Biomedical subjects

M Volm

Publications and source records attributed to M Volm.

297 records · Page 17Linked to original sources

PubMedDate not supplied

Up-regulation of heat shock protein 70 in adenocarcinomas of the lung in smokers.

Tumour samples of smokers (n = 32) and non-smokers (n = 21) with previously untreated adenocarcinomas of the lung were analysed, immunohistochemically, for expression of the heat shock protein 70 (hsp70). A correlation between smoking habits and expression of hsp70 was found. Of the tumours from the 21 non-smokers 12 (57%) and of the 32 smokers 24 tumours (75%) showed high hsp70 expression. The expression of hsp70 depended on the number of cigarettes smoked daily. Of the patients who smoked more than 20 cigarettes, 16 out of 18 had tumours with a high hsp70 expression (89%; p = 0.028).

Adenocarcinoma↗

PubMedDate not supplied

Retinoblastoma (Rb) protein expression and resistance in squamous cell lung carcinomas.

The purpose of this study was to prove the value of Rb protein expression as a prognostic factor for patients with squamous cell lung carcinoma. The expression of Rb in 75 carcinomas was analyzed immunohistochemically and the resistance to doxorubicin was investigated in vitro. Rb-negative carcinomas were more frequently resistant than Rb-positive carcinomas (p<0.05). A trend for a correlation between the expression of Rb and the expression of glutathione S-transferase-pi was detectable (p=0.08). Patients with Rb-positive carcinomas had a trend for better prognosis, but this result was not statistically significant.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMedDate not supplied

Association of vascular endothelial growth factor expression with tumor cell proliferation in ovarian carcinoma.

Vascular endothelial growth factor (VEGF) is a potent angiogenic factor that may also function as an autocrine growth regulator. Thirty-one ovarian carcinomas were investigated for mRNA expression of VEGF and of a proliferation-dependent gene (histone H3) using slot-blot analysis. Tumor vascularity was assessed by immunohistochemistry and factor VIII. All tumors were demonstrated to express VEGF and histone H3, though to various degrees. There was a good correlation between VEGF mRNA values and histone H3 mRNA values (r = 0.71, p < 0.05). No correlation was found between tumor cell proliferation and tumor vascularity. There was no significant difference in relapse-free interval or overall survival between tumors with low and high VEGF expression. The close correlation of VEGF expression with tumor cell proliferation in this study raises the possibility of autocrine stimulation of ovarian carcinoma.

Adolescent↗

PubMedDate not supplied

Angiogenic growth factors and their receptors in non-small cell lung carcinomas and their relationships to drug response in vitro.

Tumor specimens of non-small cell lung carcinomas (NSCLC) from previously untreated patients (n = 153) were analysed immunohistochemically for expression of vascular endothelial growth factor (VEGF), VEGF-receptor (Flt-1), basic fibroblast growth factor (bFGF) and FGF-receptor (FGFR-1, (Flg). Expression of the proteins was compared with the in vitro response of the tumors against doxorubicin. The data clearly demonstrate that a significant relationship exists between VEGF (p < 0.001) and Flt-1 expression (p < 0.01) and drug response. The expression of VEGF and Flt-1 was lower in resistant than in sensitive tumors. In contrast, no significant interrelationship was found between expression of bFGF and response to doxorubicin. However, there exists a significant correlation between the expression of FGF-receptor (FGFR-1) and the response of the carcinomas to doxorubicin (p < 0.05). Expression of FGFR-1 was more frequently negative or weak in resistant and more frequently moderate or high in sensitive NSCLC. The data from this investigation clearly demonstrate that a significant interrelationship exists between the expression of VEGF, VEGF-receptor Flt-1 and FGF-receptor, FGFR-1 and the response of NSCLC to doxorubicin in vitro.

Carcinoma, Non-Small-Cell Lung↗

PubMedDate not supplied

Coexpression of VEGF and bFGF in human epidermoid lung carcinoma is associated with increased vessel density.

Tumor specimens from 84 patients with untreated epidermoid lung carcinomas were analysed immunohistochemically for the expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), tumor cell proliferation (PCNA index) and tumor vascularity (vessel density). The purpose of this study was to find out whether differences in tumor cell proliferation and tumor vascularity might be associated with differential angiogenic growth factor expression. The present results indicate that the proliferation of the tumors is closely related to their expression of VEGF, but not for bFGF. The PCNA labelling index in VEGF positive tumors (VEGF+/bFGF- or VEGF+/bFGF+) was significantly higher than that in VEGF negative tumors (VEGF-/bFGF- or VEGF-/bFGF+; Wilcaxon rank sum test, p < 0.0001). To investigate whether VEGF or bFGF is involved in lung tumor angiogenesis, the data of VEGF and bFGF expression were correlated with vessel density. It was found that the expression of VEGF and bFGF were associated with increment of vessel density, however, vessel density was significantly increased only when VEGF and bFGF were coexpressed (p < 0.02). It is suggested that VEGF and bFGF might act cooperatively in the neovascularization of human epidermoid lung carcinomas.

Carcinoma, Squamous Cell↗

PubMedDate not supplied

Multiple resistance mechanisms in acute nonlymphoblastic leukemia (ANLL).

The expression of the resistance-related proteins P-glycoprotein 170 (P-170), glutathione-S-transferase pi (GST-pi), topoisomerase II (Topo II), thymidylate synthase (TS) and metallothionein (MT) was investigated in leukemic cells of 19 children with newly diagnosed acute nonlymphoblastic leukemia. P-170 was expressed in 84%, GST-pi in 37%, TS in 47%, MT in 68%, and Topo II was downregulated in 37% of the cases investigated. No resistance factors were found in two patients, one positive factor was found in two patients, three factors in three patients, four factors in 7 patients, and all resistance factors investigated were present in one patient. Patients who developed a relapse expressed more than two resistance mechanisms significantly more often than patients who remained in remission (p = 0.005). The probability of continuous first remission was significantly lower where more than two resistance mechanisms were expressed. The results indicate that the higher the number of resistance-related proteins in childhood ANLL the poorer the prognosis of the patients.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMedDate not supplied

Prognostic value of p16INK4A expression in lung adenocarcinoma.

The analysis attempted to determine whether the expression of p16INK4A has prognostic relevance for patients with lung adenocarcinomas. For this purpose, immunohistochemistry was used to analyze 58 adenocarcinomas. Of the tumors investigated, 20 did not express p16INK4A, while 38 yielded a positive staining result. Median survival time was shorter for patients with p16INK4A negative carcinomas than for those with p16INK4A positive tumors (47 vs. 79 weeks, P = 0.11). The relative risk for patients with p16INK4A negative tumors was increased by a factor of 1.6 in comparison to positively stained tumors. There exists a direct correlation between the proportion of G0/G1 phase cells and the p16INK4A expression. Additionally, there is an inverse relationship between S phases and p16INK4A expression. Furthermore, p16INK4A negative adenocarcinomas show more frequent growth in nude mice than p16INK4A positive carcinomas.

Adenocarcinoma↗

PubMedDate not supplied

Multidrug resistance and its reversal.

Cross-resistance between different cytostatic agents which are structurally and functionally dissimilar is a common phenomenon called multidrug resistance (MDR). The best characterized mechanism of MDR involves P-glycoprotein. However, this does not completely explain MDR. Within the last few years, two new genes that can confer MDR have been identified (MRP and LRP). Furthermore, topoisomerase II has been associated with a special form of MDR. During the past several years, considerable interest has been shown in strategies to reverse MDR by using pharmacological compounds, monoclonal antibodies, immunotoxins, bispecific antibodies, antisense oligodeoxynucleotides, ribozymes, and albumin-conjugated drugs in in vitro and in vivo assays. All these experimental assays demonstrated that MDR can be circumvented. Two agents that have received the most attention in the clinic are verapamil and cyclosporin A. Despite some promising results (especially in hematological malignancies), the results obtained in the treatment of solid tumors with modulators have so far been quite disappointing. This may be explained by the fact that the MDR phenotype alone does not completely account for the resistance of human cancer. Several other resistance-related proteins (e.g., glutathione S-transferase, metallothionein, O6-alkylguanine-DNA-alkyltransferase, thymidylate synthase, dihydrofolate reductase, heat shock proteins) can be also expressed in resistant tumors. Additionally, cell proliferation, vascularization and apoptosis are involved in resistance.

Animals↗

PubMedDate not supplied

nm23-H1 protein expression in newly diagnosed and relapsed childhood acute lymphoblastic leukemia.

In a retrospective study, immunocytochemistry was used to analyze the cells of 62 newly diagnosed and 28 relapsed childhood acute lymphoblastic leukemias (ALL) for the expression of nm23-H1 protein. Of the 62 newly diagnosed ALL, only 9 cases exhibited positive staining (15%) while 10 of the 28 relapsed ALL did (36%). This difference is statistically significant (P = 0.03, Fisher's exact test). Furthermore, the presence of mutations in the exons 1-5 was investigated by RT-PCR and single-strand conformation polymorphism (SSCP) analysis. No mutations could be detected in either the newly diagnosed or relapsed ALL. This finding suggests that nm23-H1 mutations may be a rare event in ALL.

Biomarkers, Tumor↗