Biomedical subjects

M Volm

Publications and source records attributed to M Volm.

At least 253 records · Page 14Linked to original sources

PubMedDate not supplied

Modulation of P-glycoprotein-mediated multidrug resistance by monoclonal antibodies, immunotoxins or antisense oligodeoxynucleotides in kidney carcinoma and normal kidney cells.

In the present investigation we show that both monoclonal antibodies against P-170 (265/F4, MRK 16, and HYB 612) and 265/F4-ricin alpha-chain immunotoxin are useful tools for the eradication of kidney carcinoma and normal kidney primary cell cultures with high P-170 expression, whereas kidney tumor and normal kidney cell lines with low amounts of P-170 are less affected. Furthermore, we found that the expression of P-170 in both kidney tumor and normal kidney cell cultures with high amounts of P-170 was inhibited by antisense oligodeoxynucleotides complementary to base pairs -9 to +6 of the MDR1 gene. These data indicate that these approaches for the eradication of P-170 expressing multidrug-resistant cells are not limited to tumors but also affect P-170 expressing normal cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMedDate not supplied

Intrinsic overexpression of two different mechanisms of resistance to chemotherapy (P-glycoprotein and GST-pi) in human endometrial carcinoma.

Endometrial carcinoma is considered a tumor which does not respond well to chemotherapeutic treatment. Among the various mechanisms of resistance to chemotherapy which are under investigation, two of them (multidrug resistance, mediated by P-glycoprotein, and glutathione-S-transferase-pi [GST-pi] overexpression) are of great interest for gynecologic oncologists, because they involve several drugs commonly used in practice, among which Adriamycin and cisplatin are probably the most important ones. We have studied 23 human endometrial carcinomas of different histological varieties and 3 normal endometrial samples for the overexpression of both P-glycoprotein and GST-pi by means of immunohistochemistry. Both resistance markers were detectable in all tumor samples, and in normal endometrial tissue as well. The concomitant intrinsic overexpression of these two resistance mechanisms may in part explain why these tumors tend to be extremely resistant to chemotherapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMedDate not supplied

Radioactive labelling of lipids in rat neurosarcoma by intravenous injection of [1-14C]-octadecenol.

Radioactivity from cis-9-[1-14C]octadecenol, injected intravenously into rats bearing neurosarcoma, is incorporated to a significantly greater extent into tumor than into muscle. In the lipids of both tissues, radioactivity is incorporated predominantly into the acyl moieties, rather than into the alkyl or alk-1-enyl moieties, of diradylglycerophosphocholines, diradylglycerophosphoethanolamines, and triradylglycerols.

Animals↗

PubMedDate not supplied

Specific positional distribution of acyl moieties in phospholipids is not generally deleted in neoplastic cells.

The distribution of acyl moieties at sn-1 and sn-2 positions of cholinphosphoglycerides (CPG) and ethanolaminephosphoglycerides (EPG) has been determined for neurosarcoma, sarcoma 180 and leukemia L 1210. In all the three samples, the positional distribution of acyl moieties in the two major classes of phospholipids is found to be similar to that in cellular phospholipids of most mammalian tissues. The saturated acyl moieties are located predominantly at sn-1 and polyunsaturated acyl moieties at sn-2, whereas the monounsaturated acyl moieties are randomly distributed between these two positions. Apparently, a disruption of specific positioning of acyl moieties in phospholipids, which hitherto has been considered to be a general metabolic deletion in neoplasia, does not exist in an all neoplastic cells.

Acylation↗

PubMedDate not supplied

Relationship of urokinase and urokinase receptor in non-small cell lung cancer to proliferation, angiogenesis, metastasis and patient survival.

The purpose of the analysis was to ascertain whether the expression of components of the plasminogen activation system possesses an association with several biological parameters. The expression of urokinase (uPA) and urokinase receptor (uPAR) was analyzed in 137 non-small cell lung carcinomas by immunohistochemistry. No relationship could be observed between the proliferative activity of the carcinomas measured by flow cytometry and the expressions of uPA and uPAR. In addition, there was no association of the expressions of uPA or uPAR and vessel density (angiogenesis), neither any significant correlation between the expressions of uPA or uPAR and metastasis. The median survival was shorter for patients with uPA positive carcinomas than for those with uPA negative tumors (60 vs. 111 weeks; p=0.018). The relative risk estimate for patients with uPA positive tumors was increased by a factor of 1.8. In contrast, the expression of uPAR showed no significant correlation with overall survival.

Adult↗

PubMedDate not supplied

Prognostic relevance of c-Myc and caspase-3 for patients with non-small cell lung cancer.

This analysis attempted to ascertain whether combining the expression of c-Myc and caspase-3 can improve the available prognostic information for patients with non-small cell lung carcinomas. To this purpose, the expression of c-Myc and caspase-3 was determined in 128 cases of non-small cell lung carcinoma. The median survival time for patients with c-Myc-negative carcinomas was 89 weeks; it was only 43 weeks for patients with c-Myc-positive tumors (p=0.03). The estimated increased relative risk for patients with c-Myc-positive tumors was 1.6. The median survival time for patients with caspase-3-negative carcinomas was 41 weeks while patients with caspase-3-positive carcinomas survived for 79 weeks (p=0.06). The relative risk for patients with caspase-3-negative tumors was 1.5. A significant inverse relationship between the expression of c-Myc and caspase-3 was observed (p=0.04). To determine whether the combination of c-Myc and caspase-3 expression has a higher prognostic significance, patients were grouped based on their expressions of both variables. Patients with c-Myc-negative and caspase-3-positive tumors had the most favorable prognosis (102 weeks) while c-Myc-positive and caspase-3-negative carcinomas had the most unfavorable prognosis (22 weeks; p=0.01).

Adult↗

PubMedDate not supplied

Protein expression profile of newly diagnosed acute lymphoblastic leukemia in children developing relapses.

The purpose of this investigation was to evaluate the expression profile of proteins involved in children with newly diagnosed acute lymphoblastic leukemia (ALL) children who are developing relapses. For this reason, the expressions of 10 proteins including proto-oncogene and tumor suppressor gene products, proliferative factors and resistance parameters in 104 initial cases of childhood ALL were analyzed and the proteins correlated with ALL patients who experienced relapses. Applying immunocytochemical assays, we found that 4 out of the 10 parameters revealed a relationship to developing relapses (Fisher's exact tests). These were the oncogene product Fos (p=0.002), the drug resistance proteins glutathione S-transferase (p=0.008) and P-glycoprotein (P-pg/MDR1) (p=0.07) and protein kinase C (p=0.01). By means of hierarchical cluster analysis, we were able to show that the patients could be separated according to their protein expression profile into clusters consisting of patients whose ALL relapsed later and of patients who did not show relapses in the future.

Child↗

PubMedDate not supplied

The implications of proliferation and apoptosis for lung cancer metastasis.

The occurrence of metastatic spread depends on many factors both the condition of the patient and the properties of the tumor. In this investigation the association between proliferation and apoptosis and the incidence of lymph node involvement of patients with non-small cell lung carcinomas was analysed (n=215 patients). In order to analyse the relationship between lymph node metastasis and proliferative activity of the carcinomas, the distribution of cell cycle phases (flow cytometry), the expression of PCNA and cyclin A (immunohistochemistry) was determined. Fas, Fas-ligand, caspase-3 and Bcl-2 were determined by immunohistochemistry. In this retrospective analysis no association between proliferative activity of the tumors and lymph node status was found. In contrast, there existed a correlation between the apoptotic factors and lymph node metastasis. Higher expression of the pro-apoptic factors Fas, Fas-ligand and caspase-3 correlated with a lower incidence of lymph node involvement (Fas-ligand, p=0.004; caspase-3, p=0.007). The trend of an inverse correlation between the anti-apoptotic factor Bcl-2 and metastasis fits well into the present knowledge about the function of the bcl-2 gene. The results obtained from all the patients could be confirmed in patients with squamous cell lung carcinomas.

Adenocarcinoma↗

PubMedDate not supplied

Analysis of cyclin D1 in de novo and relapsed childhood acute lymphoblastic leukemia.

In a retrospective analysis we investigated 59 children with de novo acute lymphoblastic leukemia (ALL) and 28 patients with relapsed ALL for the expression of cyclin D1 using RT-PCR. In addition, the relationships of cyclin D1 to the retinoblastoma tumor suppressor gene and the Ki-67-expression were analyzed. Cyclin D1-mRNA was detectable in 42 out of 58 patients with de novo ALL (72%) and in 26 out of 28 relapsed patients (93%). The blast cells of the relapsed patients contained significantly higher levels of cyclin D1-mRNA compared with the de novo group (p = 0.0007). The cyclin D1 expression was independent of the proliferative activity of the cells and inversely correlated to the expression of the retinoblastoma tumor suppressor gene (r = -0.27, p = 0.03). Prognostic considerations using Kaplan Meier estimates for the relapse-free interval showed that patients with high cyclin D1- mRNA levels had a poorer prognosis (p = 0.046).

Adolescent↗

PubMedDate not supplied

PD-ECGF, bFGF, and VEGF expression in non-small cell lung carcinomas and their association with lymph node metastasis.

The angiogenic factors PD-ECGF, bFGF and VEGF were determined immunohistochemically in 168 non-small cell lung carcinomas to investigate whether the expression of these parameters is correlated with lymph node metastasis of patients. The expressions of the above mentioned factors was indeed associated with lymph node metastasis, but the results were not statistically significant. However, a combination of the factors PD-ECGF, bFGF and VEGF significantly improved the prognostic information. The number of tumors with lymph node involvement increased with the number of angiogenic factors. Only 43% of the patients had-lymph node involvement when all factors were negative whereas 77% showed metastasis when all factors were positive (one factor positive: 53%, two factors positive: 68). This result is statistically significant (p = 0.002, test for trend).

Adenocarcinoma↗

PubMedDate not supplied

Angiogenesis and cigarette smoking in squamous cell lung carcinomas: an immunohistochemical study of 28 cases.

Angiogenesis in tumors is influenced by several factors which in turn are associated with chemoresistance or radioresistance. Moreover, the tumors of smokers are known to be relatively resistant to chemotherapy. This investigation attempts to determine whether or not a relationship exists between cigarette smoking and angiogenesis in lung cancer. Tumor samples from 14 non-smokers and 14 heavy cigarette smokers were selected for this study. The populations were matched for age, sex and tumor stage. Resistance to doxorubicin, microvessel density, the expression of vascular endothelial growth factor (VEGF) and thrombospondin (TSP) were analyzed in both populations. Tumors of smokers were more frequently resistant to doxorubicin in vitro, had lower vessel counts and a reduced expression of VEGF compared to tumors of nonsmokers. In contrast, TSP was significantly increased in the tumors of smokers. These data show that angiogenesis in lung tumors is linked to a patient's smoking habits.

Carcinoma, Squamous Cell↗

PubMedDate not supplied

Inverse correlation between apoptotic (Fas ligand, caspase-3) and angiogenic factors (VEGF, microvessel density) in squamous cell lung carcinomas.

In order to explore whether apoptosis is associated with angiogenesis in lung cancer, immunohistochemistry was employed to determine the pro-apoptotic factors Fas ligand (FasL) and caspase-3 (Cas-3) in 70 squamous cell lung carcinomas. Furthermore, the vascular endothelial growth factor (VEGF) and the microvessel density (MVD) were analyzed. The comparison between MVD and the pro-apoptotic factors demonstrated that the apoptotic factors are inversely related to MVD (Cas-3: p = 0.011, FasL: not significant). In order to confirm this result, FasL and Cas-3 were also compared with the expression of VEGF. Again, an inverse correlation between VEGF and the pro-apoptotic factors was found (Cas-3: p = 0.019, FasL: p = 0.008). The inverse correlation between angiogenesis and apoptosis may be explained by the activation of pro-apoptotic and anti-angiogenic factors caused by hypoxia.

Adult↗

PubMedDate not supplied

Xenotransplantability of human squamous cell lung cancer in nude mice is not affected by angiogenic factors.

Sixty-two human squamous cell lung carcinomas were analyzed for expression of various angiogenic growth factors and their receptors using immunohistochemistry. The data were correlated with xenotransplantability of these tumors in nude mice. None of the factors investigated did show an association with xenotransplantability. However, there was a trend that specimens lacking VEGF165 were established as xenografts at a higher incidence (52%) than those expressing VEGF165 (39%).

Adult↗

PubMedDate not supplied

Proliferation and apoptosis in newly diagnosed and relapsed childhood acute lymphoblastic leukemia.

Children with acute lymphoblastic leukemia (ALL) who are treated with chemotherapy have remissions in more than 95% of the cases. However, 25% of the patients relapse and show resistance to chemotherapy. In this investigation we compared 25 newly diagnosed and 25 relapsed cases of ALL with respect to proliferation and apoptosis. Using immunocytochemistry and Western blotting, we determined the expression of cyclin A protein as a measure of the proliferative activity and the pro-apoptotic and anti-apoptotic factors, Fas, Fas ligand, caspase-3 and Bcl-2. Cyclin A expression was observed in 32% of the newly diagnosed cases and in 52% of the relapsed cases. Expression of Fas was found in 58% of the newly diagnosed and in only 27% of the relapsed samples. Of the newly diagnosed ALL, 88% expressed the Fas ligand while such expression was observed in 54% of the relapsed ALL. Sixty-four percent of the newly diagnosed cases expressed caspase-3 while only 48% of the relapsed samples did so. The anti-apoptotic factor, Bcl-2, was more frequently expressed in relapsed than in newly diagnosed cases. These data indicate that relapsed ALL more frequently exhibits high proliferative activity and reduced apoptosis than does newly diagnosed ALL.

Apoptosis↗

PubMedDate not supplied

Glucose-related protein (GRP78) and its relationship to the drug-resistance proteins P170, GST-pi, LRP56 and angiogenesis in non-small cell lung carcinomas.

Several studies have documented that induction of the glucose-related protein (GRP78) is associated with the development of drug-resistance to antitumor drugs. However, nothing has been reported concerning GRP78 in human lung tumors and its relationship to several resistance proteins and angiogenesis. Therefore, this study analyzed the expression of GRP78 in a series of 62 consecutive lung cancer patients and examined whether or not a relationship exists between GRP78, several resistance proteins and microvessel density (MVD). Secondary, it evaluated the relationship of GRP78, LRP56 and GST-pi in cancer cell lines under hypoxic conditions and in sensitive and resistant cell lines. We determined that a relationship exists between GRP78 and the resistance proteins P170, LRP56 and GST-pi in human lung cancer. Furthermore, we observed an up-regulation of GRP78 in the resistant cell lines LUTC-ML54, OAW-Dox and OAW-Tax, but not in sensitive cell lines. Abnormal vascularization of malignant tumors is associated with the development of hypoxic regions. In hypoxic regions, several proteins, including drug resistance proteins, are expressed in greater quantities. Our study detected an inverse correlation between GRP78 and MVD. Carcinomas with low MVD exhibited a higher expression of GRP78. Furthermore, protein expression of GRP78, GST-pi and LRP56 increased in the cell lines A-549, RPMI-2650 and SC-MES-1 under hypoxic conditions. These observations suggest that hypoxia, tumor vascularization and the simultaneous expression of many resistance-related proteins, including GRP78, may play an important role in drug response and therapeutic effectiveness.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMedDate not supplied

Expression of Fas ligand in newly diagnosed childhood acute lymphoblastic leukemia.

Immunocytochemistry was used to analyze the expression of the Fas ligand (FasL) in sixty-four children with newly diagnosed acute lymphoblastic leukemia (ALL). FasL expression was detected in 55 of 64 children (86%). Children with newly diagnosed ALL and FasL expression exhibited longer relapse-free and overall survival times under chemotherapy than did patients who did not express the Fas ligand. These data suggest that Fas/FasL mediated signaling may play a general role in the cytotoxicity of anticancer drugs.

Blotting, Western↗

PubMedDate not supplied

Relationship between the expression of caspase-3 and the clinical outcome of patients with non-small cell lung cancer.

This study examined whether a relationship exists between the expression of caspase-3 in 135 non-small cell lung carcinomas and clinical outcome. Immunohistochemistry and Western blot analyses were used to analyze the expression of caspase-3 in solid tumors and cell lines. A significant correlation was observed between the expression of caspase-3, survival and metastasis. Caspase-3 expression correlated with a lower incidence of lymph node involvement (p = 0.0007). The median survival was longer for patients with caspase-3 positive carcinomas than for those with caspase-3-negative tumors (41 vs 87 weeks, p = 0.038).

Adult↗

PubMedDate not supplied

Hypoxia-inducible factor (HIF-1) and its relationship to apoptosis and proliferation in lung cancer.

Hypoxia-inducible factor 1 (HIF-1) plays an important role in the pleiotropic response observed under hypoxia. In this study we examined whether a relationship exists between HIF-1 proteins and proliferation and apoptosis in lung cancer. To this purpose, we used immunohistochemistry to analyze HIF-1 alpha and HIF-1 beta in formalin-fixed, paraffin-embedded, non-small cell lung carcinomas (n = 96) and compared the HIF expression with cyclin A protein expression, cell cycle phases, the apoptotic index and the expression of caspase 3, Fas and Fas ligand. Additionally, we examined whether HIF-1 determinations can improve the prognostic information concerning a patient's overall survival. A relationship between HIF-1 alpha or HIF-1 beta and proliferation could not be observed. However, a significant correlation between HIF-1 expression, apoptosis and the pro-apoptotic factors caspase-3, Fas, and Fas ligand could be detected. Patients with HIF-positive carcinomas had significantly longer median survival times than patients with HIF-negative carcinomas (HIF-1 alpha: 191 vs. 60 weeks; P = 0.05; HIF-1 beta: 111 vs. 41 weeks; P = 0.003). Multivariate analyses demonstrated that the presence of HIF-1 at a given stage or extent of lymph node involvement is an independent prognostic factor for the survival of patients with non-small cell lung carcinomas.

Apoptosis↗