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Biomedical subjects

J Hamada

Publications and source records attributed to J Hamada.

At least 145 records · Page 8Linked to original sources
PubMed1988

Host immune responses to tumor cells augmented by bleomycin and their therapeutic effects on rat fibrosarcoma.

The administration--timing-dependent therapeutic effects of bleomycin (BLM) were observed on a fibrosarcoma implanted SC in WKA rats. Five consecutive IP administrations of BLM (5 mg/kg/d) were found to be more effective when BLM was given from Day 8 than when it was given from Day 1 for tumors implanted on Day 0. The therapeutic effects correlated well with antitumor immune responses, which were examined on Day 13 when the tumor had not yet regressed even in surviving rats. The tumor-neutralizing activity of spleen cells was augmented in rats treated with BLM from Day 8 to Day 12, and the suppressor cell activity detected in the spleen cells of tumor-bearing rats was eliminated by the BLM treatment. The tumoricidal activity of peritoneal exudate cells (PEC) was detected in rats treated from Day 8 but not in rats untreated or treated from Day 1. The in vitro treatment of KMT-17 cells with BLM (20 micrograms/ml) for two hours enhanced the sensitivity of the tumor cells to the activity of tumoricidal PEC. This suggests that the direct action of BLM on tumor cells also plays an immunologic role in BLM treatment. The findings reveal that the therapeutic effect of BLM is elicited by its ability to augment the host immune responses to tumor cells.

Animals↗
PubMed1988

[Inhibitory effect of UFT on postoperative lung metastasis of mammary adenocarcinoma in SHR rats].

It is well known that UFT has significant therapeutic effects against experimental and clinical cancers at the primary sites. In this experiment, we studied the inhibitory effect of UFT on the lung metastasis of spontaneously developed rat mammary carcinoma (SST-2) after surgical excision of the primary site. In comparison of UFT-treated (15 or 30 mg/kg/day) with 5-FU-treated (9.7 or 19.5 mg/kg/day) groups, UFT was more effective than 5-FU in the antitumor activity and the inhibitory effect of lung metastasis with/without surgical excision of the primary sites. Rats (5-10 rats per group) were inoculated s.c. with 1 x 10(6) SST-2 cells and administered with UFT orally (15, 30 or 60 mg/kg/day) starting the day after tumor inoculation for 30 days. The therapeutic effect of UFT was studied by the growth rate of primary tumor and the numbers of metastatic colonies in the lung 35 days after tumor inoculation, comparing the UFT-treated with control groups. UFT administration at the doses of 30 or 60 mg/kg/day markedly inhibited the growth of the primary tumors and the number of metastatic lung colonies decreased, compared with that of the control group. However, in the group of rats treated at the dose of 60 mg/kg/day, 60% of rats died from the side effects of UFT such as weight loss, hemorrhage etc. In all groups in which the primary tumors were surgically excised 20 days after tumor inoculation and then treated with UFT (15, 20 or 30 mg/kg/day), we observed marked prolongation of survival period and inhibition of lung metastasis as well. Furthermore, we studied the effect of combination therapy of UFT and lentinan (1 mg/kg/day i.p.) on the metastasis of SST-2 cells after surgical excision of the primary sites. It was more effective than UFT alone. Thus, it is clear that UFT is an effective anticancer drug to inhibit metastasis of tumors in the lung after surgical excision of primary tumor.

Adenocarcinoma↗
PubMed1988

[A case of cerebral gumma].

A case of cerebral gumma in the left trigonal region is reported. A 74-year-old man was admitted to our hospital on Apr. 23, 1985 with unsteady gait and memory disturbance. Neurological examination revealed slight disorientation, memory disturbance, right homonymous hemianopsia and right hemiparesis. Serological reaction for syphilis was strongly positive, and so was CSF. The CSF showed slight pleocytosis (8/3 lymphocytes) and increased protein content (130 mg/dl). DSA showed no hypervascularity nor tumor stain. Ga brain scan showed no abnormality. The CT scan revealed an irregular low density area near the left trigone with abnormal contrast enhancement. Because of the radiological findings a malignant lymphoma was diagnosed and biopsy was performed, however, histological investigation confirmed the diagnosis of cerebral gumma. The patient was treated with penicillin and reduction of the tumor size was observed on CT scan. Cerebral gumma has been reported only rarely during the last few decades, and there are only a few descriptions of the neuroradiological characteristics of this disease. An accurate diagnosis can be made only by taking into consideration the clinical findings and course, the serological results, and the effect of the antisyphilitic treatment. When dealing with CT imaging similar to an intracranial malignant lymphoma, syphilitic disease of the brain should be regarded as possibly being present.

Aged↗
PubMed1987

Changes in the tumorigenic and metastatic properties of tumor cells treated with quercetin or 5-azacytidine.

The effect of quercetin, a flavonoid derivative, on the transplantability (tumorigenicity) and metastatic behavior of mouse tumor cells was studied. BMT-11 c1-9 fibrosarcoma cells were treated in vitro with quercetin, and after cloning by limiting dilution, cell suspensions of each clone were injected subcutaneously (s.c.) into syngeneic C57BL/6 mice at a dose of 2 X 10(5) cells per mouse. Out of 17 clones examined, 8 were nontumorigenic in normal mice ("regressor" clones), whereas these clones were able to grow in immunosuppressed (600-rad-irradiated) mice. Furthermore, 1 out of 9 tumorigenic clones metastasized spontaneously to the lungs despite the very low metastatic potential of the parent BMT-11 c1-9 cells. In contrast, all 15 clones selected from the untreated parental line grew progressively in normal mice with no evidence of metastases. The appearance of both regressor and metastatic clones was also observed after treatment with a DNA hypomethylating agent, 5-azacytidine. These altered phenotypes resulting from treatment with both chemicals, however, were not necessarily stable if maintained in culture for several months. The data suggest that quercetin may be a useful new material for obtaining regressor or metastatic clones from parental tumor lines.

Animals↗
PubMed1987

Brainstem auditory evoked responses and CT findings in multiple system atrophy.

Brainstem auditory evoked responses (BAERs) and CT findings were comparatively studied in 11 patients with Shy-Drager syndrome and 10 patients with olivopontocerebellar atrophy. The I-III interpeak latencies (IPLs) were prolonged in 6 patients with Shy-Drager syndrome and in 6 patients with olivopontocerebellar atrophy. Mean values of the I-III IPLs were 2.54 +/- 0.28 ms (Shy-Drager syndrome) and 2.62 +/- 0.15 ms (olivopontocerebellar atrophy). In each disease, the I-III IPLs correlated well with the degree of the pontine atrophy estimated from the CT scan. The patients with Shy-Drager syndrome could be clinically divided into two varieties. In addition to autonomic dysfunction, one variety (4 patients) was linked with parkinsonism, and the other (7 patients) with signs of multiple nervous systems involvement. Prolongation of I-III IPLs and pontine atrophy were noted in 6 out of the latters patients, whereas the former patients did not show such abnormalities. The combination of BAERs and CT scan provides useful clinical information on multiple system atrophy.

Adult↗
PubMed1987

Inverse correlation between the metastatic capacity of cell clones derived from a rat mammary carcinoma and their intercellular communication with normal fibroblasts.

We used three highly and two weakly metastatic clones obtained from a rat mammary carcinoma cell line (c-SST-2) to examine the relationship between the metastatic capacity of tumor cells and their intercellular communication with normal fibroblasts. By employing the dye-transfer method, we found that the frequency of intercellular communication between weakly metastatic clone cells and fibroblasts was significantly higher than that between highly metastatic clone cells and fibroblasts. These results suggest that normal fibroblasts may regulate the metastatic capacity of tumor cells by intercellular communication.

Animals↗
PubMed1987

[Influence of intercellular interaction between cancer cells and normal cells on cancer metastasis].

Three highly metastatic and two weakly metastatic clones were obtained from a spontaneously arising mammary adenocarcinoma in an SHR rat. The difference in their capacity to metastasize in lungs was recognized only when the cancer cells were inoculated subcutaneously but not when they were inoculated intravenously. This evidence possibly indicates that the difference in the metastatic capacity of these clones is caused by different potential for detachment from the primary site and for intravasation during the various steps of metastasis. The motility of cancer cells, which is one of the most important factors in these steps of metastasis, showed no difference between the highly and weakly metastatic clones. However, the motility of cancer cells was decreased after the coculture with normal fibroblasts, and the motility of weakly metastatic clones used was more strongly decreased than that of highly metastatic clones. On the other hand, using a dye transfer method to examine the relationship between the metastatic capacity of cancer cells and the capacity of cancer cells to make junctional communications with normal fibroblasts, it was demonstrated that the frequency of communication between weakly metastatic clone cells and fibroblasts was significantly higher than that between highly metastatic clone cells and fibroblasts. These results suggest that the motility of cancer cells is inhibited by interaction with normal fibroblasts, and that one of these forms of interaction may be mediated by intercellular communication.

Animals↗
PubMed1987

[Cancer metastasis and intercellular communication].

Three highly metastatic and two weakly metastatic clones were obtained from a spontaneously arising mammary adenocarcinoma in an SHR rat. The difference in their capacity to generate metastatic activity was recognized only when the cancer cells were inoculated s.c. but not when they were inoculated i.v. This evidence possibly indicates that the difference in the metastatic capacity of these clones is caused by different potential for detachment from the primary site and for intravasation during the various steps of metastasis. The motility of cancer cells, which is one of the most important factors in these steps of metastasis, showed no difference between the highly and weakly metastatic clones. However, the motility of cancer cells was decreased after coculture with fibroblasts, and the motility of weakly metastatic clones was more strongly decreased than that of highly metastatic clones. On the other hand, using a dye transfer method to examine the relationship between the metastatic capacity of cancer cells and the capacity of cancer cells to form junctional communications with normal fibroblasts, it was demonstrated that the communication between highly metastatic clone cells and fibroblasts was poorer in comparison to that between weakly metastatic clone cells and fibroblasts. These results suggest that the motility of cancer cells is inhibited by interaction with normal fibroblasts, and that one of these forms of interaction may be mediated by intercellular communication.

Adenocarcinoma↗
PubMed1987

[Pathogenesis and the treatment of secondary syringomyelia].

Six cases with secondary syringomyelia were evaluated clinically and the pathogenesis was discussed. Three cases had the tumors; an ependymoma arising from the conus medullaris and the filum terminale, a foramen magnum meningioma extending to C2 and a thoracic astrocytoma. Two cases had past history of spinal cord injury with L1 and L2 fracture-dislocation, respectively. One case showed hydromyelic symptoms associated with isolated fourth ventricle after post-meningitic hydrocephalus. Clinical symptoms and signs were complex and various in each case due to the association of the original disease and the syrinx. Syringomyelic symptoms were dominant in three cases of which the syrinx extended from the conus to the cervical cord. Initial symptoms of two cases with post-traumatic syringomyelia were tingling pains which began near the site of injury and extended rostrally. Metrizamide myelography revealed complete or incomplete block at the location of the tumors or the injuries. Delayed CT demonstrated the syrinx in all cases. The syrinx was always present near the sites of primary lesions. The communication between the syrinx and the fourth ventricle was suspected in three cases, and the communication of the syrinx and the spinal subarachnoid space was suspected in two cases. All cases underwent the surgical treatments. Total removal of the tumors were completed in two cases and relieved the majority of symptoms. On the other hand, a case with a thoracic astrocytoma underwent biopsy of the tumor and irradiation, followed by poor outcome. Syringo-peritoneal shunts were performed in two cases with post-traumatic syringomyelia and relieved pain, but neurological signs were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1986

Possible participation of tumoricidal macrophages in the therapeutic effect of bleomycin on a transplantable rat fibrosarcoma.

When bleomycin (BLM) (5 mg/kg/day) was administered i.p. to WKA rats for 5 days from the eighth day after KMT-17 implantation, the therapeutic effects of BLM were demonstrated by complete tumor regression in 50% of the cases and prolongation of the mean survival time of the remainder [survival days, 44.3 +/- 13.6 (SD)]. The combined administration of an antimacrophage agent, carrageenan, with BLM significantly inhibited the therapeutic effects of BLM (cure rate, 33%; survival days, 29.8 +/- 5.8). By means of a Winn assay, the tumor neutralizing activity of both spleen cells and peritoneal cells (PC) against KMT-17 cells was found to be augmented in BLM-treated tumor bearing rats as compared with that in nontreated tumor bearing rats. The enhanced tumor neutralizing activity of spleen cells was not abolished by an anti-rat T-cell serum plus complement treatment and was present in an adherent macrophage enriched population. Similarly, an in vitro [125I]iododeoxyuridine release test enabled us to observe the enhancement of the cytotoxic activity of adherent spleen cells and adherent PC in BLM-treated rats. The cytotoxic activity of the PC of BLM-treated rats was not specific to KMT-17 cells alone but was also observed to operate against antigenically different tumor cells such as WFT-2N, KST-20, and K562 cells. An in vitro carrageenan treatment of PC taken from BLM-treated rats reduced their cytotoxic activity. At the same time, the combined administration of carrageenan and BLM also reduced the cytotoxic activity of PC. These results suggest that the tumoricidal activity of macrophages in tumor bearing rats is augmented after BLM therapy and that the activated tumoricidal macrophages may participate in the host-mediated antitumor effects of BLM.

Animals↗
PubMed1986

Metastatic ability and expression of c-fos oncogene in cell clones of a spontaneous rat mammary tumor.

It was found that cell clones c1-2, cl-2r, c1-3, c1-4 and c1-6 of a spontaneous rat mammary tumor, c-SST-2, exhibit different degrees of metastatic ability: c1-2, c1-3, c1-6 were highly metastatic, while c1-2r and c1-4 were weakly metastatic. The expression of several oncogenes in these clones was examined. The amounts of myc mRNA in the clones were nearly the same. Expression of N-ras mRNA was higher in c1-2r and c1-4 than in c1-2, c1-3 and c1-6. On the other hand, the amounts of fos mRNA in the weakly metastatic clones were markedly lower than those in the highly metastatic clones. These results suggest that fos oncogene plays a role in the high metastatic ability of c-SST-2.

Animals↗
PubMed1985

Activation of natural resistance against lung metastasis of an adenocarcinoma in T-cell depressed spontaneously hypertensive rats by infection with Listeria monocytogenes.

We report here our study of the role of natural host defense mechanisms mediated by macrophages and natural killer (NK) cells in an experimental model of spontaneous pulmonary metastases of a mammary adenocarcinoma SST-2 in spontaneously hypertensive rats (SHR) with congenital T-cell depression. To activate macrophages and NK cells, Listeria monocytogenes (LM) was injected IV into SHR which had received a transplantation of SST-2. To assess the antimetastatic responses induced by LM, the number of lung nodules and the lung weight in SHR were evaluated 30 days after tumor inoculation. The growth of lung metastases, though not of primary tumors, was significantly reduced if 10(7) LM were injected IV into SHR 2, 10 and 20 days after the SC transplantation of 5 X 10(4) or 5 X 10(5) SST-2. An inhibitory effect of LM on pulmonary metastases was also observed in tumor-excised rats, in which the number of lung metastases and the lung weight were enhanced as compared with those in tumor-bearing rats which had not undergone surgery. Peritoneal resident cells which were harvested from rats injected with LM showed a significant augmentation of tumoricidal activity against SST-2 cells as measured by in vitro cytotoxicity. Similarly, the NK activity of spleen cells of SHR injected with LM increased significantly when compared with untreated SHR. These data suggest that the inhibition of metastatic growth, though not of primary tumor growth, was accomplished by the, possibly T-cell independent, activation of macrophages and NK cells.

Adenocarcinoma↗
PubMed1985

Asymmetric lightness cancellation in Craik-O'Brien patterns of negative and positive contrast.

The Craik-O'Brien illusion was measured for patterns of negative and positive contrast by a compensation method. The illusion of negative contrast (black teeth on uniform field) was stronger than that of positive one (white teeth). The amount of compensation increased linearly with increasing tooth width, but was nonlinear, showing two phases with increasing tooth height. The results might be explained by the concept of the antagonistic and nonantagonistic mechanisms in the lower stage of the visual system, and the reconstructive process of the barrier activity against the lateral spread in the higher stage.

Darkness↗
PubMed1985

Host-mediated therapeutic effects produced by appropriately timed administration of bleomycin on a rat fibrosarcoma.

The timing of bleomycin (BLM) administration after KMT-17 tumor inoculation was found to be important for optimizing its therapeutic effect on tumor-bearing rats. A remarkable therapeutic effect was observed when BLM (5 mg/kg/day) was administered i.p. for 5 days from the eighth day after tumor inoculation (Day 8 to Day 12) rather than when BLM was administered i.p. for 5 days during the days immediately following tumor inoculation (Day 1 and Day 5) (cured rats/treated rats: 10/21 and 2/16, respectively). By means of a Winn assay, stronger tumor-neutralizing activities were observed in spleen cells from BLM (Day 8 to Day 12)-treated tumor-bearing rats than were observed in spleen cells from BLM (Day 1 to Day 5)-treated tumor-bearing rats (% Inhibition: 70.9 and 49.3%, respectively). These therapeutic effects were thus found to be consistent with the antitumor immunity against KMT-17. The enhanced tumor-neutralizing activities of spleen cells from BLM-treated tumor-bearing rats were suppressed by adding spleen cells from nontreated tumor-bearing rats. In cell transfer experiments, an antitumor transplantation resistance in rats immunized with irradiated KMT-17 cells was abrogated by an adoptive transfer of spleen cells from untreated tumor-bearing rats or BLM (Day 1 to Day 5)-treated tumor-bearing rats but not from BLM (Day 8 to Day 12)-treated tumor-bearing rats. These results suggest that, when BLM is administered during a late stage of tumor growth, it is effective in eliminating suppressor cells and that this leads to an improvement in the therapeutic effects of the drug.

Animals↗
PubMed1985

Enhancing effect of quercetin on 3-methylcholanthrene carcinogenesis in C57Bl/6 mice.

We investigated the effect of quercetin on 3-methylcholanthrene (MCA) carcinogenesis in C57Bl/6 mice. We found that quercetin itself was not carcinogenic when administered i.m., even at a dose of 20 mg, throughout an observation period of 420 days. An i.m. administration of various doses of quercetin admixed with 1.0 mg of MCA, however, significantly shortened the mean latency periods for the development of local primary tumors compared with those of the group which had been given MCA alone. The shortening of latency periods was also found in the experiments using 0.1 mg of MCA after the administration of quercetin either admixed with MCA or fed with a diet containing it. Moreover, lung metastasis increased in mice given the mixture of MCA (0.1 mg) and quercetin compared with its occurrence in mice given MCA alone. A simultaneous administration of MCA and quercetin significantly increased the in vivo sister chromatid exchanges (SCE) formation of bone marrow cells when compared with its occurrence in the group given MCA alone. These results suggest that quercetin has an enhancing effect on MCA carcinogenesis and that this enhancement may be associated with such a genetic effect as an increased mutation rate in the host.

Animals↗