Student Project abstract The investigation of platinum-based drug colorectal cancer therapy on tumor stem cells responsible for tumor generation and propagation is a novel and expanding field, and in the colorectal cancer casuistry they are many features uncovered. Studies concerning the action of platinum compounds against immune mechanisms focusing activated lymphocytes involved could bring novelties in the field of cancer cell biochemistry and function.
Our aim is to colorectal cancer therapy a multidisciplinary and translational study that impact patient care in colorectal carcinoma. The project objective is to evaluate the platinum-containing drugs effect on stem cells in colorectal carcinoma, this population being responsible for the resistance against chemotherapy treatment. It is feasible to assess the platinum-treated stem cells, with accent on apoptosis, multidrug resistance, metabolism and cell signaling.
The project intends to investigate the percent of stem cells having genetic mutations, and the effect of platinum-based compounds on cell populations which display chemoresistance versus targeted anti-EGFR therapy. We propose also to examine the lymphocyte populations implicated in antitumoral immune response, in order to establish the magnitude of immunomodulation following the platinum compounds action.
colorectal cancer therapy
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General objectives of the project A multidisciplinary assessment is proposed, which is capable to merge the hpv high risk positiv kinderwunsch achievements of basic and clinical studies and to improve the results quality. Our aim is to perform a basic and translational study that impact patient care in colorectal carcinoma.
The project main objective is to evaluate the platinum-containing drugs impact on stem cells, these population being responsible for the tumoral dissemination and resistance against chemotherapy treatment. The clue of the treatment resides in the proportion of stem cells inhibited by the drug in the whole tumoral population, and the project proposes to identify and characterize the changes which occur in colon carcinoma stem cells during platinum chemotherapy.
It is feasible to compare colorectal cancer therapy functional genomic methods the platinum-treated stem and colorectal cancer therapy in the tumoral mass with accent on cells apoptosis, colorectal cancer therapy resistance, metabolism and cell signaling. The project intends to investigate the percent of stem cells having genetic mutations, and the effect of platinum-based compounds on EGFR-chemoresistant cell populations. One of our objectives is to scan the lymphocyte populations implicated in antitumoral immune response, emphasizing the CD8 positive T lymphocytes and the natural killer cells, in order to establish the magnitude of the changes in human body immune response potential following the platinum compounds action.
Lymphocytes from both peripheral blood and lymph nodes will be evaluated. The proposed objectives were colorectal cancer therapy, bringing colorectal cancer therapy, significant results in biochemistry of the platinum compounds, the most important metal involved in chemotherapy, but also the platinum-group metals PGMother metal complexes and their ligands showing therapeutic potential.
We revealed multiple aspects of platinum-based chemotherapy, which join colorectal cancer therapy outcomes of basic biochemical, genomic, proteomic and immune methods in order to improve the therapeutically benefits. After accomplishing all phases of the project, the final results of the project are: Scientific publications which acknowledges the project, indexed on Web of Science Thomson Reuters ISI: 1.
IF 0,; influency score 0, Synthesis of structural analogues of hexadecylphosphocholine and their antineoplastic, antimicrobial and amoebicidal activity. European Journal of Medicinal Chemistry, Imunomodulatory potential of palladium II complexes with 1E,6E -1,7-bis 3,4-dimethoxyphenyl hepta-1,6-diene-3,5-dione.
Notulae Botanicae Horti Agrobotanici,43 2 : Platinum derivatives: generic brands medicament ușor pentru paraziți. Journal: Inorganic Chemistry Communications Elsevier, — Papers in journals indexed by international databases: Clujul Colorectal cancer therapy 3 : Ferdinand Devinsky from the Comenius University in Bratislava. Gregory S. Virag, M. Perde-Schrepler, C. Tatomir, H.
Decean, E. Fischer-Fodor: UVB-activated signaling pathways and their modulation with Vitis vinifera seeds extract in human skin cells, Abstract Book, pages Virag, E. Improved oxygen-carrying blood substitutes in vitro effect on hematopoietic and endothelial cells.
Poster presentation. Virag, O. Balacescu, E.
Florin Filipoiu, Prof. Mircea Beuran Course Overview This workshop is designed to review the information on the diagnosis and management of rectal cancer.
Fischer-Fodor, M. Perde Schrepler, C. Tatomir, L.
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- Colorectal cancer therapy obiectiv îndrăzneţ al proiectului va fi realizat prin achiziţionarea de aparatură medical, activităţi de formare a personalului medical implicat în diagnosticarea şi managementul acestor patologii în cadrul unor workshopuri şi sesiuni de training, dar şi prin acţiuni de informare a populaţiei asupra necesităţii screeningului pentru prevenirea şi diagnosticul precoce al cancerelor de colon şi respective de col uterin, prin materiale de promovare, forumuri de conştientizare pentru publicul larg privind stilul de viaţă sănătos şi riscul de apariţie al acestor tipuei de patologii.
colorectal cancer therapy Balacescu, I. Colorectal cancer therapy aspects of apoptosis and immunomodulation as a consequence of the treatment with platinum complexes and other metal-based compounds with antitumor therapeutic potential Through two main activities: 6.
Evaluation of the molecules implicated in apoptotic signaling pathways in colorectal cells treated with metal complexes 6. Assessment of the metal compounds effect on lymphocyte subsets and cellular adhesion molecules The final phase of the project, PHASE VI December 10th December 31st was implemented by completing the following objective: 6. Evaluation of the molecules implicated in apoptotic signaling pathways in colorectal cells treated with metal complexes In order to identify new biomarkers connected to the apoptotic processes induced by metal compounds, the biologic effect of a new class colorectal cancer therapy dysprosium complexes was studied; the antiproliferative effect of the Dy compounds was compared with that of standard platinum-based drugs.
The complex and its ligand toxicity were and we proved the decisive role of the central metal in the compounds biologic activity and in early apoptosis triggering. The treated tumor cell populations were exposed to a uniform magnetic filed, with an intensity which does not affected the cells viability, and we observed that unlike to the ligand or the platinum drugs, the magnetic field applied concomittant with in Dy III Na ampy 4]n treatment induced a stronger growth inhibitory effect on tumor populations.
The cancer cells drug resistance was impeded by the simultaneous application of the Dy complex and the magnetic field; this phenomenon was monitored through the evaluation of the MDR-1 biomarker of drug efflux in the cell, and a statistic significance was proved. The results of the research were published in the manuscript entitled: Multifunctional applications of a dysprosium-based metal—organic chain with human papillomavirus icd 10 magnet behavior, Colorectal cancer therapy Fernández, Itziar Oyarzabal, Eva Fischer-Fodor, Sergiu Macavei, Ignacio Sánchez, José M.
CrystEngComm,18, Under the frame of the 6. The compounds were synthesized and fully characterized by the team of Prof. Smith from the University of Colorectal cancer therapy Town, and published in J.
Chem, The colorectal cancer therapy were tested in vitro in order to elucidate their biologic activity against human colon cells in vitro. The inhibitory effect against the tumor cell populations was tested by MTT method and the degree of the toxicity was quantified using the IC50 half inhibitory concentration parameter, which revealed a superior toxicity against the invasive, mutant colon cancer cells.
The compounds potential to induce the programmed cell death was evaluated through the colorectal cancer therapy by Annexin V binding of phosphatidyl-serine translocated to the cell outer membrane during apoptosis.
In parallel, the number of necrotic cells was evaluated.
This data are well correlated with the iron cellular uptake, measured with colorectal cancer therapy absorption spectrometry. A manuscript was elaborated jointly with the research partners from South Africa.
Colorectal cancer neoadjuvant therapy Neoadjuvant and Adjuvant Therapy in Metastatic Colorectal Cancer human papillomavirus vaccine problems Provides state of the art information on surgery, oncology, imaging, staging, pathology, and palliation Explains how to organize the multidisciplinary team Addresses key controversies Aids understanding and communication among team members About this book This book is intended as the equivalent of the Swiss Army knife for all members of colorectal cancer CRC multidisciplinary teams and those training in colorectal cancer therapy fields of CRC management.
Assessment of the metal compounds effect on lymphocyte subsets and cellular adhesion molecules The activity implied to achieve the phase VI objective was the study of two complexes of the Platinum Group Metals PGMsteric isomers, having as colorectal cancer therapy metal Pd II and the ligand 1e,6e -1,7-bis 4-dimethylamino phenyl hepta-1,6-diene-3,5 dione, in two different conformations.
Their antiproliferative effect was tested with colorimetric viability methods; the ligand was inactive, while the two complexes half inhibitory concentrations were significant lower was of ligand, proving a structure-activity relationship.
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More, the dose-response correlation was found in both complexes; the cis conformer A being more active against colon tumor cells. The compounds inclusion inside the tumor cells was evaluated based on their autofluorescence; a higher accumulation was observed in k-ras mutant DLD-1 cells.
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The second research direction was to elucidate the role of A si B, on cellular adhesion molecules. In this purpose we studied colorectal cancer therapy effect of the metal complexes A and B against the peripheral blood mononuclear cells PBMCemphasizing on the compounds modulator effect on the neural cell adhesion molecule NCAM or CD56 biomarker, which characterizes the cytotoxic natural killer cell subset. In the antitumor immune response an important role is of adhesion and activation marker CD11a Colorectal cancer therapy and of tumor necrosis factor CD27; their expression was quantified using the flow cytometry and a statistic significant correlation was found with the presence of CD56 markers on the PBMC cell membrane.
SYSTEMIC CHRONIC INFLAMMATION AND COLORECTAL CANCER - AN UNSOLVED PUZZLE.
The expression of these membrane markers was significantly different in untreated cells versus the cells treated with A and B, in CD56 pisotive NK cells and in CD14 positive monocytes. The research results were published in Studia Universitatis UBB Chemia,61, 3 I :with the title: Cytotoxic activity of palladium II complexes of 1e,6e -1,7-bis 4-dimethylamino phenyl hepta-1,6-diene-3,5-dione against human colon carcinoma, authors: N.
Miklasova, R. Miklas, P. Virag, C. Oxiuros informacion, C.
Szalontai, D. Cenariu, F. Devinsky, E. Colorectal cancer therapy structures of PGM metal complexes Pd 1 and Pt 2 with the ligand 1e,6e -1,7-bis 4-dimethylamino phenyl hepta,5 dione were tested for their immunomudulator effects.
The testing was performed o CD4 positive helper and CD8 positive cytotoxic T lymphocyte subpopulations, involved in antitumor respeonse of the cellular immune system. The ligand alone has a slight effect on the studied membrane markers, and complex 1 strongly interfere with the costimulatory prcesses in the cellular immune system.
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Using proteomic methods, a quantitatively evaluation was performed on the intracellular and extracellular colorectal cancer therapy of interleukines IL-2, IL-6, IL-8 andIL, and the date were correlated with the adhesion and activation markers expression.
We concluded that these group of metal complexes exhibited in vitro a significant immune modulator potential, besides the cytotoxic effect, through the main signalling pathways CDCDIL 2 and GITR-T regulator cells.
Previous activities: The objective of Phase V December 10th December 31st of the project was: 5. Based on the hypothesis that the platinum-based drugs and other metal compounds action modify the tumor microenvironment and these modifications conduct to the tumor cells suppression or contrary, to the development of drug resistance, we examined the ex vivo modulation of colorectal cancer therapy cell types, the principal components of the tumor stroma, and we evaluated as well the lymphocyte infiltration in lymph nodes, emphasizing on CD8 positive cytotoxic T cell subset.
The histological type of the tumors was adenocarcinoma, and all the lymphatic nodes have had tumoral infiltrations; primary cell cultures were carried out, treated in vitro with the antitumor drug oxaliplatin, and than the cell subpopulations were colorectal cancer therapy using the flow cytometry. The CD8 positive lymphocytes were detected using the standard fluorescence labeling, the endothelial cells were characterized using the surface marker CD and the anti-fibroblast antibodies enabled the quantification of fibroblast expression in tumor mass.
The percent of the stem-like CD positive cells and EpCAM CD positive tumor cells presence was detected in the lymphatic colorectal cancer therapy samples, which confirmed the tumor infiltration, the marker being a specific feature of epithelial tumor cells. As a result of the platinum drug therapy, a raise in the fibroblast and a decrease in the endothelial cells proportion, which can influence the proliferation indirectly, acting on tumor microenvironment.
Two directions were approached; one of them analyzed the implications of platinum-based neoadjuvant chemotherapy treatment on lymphocyte subsets involved in antitumor immune response in colorectal cancers, the activation processes in cells obtained from lymphatic nodes resection.
The testing was conducted in vitro, they were studied the effector T cells isolated from tissue samples, activated through CD25, CD69 and CD27 molecules; the expression of these surface markers was assessed through flow-cytometry, and an experimental validation was made using verucă plantară Surgitron techniques qT PCR Elisa testing for the soluble form of the molecules.
The conclusions of the study point towards a good preservation of the activated effector lymphocyte subset during the oxaliplatin-based treatment in colorectal cancers. The second line of the study was to elucidate colorectal cancer therapy in vitro effect exerted by the metal compounds colorectal cancer therapy a central metal from the platinum group, against the cells implicated in antitumor immune response, and the validation of this outcome by measuring the soluble form of the involved molecules, especially interleukins.
Two novel synthesized Palladium II compounds were studied, having a curcuminoid ligand: 1E,6E -1,7-bis 3,4-dimethoxypenyl hepta-1,6-diene-3,5-dione, which showed limited toxicity against the normal peripheral blood colorectal cancer therapy cells PBMC.
The ligand suppressed the CD8 positive T cells expression, but induced the overexpression of CD4, and has no effect on other markers.
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Despite the fact that complex 1 slightly inhibited the CD8 expression, it has a benefic effect on other cellular subpopulations implicated in the immune response.
Complex 2 has had an inhibitory effect not only on CD8 positive lymphocytes, but also against CD19 positive B cells and induced reduction in GITR positive cell population, which predicts a moderate immune suppression.
Overall, the compounds exhibit applicability colorectal cancer therapy for antitumor prodrugs development. Evaluation of the metal-based compounds in vitro effect on colorectal tumor stem-like cells; having the activities: - Comparison between original versus generic platinum drugs, emphasizing on stem cell proliferation and multidrug la enterobiasis definicion There were assessed the differences between the generic and original platinum-based drugs, in order to elucidate some of the reasons why the patients respond differently to the treatment when generic or original drugs are used, an aspect which concern the scientific community and the clinicians as well.
Under the frame of this activity an evaluation of the in vitro cytotoxicity was made for the original and generic versions of oxaliplatin and carboplatin on tumor cell lines DLD-1, HT and A The inhibitory effect the original oxaliplatin colorectal cancer therapy against colon cell lines was not significantly higher, but the effect on the stem-like CD positive cells isolated from the whole cell population was superior in the K-ras mutant DLD-1 cell line after 24 hours exposure.
The chemoresistance towards the platinum-based drugs was higher in the HT Braf-mutant cell line, the toxicity being below of that for DLD We found morphologic evidences such prevailing membrane structure alteration, chromatin condensation in the tumor cells treated with original drugs.
The phenomenon studied in vitro can be extrapolated to the clinics to anticipate the drugs efficacy, and to predict at some extent the hypersensibility reactions and the adverse effects of the drugs.
The experiment was conducted in vitro on human colorectal cell lines, the toxicity was evaluated with colorimetric methods, and the simultaneous expression of the molecules was quantified using the flow cytometry.
The transcription factors were correlated with the expression of the molecules colorectal cancer therapy in VEGF signaling. Overall, the studied compounds exhibit antiproliferative effect against the tumor cells in vitro, they influenced the NF-kβ signaling and the angiogenesis.