?
Prevention of tumor growth driven by PIK3CA and HPV oncogenes by targeting mTOR signaling with metformin in oral squamous carcinomas expressing OCT3
Cancer Prevention Research. 2015. Vol. 8. No. 3. P. 197–207.
Madera D., Vitale-Cross L., Martin D., Schneider A., Molinolo A., Gangane N., Carey T., McHugh J., Komarck C., Walline H., William, Jr. W., Seethala R., Ferris R., Gutkind J. S.
Most head and neck squamous cell carcinomas (HNSCC) exhibit a persistent activation of the PI3K-mTOR signaling pathway. We have recently shown that metformin, an oral antidiabetic drug that is also used to treat lipodystrophy in HIV-infected (HIV+) individuals, diminishes mTOR activity and prevents the progression of chemically-induced experimental HNSCC premalignant lesions. Here, we explored the preclinical activity of metformin in HNSCCs harboring PIK3CA mutations and HPV oncogenes, both representing frequent HNSCC alterations, aimed at developing effective targeted preventive strategies.
The biochemical and biological effects of metformin were evaluated in representative HNSCC cells expressing mutated PIK3CA or HPV oncogenes (HPV+). The oral delivery of metformin was optimized to achieve clinical relevant blood levels. Molecular determinants of metformin sensitivity were also investigated, and their expression levels examined in a large collection of HNSCC cases.
We found that metformin inhibits mTOR signaling and tumor growth in HNSCC cells expressing mutated PIK3CA and HPV oncogenes, and that these activities require the expression of organic cation transporter 3 (OCT3/SLC22A3), a metformin uptake transporter. Co-expression of OCT3 and the mTOR pathway activation marker pS6 were observed in most HNSCC cases, including those arising in HIV+ patients.
Activation of the PI3K-mTOR pathway is a widespread event in HNSCC, including HPV− and HPV+ lesions arising in HIV+ patients, all of which co-express OCT3. These observations may provide a rationale for the clinical evaluation of metformin to halt HNSCC development from precancerous lesions, including in HIV+ individuals at risk of developing HPV-associated cancers.
Kashevnik A., Glekler E., Artemenko E. et al., Scientific data 2026 Article 7209
We present a multimodal dataset containing electroencephalography (EEG), electrocardiography (ECG), and video recordings from 49 participants. Each participant completed a single session lasting approximately 45 minutes. During each session they performed five tasks: resting state, inward concentration (focusing on the center of the forehead), outward concentration (visual search), and mind-wandering. EEG data were recorded from ...
Added: April 23, 2026
Kopoleva E., Sergey A. Tsymbal, Kuchur O. et al., Drug Delivery and Translational Research 2026 P. 1–16
Multidrug resistance (MDR) remains one of the principal challenges in cancer chemotherapy, necessitating new strategies to restore drug efficacy. In this study we developed and characterize a redox-responsive nanoplatform based on trithiocyanuric acid and polyethylene glycol (TTCA-PEG NPs) as a potential tool to overcome MDR and provide a biocompatible delivery system for conventional antitumor drugs. ...
Added: April 20, 2026
G.V.Klink, Gulov D. M., Elumeeva T. G. et al., Журнал общей биологии 2024 Т. 85 № 2 С. 83–94
Plant functional traits are important for the formation of plant communities and for the ability of plants to dominate there. The comparison of mean trait values of organisms within community with that for the random samples of the local biota allows estimating the importance of the trait for the formation of the community composition. The ...
Added: April 19, 2026
G.V.Klink, Semenkov I. N., Enchilik P. R., Science of the Total Environment 2025 Vol. 998 Article 180219
Natural regeneration of forest soils affected by agricultural practices is a common phenomenon in many regions worldwide, particularly in boreal ecosystems. Affecting soil quality, the partitioning of extractable fractions of heavy metals and metalloids (HMMs) is not studied during natural regeneration. The following stages of natural regeneration after plowing have been identified in the Smolenskoye ...
Added: April 19, 2026
Makarova M., Fedosov N., Mikhailova I. et al., FRONTIERS IN SIGNAL PROCESSING 2026
Introduction:
While self-referential attention is thought to enhance interoceptive sensitivity, its effect on cardiac modulation of corticospinal excitability remains unexplored. This pilot study investigated how viewing one’s own face (self-face processing) modulates the cardiac-phase coupling of motor output and whether this heart-brain coupling depends on interoceptive accuracy (heartbeat perception).
Methods:
In 15 healthy adults, motor-evoked potentials (MEPs) were ...
Added: April 17, 2026
Pogodaeva S. S., Miletina O. O., Mammadova L. V. et al., Frontiers in Bioscience - Landmark 2026 Vol. 31 No. 4 P. 48544–48557
Background: Neuroblastoma (NB), a transcriptionally driven pediatric malignancy, exhibits a remarkable clinical and biological heterogeneity. Two major subtypes, adrenergic and mesenchymal, are differentially governed by distinct subsets of transcription factors that constitute the core regulatory circuitry (CRC). The adrenergic subtype is often associated with MYCN amplification and is particularly aggressive and therapy-resistant, underscoring the need ...
Added: April 15, 2026
Chernov I., Protas A., Popova E. et al., Biochemistry. Biokhimiia 2025 Vol. 19 No. 3 P. 279–287
This article reports the synthesis, characterization, cytotoxic activity, DNA binding study and antioxidant activity of N-(2-(2-(2-azidoethoxy)ethoxy)ethyl)-4,6-di(aziridin-1-yl)-1,3,5-triazin-2-amine. The synthesized compound was found to possess cytotoxic effects against six various cancer cell lines including HeLa, HCT116, T96G, A549, MCF7, and PANC-1 and non-cancer ECV cell line. Additionally, the capacity for DNA binding was assessed. The addition of 1,3,5-triazine ...
Added: April 15, 2026
Pogodaeva S., Miletina O., Antipova N. et al., Cancers 2025 Vol. 17 No. 19 Article 3228
Pediatric tumors such as neuroblastoma are characterized by a genome-wide ‘transcriptional burden’, surmising the involvement of multiple alterations of gene expression. Search for master regulators of transcription whose inactivation is lethal for tumor cells identified the non-POU domain-containing octamer-binding protein (NONO), a member of the Drosophila Behavior/Human Splicing family known for the ability to form ...
Added: April 15, 2026
Chernov K., Savin A., Otvodnikova D. et al., Oncology Research 2026 Vol. - No. -
The formation of drug resistance poses the ultimate threat in modern oncology. Targeted therapy lacks versatility, while conventional therapy is famous for its side effects. However, for the new therapeutics to address the challenge of drug resistance, such compounds should combine properties of both modalities. In this review, we argue that metal-based therapeutics are paramount ...
Added: April 15, 2026
Kochetkova E., Мачинская Р. И., Журнал высшей нервной деятельности им. И.П. Павлова 2025 Т. 75 № 2 С. 170–188
The review provides an analysis of modern cognitive psychological theories of emotions and neural basis
of mechanisms standing behind retention of emotional information in working memory. The tendency seen
in modern neurocognitive theories is characterized by the rejection of localization for any psychological
functions in favor of network models, where higher-order processes are supported by distributed neural
networks connecting ...
Added: April 15, 2026
Chernov K. V., Savin A. M., Otvodnikova D. E. et al., Oncology Research 2026 Vol. 34 No. 5 P. 1–40
The formation of drug resistance poses the ultimate threat in modern oncology. Targeted therapy lacks versatility, while conventional therapy is famous for its side effects. However, for the new therapeutics to address the challenge of drug resistance, such compounds should combine properties of both modalities. In this review, we argue that metal-based therapeutics are paramount ...
Added: April 15, 2026
Kochetkova E., Machinskaya R., Human Physiology 2025 Vol. 51 No. 6 P. 580–590
Growing evidence suggests the specific systems for emotional information maintenance and processing in working memory, highlighting the role of cognitive domains in emotional awareness. The question of neural basis of social-emotional processing in working memory remains open. We hypothesized that the neural systems supporting working memory for emotional processing may rely on shared ‘core’ networks ...
Added: April 15, 2026
Barskaya E. S., Savin A. M., Chernov K. V. et al., International Journal of Molecular Sciences 2026 Vol. 27 No. 6 Article 2800
Copper–organic compounds are being investigated as antitumor candidates. Besides their efficacy as cytotoxic agents alone, the oxidative potential of electrochemical Cu2+-to-Cu1+ transition emerges as an attractive approach for elimination of tumor cells otherwise resistant to chemotherapy. To minimize side effects of the potent oxidative burst upon Cu(II) reduction, the metal cations should be delivered to the ...
Added: April 15, 2026
S. V. Nikulin, Olkhovik D., A.V. Razumovskaya et al., Doklady Biochemistry and Biophysics 2026
A novel trend in anticancer therapy is based on the combination of cytotoxic and metabolic drugs. Bach1 is a transcription factor activating glycolysis and increasing proliferation and metastatic potential in cancer cells. The cytotoxic effect was evaluated for a combination of rotenone, an inhibitor of mitochondrial respiration, and two different inhibitors of Bach1 transcription factor ...
Added: April 13, 2026
Prokofieva A., Ryabaya O., Akasov R. et al., Biomedicine and Pharmacotherapy 2019 Vol. 109 P. 2548–2560
Melanoma is one of the most aggressive and treatment-resistant tumors that responsible for majority of skin-cancer related deaths. Here we propose a combination of MEK inhibitor binimetinib with metformin as a promising therapy against human melanoma cells in vitro, including BRAF -mutated A375, Mel Z, and Mel IL cells, and NRAS-mutated Mel MTP and Mel ...
Added: October 30, 2024
Klink G. V., Kalinina O. V., Bazykin G. A., PLoS Computational Biology 2022 Vol. 18 No. 2 Article e1009878
Fitness conferred by the same allele may differ between genotypes and environments, and these differences shape variation and evolution. Changes in amino acid propensities at protein sites over the course of evolution have been inferred from sequence alignments statistically, but the existing methods are data-intensive and aggregate multiple sites. Here, we develop an approach to ...
Added: June 26, 2024
Uusküla A., Rannap J., Weijler L. et al., Addiction 2023
Aims
We measured the association between a history of incarceration and HIV positivity among people who inject drugs (PWID) across Europe.
Design, Setting and Participants
This was a cross-sectional, multi-site, multi-year propensity-score matched analysis conducted in Europe. Participants comprised community-recruited PWID who reported a recent injection (within the last 12 months).
Measurements
Data on incarceration history, demographics, substance use, sexual behavior ...
Added: August 24, 2023
Walters M., Jahagirdar D., Novotney A. et al., The Lancet HIV 2021 Vol. 8 No. 10 P. 633–651
Background
The sustainable development goals (SDGs) aim to end HIV/AIDS as a public health threat by 2030. Understanding the current state of the HIV epidemic and its change over time is essential to this effort. This study assesses the current sex-specific HIV burden in 204 countries and territories and measures progress in the control of the ...
Added: January 24, 2022
Ward Z., Stone J., Bishop C. et al., The Lancet HIV 2022 Vol. 9 No. 1 P. E42–E53
Background
HIV incidence is increasing in eastern Europe and central Asia, primarily driven by injecting drug use. Coverage of antiretroviral therapy (ART) and opioid agonist therapy are suboptimal, with many people who inject drugs (PWID) being incarcerated. We aimed to assess whether use of monies saved as a result of decriminalisation of drug use or possession to scale up ART ...
Added: December 10, 2021
Abotsi R., Nicol M., Odland J. Ø. et al., BMC Infectious Diseases, United Kingdom 2021 Vol. 21 Article 216
HIV-associated chronic lung disease (CLD) is common among children living with HIV (CLWH) in sub-Saharan Africa, including those on antiretroviral therapy (ART). However, the pathogenesis of CLD and its possible association with microbial determinants remain poorly understood. We investigated the prevalence, and antibiotic susceptibility of Streptococcus pneumoniae (SP), Staphylococcus aureus (SA), Haemophilus influenzae (HI), and Moraxella catarrhalis (MC) among CLWH (established on ART) ...
Added: November 30, 2021
McHugh G., Rehman A., Simms V. et al., Tropical Medicine and International Health 2020 Vol. 25 No. 5 P. 590–599
Objective: To describe the features of HIV-associated chronic lung disease (CLD) in older children and adolescents living with HIV and to examine the clinical factors associated with CLD. This is a post-hoc analysis of baseline data from the BREATHE clinical trial (ClinicalTrials.gov, NCT02426112). Methods: Children and adolescents aged 6-19 years were screened for CLD (defined ...
Added: October 14, 2020
Odland J. Ø., Medicine (United States) 2020 Vol. 99 No. 17 P. e19554
Increased carotid intima-media thickness (cIMT) is reported in both adults and children with human immunodeficiency virus (HIV) in high income settings and is associated with an increased risk of cardiovascular disease, but data from sub-Saharan Africa is lacking.We assessed cIMT using ultrasound in perinatally HIV-infected children aged 6 to 16 years taking antiretroviral therapy (ART) ...
Added: October 14, 2020
Otstavnov S., The Lancet HIV 2019 Vol. 6 No. 12 P. E831–E859
Background
Understanding the patterns of HIV/AIDS epidemics is crucial to tracking and monitoring the progress of prevention and control efforts in countries. We provide a comprehensive assessment of the levels and trends of HIV/AIDS incidence, prevalence, mortality, and coverage of antiretroviral therapy (ART) for 1980–2017 and forecast these estimates to 2030 for 195 countries and territories.
Methods
We ...
Added: September 30, 2019
Sakevich V. I., Демоскоп Weekly 2018 № 793-794
Согласно ВОЗ, Российская Федерация лидирует в Европейском регионе по показателям заболеваемости ВИЧ-инфекцией. Министерство здравоохранения РФ с этим не согласно. Разбираемся, как устроен учет новых случаев ВИЧ-инфекции в России. ...
Added: February 13, 2019