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Ультрафиолетовое излучение и нейродегенерация: молекулярные механизмы, лежащие в основе двойного нейрозащитного и нейротоксичного воздействия.

Ультрафиолетовое излучение имеет сложную, зачастую противоречивую связь с риском/прогрессом нейродегенерации, охватывающую клинически диагностированные заболевания [Заболевания Паркинсона (PD), болезни Альцгеймера (AD), множественный склероз (MS) и амиотропический боковой склероз (ALS)] или промежуточные фенотипы (уменьшенный нейрогенесис, потеря гиппокампального объема). Цель этого обзора заключается в выявлении двойного воздействия УФ-излучения путем сбора и обобщения экспериментальных (доклинических и переводческих) данных, а также эпидемиологических данных. Нынешняя литература демонстрируе

Совпадение в полном тексте источника
… This radiation is capable of inducing direct DNA damage, for example, via single strand crosslinking by catalyzing the formation of cyclobutene pyrimidine dimers (CPDs) and pyrimidine (6–4) pyrimidone products (64PPs) ( Cadet and Douki, 2018 ). …

Molecular targeted therapy for anticancer treatment.

Since the initial clinical approval in the late 1990s and remarkable anticancer effects for certain types of cancer, molecular targeted therapy utilizing small molecule agents or therapeutic monoclonal antibodies acting as signal transduction inhibitors has served as a fundamental backbone in precision medicine for cancer treatment. These approaches are now used clinically as first-line therapy for various types of human cancers. Compared to conventional chemotherapy, targeted therapeutic agents have efficient anticancer effects with fewer side effects. However, the emergence of drug resistanc

Phytochemicals as Chemo-Preventive Agents and Signaling Molecule Modulators: Current Role in Cancer Therapeutics and Inflammation.

Cancer is one of the deadliest non communicable diseases. Numerous anticancer medications have been developed to target the molecular pathways driving cancer. However, there has been no discernible increase in the overall survival rate in cancer patients. Therefore, innovative chemo-preventive techniques and agents are required to supplement standard cancer treatments and boost their efficacy. Fruits and vegetables should be tapped into as a source of compounds that can serve as cancer therapy. Phytochemicals play an important role as sources of new medication in cancer treatment. Some synthet

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… Green tea polyphenol-treated volunteer skin was examined for erythema, and DNA damage (represented by cyclobutene pyrimidine dimers) was measured before and after UVB exposure. Lower levels of these dimers were seen in both the dermis and epidermis post-treatment with green tea phenols [ 223 ]. …

The Application of Artificial Intelligence and Drug Repositioning for the Identification of Fibroblast Growth Factor Receptor Inhibitors: A Review.

Artificial intelligence talks about modeling intelligent behavior through a computer with the least human involvement. Drug repositioning techniques based on artificial intelligence accelerate the research process and decrease the cost of experimental studies. Dysregulation of fibroblast growth factor (FGF) receptors as the tyrosine kinase family of receptors plays a vital role in a wide range of malignancies. Because of their functional significance, they were considered promising drug targets for the therapy of various cancers. This review has summarized small molecules capable of inhibiting

Evolving cognition of the JAK-STAT signaling pathway: autoimmune disorders and cancer.

The Janus kinase (JAK) signal transducer and activator of transcription (JAK-STAT) pathway is an evolutionarily conserved mechanism of transmembrane signal transduction that enables cells to communicate with the exterior environment. Various cytokines, interferons, growth factors, and other specific molecules activate JAK-STAT signaling to drive a series of physiological and pathological processes, including proliferation, metabolism, immune response, inflammation, and malignancy. Dysregulated JAK-STAT signaling and related genetic mutations are strongly associated with immune activation and c

Cancer therapy-associated Takotsubo cardiomyopathy: A narrative review of mechanisms, drug associations, and clinical implications.

Anticancer therapies have been increasingly associated with Takotsubo cardiomyopathy (TTC). As prior reports remain fragmented across case studies and drug-specific reviews, this paper offers one of the most comprehensive reviews to date of cancer therapy-associated TTC. While classically triggered by emotional or physical stress, TTC has been increasingly associated with chemotherapy and other cancer-directed therapies. This literature review explores the pathophysiology, clinical features, and evolving evidence linking anticancer agents to TTC, with a focus on cytotoxic cancer therapy, hormo

Invited Lectures : Overviews Purinergic signalling: past, present and future.

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Inhibition of the fibroblast growth factor receptor (FGFR) pathway: the current landscape and barriers to clinical application.

The fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR) is a tyrosine kinase signaling pathway that has a fundamental role in many biologic processes including embryonic development, tissue regeneration, and angiogenesis. Increasing evidence indicates that this pathway plays a critical role in oncogenesis via gene amplification, activating mutations, or translocation in tumors of various histologies. With multiplex sequencing technology, the detection of FGFR aberrations has become more common and is tied to cancer cell proliferation, resistance to anticancer therapies, and n

Small molecules in targeted cancer therapy: advances, challenges, and future perspectives.

Due to the advantages in efficacy and safety compared with traditional chemotherapy drugs, targeted therapeutic drugs have become mainstream cancer treatments. Since the first tyrosine kinase inhibitor imatinib was approved to enter the market by the US Food and Drug Administration (FDA) in 2001, an increasing number of small-molecule targeted drugs have been developed for the treatment of malignancies. By December 2020, 89 small-molecule targeted antitumor drugs have been approved by the US FDA and the National Medical Products Administration (NMPA) of China. Despite great progress, small-mol

Vincristine-Induced Peripheral Neuropathy in Childhood Acute Lymphoblastic Leukemia: Genetic Variation as a Potential Risk Factor.

Vincristine (VCR) is the first-line chemotherapeutic medication often co-administered with other drugs to treat childhood acute lymphoblastic leukemia. Dose-dependent neurotoxicity is the main factor restricting VCR's clinical application. VCR-induced peripheral neuropathy (VIPN) sometimes results in dose reduction or omission, leading to clinical complications or affecting the patient's quality of life. With regard to the genetic basis of drug responses, preemptive pharmacogenomic testing and simultaneous blood level monitoring could be helpful for the transformation of various findings into

MYC inhibitors in multiple myeloma.

The importance of MYC function in cancer was discovered in the late 1970s when the sequence of the avian retrovirus that causes myelocytic leukemia was identified. Since then, over 40 years of unceasing research have highlighted the significance of this protein in malignant transformation, especially in hematologic diseases. Indeed, some of the earliest connections among the higher expression of proto-oncogenes (such as MYC), genetic rearrangements and their relation to cancer development were made in Burkitt lymphoma, chronic myeloid leukemia and mouse plasmacytomas. Multiple myeloma (MM), in

Second-Generation Jak2 Inhibitors for Advanced Prostate Cancer: Are We Ready for Clinical Development?

Androgen deprivation therapy (ADT) for metastatic and high-risk prostate cancer (PC) inhibits growth pathways driven by the androgen receptor (AR). Over time, ADT leads to the emergence of lethal castrate-resistant PC (CRPC), which is consistently caused by an acquired ability of tumors to re-activate AR. This has led to the development of second-generation anti-androgens that more effectively antagonize AR, such as enzalutamide (ENZ). However, the resistance of CRPC to ENZ develops rapidly. Studies utilizing preclinical models of PC have established that inhibition of the Jak2-Stat5 signaling

NF-κB: master regulator of cellular responses in health and disease.

The NF-κB transcription control proteins play widespread roles in cellular behavior, regulating immune responses, inflammation, cell survival, proliferation, and development. Here, we attempt to comprehensively review these diverse functions and underlying mechanisms, leading readers to relevant references of both historic and topical importance. Because of the huge number of NF-κB control mechanisms and functions, and the vast literature that describes these, being comprehensive is a daunting task but we hope that readers will find clues to lead them to whatever understanding they may seek. A

Clinical development of targeted and immune based anti-cancer therapies.

Cancer is currently the second leading cause of death globally and is expected to be responsible for approximately 9.6 million deaths in 2018. With an unprecedented understanding of the molecular pathways that drive the development and progression of human cancers, novel targeted therapies have become an exciting new development for anti-cancer medicine. These targeted therapies, also known as biologic therapies, have become a major modality of medical treatment, by acting to block the growth of cancer cells by specifically targeting molecules required for cell growth and tumorigenesis. Due to

Hypoxia-inducible factor-prolyl hydroxylase inhibitors in treatment of anemia with chronic disease.

AbstractAnemia of chronic disease (ACD) is the most frequent clinical issue in patients with chronic disease. ACD is usually secondary to chronic kidney disease (CKD), cancer, and chronic infection, which is associated with poor health outcomes, increased morbidity and mortality, and substantial economic costs. Current treatment options for ACD are very limited. The discovery of the hypoxia-inducible factor-prolyl hydroxylase (HIF-PHD) pathway made it possible to develop novel therapeutic agents (such as hypoxia-inducible factor-prolyl hydroxylase inhibitor, HIF-PHI) to treat ACD by stabilizin

Antibody drug conjugate: the "biological missile" for targeted cancer therapy.

Antibody-drug conjugate (ADC) is typically composed of a monoclonal antibody (mAbs) covalently attached to a cytotoxic drug via a chemical linker. It combines both the advantages of highly specific targeting ability and highly potent killing effect to achieve accurate and efficient elimination of cancer cells, which has become one of the hotspots for the research and development of anticancer drugs. Since the first ADC, Mylotarg® (gemtuzumab ozogamicin), was approved in 2000 by the US Food and Drug Administration (FDA), there have been 14 ADCs received market approval so far worldwide. Moreove

Emerging evidence of the molecular landscape specific for hematogenous metastasis from gastric cancer.

Gastric cancer (GC) is one of the most frequently diagnosed cancers in the world. Most GC patients are diagnosed when the cancer is in an advanced stage, and consequently, some develop metastatic lesions that generally cause cancer-related death. Metastasis establishment is affected by various conditions, such as tumor location, hemodynamics and organotropism. While digestive cancers may share a primary site, certain cases develop hematogenous metastasis with the absence of peritoneal metastasis, and vice versa. Numerous studies have revealed the clinicopathological risk factors for hematogeno

Pathogenic Role of FGFR3 Autoantibodies in Small Fiber Neuropathy.

Sensory neuronopathies (SNN) and small fiber neuropathies (SFN) are debilitating disorders associated with neuropathic pain, yet their underlying mechanisms remain poorly understood. Autoantibodies against fibroblast growth factor receptor 3 define a subset of patients with consistent reports of neuropathic pain harboring a distinct clinical phenotype characterized by small-fiber and non-length-dependent neuropathy, suggesting dorsal root ganglia (DRG) dysfunction. FGFR3-autoantibody-positive sera (FGFR3-AbS) bind to sensory neurons within dorsal root ganglia (DRG). The target of autoantibodie

Phosphodiesterase 7: a potential novel therapeutic target in ovarian cancer.

INTRODUCTION: Chemoresistance and disease relapses in epithelial ovarian cancer (EOC) highlight the need for novel therapeutic strategies. Here, we investigated phosphodiesterase 7A (PDE7A) as a potential target in ovarian cancer treatment. METHODS: Gene expression was performed by RNA sequencing data comparing high-grade serous ovarian carcinoma (HGSOC) and fallopian tube samples. The PDE7 inhibitor BRL 50481, alone or combined with paclitaxel (PTX), was tested in drug-sensitive A2780 and multi-resistant OVCAR3 cells by Diphenyltetrazolium bromide (MTT) assay. To validate data from the high

Tumor biomarkers for diagnosis, prognosis and targeted therapy.

Tumor biomarkers, the substances which are produced by tumors or the body's responses to tumors during tumorigenesis and progression, have been demonstrated to possess critical and encouraging value in screening and early diagnosis, prognosis prediction, recurrence detection, and therapeutic efficacy monitoring of cancers. Over the past decades, continuous progress has been made in exploring and discovering novel, sensitive, specific, and accurate tumor biomarkers, which has significantly promoted personalized medicine and improved the outcomes of cancer patients, especially advances in molecu