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Crosstalk of thioredoxin system and programmed cell death: from pathophysiology to novel therapy.

The thioredoxin (Trx) system, an integral component of cellular redox regulation, preserves protein dithiol-disulfide equilibrium through its conserved Cys-Gly-Pro-Cys active site and is involved in key cellular functions, including cell proliferation, apoptosis, and signal transduction. In cancer biology, the thioredoxin system plays dual roles: overexpression can suppress oxidative stress and promote tumor growth, whereas dysfunction can trigger programmed cell death (PCD). However, a critical area for future research is to delineate how Trx modulates the intricate networks of PCD, and to id

Selinexor, a selective inhibitor of nuclear export, shows anti-proliferative and anti-migratory effects on male germ cells in vitro.

BackgroundSelinexor (SLX), a selective inhibitor of nuclear export (SINE), has been shown to interfere with nuclear export mechanisms and to exert antitumor effects in a variety of cancer cell types. It is known to regulate multiple fundamental cellular processes, including the DNA damage response, cell proliferation, and stress signaling pathways. Nevertheless, its potential effects on reproductive cells remain inadequately characterized. The present study was aimed to investigate the cytotoxic, apoptotic, anti-proliferative and anti-migratory effects of SLX on GC1 (spermatogonia) and GC2 (sp

Structure, function, and pathology of PHF23.

Plant Homeodomain Finger Protein 23 (PHF23) is a member of the Plant Homeodomain (PHD) finger protein family and has been extensively reported since its discovery. Numerous studies have demonstrated that PHF23 plays a crucial role in various biological processes, such as gene expression regulation, autophagy, and tumorigenesis. Additionally, PHF23 is associated with various diseases including various malignancies, osteoarthritis, and tuberculosis, all of which currently lack effective and targeted treatment options. Therefore, this review systematically summarizes the existing literature on PH

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… Lycorine induces apoptosis of A549 cells via AMPK-mammalian target of rapamycin (mTOR)-S6K signaling pathway. Med. Sci. Monit. 23, 2035–2041. 10.12659/msm.900742 Zhang Y., Guo Y., Gough S. M., Zhang J., Vann K. R., Li K., et al. (2020). …

The inhibition of RANKL-induced osteoclastogenesis through the suppression of p38 signaling pathway by naringenin and attenuation of titanium-particle-induced osteolysis.

The aim of this study was to assess the effect of naringenin on osteoclastogenesis and titanium particle-induced osteolysis. Osteolysis from wear-induced particles and aseptic loosening are the most frequent late complications of total joint arthroplasty leading to revision of the prosthesis. Osteolysis during aseptic loosening is most likely due to increased bone resorption by osteoclasts. Through in vitro studies, we demonstrated that naringenin, a naturally occurring flavanone in grapefruit and tomatoes, exerts potent inhibitory effects on the ligand of the receptor activator of nuclear fac

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… Naringin attenuates EGF-induced MUC5AC secretion in A549 cells by suppressing the cooperative activities of MAPKs-AP-1 and IKKs-IkappaB-NF-kappaB signaling pathways. Eur. J. Pharmacol. 2012;690:207–213. doi: 10.1016/j.ejphar.2012.06.040. 29. …

Epithelial-Mesenchymal Transition in Cancer: Insights Into Therapeutic Targets and Clinical Implications.

Radiation therapy is a fundamental component of cancer treatment, benefiting 50%-70% of patients by selectively targeting malignant tissues. However, radioresistance remains a significant challenge, often driven by epithelial-mesenchymal transition (EMT). EMT increases cancer invasiveness and metastasis by upregulating mesenchymal markers, including vimentin and N-cadherin, and downregulating epithelial markers, such as E-cadherin. EMT under radiation involves principal signaling pathways, including TGF-β, Wnt/β-catenin, Notch, and ERK, which regulate EMT through transcription factors such as

Targeting SREBP-2-Regulated Mevalonate Metabolism for Cancer Therapy.

Recently, targeting metabolic reprogramming has emerged as a potential therapeutic approach for fighting cancer. Sterol regulatory element binding protein-2 (SREBP-2), a basic helix-loop-helix leucine zipper transcription factor, mainly regulates genes involved in cholesterol biosynthesis and homeostasis. SREBP-2 binds to the sterol regulatory elements (SREs) in the promoters of its target genes and activates the transcription of mevalonate pathway genes, such as HMG-CoA reductase (HMGCR), mevalonate kinase and other key enzymes. In this review, we first summarized the structure of SREBP-2 and

Integrated Network Pharmacology Approach for Drug Combination Discovery: A Multi-Cancer Case Study.

Despite remarkable efforts of computational and predictive pharmacology to improve therapeutic strategies for complex diseases, only in a few cases have the predictions been eventually employed in the clinics. One of the reasons behind this drawback is that current predictive approaches are based only on the integration of molecular perturbation of a certain disease with drug sensitivity signatures, neglecting intrinsic properties of the drugs. Here we integrate mechanistic and chemocentric approaches to drug repositioning by developing an innovative network pharmacology strategy. We developed

The Role of Extracellular Vesicles in Bone Metastasis.

Multiple types of cancer have the specific ability to home to the bone microenvironment and cause metastatic lesions. Despite being the focus of intense investigation, the molecular and cellular mechanisms that regulate the metastasis of disseminated tumor cells still remain largely unknown. Bone metastases severely impact quality of life since they are associated with pain, fractures, and bone marrow aplasia. In this review, we will summarize the recent discoveries on the role of extracellular vesicles (EV) in the regulation of bone remodeling activity and bone metastasis occurrence. Indeed,

The PI3K inhibitor buparlisib suppresses osteoclast formation and tumour cell growth in bone metastasis of lung cancer, as evidenced by multimodality molecular imaging.

Non‑small cell lung cancer (NSCLC) metastasis commonly occurs in bone, which often results in pathological fractures. Sustained phosphoinositide‑3‑kinase (PI3K) signalling promotes the growth of PI3K‑dependent NSCLC and elevates osteoclastogenic potential. The present study investigated the effects of a PI3K inhibitor on NSCLC growth in bone and osteoclast formation, and aimed to determine whether it could control symptoms associated with bone metastasis. A bone metastasis xenograft model was established by implanting NCI‑H460‑luc2 lung cancer cells, which contain a phosphatidylinositol‑​4,5‑b

Adeno-associated virus as a delivery vector for gene therapy of human diseases.

Adeno-associated virus (AAV) has emerged as a pivotal delivery tool in clinical gene therapy owing to its minimal pathogenicity and ability to establish long-term gene expression in different tissues. Recombinant AAV (rAAV) has been engineered for enhanced specificity and developed as a tool for treating various diseases. However, as rAAV is being more widely used as a therapy, the increased demand has created challenges for the existing manufacturing methods. Seven rAAV-based gene therapy products have received regulatory approval, but there continue to be concerns about safely using high-dos

Cancer Neoaxonogenesis: Mechanisms and Factors Involved in the Recruitment of Peripheral Nerves by Cancer Tissue.

Peripheral nerves provide a direct connection between the brain and the tumor microenvironment. This connection allows the nervous system to influence processes associated with the development, progression, and metastasis of different tumor types. Therefore, tumor innervation by peripheral nerve fibers is currently emerging as a characteristic that contributes to multiple hallmarks of cancer. Several experimental studies have shown that cancer progression involves actively inducing the ingrowth of autonomic and sensory nerve fibers into tumor tissue. In this process, known as neoaxonogenesis,

Matrix stimulation in cancer pain: Methodology, safety and effectiveness.

BackgroundThis feasibility study addresses the applicability of matrix electrodes for the reduction of ongoing pain in cancer patients via low-frequency electrical stimulation (LFS).MethodsLow-frequency matrix stimulation (4 Hz) was applied to the skin within the 'Head's zones' referring to the tumour localization of cancer pain patients. Pain at baseline was compared to a 3-day treatment interval consisting of 5 min of matrix stimulation in the morning and evening followed by a 3-day follow-up period without therapy. Main outcome parameters included numeric rating scale values (rating scale 0

Cancer incidence attributable to tuberculosis in 2015: global, regional, and national estimates.

BackgroundTuberculosis is associated with increased risk of cancer. However, the impact of tuberculosis on global cancer burden is unknown.MethodsWe performed random-effects meta-analyses and meta-regressions of studies reporting the association between tuberculosis and cancer risks by searching PubMed, Web of Science, Embase, Cochrane library, and CINAHL from inception to 1 June 2019. Population attributable fractions (PAFs) of cancer incidence attributable to tuberculosis were calculated using relative risks from our meta-analyses and tuberculosis prevalence data from Global Health Data Exch

Modulating the JAK/STAT pathway with natural products: potential and challenges in cancer therapy.

The Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) pathway is a critical signaling network governing cellular functions such as immune responses, proliferation, and apoptosis. Dysregulation of this pathway is strongly implicated in cancer progression. This review explores the therapeutic potential of natural products, including Curcumin, Resveratrol, Apigenin, and Epigallocatechin Gallate (EGCG), as modulators of the JAK/STAT pathway. These phytochemicals exhibit anticancer activity by inhibiting JAK/STAT phosphorylation, blocking STAT dimerization, and interfering wi

Unlocking the potential of tumor-targeting peptides in precision oncology.

Targeted cancer therapy has emerged as a promising alternative to conventional chemotherapy, which is often plagued by poor selectivity, off-target effects, and drug resistance. Among the various targeting agents in development, peptides stand out for their unique advantages, including minimal immunogenicity, high tissue penetration, and ease of modification. Their small size, specificity, and flexibility allow them to target cancer cells while minimizing damage to healthy tissue selectively. Peptide-based therapies have shown great potential in enhancing the efficacy of drug delivery, improvi

Протеин тиросин фосфатаза-рецептор типа каппа (ПТПРК) вернулся к рассмотрению: развивающееся понимание структуры, функций и патологии.

Protein Tyrosine Phosphataze Type Cappa (PTPRK) — мембранная тиросина фосфатаза, кодируемая часто удаляемой областью хромосомы 6q, которая играет ключевую роль в регулировании сигнала, сцепления и иммунной реакции клеток. Структурно PTPRK включает внеклеточную область, связанную с сцеплением клеток, область трансмембрана и две внутриклеточные каталитические области, ответственные за фосфатазу. В частности, PTPRK подвергается протеолитическому декольте с помощью Furin и ADAM10, в результате чего образуется внеклеточная подгруппа E и подгруппа P. Дальнейшая обработка с помощью β-Secretasa выпуск

Molecular factors associated with lung cancer in people living with HIV.

Lung cancer is the most common Non-AIDS-Defining Cancer (NADC) and a leading cause of cancer-related death in People Living With HIV (PLWH). Despite antiretroviral therapy, PLWH are at higher risk of developing cancer compared to the general population. This increased susceptibility reflects a combination of immunosuppression, chronic inflammation, smoking, and direct oncogenic effects of HIV proteins. Tat, gp120, and Nef modulate cell cycle control, apoptosis, epithelial-mesenchymal transition, angiogenesis, and immune evasion. Persistent HIV reservoirs in lung tissue (mainly effector memory

Cold Atmospheric Plasma in the Treatment of Osteosarcoma.

Human osteosarcoma (OS) is the most common primary malignant bone tumor occurring most commonly in adolescents and young adults. Major improvements in disease-free survival have been achieved by implementing a combination therapy consisting of radical surgical resection of the tumor and systemic multi-agent chemotherapy. However, long-term survival remains poor, so novel targeted therapies to improve outcomes for patients with osteosarcoma remains an area of active research. This includes immunotherapy, photodynamic therapy, or treatment with nanoparticles. Cold atmospheric plasma (CAP), a hig

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… Non-thermal plasma treatment altered gene expression profiling in non-small-cell lung cancer A549 cells BMC Genom. 2015 16 435 10.1186/s12864-015-1644-8 26116417 PMC4483225 43. Joh H.M. Choi J.Y. Kim S.J. Chung T.H. Kang T.H. …

Emerging Research and Future Directions on Doxorubicin: A Snapshot.

Doxorubicin, a widely used anthracycline antibiotic, has been a cornerstone in cancer chemotherapy since the 1960s. In addition to doxorubicin, anthracycline chemotherapy medications include daunorubicin, idarubicin, and epirubicin. For many years, doxorubicin has been the chemotherapy drug of choice for treating a broad variety of cancers. Despite its efficacy, doxorubicin therapy is hindered by serious side effects, primarily cardiotoxicity, and the challenges of drug resistance. Recent research has focused on optimizing doxorubicin's therapeutic index by developing cardioprotective strategi

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… Zhang et al., demonstrated that hollow polydopamine (HPDA)/Au@DOX accelerated DOX release and enhanced uptake by A549 cells, furthermore Both in vitro and in vivo experiments demonstrated that the photothermal-chemotherapy combination group (HPDA/Au@DOX+NIR) exhibited stronger anti-metastatic and anti-tumor …

Linoleate-pazopanib conjugation as active pharmacological ingredient to abolish hepatocellular carcinoma growth.

Small molecule compounds targeting multiple kinases involved in neoangiogenesis have shown survival benefits in patients with unresectable hepatocellular carcinoma (HCC). Nonetheless, despite the beneficial effects of multikinase inhibitors (MKIs), a lack of boosting adjuvant limits their objective response rate. Lipid conjugates have been used to improve delivery efficacy or pharmaceutical benefits for decades. However, the feasibility of utilizing lipid-drug conjugates (LDCs) in HCC regimens remains untested. In this study, oral feeding of linoleate-fluorescein isothiocyanate conjugates show

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… Phosphoinositide specific phospholipase Cγ1 inhibition-driven autophagy caused cell death in human lung adenocarcinoma A549 cells in vivo and in vitro . Int. J. Biol. Sci. 16 (8), 1427–1440. 10.7150/ijbs.42962 Luo C., Sun J., Liu D., Sun B., Miao L., Musetti S., et al. (2016). …