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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.
Namsaraev Z., Nanzatov B., Kozlova A. et al., Scientific Reports 2026 Vol. 16 No. 1 Article 17769
Distilled fermented milk beverages are rare in food technology, despite the global prevalence of plant-based spirits. Currently, the production of distilled strong alcoholic beverages from fermented milk using traditional technologies is known only among Mongolic-speaking peoples and their Siberian neighbors. This study provides the first interdisciplinary analysis of darasun, a traditional Buryat spirit made from fermented ...
Added: June 10, 2026
Blank I., Klucharev V., Shestakova A., Frontiers in Human Neuroscience 2026 Vol. 20 Article 1687121
In video games, the participants are active agents who pursue various goals within gaming environments that increasingly resemble real life. As a result, video games are increasingly offering tools for neuroimaging studies aiming to elucidate the neural basis of human perceptual, cognitive, and emotional functions. Here, we review these studies. The first studies used computerized ...
Added: June 6, 2026
Boldyreva M., Mohammad R., Agareva M. et al., FRONTIERS IN ANIMAL SCIENCE 2026 Vol. 7 Article 1837838
Mammals from arid ecosystems face distinct physiological challenges: water scarcity and unpredictable food availability require the integration of energy storage, maintenance of water balance, and flexible switching between nutrients. Our previous study demonstrated lower fasting blood glucose levels in the desert rodent Acomys cahirinus (African spiny mouse), which also possesses a unique regenerative ability. The aim of ...
Added: June 3, 2026
Kazantseva A. V., A.V. Toropova, Khusnutdinova E. K. et al., ВАВИЛОВСКИЙ ЖУРНАЛ ГЕНЕТИКИ И СЕЛЕКЦИИ, Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук» (ИЦиГ СО РАН) (Новосибирск) 2025 Vol. 30 No. 3 P. 470–481
The development of musical abilities, including absolute pitch, musical memory, rhythm sense, and musicality, at a high degree is determined by a hereditary component (up to 68 %). The studies implementing a genome-wide linkage and association approach to musical aptitude have revealed more than 100 genetic loci. This spectrum is comprised of the genes encoding ...
Added: May 29, 2026
Anna Davidovich, Anna N. Shestakova, Arzumanyan N. et al., Frontiers in Psychology 2026 Vol. 17 Article 1764306
Background:
Delay discounting refers to the tendency to choose sooner, smaller rewards over larger, later rewards. Many previous studies link this tendency positively to reward sensitivity, yet the specific mechanisms behind this association remain poorly understood. Reward sensitivity may relate to delay discounting through at least three possible pathways: increased sensitivity to reward size, increased sensitivity ...
Added: May 27, 2026
Kochetkova E., Kostanian D., Martynova O. et al., Brain Topography 2026 Vol. 39 No. 4 Article 51
Letter recognition is assumed to involve several levels of analysis, including coarse tuning for category and novelty and more fine tuning for specific features, related to letter orientation. We employed an oddball fast periodic visual stimulation (FPVS) paradigm with magnetoencephalography (Elekta VectorView, 306 sensors) to study neural discrimination responses in the source space. Using contrasts ...
Added: May 24, 2026
Borovikova I., Uporov I., Okhrimenko G. et al., Journal of Structural Biology 2026 Vol. 218 No. 2 Article 108315
Single amino acid substitutions in the ATP-binding domain of ACVRL1, a key receptor in the bone morphogenetic protein (BMP) signaling pathway, are frequently classified as variants of uncertain significance (VUS), complicating molecular diagnosis for pulmonary arterial hypertension (PAH) and Hereditary Hemorrhagic Telangiectasia (HHT). Since aberrant ATP binding disrupts downstream SMAD1/5/8 phosphorylation, we employed molecular dynamics ...
Added: May 20, 2026
Goltseva Y., Tsokolaeva Z., Beloglazova I. et al., Stem Cell Research and Therapy 2026 Vol. 17 No. 1 Article 112
Background Cardiac fibrosis represents a significant health burden, with endothelial dysfunction and damaged
perivascular microenvironment increasingly recognized as key contributors to fibrotic remodeling. The urokinase
plasminogen activator receptor (uPAR), a critical component of the urokinase system, plays a pivotal role in vascular
remodeling and fibrosis. While prior evidence indicates that uPAR deficiency leads to microvascular dysfunction and
perivascular fibrosis, ...
Added: May 19, 2026
Perevoznyuk G., Batov A., Pleskovskaya A. et al., Scientific Reports 2026 Vol. 16 Article 13098
Motor imagery (MI) allows individuals to mentally simulate movements without execution, engaging neural pathways that overlap with those used during real actions. However, how imagery perspective influences corticospinal excitability across different effectors remains unclear. Using neuronavigated transcranial magnetic stimulation (TMS), we compared kinesthetic (KMI), first-person visual (VMI-1PP), and third-person visual (VMI-3PP) imagery of elbow flexion-extension ...
Added: May 5, 2026
Назаренко А. Г., Федоров М. В., Moshkin A. et al., Вестник Росздравнадзора 2026 № 1 С. 14–29
Multimodal foundation models and medical multimodal large language models are establishing a new class of diagnostic clinical decision support systems capable of operating on heterogeneous data sources, including medical imaging (X-ray, CT, MRI, ultrasound, histopathology), physiological signals (ECG, EEG), clinical text (electronic health records, reports, discharge summaries), laboratory measurements, molecular profiling data, and related modalities. ...
Added: May 4, 2026
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
Гулов Д. М., Елумеева Т. Г., Федоров Н. И. 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
Enchilik P. R., G.V.Klink, Semenkov I. N., 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 Vol. 6 Article 1776807
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 Article 48544
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
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