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H Dosaka

Publications and source records attributed to H Dosaka.

13 recordsLinked to original sources
PubMed1991

The transactivating domain of the c-Jun proto-oncoprotein is required for cotransformation of rat embryo cells.

The nuclear phosphoprotein c-Jun, encoded by the proto-oncogene c-jun, is a major component of the AP-1 complex. A potent transcriptional regulator, c-jun is also able to transform normal rat embryo cells in cooperation with an activated c-Ha-ras gene. By deletion analysis, we identified the regions of c-Jun encoding transformation and transactivation functions. Our studies indicate that there is a direct correlation between the ability of the c-Jun protein to activate transcription and cotransform rat embryo cells. The regions involved in these functions include the conserved leucine zipper/DNA binding domain and an effector domain near its N terminus. This N-terminal region spans amino acids 61 to 146 of the c-Jun protein and is highly conserved among all Jun family members. These results support the hypothesis that c-Jun transforms cells by stimulating the expression of transformation-mediating genes.

Animals↗
PubMed1989

A transfected L-myc gene can substitute for c-myc in blocking murine erythroleukemia differentiation.

We investigated the ability of the proto-oncogene L-myc to substitute for c-myc in blocking murine erythroleukemia differentiation. Murine erythroleukemia cells (line C19) were transfected with recombinant plasmids containing genomic and cDNA fragments of the L-myc gene driven by a Moloney murine leukemia virus long terminal repeat. Clones expressing constitutive high levels of L-myc failed to differentiate in response to the chemical inducer N,N'-hexamethylene bisacetamide (HMBA). The block to differentiation correlated with the level of L-myc expression. Furthermore, transfected clones grown in the presence of inducer for an extended period of time showed an increased level of L-myc expression. These results suggest that functional domains of the c-myc gene involved in differentiation are located in the discrete regions of homology between the c- and L-myc genes.

Acetamides↗
PubMed1988

Transplantation resistance to a Rous sarcoma virus-induced tumor in mice immunized with v-src protein.

It is of great interest in tumor immunology to know whether oncogene products could be used not only as tumor markers for cancer diagnosis, but also as immunogens for cancer therapy. BALB/c mice immunized with syngeneic fibroblasts, Escherichia coli cells producing p60v-src, or the purified p60v-src protein extracted from the E. coli producer cells showed transplantation resistance to a Rous sarcoma virus-induced tumor but not a Kirsten sarcoma virus-induced tumor. In contrast, mice immunized with cells not producing p60v-src or their derived proteins or with chicken ovalbumin did not show any significant resistance. These findings suggest that p60v-src can act as a specific transplantation rejection antigen in mice.

Animals↗
PubMed1988

Enhanced expression of ras gene products in psoriatic epidermis.

The ras oncogene product ras p21 is structurally homologous to guanine nucleotide-binding proteins and plays an important role in transducing signals elicited by membrane receptors into intracellular metabolism. We examined psoriatic tissues for expression of ras p21 and compared them with normal skin, using the indirect immunofluorescence technique with the anti-ras p21 monoclonal antibody (MoAb), rp-35. In normal epidermis of five healthy individuals and uninvolved epidermis of three psoriatic patients, only the basal layer was positively stained by rp-35. The spinous layer was negative or faintly positive. In contrast, all psoriatic epidermis obtained from 13 psoriatic patients had strong reactivity with rp-35 throughout the epidermis. There were no differences in the staining pattern of hair follicles, sebaceous glands, eccrine glands, and eccrine ducts, which positively reacted with rp-35, between psoriatic and normal skin. The functions of ras p21 have not been clearly identified in mammalian cells; however recent reports reveal that cyclic AMP production is inhibited by the transfection of activated ras gene into normal cells. Enhanced expression of ras p21 in psoriatic epidermis may be indicative of some mechanism of defective beta-adrenergic responsiveness, which is considered to be one of the important pathophysiological phenomena causing the hyperproliferative condition in psoriasis.

Antibodies, Monoclonal↗
PubMed1988

The relationship of clinical classification to ras p21 expression in human non-small cell lung cancer.

The relationship of tumor size, status of disease in the TNM classification, and stage of disease to ras oncogene expression was studied in human non-small cell lung cancer materials immunohistochemically using monoclonal antibody rp-35 against ras 21. Materials of adenocarcinoma and squamous cell carcinoma obtained from primary sites larger than 30 mm in diameter exhibited intensely positive reactions with rp-35 significantly more frequently than those with primary sites, 30 mm in diameter or smaller (p less than 0.01). Furthermore in the TNM classification, cases with T2 (with primary sites larger than 30 mm in diameter) or T3 (with direct extension to adjacent structures) showed significantly higher reaction with rp-35 than those with T1 (with primary sites 30 mm in diameter or smaller) (p less than 0.01), although N and M status did not correlate with ras p21 expression. These results suggest that ras oncogene may play a significant role in growth or tumorigenesis at the primary site in human non-small cell lung cancer.

Antibodies, Monoclonal↗
PubMed1987

Serum selenium and vitamin E concentrations in families of lung cancer patients.

Whether or not serum selenium and vitamin E (alpha-tocopherol) concentrations were changed was examined among healthy families of lung cancer patients. Family members as a whole (115 sons and daughters of 55 patients with primary lung cancer) were found to have a trend to lower serum selenium levels (0.116 +/- SD 0.024 microgram/ml, 0.05 less than P less than 0.1). Particularly among families of adenocarcinoma patients, the mean level was significantly lower (0.111 +/- 0.019 microgram/ml, P less than 0.05) than that (0.122 +/- 0.014 microgram/ml) in age-ratio matched controls who did not have cancer patients among their second-degree relatives. Serum vitamin E levels (11.85 +/- 2.85 micrograms/ml) were significantly lower among family members of adenocarcinoma patients than the controls (14.1 +/- 3.1 micrograms/ml, P less than 0.01). Serum selenium and vitamin E levels were significantly lower in lung cancer patients (n = 37, mean age, 63.9 +/- 11.2 yr) than in the controls (P less than 0.001). These data suggest that there are familial factors in serum selenium and vitamin E levels among families of lung cancer patients.

Adenocarcinoma↗
PubMed1987

Sister chromatid exchange induction by benzo(a)pryene in cultured peripheral blood lymphocytes of lung cancer patients and healthy individuals with or without familial history of neoplasms.

The inducibility of sister chromatid exchanges (SCEs) by benzo(a)pyrene (BP) was studied in cultured peripheral blood lymphocytes of 15 untreated lung cancer patients and 25 healthy persons including 11 high- and 14 low-cancer-risk individuals tentatively classified by the familial history of lung cancer and other neoplasms. The baseline SCE frequency in cultured lymphocytes was significantly high in lung cancer patients, as compared with all healthy persons or low-cancer-risk individuals. Following exposure to BP, the lymphocytes of lung-cancer patients and high-cancer-risk individuals exhibited significantly greater SCE yields than those of persons at low risk, although no significant difference was observed in the lymphocyte SCE yields when the levels of lung cancer patients were compared with those of all healthy persons. A comparison of the net SCE increase (delta SCE) in BP-exposed lymphocytes among the study groups, however, revealed a significant difference in delta SCE values only between high- and low-cancer-risk individuals. The present findings on both the observed SCE yields and delta SCE values suggest that lymphocytes of high-risk individuals may be more susceptible to BP-induced DNA damage than those of persons at low risk, and that such a chromosomal hypersensitivity to genotoxins may be associated with a high risk of neoplasms.

Adult↗
PubMed1985

[Host factors in lung cancer patients--with reference to family and past histories].

An analysis of cigarette smoking habits and family and past histories of 494 lung cancer patients was undertaken to determine whether host factors in such patients could be related to cancer. In men, 35.8% of the patients with squamous cell carcinoma had family histories of cancer, which is significantly higher than the ratio in control subjects (P less than 0.05). In women, 58.3% of the patients with bronchoalveolar cell carcinoma had family histories of cancer, and, in six out of eight of them, their parents had had the disease. As for past histories, 7.7% of the women with lung cancer had undergone surgery ovarian tumor. These results suggest that familial (hereditary) factors and predisposition play a role in the etiology of lung cancer.

Adenocarcinoma↗
PubMed1984

[Effects of oral etoposide in small cell carcinoma of the lung].

Eleven patients with small cell carcinoma of the lung were treated with 120 mg/m2/day of Etoposide (VP-16-213) given orally for 5 days every 3 or 4 weeks. One of these eleven achieved complete response and two partial response. The response characteristically occurred within one or two courses of therapy, but the duration of the effect was short with relapse after 10 to 54 days (mean 23 days). It is concluded that Etoposide is an effective agent in treating small cell carcinoma of the lung, but of limited values when used as a single agent. This drug may be useful in combination chemotherapy regimens.

Administration, Oral↗
PubMed1984

[Etoposide effect on cell cycle kinetics of a human lung cancer cell line].

The lethal and kinetic effects of Etoposide on a cell line of human small cell carcinoma of the lung (PC-6) were analyzed in vitro using flow cytometric measurement of DNA content. The drug effect is dependent on concentration and exposure time. When PC-6 cells were exposed to Etoposide for 1 hour then washed, a increase of cells in G2 phase was observed followed by prompt recovery. Continuous treatment with Etoposide for 24 hours caused a retardation of S phase transit, and high concentrations (greater than 10 micrograms/ml) resulted in stoppage of the whole cell cycle. This drug may be useful in combination chemotherapy regimens.

Cell Count↗
PubMedDate not supplied

Immunohistochemical analysis of human lung cancers with anti-ras p21 monoclonal antibodies.

The expression of ras oncogene product p21 in human malignant pleurisy and primary lung cancer was studied immunocyto-histochemically with monoclonal antibodies (MoAbs) rp-28 and rp-35 against ras p21. In pleural effusion cells, cancer cells revealed more intensively positive reaction with MoAb rp-35 than with MoAb rp-28, especially in the plasma membrane, and no positive reaction was obtained in any kind of inflammation cells with the exception of faintly positive reaction in the cytoplasm of macrophages. In primary lung cancers, well or moderately differentiated adenocarcinoma tissues showed higher reactivity with MoAb rp-28 than those of poorly differentiated adenocarcinoma or any other histological subtype of lung cancer. With MoAb rp-35, intensively positive reaction was obtained in most of cases with all different histological subtypes of lung cancer. The staining in cancer cells was usually localized intensively to the plasma membrane and weakly to the cytoplasm with both MoAbs. Normal bronchial epithelial and glandular tissues showed only cytoplasmic staining. These two MoAbs, especially MoAb rp-35, may be useful in clinicopathological applications for the diagnosis of malignant pleurisy and primary lung cancer.

Antibodies, Monoclonal↗