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Papers by Serban Negru

Medicina-lithuania, Jul 21, 2022

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

European Scientific Journal, ESJ, Jun 30, 2013

Introduction: The diagnostic of prostate cancer (PCa) using serumbased prostate specific antigen ... more Introduction: The diagnostic of prostate cancer (PCa) using serumbased prostate specific antigen (PSA) has some limitations due to falsepositive and negative results. The purpose of our study was to analyse the hypermethylation of three genes from plasma samples and to determine the feasibility of these genes to aid as biomarkers in detecting PCa in plasma by noninvasive methods. Materials and Methods: Genomic DNA was extracted from the peripheral blood plasma of 74 patients with localized PCa. All the samples were examined for aberrant hypermethylation in retinoic acid receptor β variant 2 (RARβ2), glutathione S-transferase P1 (GSTP1) and Ras association domain family 1 isoform A(RASSF1A) genes, using methylation-specific PCR (MSP), and the results were correlated with the clinicopathological parameters. Results: The percent of methylation of the analyzed genes was as follows: RARβ2 was found methylated in 54 cases (73 %), GSTP1 in 58 cases (78.4%), and RASSF1A was found methylated in all 74 cases (100%). Conclusion: Our study demonstrates that, using a panel of DNA methylated biomarkers aids the identification of PCa patients and with minimally invasive techniques , may yield information independent of serum PSA or the TNM stage.

Experimental and Therapeutic Medicine, Mar 22, 2021

Currently, surgical techniques, such as internal limiting membrane peeling, are used widely for m... more Currently, surgical techniques, such as internal limiting membrane peeling, are used widely for macular holes, macular puckers, epiretinal membranes, diabetic macular edema, retinal detachment, retinal vein occlusions, vitreomacular traction, optic pit maculopathy, and Terson syndrome. This study aimed to highlight any differences regarding visual acuity and ocular tomography coherence changes after staining the internal limiting membrane with dilutions of Brilliant Blue G vs. lutein/zeaxanthin-based dyes. This study involved 30 eyes of 30 patients who had undergone posterior pole vitrectomy for idiopathic stage 4 macular hole. The study lot was divided in two subgroups, 15 eyes colored with Brilliant Blue and the other 15 eyes colored with lutein and zeaxanthin dyes. The association between visual prognosis, ocular tomography coherence changes and intraocular pressure was analyzed. The surgical treatment with required endoillumination levels and a 2-min period of dye using the Alcon Constellation Vision System had no negative impact on cell viability and improved visual acuity by 30%. Staining makes it easier to remove, to be quick and precise while performing macular surgeries. In has been observed that lutein and zeaxanthin dyes offer an intraoperative protective screen that protects photoreceptors more than Brilliant Blue while performing pars plana vitrectomy. Both study groups had good results in time. Surgical visualization is an evolving technology.

Medicina-lithuania, Jul 14, 2022

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Neoplasma, 2016

Chemokines are a family of small, structurally related cytokines with chemoattractant and activat... more Chemokines are a family of small, structurally related cytokines with chemoattractant and activation properties. In breast cancer, both epithelial cancer cells and cells within the microenvironment secrete chemokines with either tumor-promoting or anti-malignant potential. The equilibrium between these two chemokine activities plays a key role in the biology of the developing tumor, including its ability to metastasize. Here we evaluated the expression of chemokines in breast tumors and the plasma of breast cancer patients before treatment in order to identify a blood-based signature that could distinguish between malignant and non-malignant processes. We screened the mRNA expression of chemokine genes using cDNA microarray on homogenous, laser-capture microdissected breast cancer specimens. Further, using a protein array approach, we determined the levels of selected chemokines in the plasma of patients with breast cancer, benign breast tumors and healthy women. Finally, we analyzed the association between the levels of chemokines in breast and blood samples with the pathological characteristics of the disease. At mRNA level, 27 chemokines and 11 chemokine receptors were differentially expressed in cancers when compared with normal breast tissue. When compared to benign tumors, the only chemokine significantly upregulated in cancers was CXCL10. At protein level, with the exception of CXCL13, nine out of the ten selected chemokines (CCL2, CCL7, CCL18, CCL22, CXCL8, CXCL9, CXCL10, CXCL11 and osteoprotegerin) were significantly overexpressed in the plasma of breast cancers patients compared to healthy controls. After grouping, CXCL8, CXCL9 and CCL22 proved to be significant predictors for breast cancers as compared to healthy controls in a model of logistic regression. We found upregulation of CXCL8, CXCL11 and CXCL9 in triple negative carcinomas, CXCL9 in low proliferative carcinomas, and CXCL10, CCL7 and osteoprotegerin in poorly differentiated carcinomas. Furthermore, CXCL9 was overexpressed in lymph node negative tumors, whereas CXCL8 and CCL18 were higher in advanced stage carcinomas. We identified a panel of chemokines dysregulated in breast cancer that could be further investigated as prospective novel diagnostic markers or for therapeutic and prognostic applications.

Geriatric nephrology and urology, 1997

Background: Prostate cancer (PCa) represents the second most prevalent malignancy among males, wh... more Background: Prostate cancer (PCa) represents the second most prevalent malignancy among males, which is characterized by a high mortality rate. The aim of our study was to evaluate the methylation status of glutathione S-transferase P1 (GSTP1) in urine specimens from males with PCa and benign prostatic hyperplasia (BPH) and its usefulness in distinguishing between males with PCa and BPH by noninvasive methods. Methods: Voided urine specimens were collected from 65 patients with PCa and 45 patients with BPH. Genomic DNA was isolated and subjected to bisulfite modification. Methylation status of the GSTP1 gene was determined by conventional methylation-specific polymerase chain reaction (MSP) analysis. Results: Promoter hypermethylation of the GSTP1 gene in voided urine samples was found in 63 of 65 (97%) males with PCa and in 5 of 45 (11%) males with BPH. The sensitivity and specificity of GSTP1 in discriminating between PCa and BPH males were 98% and 89%, respectively. Conclusions: Gene analysis of GSTP1 using conventional MSP in urine specimens can be used as a noninvasive biomarker to distinguish between men with malignant and benign prostatic diseases.

Romanian Journal of Ophtalmology, Jun 12, 2021

This is an open-access article distributed under the terms of the Creative Commons Attribution Li... more This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Psychology, Health & Medicine

In the context of the traumas suffered by patients following the oncological diagnosis and the ex... more In the context of the traumas suffered by patients following the oncological diagnosis and the expectation of the surgical intervention, it is important to unitary and multidimensional identify the psychological status, using a single interview structured to cover these psychological vulnerabilities. The overall psychological picture can help the psycho-oncologist to adapt his psychotherapeutic interventions to relieve the stress caused by the oncological diagnosis and specific treatment. 58 patients with a breast cancer diagnosis and 61 patients with breast lumps diagnosis who were waiting for the histopathological result, received several scales for assessing emotional distress, the level self-esteem, depression, anxiety and cognitive dysfunctions levels. The analysis of the answers led to the multidimensional identification of differences between the two categories of patients and establishing correlations between personality traits and the development of certain psychological changes. Statistically significant differences (p < 0.05) were observed between patients with breast cancer and those with breast lumps awaiting histopathological diagnosis, in the areas of self-esteem, depression and cognitive schemas. Diagnosed patients have predominantly dysfunctional attitudes such as negative emotions and cognitive schemas related to catastrophe and self-deprecation, while undiagnosed patients, have cognitive schemas related to low tolerance for frustration and absolutist requirements and lower dysfunctional attitudes. A global assessment with a single psychological tool can capture the overall picture of the cancer patient, including possible triggers and maintenance of symptoms, with the psychological consequences of the disease that are reflected somatically, as well as predisposing factors in the history that generates these feelings.

PLOS ONE

Introduction Kidney dysfunction is prevalent in oncology patients and has an impact on their trea... more Introduction Kidney dysfunction is prevalent in oncology patients and has an impact on their treatment and quality of life. The aim of our study was to analyze the prevalence of CKD in a large cohort of several types of cancer patients in an East European Region. Material and methods We conducted an observational retrospective cohort study on 5831 consecutive, biopsy-diagnosed cancer patients between January 2019 –December 2020 in the largest oncology hospital and outpatient clinic in Western Romania. 4342 subjects were included in the statistical analysis. Results and discussion From the 24 cancer types, the most prevalent cancers were represented by: breast (22.02%), lung (10.18%) and colonic cancer (9.51%). The prevalence of CKD (G3 –G5) was 12.27% after the first year of follow-up and 13.42 after the second year. The prevalence of CKD was higher in patients with renal (50%), urinary tract (33.6%) and pancreatic cancers (19.6%) and lower in patients with colonic cancers (5.3%) an...

The Lancet Gastroenterology & Hepatology

Background Combating viral hepatitis is part of the UN Sustainable Development Goals (SDGs), and ... more Background Combating viral hepatitis is part of the UN Sustainable Development Goals (SDGs), and WHO has put forth hepatitis B elimination targets in its Global Health Sector Strategy on Viral Hepatitis (WHO-GHSS) and Interim Guidance for Country Validation of Viral Hepatitis Elimination (WHO Interim Guidance). We estimated the global, regional, and national prevalence of hepatitis B virus (HBV), as well as mortality and disability-adjusted life-years (DALYs) due to HBV, as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. This included estimates for 194 WHO member states, for which we compared our estimates to WHO elimination targets. Methods The primary data sources were population-based serosurveys, claims and hospital discharges, cancer registries, vital registration systems, and published case series. We estimated chronic HBV infection and the burden of HBV-related diseases, defined as an aggregate of cirrhosis due to hepatitis B, liver cancer due to hepatitis B, and acute hepatitis B. We used DisMod-MR 2.1, a Bayesian mixed-effects meta-regression tool, to estimate the prevalence of chronic HBV infection, cirrhosis, and aetiological proportions of cirrhosis. We used mortality-to-incidence ratios modelled with spatiotemporal Gaussian process regression to estimate the incidence of liver cancer. We used the Cause of Death Ensemble modelling (CODEm) model, a tool that selects models and covariates on the basis of out-ofsample performance, to estimate mortality due to cirrhosis, liver cancer, and acute hepatitis B. Findings In 2019, the estimated global, all-age prevalence of chronic HBV infection was 4•1% (95% uncertainty interval [UI] 3•7 to 4•5), corresponding to 316 million (284 to 351) infected people. There was a 31•3% (29•0 to 33•9) decline in all-age prevalence between 1990 and 2019, with a more marked decline of 76•8% (76•2 to 77•5) in prevalence in children younger than 5 years. HBV-related diseases resulted in 555 000 global deaths (487 000 to 630 000) in 2019. The number of HBV-related deaths increased between 1990 and 2019 (by 5•9% [-5•6 to 19•2]) and between 2015 and 2019 (by 2•9% [-5•9 to 11•3]). By contrast, all-age and age-standardised death rates due to HBV-related diseases decreased during these periods. We compared estimates for 2019 in 194 WHO locations to WHO-GHSS 2020 targets, and found that four countries achieved a 10% reduction in deaths, 15 countries achieved a 30% reduction in new cases, and 147 countries achieved a 1% prevalence in children younger than 5 years. As of 2019, 68 of 194 countries had already achieved the 2030 target proposed in WHO Interim Guidance of an all-age HBV-related death rate of four per 100 000. Interpretation The prevalence of chronic HBV infection declined over time, particularly in children younger than 5 years, since the introduction of hepatitis B vaccination. HBV-related death rates also decreased, but HBV-related death counts increased as a result of population growth, ageing, and cohort effects. By 2019, many countries had met the interim seroprevalence target for children younger than 5 years, but few countries had met the WHO-GHSS interim targets for deaths and new cases. Progress according to all indicators must be accelerated to meet 2030 targets, and there are marked disparities in burden and progress across the world. HBV interventions, such as vaccination, testing, and treatment, must be strategically supported and scaled up to achieve elimination. Funding Bill &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp; Melinda Gates Foundation.

Experimental and Therapeutic Medicine

Identifying markers capable of predicting outcomes in lung cancer patients treated with nivolumab... more Identifying markers capable of predicting outcomes in lung cancer patients treated with nivolumab represents a growing research interest. The combination of neutrophil-to-lymphocyte ratio (NLR) and body mass index (BMI) may help predict treatment efficacy. Thus, the present study aimed to investigate the influence of NLR and BMI on progression-free survival (PFS) in non-small-cell lung cancer (NSCLC) patients treated with nivolumab. A retrospective study was made on 80 patients with NSCLC that were treated with nivolumab at the OncoHelp Oncology Center, Timisoara, Romania after platinum-based chemotherapy, from January 2018 to April 2020. Patients were administered nivolumab at a dose of 3 mg/m 2 or 240 mg total dose, every 2 weeks. The predictive impact of NLR (baseline at 2 and 4 weeks after the start of nivolumab) and BMI for disease progression was assessed. Median PFS for subjects with NLR <3 before treatment was 18.5 weeks, while in subjects with NLR ≥3 was 14 weeks (P=0.50). Median PFS for subjects with NLR2 <3 at 2 weeks after treatment was 21 weeks, while in subjects with NLR2 ≥3, PFS was 14 weeks (P=0.17). Median PFS for subjects with NLR4 <3 at 4 weeks after treatment was 23 weeks, while in subjects with NLR4 ≥3, PFS was 19 weeks (P= 0.33). Multivariate analysis for the association with PFS showed that baseline NLR, male sex and BMI were associated independently, thus we could develop a significant statistical model [AUROC= 0.76, 95% CI (0.45-0.89), P= 0.03], a new predictive score for PFS. The assessment of NLR and BMI may represent simple and useful biomarkers; combining them and taking into consideration the male sex may predict PFS in patients with advanced NSCLC treated with nivolumab.

Experimental and Therapeutic Medicine, 2021

The aim of the present study was to examine both the feasibility and toxicity of neoadjuvant dose... more The aim of the present study was to examine both the feasibility and toxicity of neoadjuvant dose-dense chemotherapy in women with non-metastatic breast cancer. A search within the OncoHelp Association breast cancer database has been performed in order to identify all non-metastatic breast cancer patients who underwent an initial consultation with a medical oncologist between March 2016 and April 2020. The inclusion criteria used were: i) Age, ii) follow-up care obtained at OncoHelp Association, iii) the intent to treat with a neoadjuvant dose-dense anthracycline every two weeks for four cycles (C1-C4) followed by paclitaxel every two weeks for four cycles, with white blood cell growth factor support, and iv) regular anthracycline-based chemotherapy every three weeks for four cycles, followed by paclitaxel every three weeks for four cycles, v) weight, vi) height, vii) Eastern Cooperative Oncology Group (ECOG) performance status, viii) hemoglobin (Hb) level, ix) Platelet count and x) neutrophil count.

Annals of Oncology, 2021

Background: Tumor cells death induced by photodynamic therapy (PDT) drives to inflammation and an... more Background: Tumor cells death induced by photodynamic therapy (PDT) drives to inflammation and antigens release and can activate specific anti-tumor immune response. In this work, we demonstrated the in vivo effect of vaccination with PDTtreated tumor cells. Methods: PDT anti-tumor vaccines were obtained by continuous wave (CW) or pulse mode (PM) 662 nm laser irradiation (light dose: 4, 8 J/cm 2 ; fluence rate: 50 mW/cm 2) of mouse cervical cancer cells (RShM-5, 5x10 5 cells) preliminarily treated with chlorine e6 based photosensitizer Radachlorin (PS; concentration: 7 mkg/ml, 10 mkg/ml). Cell viability were assessed using Annexin V-FITC/PI assay and analyzed by flow cytometry. After 24 h PDT-treated RShM-5 cells (1.25x10 5 cells) were harvested and subcutaneous injected into right flank of CBA mice. 8 days after vaccination mice were subcutaneous injected with 5x10 5 live RShM-5 cells in another flank. The size of the initiated tumor node in the challenge site was monitored up to 70 days after the inoculation. The survival rate was assessed in the control group (CG n¼10), CW PDT group (CWG, n¼9), PM PDT group (PMG, n¼9) and freeze-thaw cell lysis group (FTG, n¼9). Mice were sacrificed when the tumor volume exceeded 4 cm 3. abstracts Annals of Oncology Volume 32-Issue S5-2021 S371

Experimental and Therapeutic Medicine, 2020

The present systematic review and meta-analysis investigated the association between exposure to ... more The present systematic review and meta-analysis investigated the association between exposure to radiofrequency radiation and the risk of breast cancer. The published studies that were available in PubMed, Embase, Cochrane Library, Ovid MEDLINE, CINAHL Plus, Web of Science, Airiti Library, Networked Digital Library of Theses and Dissertations and ProQuest until May 2020 were investigated. A total of eight studies (four case-control and four cohort studies) were eligible for quantitative analysis. A significant association between radiofrequency radiation exposure and breast cancer risk was detected [pooled relative risk (RR)=1.189; 95% confidence interval (CI), 1.056-1.339]. Subgroup analyses indicated that radiofrequency radiation exposure significantly increased the risk of breast cancer susceptibility among subjects aged ≥50 years (RR=2.179; 95% CI, 1.260-3.770). Pooled estimates revealed that the use of electrical appliances, which emit radiofrequency radiation, such as mobile phones and computers, significantly increased breast cancer development (RR=2.057; 95% CI, 1.272-3.327), while occupational radiofrequency exposure and transmitters did not increase breast cancer development (RR=1.274; 95% CI, 0.956-1.697; RR=1.133; 95% CI, 0.987-1.300, respectively). It was concluded that radiofrequency radiation exposure significantly increased the risk of breast cancer, especially in women aged ≥50 years and in individuals who used electric appliances, such as mobile phones and computers. In accordance with Preferred Reporting Items for Systematic Reviews and Meta-analysis, an evaluation protocol was prepared and registered with the PROSPERO database (registration no. CRD42018087283).

Experimental and Therapeutic Medicine, 2020

Hematopoietic bone marrow toxicity is most often the limiting factor for chemotherapy doses. Incr... more Hematopoietic bone marrow toxicity is most often the limiting factor for chemotherapy doses. Increasing the intensity of chemotherapy doses (higher doses or more frequent administration) would improve antitumor effects, but the hematological toxicity does not allow these dose increases. This study evaluated the impact of chemotherapies on the parameters belonging to the red blood cell series in the hemogram and aimed to identify some particular evolution profiles. We selected 855 evaluations performed before the administration of chemotherapy belonging to the treatments initiated during the period December 2018-February 2020, containing 5-fluorouracil, cisplatin, docetaxel, epirubicin or pemetrexed. The data of the 644 evaluations related to the cycles 1-4 of chemotherapy were subject to this processing. The average relative loss of hemoglobin is-11% after the first three cycles of treatment, with statistically significant differences in hemoglobin levels in favor of men. There are risk factors associated with higher average losses, such as age <50 years or >65 years (statistically significant), body mass index (BMI) >25, cisplatin treatment (insufficient number of cases to reach statistical significance).

romanian journal of ophthalmology, 2020

PD-1 is expressed on the surface of activated T lymphocytes and belongs to the category of negati... more PD-1 is expressed on the surface of activated T lymphocytes and belongs to the category of negative immune stimuli. Its blocking stimulates the immune response to tumor antigens. Ocular melanomas represent 3-4% of the total melanomas and have metastatic potential, especially to the liver but also to the lungs, skin, and bones. In the case of metastatic melanoma, immunotherapy has a unique role due to the lower frequencies of BRAF mutation in choroidal melanomas and consecutive exclusion from treatment with specific BRAF tyrosine kinase inhibitors. A retrospective observational study was performed in 42 patients who received immunotherapy (IT) with nivolumab for cutaneous and ocular metastatic melanomas, aimed at highlighting the association between the topography of metastases and the duration of immunotherapy until progressive disease. The results indicated the presence of liver metastases as a negative predictive factor for IT duration in patients with melanoma and the presence of lymphatic metastases as a predictive factor for longer IT in patients with melanoma under 65 years old.

romanian journal of ophthalmology, 2020

The height of the adult individual is a balance of the expression of some genetic factors (especi... more The height of the adult individual is a balance of the expression of some genetic factors (especially the Y-M 170 haplotype of the Y chromosome) and the environment (nutrition and morbidity during childhood). Higher height is associated with a low risk of developing coronary heart disease, hypertension, gastroesophageal reflux, diaphragmatic hernia, but with a higher risk for atrial fibrillation, venous thromboembolism, intervertebral disc pathology, vasculitis and cancer. The research consisted of a retrospective observational study on patients who received immunotherapy (IT) with nivolumab for cutaneous and ocular melanoma neoplasms. We intended to highlight the associations between the duration of immunotherapy and sex profiles, age, anthropometric data (height, weight). Even though the number of available cases was relatively small (42), an inverse association between the body mass index of the subjects and the duration of immunotherapy could be proved, a more expressed association in case of male patients.

Acta Endocrinologica (Bucharest), 2019

We report the case of a 55-year-old-male with a large cell metastatic pancreatic neuroendocrine c... more We report the case of a 55-year-old-male with a large cell metastatic pancreatic neuroendocrine carcinoma treated for 14 months with lanreotide autogel having a stable disease (SD) and not responding to chemotherapy. The somatostatin analogues (SSA) were introduced after an episode of diarrhea and controlled the disease. Progression-free survival (PFS) as determined by Computerized Tomography (CT) scans was obtained for 14 months. After more than a year, the patient's health state deteriorated along with progressive disease. The capecitabine-temozolomide regimen was challenged, but after three cycles, a rapid clinical decline was noted. Conclusion. This unexpected event (diarrhea) in the course of the disease could represent the beginning of carcinoid syndrome. While the lanreotide autogel helped the episode of diarrhea pass, it also helped gain control over the disease itself.

PubMed, Feb 16, 2002

This study was performed on a lot of 51 patients and intends to correlate the autoimmune thyroidi... more This study was performed on a lot of 51 patients and intends to correlate the autoimmune thyroiditis to the synthesis of Th1 cytokines and to the activation of T lymphocytes. We find out that CD25, an activation marker of T lymphocytes, is significantly increased in these patients. We also find out that certain cytokine serum levels are increased (IL-2, TNF-alpha, IFN-gamma). These cytokines correspond to the secretor profile of the Th1 subset. Mononuclear cell culture supernatants showed an increased level of IL-2 and TNF-alpha in samples stimulated with ConA in comparison to unstimulated samples from the same patient, suggesting the existence of an expansioned Th1 and CD8+ cytotoxic population.

Medicina-lithuania, Jul 21, 2022

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

European Scientific Journal, ESJ, Jun 30, 2013

Introduction: The diagnostic of prostate cancer (PCa) using serumbased prostate specific antigen ... more Introduction: The diagnostic of prostate cancer (PCa) using serumbased prostate specific antigen (PSA) has some limitations due to falsepositive and negative results. The purpose of our study was to analyse the hypermethylation of three genes from plasma samples and to determine the feasibility of these genes to aid as biomarkers in detecting PCa in plasma by noninvasive methods. Materials and Methods: Genomic DNA was extracted from the peripheral blood plasma of 74 patients with localized PCa. All the samples were examined for aberrant hypermethylation in retinoic acid receptor β variant 2 (RARβ2), glutathione S-transferase P1 (GSTP1) and Ras association domain family 1 isoform A(RASSF1A) genes, using methylation-specific PCR (MSP), and the results were correlated with the clinicopathological parameters. Results: The percent of methylation of the analyzed genes was as follows: RARβ2 was found methylated in 54 cases (73 %), GSTP1 in 58 cases (78.4%), and RASSF1A was found methylated in all 74 cases (100%). Conclusion: Our study demonstrates that, using a panel of DNA methylated biomarkers aids the identification of PCa patients and with minimally invasive techniques , may yield information independent of serum PSA or the TNM stage.

Experimental and Therapeutic Medicine, Mar 22, 2021

Currently, surgical techniques, such as internal limiting membrane peeling, are used widely for m... more Currently, surgical techniques, such as internal limiting membrane peeling, are used widely for macular holes, macular puckers, epiretinal membranes, diabetic macular edema, retinal detachment, retinal vein occlusions, vitreomacular traction, optic pit maculopathy, and Terson syndrome. This study aimed to highlight any differences regarding visual acuity and ocular tomography coherence changes after staining the internal limiting membrane with dilutions of Brilliant Blue G vs. lutein/zeaxanthin-based dyes. This study involved 30 eyes of 30 patients who had undergone posterior pole vitrectomy for idiopathic stage 4 macular hole. The study lot was divided in two subgroups, 15 eyes colored with Brilliant Blue and the other 15 eyes colored with lutein and zeaxanthin dyes. The association between visual prognosis, ocular tomography coherence changes and intraocular pressure was analyzed. The surgical treatment with required endoillumination levels and a 2-min period of dye using the Alcon Constellation Vision System had no negative impact on cell viability and improved visual acuity by 30%. Staining makes it easier to remove, to be quick and precise while performing macular surgeries. In has been observed that lutein and zeaxanthin dyes offer an intraoperative protective screen that protects photoreceptors more than Brilliant Blue while performing pars plana vitrectomy. Both study groups had good results in time. Surgical visualization is an evolving technology.

Medicina-lithuania, Jul 14, 2022

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Neoplasma, 2016

Chemokines are a family of small, structurally related cytokines with chemoattractant and activat... more Chemokines are a family of small, structurally related cytokines with chemoattractant and activation properties. In breast cancer, both epithelial cancer cells and cells within the microenvironment secrete chemokines with either tumor-promoting or anti-malignant potential. The equilibrium between these two chemokine activities plays a key role in the biology of the developing tumor, including its ability to metastasize. Here we evaluated the expression of chemokines in breast tumors and the plasma of breast cancer patients before treatment in order to identify a blood-based signature that could distinguish between malignant and non-malignant processes. We screened the mRNA expression of chemokine genes using cDNA microarray on homogenous, laser-capture microdissected breast cancer specimens. Further, using a protein array approach, we determined the levels of selected chemokines in the plasma of patients with breast cancer, benign breast tumors and healthy women. Finally, we analyzed the association between the levels of chemokines in breast and blood samples with the pathological characteristics of the disease. At mRNA level, 27 chemokines and 11 chemokine receptors were differentially expressed in cancers when compared with normal breast tissue. When compared to benign tumors, the only chemokine significantly upregulated in cancers was CXCL10. At protein level, with the exception of CXCL13, nine out of the ten selected chemokines (CCL2, CCL7, CCL18, CCL22, CXCL8, CXCL9, CXCL10, CXCL11 and osteoprotegerin) were significantly overexpressed in the plasma of breast cancers patients compared to healthy controls. After grouping, CXCL8, CXCL9 and CCL22 proved to be significant predictors for breast cancers as compared to healthy controls in a model of logistic regression. We found upregulation of CXCL8, CXCL11 and CXCL9 in triple negative carcinomas, CXCL9 in low proliferative carcinomas, and CXCL10, CCL7 and osteoprotegerin in poorly differentiated carcinomas. Furthermore, CXCL9 was overexpressed in lymph node negative tumors, whereas CXCL8 and CCL18 were higher in advanced stage carcinomas. We identified a panel of chemokines dysregulated in breast cancer that could be further investigated as prospective novel diagnostic markers or for therapeutic and prognostic applications.

Geriatric nephrology and urology, 1997

Background: Prostate cancer (PCa) represents the second most prevalent malignancy among males, wh... more Background: Prostate cancer (PCa) represents the second most prevalent malignancy among males, which is characterized by a high mortality rate. The aim of our study was to evaluate the methylation status of glutathione S-transferase P1 (GSTP1) in urine specimens from males with PCa and benign prostatic hyperplasia (BPH) and its usefulness in distinguishing between males with PCa and BPH by noninvasive methods. Methods: Voided urine specimens were collected from 65 patients with PCa and 45 patients with BPH. Genomic DNA was isolated and subjected to bisulfite modification. Methylation status of the GSTP1 gene was determined by conventional methylation-specific polymerase chain reaction (MSP) analysis. Results: Promoter hypermethylation of the GSTP1 gene in voided urine samples was found in 63 of 65 (97%) males with PCa and in 5 of 45 (11%) males with BPH. The sensitivity and specificity of GSTP1 in discriminating between PCa and BPH males were 98% and 89%, respectively. Conclusions: Gene analysis of GSTP1 using conventional MSP in urine specimens can be used as a noninvasive biomarker to distinguish between men with malignant and benign prostatic diseases.

Romanian Journal of Ophtalmology, Jun 12, 2021

This is an open-access article distributed under the terms of the Creative Commons Attribution Li... more This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Psychology, Health & Medicine

In the context of the traumas suffered by patients following the oncological diagnosis and the ex... more In the context of the traumas suffered by patients following the oncological diagnosis and the expectation of the surgical intervention, it is important to unitary and multidimensional identify the psychological status, using a single interview structured to cover these psychological vulnerabilities. The overall psychological picture can help the psycho-oncologist to adapt his psychotherapeutic interventions to relieve the stress caused by the oncological diagnosis and specific treatment. 58 patients with a breast cancer diagnosis and 61 patients with breast lumps diagnosis who were waiting for the histopathological result, received several scales for assessing emotional distress, the level self-esteem, depression, anxiety and cognitive dysfunctions levels. The analysis of the answers led to the multidimensional identification of differences between the two categories of patients and establishing correlations between personality traits and the development of certain psychological changes. Statistically significant differences (p < 0.05) were observed between patients with breast cancer and those with breast lumps awaiting histopathological diagnosis, in the areas of self-esteem, depression and cognitive schemas. Diagnosed patients have predominantly dysfunctional attitudes such as negative emotions and cognitive schemas related to catastrophe and self-deprecation, while undiagnosed patients, have cognitive schemas related to low tolerance for frustration and absolutist requirements and lower dysfunctional attitudes. A global assessment with a single psychological tool can capture the overall picture of the cancer patient, including possible triggers and maintenance of symptoms, with the psychological consequences of the disease that are reflected somatically, as well as predisposing factors in the history that generates these feelings.

PLOS ONE

Introduction Kidney dysfunction is prevalent in oncology patients and has an impact on their trea... more Introduction Kidney dysfunction is prevalent in oncology patients and has an impact on their treatment and quality of life. The aim of our study was to analyze the prevalence of CKD in a large cohort of several types of cancer patients in an East European Region. Material and methods We conducted an observational retrospective cohort study on 5831 consecutive, biopsy-diagnosed cancer patients between January 2019 –December 2020 in the largest oncology hospital and outpatient clinic in Western Romania. 4342 subjects were included in the statistical analysis. Results and discussion From the 24 cancer types, the most prevalent cancers were represented by: breast (22.02%), lung (10.18%) and colonic cancer (9.51%). The prevalence of CKD (G3 –G5) was 12.27% after the first year of follow-up and 13.42 after the second year. The prevalence of CKD was higher in patients with renal (50%), urinary tract (33.6%) and pancreatic cancers (19.6%) and lower in patients with colonic cancers (5.3%) an...

The Lancet Gastroenterology & Hepatology

Background Combating viral hepatitis is part of the UN Sustainable Development Goals (SDGs), and ... more Background Combating viral hepatitis is part of the UN Sustainable Development Goals (SDGs), and WHO has put forth hepatitis B elimination targets in its Global Health Sector Strategy on Viral Hepatitis (WHO-GHSS) and Interim Guidance for Country Validation of Viral Hepatitis Elimination (WHO Interim Guidance). We estimated the global, regional, and national prevalence of hepatitis B virus (HBV), as well as mortality and disability-adjusted life-years (DALYs) due to HBV, as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. This included estimates for 194 WHO member states, for which we compared our estimates to WHO elimination targets. Methods The primary data sources were population-based serosurveys, claims and hospital discharges, cancer registries, vital registration systems, and published case series. We estimated chronic HBV infection and the burden of HBV-related diseases, defined as an aggregate of cirrhosis due to hepatitis B, liver cancer due to hepatitis B, and acute hepatitis B. We used DisMod-MR 2.1, a Bayesian mixed-effects meta-regression tool, to estimate the prevalence of chronic HBV infection, cirrhosis, and aetiological proportions of cirrhosis. We used mortality-to-incidence ratios modelled with spatiotemporal Gaussian process regression to estimate the incidence of liver cancer. We used the Cause of Death Ensemble modelling (CODEm) model, a tool that selects models and covariates on the basis of out-ofsample performance, to estimate mortality due to cirrhosis, liver cancer, and acute hepatitis B. Findings In 2019, the estimated global, all-age prevalence of chronic HBV infection was 4•1% (95% uncertainty interval [UI] 3•7 to 4•5), corresponding to 316 million (284 to 351) infected people. There was a 31•3% (29•0 to 33•9) decline in all-age prevalence between 1990 and 2019, with a more marked decline of 76•8% (76•2 to 77•5) in prevalence in children younger than 5 years. HBV-related diseases resulted in 555 000 global deaths (487 000 to 630 000) in 2019. The number of HBV-related deaths increased between 1990 and 2019 (by 5•9% [-5•6 to 19•2]) and between 2015 and 2019 (by 2•9% [-5•9 to 11•3]). By contrast, all-age and age-standardised death rates due to HBV-related diseases decreased during these periods. We compared estimates for 2019 in 194 WHO locations to WHO-GHSS 2020 targets, and found that four countries achieved a 10% reduction in deaths, 15 countries achieved a 30% reduction in new cases, and 147 countries achieved a 1% prevalence in children younger than 5 years. As of 2019, 68 of 194 countries had already achieved the 2030 target proposed in WHO Interim Guidance of an all-age HBV-related death rate of four per 100 000. Interpretation The prevalence of chronic HBV infection declined over time, particularly in children younger than 5 years, since the introduction of hepatitis B vaccination. HBV-related death rates also decreased, but HBV-related death counts increased as a result of population growth, ageing, and cohort effects. By 2019, many countries had met the interim seroprevalence target for children younger than 5 years, but few countries had met the WHO-GHSS interim targets for deaths and new cases. Progress according to all indicators must be accelerated to meet 2030 targets, and there are marked disparities in burden and progress across the world. HBV interventions, such as vaccination, testing, and treatment, must be strategically supported and scaled up to achieve elimination. Funding Bill &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp; Melinda Gates Foundation.

Experimental and Therapeutic Medicine

Identifying markers capable of predicting outcomes in lung cancer patients treated with nivolumab... more Identifying markers capable of predicting outcomes in lung cancer patients treated with nivolumab represents a growing research interest. The combination of neutrophil-to-lymphocyte ratio (NLR) and body mass index (BMI) may help predict treatment efficacy. Thus, the present study aimed to investigate the influence of NLR and BMI on progression-free survival (PFS) in non-small-cell lung cancer (NSCLC) patients treated with nivolumab. A retrospective study was made on 80 patients with NSCLC that were treated with nivolumab at the OncoHelp Oncology Center, Timisoara, Romania after platinum-based chemotherapy, from January 2018 to April 2020. Patients were administered nivolumab at a dose of 3 mg/m 2 or 240 mg total dose, every 2 weeks. The predictive impact of NLR (baseline at 2 and 4 weeks after the start of nivolumab) and BMI for disease progression was assessed. Median PFS for subjects with NLR <3 before treatment was 18.5 weeks, while in subjects with NLR ≥3 was 14 weeks (P=0.50). Median PFS for subjects with NLR2 <3 at 2 weeks after treatment was 21 weeks, while in subjects with NLR2 ≥3, PFS was 14 weeks (P=0.17). Median PFS for subjects with NLR4 <3 at 4 weeks after treatment was 23 weeks, while in subjects with NLR4 ≥3, PFS was 19 weeks (P= 0.33). Multivariate analysis for the association with PFS showed that baseline NLR, male sex and BMI were associated independently, thus we could develop a significant statistical model [AUROC= 0.76, 95% CI (0.45-0.89), P= 0.03], a new predictive score for PFS. The assessment of NLR and BMI may represent simple and useful biomarkers; combining them and taking into consideration the male sex may predict PFS in patients with advanced NSCLC treated with nivolumab.

Experimental and Therapeutic Medicine, 2021

The aim of the present study was to examine both the feasibility and toxicity of neoadjuvant dose... more The aim of the present study was to examine both the feasibility and toxicity of neoadjuvant dose-dense chemotherapy in women with non-metastatic breast cancer. A search within the OncoHelp Association breast cancer database has been performed in order to identify all non-metastatic breast cancer patients who underwent an initial consultation with a medical oncologist between March 2016 and April 2020. The inclusion criteria used were: i) Age, ii) follow-up care obtained at OncoHelp Association, iii) the intent to treat with a neoadjuvant dose-dense anthracycline every two weeks for four cycles (C1-C4) followed by paclitaxel every two weeks for four cycles, with white blood cell growth factor support, and iv) regular anthracycline-based chemotherapy every three weeks for four cycles, followed by paclitaxel every three weeks for four cycles, v) weight, vi) height, vii) Eastern Cooperative Oncology Group (ECOG) performance status, viii) hemoglobin (Hb) level, ix) Platelet count and x) neutrophil count.

Annals of Oncology, 2021

Background: Tumor cells death induced by photodynamic therapy (PDT) drives to inflammation and an... more Background: Tumor cells death induced by photodynamic therapy (PDT) drives to inflammation and antigens release and can activate specific anti-tumor immune response. In this work, we demonstrated the in vivo effect of vaccination with PDTtreated tumor cells. Methods: PDT anti-tumor vaccines were obtained by continuous wave (CW) or pulse mode (PM) 662 nm laser irradiation (light dose: 4, 8 J/cm 2 ; fluence rate: 50 mW/cm 2) of mouse cervical cancer cells (RShM-5, 5x10 5 cells) preliminarily treated with chlorine e6 based photosensitizer Radachlorin (PS; concentration: 7 mkg/ml, 10 mkg/ml). Cell viability were assessed using Annexin V-FITC/PI assay and analyzed by flow cytometry. After 24 h PDT-treated RShM-5 cells (1.25x10 5 cells) were harvested and subcutaneous injected into right flank of CBA mice. 8 days after vaccination mice were subcutaneous injected with 5x10 5 live RShM-5 cells in another flank. The size of the initiated tumor node in the challenge site was monitored up to 70 days after the inoculation. The survival rate was assessed in the control group (CG n¼10), CW PDT group (CWG, n¼9), PM PDT group (PMG, n¼9) and freeze-thaw cell lysis group (FTG, n¼9). Mice were sacrificed when the tumor volume exceeded 4 cm 3. abstracts Annals of Oncology Volume 32-Issue S5-2021 S371

Experimental and Therapeutic Medicine, 2020

The present systematic review and meta-analysis investigated the association between exposure to ... more The present systematic review and meta-analysis investigated the association between exposure to radiofrequency radiation and the risk of breast cancer. The published studies that were available in PubMed, Embase, Cochrane Library, Ovid MEDLINE, CINAHL Plus, Web of Science, Airiti Library, Networked Digital Library of Theses and Dissertations and ProQuest until May 2020 were investigated. A total of eight studies (four case-control and four cohort studies) were eligible for quantitative analysis. A significant association between radiofrequency radiation exposure and breast cancer risk was detected [pooled relative risk (RR)=1.189; 95% confidence interval (CI), 1.056-1.339]. Subgroup analyses indicated that radiofrequency radiation exposure significantly increased the risk of breast cancer susceptibility among subjects aged ≥50 years (RR=2.179; 95% CI, 1.260-3.770). Pooled estimates revealed that the use of electrical appliances, which emit radiofrequency radiation, such as mobile phones and computers, significantly increased breast cancer development (RR=2.057; 95% CI, 1.272-3.327), while occupational radiofrequency exposure and transmitters did not increase breast cancer development (RR=1.274; 95% CI, 0.956-1.697; RR=1.133; 95% CI, 0.987-1.300, respectively). It was concluded that radiofrequency radiation exposure significantly increased the risk of breast cancer, especially in women aged ≥50 years and in individuals who used electric appliances, such as mobile phones and computers. In accordance with Preferred Reporting Items for Systematic Reviews and Meta-analysis, an evaluation protocol was prepared and registered with the PROSPERO database (registration no. CRD42018087283).

Experimental and Therapeutic Medicine, 2020

Hematopoietic bone marrow toxicity is most often the limiting factor for chemotherapy doses. Incr... more Hematopoietic bone marrow toxicity is most often the limiting factor for chemotherapy doses. Increasing the intensity of chemotherapy doses (higher doses or more frequent administration) would improve antitumor effects, but the hematological toxicity does not allow these dose increases. This study evaluated the impact of chemotherapies on the parameters belonging to the red blood cell series in the hemogram and aimed to identify some particular evolution profiles. We selected 855 evaluations performed before the administration of chemotherapy belonging to the treatments initiated during the period December 2018-February 2020, containing 5-fluorouracil, cisplatin, docetaxel, epirubicin or pemetrexed. The data of the 644 evaluations related to the cycles 1-4 of chemotherapy were subject to this processing. The average relative loss of hemoglobin is-11% after the first three cycles of treatment, with statistically significant differences in hemoglobin levels in favor of men. There are risk factors associated with higher average losses, such as age <50 years or >65 years (statistically significant), body mass index (BMI) >25, cisplatin treatment (insufficient number of cases to reach statistical significance).

romanian journal of ophthalmology, 2020

PD-1 is expressed on the surface of activated T lymphocytes and belongs to the category of negati... more PD-1 is expressed on the surface of activated T lymphocytes and belongs to the category of negative immune stimuli. Its blocking stimulates the immune response to tumor antigens. Ocular melanomas represent 3-4% of the total melanomas and have metastatic potential, especially to the liver but also to the lungs, skin, and bones. In the case of metastatic melanoma, immunotherapy has a unique role due to the lower frequencies of BRAF mutation in choroidal melanomas and consecutive exclusion from treatment with specific BRAF tyrosine kinase inhibitors. A retrospective observational study was performed in 42 patients who received immunotherapy (IT) with nivolumab for cutaneous and ocular metastatic melanomas, aimed at highlighting the association between the topography of metastases and the duration of immunotherapy until progressive disease. The results indicated the presence of liver metastases as a negative predictive factor for IT duration in patients with melanoma and the presence of lymphatic metastases as a predictive factor for longer IT in patients with melanoma under 65 years old.

romanian journal of ophthalmology, 2020

The height of the adult individual is a balance of the expression of some genetic factors (especi... more The height of the adult individual is a balance of the expression of some genetic factors (especially the Y-M 170 haplotype of the Y chromosome) and the environment (nutrition and morbidity during childhood). Higher height is associated with a low risk of developing coronary heart disease, hypertension, gastroesophageal reflux, diaphragmatic hernia, but with a higher risk for atrial fibrillation, venous thromboembolism, intervertebral disc pathology, vasculitis and cancer. The research consisted of a retrospective observational study on patients who received immunotherapy (IT) with nivolumab for cutaneous and ocular melanoma neoplasms. We intended to highlight the associations between the duration of immunotherapy and sex profiles, age, anthropometric data (height, weight). Even though the number of available cases was relatively small (42), an inverse association between the body mass index of the subjects and the duration of immunotherapy could be proved, a more expressed association in case of male patients.

Acta Endocrinologica (Bucharest), 2019

We report the case of a 55-year-old-male with a large cell metastatic pancreatic neuroendocrine c... more We report the case of a 55-year-old-male with a large cell metastatic pancreatic neuroendocrine carcinoma treated for 14 months with lanreotide autogel having a stable disease (SD) and not responding to chemotherapy. The somatostatin analogues (SSA) were introduced after an episode of diarrhea and controlled the disease. Progression-free survival (PFS) as determined by Computerized Tomography (CT) scans was obtained for 14 months. After more than a year, the patient's health state deteriorated along with progressive disease. The capecitabine-temozolomide regimen was challenged, but after three cycles, a rapid clinical decline was noted. Conclusion. This unexpected event (diarrhea) in the course of the disease could represent the beginning of carcinoid syndrome. While the lanreotide autogel helped the episode of diarrhea pass, it also helped gain control over the disease itself.

PubMed, Feb 16, 2002

This study was performed on a lot of 51 patients and intends to correlate the autoimmune thyroidi... more This study was performed on a lot of 51 patients and intends to correlate the autoimmune thyroiditis to the synthesis of Th1 cytokines and to the activation of T lymphocytes. We find out that CD25, an activation marker of T lymphocytes, is significantly increased in these patients. We also find out that certain cytokine serum levels are increased (IL-2, TNF-alpha, IFN-gamma). These cytokines correspond to the secretor profile of the Th1 subset. Mononuclear cell culture supernatants showed an increased level of IL-2 and TNF-alpha in samples stimulated with ConA in comparison to unstimulated samples from the same patient, suggesting the existence of an expansioned Th1 and CD8+ cytotoxic population.