Vol 2, No 2 (2015)

Advances in Molecular Oncology. 2015;2(2):6-16

6-16

The proteomics in prostate cancer biomarker discovery

Shevchenko V.E., Olenich A.V., Olenich N.E.

Abstract

Prostate cancer (PC) represents the second most frequent type of tumor in men worldwide. Proteomics represents a promising approach for the discovery of new biomarkers able to improve the management of PC patients. Markers more specific and sensitive than prostate-specific antigen are needed for PC diagnosis, prognosis and response to treatment. Moreover, proteomics could represent an important tool to identify new molecular targets for PC tailored therapy. Now several possible PC biomarkers sources, each with advantages and limitations, are under investigation, including tissues, urine, serum, plasma and prostatic fluids. Innovative high-throughput proteomic platforms are now identifying and quantifying new specific and sensitive biomarkers for PC detection, stratification and treatment. Nevertheless, many putative biomarkers are still far from being applied in clinical practice.

This review aims to discuss the recent advances in PC proteomics, emphasizing biomarker discovery and their application to clinical utility for diagnosis and patient stratification.

Advances in Molecular Oncology. 2015;2(2):17-28

17-28

Molecular features and genetic markers of gastrointestinal stromal tumors

Mazurenko N.N., Tsyganova I.М.

Abstract

Gastrointestinal stromal tumors (GISTs) are the most spread mesenchymal tumors located within the gastrointestinal tract that have particular clinico-morphological, immunohistochemical and molecular characteristics. The distinguishing mark of GISTs is the presence of the cell-surface antigen CD117 (KIT receptor tyrosine kinase), identified by immunohistochemistry. GISTs consist of tumors with various activating mutations in KIT (75–80 %) or PDGFRA (5–15 %) receptor tyrosine kinases. Numerous KIT and PDGFRA mutations are associated with specific GIST morphology, histologic phenotype, metastasizing and prognosis. 10–15 % of GISTs contain KIT and PDGFRA wild type genes, some of them have driver BRAF, IGF1R or PIK3CA mutations. The other GISTs patients have familial syndromes (neurofibromatosis type 1, Carney–Stratakis syndrome, Carney triad) and contain germline mutations of NF1 or the genes coding for the succinate dehydrogenase subunits SDHA, SDHB, SDHC, and SDHD. GISTs are first and the most studied model for development of principles and methods of personalized targeted therapy of solid tumors with tyrosine kinase inhibitors.

Advances in Molecular Oncology. 2015;2(2):29-40

29-40

Trabectedin – the DNA minor groove binder

Belitsky G.A., Kirsanov K.I., Lesovaya E.A., Yakubovskaya M.G.

Abstract

Trabectedin (ET-743, Yondelis) is an alkaloid that was originally isolated from the Caribbean Sea squirt, Ecteinascidia turbinata and is now produced synthetically. Its chemical structure consists in three fused tetrahydroisoquinoline rings. Two of them, A and B, binds covalently to guanine residues in the minor groove of the DNA double helix to bend the molecule toward the major groove and the third ring C protrudes from the DNA duplex, apparently allowing interactions with several nuclear proteins. Binding to the minor groove of DNA, trabectedin trigger a cascade of events that interfere with several transcription factors, DNA binding proteins, and DNA repair pathways in particular nucleotide excision repair. It acts both as a DNA-alkylating drug and topoisomerase poison. Trabectedin-DNA adduct traps the nucleotide excision repair proteins repairing the DNA damage in transcribing genes and induces DNA strand breaks. Cells deficient in homologous recombination pathway which repairs these double-strand breaks show increased sensitivity to trabectedin. The most sensitive of them were myxoid liposarcomas. Trabectedin is also effective in chemotherapy-experienced patients with advanced, recurrent liposarcoma or leiomyosarcoma as well as in women with ovarian cancer and breast cancer with BRCAness phenotype. Besides of tumor cells Trabectedin inhibits inflammatory cells by affecting directly monocytes and tumorassociated macrophages and indirectly by inhibiting production of inflammatory mediators, the cytokines and chemokines. It inhibits also the MDR-1 gene, which is responsible for the resistance of cancer cells to chemotherapeutic agents and strikes tumor angiogenesis.

Advances in Molecular Oncology. 2015;2(2):41-49

41-49

RESEARCH ARTICLES

Intercellular interactions and progression of hormonal resistance of breast cancer cells

Semina S.E., Bagrov D.V., Krasil’nikov M.A.

Abstract

Advances in Molecular Oncology. 2015;2(2):50-55

50-55

Diagnostic significance of DNA and antibodies against capsid antigens of anti-Epstein–Barr virus antibodies levels in blood plasma of nasopharyngeal carcinoma patients from non-endemic region

Gurtsevich V.E., Senyuta N.B., Kondratova V.N., Goncharova E.V., Ignatova A.V., Lomaya M.V., Kropotov M.A., Mudunov A.M., Lichtenstein A.V.

Abstract

Epstein–Barr virus (EBV), a representative of the herpesvirus family, is the etiological agent for a number of benign and malignant human neoplasms. Among the latter, the nasopharyngeal carcinoma (NPC) occupies a special place. In NPC development EBV plays a key role stimulating the progression of the pathological process from precancerous lesions to the cancer development. For most NPC patients, elevated levels of humoral IgG and IgA antibodies against capsid and early EBV antigens are characteristic and their antibody titers rise to high levels long before the diagnosis of cancer. Using this phenomenon, virus-specific antibodies are used for many years as markers for NPC screening, especially in cases of undiagnosed primary lesion. In recent years, in endemic for NPC regions (South China, South-East Asia) a great attention has been paid to the use of quantitative determination of EBV DNA copies in the blood plasma of patients with NPC as a method of early cancer detection and monitoring.

The aim of this study was to compare clinical significance of EBV DNA and humoral antibodies levels in blood plasma of NPC patients in non-endemic region, Russia. The results obtained indicate that both markers DNA / EBV and IgA antibodies against capsid EBV antigens can be successfully used for diagnosis of NPC in non-endemic region. However, in comparison with the virus-specific antibody titers, the viral DNA levels in the patients plasma are more sensitive and specific as NPC marker reflecting the efficacy of the therapy, and the state of remission or relapse.

Advances in Molecular Oncology. 2015;2(2):56-62

56-62

The features of leptin and its receptor expression in metastatic cutaneous melanoma

Lushnikova A.A., Balbutsky A.V., Ponkratova D.A., Kazubskaya T.P.

Abstract

Advances in Molecular Oncology. 2015;2(2):63-67

63-67

AUTHORS’ DATA

Информация для авторов

Abstract

Информация для авторов

Advances in Molecular Oncology. 2015;2(2):68