Результаты поиска

WT1 gene: a potential therapeutic target for multiple cancer treatment strategies.

The Wilms' Tumor 1 (WT1) gene has attracted significant attention in oncological research owing to its involvement in the pathogenesis of a variety of malignancies. Initially identified in association with Wilms' tumor, a pediatric renal carcinoma, WT1 is now recognized for its broader implications in the etiology of multiple cancers, including leukemia, ovarian cancer, and lung cancer. This review offers a comprehensive analysis of the historical development of WT1 research, explores its mechanisms in cancer progression, and assesses its potential as a therapeutic target, with an emphasis on

Drug repurposing in oncology: Compounds, pathways, phenotypes and computational approaches for colorectal cancer.

The strategy of using existing drugs originally developed for one disease to treat other indications has found success across medical fields. Such drug repurposing promises faster access of drugs to patients while reducing costs in the long and difficult process of drug development. However, the number of existing drugs and diseases, together with the heterogeneity of patients and diseases, notably including cancers, can make repurposing time consuming and inefficient. The key question we address is how to efficiently repurpose an existing drug to treat a given indication. As drug efficacy rem

Совпадение в полном тексте источника
… These include in silico modeling, synthetic chemistry, in vitro screens, systems pharmacology approaches, in vitro and in vivo functional phenotypic analyses with human tumor cells (using for instance mouse xenografts [ 24 ] or organoids [ 25 ]), and most importantly clinical studies in patients with …

NKG2D CAR-T cells for solid tumor immunotherapy: advances, challenges, and future directions.

Chimeric antigen receptor (CAR) T-cell therapy has achieved significant success in hematologic malignancies, but its efficacy in solid tumors remains limited, primarily due to the immunosuppressive tumor microenvironment (TME) that hinders CAR-T cell trafficking and function. NKG2D CAR-T cells, which target stress-induced NKG2D ligands (NKG2DLs) broadly expressed on tumor cells, have shown promising potential in overcoming the immunosuppressive barriers of the solid TME. This review highlights recent advances in NKG2D CAR-T cell strategies for solid tumors, including innovations in CAR archite

Совпадение в полном тексте источника
… Although patient-derived organoids (PDOs) and patient-derived xenografts (PDXs) provide more clinically relevant systems, their high cost and limited throughput restrict widespread application. …

miR-135b: A key role in cancer biology and therapeutic targets.

miR-135b, a microRNA, is consistently up-regulated in various cancer tissues and cells, promoting cancer progression. By inhibiting one or more target genes, miR-135b regulates phenotypes such as cancer growth, apoptosis, migration, invasion, drug resistance, and angiogenesis, establishing it as a critical driver of cancer progression. Additionally, miR-135b is regulated by various oncogenes and therapeutic drugs, highlighting its complexity and therapeutic potential. Significant progress has been made in understanding miR-135b's impact on cancer cell behavior, establishing it as a promising b

Mesenchymal stem cell transplantation plays a role in relieving cancer pain.

Tumors can invade, compress, and damage nerves, leading to persistent pain and seriously affecting the quality of life of patients. However, their treatment is challenging. Sensitization of peripheral receptors, abnormal activity of primary sensory neurons, activation of glial cells, enhanced inflammatory responses, and sensory information transmission contribute towards cancer pain. Therefore, considerable attention has been paid to exploring prospective methods to inhibit the occurrence of these factors and relieve cancer pain. Studies on different types of pains have revealed that the trans

Совпадение в полном тексте источника
… Mesenchymal stem cells support growth and organization of host-liver colorectal-tumor organoids and possibly resistance to chemotherapy. Biofabrication 9 (2), 021002. 10.1088/1758-5090/aa7484 Di P. G., Lemma S., Canti L., Rucci N., Ponzetti M., Errani C., et al. (2017). …

Liposomes for the Treatment of Brain Cancer-A Review.

Due to their biocompatibility, non-toxicity, and surface-conjugation capabilities, liposomes are effective nanocarriers that can encapsulate chemotherapeutic drugs and facilitate targeted delivery across the blood-brain barrier (BBB). Additionally, strategies have been explored to synthesize liposomes that respond to internal and/or external stimuli to release their payload controllably. Although research into liposomes for brain cancer treatment is still in its infancy, these systems have great potential to fundamentally change the drug delivery landscape. This review paper attempts to consol

Exosomes for angiogenesis induction in ischemic disorders.

Ischaemic disorders are leading causes of morbidity and mortality worldwide. While the current therapeutic approaches have improved life expectancy and quality of life, they are unable to "cure" ischemic diseases and instate regeneration of damaged tissues. Exosomes are a class of extracellular vesicles with an average size of 100-150 nm, secreted by many cell types and considered a potent factor of cells for paracrine effects. Since exosomes contain multiple bioactive components such as growth factors, molecular intermediates of different intracellular pathways, microRNAs and nucleic acids, t

Old Player-New Tricks: Non Angiogenic Effects of the VEGF/VEGFR Pathway in Cancer.

Angiogenesis has long been considered to facilitate and sustain cancer growth, making the introduction of anti-angiogenic agents that disrupt the vascular endothelial growth factor/receptor (VEGF/VEGFR) pathway an important milestone at the beginning of the 21st century. Originally research on VEGF signaling focused on its survival and mitogenic effects towards endothelial cells, with moderate so far success of anti-angiogenic therapy. However, VEGF can have multiple effects on additional cell types including immune and tumor cells, by directly influencing and promoting tumor cell survival, pr

Совпадение в полном тексте источника
… Flt-1-Dependent Survival Characterizes the Epithelial-Mesenchymal Transition of Colonic Organoids. Curr. Biol. 2003;13:1721–1727. doi: 10.1016/j.cub.2003.09.002. 69. Bates R.C., Pursell B.M., Mercurio A.M. …

Mesenchymal stromal cells for bone sarcoma treatment: Roadmap to clinical practice.

Over the past few decades, there has been growing interest in understanding the molecular mechanisms of cancer pathogenesis and progression, as it is still associated with high morbidity and mortality. Current management of large bone sarcomas typically includes the complex therapeutic approach of limb salvage or sacrifice combined with pre- and postoperative multidrug chemotherapy and/or radiotherapy, and is still associated with high recurrence rates. The development of cellular strategies against specific characteristics of tumour cells appears to be promising, as they can target cancer cel

A malignant symbiosis: The neuro-metabolic symphony rewires the tumor microenvironment.

Emerging evidence in cancer neuroscience has established a reciprocal bidirectional loop between neural signaling and tumor metabolism as a central driver of malignant progression. This review critically evaluates bidirectional neuro-metabolic symbiosis and its profound implications for overcoming treatment refractoriness. We first analyzed the anterograde mechanism, in which peripheral nerve terminals and systemic endocrine factors impose distinct metabolic dependencies on malignant and stromal cell populations. By forcing alterations in nutrient utilization pathways, these neural cues create

Research Progress on Chinese Herbal Medicine Components Targeting Ferroptosis for Cancer Therapy.

Recent studies indicate that ferroptosis shows unique advantages in oncotherapy, particularly in reversing multidrug resistance (MDR). Despite current therapeutic advancements, the treatment of high-incidence malignancies with dismal prognoses continues to face challenges, including limited clinical efficacy, significant side effects, and drug resistance. In recent years, Chinese herbal medicine (CHM) has gained increasing attention in anti-tumor therapy. CHM bioactive components are highly effective in inducing tumor cell ferroptosis, inhibiting tumor proliferation and migration, and reversin

Update on preclinical models of cancer therapy-related cardiac dysfunction: Challenges and perspectives. A scientific statement of the Heart Failure Association (HFA) of the ESC, the ESC Council of Cardio-Oncology, and the ESC Working Group on Cellular Biology of the Heart.

New anticancer therapies with potential cardiovascular side effects are continuously being introduced into clinical practice, with new and often unexpected toxicities becoming apparent only after clinical introduction. These unknown toxicities should be identified and understood beforehand to better prepare patients and physicians, enabling the implementation of effective treatments. Therefore, there is a crucial need for appropriate preclinical models to understand the biological basis of their cardiotoxicity. This scientific statement summarizes the preclinical models hitherto used, from in

Совпадение в полном тексте источника
… senescence did not show any functional improvement in these models, calling into question the use of senolytic drugs as a potential cardioprotective therapy. 76 Other maturation strategies for iPSC‐CMs currently being explored include long‐term culture, mechanical and/or electrical stimulation, 3D cardiac organoids …

MAPK inhibitor sensitivity scores predict sensitivity driven by the immune infiltration in pediatric low-grade gliomas.

Pediatric low-grade gliomas (pLGG) show heterogeneous responses to MAPK inhibitors (MAPKi) in clinical trials. Thus, more complex stratification biomarkers are needed to identify patients likely to benefit from MAPKi therapy. Here, we identify MAPK-related genes enriched in MAPKi-sensitive cell lines using the GDSC dataset and apply them to calculate class-specific MAPKi sensitivity scores (MSSs) via single-sample gene set enrichment analysis. The MSSs discriminate MAPKi-sensitive and non-sensitive cells in the GDSC dataset and significantly correlate with response to MAPKi in an independent P

Совпадение в полном тексте источника
… microglia cell models present limitations 90 , the most important being their immortalization with the SV40-largeT antigen, preventing any TP53-related apoptosis, as already observed in SV40-transformed pLGG models 45 . scRNA sequencing on short-term cultured primary samples treated with MAPKi, or pLGG organoids …

Pluripotent Stem Cells for Disease Modeling and Drug Discovery in Niemann-Pick Type C1.

The lysosomal storage disorders Niemann-Pick disease Type C1 (NPC1) and Type C2 (NPC2) are rare diseases caused by mutations in the NPC1 or NPC2 gene. Both NPC1 and NPC2 are proteins responsible for the exit of cholesterol from late endosomes and lysosomes (LE/LY). Consequently, mutations in one of the two proteins lead to the accumulation of unesterified cholesterol and glycosphingolipids in LE/LY, displaying a disease hallmark. A total of 95% of cases are due to a deficiency of NPC1 and only 5% are caused by NPC2 deficiency. Clinical manifestations include neurological symptoms and systemic

Совпадение в полном тексте источника
… Although model systems based on organoids or 3D-culture systems have great potential to reproduce the in vivo situation in a more complex way than 2D-culture systems, these models also have disadvantages. …

Beyond Vaccines: Clinical Status of Prospective COVID-19 Therapeutics.

Since November 2019 the SARS-CoV-2 pandemic has caused nearly 200 million infection and more than 4 million deaths globally (Updated information from the World Health Organization, as on 2nd Aug 2021). Within only one year into the pandemic, several vaccines were designed and reached approval for the immunization of the world population. The remarkable protective effects of the manufactured vaccines are demonstrated in countries with high vaccination rates, such as Israel and UK. However, limited production capacities, poor distribution infrastructures and political hesitations still hamper th

Совпадение в полном тексте источника
… A soluble version of the human ACE2 protein (hrsACE2, APN01) reduces the SARS-CoV-2 viral load 1000-5000- fold in cell cultures and shows an inhibitory effect on cell attachment in human blood vessel and kidney organoids. …

Chemokine-Directed Tumor Microenvironment Modulation in Cancer Immunotherapy.

Chemokines are a large family of small chemotactic cytokines that coordinates immune cell trafficking. In cancer, they have a pivotal role in the migration pattern of immune cells into the tumor, thereby shaping the tumor microenvironment immune profile, often towards a pro-tumorigenic state. Furthermore, chemokines can directly target non-immune cells in the tumor microenvironment, including cancer, stromal and vascular endothelial cells. As such, chemokines participate in several cancer development processes such as angiogenesis, metastasis, cancer cell proliferation, stemness and invasivene

Совпадение в полном тексте источника
… To improve the success rate of immuno-oncology research and preclinical testing of immune-based anticancer therapies, preclinical models are being further refined to improve the tumoral immunogenicity by including humanised mouse models, genetically re-engineered mouse models, organoids and mammospheres …

Repurposing anticancer drugs for the management of COVID-19.

Since its outbreak in the last December, coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has rapidly spread worldwide at a pandemic proportion and thus is regarded as a global public health emergency. The existing therapeutic options for COVID-19 beyond the intensive supportive care are limited, with an undefined or modest efficacy reported so far. Drug repurposing represents an enthusiastic mechanism to use approved drugs outside the scope of their original indication and accelerate the discovery of new therapeutic options. With the emergence of COVID-19, drug repurposing has been la

Совпадение в полном тексте источника
… In addition, the use of soluble human ACE2 can inhibit early stage SARS-CoV-2 infections as revealed by a recent study including human organoids, by using the recombinant ACE2 as a decoy receptor [ 121 ]. Fig. 1 B shows an overview about the potential targets for COVID-19 therapy. …

HMMR in human cancers: regulatory mechanism and biological function.

Hyaluronan-mediated motility receptor (HMMR), also referred to as RHAMM or CD168, has gained recognition as a multifunctional protein that mediates the transmission of extracellular matrix-derived hyaluronan (HA) signals to intracellular pathways regulating tumor growth, migration, and mitosis. Overexpression of HMMR is observed in various cancers, including head and neck squamous cell carcinoma, breast cancer, lung cancer, and prostate cancer, as well as several hematologic malignancies. This elevated expression correlates with poor prognosis, rendering it a valuable marker for survival predi

The important role of the histone acetyltransferases p300/CBP in cancer and the promising anticancer effects of p300/CBP inhibitors.

Histone acetyltransferases p300 (E1A-associated protein p300) and CBP (CREB binding protein), collectively known as p300/CBP due to shared sequence and functional synergy, catalyze histone H3K27 acetylation and consequently induce gene transcription. p300/CBP over-expression or over-activity activates the transcription of oncogenes, leading to cancer cell growth, resistance to apoptosis, tumor initiation and development. The discovery of small molecule inhibitors targeting p300/CBP histone acetyltransferase activity, bromodomains, dual inhibitors of p300/CBP and BRD4 bromodomains, as well as p

Molecular Diversity of Lupane Hybrids in Drug Design and Materials Science.

The need for new, more effective drugs to treat cancer, infectious diseases, various parasitic infestations, and metabolic disorders requires innovative approaches to the design of promising molecules. One of these areas is the creation of hybrid structures. Lupane triterpenoids are of significant interest for such research due to their high abundance in natural sources and their renewable nature, their molecular architecture, presence of several easily modifiable functional groups, enantiomeric purity, broad spectrum of biological activity, and low toxicity. Active research into the biologica

Совпадение в полном тексте источника
… Cavalcante B. et al. [ 113 ] reported that the neuroprotective anti-ZIKV effect of BA is dose-dependent, as demonstrated in experiments using 3D cultures with brain organoids derived from neuronal progenitor cells (NPCs). …