Biomedical subjects

M Volm

Publications and source records attributed to M Volm.

At least 37 records · Page 2Linked to original sources

PubMed1998

Smoking-related increase of O6-methylguanine-DNA methyltransferase expression in human lung carcinomas.

Eighty-three non-small cell lung carcinomas (NSCLC) of previously untreated patients were analysed for expression of O6-methylguanine-DNA methyltransferase (MGMT) by means of immunohistochemistry. Expression of MGMT was detected in 62 of 83 tumours (75%). There was a significant difference in MGMT staining between smokers and non-smokers (P = 0.001). Tumours of smokers expressed more frequently MGMT than tumours of non-smokers. There was a trend of MGMT expression to be higher in tumours of patients smoking >20 cigarettes/day than patients smoking <20 cigarettes/day. Abstinence from smoking resulted in a significant decrease in MGMT expression (lin reg r = -0.59, P < 0.05). These results demonstrate that MGMT expression in human lung carcinomas is influenced by smoking habits of the patients.

Adult↗

PubMed1998

Expression of the retinoblastoma tumor suppressor gene (RB-1) in acute leukemia.

In this report we review current studies concerning the RB-1 gene expression in acute leukemias. The RB-1 gene was analyzed in several studies by protein-, RNA and DNA-techniques in acute lymphoblastic leukemia (ALL) as well as in acute myelogenous leukemia (AML). The frequency of RB-1 inactivation in ALL-patients ranged between 30% and 64% in several studies. Structural abnormalities of the RB-1 gene were reported in 18% of ALL-patients and in 27% of Philadelphia chromosome-positive ALL, respectively. The proportion of AML-patients with absent RB-1 protein expression ranged between 19% and 55%. Structural RB-1-abnormalities in AML were predominantly reported in leukemias with monocytic differentiation. Furthermore, the prognostic value of an abnormal RB-1 gene expression was also estimated in some studies. In childhood ALL RB-1 inactivation was reported to have prognostic significance while in contrast, in another study on adults no prognostic value of RB-1 was found. In 4 out of 5 documented studies AML-patients with RB-1 inactivation generally had a poorer prognosis. In conclusion, RB-1 inactivation is frequently observed in acute leukemia. The prognostic value of low RB-1 expression is controversial but the majority of published studies found low RB-1 expression to be a negative prognostic predictor, in acute leukemia.

Adult↗

PubMed1998

Expression of platelet-derived endothelial cell growth factor in non-small cell lung carcinomas: relationship to various biological factors.

The expression of platelet-derived endothelial cell growth factor (PD-ECGF) was determined immunohistochemically in 143 non-small cell lung carcinomas. Staining was observed in 48% of the cases. A relationship between histology, stage, erbB-1, erbB-2, ras and PD-ECGF expression was not found. A relationship of borderline significance was observed between PD-ECGF and p53 expression. There was also no relationship between PD-ECGF expression and proliferative activity (G1 phases, S phases, cyclin A). In contrast, a correlation between PD-ECGF- and VEGF-expression was detectable (p=0.009). Furthermore, PD-ECGF expression was related to the response of lung carcinomas to doxorubicin (p=0.0004). Of 35 sensitive tumors, 26 carcinomas were PD-ECGF-positive (74%) while of 108 resistant carcinomas only 43 tumors (40%) exhibited PD-ECGF expression.

Antineoplastic Agents↗

PubMed1998

Spontaneous apoptosis in ovarian cancer: an unfavorable prognostic factor.

Apoptosis and cell proliferation play important roles in the cellular response to chemotherapy, and may have prognostic value. The percentage of apoptotic cells [apoptotic index (AI)] was evaluated in ovarian carcinomas of 25 patients by the terminal desoxynucleotidyl transferase-mediated dUTP-nick end labeling (TUNEL) technique. All patients were surgically treated and received postoperatively chemotherapy consisting of cytoxan and cisplatin or carboplatin. As a marker of proliferation the mRNA expression of histone H3 in tumor tissue was determined. In addition, tumor vascularity was assessed by immunohistochemistry and factor VIII. Patients with high AI had significantly shorter survival times (p=0. 0001) or recurrence-free intervals (p=0.004) than patients with low AI. No significant relationship was found between AI and histone H3 mRNA expression, however, an inverse correlation of AI with microvessel density was detected. Tumors with high AI had significantly lower microvessel count than tumors with low AI (p=0. 002). The obtained data suggest that AI can be predictive of treatment outcome in ovarian cancer.

Antineoplastic Agents↗

PubMed1998

Taxanes in adjuvant and neoadjuvant therapies for breast cancer.

Paclitaxel (Taxol) is a diterpene originally obtained from the bark of the Pacific Yew Tree, Taxus Brevifolia. Its mechanism of action is unique. It stabilizes microtubule polymerization, thus blocking cells in the G2/M phase of the cell cycle. In breast cancer, initial studies using paclitaxel demonstrated high activity. The first study was reported in 1991 by Holmes et al who gave paclitaxel as a 24-hour infusion at 250 mg/m2 to 25 patients with metastatic breast cancer following only one prior chemotherapy regimen--they achieved a 56% response rate. Since then, numerous studies have confirmed the effectiveness of paclitaxel in patients with metastatic disease. A second taxane, docetaxel (Taxotere), has also demonstrated excellent activity. Clinical research is now focused on integrating the taxanes into combination drug regimens and into neoadjuvant and adjuvant schedules for patients with early stage breast cancer, as well as looking at the biologic determinants of response and resistance to taxanes. This article will review developments in the use of taxanes in the adjuvant and neoadjuvant settings and it will review the information on possible molecular markers that may be useful in predicting tumor responsiveness to taxanes.

Antineoplastic Agents, Phytogenic↗

PubMed1997

Tc-99m LL-2 Fab' monoclonal antibody imaging in acquired immune deficiency syndrome-related lymphoma.

BACKGROUND: Both systemic and primary central nervous system (CNS) non-Hodgkin's lymphomas (NHL) occur in people with acquired immune deficiency syndrome (AIDS). The radiographic manifestations may be similar to other neoplasms and opportunistic infections that are also found frequently in AIDS. Furthermore, these diseases may coexist with NHL in the AIDS patient. METHODS: To evaluate the use of Tc-99m Lymphoscan (the Fab' fragment of the anti-CD-22 antibody LL-2; Immunomedics, Inc., Morris Plains, NJ) in patients with suspected AIDS lymphoma, we studied 7 patients with 35 sites of suspected disease. Six had CNS lesions suspicious for parenchymal brain lymphoma. Each patient underwent planar and single photon emission computed tomography imaging at 3-5 and 18-24 hours after administration of Lymphoscan. Scintigraphic results were compared with results of conventional diagnostic modalities. RESULTS: Overall, the sensitivity of Lymphoscan was 92% and the specificity was 86%. In brain lesions, there was 100% sensitivity and 100% specificity. Lymphoscan also had 100% sensitivity for sites of lymphomatous lymphadenopathy and for liver involvement. Although less specific in extracranial sites, Lymphoscan was correctly negative in sites of coexisting adenocarcinoma and pneumonia. Two patients had both parenchymal CNS and systemic lymphoma proven by biopsy. CONCLUSIONS: Lymphoscan appears to be a sensitive and specific method for diagnosing CNS lymphoma in AIDS patients. Although slightly less specific in extracranial sites, it may be helpful in differentiating lymphoma from other etiologies in these patients at risk for multiple neoplasms and opportunistic infections.

Adult↗

PubMed1997

Prognostic implications of cyclins (D1, E, A), cyclin-dependent kinases (CDK2, CDK4) and tumor-suppressor genes (pRB, p16INK4A) in childhood acute lymphoblastic leukemia.

Immunohistochemistry was used to analyze samples of 40 newly diagnosed childhood acute lymphoblastic leukemias (ALL) for their expression of cyclins (D1, E, A), cyclin-dependent kinases (cdk2, cdk4) and tumor-suppressor genes (pRb, p16INK4A), in order to discover whether or not the expression of these various proteins may be of prognostic relevance for the survival of children with ALL. Patients with ALL who were strongly positive for cyclin D1 had a lower probability of remaining in first continuous remission than ALL patients who were negative or weakly positive for this trait. There was also a significant correlation between expression of cyclin D1 and frequency of recurrence. For cyclin E and cyclin A, in contrast, there was no difference in the duration of relapse-free-intervals or the frequency of recurrence in patients. Children with cdk4-positive ALL had a lower probability of remaining in first continuous remission than children with cdk4-negative ALL. No prognostic relevance was found for cdk2. Patients with ALL who expressed pRb had a higher probability and patients who expressed p16 a lower probability of remaining in first continuous remission, but the results were not statistically significant. This investigation demonstrated that cyclin D1 and cdk4 were the most important prognostic factors for children with ALL, and that the combination of them showed the strongest prognostic relevance.

Adolescent↗

PubMed1997

Prognostic value of vascular endothelial growth factor and its receptor Flt-1 in squamous cell lung cancer.

Tumor specimens from 109 patients with previously untreated squamous cell lung carcinomas were analyzed immunohistologically for the expression of vascular endothelial growth factor (VEGF) and its receptor Flt-1. Our analysis attempted to determine whether these factors have additional prognostic value for the patients' survival. VEGF staining was seen in 59% and Flt-1 staining in 68% of the cases. No significant correlations were detected between VEGF or Flt-1 expression and stage or metastasis. Patients with VEGF-stained tumors had significantly lower survival times than patients with negative tumors. Expression of Flt-1 showed no significant correlation with survival. Combining VEGF and Flt-1 expressions did not improve the prognostic value. Multivariate analysis showed that metastasis and VEGF expression are significant and independent prognostic factors for the survival of patients with squamous cell lung carcinomas.

Adult↗

PubMed1997

Prognostic value of protein kinase C, proto-oncogene products and resistance-related proteins in newly diagnosed childhood acute lymphoblastic leukemia.

In this investigation, untreated non-B-type acute lymphoblastic leukemia (ALL) of 104 children was analyzed using immunocytochemistry for expression of protein kinase C, proto-oncogene products (Fos, Jun, Ras) and resistance-related proteins (topoisomerase II, P-glycoprotein, glutathione S-transferase-pi, metallothionein, dihydrofolate-reductase, thymidylate-synthase). The aim of the analysis was to find out whether combining those factors with the most important clinical prognostic factor (blast cell count) can improve the prognostic value (relapse-free interval). Univariate analysis shows that protein kinase D (PKC), Fos, P-glycoprotein (P-170) and glutathione S-transferase-pi (GST-pi) are significant prognostic factors independent of blast cell count (PBC) for the relapse-free intervals of children with ALL. The presence of the proteins Fos, PKC, P-170 and GST-pi was not independent within the patient population. The multivariate analysis showed that in combination with PBC and PKC, both P-170 and GST-pi have only limited prognostic influence. Combining the factors PKC, Fos and GST-pi as a categorical variable showed that this variable is a strong prognostic factor in addition to PBC.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1997

Prognostic value of basic fibroblast growth factor and its receptor (FGFR-1) in patients with non-small cell lung carcinomas.

Tumour specimens of 206 patients with untreated non-small cell lung carcinomas (NSCLC) were analysed immunohistochemically for the expression of the basic fibroblast growth factor (bFGF) and for its receptor (FGFR-1, Flg). Seventy of the tumours showed weak expression, 109 moderate and 27 high expression of bFGF. Thirty-eight tumours had low expression of FGFR-1, 116 had moderate and 52 cases high expression. Patients with high FGFR-1 expression had significantly shorter survival times than patients with weak or moderate expressions (P < 0.05), but there was no significant correlation between bFGF expression and patient survival. The results of the multivariate analysis demonstrated that FGFR-1 in the presence of stage is not an independent prognostic factor.

Carcinoma, Non-Small-Cell Lung↗

PubMed1997

Apoptotic index, Fas and bcl-2 in initial and relapsed childhood acute lymphoblastic leukaemia.

Seventy-two samples with initial and 23 samples with relapsed childhood acute lymphoblastic leukaemia (ALL) were investigated for apoptotic index (AI) and for Fas expression. AI was determined by DNA-fragmentation using deoxynucleotidyl terminal transferase and Fas expression by immunocytochemistry. bcl-2 mRNA expression was measured in 50 initial and 20 relapsed ALL. The patients were discriminated in groups with low and high AI, Fas-protein expression and bcl-2mRNA expression by the mean value. AI was higher in relapsed than in initial ALL. The mean survival was significantly higher in patients with low AI (p= 0.034). This was also true for the relapse-free interval, however, this result was borderline significant (p= 0.064). AI was directly correlated with expression of Fas and inversely correlated with bcl-2 mRNA expression. These results suggest that Fas and - with limitations - bcl-2 may influence the apoptotic process in childhood ALL and that enhanced apoptotic activity predicts poor prognosis.

Journal Article↗

PubMed1997

Cyclin A is associated with an unfavourable outcome in patients with non-small-cell lung carcinomas.

Specimens of formalin-fixed, paraffin-embedded non-small-cell lung carcinomas (NSCLCs; n = 187) were analysed immunohistochemically for expression of cyclin A. The analysis was intended to determine whether cyclin A has additional prognostic value for predicting patients' survival and drug response. Of the 187 NSCLCs, 141 cases (75%) showed expression of cyclin A. Patients with cyclin A-positive carcinomas had significantly shorter median survival times than patients with cyclin A-negative carcinomas (79 vs 129 weeks, P = 0.045). Similar results were obtained with more homogeneous groups of patients: patients with only T3 tumours, patients with epidermoid carcinomas and patients with lymph node involvement. The clinical parameters (age, stage, histology, extent of tumour size, lymph node involvement) had no influence on expression of cyclin A. A direct correlation between cyclin A and the proportion of S-phase cells (P = 0.08) and an inverse relationship between cyclin A and the proportion of G0/G1-phase cells (P = 0.04) were found. Furthermore, a significant correlation between the expression of cyclin A and the response of NSCLC to doxorubicin in vitro was detected (P = 0.026).

Adenocarcinoma↗

PubMed1997

Messenger RNA expression of resistance proteins and related factors in human ovarian carcinoma cell lines resistant to doxorubicin, taxol and cisplatin.

Doxorubicin- (OAW-dox, SK-OV-dox), taxol- (OAW-tax, SK-OV-tax) and cisplatin- (SK-OV-cis) resistant cells derived from the parental OAW-42 and SK-OV-3 cell lines were established. OAW-42 sublines showed high resistance, the SK-OV-3 sublines only low resistance. OAW-42 sublines showed a cross-resistance profile typical of multidrug resistance (MDR). The sublines of SK-OV-3 showed a cross-resistance profile different from the OAW-42 sublines. The mRNA expression of several resistance proteins and related factors was analyzed. An overexpression of P-glycoprotein 170 (P-170), glutathione-S-transferase-pi (GST-pi), thymidylate synthase (TS), glutathione peroxidase (GP) and c-jun was found in OAW-dox and OAW-tax cells. Additionally, OAW-tax cells expressed a higher mRNA level of protein kinase Cbeta2. DNA analysis revealed a 2-fold gene amplification of P-170, whereas the genes for GST-pi, TS and GP were not amplified. SK-OV-dox and SK-OV-tax cells showed a decreased level of histone 3 (H3) and TS mRNA. This shows that the sublines of OAW-42 developed resistance by co-expression of several resistance-related proteins and proto-oncogenes whereas the sublines of SK-OV-3 expressed resistance by decreased expression of the proliferation-dependent proteins H3 and TS.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1997

Green tea catechins (EGCG and EGC) have modulating effects on the activity of doxorubicin in drug-resistant cell lines.

The chemopreventive effect of polyphenols from green tea [e.g. (-)-epigallocatechin gallate (EGCG) and (-)-epigallocatechin (EGC)] against cancer has been demonstrated in several studies. The aim of this investigation was to prove whether these compounds modulate the activity of antineoplastic drugs. Therefore, the influence of EGCG and EGC was tested on doxorubicin-resistant murine sarcoma (S180-dox) and human colon carcinoma (SW620-dox) cell lines. Both substances showed a sensitizing effect on the cell lines if they had been treated with doxorubicin. These results suggest that protein kinase C may be inhibited by EGCG and EGC, and this may lead to a reduced expression of some drug resistance related proteins.

Animals↗

PubMed1997

Deoxycytidine kinase mRNA expression in childhood acute lymphoblastic leukemia.

Initial and relapsed childhood acute lymphoblastic leukemias (ALL) were investigated for mutations and expression of deoxycytidine kinase (dCK). dCK mediating toxicity of 1-beta-D-arabinofuranosylcytosine was analyzed semiquantitatively by RT-PCR and by single-strand conformation polymorphism. We found that patients with initial ALL experienced more frequently a relapse if dCK expression was low or absent. No mutations were found in initial and relapsed ALL.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1997

Expression of lung resistance-related protein (LRP) in initial and relapsed childhood acute lymphoblastic leukemia.

Thirty-eight children with initial and 25 children with relapsed lymphoblastic leukemia (ALL) were analyzed for the expression of LRP (lung resistance protein or p110 major vault protein) using immunocytochemistry. LRP expression was found in 18 of 38 (47%) children with initial ALL and in 17 of 25 (68%) children with relapsed ALL. Children with initial ALL and without LRP expression had significantly longer relapse-free intervals than patients with LRP expression.

Child↗

PubMed1997

Expression of lung resistance-related protein (LRP) in non-small cell lung carcinomas of smokers and non-smokers and its predictive value for doxorubicin resistance.

Immunohistochemical methods were used to determine the expression of the lung resistance-related protein (LRP) in 87 cases of untreated non-small cell lung carcinoma. LRP expression was detected in 39 patients (45%). A significant correlation between LRP expression and tumor resistance to doxorubicin was found (p=0.03, Fisher's exact test). An inter-relationship between LRP expression and gender, age, stage, lymph node status and survival times was not observed. Furthermore, a relationship between LRP expression and proliferation (cell cycle phases, take rate of lung tumors in nude mice and cyclin A expression) was not detectable. However, a correlation of borderline significance was noticed between LRP expression and the patients' smoking habits. Carcinomas in heavy smokers (more than 30 cigarettes daily) were more frequently LRP-positive than carcinomas found in non-smokers (p=0.09, Fisher's exact test).

Animals↗

PubMed1996

Expression of resistance-related proteins in tumoral and peritumoral tissues of patients with lung cancer.

Twenty tumoral and peritumoral tissues from patients with lung cancer were analyzed immunohistochemically for the drug resistance-related proteins P-glycoprotein (P-170), topoisomerase II (Topo-II), glutathione S-transferase-pi (GST-pi), metallothionein (MT), heat shock protein-70 (HSP-70) and the putative regulators of resistance (ErbB1, Fos and Jun). Protein expression of Topo-II, GST-pi, MT, HSP-70, ErbB1, Fos and Jun was elevated in tumor tissue in comparison to normal tissue. The different expression of the proteins between tumoral and normal tissues was statistically significant for Topo-II (P = 0.05), MT (P = 0.03), and HSP-70 (P = 0.01), whereas ErbB1 showed a borderline significance. The expression of the proteins was frequently increased in smokers in comparison to non-smokers. In general, the increase of the proteins of smokers corresponded in tumoral and non-tumoral tissue. Different expression was only found with MT and HSP-70 which were higher in tissues of smokers.

ATP Binding Cassette Transporter, Subfamily B, Mem↗