Vincristine in Combination Therapy of Cancer: Emerging Trends in Clinics

Biology, Journal Year: 2021, Volume and Issue: 10(9), P. 849 - 849

Published: Aug. 31, 2021

Treatment of blood malignancies and other cancer diseases has been mostly unfeasible, so far. Therefore, novel treatment regimens should be developed the currently used ones further elaborated. A stable component in various consists vincristine, an antimitotic compound natural origin. Despite its strong anticancer activity, mostly, it cannot administered as monotherapy due to unspecific action severe side effects. However, vincristine is suitable for combination therapy. Multidrug including are standardly applied therapy non-Hodgkin lymphoma malignancies, which combined with drugs different mechanisms action, mainly DNA-interacting compounds (for example cyclophosphamide), or interfering DNA synthesis methotrexate). Besides, co-administration monoclonal antibodies also emerged, typical anti-CD20 antibody rituximab. Although some therapies, replaced exhibiting lesser effects, though, most cases, still irreplaceable. This strongly evidenced by number active clinical trials evaluating this article, we have reviewed common employing bring overview current trends development compound.

Language: Английский

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Galectins and galectin-mediated autophagy regulation: new insights into targeted cancer therapy

Biomarker Research, Journal Year: 2023, Volume and Issue: 11(1)

Published: Feb. 22, 2023

Abstract Galectins are animal lectins with specific affinity for galactosides via the conserved carbohydrate recognition domains. Increasing studies recently have identified critical roles of galectin family members in tumor progression. Abnormal expression galectins contributes to proliferation, metastasis, epithelial-mesenchymal transformation (EMT), immunosuppression, radio-resistance and chemoresistance various cancers, which has attracted cumulative clinical interest galectin-based cancer treatment. Galectin been reported participate autophagy regulation under physiological conditions non-tumoral diseases, implication multiple processes carcinogenesis also involves autophagy, however, relationship between galectins, remains largely unclear. In this review, we introduce structure function at molecular level, summarize their engagements progression, highlight by as well therapeutic potentials autophagy-based strategies. Elaborating on mechanism galectin-regulated cancers will accelerate exploitation galectins-autophagy targeted therapies treatment cancer.

Language: Английский

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Cell death pathways: molecular mechanisms and therapeutic targets for cancer

MedComm, Journal Year: 2024, Volume and Issue: 5(9)

Published: Sept. 1, 2024

Abstract Cell death regulation is essential for tissue homeostasis and its dysregulation often underlies cancer development. Understanding the different pathways of cell can provide novel therapeutic strategies battling cancer. This review explores several key mechanisms apoptosis, necroptosis, autophagic death, ferroptosis, pyroptosis. The research gap addressed involves a thorough analysis how these be precisely targeted therapy, considering tumor heterogeneity adaptation. It delves into genetic epigenetic factors signaling cascades like phosphatidylinositol 3‐kinase/protein kinase B/mammalian target rapamycin (PI3K/AKT/mTOR) mitogen‐activated protein kinase/extracellular signal‐regulated (MAPK/ERK) pathways, which are critical death. Additionally, interaction microenvironment with cells, particularly influence hypoxia, nutrient deprivation, immune cellular interactions, explored. Emphasizing strategies, this highlights emerging modulators inducers such as B lymphoma 2 (BCL2) homology domain 3 (BH3) mimetics, tumour necrosis factor‐related apoptosis‐inducing ligand (TRAIL), chloroquine, innovative approaches to induce ferroptosis provides insights therapy's future direction, focusing on multifaceted circumvent drug resistance. examination evolving underlines considerable clinical potential continuous necessity in‐depth exploration within scientific domain.

Language: Английский

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Blockage of Autophagy for Cancer Therapy: A Comprehensive Review

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 7459 - 7459

Published: July 7, 2024

The incidence and mortality of cancer are increasing, making it a leading cause death worldwide. Conventional treatments such as surgery, radiotherapy, chemotherapy face significant limitations due to therapeutic resistance. Autophagy, cellular self-degradation mechanism, plays crucial role in development, drug resistance, treatment. This review investigates the potential autophagy inhibition strategy for cancer. A systematic search was conducted on Embase, PubMed, Google Scholar databases from 1967 2024 identify studies inhibitors their mechanisms therapy. includes original articles utilizing vitro vivo experimental methods, literature reviews, clinical trials. Key terms used were "Autophagy", "Inhibitors", "Molecular mechanism", "Cancer therapy", "Clinical trials". Autophagy chloroquine (CQ) hydroxychloroquine (HCQ) have shown promise preclinical by inhibiting lysosomal acidification preventing autophagosome degradation. Other like wortmannin SAR405 target specific components pathway. Combining these with has demonstrated enhanced efficacy, cells more susceptible cytotoxic agents. Clinical trials involving CQ HCQ encouraging results, although further investigation is needed optimize use exhibits dual cancer, functioning both survival mechanism cell Targeting presents viable therapy, particularly when integrated existing treatments. However, complexity regulation side effects necessitate research develop precise context-specific approaches.

Language: Английский

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Cell death in cancer chemotherapy using taxanes

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 5, 2024

Cancer cells evolve to be refractory the intrinsic programmed cell death mechanisms, which ensure cellular tissue homeostasis in physiological conditions. Chemotherapy using cytotoxic drugs seeks eliminate cancer but spare non-cancerous host by exploring a likely subtle difference between malignant and benign cells. Presumably, chemotherapy agents achieve efficacy triggering machineries Currently, many major solid tumors are treated with composed of combination platinum taxanes. Platinum agents, largely cis-platin, carboplatin, oxaliplatin, DNA damaging that covalently form addicts, repair response pathways. Taxanes, including paclitaxel, docetaxel, cabazitaxel, microtubule stabilizing often very effective purging clinical settings. Generally, it is thought stabilization microtubules taxanes leads mitotic arrest, catastrophe, apoptotic death. However, precise mechanism(s) how arrest catastrophe activate caspase pathway has not been established. Here, we briefly review literature on involvement potential mechanisms therapy. These include classical caspase-mediated death, necroptosis mediated MLKL, pore forming immune cells, etc. In particular, discuss newly recognized mechanism taxane-treatment involves micronucleation irreversible rupture nuclear membrane. Since commonly retarded responding signaling, stabilized bundle-induced membrane rupture, rather than apoptosis, may key accounting for success as anti-cancer agents.

Language: Английский

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Punicalagin in Cancer Prevention—Via Signaling Pathways Targeting

Nutrients, Journal Year: 2021, Volume and Issue: 13(8), P. 2733 - 2733

Published: Aug. 9, 2021

The extract of pomegranate (Punica granatum) has been applied in medicine since ancient times due to its broad-spectrum health-beneficial properties. It is a rich source hydrolyzable tannins and anthocyanins, exhibiting strong antioxidative, anti-inflammatory, antineoplastic Anticancer activities with reference modulated signaling pathways various cancer diseases have recently reviewed. However, less known about punicalagin (Pug), prevailing compound pomegranate, seemingly responsible for most beneficial In this review, the newest data derived from recent scientific reports addressing Pug impact on neoplastic cells are summarized discussed. Its attenuating effect circuits promoting growth invasion depicted. Pug-induced redirection signal-transduction survival proliferation into cell-cycle arrest, apoptosis, senescence, autophagy (thus compromising progression) delineated. Considerations presented review based mainly obtained vitro cell line models concern influence human cervical, ovarian, breast, lung, thyroid, colorectal, central nervous system, bone, as well other types.

Language: Английский

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The Role of Autophagy and Pyroptosis in Liver Disorders

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(11), P. 6208 - 6208

Published: June 1, 2022

Pyroptosis is a programmed cell death caused by inflammasomes, which can detect cytosolic contamination or disturbance. In pyroptosis, caspase-1 caspase-11/4/5 activated, cleaving gasdermin D to separate its N-terminal pore-forming domain (PFD). The oligomerization of PFD forms macropores in the membrane, resulting swelling and membrane rupture. According different mechanisms, pyroptosis be divided into three types: canonical pathway-mediated non-canonical caspase-3-induced pyroptosis. has been reported play an important role many tissues organs, including liver. Autophagy highly conserved process eukaryotic cycle. It plays survival maintenance degrading organelles, proteins macromolecules cytoplasm. Therefore, dysfunction this involved variety pathological processes. recent years, autophagy their interactions have proven various physiological processes, gradually attracted more attention become research hotspot. review summarized liver disorders, analyzed related mechanism provide basis for future research.

Language: Английский

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Modulation of Autophagy Direction to Enhance Antitumor Effect of Endoplasmic‐Reticulum‐Targeted Therapy: Left or Right?

Advanced Science, Journal Year: 2023, Volume and Issue: 10(23)

Published: June 8, 2023

Strategies that induce dysfunction in the endoplasmic reticulum (ER) hold great promise for anticancer therapy, but remain unsatisfactory due to compensatory autophagy induction after ER disruption. Moreover, as can either promote or suppress cell survival, which direction of better suits ER-targeting therapy remains controversial. Here, a targeted nanosystem is constructed, efficiently escorts therapeutics into ER, triggering substantial stress and autophagy. Concurrently, an enhancer inhibitor combined same nanoparticle, their impacts on ER-related activities are compared. In orthotopic breast cancer mouse model, increases antimetastasis effect suppresses over 90% metastasis, while has bare effect. Mechanism studies reveal further enhancing accelerates central protein snail family transcriptional repressor 1 (SNAI1) degradation, suppressing downstream epithelial-mesenchymal transition, inhibiting does opposite. With trend, with provokes stronger immune response tumor inhibition than inhibitor. elevates Ca

Language: Английский

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Baicalein Suppresses NLRP3 and AIM2 Inflammasome-Mediated Pyroptosis in Macrophages Infected by Mycobacterium tuberculosis via Induced Autophagy

Microbiology Spectrum, Journal Year: 2023, Volume and Issue: 11(3)

Published: May 1, 2023

Mycobacterium tuberculosis (Mtb) continues to pose a significant threat global health because it causes granulomas and systemic inflammatory responses during active (TB). Mtb can induce macrophage pyroptosis, which results in the release of IL-1β tissue damage, thereby promoting its spread. In absence anti-TB drugs, host-directed therapy (HDT) has been demonstrated be an effective strategy against TB. this study, we used vitro Mtb-infected model assess effect baicalein, derived from Scutellariae radix, on pyroptosis induced macrophages. Further, investigated molecular mechanisms underlying actions baicalein. The study suggest that baicalein inhibits macrophages by downregulating assembly AIM2 NLRP3 inflammasome autophagy. Further research also shown mechanism promotes autophagy may involve inhibition activation Akt/mTOR pathway protein, affects levels CHMP2A protein required promote Thus, our data show inhibit infection-induced potential new adjunctive HDT drug. IMPORTANCE Current strategies for treating drug-resistant have limited efficacy undesirable side effects; hence, treatments, including innovative medications, is required. Host-directed emerged as viable modulating host cell order enhance protective immunity infections. Baicalein, extracted was caused tuberculosis-infected associated with Our findings reveal treatment or other diseases regulating immune function enhancing antibacterial ability host. It provides idea exploring anti-inflammatory

Language: Английский

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Cross-talk between autophagy and ferroptosis contributes to the liver injury induced by fluoride via the mtROS-dependent pathway

Ecotoxicology and Environmental Safety, Journal Year: 2023, Volume and Issue: 250, P. 114490 - 114490

Published: Jan. 1, 2023

Fluoride can induce hepatotoxicity, but the mechanisms responsible are yet to be investigated. This study sought investigate role and mechanism of mitochondrial reactive oxygen species (mtROS), autophagy, ferroptosis in fluoride-induced hepatic injury with a focus on mtROS-mediated cross-talk between autophagy ferroptosis. To this end, an vivo Sprague-Dawley rat model vitro BRL3A cells were exposed sodium fluoride (NaF). The results revealed that NaF exposure diminished membrane potential, increased mtROS production TOMM20 expression, induced autophagic flux blockage vitro. Furthermore, activator (RAPA) enhanced GPX4 expression while inhibiting ACSL4 reduced accumulation ferrous ions cells, restored lipid peroxidation levels, thus Fer-1, ferritinase inhibitor, downregulated LC3-II p62, number autolysosomes decreasing autophagosomes, alleviated by improving degradation. These suggest occurrence inhibitor (Mito-TEMPO) could alleviate inhibit NaF-induced liver injury. In addition, was dependent pathway.

Language: Английский

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