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Biomedical subjects

M Bak

Publications and source records attributed to M Bak.

At least 109 records · Page 6Linked to original sources

Human tumor xenografts as model for drug testing.

This paper reviews the history of xenografts, the endpoints commonly used to evaluate response and chemotherapeutic results obtained with serially maintained human tumor xenografts from different laboratories, and discusses the potential clinical relevance of the heterotransplant model for cancer chemotherapy. Specifically, an attempt is made to correlate the published xenograft data with the clinical data. Drug testing with different types of xenotransplanted tumors has shown that the response of xenografts obtained in immune-deficient animals is comparable to that in clinical practice. In addition, xenografts of a particular tumor type are able to identify agents of known clinical activity against that disease.

Animals↗

Adenocarcinoid of the vermiform appendix. A clinicopathologic study of 20 cases.

Adenocarcinoid of the appendix is a tumor that shares the histologic features of both carcinoids and adenocarcinomas. The metastatic ability of the tumor is uncertain. Twenty consecutive cases of adenocarcinoids were compared with 88 cases of conventional appendiceal carcinoids. Metastatic tumor spread was found in six of 20 cases of adenocarcinoids, but in none of the conventional carcinoids. Metastasizing tumors were characterized by a moderate to severe nuclear atypia and a high mitotic count. These features were present in only two of the nonmetastasizing tumors, one of which was treated by hemicolectomy. Adenocarcinoids showing moderate or severe nuclear atypia, a mitotic count of two or more mitoses/10 high power fields, or spread beyond the appendix should be treated by hemicolectomy. If these features are not present, simple appendectomy is adequate.

Adenocarcinoma↗

Development of drug resistance in a human epidermoid lung carcinoma xenograft line.

The development of resistance to vincristine, actinomycin D and cisplatin has been examined in a human epidermoid lung carcinoma xenograft line (HXL 55) growing in nude mice. Treatment of HXL 55 with 1 mg kg-1 vincristine or 0.5 mg kg-1 actinomycin D once in each in vivo passage resulted in a rapid reduction in tumour responsiveness to these drugs. A partial resistance was already acquired at the 2nd transplant generation. In contrast, a gradual decrease in therapeutic response was observed with 10 mg kg-1 cisplatin. Irradiation with a local dose of 10 Gy induced no resistance. The three induced drug-resistant sublines were characterized in terms of the time course of development of resistance, the degree of induced resistance, cross-resistance, growth rate and stability of the phenotype.

Animals↗

Intrinsic drug resistance in a human lung carcinoma xenograft is associated with overexpression of multidrug-resistance DNA-sequences and of plasma membrane glycoproteins.

The purpose of this study was to examine whether multidrug resistance can be detected in human lung tumors not previously treated with chemotherapy. Therefore, the intrinsic sensitivity or resistance of 8 human epidermoid lung cancer xenografts grown in nude mice has been examined. The tumor lines responded differently to vincristine and the other cytostatic agents. When the effects of vincristine on the 8 tumor lines are correlated with the effect of dactinomycin (actinomycin D), a close relationship could be found (r = 0.96). These results demonstrate that xenografts derived from human lung tumors not previously treated with chemotherapy exhibited a similar pattern of cross-resistance as is observed in sublines of murine and human tumors which were resistant to various drugs following repeated exposure of the cells to a sublethal concentration of these drugs. The resistant lung tumor HXL 54 also shows an overexpression of the P170-membrane glycoprotein (detected by Mab 265/F4). To determine whether multidrug genes were expressed in resistant lung tumors, slot blots and Northern blots were performed using the probes pDR 7.8 and pcDR 1.5. The level of expression can be correlated with the degree of drug resistance.

Animals↗

Adenocarcinoid of the appendix presenting with metastases to the liver.

A case of hepatomegalia due to multiple metastases of unknown origin to the liver is described. At autopsy the primary tumor, an adenocarcinoid tumor of the appendix, was identified along with multiple metastases to the lymph nodes and widespread peritoneal carcinoidosis. Hepatic metastases from an appendiceal adenocarcinoid tumor has not been described previously. In the liver and lymph nodes the tumor had an insular growth pattern and was composed predominantly of cells of carcinoid type, whereas the carcinoidosis was composed almost entirely of signet-ring cells. It is suggested that differentiation of the metastases of appendiceal adenocarcinoids is modulated by factors in the recipient organ.

Aged↗

Occurrence of a multidrug-resistant phenotype in human lung xenografts.

The intrinsic sensitivity of a panel of 8 human epidermoid lung cancer xenografts to vincristine and actinomycin D has been examined and the cross-resistance patterns of the most vincristine-resistant and vincristine-sensitive tumour line were tested to a variety of other drugs, including radiation. The results demonstrate that xenograft lines derived from human lung tumours not previously treated with chemotherapy exhibit a similar general pattern of cross-resistance to the drugs vincristine, actinomycin D and adriamycin as is observed in human cell lines and in animal models selected for resistance to these drugs. It is also shown that intrinsic resistance to vincristine can be partially overcome by verapamil. This may indicate a potential role of this substance in circumventing clinically observed drug resistance.

Animals↗

Influence of insulin on plasma concentration and renal excretion of sodium and potassium in normal, electrolytes depleted and aldosterone treated dogs.

Effects of insulin on plasma concentration and renal excretion of sodium and potassium were compared in conscious dogs 1) maintained in water and electrolytes balance (Series 1, 10 dogs), 2) depleted of electrolytes by repeated i.v. loading with 20% mannitol (Series 2, 10 dogs), and 3) aldosterone treated (0.8 micrograms.kg-1.h-1 i.v., Series 3, 10 dogs). In each Series intravenous infusion of insulin at a rate of 0.05 U.kg-1.h-1 elicited transient increase in plasma sodium concentration and prolonged hypokalemia. Repeated loading with mannitol in Series 2 elicited significant elevation of plasma sodium, ADH and aldosterone concentrations, as well as decrease in extracellular fluid volume. Infusion of insulin in this Series elicited smaller decrease in plasma potassium concentration and longer lasting hypernatremia than in dogs in water-electrolytes balance. Aldosterone infusion in Series 3 did not change hypokalemic effect of insulin but attenuated hypernatremia. Infusion of insulin in Series 1 elicited increase of sodium excretion and decrease in potassium excretion. These effects were absent in Series 2 and 3. The results indicate that depletion of electrolytes and blood aldosterone elevation modify the effects of insulin on plasma concentration and renal excretion of sodium and potassium.

Aldosterone↗

Aspiration cytodiagnostics of breast tumours.

Aspiration cytology has been performed in 2,180 cases of breast alterations. Cytological examination was followed by histological control in 967 cases. Diagnostic value (sensitivity) of the method proved to be as high as 83%. As a matter of principle, the technique cannot substitute histology. Using in combination with other clinical diagnostic measures like palpation, mammography, xeromammography, thermography the diagnostic possibilities are multipled. This preoperative morphological test of orientatory value which is rapid, cheap and painless and devoid of any complications is worth of widespread use. According to the authors opinion its routine application in the clinical practice is highly desirable.

Adenocarcinoma, Mucinous↗