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Drug Repurposing Opportunities in Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is considered one of the deadliest tumors worldwide. The diagnosis is often possible only in the latter stages of the disease, with patients already presenting an advanced or metastatic tumor. It is also one of the cancers with poorest prognosis, presenting a five-year survival rate of around 5%. Treatment of PDAC is still a major challenge, with cytotoxic chemotherapy remaining the basis of systemic therapy. However, no major advances have been made recently, and therapeutic options are limited and highly toxic. Thus, novel therapeutic options are urgen

MSC-EV therapy for bone/cartilage diseases.

Mesenchymal stromal cells (MSCs) have been utilized in cell therapy for various diseases. Recent studies have demonstrated that extracellular vesicles (EVs) released by MSCs play an important role in their therapeutic activities. EVs contain a variety of bioactive molecules such as proteins, messenger RNAs (mRNAs), and micro RNAs (miRNAs) and modify the function of the recipient cells by transferring these molecules. Despite the promising potential of EV therapy as a substitute for MSC therapy, there are challenges that need to be addressed for the clinical success of EV therapy. EV quality ha

Circular RNAs in cancer.

Circular RNA (circRNA), a subtype of noncoding RNA, has emerged as a significant focus in RNA research due to its distinctive covalently closed loop structure. CircRNAs play pivotal roles in diverse physiological and pathological processes, functioning through mechanisms such as miRNAs or proteins sponging, regulation of splicing and gene expression, and serving as translation templates, particularly in the context of various cancers. The hallmarks of cancer comprise functional capabilities acquired during carcinogenesis and tumor progression, providing a conceptual framework that elucidates t

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… The downregulation of circCIMT in this model functioned as a tumor suppressor that inhibited DNA damage by directly binding to APEX1, thereby regulating the DNA base excision repair (BER) pathway, which can remove small and nonhelix‐distorting base damages. 237 CircSMARCA5 can form an R‐loop with its …

Precision Reprogramming in CAR-T Cell Therapy: Innovations, Challenges, and Future Directions of Advanced Gene Editing.

Chimeric antigen receptor (CAR)-T cell therapy represents a breakthrough in cancer immunotherapy, demonstrating impressive clinical outcomes, particularly for hematologic malignancies. However, its broader therapeutic application, especially against solid tumors, remains limited. Key challenges include T cell exhaustion, limited persistence, cytokine-mediated toxicities, and logistical hurdles associated with manufacturing autologous products. Emerging gene editing technologies, such as CRISPR/Cas systems, base editing, and prime editing, offer novel approaches to optimize CAR-T cells, aiming

Hallmarks of Cancer Affected by the MIF Cytokine Family.

New diagnostic methods and treatments have significantly decreased the mortality rates of cancer patients, but further improvements are warranted based on the identification of novel tumor-promoting molecules that can serve as therapeutic targets. The macrophage migration inhibitory factor (MIF) family of cytokines, comprising MIF and DDT (also known as MIF2), are overexpressed in almost all cancer types, and their high expressions are related to a worse prognosis for the patients. MIF is involved in 9 of the 10 hallmarks of cancer, and its inhibition by antibodies, nanobodies, or small synthe

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… Flap Endonuclease 1 Efficiently Cleaves Base Excision Repair and DNA Replication Intermediates Assembled into Nucleosomes. Mol. Cell. 2002;10:1201–1211. doi: 10.1016/S1097-2765(02)00736-0. 108. Wang D., Luo L., Chen W., Chen L.Z., Zeng W.T., Li W., Huang X.H. …

Management of Medication-Related Osteonecrosis of the Jaw (MRONJ) Using Leukocyte- and Platelet-Rich Fibrin (L-PRF) and Photobiomodulation: A Retrospective Study.

BACKGROUND: The aim of this study was to compare retrospectively the effect of three different treatment protocols on the healing outcome in patients with established medication-related osteonecrosis of the jaw (MRONJ). METHODS: A total of 34 MRONJ patients were recruited from the Department database and were divided according to the treatment protocols in a study group (G1) and two control groups (G2 and G3). G1 was treated with antibiotic therapy, surgery, leukocyte- and platelet-rich fibrin (L-PRF), and photobiomodulation; G2 was treated with antibiotic therapy and surgery; G3 was treated

LncRNA RHPN1-AS1 Targeting miR-625/REG3A Promotes Cell Proliferation And Invasion Of Glioma Cells.

IntroductionGlioma arises from the proliferation of neuroglial cells differentiated from the ectoderm. Evidence has confirmed that differentially expressed long non-coding RNAs (lncRNAs) may be involved in the development and progression of various tumors. The present study aimed to explore the biological function of lncRNA RHPN1-AS1 in glioma.Materials and methodsThe expressions of RHPN1-AS1 in glioma tissues and cells were examined using RT-PCR. Colony formation assay, MTT assay, wound healing assay and transwell assay were performed to detect cell cloning efficiency, proliferation, migratio

Sorcin: a novel potential target in therapies of cancers.

Soluble resistance-related calcium-binding protein (sorcin) is a member of the penta-EF-hand protein family. Sorcin is widely distributed in normal human tissues, such as the brain, heart, lymphocytes, kidneys, breast and skin. Findings suggest that sorcin is associated with the regulation of calcium homeostasis, cell cycle and vesicle trafficking. It has been reported that many types of non-neoplastic diseases such as diabetes, viral infection, infertility, and nervous system diseases were affected by the expression of sorcin. One of the main issues is the role of sorcin in neoplastic disease

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… Additionally, this operation led to a messenger RNA and protein expression of multidrug resistance gene (MDR1), multidrug resistance-associated protein (MRP1), excision repair cross-complementing gene 1 (ERCC1), glutathione S-transferase-p (GST-n), RhoE, Bcl-2, and surviving in sorcin silencing CNE2/ …

Influence of Hypoxia on Tumor Heterogeneity, DNA Repair, and Cancer Therapy: From Molecular Insights to Therapeutic Strategies.

Hypoxia, characterized by a reduction in tissue oxygen levels, is a hallmark of many solid tumors and affects a range of cellular processes, including DNA repair. In low-oxygen conditions, cancer cells often suppress key DNA repair pathways such as homologous recombination (HR), leading to the accumulation of DNA damage and increased genomic instability. These changes not only drive tumor progression but also contribute to resistance against conventional therapies. Hypoxia significantly reduces the effectiveness of oxygen-dependent treatments, including radiotherapy and many chemotherapeutic a

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… In the form of a heterodimer, their products function as important tumor suppressor factors involved in many DNA repair forms, including homologous recombination and base excision repair. …

Hematopoietic Tumors

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Drug repurposing: A novel strategy to target cancer stem cells and therapeutic resistance.

Chemotherapy is an effortless and frequently used approach in cancer therapy. However, in most cases, it can only prolong life expectancy and does not guarantee a complete cure. Furthermore, chemotherapy is associated with severe adverse effects, one of the major complications of effective cancer therapy. In addition, newly published research outputs show that cancer stem cells are involved in cancer disease progression, drug resistance, metastasis, and recurrence and that they are functional in the trans-differentiation capacity of cancer stem cells to cancer cells in response to treatments.

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… The DNA repair mechanisms, namely nucleotide excision repair and homologous recombination, are the primary DNA repair mechanisms that reverse cisplatin-caused damage. 93 Hence, it is suggested that a combination of repair pathway inhibitors with DNA-damaging chemotherapy can increase the efficacy of …

Экспериментальное вливание повреждений миелина в посмертных ломках человеческого мозга.

Механизмы, которые приводят к повреждению миелина, как это видно в таких демиелионирующих расстройствах, как множественный склероз, остаются неясными. Значительная часть наших нынешних знаний основана на моделях животных, но различия между видами ограничивают их актуальность в контексте человеческой патологии и могут объяснить, почему различные перспективные методы лечения не сработали во время клинического перевода. После смерти органотипные культуры мозга человека обеспечивают уникальную платформу для изучения биологии миелина человека, поскольку они сохраняют генетический, цитоархитектуальн

The roles of inflammasomes in cancer.

Inflammation is a key characteristic of all stages of tumor development, including tumor initiation, progression, malignant transformation, invasion, and metastasis. Inflammasomes are an important component of the inflammatory response and an indispensable part of the innate immune system. Inflammasomes regulate the nature of infiltrating immune cells by signaling the secretion of different cytokines and chemokines, thus regulating the anti-tumor immunity of the body. Inflammasome expression patterns vary across different tumor types and stages, playing different roles during tumor progression

Targeting histone deacetylases in head and neck squamous cell carcinoma: molecular mechanisms and therapeutic targets.

The onerous health and economic burden associated with head and neck squamous cell carcinoma (HNSCC) is a global predicament. Despite the advent of novel surgical techniques and therapeutic protocols, there is an incessant need for efficacious diagnostic and therapeutic targets to monitor the invasion, metastasis and recurrence of HNSCC due to its substantial morbidity and mortality. The differential expression patterns of histone deacetylases (HDACs), a group of enzymes responsible for modifying histones and regulating gene expression, have been demonstrated in neoplastic tissues. However, th

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… Acetylation of the histone H3 tail domain regulates base excision repair on higher-order chromatin structures. Sci Rep. 2019;9(1):15972. doi: 10.1038/s41598-019-52340-0. 23. Dahlin JL, et al. …

Clinical Efficacy and Potential Mechanisms of Acupoint Stimulation Combined With Chemotherapy in Combating Cancer: A Review and Prospects.

Although chemotherapy is the first-line treatment strategy for a variety of tumors, its side effects have limited its efficacy. This review summarizes the progress on the use of acupoint stimulation to combat chemotherapy-associated side effects, including chemotherapy-induced peripheral neuropathy (CIPN), cognitive impairment (CICI), and gastrointestinal toxicity (GI), as well as myelosuppression and immunosuppression. It was found that acupoint stimulation attenuated CIPN and GI by modulating the 5-hydroxytryptamine system in dorsal root ganglia, the dorsal horn of the spinal cord, and the d

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… Effects of Acupuncture and Moxibustion on DNA Excision Repair-Related Proteins of Bone Marrow Cell in Cyclophosphamide-Induced Mice. Zhongguo Zhen Jiu (2009) 29(10):821–4. 54. Spiegel A, Shivtiel S, Kalinkovich A, Ludin A, Netzer N, Goichberg P, et al. …

Эпигенетическая ось Лактата-H4K12la-HDAC1 регулирует переход к микроглиальному состоянию во время экспериментального аутоиммунного энцефаломиелита у женских мышей.

Микроглиальная функциональная пластичность формируется метаболическим и эпигенетическим перепрограммированием, но то, как эти процессы регулируют автоиммунитет центральной нервной системы, остается неясным. Мы находим, что уровень цереброспинарной жидкости лактат коррелирует с множественным склерозом. Используя женские модели мыши экспериментального аутоиммунного энцефаломиэлита, аккумуляция спинного лакта приводит к стойкой микроглиальной гистоне лактилации, связывающей с гликолитической активацией. Микроглиавое исключение лактата дегидрогеназы А уменьшает эту лактиляцию и усугубляет остроту

Molecular Inhibitors of Growth Signals

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… The agent prevents nucleotide excision repair by inhibiting the G 2 checkpoint kinase CHK1, which results in apoptosis . Thus, it may enhance the effects of DNA damaging drugs. 7-hydroxystaurosporine is under study for treating melanoma and lymphoma. …

DHCR24 in Tumor Diagnosis and Treatment: A Comprehensive Review.

As an important nutrient in the human body, cholesterol can not only provide structural components for the body's cells, but also can be transformed into a variety of active substances to regulate cell signaling pathways. As an important cholesterol synthase, DHCR24 participates in important regulatory processes in the body. The application of DHCR24 in tumor clinical diagnosis and treatment also attracts much attention. This article reviews the structure and regulatory characteristics of DHCR24, and the research of DHCR24 on tumor progression. We summarize the possible mechanisms of DHCR24 pr

Biomarkers in Multiple Sclerosis: An Up-to-Date Overview

During the last decades, the effort of establishing satisfactory biomarkers for multiple sclerosis has been proven to be very difficult, due to the clinical and pathophysiological complexities of the disease. Recent knowledge acquired in the domains of genomics-immunogenetics and neuroimmunology, as well as the evolution in neuroimaging, has provided a whole new list of biomarkers. This variety, though, leads inevitably to confusion in the effort of decision making concerning strategic and individualized therapeutics. In this paper, our primary goal is to provide the reader with a list of the

Reversing Autoimmunity Combination of Rituximab and Intravenous Immunoglobulin.

In this concept paper, the authors present a unique and novel protocol to treat autoimmune diseases that may have the potential to reverse autoimmunity. It uses a combination of B cell depletion therapy (BDT), specifically rituximab (RTX) and intravenous immunoglobulin (IVIg), based on a specifically designed protocol (Ahmed Protocol). Twelve infusions of RTX are given in 6-14 months. Once the CD20+ B cells are depleted from the peripheral blood, IVIg is given monthly until B cells repopulation occurs. Six additional cycles are given to end the protocol. During the stages of B cell depletion,