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M Volm

Publications and source records attributed to M Volm.

At least 145 records · Page 8Linked to original sources

Prognostic relevance of ploidy, proliferation, and resistance-predictive tests in ovarian carcinoma.

In a cooperative study specimens of 37 patients with stage III and IV ovarian carcinomas who had been treated with chemotherapy were investigated utilizing flow cytometry and an in vitro short-term test for predicting resistance. Patients with aneuploid tumors had significantly shorter survival rates than did those with diploid tumors. Patients whose tumors showed a low G0/G1 cell proportion or a high proliferation pool (S- and G2/M cell-proportion) seemed to die earlier. There was also a tendency for patients with in vitro resistant tumors to die earlier under chemotherapy than those with sensitive tumors.

Adult↗

Use of tritiated nucleotide incorporation for prediction of sensitivity of tumors to cytostatic agents.

Development of a means for prediction of sensitivity or resistance of tumors is of paramount importance for future patient specific tumor therapy. A simple, easily performed short-term in vitro test is described whose basic feature is measurement of changes in incorporation of radioactive nucleic acid precursors into tumor cells after addition of cytostatic agents. In order to determine whether acquired resistance is detectable by means of this in vitro short-term test, resistant animal tumor cell lines were developed to different cytostatic agents. This developed resistance was detectable in the in vitro test system. It was observed that the short-term test could demonstrate cross-resistance, and also development and reversibility of resistance to cytostatics. Further, it is possible to assess the role of proliferative activity of tumors. In a clinical study patients with inoperable ovarian and lung carcinomas (n = 49) were treated by chemotherapy and the results of the treatment compared with the results of the in vitro tests. Tumors which show only a weak response in the in vitro test, also failed to respond to chemotherapy in the clinic. In a cooperative study - conducted by nine different hospitals - results of the short-term test in vitro were compared with results of drug therapy in 151 patients. Of these, 76 were judged resistant and 75 sensitive in the in vitro test. Of these 76 resistant tumors, 56 were clinically progressive (73%), 2 (2%) were in remission and 19 (25%) showed no change. Whilst in the 75 sensitive tumors 18 (24%) progressed clinically, 40 (53%) were in clinical remission and 17 (23%) were unchanged. Therefore if only the definite progression or remission evaluations are compared with the in vitro results 55 of the 57 tumors which were resistant in the test were clinically progressive (96%) and 40 of 58 tumors which were sensitive in the test showed clinical remission (69%). There is also good agreement between the in vitro test results and survival time. Patients whose tumors were resistant in the test generally died sooner than those whose tumors were sensitive. In the studies described - as in other investigations - chemoresistance is shown to be more successfully predicted than chemosensitivity.

Antineoplastic Agents↗

Preclinical evaluation of diethoxy-(1-phenyl-1,3-butanedionato) titanium (IV) in human tumour xenografts.

The antitumour activity of diethoxy-(1-phenyl-1,3-butanedionato)titanium (IV) (DBT) in comparison to cis-dichlorodiammine platinum (cisplatin, cis-DDP) and cyclophosphamide (CTX) against human breast, colo-rectal and lung tumour lines growing as xenografts in nude mice was investigated. The antitumour activities and toxicities of DBT and cis-DDP are comparable whereas CTX was the most effective agent.

Animals↗

Effect of five antineoplastic agents on tumor xenografts with different growth rates.

The effects of cyclophosphamide (Cy), doxorubicin (Dx), cisplatin (DDP), melphalan (L-PAM), and vincristine (VCR) on various human and animal tumor lines with different growth rates, growing as xenografts in NMRI (nu/nu) mice, were studied. Two types of response were observed: For Cy and Dx, the response of the xenografts was negatively correlated with tumor volume doubling time (TD), indicating that rapidly growing tumors were more sensitive to these drugs than were slowly growing tumors. For DDP, L-PAM, and VCR, the effects were positively correlated with the TD, indicating that slowly growing tumors were more sensitive to these drugs than rapidly growing tumors. The data are discussed in relation to the effects of the drugs on proliferating and nonproliferating cells obtained with other cell lines.

Animals↗

Differential expression of intermediate-filament proteins in murine sarcoma 180 ascites or solid tumor.

The intermediate-filament proteins in Sarcoma 180 ascites cells and solid tumors generated by s.c. injection of ascites cells in NMRI or nude mice were analyzed by one- and two-dimensional gel electrophoresis and identified by immunological methods. The ascites form of Sarcoma 180 coexpresses keratin and vimentin, whereas the solid tumor ceases to synthesize keratins but continues to express vimentin. These reversible changes in the expression of intermediate-filament proteins may be due to a change in the differentiation program induced by environmental conditions like growth with or without cell contact.

Animals↗

Isopycnic density-gradient centrifugation: a separation parameter which improves flow cytometric measurements on heterogeneous tumors.

The analytic and prognostic value of flow cytometric measurements can generally be improved by preseparation of cells. The present data demonstrate clearly the distinct character of bands obtained in density-gradient separation. Density-gradient centrifugation in Percoll after extensive Ca2+ + Mg2+ elimination helps to resolve more detail in flow cytometric measurements (e.g., additional DNA stem lines in human tumors) and can be used in studies of tumor heterogeneity. The significance of investigations of tumor heterogeneity is demonstrated by the different reactivity of subpopulations of the experimental murine tumor S 180 to vincristine.

Animals↗

[Pretherapeutic detection of tumour resistance to cytostatic agents].

Malignant tumours--even when they are of similar localization and histological type--very often react differently to cytostatic treatment. In order to determine the sensitivity or the resistance of malignant tumours, various test systems have been developed over the past few years: a) tissue or organ culture, b) assay for clonogenic tumour cells in soft agar, c) short-term culture of tumour cells, d) heterotransplantation of tumour material to nude mice. Practicability and limits of these methods are compared on the basis of the correlation between predictive test results and clinical results.

Animals↗

[Sensitivity testing of chemotherapeutic agents for ovarian and breast cancers--possibilities and limits of different methods and of their application (author's transl)].

Well-defined and individualised chemotherapy of human malignant tumours can be initiated with the aid of sensitivity tests for chemotherapeutic agents prior to treatment. The effectiveness of the specific cytotoxic agent can be determined by sensitivity testing. For these investigations three methods are available at present: 1. a short-term incubation method (biochemical assay). 2. an agar-cloning assay as a specific tissue culture method and 3. a heterotransplantation method with transplantation of tumour cells into thymus-aplastic animals. For routine clinical testing only the biochemical short-time assay and the agar colony assay are of practical significance. The test rates and growth rates in the two methods are composed. The in-vitro and in-vivo correlations of sensitivity testing of chemotherapeutic agents and resistance to chemotherapeutic agents in the different test systems show that the accuracy of prediction for the correct positive or correct negative result is 90%. These results are based on retrospective analysis. For the evaluation of the different prediction assays and for the evaluation of the clinical application of these methods only a randomised prospective therapeutic study can give the answers. However, this has not yet been carried out to date.

Animals↗

Polysomal polyadenylated RNA and albumin messenger RNA in Mastomys liver and in a chemically induced hepatocellular carcinoma.

A hepatocellular carcinoma line (H78) was established from a primary liver tumor induced in Mastomys natalensis by a single administration of dimethylnitrosamine. Six to 8 months after transplantation (passages 5 to 7), well-differentiated tumors, still containing glucogen-storing cells, were isolated and used for the preparation of RNA. Polysomal polyadenylated RNAs from Mastomys liver and from H78 tumor line were then compared by hybridization kinetics. Total kinetic complexities were 6.6 X 10(9) and 6.3 X 10(9) daltons for liver and tumor, respectively. Complexities of the high and middle abundant class were reduced in the hepatoma. Heterologous hybridization reactions revealed that, in terms of RNA mass, all or most of the polysomal polyadenylated RNA present in the liver was also present in the tumor and vice versa. However, shifts in the relative abundance of messenger RNA sequences were detected. In contrast to most other transplanted hepatomas, H78 has approximately the same content of albumin messenger RNA on its polysomes as has untreated liver.

Albumins↗

Chemical carcinogenesis by the two-stage protocol in the skin Mastomys natalensis (Muridae) using topical initiation with 7,12-dimethylbenz(a)anthracene and topical promotion with 12-0-tetradecanoylphorbol-13-acetate.

The long-term (34 weeks) topical administration of 7,12-dimethylbenz(a)anthracene (DMBA) to the skin of male and female Mastomys induced a broad spectrum of benign and malignant tumors in all animals treated. In a two-stage carcinogenesis experiment with topical initiation with DMBA and topical promotion with TPA, 50% of the animals developed both benign and malignant skin tumors. In general, benign tumors occurred between weeks 15 and 25, whereas malignant tumors were seen 40 weeks after initiation. In contrast to the situation in Mus musculus, the benign tumors consisted mainly of keratoacanthomas instead of fibroepitheliomas. In the non-initiated, TPA-treated, control group four benign and four malignant tumors were seen, whereas animals of the DMBA-initiated, acetone-treated control group were free of tumors. The promotion of virus transformed cells with TPA is discussed.

9,10-Dimethyl-1,2-benzanthracene↗

Growth kinetics of human lung tumours in nude mice.

In order to investigate the growth characteristics of xenografts of human tumours in nude mice, we heterotransplanted 22 human tumours of the lung into nude mice. We noted growth in 11 of these tumours (50%). The histological appearance of most of the tumours growing in the first passage in nude mice was comparable with that of the donor tumours. In further passages, however, a progressive dedifferentiation was noted in many tumours, depending on their growth rate. With the aid of growth curves and cell cycle kinetics (FMF analysis) it is shown that the growth kinetics of these tumours is affected by the transplantation and that the growth rate of such xenografts in nude mie is different from that of the original tumour in the patient.

Animals↗

In vivo and in vitro detection of induced resistance to daunorubicin in murine leukemia L 1210.

By treatment of the mouse leukemia L 1210 with daunorubicin (2 mg/kg per week) a tumour cell line was developed which was resistant to this cytostatic agent. The sensitive and resistant tumour cell line could be distinguished using an in vitro short-term test. Cross resistance could also be reliably detected by this method. In all cases, a good correlation was observed between the results of in vitro short-term tests and animal experiments.

Animals↗

Albumin messenger RNA after partial hepatectomy and sham operation.

Albumin mRNA was quantified in nuclear RNA and in polysomal and post-polysomal poly(A)-containing RNA from untreated, hepatectomized and laparotomized rat livers. A prominent reduction of albumin-specific RNA sequences was observed in all subcellular fractions 50 h after partial hepatectomy, compared to both untreated and sham-operated livers. Surprisingly, laparotomy itself also induced a dilution of albumin-specific sequences at earlier times after operation in nuclei and in post-polysomal supernatant, but not in polysomes.

Albumins↗

[Testing of sensitivity of human tumours to cytostatics in a rapid in vitro test (author's transl)].

In a cooperative study the predictability of results of cytostatic treatment in patients with tumours using a rapid in vitro test was assessed in 9 university hospitals. Treatment of tumour patients (carcinomas of the ovary, bronchus and various localisations) was performed independently of test results. In vitro tests estimating proliferation-dependent action of cytostatics agree readily with clinical treatment results. Tumours responding badly to cytostatics in the test were also progressive clinically. Results of the rapid in vitro test may thus be used in the decision to perform or withhold cytostatic treatment.

Antineoplastic Agents↗

Therapy of solid Walker carcinosarcoma 256 with bleomycin after synchronization with hydroxyurea.

Rats with the solid Walker carcinosarcoma 256 were synchronized with hydroxyurea (6 x 50 mg/kg or 1 x 300 mg/kg body weight) and treated with bleomycin (32 mg/kg body weight) at different time points thereafter. Bleomycin clearly affects Walker carcinosarcoma cells at the G1/S boundary or in S-phase. The improvement in the results of bleomycin therapy after pretreatment with hydroxyurea can mainly be accounted for by the synchronization of the tumour cells.

Animals↗