Trends in pediatric CNS tumors in Armenia: a multicenter retrospective study.

PURPOSE: Central nervous system (CNS) tumors are the most common solid malignancies in children worldwide, including in Armenia. The current study aims to analyze epidemiological data, treatment, and outcomes of children and young adults (≤25 years) with CNS tumors in Armenia during the last 26 years. METHODS: We collected data from pediatric and young adult patients treated in selected sites in Armenia from 1st January 1995 to 31st December 2020. Incidence by sex, age at diagnosis, time from first complaints to diagnosis, histopathology results, treatment strategies, complications, and overall survival (OS) rates were calculated. RESULTS: The multicenter data analysis revealed 149 patients with diagnosed primary CNS tumors over 26 years. Among them, 84 (56.4%) were male. The median age at diagnosis was 7 years (range, 3 months to 25 years), and the median time from the first complaints to diagnosis was 2 months (range, 1 week to 70 months). Medulloblastomas and other embryonal tumors (47), low-grade gliomas (32), and high-grade gliomas (22) were the most commonly diagnosed malignancies. Ependymomas, craniopharyngiomas, germ cell tumors, and other malignancies were observed in 22 patients. For 26 patients, no histopathological or radiological diagnosis was available. Follow-up information was available for 98 (65.8%) patients. The 5-year OS rate for the whole study group was 67.7%. CONCLUSION: Consistent with international data, embryonal tumors, and gliomas were the most commonly diagnosed CNS malignancies in Armenia. Multimodal treatment was often not available in Armenia during the study period, especially for early cases.

Coordination of Ru(II)-Arene Fragments to Dipyridophenazine Ligands Leads to the Modulation of Their In Vitro and In Vivo Anticancer Activity.

Despite extensive research on the anticancer properties of Ru complexes with dipyrido[3,2-a:2',3'-c]phenazine (dppz) ligands, their in vivo efficacy is rarely investigated. Aiming to understand whether the coordination of certain half-sandwich Ru(II)-arene fragments might improve the therapeutic potential of dppz ligands, we prepared a series of Ru(II)-arene complexes with the general formula [(η6-arene)Ru(dppz-R)Cl]PF6, where the arene fragment was benzene, toluene, or p-cymene and R was -NO2, -Me, or -COOMe. All compounds were fully characterized by 1H and 13C NMR spectroscopy and high-resolution ESI mass-spectrometry, and their purity was verified by elemental analysis. The electrochemical activity was investigated using cyclic voltammetry. The anticancer activity of dppz ligands and their respective Ru complexes was assessed against several cancer cell lines, and their selectivity toward cancer cells was assessed using healthy MRC5 lung fibroblasts. The substitution of benzene with a p-cymene fragment resulted in a more than 17-fold increase of anticancer activity and selectivity of Ru complexes and significantly enhanced DNA degradation in HCT116 cells. All Ru complexes were electrochemically active in the biologically accessible redox window and were shown to markedly induce the production of ROS in mitochondria. The lead Ru-dppz complex significantly reduced tumor burden in mice with colorectal cancers without inducing liver and kidney toxicity.

Effects of Bis(imino)acenaphthene (Bian)-Derived Ligands on the Cytotoxicity, DNA Interactions, and Redox Activity of Palladium(II) Bipyridine Complexes.

A series of heteroleptic bipyridine Pd(II) complexes based on 1,2-bis[(2,6-diisopropylphenyl)imino]acenaphthene (dpp-Bian) or 1,2-bis[(2,4,6-trimethylphenyl)imino]acenaphthene (tmp-Bian) were prepared. All complexes were fully characterized by spectrochemical methods, and their crystal structures were confirmed by X-ray diffraction analysis. The 72 h stability of heteroleptic bipyridine Pd(II) complexes with Bian ligands under physiological conditions was investigated using 1H NMR spectroscopy. The anticancer activity of all complexes was assessed in a panel of cancer cell lines in comparison with uncoordinated ligands and clinically used drugs cisplatin and doxorubicin. The ability of the complexes to bind DNA was investigated using several methods, including EtBr replacement assay, density functional theory calculations, circular dichroism spectroscopy, DNA gel electrophoresis, and TUNEL assay. The electrochemical activity of all complexes and the uncoordinated ligands was studied using cyclic voltammetry, and reactive oxygen species production in cancer cells was investigated using confocal microscopy. Heteroleptic bipyridine PdII-Bian complexes were cytotoxic in a low micromolar concentration range and showed some selectivity toward cancer cells in comparison with noncancerous MRC-5 lung fibroblasts.

Molecular profile of pancreatic neuroendocrine neoplasms (PanNENs): Opportunities for personalized therapies.

Pancreatic neuroendocrine neoplasms (panNENs) are the second most common epithelial tumors of the pancreas. Despite improvements in prognostic grading and staging systems, it remains a challenge to predict the clinical behavior of panNENs and the response to specific therapies given the high degree of heterogeneity of these tumors. Most panNENs are nonfunctional and present as advanced disease. However, systemic therapies provide modest benefits. Therefore, there is a need for predictive biomarkers to develop personalized treatment and to advance new drug development. The somatostatin receptors remain the only clinically established prognostic and predictive biomarkers in panNENs. Oncogenic drivers are at a very low frequency. Commonly mutated genes in panNENs include MEN1, chromatin remodeling genes (DAXX and ATRX), and mammalian target of rapamycin pathway genes. In contrast, poorly differentiated neuroendocrine carcinomas (panNECs), which carry a very poor prognosis, have distinctive mutations in certain genes (eg, RB1 and p53). Ongoing research to integrate epigenomics will provide tremendous opportunities to improve current understanding of the clinical heterogeneity of pancreatic neuroendocrine tumors and provide invaluable insight into the biology of these tumors, new drug development, and establishing personalized therapies.

First Global Summit on War and Cancer: The Hidden Impact of War on Cancer-Urging Global Action for Change.

The 1st Global Summit on War and Cancer (GSWC) united leaders, medical professionals, policymakers, and advocates to address cancer issues in conflict zones featuring speakers from around 50 countries.

Barriers to access to cancer care for patients from the conflict-affected region of the Nagorno-Karabakh Republic: A qualitative study.

Access to essential health services is a basic human right, yet many cancer patients living in conflict-affected regions face multiple obstacles to service use. The (former) Nagorno-Karabakh Republic was a conflict-affected region in the South Caucasus populated predominantly by ethnic Armenians. Multiple acute armed conflicts, the recent military occupation of the region, and the prolonged military blockade of the Lachin Corridor (a humanitarian corridor connecting Nagorno-Karabakh to Armenia) exacerbated existing social, health, economic, and political fragilities in this region. As a result, cancer services were disrupted, with limited clarity on how the ongoing military blockade of a humanitarian corridor affected cancer patients' experiences of accessing cancer care locally and in bordering Armenia. Our study aimed to describe the experiences of patients from Nagorno-Karabakh in accessing the cancer care services they needed. We conducted remote semi-structured interviews with adult (aged ≥18 years) cancer patients receiving cancer care from three university hospitals in Armenia and face-to-face interviews with cancer care professionals from these hospitals. Interviews were conducted during the blockade of the Lachin Corridor between March and May 2023. Data were analysed thematically using a deductive approach. Twelve adult cancer patients (9 women) and 12 cancer care professionals participated. A key barrier to accessing cancer services was attributed to the Azerbaijani military occupation of the region and the blockade of a major roadway connecting Nagorno-Karabakh to Armenia. Patients talked in length about the challenges of finding transport and travelling long distances to reach essential cancer services in Armenia. Policies of free anti-cancer medication provision and decentralised medication supply were paused because of the military occupation, affecting patients' timely access to anti-cancer medication. Out-of-pocket expenses for treatment, anti-cancer medication, travel, and temporary accommodation in Armenia placed a significant financial burden on cancer patients, exacerbated by the humanitarian crisis. Conflict-affected regions blockaded by military forces lack the capacity and targeted support to sustain their essential health services and provide care to those in need of life-saving treatments. Coordinated action from national and international organisations and governments is urgently needed to enhance humanitarian assistance and healthcare support to patients, their families and wider communities affected by military blockades and armed conflicts.

Genomics-driven derivatization of the bioactive fungal sesterterpenoid variecolin: Creation of an unnatural analogue with improved anticancer properties.

A biosynthetic gene cluster for the bioactive fungal sesterterpenoids variecolin (1) and variecolactone (2) was identified in Aspergillus aculeatus ATCC 16872. Heterologous production of 1 and 2 was achieved in Aspergillus oryzae by expressing the sesterterpene synthase VrcA and the cytochrome P450 VrcB. Intriguingly, the replacement of VrcB with homologous P450s from other fungal terpenoid pathways yielded three new variecolin analogues (5-7). Analysis of the compounds' anticancer activity in vitro and in vivo revealed that although 5 and 1 had comparable activities, 5 was associated with significantly reduced toxic side effects in cancer-bearing mice, indicating its potentially broader therapeutic window. Our study describes the first tests of variecolin and its analogues in animals and demonstrates the utility of synthetic biology for creating molecules with improved biological activities.

An Update to Hallmarks of Cancer.

In the last decade, there has been remarkable progress in research toward understanding and refining the hallmarks of cancer. In this review, we propose a new hallmark - "pro-survival autophagy." The importance of pro-survival autophagy is well established in tumorigenesis, as it is related to multiple steps in cancer progression and vital for some cancers. Autophagy is a potential anti-cancer therapeutic target. For this reason, autophagy is a good candidate as a new hallmark of cancer. We describe two enabling characteristics that play a major role in enabling cells to acquire the hallmarks of cancer - "tumor-promoting microenvironment and macroenvironment" and "cancer epigenetics, genome instability and mutation." We also discuss the recent updates, therapeutic and prognostic implications of the eight hallmarks of cancer described by Hanahan et al. in 2011. Understanding these hallmarks and enabling characteristics is key not only to developing new ways to treat cancer efficiently but also to exploring options to overcome cancer resistance to treatment.

Incidence patterns and review of Hodgkin lymphoma in the Republic of Armenia.

Hodgkin lymphoma (HL) accounts for roughly 10% of all lymphomas and 0.6% of all malignant tumours analysed worldwide yearly. Data regarding HL in developing world are exceptionally constrained. The main objective of this research is to investigate the incidence patterns of HL within the Republic of Armenia and to portray disease distribution according to age and sex. There is a very strict evidence on the frequency of HL in Armenia. The results of our research find out that the frequency of HL in Armenia has not changed altogether over the past 15 years and is comparable to that detailed from the USA and Europe.

Treatment and Outcomes of Colorectal Cancer in Armenia: A Real-World Experience From a Developing Country.

PURPOSE: In Armenia, colorectal cancer (CRC) is one of the most frequently diagnosed cancers. It is in the third place by incidence. The aim of this study was to evaluate treatment and outcomes of CRC in Armenia during the last 9 years. MATERIALS AND METHODS: For this retrospective hospital-based study, we have collected data from two main oncology centers in Armenia: National Oncology Center and "Muratsan" Hospital of Yerevan State Medical University. The information about patients with CRC who were treated at these two centers between January 1, 2010 and July 1, 2018 was collected from the medical records. Log-rank test and Kaplan-Meier curves were used for survival analysis. Prognostic factors were identified by Cox regression. RESULTS: A total of 602 patients with CRC were involved in the final analysis. Median follow-up time was 37 months (range, 3-207 months). A total of 8.6% of patients had stage I, 32.9% stage II, 38.0% stage III, and 17.6% stage IV cancer; for 2.7% patients, the stage was unknown. The main independent prognostic factors for overall survival (OS) were tumor stage, grade, and histology. Adjuvant chemotherapy has been shown to improve survival in stage II colon cancer and stage III rectal but not in stage II rectal cancer. Radiotherapy did not yield survival improvement in stage II or III rectal cancer. Three- and 5-year OS rates were 62.9% and 51.8% for all stages combined and 79.7% and 68.5% for stages I-II, 62.5% and 48.4% for stage III, and 24.4% and 17% for stage IV respectively. CONCLUSION: As seen from our results, our survival rates are lower than those of the developed world. Additional research is needed to identify the underlying reasons and to improve patients' treatment and outcomes in Armenia.

Younger age and previous exposure to radiation therapy are correlated with the severity of chemotherapy-induced thrombocytopenia.

BACKGROUND: Chemotherapy-induced thrombocytopenia (CIT) is a significant complication of cancer therapy. Data on the optimal management approaches of this morbidity in children and young adults are still limited. AIM: The aim of the study is to estimate the frequency and severity of CIT and associated clinically significant bleeding in children and young adults with solid tumours and haematologic malignancies. METHODS: For this retrospective, hospital-based study, children (0-18 y) and young adults (19-40 y) with different types of solid tumours and haematologic malignancies who received chemotherapy at the Muratsan Hospital Complex of Yerevan State Medical University were identified from the patients' database and included in the study (overall 122 patients). Thrombocytopenia was defined as a decrease of platelet count below <100 × 109/L. For assessing bleeding, WHO scale had been used. RESULTS: Overall, the whole group of patients received 430 chemotherapy cycles. During 131 (31.6%) chemotherapy cycles, patients developed CIT. The study revealed a statistically significant inversely proportional correlation between the age and the severity of CIT. Another important finding of the study was that the patients, who previously were exposed to radiation therapy, were more likely to develop CIT, than those who have not received radiation therapy (68% and 28.7%, p = 0.001). From 430 cycles of chemotherapy, 31 (7.2%) cycles reported to have bleeding events. CONCLUSION: Our study showed that clinically significant thrombocytopenia and bleeding are quite rare among children and young adults. Younger age and previous exposure to radiation therapy are positively correlated with the severity of thrombocytopenia. Larger studies are needed to investigate these findings.