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Biomedical subjects

A Murakami

Publications and source records attributed to A Murakami.

At least 343 records · Page 19Linked to original sources

Enhancement of tumorigenic potential in virgin mice of a pregnancy-dependent mouse mammary tumor (TPDMT-4) by enzymatic cell dissociation.

The transplantable pregnancy-dependent mouse mammary tumor line TPDMT-4 behaves like a preneoplastic lesion in virgin mice when implanted with tissue pieces. This study was conducted to elucidate whether enzymatic cell dissociation enhances the tumorigenic potential as in hyperplastic mammary nodules. When tissue pieces were implanted in virgin mice, there was an increase in tumor incidence from 0% at generation 14 (F14) to 40% at 38 (F38) during the 6-month observation; early (F8), middle (F16-18) and late (F39-40) transplant generation (ETG, MTG and LTG respectively) tumors were dissociated with collagenase and hyaluronidase. DDD strain females receiving an injection of 10(5) dissociated cells into the fat pad were observed as virgin or ovariectomized. ETG cells formed palpable tumors in 18 (43%) and 21 (50%) of 28 virgins at latent periods of 133 +/- 11 (mean +/- SE) and 142 +/- 10 days for 6 and 8 months respectively. MTG and LTG cells did so in 24 (60%) of 40 and 25 (89%) of 28 virgins at 77 +/- 5 and 68 +/- 5 days respectively for 6 months. In ovariectomized mice, however, no palpable tumors developed from any of these cells. Most ETG and MTG cell-derived tumors repeated palpable growth and total regression one or more times, and subsequently disappeared or grew slowly, whereas almost all LTG tumors grew progressively from the onset. MTG cells infiltrated into the fat pad more extensively than ETG and LTG cells: MTG cells occupied almost the whole fat pad at 6 weeks, whereas the outgrowths of the other cells were confined to one-eight of the fat pad. Southern blot analyses demonstrated the absence of certain extra MMTV DNA fragments in MTG tumors, although the distinct behaviors of MTG cells could not be ascribed to it alone. The results suggest that enzymatic cell dissociation may enhance tumorigenesis by hormone-dependent mammary tumor cells at lower hormone levels.

Animals↗

Structural and functional analysis of long terminal repeats of Suncus murinus mammary tumor virus.

A 2.7-kilobase (kb) cDNA sequence complementary to Suncus murinus mammary tumor virus (Sm-MTV) genomic RNA [corrected] was prepared using purified virions produced by the Sm-MT cell line, which had been established from a spontaneous mammary tumor of S. murinus. It was found, by using this cDNA in Southern hybridization experiments, that Sm-MTV was endogenous to this animal and that some 50 copies of endogenous provirus were present per haploid cellular genome. In addition, a proviral Sm-MTV DNA sequence, 9.4 kb long (Sm-P-MTV10), was cloned from a Sm-MT cell genomic library, and its long terminal repeat was found to be 720 base pairs (bp) long, with the U3.R and U5 regions 574 and 146 bp long, respectively. The boundary between U3 and R was not determined with certainty, though in the cDNA, the U3 and R regions were 462 and 105 bp long, respectively. The overall homology between the U3.R regions in the cDNA and Sm-P-MTV was 75%. These two DNAs differed in such transcription regulatory signals as CCAAT and TATAA, the first being missing from the cDNA. Nevertheless, chloramphenicol acetyltransferase assays showed that the long terminal repeats of the cDNA and the Sm-P-MTV were transcriptionally active but not steroid hormone responsive. Like Mason-Pfizer monkey virus, Sm-MTV used tRNA(1,2Lys) as a primer for reverse transcription. In addition, the immunosuppressive peptide sequence common to many retroviruses was found in the env region of Sm-MTV. In these two points, Sm-MTV differed from mouse MTV.

Animals↗

Thermochemosensitivity: augmentation by hyperthermia of cytotoxicity of anticancer drugs against human colorectal cancers, measured by the human tumor clonogenic assay.

Thermochemosensitivity was examined in vitro by a human tumor clonogenic assay (HTCA) using specimens obtained surgically from 43 patients with colorectal cancer. We found that the percentages of patients whose cells showed higher sensitivity (greater than 70% inhibition of colony formation) to hyperthermia alone were 29.6 and 55.6% at 42 and 43 degrees C each for 1 h, respectively. Similarly, percentages of patients whose cells were sensitive to drugs alone were 13.8, 24.1 and 48.3%, for cis-diamminedichloroplatinum(II), 5-fluorouracil and mitomycin C, respectively. These sensitivities were augmented when hyperthermia was combined with administration of anticancer agents. Even in tumor cells that were insensitive to anticancer drugs alone or to hyperthermia alone, sensitivity was enhanced when administration of drugs was combined with hyperthermia. Our results demonstrate that HTCA of tumor cells, obtained from suitable patients, may be useful as a predictive test for application of thermotherapy and for individualization of chemotherapy.

Antineoplastic Agents↗

[Hepatic arterial chemotherapy combined with hyperthermia or arterial embolization in unresectable liver tumor].

Fifty-four patients with unresectable malignant liver tumors (14 of hepatocellular carcinoma, 40 of metastasis to the liver from gastric or colo-rectal cancer) were treated with intra-hepato-arterial (IHA) injections of cis-diamminedichloroplatinum (II) (CDDP) plus 5-fluorouracil (5-FU). In 32 of the patients, the liver tumors were detected synchronously with the diagnosis of the primary cancers, which were resected palliatively. Therapeutic schedules consisted of bolus injections of CDDP (50 mg/body/week) and 5-FU (250 mg/body/day) [Regimen I], and CDDP (50 mg/body/10-14 days) and 5-FU (100 mg/body/day) [Regimen II]. In 48 patients treated with IHA chemotherapy only, a partial response (PR) was obtained in 6 of 14 (43%) evaluable patients for Regimen I and in 11 of 30 (37%) patients for Regimen II. The dose-limiting factor for treatment with CDDP was bone marrow toxicity, but this toxicity was remarkably alleviated in Regimen II without any decrease in antitumor effectiveness. In 13 patients, other modalities, such as total-body hyperthermia (4 patients), radiofrequency capacitive local hyperthermia (5), and temporary arterial embolization (4), were combined with IHA chemotherapy. PR was obtained in 7 of 13 (54%) patients with the combined therapy. This combined therapy was efficacious in 7 patients in whom no desired results were obtained by IHA chemotherapy only. The survival rate was 50% at 12 months. IHA chemotherapy with CDDP plus 5-FU, especially when according to Regimen II, appears to be a strongly recommended strategy for treatment of unresected primary or metastatic liver tumor. Further, addition of the hyperthermia or the arterial embolization might enhance the antitumor effect of IHA chemotherapy.

Aged↗

[Treatment of renal vein thrombosis associated with nephrotic syndrome].

Renal vein thrombosis is a rare entity in which true incidence is unknown. The disease occurs most frequently in patients with nephrotic syndrome, but it also can occur in the presence of other hypercoagulable state. Two cases of renal vein thrombosis with nephrotic syndrome which were treated by thrombectomy are reported here. One patient was successfully treated by renal vein and inferior vena cava thrombectomy before developing severe pulmonary embolism. The other was treated by renal vein thrombectomy by which fatal shock was able to be prevented. In those cases, immediate operation was indicated, primarily to prevent additional, possibly fatal, pulmonary embolism and also to improve perfusion of the kidney. In the hope of salvaging the kidney, thrombectomy may be the treatment of choice for acute renal vein thrombosis, complication of pulmonary embolism and inferior vena cava thrombosis, right renal vein thrombosis without collateral flow and acute renal vein thrombosis with shock.

Adult↗

[A case of leukoencephalopathy caused by HCFU].

After a hysterectomy, a bilateral salpingo-oophorectomy, two courses of intra-peritoneal chemotherapy of Cisplatinum, Carmofur (HCFU, 600 mg/day [per os]) were given a patient who had ovarian granulosa cell tumor (malignant, stage Iai). Dizziness and loss of consciousness developed about 60 days after administration of HCFU, and leucoencephalopathy was diagnosed. A CT revealed a diffuse low density area in the white matter of the cerebrum. Myelin Basic Protein in the spinal fluid was found to amount to 9.8 mg/dl, which in norm. person is less than 4.0 mg/dl. Also, it showed parallel changes with the course of the clinical findings. HCFU easily dissolves to fat and changes to 5-FU without enzymes in the liver cell. Further HCFU also passes through Blood Brain Barrier to Produce 5-FU and its derivatives, in which the alpha-Fluoro-beta-Alanine is thought to be the culprit that brings on leucoencephalopathy. Even so, HCFU should be dosed when needed in spite of this risk. Other 5-FU modifiers also have been reported to produce the same effect in several cases.

Adult↗

[Clinical results and problems of total-body thermochemotherapy].

The clinical results and problems of extracorporeally-induced total-body thermochemotherapy (TBHT) for recurrent cancer are presented. A total of 127 hyperthermic treatments were performed in 45 patients who had undergone unsuccessful conventional systemic anticancer chemotherapy. Partial response was observed in 11 of 34 evaluable patients (32%). In analysing the anticancer effects of TBHT according to cancer site, a high efficacy was observed in patients with their main tumor in the lung, liver and lymph nodes. The anticancer effects were most enhanced when TBHT was performed in combination with cisplatin and 5-fluorouracil. In order to augment the anticancer effects of TBHT, the choice of combined agents and administration timing are important. A useful method for determining the thermochemosensitivity of individual cancer cells to agents selected for drug treatment is the human tumor clonogenic assay. Furthermore, the usefulness of angiotensin II-induced hypertensive chemotherapy during TBHT for augmenting selective drug delivery to cancer tissue is stressed.

Antineoplastic Combined Chemotherapy Protocols↗

Establishment of a CSF-producing cell line from a human gastric carcinoma and characteristics of the CSF produced by that cell line.

A human cell line producing colony-stimulating factor has been established in vitro from a human gastric carcinoma. The cell line was transplantable into nude mice which developed a marked neutrophilia. The cell line has been maintained for three years. The cells grew in a monolayered sheet and produced colony-stimulating factors that enhanced the formation of granulocyte and monocyte colonies in vitro with mouse bone marrow cells as the target and granulocyte colonies with human bone marrow cells as the target.

Animals↗

Control of ciliary beat frequency in the gill of Mytilus--I. Activation of the lateral cilia by cyclic AMP.

The effect of cyclic AMP on the beat frequency of the lateral cilia on the gill of Mytilus edulis was investigated. Dibutyryl cyclic AMP (0.1 mM) weakly stimulated the cilia to beat. The activation was augmented by 1 mM theophylline. The cilia were hardly activated by cyclic AMP (0.1 mM) but a strong activation was observed when it was applied with saponin (0.0025-0.01% w/v) and theophylline (1 mM). The results suggest that cyclic AMP is involved in the mechanism of ciliary activation by 5-hydroxytryptamine.

Animals↗

Control of ciliary beat frequency in the gill of Mytilus--II. Effects of saponin and Brij-58 on the lateral cilia.

The effects of saponin and Brij-58 on the beat activation of the lateral cilia on the gill of Mytilus edulis were investigated. The ciliary activation by 5-hydroxytryptamine (5HT) decreased as the saponin-induced permeabilization progressed, increasing the reactivation of the ciliary beat by extracellularly applied ATP (1 mM). The cilia were activated by 5HT even after the treatment with saponin (0.01 and 0.02% w/v) or Brij-58 (0.07%) rendered the preparation capable of the reactivation by ATP. The saponin treatment itself stimulated the beat of the cilia. Theophylline (1 mM) augmented the saponin-induced activation of the cilia.

Adenosine Triphosphate↗

Carcinoembryonic antigen in gastric cancer patients.

Carcinoembryonic antigen (CEA) levels were determined in 252 gastric cancer patients. In patients with resectable cancer, the preoperative CEA values and CEA positivity rates were 2.4 +/- 1.5 ng/ml and 7.7% for stage I, 24.9 +/- 72.0 ng/ml and 10.0% for stage II, 21.6 +/- 84.1 ng/ml and 17.9% for stage III, and 6.3 +/- 8.4 ng/ml and 27.1% for stage IV cancers, respectively. In patients with nonresectable cancers, the CEA value was 83.0 +/- 235.5 ng/ml, the CEA positivity rate was 47.8%. Overall, of 252 patients with primary gastric cancer, 47(18.7%) were positive for CEA. In patients with cancer recurrence, the CEA value averaged 41.8 +/- 101.8 ng/ml, the positivity rate was 63%. This rate increased as the cancer stage increased; it was highest in gastric cancer patients with liver metastasis. In 4 of 13 patients with recurrence, an elevation in CEA was observed about 4.8 months before the clinical detection of cancer recurrence. Our results suggest that in gastric cancer patients, the preoperative and periodic postoperative assay of CEA levels has predictive value in determining cancer stage, progression and recurrence.

Carcinoembryonic Antigen↗

The histogenesis of DMH-induced colonic carcinoma in rats.

Twenty-one Donryu male rats of six weeks old were injected with 1,2-dimethyl-hydrazine hydrochloride (DMH), once a week, for 4 to 20 weeks, and sacrificed at intervals of two weeks since a lapse of four weeks after the commencement of the injections. The DMH induced 320 atypia lesions, from 0.03 through 20 mm in size, of grade II or higher. The rate of benign lesions was higher in the group receiving less than 20 injections than in the group of 20 injections of DMH, while in the latter group, the rates of the benign, borderline and malignant lesions were stable, suggesting that benign lesions mainly develop in the earlier period of the DMH treatment, and thereafter various grades of lesions develop at a constant rate. All the benign lesions were less than 1 mm in size, and all lesions greater than 1 mm were malignant. In addition, the size of the lesion was significantly greater when it was occupied by malignant crypts in a greater rate. These results indicate that the benign lesions become cancerous before they reach a certain size (adenoma-carcinoma sequence). Twenty-seven minute lesions (less than 1 mm) were mixed lesions of malignant and benign atypia, suggesting that the adenoma-carcinoma sequence is elicited in any size of lesion. On the other hand, there were 41 minute malignant-only lesions, which constituted 27.7% of the overall minute lesions and included three "single crypt" cancers. In addition, malignant-only lesions were smaller when compared to the malignant-dominant mixed lesions. These results indicate that about 30% of colon cancers develop de-novo.

Animals↗