Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Keywords: CANCER ; GROWTH ; SURVIVAL ; tumor ; COMBINATION ; Germany ; human ; LUNG ; THERAPY ; DIAGNOSIS ; DISEASE ; DRUG ; TUMORS ; LINES ; PATIENT ; colon ; CELL-LINES ; treatment ; TRIAL ; EXPERIENCE ; NUMBER ; metastases ; CELL-LINE ; chemotherapy ; leukemia ; LINE ; MELANOMA ; DERIVATIVES ; COLON-CANCER ; CANCER-PATIENTS ; SAFETY ; CANCER PATIENTS ; RANDOMIZED TRIAL ; cell lines ; DACARBAZINE ; RANDOMIZED-TRIAL ; FOTEMUSTINE ; INTERLEUKIN-2 ; CYTOTOXICITY ; STANDARD ; ONCOLOGY ; colon cancer ; TUMOR-GROWTH ; HUMAN CANCER ; IV ; CHINESE ; uveal melanoma ; MALARIA ; antimalarial ; artemisinin ; artesunate ; DIHYDROARTEMISININ ; HOLOTRANSFERRIN ; QINGHAOSU ; TOLERABILITY ; uvea
    Abstract: Artesunate (ART) is a derivative of artemisinin, the active principle of the Chinese herb Artemisia annua L. Artesunate is approved for the treatment of multidrug-resistant malaria and has an excellent safety profile. It has been shown that Artesunate, apart from its anti-malarial activity, has cytotoxic effects on a number of human cancer cell lines, including leukemia, colon cancer and melanoma. We report on the first long-term treatment of two cancer patients with ART in combination with standard chemotherapy. These patients with metastatic uveal melanoma were treated on a compassionate-use basis, after standard chemotherapy alone was ineffective in stopping tumor growth. The therapy-regimen was well tolerated with no additional side effects other than those caused by standard chemotherapy alone. One patient experienced a temporary response after the addition of ART to Fotemustine while the disease was progressing under therapy with Fotemustine alone. The second patient first experienced a stabilization of the disease after the addition of ART to Dacarbazine, followed by objective regressions of splenic and lung metastases. This patient is still alive 47 months after first diagnosis of stage IV uveal melanoma, a situation with a median survival of 2-5 months. Despite the small number of treated patients, ART might be a promising adjuvant drug for the treatment of melanoma and possibly other tumors in combination with standard chemotherapy. Its good tolerability and lack of serious side effects will facilitate prospective randomized trials in the near future
    Type of Publication: Journal article published
    PubMed ID: 16273263
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Keywords: EXPRESSION ; GROWTH ; proliferation ; carcinoma ; Germany ; INHIBITION ; PATHWAY ; DISTINCT ; GENE ; GENES ; microarray ; PROTEIN ; DIFFERENTIATION ; TISSUE ; TUMORS ; SKIN ; IN-SITU ; AMPLIFICATION ; COPY NUMBER ; immunohistochemistry ; NUMBER ; MUTATIONS ; ONCOGENE ; HUMAN HOMOLOG ; HEAD ; PREVALENCE ; PRECURSORS ; EFFECTOR ; basal cell carcinoma ; N-MYC ; CELL CARCINOMA ; SUBSET ; fluorescence in situ hybridisation ; LOCUS ; tissue microarray ; NMYC ; HUMAN NEUROBLASTOMA ; SPECIMENS
    Abstract: Formation of basal cell carcinoma (BCC) has been linked to deregulation in the sonic hedgehogh (Shh) signalling pathway. Though mutations of the genes, PTCHI and SMO, are known to be involved in aberrant Shh signalling, the distinct downstream effectors of these genes are poorly described. Studies have indicated that the NMYC oncogene is a potential Shh downstream effector. To assess the expression of Nmyc protein and gene copy numbers of the NMYC gene locus in a representative BCC tumour collection, immunohistochemistry (IHC) and fluorescence in situ hybridisation (FISH) were performed on 273 BCC specimens of different growth patterns and anatomic localisations on tissue microarray (TMA) sections. High Nmyc protein expression was detected in 72.7% (160/220) of all BCC specimens. Strong Nmyc immunopositivity was more frequently found in infiltrative BCCs compared to nodular/superficial BCCs (p=0.005), and in BCCs of the head compared to BCCs of other anatomic localisations (p=0.021). The prevalence of NMYC copy number gains was 17.5% (37/211), including three tumours with nodular differentiation that exhibited a distinct high-level amplification of the NMYC locus. These data indicate that high expression of the Shh downstream mediator, Nmyc, is a frequent event in BCC, predominantly in more aggressive subtypes. Although the NMYC copy number gain found in a subset of cases might contribute to this aberrant Nmyc protein expression by a gene dosage effect, our data suggests that Nmyc protein can also be induced by aberrant Shh signalling, acting as an effector molecule of the Shh pathway. Novel systemic anti-sense NMYC inhibition strategies could be a promising option for therapy-refractory BCC
    Type of Publication: Journal article published
    PubMed ID: 16596176
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    Keywords: APOPTOSIS ; CELLS ; carcinoma ; Germany ; LUNG ; THERAPY ; TOOL ; TIME ; resistance ; INITIATION ; pancreas ; RE ; pancreatic ; rectum ; viability ; MOLECULAR ANALYSIS ; tumour specimen ; surgical resection ; rectum carcinoma
    Abstract: Surgical resected tumours are often stored for hours in the clinic upon transfer to the bench leading to apoptosis of tumour cells making them no longer suitable for molecular analysis and diagnostic procedures. The way out of this problem may be a new oxygen-enriched solution (OES). We tested this agent using surgical resections of carcinomas of lung, rectum and pancreas. Immediately after resection, one part of each individual tumour was stored in PBS and the other part in OES, and the content of viable or dead cells was determined by trypan blue exclusion and MTT-assay. We found that OES keeps tumour cells up to 3 days and longer more viable than PBS and reduces the percentage of dead cells without inducing therapy resistance and affecting the outcome of experimental procedures. Thus, storing freshly resected tumours in OES may save time for tumour transfer and initiation of experiments
    Type of Publication: Journal article published
    PubMed ID: 16596178
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    Keywords: CANCER ; CELLS ; SURVIVAL ; carcinoma ; CELL ; LUNG ; INFORMATION ; lung cancer ; LUNG-CANCER ; GENE ; PROTEIN ; TISSUE ; PATIENT ; MACROPHAGES ; MARKER ; prognosis ; CONTRAST ; LYMPH-NODES ; STAGE ; PROGRESSION ; HIGH-RISK ; LOCALIZATION ; HEAD ; HIGH-LEVEL ; non-small cell lung cancer ; CATHEPSIN-B ; STEFIN-A ; TUMOR TISSUE ; LEVEL ; IMMUNOHISTOCHEMICAL ANALYSIS ; NSCLC ; CYSTEINE PROTEASE ; RELEVANCE ; macrophage ; PREDICTOR ; inflammatory cells ; biological markers ; cystatin ; cathepsin ; CYSTEINE PROTEINASE-INHIBITOR ; ENDOGENOUS INHIBITORS ; PROTEASE INHIBITORS ; stefin
    Abstract: Cystatins regulate tumour-associated cysteine proteases, however, their role in tumour progression is not clear yet. To assess their relevance in the progression of nonsmall cell lung cancer (NSCLC) the protein level, cysteine protease activity (CPI) and localization of type I (stefins A and B) and type H (C, E/M and F) cystatins were defined in tumours and control lung counterparts from 165 patients. The medians of CPI activity, stefins A and B were significantly greater in tumour than in lung tissue (2.1-fold, 1.7-fold, 1.2-fold, respectively, all p 〈 0.001). The median levels of cystatin C and cystatin E/M were lower in tumour tissue (0.9-fold, p=0.06; 0.6-fold, p 〈 0.01). In all the samples the levels of cystatin F were below the detection limit. Immunohistochemical analysis revealed the presence of all cystatins in tumour cells and infiltrated inflammatory cells such as macrophages and neutrophils. In univariate survival analysis patients with high levels of stefin A, stefin B and CPI activity exhibited a better survival probability (p=0.05, p=0.05, p 〈 0.01, respectively). In contrast, cystatins C and E/M provided no prognostic information. In multivariate analysis the most powerful predictor of survival was the pTNM stage (p 〈 0.0001; RR 3.5), followed by stefin A, stefin B and CPI activity (all p=0.03; RR 1.5). Our results suggest that only stefins A and B, i.e. type I cystatins, are up-regulated in lung tumours and thus able to counteract harmful tumour-associated proteolytic activity. As biological markers they may add independent prognostic information for better assessment of low- and high-risk patients with NSCLC
    Type of Publication: Journal article published
    PubMed ID: 16969475
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    Keywords: ADHESION, ADHESION MOLECULE, BREAST, breast cancer, BREAST-CANCER, CANCER, CANCERS, carcinoma, CARCI
    Abstract: The L1 adhesion molecule (L1-CAM) is associated with impaired prognosis in many carcinomas. However, limited information about its expression in breast cancer tissue is available. Therefore, we carried out an analysis on L1 expression in primary breast cancers using a combination of Western blot, DNA-microarray analysis and immunohistochemistry. We observed L1 protein and mRNA overexpression in 14-15% of the carcinomas and this was confirmed by immunohistochemical staining. High L1 expression was associated with nodal involvement, high grading, human epidermal growth receptor 2 (Her-2), plasminogen activator inhibitor 1 (PAI-1) and vascular endothelial growth factor (VEGF) expression and a negative estrogen receptor (ER) status, but not with neuroendocrine markers. Moreover, patients with tumors showing high L1-CAM expression had a shorter disease-free and overall survival. Given the emerging functional role of L1 in promoting tumor cell migration, invasion, tumor growth and metastasis, our results suggest that L1 may have this function in breast cancer as well
    Type of Publication: Journal article published
    PubMed ID: 19787228
    Signatur Availability
    BibTip Others were also interested in ...
  • 6
    Keywords: CELLS ; INHIBITION ; MONOCLONAL-ANTIBODY ; PROSTATE-CANCER ; ACUTE LYMPHOBLASTIC-LEUKEMIA ; tumor-antigen ; PEANUT AGGLUTININ ; Thomsen-Friedenreich antigen ; TN-EPITOPES ; TF ANTIGEN
    Abstract: CD176 (Thomsen-Friedenreich antigen) is a tumor-associated carbohydrate structure. CD176 is expressed at the surface of human leukemic cells but is almost absent in normal and benign adult human tissues. Therefore, CD176 could be a promising target for antitumor immunotherapy. In the present study, pre-immunization with asialoglycophorin A (containing the CD176 oligosaccharide chains) was able to significantly improve the survival time of mice carrying CD176+ leukemia as compared to the control mice without the immunization. Furthermore, the passive transfer of CD176 antiserum which reacted only with the tumor-associated CD176 in cancer cells, was able to effectively prolong the survival time of CD176+ leukemia mice. In particular, the CD176 antiserum treatment could inhibit the growth and spreading of CD176+ leukemic cells in bone marrow, spleen, liver, and lung as evidenced by histopathological examination. CD176 antiserum could induce the apoptosis of CD176+ leukemic cells in vivo in a manner as previously observed in vitro. The data provided strong evidence that both CD176 antigen-based active immunotherapy and CD176 antibody-based passive immunotherapy lead to a therapeutic response in CD176+ leukemia mice. Therefore, both CD176 vaccine and CD176 antibody drug may be beneficial for the treatment of CD176+ leukemia patients.
    Type of Publication: Journal article published
    PubMed ID: 23900643
    Signatur Availability
    BibTip Others were also interested in ...
  • 7
    Keywords: EXPRESSION ; MESSENGER-RNA ; CELL-LINES ; VARIANTS ; TUMOR PROGRESSION ; CARCINOMAS ; PROTOONCOGENE ; receptor tyrosine kinase ; TUMORIGENIC ACTIVITIES
    Abstract: The proto-oncogene recepteur d'origine nantais (RON, MST1R) and its alternatively spliced variants are involved in various tumor biological processes, such as cell motility, adhesion, proliferation, apoptosis and epithelial-to-mesenchymal transition (EMT). RON overexpression and the occurrence of specific alternatively spliced RON isoforms have been detected in ovarian cancer. In the present study, we evaluated the role and regulation of cancer-related RON splicing isoforms in primary ovarian cancer. Expression of RON variants (RONDelta165, RONDelta160) was determined in 45 primary ovarian cancer and 4 physiological ovarian tissue specimens by RT-PCR and western blot analysis. The results were correlated to clinicopathological parameters. Additionally, expression of splicing factors with known involvement in RON alternative splicing regulation was examined. Increased RON levels were detected in all tumor samples (p=0.001) without differences between the primary tumors and metastases. Alternative RON variants were present in the majority of tumor samples (39 of 45; 86.67%). Potential RONDelta165 occurred more often (82.22%) than potential RONDelta160 or RONDelta155 (24.40%). Several significant correlations of RON and splicing factor expression [e.g. ASF/SFRS1 (p=0.035)] were detected. Correlations of RON expression to clinicopathological parameters were not observed. Significant splicing factor interactions (e.g. SRp55/SRp75: p〈0.001) were observed in tumor samples with alternative RON splicing. Our data demonstrated upregulated RON isoform expression and significant changes in splicing factor expression in primary ovarian cancer. These findings account for an essential regulatory interplay of splicing factor-driven alterations in the RON alternative splicing pattern with subsequent tumor biological consequences in ovarian cancer.
    Type of Publication: Journal article published
    PubMed ID: 25997828
    Signatur Availability
    BibTip Others were also interested in ...
  • 8
    Keywords: IN-VITRO ; SURVIVAL ; KINASE ; GROWTH-FACTOR RECEPTOR ; CANCER-CELLS ; EGFR ; ADAPTER PROTEIN ; INDUCED GENOTOXIC INJURY ; MOLECULAR DISSECTION ; SHAPE MODULATION
    Abstract: Epidermal growth factor receptor (EGFR) signaling plays an important role in tumor cell resistance to therapy. In addition to ligand binding, mutual and cooperative interactions of EGFR with integrin cell adhesion receptors critically influence proper downstream signaling through a number of bridging adapter proteins. In the present study, we analyzed the role of two of these adapter proteins, called PINCH1 and Nck2, for cellular radioresistance in combination with EGFR-targeting using the monoclonal antibody cetuximab. siRNA-mediated knockdown of PINCH1 or Nck2 resulted in enhanced radiosensitivity of 3D grown human squamous cell carcinoma cell lines FaDu (head and neck) and A431 (epidermis) comparable with effects seen after cetuximab treatment. Combination of knockdown and cetuximab did not result in additive nor synergistic effects regarding clonogenic radiation survival. Modifications in MAPK, Akt and FAK phosphorylation occurred upon cetuximab treatment as well as PINCH1 or Nck2 depletion. We further found this tumor cell radiosensitization to be due to attenuated repair of DNA double strand breaks and altered Rad50 and Nbs1 expression but without changes in other DNA repair proteins such as ATM, DNA-PK and Mre11. Our data suggest that the adaptor proteins PINCH1 and Nck2 critically contribute to cellular radioresistance and proper EGFR signaling in 3D lrECM grown human squamous cell carcinoma cells. Further investigations are warranted to identify the intracellular signaling network controlled by EGFR, PINCH1 and Nck2.
    Type of Publication: Journal article published
    PubMed ID: 26004008
    Signatur Availability
    BibTip Others were also interested in ...
  • 9
    Keywords: CELLS ; GROWTH ; tumor ; carcinoma ; CELL ; COMBINATION ; evaluation ; Germany ; MODEL ; liver ; BLOOD-FLOW ; REDUCTION ; RAT ; animals ; RATS ; INJECTION ; 5-FLUOROURACIL ; RAT-LIVER ; NUMBER ; METASTASIS ; COLORECTAL-CANCER ; EFFICACY ; chemotherapy ; arteries ; GREECE ; INFUSION ; PHASE-II TRIAL ; STARCH MICROSPHERES ; beta-galactosidase,CC531-lac-Z,chemiluminescence,chemoembolization,gemcitabine,5-fluorouracil,liver ; DEGRADABLE STARCH MICROSPHERES ; HEPATIC ARTERIAL EMBOLIZATION
    Abstract: An orthotopic, isogenic rat model was used to determine the potential of chemoembolization (CHE) for reducing the tumor cell load of a diffusely metastatic liver. Seven days after injecting CC531-lac-Z cells intraportally to male WAG/Rij rats, tumor positive animals were treated by injection into the hepatic artery with solvent (n=17), degradable starch microspheres (DSM, 30 mg/kg; n=16), DSM plus 5-fluorouracil (5-FU, dosages: 90, 60, and 40 mg/kg) or DSM plus gemcitabine (Gem, dosages: 100, 80, 50, and 10 mg/kg). After 3 more weeks the experiment was terminated, the livers were weighted and the number of CC531-lac-Z cells per liver was determined. Injection of DSM reduced the tumor cell load by 21% (T/C%=79), the combination with 5-FU caused a stimulation of growth at 40 mg/kg (T/C%=291; n=10), but effected dose-dependent reductions in tumor cell number at 60 mg/kg (T/C%=86; n=16), and 90 mg/kg (T/C=19; n=17). None of these effects was significantly different from controls. The combination of DSM plus Gem was toxic at the highest dose (100 mg/kg), but well tolerated and highly effective at 80 mg/kg (T/C%= 16; n=12), 50 mg/kg (T/C%=9; n=12), and 10 mg/kg (T/C%=26; n=14). These results were significantly different from controls (p〈0.05), respectively. In summary, the comparison of CHE with 5-FU or Gem shows that the efficacy of Gem in reducing the hepatic tumor cell load was significantly higher and its therapeutic ratio was greater than that of 5-FU
    Type of Publication: Journal article published
    PubMed ID: 15069554
    Signatur Availability
    BibTip Others were also interested in ...
  • 10
    facet.materialart.
    facet.materialart.
    Oncology Reports 13 (3), 459-463 
    Keywords: APOPTOSIS ; CANCER ; CELLS ; EXPRESSION ; tumor ; TUMOR-CELLS ; Germany ; PATHWAY ; PATHWAYS ; GENE ; GENES ; microarray ; LINES ; DNA ; CELL-LINES ; SEQUENCE ; DISCOVERY ; microarrays ; resistance ; DNA-REPAIR ; REPAIR ; chemotherapy ; LINE ; DAMAGE ; DATABASE ; DNA-DAMAGE ; PREDICTION ; sensitivity ; drug resistance ; cell lines ; DNA repair ; CLUSTER ; CYTOTOXICITY ; molecular ; EXPRESSED SEQUENCE TAGS ; DNA damage ; IC50 ; cluster analysis ; TETRAZOLIUM ASSAY ; hierarchical cluster analysis
    Abstract: Cantharidin (CAN) is the active principle of: the Chinese blister beetle (Mylabris phalerata) which exerts profound cytotoxicity towards tumor cells. The aim of this study was to identify the molecular determinants of sensitivity and resistance of tumor cells to CAN. We mined the microarray database of the National Cancer Institute (NCI), for genes whose expression correlated with the IC50 values for CAN of 60 cell lines of different tumor types. By COMPARE analysis Kendall's tau test, and false discovery rate (FDR) analysis, 21 out of 9706 genes or expressed sequence tags (ESTs) were identified. If the mRNA expression of the 21 genes or ESTs was subjected to hierarchical cluster analysis and cluster image mapping, sensitivity or resistance of the 60 cell lines to CAN was predictable with statistical significance. The majority of these genes are involved in DNA damage 1 response, DNA repair, and/or apoptosis. In conclusion, sensitivity or resistance of tumor cells to CAN is multifactorial in nature. DNA repair and apoptosis play a major role as determinants of cellular response to CAN. The present investigation represents a starting point to dissect the genes and molecular pathways responsible for cellular response to cantharidin in more detail
    Type of Publication: Journal article published
    PubMed ID: 15706417
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...