Sex-Related Differences in Pancreatic Ductal Adenocarcinoma Progression and Response to Therapy.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly malignancies with an increasing incidence rate and limited therapeutic options. Biological sex has an impact on many aspects of PDAC development and response to therapy, yet it is highly unappreciated in both basic and translational research, and worryingly in PDAC clinical trials. In this review, we summarize how biological sex influences PDAC incidence and mortality, genetic and epigenetic landscapes, anti-tumor immunity, responses to hormones, cachexia, and the efficacy of therapy.

Two Decades of Progress in Personalized Medicine of Colorectal Cancer in Serbia-Insights from the Institute for Oncology and Radiology of Serbia.

Background: It is projected that, by 2040, the number of new cases of colorectal cancer (CRC) will increase to 3.2 million, and the number of deaths to 1.6 million, highlighting the need for prevention strategies, early detection and adequate follow-up.

Li-Fraumeni Syndrome With Six Primary Tumors-Case Report.

Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome associated with a high, lifetime risk of a broad spectrum of cancers caused by pathogenic germline TP53 mutations. Numerous different germline TP53 mutations have been associated with LFS, which has an exceptionally diverse clinical spectrum in terms of tumor type and age of onset. Our patient has developed six asynchronous tumors to date: a phyllode tumor of the breast, a pheochromocytoma, a rosette-forming glioneuronal tumor (RGNT), an adrenocortical carcinoma (ACC), a ductal carcinoma of the breast, and a thymoma.

Detection of humoral and cellular immune response to anti-SARS-CoV-2 BNT162b2 vaccine in breastfeeding women and naïve and previously infected individuals.

This study explored humoral and cellular responses to anti-SARS-CoV-2 BNT162b2 mRNA vaccine in breastfeeding women and naïve and seropositive individuals in the first six months after vaccination.Sixty-one volunteers vaccinated with two doses of the BNT162b2 mRNA vaccine were enrolled in the study. In-house developed ELISA was used for the quantification of SARS-CoV-2 RBD-specific antibodies.

Pathological Diagnosis, Work-Up and Reporting of Breast Cancer 1st Central-Eastern European Professional Consensus Statement on Breast Cancer.

This text is based on the recommendations accepted by the 4th Hungarian Consensus Conference on Breast Cancer, modified on the basis of the international consultation and conference within the frames of the Central-Eastern European Academy of Oncology. The recommendations cover non-operative, intraoperative and postoperative diagnostics, determination of prognostic and predictive markers and the content of cytology and histology reports. Furthermore, they address some specific issues such as the current status of multigene molecular markers, the role of pathologists in clinical trials and prerequisites for their involvement, and some remarks about the future.

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.

3D HeLa spheroids as a model for investigating the anticancer activity of Biginelli-hybrids.

In previous study, we examined the anticancer effects of novel Biginelli-hybrids against HeLa cell line on 2D monolayer culture. The five most effective compounds were chosen for further analysis of their anticancer activity against HeLa spheroids. Using the 3D models implies the possible differences in anticancer effects and mechanisms of activity of tested compounds.

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.

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.

Exploring the real-world effect of the SARS-CoV-2 pandemic on the molecular diagnostics for cancer patients and high-risk individuals.

: The SARS-CoV-2 pandemic introduced a global distraction effect in cancer patients' care. The aim of this study was to explore the effect of the pandemic on the largest molecular diagnostics center for cancer patients and high-risk individuals in Serbia.: and mutation testing were performed by qPCR and NGS.

Interleukin-4-induced natural killer cell antitumor activity in metastatic melanoma patients.

NK cells are important effectors of innate immunity that mount the first line of defense toward tumor growth. Interleukin-4 (IL-4) has recently been shown to regulate NK cell function, although its role in the regulation of NK cell function in cancer patients has not been clarified. The aim of this study was to investigate the effect of IL-4 on the function and the receptor characteristics of CD16-defined NK cells and their cytotoxic CD16bright and regulatory CD16dim subsets.

Extracts Promote Doxorubicin Effects against Lung Adenocarcinoma Cells In Vitro.

and its secondary metabolites have been shown to have anticancer potential. We performed MTT, scratch, and colony formation assays; analyzed cell cycle phase distribution and doxorubicin uptake and retention with flow cytometry; and detected alterations in the expression of genes involved in the formation of cell-cell interactions and migration using quantitative real-time PCR following treatment of lung adenocarcinoma cells with doxorubicin, extracts, or their combination. MTT assay results suggested strong synergistic effects of the combined treatments, and their application led to an increase in cell numbers in the subG1 phase of the cell cycle.

The Interplay between Cancer Biology and the Endocannabinoid System-Significance for Cancer Risk, Prognosis and Response to Treatment.

The various components of the endocannabinoid system (ECS), such as the cannabinoid receptors (CBRs), cannabinoid ligands, and the signalling network behind it, are implicated in several tumour-related states, both as favourable and unfavourable factors. This review analyses the ECS's complex involvement in the susceptibility to cancer, prognosis, and response to treatment, focusing on its relationship with cancer biology in selected solid cancers (breast, gastrointestinal, gynaecological, prostate cancer, thoracic, thyroid, CNS tumours, and melanoma). Changes in the expression and activation of CBRs, as well as their ability to form distinct functional heteromers affect the cell's tumourigenic potential and their signalling properties, leading to pharmacologically different outcomes.

Expression of SIRT1, SIRT3 and SIRT6 Genes for Predicting Survival in Triple-Negative and Hormone Receptor-Positive Subtypes of Breast Cancer.

Triple-negative breast cancer (TNBC) is characterized by aggressive phenotype and a poorer prognosis compared to the estrogen and progesterone receptor positive, Her2 negative (ER + PR + Her2-) breast cancer. Increasing evidence suggests that sirtuins, a family of histone deacetylases, could have an important role in aggressiveness of TNBC's. The current study evaluated the potential clinical relevance of SIRT1, SIRT3 and SIRT6 gene expressions in two prognostically distinctive subtypes of breast cancer, the most aggressive TNBC and the least aggressive ER + PR + Her2- tumors.

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.

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.

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.

Association of uPA and PAI-1 tumor levels and 4G/5G variants of PAI-1 gene with disease outcome in luminal HER2-negative node-negative breast cancer patients treated with adjuvant endocrine therapy.

Background: The aim of this study was to evaluate the prognostic potential of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) tumor tissue levels and examine the association between these biomarkers and classical prognostic factors in early node-negative luminal breast cancer patients. The clinical value of 4G/5G variants of PAI-1 gene was evaluated.

Patients And Methods: This study involved 81 node-negative, estrogen receptor-positive and/or progesterone receptor-positive and human epidermal growth factor receptor 2-negative operable breast cancer patients who underwent radical surgical resection and received adjuvant endocrine therapy.

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.

Molecular signature of response to preoperative radiotherapy in locally advanced breast cancer.

Background: Radiation therapy is an indispensable part of various treatment modalities for breast cancer. Specifically, for non-inflammatory locally advanced breast cancer (LABC) patients, preoperative radiotherapy (pRT) is currently indicated as a second line therapy in the event of lack of response to neoadjuvant chemotherapy. Still approximately one third of patients fails to respond favourably to pRT.

Promoter hypermethylation of p16, BRCA1 and RASSF1A genes in triple-negative breast cancer patients from Serbia.

Purpose: In order to investigate if aberrant promoter methylation of p16, BRCA1 and RASSF1A genes contributes to biological behavior of triple-negative breast cancer (TNBC), marked as the most aggressive phenotype of breast cancer, we compared the hypermethylation pattern between TNBC and ER+PR+Her2- breast cancer.

Methods: 131 patients with histologically confirmed breast cancers were included - 61 TNBC and 70 ER+PR+Her2- cases. The patients were followed up for 1-87 months (median 78).

Highly selective anthraquinone-chalcone hybrids as potential antileukemia agents.

A series of 23 novel anthraquinone-chalcone hybrids containing amide function was synthesized and structurally characterized. Sixteen compounds exerted strong cytotoxic activities against K562, Jurkat and HL-60 leukemia cell lines and significantly lower cytotoxic effects against normal MRC-5 cells, indicating very high selectivity in their anticancer action. The compounds 6g, 6u and 6v activate apoptosis in K562 cells through the extrinsic and intrinsic apoptotic pathway.

Evaluation of the Functional Capacity of NK Cells of Melanoma Patients in an In Vitro Model of NK Cell Contact with K562 and FemX Tumor Cell Lines.

NK cells of metastatic melanoma (MM) patients display impaired function, making them incapable to mount an effective antitumor response. In this study, we evaluated immunophenotypic characteristics and functional capacity of CD3CD16 NK cells of MM patients in an in vitro model based on NK cell contact with an NK sensitive, K562, and a tumor-specific, melanoma FemX tumor cell line. Although our results indicate similar NK cell antitumor cytotoxic potential of MM patients in contact with both cell lines based on the expression of CD107a degranulation marker, there is a discrepancy in NK cell IFNγ production, as it is not significantly induced by FemX tumor cells, found to be, contrary to K562, HLA class I positive.

Anticancer potential of new steroidal thiazolidin-4-one derivatives. Mechanisms of cytotoxic action and effects on angiogenesis in vitro.

The synthesis and cytotoxic activities determination of new steroidal mono- and bis(thiazolidin-4-ones) 4a-f and 5a-f have been performed. Their anticancer action was also evaluated in comparison to previously synthesized and reported corresponding steroidal thiosemicarbazones. All compounds were obtained as stereoisomeric mixtures with different configuration (E or Z) in the hydrazone moiety at the C-3 position.

Synthesis, antioxidant and antiproliferative activities of 1,3,4-thiadiazoles derived from phenolic acids.

Two 2-amino-1,3,4-thiadiazoles containing phenolic hydroxyl groups were combined with different carboxylic acid chlorides giving sixteen amide derivatives with good antioxidant and antiproliferative potential. The compound 3'c with an adamantane ring displayed excellent DPPH radical scavenging activity and good cytotoxic activity against human acute promyelocytic leukemia HL-60 cells, while 1,3,4-thiadiazole 3'h with 4-chlorophenyl moiety was found to be the most effective in inhibition of survival of lung carcinoma A549 cells. All examined thiadiazoles except 3a and 3'a exerted higher cytotoxic activities on A549 and HL-60 cancer cells when compared with normal fibroblasts MRC-5, pointing to selectivity in their antiproliferative action.