Mutational profile of hereditary breast and ovarian cancer - Establishing genetic testing guidelines in a developing country.

Purpose: Because many countries lack the capacity to follow the international guidelines for genetic testing, we suggest the specific approach for establishing local genetic testing guidelines that could be applied in developing countries. We focus on hereditary breast (BC) and ovarian cancer (OC) in Serbia.

Methods: From the cohort of 550 persons who were referred for genetic counseling at the Institute for Oncology and Radiology of Serbia, 392 were selected.

Between immunomodulation and immunotolerance: The role of IFNγ in SARS-CoV-2 disease.

Interferons have prominent roles in various pathophysiological conditions, mostly related to inflammation. Interferon-gamma (IFNγ) was, initially discovered as a potent antiviral agent, over 50 years ago, and has recently garnered renewed interest as a promising factor involved in both innate and adaptive immunity. When new disease epidemics appear such as SARS-CoV (severe acute respiratory syndrome coronavirus), MERS-CoV (Middle East respiratory syndrome coronavirus), IAV (Influenza A virus), and in particular the current SARS-CoV-2 pandemic, it is especially timely to review the complexity of immune system responses to viral infections.

Performance of Charlson and Elixhauser Comorbidity Index to Predict in-Hospital Mortality in Patients with Stroke in Sumadija and Western Serbia.

Background: Comorbidities are major predictors of in-hospital mortality in stroke patients. The Charlson comorbidity index (CCI) and the Elikhauser comorbidity index (ECI) are scoring systems for classifying comorbidities. We aimed to compare the performance of the CCI and ECI to predict in-hospital mortality in stroke patients.

Natural Products as a Promising Therapeutic Strategy to Target Cancer Stem Cells.

Cancer remains a deadly disease, and its treatment desperately needs to be managed through novel, rapidly advancing strategies. Most cancer cases eventually develop into recurrences, for which cancer stem cells (CSCs) are thought to be responsible. These cells are considered a subpopulation of all tumor cancer cells, with aberrant regulation of self-renewal, unbalanced proliferation, and cell death properties.

Exploratory composite endpoint demonstrates benefit of trilaciclib across multiple clinically meaningful components of myeloprotection in patients with small cell lung cancer.

Chemotherapy-induced myelosuppression is an acute, dose-limiting toxicity of chemotherapy regimens used in the treatment of extensive-stage small cell lung cancer (ES-SCLC). Trilaciclib protects haematopoietic stem and progenitor cells from chemotherapy-induced damage (myeloprotection). To assess the totality of the myeloprotective benefits of trilaciclib, including analysis of several clinically relevant but low-frequency events, an exploratory composite endpoint comprising five major adverse haematological events (MAHE) was prospectively defined: all-cause hospitalisations, all-cause chemotherapy dose reductions, febrile neutropenia (FN), prolonged severe neutropenia (SN) and red blood cell (RBC) transfusions on/after Week 5.

A new approach for activation of the kiwifruit cysteine protease for usage in in-vitro testing.

Actinidin (Act d 1), a highly abundant cysteine protease from kiwifruit, is one of the major contributors to the development of kiwifruit allergy. Many studies have focused on the optimization of Act d 1 purification and its role in the development of food allergies. Testing on cell culture monolayers is a common step in the elucidation of food allergen sensitization.

Chromogenic In Situ Hybridization (CISH) as a Method for Detection of C-Myc Amplification in Formalin-Fixed Paraffin-Embedded Tumor Tissue: An Update.

In situ hybridization (ISH) allows evaluation of genetic abnormalities, such as changes in chromosome number, chromosome translocations, or gene amplifications, by hybridization of tagged DNA (or RNA) probes with complementary DNA (or RNA) sequences in interphase nuclei of target tissue. However, chromogenic in situ hybridization (CISH) is also applicable to formalin-fixed, paraffin-embedded (FFPE ) tissues, besides metaphase chromosome spreads. CISH is similar to fluorescent in situ hybridization (FISH) regarding pretreatments and hybridization protocols but differs in the way of visualization.

The Association of Polymorphisms in and Genes Involved in Redox Homeostasis in the Development and Progression of Clear Cell Renal Cell Carcinoma.

Deleterious effects of SNPs found in genes encoding transcriptional factors, as well as antioxidant and detoxification enzymes, are disputable; however, their functional significance seems to modify the risk for clear cell renal cell carcinoma (ccRCC) development and progression. We investigated the effect of specific , , gene variants and haplotype on ccRCC risk and prognosis and evaluated the association between GSTP1 and regulatory (JNK1/2) and executor (caspase-3) apoptotic molecule expression in ccRCC tissue samples and the presence of GSTP1 : JNK1/2 protein : protein interactions. Genotyping was performed in 223 ccRCC patients and 336 matched controls by PCR-CTTP and qPCR.

Polymorphisms in Genes Encoding Glutathione Transferase Pi and Glutathione Transferase Omega Influence Prostate Cancer Risk and Prognosis.

Considering the pleiotropic roles of glutathione transferase (GST) omega class members in redox homeostasis, we hypothesized that polymorphisms in and might contribute to prostate cancer (PC) development and progression. Therefore, we performed a comprehensive analysis of and SNPs' role in susceptibility to PC, as well as whether they might serve as prognostic biomarkers independently or in conjunction with other common GST polymorphisms (, , and ). Genotyping was performed in 237 PC cases and 236 age-matched controls by multiplex PCR for deletion of GST polymorphisms and quantitative PCR for SNPs.

Adolescents and young adults (AYA) with cancer: a position paper from the AYA Working Group of the European Society for Medical Oncology (ESMO) and the European Society for Paediatric Oncology (SIOPE).

It is well recognised that adolescents and young adults (AYA) with cancer have inequitable access to oncology services that provide expert cancer care and consider their unique needs. Subsequently, survival gains in this patient population have improved only modestly compared with older adults and children with cancer. In 2015, the European Society for Medical Oncology (ESMO) and the European Society for Paediatric Oncology (SIOPE) established the joint Cancer in AYA Working Group in order to increase awareness among adult and paediatric oncology communities, enhance knowledge on specific issues in AYA and ultimately improve the standard of care for AYA with cancer across Europe.

Functional Fine-Tuning of Metabolic Pathways by the Endocannabinoid System-Implications for Health and Disease.

The endocannabinoid system (ECS) employs a huge network of molecules (receptors, ligands, and enzymatic machinery molecules) whose interactions with other cellular networks have still not been fully elucidated. Endogenous cannabinoids are molecules with the primary function of control of multiple metabolic pathways. Maintenance of tissue and cellular homeostasis by functional fine-tuning of essential metabolic pathways is one of the key characteristics of the ECS.

Impact of COVID-19 on social media as perceived by the oncology community: results from a survey in collaboration with the European Society for Medical Oncology (ESMO) and the OncoAlert Network.

Background: The COVID-19 pandemic has impacted all aspects of modern-day oncology, including how stakeholders communicate through social media. We surveyed oncology stakeholders in order to assess their attitudes pertaining to social media and how it has been affected during the pandemic.

Materials And Methods: A 40-item survey was distributed to stakeholders from 8 July to 22 July 2020 and was promoted through the European Society for Medical Oncology (ESMO) and the OncoAlert Network.

Gene Overexpression Is Associated with Poor Prognosis of Triple-Negative Breast Cancer Patients.

Differential expressions of cancer-associated genes, including histone deacetylases (HDACs), were identified in distinctive molecular subtypes of breast cancer. Compared with hormone receptor-positive breast cancer, triple-negative (TNBC, ER-PR-HER2-) is the most aggressive form of breast cancer. To determine the association of mRNA expression levels with clinicopathological features and patients' survival with TNBC or ER+PR+HER2- breast cancers.

A Fluorescence-Based Assay for Measuring Glucose Uptake in Living Melanoma Cells.

Melanoma cells have high glycolytic capacity. Glucose uptake is a key rate-limiting step in glucose utilization. Here we describe a simple protocol for measuring direct glucose uptake in living melanoma cells by flow cytometry.

Hematological parameters in EGFR-mutated advanced NSCLC patients treated with TKIs: predicting survival and toxicity.

: The aim of this study was to analyze the prognostic value of pre-treatment hematological parameters in -mutated non-small cell lung cancer patients treated with tyrosine-kinase inhibitors (TKIs).: Patients with mutations were treated with EGFR-TKIs in the first line until progression/unacceptable toxicity. Hematological parameters were derived from the absolute baseline differential counts of a complete blood count.

Palbociclib and cetuximab compared with placebo and cetuximab in platinum-resistant, cetuximab-naïve, human papillomavirus-unrelated recurrent or metastatic head and neck squamous cell carcinoma: A double-blind, randomized, phase 2 trial.

Objectives: This study examined whether palbociclib and cetuximab prolonged overall survival (OS) versus placebo and cetuximab.

Materials And Methods: In this double-blind, randomized, phase 2 trial (PALATINUS), patients with platinum-resistant, cetuximab-naïve, human papillomavirus-unrelated recurrent/metastatic head and neck squamous-cell carcinoma received cetuximab and either palbociclib (arm A) or placebo (arm B). The primary endpoint was OS; 120 patients were required to have ≥80% power to detect a hazard ratio (HR) of 0.

The role of cytokines in the evolution of cancer: IFN-γ paradigm.

The evolution of malignant cells implies an increase in oncogenic fitness of cells which arises in active and reciprocal interaction with the tumor microenvironment. The mechanisms facilitating the adaptive evolution of cancer cells involve clonal selection of cancer cells, in a direction of increased adaptive potential under the selective pressure of host defensive strategies. Once reached, this potential could go the other way, changing the same evolutionary force in the tumor microenvironment which influenced its emergence and favoring cancer progression.

Breast Cancer Response to Therapy: Can microRNAs Lead the Way?

Breast cancer (BC) is a leading cause of death among women with malignant diseases. The selection of adequate therapies for highly invasive and metastatic BCs still represents a major challenge. Novel combinatorial therapeutic approaches are urgently required to enhance the efficiency of BC treatment.

Synthesis and evaluation of anticancer activity of new 9-acridinyl amino acid derivatives.

A series of eleven 9-acridinyl amino acid derivatives were synthesized using a two-step procedure. Cytotoxicity was tested on the K562 and A549 cancer cell lines and normal diploid cell line MRC5 using the MTT assay. Compounds , , and were the most active, with IC values comparable to or lower than that of chemotherapeutic agent amsacrine.

EGFR mutation testing from liquid biopsy of non-small cell lung cancer at the Institute for Oncology and Radiology of Serbia.

Purpose: Resistance to tyrosine kinase inhibitors (TKIs) in lung cancer often occurs, so mutation testing from liquid biopsy is the method of choice as a minimally invasive approach that quickly provides information for additional therapeutic options. The purpose of this study was to assess the success rate and usefulness of EGFR testing from liquid biopsy at the Institute for Oncology and Radiology of Serbia (IORS).

Methods: EGFR mutation testing was performed by real-time qPCR in 4750 tumor samples using the Cobas® EGFR Mutation Test v2.

Friend or foe: ABCG2, ABCC1 and ABCB1 expression in triple-negative breast cancer.

Background: ATP-binding cassette (ABC) transporters are responsible for the efflux of a wide variety of anti-cancer agents and have been implicated in the chemoresistance of various solid tumors. Chemoresistance is a major cause of therapeutic failure, especially in the highly aggressive triple-negative breast cancer (TNBC) in which, unlike estrogen receptor-expressing (ER+) BC, both endocrine and targeted treatments are ineffectual. We aimed to investigate the level and frequency of expression of the three most important ABC transporter, ABCG2, ABCC1, and ABCB1, according to breast cancer subtype.