Publications (15)36.91 Total impact
-
Article: Soluble CD163 serum levels are elevated and correlated with IL-12 and CXCL10 in patients with long-standing rheumatoid arthritis.
[show abstract] [hide abstract]
ABSTRACT: CD163, a membrane glycoprotein restricted to monocyte-macrophage cell lineage, is released in the terminal phase of acute inflammation and during chronic inflammation, with anti-inflammatory and antiangiogenic role. The proteolytically detached ectodomain of CD163 is the soluble component sCD163. A few studies were performed regarding circulating sCD163 in human diseases. Only two were accomplished in patients with rheumatoid arthritis (RA). Our concern was (1) to evaluate sCD163 serum concentrations in active RA patients with long-standing evolution, (2) to correlate them with clinical parameters, laboratory markers, disease activity, and (3) to search possible relationships with some cytokines (IL-12, IL-17) and chemokine (CXCL10), involved in RA pathogenesis. First and third topics were not achieved until now, and the second one points out discordant findings and unspecified aspects. It was achieved immunoassay of serum sCD163, IL-12, IL-17, CXCL10 and traditional methods for RA laboratory markers. The mean sCD163 level of 33 patients was significantly higher than in 20 normal controls (p = 0.0001), 59.3 % of them with concentrations above normal cut-off value. sCD163 levels were weakly correlated with CRP and RF but not with ERS and disease activity. IL-12 and CXCL10 serum levels strongly correlated with sCD163 concentrations, while IL-17 positively but insignificantly correlated. In conclusion, serum sCD163 levels are significantly elevated in long-standing RA patients, but sCD163 has no role as a biomarker of disease activity. High correlation of sCD163 with IL-12 and CXCL10 suggests the association of their well-known anti-inflammatory function in long-standing RA patients.Rheumatology International 08/2013; 33(4):1031-1037. · 1.88 Impact Factor -
Article: 5-Fluorouracil potentiates the anti-cancer effect of oxaliplatin on Colo320 colorectal adenocarcinoma cells.
[show abstract] [hide abstract]
ABSTRACT: BACKGROUND & AIMS. The present study was designed to examine the combined effects of Oxaliplatin (OXA) and 5-Fluorouracil (5-FU) in the Colo320 cell line. METHODS. The antiproliferative effects were evaluated using the MTT assay, apoptosis by flow cytometry, and RT-PCR-array technology was used to determine the major effects of the two chemotherapeutic drugs upon the most important genes involved in apoptosis. RESULTS. The antiproliferative effects of the therapeutic agents, as individual therapy or combined, proved to be dose and time-dependent, with increased efficiency for the combined treatment. Flow cytometry data revealed increased apoptotic processes in the case of the combined treatment at 24 hours after administration. The RT-PCR-array data indicated that at 24 hours after OXA treatment, 49 genes were differentially expressed, of which 45 were up-regulated and 4 down-regulated. In the case of the 5-FU treatment, 35 genes were down regulated and 2 up regulated. In the combined treatment of 5-FU and OXA, 19 genes were up-regulated and 15 down-regulated. CONCLUSIONS. This study proved that drug resistance could be counteracted by combining OXA with 5-FU to form a tandem that is capable of reducing cell proliferation and to stimulate extrinsic apoptosis pathway by targeting death receptors on the cell surface.Journal of gastrointestinal and liver diseases: JGLD 03/2013; 22(1):37-43. · 1.81 Impact Factor -
Article: Novel cellular and molecular approaches to stratification and treatment of colorectal cancer.
[show abstract] [hide abstract]
ABSTRACT: Colorectal cancer is an important disease of the modern world, generating significant mortality and morbidity rates. Its therapy, although considerably improved, continues to be unhelpful for a large percentage of patients, especially for those in advanced stages. This justifies the efforts toward producing new therapies, as well as for stratifying patients according to risk factors and prediction of therapeutic response. In this respect, the contributions of modern science are essential for defining the most intimate mechanisms and players of tumorigenesis and for proposing new biomarkers. The study of antitumor immune responses has revealed new insights into the tumor microenvironment, leading to the development of vaccines and adoptive transfer of immunocompetent cells. Circulating tumor cells are a real opportunity to detect early relapses and to define risk categories, while miRNAs, a family of small non-coding RNA implicated in regulation of gene expression, evolved as a new class of biomarkers with high potential for diagnosis, prognosis and prediction of colorectal cancers.Journal of gastrointestinal and liver diseases: JGLD 12/2012; 21(4):413-21. · 1.81 Impact Factor -
Article: Quantitative mRNA expression of genes involved in angiogenesis, coagulation and inflammation in multiforme glioblastoma tumoral tissue versus peritumoral brain tissue: lack of correlation with clinical data.
[show abstract] [hide abstract]
ABSTRACT: Glioblastoma multiforme is a very aggressive brain tumor. Angiogenesis, the formation of new blood vessels from pre-existing ones, is a process that plays an essential role in cancer development. The evolution of this process depends upon several proangiogenic factors as well as inhibitors of angiogenesis. Coagulation and inflammation also play an important role in tumorigenesis. Their expression is controlled by over- or under-expression of certain genes. The objective of our study was to evaluate the expression, in tissue samples, of a set of six genes involved in tumoral angiogenesis. The study concerned a group of 14 patients with pathologically-confirmed glioblastoma multiforme. Samples of tumoral and peritumoral brain tissue were taken during surgery. We used RT-PCR to evaluate the expression of six genes involved in angiogenesis: VEGF, PDGF, EPCR, TNF, ICAM-1 and CTGF. Gene expression was calculated by comparing the values obtained for the tumoral tissue with those obtained for the peritumoral tissue. Increased transcription of VEGF, PDGF and ICAM-1 genes were observed in glioblastoma tumoral tissues compared with peritumoral brain tissues. Correlations were observed between transcription of the CTGF and TNF genes (rho = 0.54, p-value = 0.05) and PDGF and ICAM-1 genes (rho = 0.54, p-value = 0.05). Under-expression of CTGF, EPCR and TNF genes was observed in glioblastoma tumoral tissue in comparison with peritumoral brain tissue. The association between gene expression and histopathological results (endothelial hyperplasia, coagulation necrosis and ischemic necrosis) was evaluated. No statistically significant associations were observed between gene expression and survival rates.European cytokine network. 05/2012; 23(2):45-55. -
Article: Early apoptosis signals induced by a low dose of epigallocatechin 3-gallate interfere with apoptotic and cell death pathways.
[show abstract] [hide abstract]
ABSTRACT: Research for natural compounds with novel advantageous biological activities or antineoplastic potential is an important issue in drug discovery. An example of this type of compound is epigallocatechin 3-gallate (EGCG), which is the major polyphenol in green tea. EGCG has therapeutic effects and modulates multiple metabolic pathways, including apoptosis. The present study evaluates the effect of 10 microM EGCG on the expression of genes that are involved in apoptosis and cell death using PCR-array technology and HeLa cells as an in vitro model. The specific modulatory effects of EGCG were demonstrated by significant alterations in the expression levels of the following genes that control the apoptosis pathway: the TNF receptor and its ligand family, the death effector domain family, the Bcl-2 family or TP73. The structure of EGCG suggests that it has the potential to be an anticancer agent and that EGCG serves as a promising starting point for the derivation of novel anticancer drugs. EGCC metabolite products, such as pyrogallol, gallic acid or quinones, may also play important roles in inducing apoptosis. Therefore, quantification of mRNA using PCR-array technology is a valuable tool for screening these anticarcinogenic compounds. By evaluating the action of EGCG on genes that regulate apoptosis, our results suggest that EGCG is as an activator of gene expression with direct implications in cancer therapy. In addition, the limited success in activation of the antiapoptotic gene Bcl-2 may be associated with resistance to cancer treatment.Journal of Nanoscience and Nanotechnology 03/2012; 12(3):2113-9. · 1.56 Impact Factor -
Article: Early transcriptional pattern of angiogenesis induced by EGCG treatment in cervical tumour cells.
[show abstract] [hide abstract]
ABSTRACT: The major green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) has been shown to exhibit antitumour activities in several tumour models. One of the possible mechanisms by which EGCG can inhibit cancer progression is through the modulation of angiogenesis signalling cascade. The tumour cells' ability to tightly adhere to endothelium is a very important process in the metastatic process, because once disseminated into the bloodstream the tumour cells must re-establish adhesive connections to endothelium in order to extravasate into the target tissues. In this study, we investigated the anti-angiogenic effects of EGCG treatment (10 μM) on human cervical tumour cells (HeLa) by evaluating the changes in the expression pattern of 84 genes known to be involved in the angiogenesis process. Transcriptional analysis revealed 11 genes to be differentially expressed and was further validated by measuring the induced biological effects. Our results show that EGCG treatment not only leads to the down-regulation of genes involved in the stimulation of proliferation, adhesion and motility as well as invasion processes, but also to the up-regulation of several genes known to have antagonist effects. We observed reduced proliferation rates, adhesion and spreading ability as well as invasiveness of HeLa tumour cells upon treatment, which suggest that EGCG might be an important anti-angiogenic therapeutic approach in cervical cancers.Journal of Cellular and Molecular Medicine 05/2011; 16(3):520-30. · 4.13 Impact Factor -
Article: Assessment of cytotoxicity, apoptosis and DNA damages in Colo320 colorectal cancer cells selected for oxaliplatin resistance.
[show abstract] [hide abstract]
ABSTRACT: Despite the notable efficacy of oxaliplatin in the treatment of colorectal cancers, the metastatic tumours ultimately become resistant to the drug. This study investigated whether the oxaliplatin-resistant cells display different behaviour to this drug versus the sensitive cells and if this difference may be further exploited into the clinical treatments improvement. In order to establish a stable cell line resistant to oxaliplatin, a human colorectal cancer cell line (Colo320) was exposed to increasing doses of the drug up to the clinically relevant plasma concentration. Four cell groups with different levels of chemoresistance were subjected to additional doses of oxaliplatin, and their cytotoxicity, apoptosis and DNA damage production were assessed. Cells selected for resistance to oxaliplatin reacted differently to the application of additional doses of the drug, displaying lower toxicity and cellular death and fewer DNA cross-links formation, in accordance with the extent of the oxaliplatin pretreatments. As the cross-links formation by oxaliplatin being the main cause for cytotoxicity of this drug and a correlation between cytotoxicity and clinical outcome being shown repeatedly, we consider that the evaluation of oxaliplatin-induced cytotoxicity, apoptosis and DNA damage could be a valuable tool to assess the tumour cells sensitivity and thus to predict the response to chemotherapy.Cell Biochemistry and Function 04/2011; 29(5):351-5. · 1.77 Impact Factor -
Article: Molecular angiogenesis profile as a tool to discriminate chronic pancreatitis (CP) from pancreatic cancer (PC).
Pancreas 04/2011; 40(3):482-3. · 2.39 Impact Factor -
Article: Risk Factors in a Sample of Patients with Advanced Cervical Cancer
[show abstract] [hide abstract]
ABSTRACT: The estimated burden of neoplasia of uterine cervix in the 27 EU member states sums up to 34300 cases and 16200 death, with higher incidence and mortality in eastern countries. A number of risk factors increase the likelihood of developing cervical cancer. Even if the risk factors significantly increase the chances of developing cervical cancer, a large number of women with risk factors do not develop the disease, and when a woman develops cancer or precancerous lesions in the cervix may be difficult to establish the causal relationship with certain risk factors. The present study aimed to appreciate the presence and magnitude of risk factors for patients diagnosed with advanced cervical cancer and to outline best strategies to reduce the incidence of this neoplasia, and improve prognosis. Risk factors have been investigated in 42 patients diagnosed with advanced cervical cancer using HPV genotyped determination and a questionnaire for the evaluation of cervical cancer risk factors. In our sample of patients a high risk profile is shaping for low socio-economical level, modulated by the impact of HPV infection with high risk stains of virus, overweight-obesity, smoking and inadequate cervical cancer screening. In this frame a special alarm signal is represented by the very high percentage of patients with overweight and obesity. From the public health perspective, we consider that efforts should be focused on preventing weight gain, regular screening and health education field.Applied Medical Informatics Original Research. 01/2011; 29:1-10. -
Article: The relationships between biological activities and structure of flavan-3-ols.
[show abstract] [hide abstract]
ABSTRACT: Flavan-3-ols are involved in multiple metabolic pathways that induce inhibition of cell proliferation. We studied the structure-activity relationship of gallic acid (GA) and four flavan-3-ols: epigallocatechin gallate (EGCG), epigallocatechin (EGC), catechin (C), and epicatechin (EC). We measured the cell viability by the MTT assay and we determined the concentration of testing compound required to reduce cell viability by 50% (IC(50)). All tested compounds showed a dose-dependent and time-dependent inhibitory antiproliferative effect on Hs578T cells; IC(50) values varying from the 15.81 to 326.8 μM. Intracellular ROS (reactive oxygen species) were quantified using a fluorescent probe 2',7'-dichlorofluorescin diacetate (DCFH-DA). Only the treatment with 10 μM EGC and EGCG was able to induce a significant decrease of ROS concentration and increased levels of ROS were registered for 100 μM EGCG, EGC and GA. Flavans-3-ols and GA induced apoptosis in a dose- and time-dependent manner, which indicated that the induction of apoptosis mediated their cytotoxic activity at least partially. The galloylated catechins have shown a stronger antiproliferative activity and apoptotic effect than the one produced by non galloylated catechins. The galloylated flavan-3-ols are potential therapeutic agents for patients with triple negative breast cancer via induction of apoptosis.International Journal of Molecular Sciences 01/2011; 12(12):9342-53. · 2.60 Impact Factor -
Article: PROTECTIVE ACTION OF DIFFERENT NATURAL FLAVAN‐3‐OLS AGAINST AFLATOXIN B1‐RELATED CYTOTOXICITY
[show abstract] [hide abstract]
ABSTRACT: The aim of this study is to investigate the ability of flavan-3-ols: catechin, epigallocatechin, epigallocatechin gallate, and epicatechin gallate to prevent aflatoxin B1 (AB1)-induced cytotoxicity in A2780 cell line. The treatment with AB1 (0.35 µM) gives an increased level of cytotoxicity versus control (30–50%). Flavan-3-ols are more efficient against AB1 cytotoxicity at 24 h after treatment than after 48 h. AB1-induced dichlorofluorescin diacetate fluorescence intensity was significantly reduced even after 1 h incubation with flavan-3-ols. Concerning the tumor necrosis factor-alpha (TNF-α) release, comparing with the control, AB1 induces a down-expression of this factor. All the flavan-3-ols induced a higher level of TNF-αrelease in the cellular supernatant comparing with the AB1 group, but much lower than the control group. The present study demonstrates the potent protective effect of flavan-3-ols against AB1 cytotoxicity in A2780 epithelial cell line. This protective effect may be due to the inhibitory effect of flavan-3-ols on AB1-induced reactive oxygen species formation and oxidative damage.PRACTICAL APPLICATIONSThere is a delicate balance between antioxidants and pro-oxidants, generally and specifically, in the cell. They are responsible for regulation of various metabolic pathways, immunosuppression, growth and development and protection against stress. Mycotoxins have negative impact on this antioxidant/pro-oxidant balance. This balance can be regulated by dietary antioxidants like flavan-3-ols.There are various approaches to control or combat mycotoxin problems; one is by developing new oxidant strategies by improving the natural defense mechanism against mycotoxins at cellular level.Considering the role of reactive oxygen species in chemically induced carcinogenesis, the ability of aflatoxins to induce cytotoxicity to cells may play an important role in aflatoxin-induced carcinogenicity. Chemopreventive strategies designed to limit the several toxic effects, caused by these mycotoxins, are important public health goals for reducing the incidence of aflatoxin-induced diseases. Flavan-3-ols, a class of phenolic compounds ubiquitous in plants and widely found in a number of fruits, vegetables and beverages, can be a choice of preventing the mycotoxin-related toxicity as we reported in this study.Journal of Food Biochemistry 05/2010; 34(3):595 - 610. · 0.81 Impact Factor -
Book: FORMULAREA SI ACTIUNEA BIOLOGICA A MEDICAMENTULUI
01/2010; Editura Argoaut. -
Article: Apoptosis in cancer: key molecular signaling pathways and therapy targets.
[show abstract] [hide abstract]
ABSTRACT: Apoptosis is a physiological process vital for embryologic development and the maintenance of homeostasis in multicellular organisms, but it is also involved in a wide range of pathological processes, including cancer. In mammalian cells, apoptosis has been divided into two major pathways: the extrinsic pathway, activated by proapoptotic receptor signals at the cellular surface, and the intrinsic pathway, which involves the disruption of mitochondrial membrane integrity. Although many of the proteins vital for apoptosis have been identified, the molecular pathways of cellular death still remain to be elucidated. This review provides references concerning the apoptotic molecules, their interactions, the mechanisms involved in apoptosis resistance, and also the modulation of apoptosis for the treatment of cancer.Acta oncologica (Stockholm, Sweden) 07/2009; 48(6):811-21. · 2.27 Impact Factor -
Article: Clinical and pharmacokinetics study of oxaliplatin in colon cancer patients.
[show abstract] [hide abstract]
ABSTRACT: to evaluate the therapeutic efficacy of oxaliplatin and to analyze the pharmacokinetics of both ultrafiltrable (free) and protein-bound platinum in patients with metastatic colon cancer. 60 patients with stage IV colon carcinoma received 4-6 (mean 4.5) cycles of oxaliplatin based combination chemotherapy. Response rate, progression-free survival (PFS) and toxicity were evaluated. The pharmacokinetics of oxaliplatin was evaluated in 8 patients who were given 85 mg/sqm or 130 mg/sqm using an infusion time of 2-4 h. Pharmacokinetic analysis was performed on blood, plasma and plasma ultrafiltrable by ICP-MS (Inductively Coupled Plasma Mass Spectrometry). Overall response rate (complete and partial) occurred in 33 (55%) patients. The median time of progression was 9.3 months. Cumulative neurotoxicity, vomiting and diarrhea, myelosuppression appeared in 32.3%, 21.3%, and 39.4% patients, respectively. The mean Cmax and AUC 0-24 of oxaliplatin increased in a dose-related manner. The pharmacokinetics of platinum after oxaliplatin administration was triphasic characterized by a short initial distribution phase and a long terminal elimination phase.The clearance of ultrafiltrable platinum was relatively high and the clearance of platinum from plasma and blood cells was relatively low, which is probably a reflection of the covalent binding of platinum to these matrices. Oxaliplatin is active and well tolerated in patients with advanced colon cancer. With a relatively low interpatient variability, it is eliminated triphasically and the mean Cmax and AUC 0-24 increases in a dose-related manner. These results provide a scientific basis for the safe and effective use of oxaliplatin in the clinic.Journal of gastrointestinal and liver diseases: JGLD 04/2009; 18(1):39-43. · 1.81 Impact Factor -
Article: Gene expression profiling of primary cutaneous melanoma and clinical outcome.
[show abstract] [hide abstract]
ABSTRACT: Gene expression profiling data for human primary cutaneous melanomas are scarce because of the lack of retrospective collections of frozen tumors. To identify differentially expressed genes that may be involved in melanoma progression and prognosis, we investigated the relationship between gene expression profiles and clinical outcome in a cohort of patients with primary melanoma. Labeled complementary RNA (cRNA) from each tissue sample was hybridized to a pangenomic 44K 60-mer oligonucleotide microarray. Class comparison and class prediction analyses were performed to identify genes whose expression in primary melanomas was associated with 4-year distant metastasis-free survival among 58 patients with at least 4 years of follow-up, distant metastasis, or death. Results were validated immunohistochemically at the protein level in 176 independent primary melanomas from patients with a median clinical follow-up of 8.5 years. Survival was analyzed with a Cox multivariable model and stratified log-rank test. All statistical tests were two-sided. We identified 254 genes that were associated with distant metastasis-free survival of patients with primary melanoma. These 254 genes include genes involved in activating DNA replication origins, such as minichromosome maintenance genes and geminin. Twenty-three of these genes were studied at the protein level; expression of five (MCM4, P = .002; MCM3, P = .030; MCM6, P = .004; KPNA2, P = .021; and geminin, P = .004) was statistically significantly associated with overall survival in the validation set. In a multivariable Cox model adjusted for tumor thickness, ulceration, age, and sex, expression of MCM4 (hazard ratio [HR] of death = 4.04, 95% confidence interval [CI] = 1.39 to 11.76; P = .010) and MCM6 (HR of death = 7.42, 95% CI = 1.99 to 27.64; P = .003) proteins was still statistically significantly associated with overall survival. We identified 254 genes whose expression was associated with metastatic dissemination of cutaneous melanomas. These genes may shed light on the molecular mechanisms underlying poor prognosis in melanoma patients.CancerSpectrum Knowledge Environment 05/2006; 98(7):472-82. · 14.07 Impact Factor
Top co-authors
Top Journals
Institutions
-
2012
-
Institutul Oncologic Prof. Dr.I. Chiricuta
Cluj-Napoca, Judetul Cluj, Romania
-
