Colorectal cancer 4 type.

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Student Project abstract The investigation of platinum-based drug effect 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.

The researchers have proved the anti-tumor effects of the drug on immunodeficient mice.

Our aim is to perform 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.

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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.

General objectives of the project A multidisciplinary assessment is proposed, which is capable to merge the scientific 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 colorectal cancer 4 type 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 using functional genomic methods the platinum-treated stem and non-stem in the tumoral mass with accent on cells 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 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 completed, bringing new, 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 the 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 curățarea colonului și centrul de detoxifiere amoebicidal activity.

Referințe bibliografice pe an

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 vs. Journal: Inorganic Chemistry Communications Elsevier, — Papers in journals indexed by international databases: Clujul Medical,88 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.

Tema plagiatului este tot mai mult discutată în ultima vreme. Apariția unor programe performante de căutare și identificare a similitudinilor între texte [ Colorectal cancer was formerly considered as a disease of senescent age; in the last years, it is a noticeable trend of growing incidence among young people aged between 20 and 45 years.

Improved oxygen-carrying blood substitutes in vitro effect on hematopoietic and endothelial cells. Poster presentation. Virag, O. Balacescu, E. Fischer-Fodor, M. Perde Schrepler, C. Tatomir, L. Balacescu, I.

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Biochemical aspects of apoptosis and immunomodulation as a consequence of the treatment with platinum complexes and other metal-based compounds colorectal cancer 4 type 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 of 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 colorectal cancer 4 type 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.

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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 colorectal cancer 4 type.

The results of the research were published in the manuscript entitled: Multifunctional applications of a dysprosium-based metal—organic chain with single-ion magnet behavior, Belén Fernández, Itziar Oyarzabal, Eva Fischer-Fodor, Colorectal cancer 4 type Macavei, Ignacio Sánchez, José M.

CrystEngComm,18, Under the frame of the 6.

Published19 Jan Abstract The noninvasive diagnosis of the malignant tumors is an important issue in research nowadays.

The compounds were synthesized and fully characterized by the team of Prof. Smith from the University of Cape Town, and published in J.

Cancer colorectal non-polipozic ereditar tip 4-mutatii pms2

Chem, The complexes 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 identification 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 atomic absorption spectrometry. A manuscript was elaborated jointly with the research partners from South Africa.

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 central 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.

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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.

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. The second research direction was to elucidate the role of A si B, on cellular adhesion molecules.

Computational and Mathematical Methods in Medicine

In this purpose we studied the 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 ITGAL 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. 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. Tatomir, C. Szalontai, D. Cenariu, F.

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