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Nucleo-cytoplasmic transport as a therapeutic target of cancer.

Shuttling of specific proteins out of the nucleus is essential for the regulation of the cell cycle and proliferation of both normal and malignant tissues. Dysregulation of this fundamental process may affect many other important cellular processes such as tumor growth, inflammatory response, cell cycle, and apoptosis. It is known that XPO1 (Exportin-1/Chromosome Region Maintenance 1/CRM1) is the main mediator of nuclear export in many cell types. Nuclear proteins exported to the cytoplasm by XPO1 include the drug targets topoisomerase IIα (topo IIα) and BCR-ABL and tumor suppressor proteins s

Investigation of the cytotoxicity induced by cannabinoids on human ovarian carcinoma cells.

Cannabinoids have been shown to induce anti-tumor activity in a variety of carcinoma cells such as breast, prostate, and brain. The aim of the present study is to investigate the anti-tumor activity of cannabinoids, CBD (cannbidiol), and CBG (cannabigerol) in ovarian carcinoma cells sensitive and resistant to chemotherapeutic drugs. Sensitive A2780 cells and resistant A2780/CP70 carcinoma cells and non-carcinoma cells were exposed to varying concentrations of CBD, CBG, carboplatin or CB1 and CB2 receptor antagonists, AM251 and AM630, respectively, alone or in combination, at different exposure

Drug Repurposing for the Management of Depression: Where Do We Stand Currently?

A slow rate of new drug discovery and higher costs of new drug development attracted the attention of scientists and physicians for the repurposing and repositioning of old medications. Experimental studies and off-label use of drugs have helped drive data for further studies of approving these medications. A deeper understanding of the pathogenesis of depression encourages novel discoveries through drug repurposing and drug repositioning to treat depression. In addition to reducing neurotransmitters like epinephrine and serotonin, other mechanisms such as inflammation, insufficient blood supp

Implications of regulatory T cells in anti-cancer immunity: from pathogenesis to therapeutics.

Regulatory T cells (Tregs) play an essential role in maintaining immune tolerance and suppressing inflammation. However, Tregs present major hurdle in eliciting potent anti-cancer immune responses. Therefore, curbing the activity of Tregs represents a novel and efficient way towards successful immunotherapy of cancer. Moreover, there is an emerging interest in harnessing Treg-based strategies for augmenting anti-cancer immunity in different types of the disease. This review summarises the crucial mechanisms of Tregs' mediated suppression of anti-cancer immunity and strategies to suppress or to

Germline loss-of-function variant in the E3 ubiquitin ligase TRAF2 in a young adult patient with medulloblastoma: a case report.

We identified a rare heterozygous germline loss-of-function variant in the tumor necrosis factor receptor-associated factor 2 (TRAF2) in a young adult patient diagnosed with medulloblastoma. This variant is located within the TRAF-C domain of the E3 ubiquitin ligase protein and is predicted to diminish the binding affinity of TRAF2 to upstream receptors and associated adaptor proteins. Integrative genomics revealed a biallelic loss of TRAF2 via partial copy-neutral loss-of-heterozygosity of 9q in the medulloblastoma genome. We further performed comparative analysis with an in-house cohort of 2

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… Our patient exhibited significantly higher expression levels of pro-apoptotic genes, such as Fas receptor ( FAS ) and harakiri ( HRK ) [ 22 , 23 ], compared to other tumors in our MB cohort (Fig. 3 C). … Strasser A, Jost PJ, Nagata S (2009) The many roles of FAS receptor signaling in the immune system. Immunity 30:180–192 23. …

The roles of curcumin in regulating the tumor immunosuppressive microenvironment.

Cancer is a harmful threat to human health. In addition to surgery, a variety of anticancer drugs are increasingly used in cancer therapy; however, despite the developments in multimodality treatment, the morbidity and mortality of patients with cancer patients are on the increase. The tumor-specific immunosuppressive microenvironment serves an important function in tumor tolerance and escape from immune surveillance leading to tumor progression. Therefore, identifying new drugs or foods that can enhance the tumor immune response is critical to develop improved cancer prevention methods and tr

Effects of the polyunsaturated fatty acids, EPA and DHA, on hematological malignancies: a systematic review.

Omega-3 polyunsaturated fatty acids (PUFAs) have well established anti-cancer properties. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are among this biologically active family of macromolecules for which various anti-cancer effects have been explained. These PUFAs have a high safety profile and can induce apoptosis and inhibit growth of cancer cells both in vitro and in vivo, following a partially selective manner. They also increase the efficacy of chemotherapeutic agents by increasing the sensitivity of different cell lines to specific anti-neoplastic drugs. Various mechanisms

Challenges and strategies associated with CAR-T cell therapy in blood malignancies.

Cellular immunotherapy, particularly CAR-T cells, has shown potential in the improvement of outcomes in patients with refractory and recurrent malignancies of the blood. However, achieving sustainable long-term complete remission for blood cancer remains a challenge, with resistance and relapse being expected outcomes for many patients. Although many studies have attempted to clarify the mechanisms of CAR-T cell therapy failure, the mechanism remains unclear. In this article, we discuss and describe the current state of knowledge regarding these factors, which include elements that influence t

A Snapshot of Photoresponsive Liposomes in Cancer Chemotherapy and Immunotherapy: Opportunities and Challenges.

To provide precise medical regimens, photonics technologies have been involved in the field of nanomedicine. Phototriggered liposomes have been cast as promising nanosystems that achieve controlled release of payloads in several pathological conditions such as cancer, autoimmune, and infectious diseases. In contrast to the conventional liposomes, this photoresponsive element greatly improves therapeutic efficacy and reduces the adverse effects of gene/drug therapy during treatment. Recently, cancer immunotherpay has been one of the hot topics in the field of oncology due to the great success a

Protein kinase CK2: a potential therapeutic target for diverse human diseases.

CK2 is a constitutively active Ser/Thr protein kinase, which phosphorylates hundreds of substrates, controls several signaling pathways, and is implicated in a plethora of human diseases. Its best documented role is in cancer, where it regulates practically all malignant hallmarks. Other well-known functions of CK2 are in human infections; in particular, several viruses exploit host cell CK2 for their life cycle. Very recently, also SARS-CoV-2, the virus responsible for the COVID-19 pandemic, has been found to enhance CK2 activity and to induce the phosphorylation of several CK2 substrates (ei

The Role of the Gut Microbiome in Pathogenesis, Biology, and Treatment of Plasma Cell Dyscrasias.

In response to emerging discoveries, questions are mounting as to what factors are responsible for the progression of plasma cell dyscrasias and what determines responsiveness to treatment in individual patients. Recent findings have shown close interaction between the gut microbiota and multiple myeloma cells. For instance, that malignant cells shape the composition of the gut microbiota. We discuss the role of the gut microbiota in (i) the development and progression of plasma cell dyscrasias, and (ii) the response to treatment of multiple myeloma and highlight faecal microbiota transplantat

The Rising Era of Immune Checkpoint Inhibitors in Myelodysplastic Syndromes.

Myelodysplastic syndromes (MDS) are a heterogeneous group of diseases characterized by ineffective hematopoiesis and a wide spectrum of manifestations ranging from indolent and asymptomatic cytopenias to acute myeloid leukemia (AML). MDS result from genetic and epigenetic derangements in clonal cells and their surrounding microenvironments. Studies have shown associations between MDS and other autoimmune diseases. Several immune mechanisms have been identified in MDS, suggesting that immune dysregulation might be at least partially implicated in its pathogenesis. This has led to rigorous inves

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… These cytokines increase the expression of Fas receptors (FasR) on hematopoietic cells and enhance their interaction with Fas ligands leading to apoptosis [ 15 ]. …

Network Pharmacology Approaches Used to Identify Therapeutic Molecules for Chronic Venous Disease Based on Potential miRNA Biomarkers.

Chronic venous disease (CVD) is a prevalent condition in adults, significantly affecting the global elderly population, with a higher incidence in women than in men. The modulation of gene expression through microRNA (miRNA) partly regulated the development of cardiovascular disease (CVD). Previous research identified a functional analysis of seven genes (CDS2, HDAC5, PPP6R2, PRRC2B, TBC1D22A, WNK1, and PABPC3) as targets of miRNAs related to CVD. In this context, miRNAs emerge as essential candidates for CVD diagnosis, representing novel molecular and biological knowledge. This work aims to i

Гетерогенность регулируемых клеток В в аутоиммунных заболеваниях: последствия для иммунного равновесия и терапевтических стратегий.

Регулирующие клетки В (Bregs) играют ключевую роль в поддержании иммунной терпимости и профилактике аутоиммунных заболеваний. Однако в условиях аутоиммунной среды количество и функции брега часто ухудшаются, что ведет к провоспалительной микроокружающей среде и регулированию иммунной дизакции. В рамках этого обзора проводится углубленный анализ последствий различных аутоиммунных заболеваний, включая множественный склероз, ревматоидный артрит, системный волчанье эритематосус, болезнь Шёгрена, аутоиммунный диабет и другие аутоиммунные заболевания. Резюмируя изменения в фенотипе Брегса и его функ

Medicinal Mushrooms: Bioactive Compounds, Use, and Clinical Trials.

Medicinal mushrooms have important health benefits and exhibit a broad spectrum of pharmacological activities, including antiallergic, antibacterial, antifungal, anti-inflammatory, antioxidative, antiviral, cytotoxic, immunomodulating, antidepressive, antihyperlipidemic, antidiabetic, digestive, hepatoprotective, neuroprotective, nephroprotective, osteoprotective, and hypotensive activities. The growing interest in mycotherapy requires a strong commitment from the scientific community to expand clinical trials and to propose supplements of safe origin and genetic purity. Bioactive compounds of

Bone marrow microenvironment in myelodysplastic neoplasms: insights into pathogenesis, biomarkers, and therapeutic targets.

Myelodysplastic neoplasms (MDS) represent a heterogeneous group of malignant hematopoietic stem and progenitor cell (HSPC) disorders characterized by cytopenia, ineffective hematopoiesis, as well as the potential to progress to acute myeloid leukemia (AML). The pathogenesis of MDS is influenced by intrinsic factors, such as genetic insults, and extrinsic factors, including altered bone marrow microenvironment (BMM) composition and architecture. BMM is reprogrammed in MDS, initially to prevent the development of the disease but eventually to provide a survival advantage to dysplastic cells. Rec

Transferrin-Bound Doxorubicin Enhances Apoptosis and DNA Damage through the Generation of Pro-Inflammatory Responses in Human Leukemia Cells.

Doxorubicin (DOX) is an effective antineoplastic drug against many solid tumors and hematological malignancies. However, the clinical use of DOX is limited, because of its unspecific mode of action. Since leukemia cells overexpress transferrin (Tf) receptors on their surface, we proposed doxorubicin-transferrin (DOX-Tf) conjugate as a new vehicle to increase drug concentration directly in cancer cells. The data obtained after experiments performed on K562 and CCRF-CEM human leukemia cell lines clearly indicate severe cytotoxic and genotoxic properties of the conjugate drug. On the other hand,

Химерический антигенный рецептор T-клеточная терапия в нейроиммунных болезнях: механистическое обоснование, клинический опыт и проблемы с переводом.

Нейроиммунные заболевания представляют собой разнородную группу расстройств, при которых клетки В, плазменные удары, плазменные клетки, автоантитела и Т клетки поразному влияют на повреждение тканей. Хотя биологика B-клеток улучшила контроль за заболеваниями, некоторые пациенты по-прежнему сталкиваются с реанимацией, рецидивом после лечения или кумулятивной неврологической инвалидностью. Химерическая антигенная рецепторная T-клетка (CAR-T-клетка) является средством достижения более глубокого и потенциально устойчивого истощения определенных патогенных иммунных клеток. Этот описательный обзор в

Vaccines against human carcinomas: strategies to improve antitumor immune responses.

Multiple observations in preclinical and clinical studies support a role for the immune system in controlling tumor growth and progression. Various components of the innate and adaptive immune response are able to mediate tumor cell destruction; however, certain immune cell populations can also induce a protumor environment that favors tumor growth and the development of metastasis. Moreover, tumor cells themselves are equipped with various mechanisms that allow them to evade surveillance by the immune system. The goal of cancer vaccines is to induce a tumor-specific immune response that ultim

Developments in nanotechnology approaches for the treatment of solid tumors.

Nanotechnology has revolutionized cancer therapy by introducing advanced drug delivery systems that enhance therapeutic efficacy while reducing adverse effects. By leveraging various nanoparticle platforms-including liposomes, polymeric nanoparticles, and inorganic nanoparticles-researchers have improved drug solubility, stability, and bioavailability. Additionally, new nanodevices are being engineered to respond to specific physiological conditions like temperature and pH variations, enabling controlled drug release and optimizing therapeutic outcomes. Beyond drug delivery, nanotechnology pla