Antitumor activity of organoruthenium complexes with chelate aromatic ligands, derived from 1,10-phenantroline: Synthesis and biological activity.

The monocationic chloro complexes containing chelating N∩N ligands: [(η-p-cymene)Ru(L1-4)Cl] (1-4), where L1 = 4-methyl-1,10-phenantroline, L2 = dipyrido[3,2-a:2',3'-c]phenazine, L3 = 11-chloro-dipyrido[3,2-a:2',3'-c]phenazine, L4 = 11-nitro-dipyrido[3,2-a:2',3'-c]phenazine; p-cymene = 1-methyl-4-isopropylbenzene) have been prepared and characterized as the hexafluorophosphate salts. The biological activity of 1-4 has been investigated in selected 2D monolayer cell cultures (A549, PANC-1, MDA-MB-231, MRC-5). All investigated ruthenium complexes showed similar or even better cytotoxicity to cisplatin.

Telmisartan induces melanoma cell apoptosis and synergizes with vemurafenib by altering cell bioenergetics.

Objective: Despite recent advancements in targeted therapy and immunotherapies, prognosis for metastatic melanoma patients remains extremely poor. Development of resistance to previously effective treatments presents a serious challenge and new approaches for melanoma treatment are urgently needed. The objective of this study was to examine the effects of telmisartan, an AGTR1 inhibitor and a partial agonist of PPARγ, on melanoma cells as a potential agent for repurposing in melanoma treatment.

From presentation to paper: Gender disparities in oncological research.

Gender disparities in scientific publications have been identified in oncological research. Oral research presentations at major conferences enhance visibility of presenters. The share of women presenting at such podia is unknown.

Confirmation of damaging effect of MSH2 c.2634+1G>C mutation on splicing, its classification and implications for counseling.

Introduction: Lynch syndrome (LS) is predisposing mainly to colorectal and endometrial carcinomas, but also to urinary tract cancers. LS association with upper urinary tract carcinomas is known, but its association with bladder cancer is not so clear. Confirmation of pathogenicity of detected mutations in LS-associated genes is required for adequate counseling.

A Brief Guide to Performing Pharmacological Studies : Reflections from the EORTC-PAMM Course "Preclinical and Early-phase Clinical Pharmacology".

One aim of cell-based in vitro assays is to identify the best drug candidate to develop using the best tumor cell model. This is challenging in every anticancer drug discovery process. Briefly, we summarize the parameters to be taken into account when performing in vitro cell assays, in order to obtain reliable and reproducible results, which was fundamentally discussed by lecturers at the educational course on preclinical and early-phase clinical pharmacology studies, at the 40th Winter Meeting of the Pharmacology and Molecular Mechanisms Group of the European Organization for Research and Treatment of Cancer.

High expression of junctional adhesion molecule-A is associated with poor survival in patients with epithelial ovarian cancer.

Purpose: Aberrant expression of different tight junction proteins, including the junctional adhesion molecule-A (JAM-A), has been frequently reported in association with tumor progression of several malignancies. To our knowledge, this is the first study examining the clinical significance of gene expression in epithelial ovarian cancer.

Methods: expression levels in 44 epithelial ovarian cancer and 12 benign formalin-fixed paraffin-embedded samples were determined by reverse transcription quantitative polymerase chain reaction.

The Endocannabinoid System as a Target in Cancer Diseases: Are We There Yet?

The endocannabinoid system (ECS) has been placed in the anti-cancer spotlight in the last decade. The immense data load published on its dual role in both tumorigenesis and inhibition of tumor growth and metastatic spread has transformed the cannabinoid receptors CB1 (CB1R) and CB2 (CB2R), and other members of the endocannabinoid-like system, into attractive new targets for the treatment of various cancer subtypes. Although the clinical use of cannabinoids has been extensively documented in the palliative setting, clinical trials on their application as anti-cancer drugs are still ongoing.

LungCARD - Report on worldwide research and clinical practices related to lung cancer.

Purpose: The management of advanced lung cancer has evolved tremendously over the past two decades. Increasing understanding of the molecular changes that drive tumor progression has transformed the treatment of this disease. Nevertheless, various countries differ in the degree of implementation of genetic tests and the availability of innovative drugs.

PIK3CA alterations and benefit with neratinib: analysis from the randomized, double-blind, placebo-controlled, phase III ExteNET trial.

Background: Neratinib is an irreversible pan-HER tyrosine kinase inhibitor that inhibits PI3K/Akt and MAPK signaling pathways after HER2 receptor activation. The ExteNET study showed that neratinib significantly improved 5-year invasive disease-free survival (iDFS) in women who completed trastuzumab-based adjuvant therapy for early breast cancer (EBC). We assessed the prognostic and predictive significance of PIK3CA alterations in patients in ExteNET.

Significance of *28 Genotype in Patients with Advanced Liver Injury Caused By Chronic Hepatitis C.

Background: Chronic hepatitis C (CHC) is a significant cause of liver related morbidity and mortality worldwide. The role of genetics in the host response to hepatitis C virus is not elucidated. Genetic variations in gene are the most common cause of hereditary unconjugated hyperbilirubinemia-Gilbert syndrome.

Discovery of the Biginelli hybrids as novel caspase-9 activators in apoptotic machines: Lipophilicity, molecular docking study, influence on angiogenesis gene and miR-21 expression levels.

In order to investigate potential therapeutically agents, novel products of Biginelli reaction (4a-l) were synthesized and exposed to cytotoxic and caspase activities, angiogenesis, cell cycle distribution, gene and microRNA expression levels, lipophilicity assessment and docking study. Among the twelve novel compounds (4a-l) evaluated for the cytotoxic activity, five of them (4c, 4d, 4f, 4k and 4l) that showed excellent activity on the tested cell lines (HeLa, LS174 and A549) were selected for further evaluation. Interestingly, compound 4f has up to three times higher selectivity index (SI) towards cancer cells than cisplatin (on HeLa, LS174 and A549 SI = 18.

New organoruthenium compounds with pyrido[2',3':5,6]pyrazino[2,3-f][1, 10]phenanthroline: synthesis, characterization, cytotoxicity, and investigation of mechanism of action.

Three new ruthenium(II)-arene complexes with pyrido[2',3':5,6]pyrazino[2,3-f][1, 10]phenanthroline (ppf) of general formula: C1 ([(ƞ-benzene)Ru(ppf)Cl]PF, C2 ([(ƞ-toluene)Ru(ppf)Cl]PF) and C3 ([(ƞ-p-cymene)Ru(ppf)Cl]PF) have been synthesized. The structures of complexes were determined by elemental analysis, IR, ESI-MS, as well as with H and C NMR spectroscopy. Cytotoxic activity has been evaluated in three different human neoplastic cell lines (A549, A375, LS 174T) and in one human non-tumor cell line (MRC-5), by the MTT assay.

Analyzing the post-contrast attenuation of the esophageal wall on routine contrast-enhanced MDCT examination can improve the diagnostic accuracy in response evaluation of the squamous cell esophageal carcinoma to neoadjuvant chemoradiotherapy in comparison with the esophageal wall thickness.

Purpose: To evaluate the accuracy of the multidetector computed tomography (MDCT) in the response evaluation of the esophageal squamous cell carcinoma (ESCC) to neoadjuvant chemoradiotherapy (nCRT) by analyzing the thickness and post-contrast attenuation of the esophageal wall after the nCRT.

Methods: Contrast-enhanced (CE)-MDCT examinations in portal venous phase of one hundred patients with locally advanced ESCC who received nCRT and underwent esophageal resection and histopathology assessment of tumor regression grade (TRG) were retrospectively analyzed by measuring the maximal thickness and mean density of the esophageal wall in the segment involved by tumor and visually searching for hyperdense foci within it. Diagnostic performance was evaluated using the ROC analysis.

Novel -methyl goniofufurone and 7--goniofufurone derivatives: synthesis, cytotoxicity and SAR analysis.

Novel goniofufurone () and 7--goniofufurone () derivatives bearing a methoxy group at the C-5 and/or C-7 positions were prepared and their antitumour activity against some human tumour cell lines was evaluated. Some of the analogues displayed powerful antiproliferative effects against the studied tumour cells, but almost all of them were non-cytotoxic toward the normal cells (MRC-5). A SAR study reveals that the introduction of a methoxy group at the C-7 position may increase the antiproliferative effects of the analogues.

Germline mutations in cancer susceptibility genes in high grade serous ovarian cancer in Serbia.

Clinical criteria for genetic testing of genes other than BRCA1/2 in epithelial ovarian cancer (EOC) still do not exist. We assessed the frequency and predictors of deleterious mutations in 19 cancer predisposition genes in high-grade serous ovarian cancer (HGSOC) in Serbia. Next-generation sequencing was used to identify germline mutations in the whole coding regions of a gene panel.

Treatment results of childhood Ewing's sarcoma of the bone in Serbia.

Purpose: The purpose of this study was to present treatment results of childhood Ewing's sarcoma (ES) of the bone in Serbia and to analyze prognostic factors.

Methods: We performed a detailed analysis on a series of 107 patients with ES of the bone treated at the Institute for Oncology and Radiology of Serbia between 2000 and 2014, using modern multimodal therapy.

Results: Median age at the time of diagnosis was 14 years, with 56.

Evaluation of predictive value of 1H MR spectroscopy for response of neoadjuvant chemotherapy in musculoskeletal tumors.

Purpose: Bone and soft tissue tumors are rare. There is a variety of types and each one has its own particular behavior, treatment and patient outcome. The assessment of treatment response following the 3rd cycle of chemotherapy is one of the most important aspects of patient care, as therapeutic options and the timing of surgery may vary depending on the achievement of response.

17β-estradiol inhibits hepatic iNOS via the activation of the estrogen receptor ER-α and inhibition of erk1/2-mir-221 axis.

17β-Estradiol (E2) is known to negatively regulate inducible nitric oxide (NO) synthase (iNOS) expression via estrogen receptor alpha (ER-α) activation in aortic vascular smooth muscle cells.Therefore, we sought to determine whether E2 can inhibit iNOS in hepatic tissue via the activation of ER-α and whether extracellular signal-regulated kinases 1/2 (ERK1/2)-miR-221 axis is involved in this process. Male Wistar rats were treated with a bolus injection of E2 intraperitoneally (40 μg/kg), and 24 hours after treatment the animals were sacrificed and the livers excised.

The impact of different infusion solutions on postoperative recovery following colorectal surgery.

Purpose: The purpose of this study was to compare two groups in postoperative recovery, whether there were any complications and whether the length of their hospital stay differed. One group received intraoperatively a combination of crystalloids and a small colloid dose, while the other group received only the crystalloids intraoperatively.

Methods: This randomized prospective study included 80 patients with colorectal cancer prepared for major elective colorectal surgery.

The influence of breast cancer subtypes on the response to anthracycline neoadjuvant chemotherapy in locally advanced breast cancer patients.

Purpose: The objective of neoadjuvant chemotherapy (NACT) for locally advanced breast cancer (LABC) is downstaging to achieve resectability. According to the protocol for the treatment of LABC more than 10 years ago, the routine NACT for LABC in Serbia consisted of 4 cycles of FAC (fluorouracil, doxorubicin, cyclophosphamide). The aim of this analysis was to assess the influence of biologic subtypes of BC on the response to NACT and on the disease outcome in these patients.

Association between miR-21/146a/155 level changes and acute genitourinary radiotoxicity in prostate cancer patients: A pilot study.

Introduction: Nearly sixty percent of patients with prostate cancer (PCa) undergo radiation therapy (RT). During the course of treatment patients may experience normal tissue reactions. It is a well established fact that genetic and epigenetic mechanisms, such as microRNA (miRNA) level changes might be associated with radiotoxicity, as a response to irradiation.

and DNA-repair gene polymorphisms genotyping as a low-cost lung adenocarcinoma screening tool.

Aim: and DNA repair polymorphisms have been proposed as cancer risk factors. This study evaluated the usability of Arg72Pro single-nucleotide polymorphism, Arg399Gln and G135C as a low-cost lung adenocarcinoma screening tool.

Patients And Methods: This case-control study included 78 atients with lung adenocarcinoma and 79 healthy matched controls.

Case Report: The impact of the ESTRO-IAEA Best Practice in Radiation Oncology train the RTT trainers project for Serbian RTTs.

The European Society of Radiotherapy and Oncology (ESTRO)/International Atomic Energy Agency (IAEA) Best Practice in Radiation Oncology project to train the RTT trainers (TTT) has had a very positive impact on improving the continuous education of Radiation Therapists (RTTs) in Serbia, as well as bringing a renewed focus to the professionalism of the role of the RTT in the radiation oncology team. In addition, the TTT project resulted in RTTs from Serbia collaborating with colleagues from the region, leading to the development of the South East Europe Technology in Radiation Oncology (SEETRO) cooperation. In this case report, the progress of education for RTTs in Serbia is documented since the advent of the TTT project.

How to become a breast cancer specialist in 2018: The point of view of the second cohort of the Certificate of Competence in Breast Cancer (CCB2).

Breast cancer (BC) is the most frequent cancer in women and the leading cause of cancer death in females worldwide. Rapid research advancements add to the complexity of treatment options for this disease. It is known that the quality of patients' care is deeply affected by healthcare professionals following these advancements.

Management and treatment of children with medulloblastoma in Serbia, a middle-income country.

Purpose: The aim of this study was to present the management and treatment of children with medulloblastoma in Serbia, a middle-income country (MIC).

Methods: The data of 87 children diagnosed with medulloblastoma and treated at the Institute for Oncology and Radiology of Serbia from 2000 to 2013 were analyzed.

Results: The children's median age was 8.