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M Bak

Publications and source records attributed to M Bak.

At least 91 records · Page 5Linked to original sources
PubMed1990

Detection of drug resistance and P-glycoprotein in human renal cell carcinomas.

Expression of the multidrug-resistance gene product P-glycoprotein (P-170) was screened in 21 untreated human renal cell carcinomas using monoclonal antibodies (265/F4, C219) and immunoperoxidase staining. The inherent drug resistance of the same samples against doxorubicin was established by a short-term chemoresistance test in order to investigate the association between the expression of P-170 and intrinsic drug resistance in kidney cancers. P-glycoprotein could be demonstrated in 10 cases. Using the short-term test for predicting resistance, 17 resistant and 4 sensitive cancers were found. In vitro 10 of 17 resistant tumors revealed an increase of P-glycoprotein. On the other hand, in the sensitive tumor in vitro, an expression of P-glycoprotein could not be demonstrated. This investigation reveals that intrinsic drug resistance exists in many renal cell carcinomas and it is associated at least in part with increased expression of P-glycoprotein. The immunohistochemical results suggest that the presence of the P-glycoprotein may be useful as a marker for screening the multidrug-resistant phenotype in renal cell carcinomas and as an indicator of the therapeutic efficacy of multidrug-resistant kidney cancers.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1989

Pleomorphic (giant cell) carcinoma of the intestine. An immunohistochemical and electron microscopic study.

Pleomorphic (giant cell) carcinomas have been described in the lungs, thyroid, pancreas, and gallbladder. Two pleomorphic carcinomas of the small bowel and two of the large bowel are presented. On light microscopic study, the carcinomas were solid, without squamous or glandular differentiation. The tumors were composed of the following three cell types: gemistocytic (giant) cells, smaller polygonal cells, and spindle cells, with identical immunohistochemical reactions. A panel of monoclonal and polyclonal antibodies was applied. All tumors were found to coexpress keratin and vimentin. A positive reaction for neuron-specific enolase (NSE) was found in three tumors and a positive reaction for chromogranin was found in one tumor. On electron microscopic study, intracytoplasmic whorls of intermediate filaments were seen in the perinuclear area. Dense core "neurosecretory" granules were rarely seen. Intestinal pleomorphic carcinomas are histologically identical to pulmonary giant cell carcinomas. The prognosis is poor due to early tumor spread, with only a few months of postoperative survival. The pleomorphic carcinomas have some of the differentiation characteristics of carcinoid tumors and are best regarded as poorly differentiated variants of neuroendocrine carcinomas.

Aged↗
PubMed1989

Detection of P-glycoprotein in human leukemias using monoclonal antibodies.

Overexpression of a Mr 170,000 membrane glycoprotein (P-glycoprotein) is consistently associated with multidrug resistance in cell lines. Two monoclonal antibodies (Mab) against P-glycoprotein (265/F4 and C 219) were used to examine tumour samples from patients with leukemias for evidence of P-glycoprotein overexpression. High levels of P-glycoprotein (greater than 5% positive cells) were detected with both antibodies in samples from 3 out of 18 patients suggesting that a multidrug resistant phenotype may also occur in human leukemias.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1989

Induced multidrug resistance in murine leukemia L1210 and associated changes in a surface-membrane glycoprotein.

The aim of this study was to find out whether only resistant cells of the "multidrug-resistant" phenotype show the described changes of plasma membrane glycoprotein (170 kDa) or whether resistant cells that do not express this phenotype reveal corresponding results. Doxorubicin-resistant (L1210dox) and daunorubicin-resistant L1210 ascites tumor cells (L1210dnr) (multidrug-resistant tumor cells) were therefore compared with cytosine-arabino-side-resistant (L1210AraC) and cyclophosphamide-resistant L1210 ascites tumor cells (L1210ctx) (not multi-drug-resistant tumor cells). The resistant cell lines were generated in vivo in tumor-bearing mice and the resistance to cytostatic agents was evaluated in vivo and in vitro. Using the accumulation assay with rhodamine-123, the multidrug resistance can be detected. In order to determine alterations in the plasma membranes we used the monoclonal antibodies 265/F4 and C219, which were prepared against the membrane glycoprotein P170 (170 kDa) in colchicin-resistant Chinese hamster ovary cells. The results demonstrate that L1210dox and L1210dnr tumor cells show an intense immunostaining by the streptavidin/biotinylated-peroxidase-complex method and by the streptavidin/biotin/phycoerythrin immunofluorescence method. In contrast no specific immunostaining was observed in parental (sensitive) and L1210AraC or L1210ctx tumor lines. The results were confirmed by immunoblotting. To determine whether multidrug-resistant DNA sequences were expressed in the multidrug-resistant tumor cells, Northern blots with RNA od sensitive and resistant cells were performed using the clone pcDR1.5. Elevated RNA levels were detected only in resistant cells with the multidrug-resistant phenotype. Thus, the results of this study demonstrate that only resistant cells with the multidrug-resistant phenotype show an increased expression of the membrane 170-kDa glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1989

Detection of drug resistance in human ovarian carcinoma.

Drug-resistant cancer cells with the multidrug-resistance phenotype show overexpression of P-glycoprotein, and we therefore tested carcinoma tissue from five patients with stage III or IV ovarian cancer for P-glycoprotein using 265/F4 and C 219 monoclonal antibodies, prepared against membrane glycoproteins in colchicine-resistant CHO cells. Using immunofluorescence and immunoblotting techniques, one of the tumors showed a positive reaction. Using the pcDR 1.5 clone we found that the same cancer tissue had elevated expression of the genes responsible for multidrug resistance. The demonstration of elevated P-glycoprotein in ovarian carcinomas indicates that P-glycoprotein overexpression is not limited to experimental tumor models.

Carcinoma↗
PubMed1989

Ultrasonically guided 125iodine seed implantation with external radiation in management of localized prostatic carcinoma.

Thirty-three patients with localized prostatic carcinoma (16 poorly differentiated) were treated with transperineal 125Iodine seed implantation (160 Gy) guided by transrectal ultrasonography and subsequent external beam irradiation (47.4 Gy). The observation time was six to sixty-eight months with a median follow-up of thirty-five months. Median change in prostatic volume was a reduction of 35 percent. Re-biopsy or transurethral resection of the prostate was performed in 25 patients after one to two years, revealing still malignant histology in 12 (48%). Development of distant metastases occurred in 14 patients (44%), and 8 have died of prostatic cancer. Fourteen patients suffered from late complications of which surgical intervention was indicated in 3 cases.

Aged↗
PubMed1989

Detection of the multidrug resistant phenotype in human tumours by monoclonal antibodies and the streptavidin-biotinylated phycoerythrin complex method.

The aim of this study was to find out whether the membrane glycoprotein P-170 can be detected in human tumours with both acquired and intrinsic resistance to chemotherapeutic agents using monoclonal antibodies (265/F4 and C219) and the streptavidin-biotinylated phycoerythrin complex method. Pretreated leukaemia cells and untreated lung and ovarian carcinomas were analysed. Two plasmacytomas and one leukaemia expressed high levels of P-glycoprotein, whereas two leukaemias showed moderate, and three leukaemias no expression of this protein. The intrinsic resistance was analysed with a panel of four human epidermoid lung cancer xenografts grown in nude mice. The expression of P-glycoprotein could be correlated with the degree of resistance. In addition, one out of five ovarian carcinomas revealed a high level of P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1989

P-glycoprotein expression in treated and untreated human breast cancer.

The expression of P-glycoprotein in primary and recurrent human breast cancer was investigated by means of immunohistochemistry, using a monoclonal antibody (C219) and the streptavidin-biotin-peroxidase method. Twelve patients received no chemotherapeutic treatment. The other 11 patients were treated with chemotherapy, and all developed clinical resistance to it. No or only minimal reactivity was found in specimens coming from the untreated patients (12 cases) or from patients treated with substances not involved in the multidrug resistance phenomenon (four cases). In contrast, three out of seven tumours from patients treated with multidrug resistance related substances showed clear reactivity (positive staining in more than 20% of the tumour cells). In one of these cases, where specimens of the tumour could be studied before and after treatment, an association between the latter and expression of P-glycoprotein was suggested. Finally, this marked expression of P-glycoprotein only took place in tumours treated over a longer space of time (five courses or more of multidrug resistance related chemotherapy).

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1989

Radiosensitivity of drug-resistant human tumour xenografts.

The radiosensitivity of three drug-resistant sublines of a human epidermoid lung carcinoma growing as xenografts in nude mice was investigated. Drug resistance to vincristine, actinomycin D and cisplatin was developed in vivo by repeated drug treatment. It was found that all three drug-resistant tumour lines were not cross-resistant to irradiation.

Animals↗
PubMed1989

[Short-term subcutaneous infusion of insulin using a portable insulin pump in the treatment of diabetes mellitus].

The authors evaluated the effectiveness of treatment by means of constant subcutaneous insulin infusions (CPWI) in patients with diabetes staying in hospital. The infusions were made by means of portable insulin pumps (Microjet Bolus 1, Microjet Bolus 2 and Promedos E 1). The therapy was applied in a group of 15 patients with diabetes admitted to hospital because of symptoms of uncontrolled diabetes, among them 3 patients with diabetes freshly diagnosed. After 2-3 days of infusions 12 patients had glycaemia level approached to the physiological level. Only in one case of diabetes with significant resistance to insulin, the physicians were not able to control the diabetes. After 4-9 days of CPWI, patients who had been given conventional insulin injection had their insulin day demand reduced by 11-33%. In 4 cases the insulin demand had been established by means of Biostator GCIIS, after the introduction of the pumps the demand decreased by 40 +/- 5%, when the open loop system was applied. The above results suggest that the use of constant subcutaneous insulin infusion by means of a dosimeter may be recommended as a method of determining day demand for insulin, significantly shortening hospitalization period in patients with uncontrolled diabetes.

Adolescent↗
PubMed1989

[Immunologic phenomena in patients with proliferative retinopathy in diabetes mellitus type 1].

As a rule, in long-lasting diabetes type 1 there appear vascular complications in a form of proliferative retinopathy. While looking for the causes of fast vascular changes, the authors considered the possibility of immunological disorders. They started prospective examinations of patients with diabetes type 1 and proliferative retinopathy changes in the fundus of the eye. The authors evaluated the activity of angiogenic factors released by mononuclear cells isolated from peripheral blood of the patients examined. The authors found a significantly higher activity of these factors in patients with proliferative retinopathy in comparison with a control group of healthy persons and a group of patients with diabetes type 1 and simple retinopathy. The results obtained may indicate to immunological changes in the pathogenesis of proliferative retinopathy.

Adult↗
PubMed1989

[Therapeutic problems of patients with diabetes mellitus after total pancreatectomy].

Followed were 11 patients after total pancreatectomy (for carcinoma--6 patients, for sequelae of the chronic pancreatitis--5 patients), aged 52-62 years. The follow-up period ranged 5 months up to 4 years. All pacreatomized patients had diabetes needing insulin administration, although the need for insulin decreased with time down to 16-40 units/24 hours after one year. The diabetes was rather brittle with high incidence of hypoglycaemia. In 7 patients keeping exact records the incidence of hypoglycaemic events was 16-24 within the first month, 9-16 in the third month following pancreatectomy. In two patients death was due to the severe hypoglycaemia developing in the later postoperative period. The observations call for a necessary "intensive metabolic care" of every patient, totally pancreatomised. This intensive metabolic care must include not only careful instructing the patients but also his or her family how to behave in a totally different metabolic condition of the patient. Self-control, including blood sugar estimation several times a day gets special importance.

Blood Glucose Self-Monitoring↗
PubMed1989

Response of the R3327-AT1 Dunning prostate tumor to fast neutrons and cobalt-60.

Reasons why neutron therapy may be successful include tumor's rate of proliferation, state of oxygenation at time of onset of radiation and the efficacy of reoxygenation during therapy, inherent radioresistance and repair capacity. In an effort to better understand the action of neutrons on tumor tissues we started studies with the Dunning rat prostate tumor system. This tumor system has sublines available with differing histologies, doubling times, hormone dependency and metastatic potential. The present report pertains to anaplastic carcinoma R3327-AT1 subline. The tumors transplanted into the distal thigh received single doses of 8 through 15 Gy of 14.5 MeV neutrons and 18 through 30 Gy Co-60 after they had reached a volume of about 450 mm3. The tumors exhibited a dose dependent retardation in further growth. An RBE of 3 was estimated by comparing the time required for a tumor to reach a normalized value of five times the initial treatment volume. We plan to extend our studies to include a slower growing well differentiated subline.

Animals↗
PubMed1989

[Morphologic and tumor-marker studies of human planocellular carcinoma of the bronchi in xenografts].

Authors have studied the morphology of 10 human planocellular bronchus carcinoma xenografts parallel with that of the donor tumour. The expression of cytokeratin, epithelial membrane antigen and carcinoembryonic tumour markers was also studied and compared. The histological structure and marker expression of xenografts did not change as compared to the donor tissue. Tumour cells were characterized by cytokeratin rather than epithelial membrane antigen. Carcinoembryonic antigen positivity occurred mainly in well-differentiated tumours. The cellular heterogeneity of human planocellular bronchus carcinomas was found to occur also in xenograft tumours.

Antibodies, Monoclonal↗
PubMed1988

DNA and S-phase distribution and incidence of metastasis in human primary lung carcinoma.

The aim of the study was to investigate the relationship between DNA and S-phase distribution in primary non-small-cell lung carcinomas with the incidence of metastasis. Patients with non-small-cell lung carcinomas were divided into two groups depending on whether at time of surgery there were metastases or not, and these groups were correlated with the data obtained by flow cytometry or autoradiography. As expected from other studies, survival time was significantly longer for those patients without metastases at time of surgery (P = .0002) and the incidence of metastasis was significantly higher when the primary tumor was greater than or equal to 70 cm3 (P = .026). In this study, a total of 185 fresh specimens of lung carcinomas were investigated by flow cytometry. Patients with aneuploid tumors had a higher tendency to have metastases (P = .016). Patients with tumors with a higher proportion of S-phase cells measured by either flow cytometry or autoradiography demonstrated significant increase in the formation of metastases (P = .02 and P = .05). We feel that these results warrant further investigation with other primary tumors. A comparison of primary tumors that are known to rapidly metastasize vs. those that either slowly or rarely metastasize may prove to yield valuable insight into the important factors associated with metastatic potential.

Carcinoma, Non-Small-Cell Lung↗