell sensitizer.

The effect of the new hypoxic cell sensitizer, 1-[2-hydroxy-1-(hydroxymethyl)-ethoxy]methyl-2-nitroimidazole (RP-170), combined with heat against EMT6/KU cells, was determined under conditions of in vitro hypoxia. Heat-induced cytotoxicity for the EMT6/KU cells was increased to a greater extent under conditions of hypoxia and a normal pH of the medium. Hypoxia also reduced the surviving fraction of the cells treated either with RP-170 alone or with RP-170 plus heat. The concomitant treatment of RP-170 and heat inhibited the clonogenic activity of the EMT6/KU cells under conditions of in vitro hypoxia in all experimental groups, with a significant difference (p < 0.05). Therefore, RP-170 combined with exposure to heat may be an effective treatment for hypoxic cells in a solid tumor, as these cells are resistant to radiation and/or to many chemotherapeutic agents.

Animals↗

Interaction of cis-diamminedichloro-platinum(II) and its analogues cis-1,1- cyclobutanedicarboxylato(2R)-2-methyl-1,4-butanediammineplatinum(II) and cis-diammine(glycolato)platinum with hyperthermia in vivo.

The interaction of cis-1,1-cyclobutanedicarboxylato(2R)-2-methyl-1,4- butanediammineplatinum(II) (NK121) and cis-diammine(glycolato)platinum(II) (254-S), analogues of cis-diamminedichloroplatinum(II) (CDDP), with hyperthermia was examined in vivo. Antitumor activity of the platinum complexes at the maximum tolerated dose (MTD) with or without hyperthermia was evaluated by the tumor growth delay assay using B16F10 melanoma growing in the legs of C57BL/6J mice. MTD of CDDP, NK121 or 254-S at the single intraperitoneal injection with hyperthermia was 8, 50 or 30 mg/kg, respectively. Treatment of the tumor-bearing limb at 43 degrees C for 30 min resulted in a tumor growth delay of 1.1 days. A single dose of CDDP produced a 3.3-day tumor growth delay. When CDDP was injected just before hyperthermia (43 degrees C, 30 min), the growth delay increased to 5.5 days (1.7-fold increase). With NK121, there was a 1.5-day growth delay. In combination with hyperthermia, the tumor growth delay by NK121 was 3.2 days (2.1-fold increase). Injection of 254-S led to a growth delay of 3.5 days, and this delay was extended to 5.7 days (1.6-fold increase) when combined with hyperthermia. Changes in serum blood urea nitrogen (BUN) were determined 5 days after intraperitoneal drug administration with or without hyperthermia. A single administration of CDDP 8 mg/kg resulted in an elevated BUN level, and this was enhanced in combination with hyperthermia (66.3 mg/dl, 2.7-fold over control). NK121 50 mg/kg at 37 degrees C did not result in elevation of BUN, but mild nephrotoxicity was noted in combination with hyperthermia (40.3 mg/dl, 1.6-fold increase over control). The administration of 254-S 30 mg/kg resulted in an elevated BUN level, and this elevation was enhanced in combination with hyperthermia (48.6 mg/dl, 2.0-fold increase over control). Our data showed that NK121 and 254-S as well as CDDP produced greater tumor growth delay together with hyperthermia than did the drug alone. Though these new compounds were designed with reduced nephrotoxicity, attention should be paid to increased nephrotoxicity when combined with hyperthermia.

Animals↗

Vasoacting agents flavone acetic acid and hydralazine given in combination enhance antitumor effects under condition of hyperthermia.

The combined effects of flavone acetic acid (FAA), hydralazine (HYD) and hyperthermia on B16 melanoma cells and solid tumor were examined in vitro and in vivo. In vitro, hyperthermia did not enhance the cytotoxicity of the combined use of FAA and HYD. In vivo, growth inhibition of B16 melanoma solid tumor by FAA (150 mg/kg) combined with HYD (5.0 mg/kg) could not be differentiated from that by FAA or HYD alone. Increased antitumor effect was recognized when FAA combined with HYD was used under conditions of hyperthermia. FAA combined with HYD significantly reduced tumor blood flow compared to FAA alone or HYD alone. We thus conclude that the significant reduction in tumor blood flow may play an important role in the enhanced antitumor effects of the combined treatment with FAA, HYD, and hyperthermia.

Animals↗

Postoperative chemotherapy for gastric cancer in the elderly.

Prolongation of the life span and improvement in technology make it more likely that the elderly will be surgically treated and chemotherapy will be prescribed, postoperatively. The relationship between postoperative chemotherapy and survival time after resection for gastric cancer in the elderly was examined in a retrospective review of data on 268 patients over the age of 70 years; all had been treated in the Department of Surgery II, between 1965 and 1987. Of these 268 patients, 161 were prescribed anticancer drugs, postoperatively. Postoperative chemotherapy was more often prescribed for those in the advanced stages of a malignancy. The survival time of those patients was shorter than for those who did not receive these drugs (p < 0.05). In a subgroup of our patients stratified to adjust for stage of the disease, there were no significant differences between the survival rates in cases of stages I, II or IV of the cancer. The survival time of patients with stage III and given chemotherapy improved compared to those not given chemotherapy (p < 0.01). Advanced chronological age is not sufficient justification to limit or withhold treatment with anticancer drugs. We propose that postoperative chemotherapy be prescribed for patients with gastric cancer, regardless of age.

Aged↗

Effect of whole-body hyperthermia on pharmacokinetics and tissue distribution of doxorubicin.

The effect of whole-body hyperthermia (41.5 degrees C, 2 h) on doxorubicin (DOX) tissue distribution and plasma pharmacokinetics was examined in rats bearing a subcutaneous fibrosarcoma. Tumour response to the hyperthermia regimen alone was minimal, but the combination of heat with DOX (5.0 mg/kg, i.v.) enhanced tumour growth delay. The combined therapy, however, showed increased toxicity to normal tissue (especially renal and cardiac). Although DOX levels in spleen tissue were higher in rats exposed to hyperthermia than in control normothermic rats, both groups had comparable levels of drug in tumour, heart, kidney, and small intestine tissue at all time-points examined. Compared with normothermic animals, hyperthermia-treated rats showed decreased DOX in the mean area under the concentration-time curve (AUC) and decreased plasma DOX t1/2 but increased plasma drug clearance. These heat-mediated alterations in DOX pharmacokinetic parameters, however, do not account for the significant increases in thermochemotherapy-mediated cytotoxicities observed in tumour, and in normal renal and cardiac tissues.

Animals↗

Prolonged survival in hereditary nonpolyposis colorectal cancer.

We compared the survival between 46 patients with hereditary nonpolyposis colorectal cancer (HNPCC) and 1185 cases with sporadic colorectal cancer, who underwent a resection for the disease between 1972 and 1995. In a univariate analysis, the survival correlated well with stage, curability, size and the presence of HNPCC. Patients with HNPCC had a longer survival than those with sporadic colorectal cancer (P=0.0277). A multivariate analysis suggested that stage, curability, age, and HNPCC were the effective combination of factors predictive of survival. The above findings are thus expected to have a major influence on the evaluation of clinical trials in patients with colorectal cancer.

Age Factors↗

Diffuse bone metastasis with hematologic disorders from gastric cancer: clinicopathological features and prognosis.

Bone metastases diffusely invading the bone marrow from gastric cancer often manifest a rapid clinical course and the prognosis is very poor due to hematologic disorders such as DIC (disseminated intravascular coagulation) and/or MAHA (microangiopathic hemolytic anemia). The objective of this study was to clarify the clinicopathological features and prognosis of patients with gastric cancer in whom diffuse bone metastasis associated with hematologic disorders were evident. Thirty-eight patients with bone metastasis from a primary gastric cancer were thus selected and placed into 2 groups consisting of 15 with diffuse bone metastasis with DIC and/or MAHA, and 23 patients who had bone metastasis without hematological disorders. We compared the clinicopathological features and prognosis between the two groups. The clinicopathological features in patients with diffuse bone metastasis accompanied by hematologic disorders were significantly related to undifferentiated adenocarcinoma, a relatively younger age, elevated levels of serum ALP-BI and LDH, and a lower frequency of extraosseous metastasis. The median survival time after manifestation was 2 and 11 months for the patients with or without hematologic disorders, respectively. The prognosis was significantly worse in cases of DIC with the median survival being only one month. Since, prognosis of diffuse bone metastasis from gastric cancer is significantly poor, close attention should be directed to the specific clinicopathologic features related to diffuse bone metastasis plus hematologic disorders. Regarding high risk patients, a regular follow-up of the serum chemistry levels and a bone scan will aid in the early detection of the disease.

Adult↗

Thymidine phosphorylase activity and angiogenesis in gastric cancer.

Angiogenesis has an important role in the growth and metastasis of solid tumors. Several angiogenic factors have been identified, one being platelet-derived endothelial cell growth factor (PD-ECGF), which is identical to thymidine phosphorylase (dThdPase). We investigated the activity of dThdPase in 84 samples of 42 human gastric cancers, by liquid chromatography. The dThdPase activity significantly correlated to the microvessel density assessed by immunostaining to CD-31 antigen (P<0.05). Expression of dThdPase has an important role in the promotion of angiogenesis in human gastric cancer.

Adult↗

Heterogeneity and clinical role of thymidine phosphorylase activity in gastric cancer.

We examined the dThdPase activity in primary gastric cancer and metastatic lymph nodes from human subjects. The dThdPase activities were significantly higher in primary tumors than in the normal gastric wall, particularly in the center of the tumor rather than in the periphery (P<0.01). Tumors with a high dThdPase activity often had venous invasion (P<0.01). The dThdPase activities were significantly higher in metastatic lymph nodes than in the nodes without metastasis (P<0.01). The intratumoral heterogeneity of dThdPase activity was identified and cancer cells with high dThdPase activity may indicate that metastasis will likely occur.

Adult↗

Paraganglioma of the cauda equina: MR findings.

The MR findings of a case with paraganglioma of the cauda equina are presented. T2-weighted images showed the tumor to have a hyposignal rim and serpiginous flow voids, suggesting vessels capping the tumor. Contrast-enhanced MR images highlighted the tumor and tumor vessels more clearly. Knowledge of MR findings in this unusual disorder may aid in diagnosis.

Adult↗

Heparanase gene expression and metastatic potential in human gastric cancer.

BACKGROUND: Heparanase has been reported to play an important role in tumor progression and metastasis. We examined the relationship between heparanase mRNA expression and biological factors regarding invasion and metastasis of human gastric cancer. MATERIALS AND METHODS: In 63 human gastric carcinomas, 42 adjacent normal gastric tissues and four gastric cancer cell lines, heparanase mRNA expression was evaluated using reverse transcription PCR (RT-PCR). Total RNA obtained from human peripheral blood (PB) leucocyte and placenta were used as positive controls. The relationship between heparanase mRNA expression and various clinicopathological factors were analyzed. RESULTS: The heparanase mRNA expression evaluated with RT-PCR revealed that 31 out of 63 gastric cancer tissues (49%), 11 out of 42 normal gastric tissues (26%) and 4 gastric cancer cell lines were positive. The positive rate in cancer tissues was significantly higher than that in normal tissues (p<0.05). In the heparanase mRNA-positive cancer tissues, venous invasion was frequent (p<0.05) and the histological differential grade was significantly poorer than in negative cases (p<0.01). CONCLUSION: We propose that heparanase mRNA expression is involved in invasion and development of human gastric cancer and detection of this expression may be a factor related to metastasis and prognosis of such patients.

Female↗

Pathogenesis of calcium crystal deposition in the ligamentum flavum correlates with lumbar spinal canal stenosis.

OBJECTIVE: To investigate the histological and immunohistochemical properties of degenerative changes and calcium crystal deposition in the lumbar ligamentum favum. METHODS: We examined the ligamentum flavum harvested from 119 surgical cases with symptomatic lumbar spinal stenosis. Sections of the ligament were examined by scanning electron microscopy (SEM), energy dispersive X-ray micro-analysis, and were immunostained for S-100 protein, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and CD34. The results were compared with those of ligament tissue harvested from 10 cases of lumbar disc herniation. RESULT: The elastic fibres of the ligamentum favum showed regular, or sometimes irregular, and fragmented fibre bundles. Large areas of fibrosis with reduced elastic component and increased collagenous tissue were frequently seen in the degenerated ligaments. Calcium crystal deposits were observed in these fibrous ligaments, associated with many hypertrophic chondrocytes, and with small blood vessel formation. These chondrocytes stained positively for S-100 protein, VEGF and bFGF Calcium pyrophosphate dihydrate crystals were identified in the calcium deposit area. CONCLUSION: We believe that rupture of elastic fibre bundles is the first change to occur in degeneration of the ligamentum favum. Calcium crystal deposition was seen within these fibrous and chondrometaplastic areas. Hypertrophic chondrocytes regulate crystal formation and tissue reconstruction by secreting cytokines.

Adult↗

Postoperative adjuvant immunochemotherapy and infiltration of dendritic cells for patients with advanced gastric cancer.

To determine the group of patients for whom a biological response modifier is useful, the efficacy of postoperative adjuvant immunotherapy was investigated with regard to infiltration of dendritic cells (DC) in patients with advanced gastric cancer who underwent absolute curative resection. The infiltration of DC was classified into marked and slight. The chemotherapy group was prescribed mitomycin C and tegafur, while for the immunochemotherapy group a biological response modifier, PSK, was also prescribed in survival between the chemotherapy and immunochemotherapy groups. In patients with slight infiltration, however, the 5 - year survival rates were 0% in the chemotherapy and 15% in the immunochemotherapy group. Patients given PSK survived longer than those given chemotherapy only (P less than 0.05). Therefore, adjuvant immunotherapy may be considered for patients with advanced gastric cancer with slight infiltration of DC.

Adjuvants, Immunologic↗