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Sialyltransferase Inhibitors for the Treatment of Cancer Metastasis: Current Challenges and Future Perspectives.

Potent, cell-permeable, and subtype-selective sialyltransferase inhibitors represent an attractive family of substances that can potentially be used for the clinical treatment of cancer metastasis. These substances operate by specifically inhibiting sialyltransferase-mediated hypersialylation of cell surface glycoproteins or glycolipids, which then blocks the sialic acid recognition pathway and leads to deterioration of cell motility and invasion. A vast amount of evidence for the in vitro and in vivo effects of sialyltransferase inhibition or knockdown on tumor progression and tumor cell meta

Revisiting Proteasome Inhibitors: Molecular Underpinnings of Their Development, Mechanisms of Resistance and Strategies to Overcome Anti-Cancer Drug Resistance.

Proteasome inhibitors have shown relevant clinical activity in several hematological malignancies, namely in multiple myeloma and mantle cell lymphoma, improving patient outcomes such as survival and quality of life, when compared with other therapies. However, initial response to the therapy is a challenge as most patients show an innate resistance to proteasome inhibitors, and those that respond to the therapy usually develop late relapses suggesting the development of acquired resistance. The mechanisms of resistance to proteasome inhibition are still controversial and scarce in the literat

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… H460 cells presented significantly more (3 and 4.5-fold) activity of β1 and β5 subunits compared to SW1573 cells, whereas A549 cells showed intermediate activity of these β subunits. …

Will a mAb-Based Immunotherapy Directed against Cancer Stem Cells Be Feasible?

The cancer stem cell (CSC) hypothesis suggests that within a tumor, there is a small subpopulation of cells with stem cell properties responsible for tumor maintenance and metastasis generation. This hypothesis also implies that new antitumor drugs, rather than targeting the bulk of the tumor mass, would be more effective if they directly targeted the CSC subpopulation. The CSCs from several types of tumors have been identified with mAbs recognizing surface antigens in these cells; however, antigens specifically or exclusively expressed in the CSC population have not yet been identified. Thus,

Anti-Cancer Potential of Cannabinoids, Terpenes, and Flavonoids Present in Cannabis.

In recent years, and even more since its legalization in several jurisdictions, cannabis and the endocannabinoid system have received an increasing amount of interest related to their potential exploitation in clinical settings. Cannabinoids have been suggested and shown to be effective in the treatment of various conditions. In cancer, the endocannabinoid system is altered in numerous types of tumours and can relate to cancer prognosis and disease outcome. Additionally, cannabinoids display anticancer effects in several models by suppressing the proliferation, migration and/or invasion of can

Suppression Effect of Astaxanthin on Osteoclast Formation In Vitro and Bone Loss In Vivo.

Osteoporosis is characterized by a reduction of the bone mineral density (BMD) and microarchitectural deterioration of the bone, which lead to bone fragility and susceptibility to fracture. Astaxanthin (AST) has a variety of biological activities, such as a protective effect against asthma or neuroinflammation, antioxidant effect, and decrease of the osteoclast number in the right mandibles in the periodontitis model. Although treatment with AST is known to have an effect on inflammation, no studies on the effect of AST exposure on bone loss have been performed. Thus, in the present study, we

Anticancer peptides as novel immunomodulatory therapeutic candidates for cancer treatment.

Cancer remains a concern after years of research in this field. Conventional therapies such as chemotherapy, radiation, and surgery are available for cancer treatment, but they are characterized by various side effects. There are several immunological challenges that make it difficult for the immune system and conventional therapies to treat cancer. Some of these challenges include heterogeneity, resistance to medicines, and cancer relapse. Even advanced treatments like immune checkpoint inhibitors (ICIs), which revolutionized cancer treatment, have associated toxicity and resistance further n

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… Yang et al. [ 109 ] (2014) used polydiacetylene micelles to deliver magainin-II and reported improved cytotoxicity both in in vitro and in vivo model systems (A549 cells and mice respectively). …

The critical role of γ-secretase and its inhibitors in cancer and cancer therapeutics.

As a multi-substrate transmembrane protease, γ-secretase exists widely in various cells. It controls multiple important cellular activities through substrate cleavage. γ-secretase inhibitors (GSIs) play a role in cancer inhibition by blocking Notch cleavage, and are considered as potential therapeutic strategies for cancer. Currently, GSIs have encouraging performance in preclinical models, yet this success does not translate well in clinical trials. In recent years, a number of breakthrough discoveries have shown us the promise of targeting γ-secretase for the treatment of cancer. Here, we in

Талидомид взаимодействует с воспалением в идиопатическом фиброзе легких.

" Трагедия Талидомида " является важной вехой в истории фармацевтической промышленности. Несмотря на ограниченные клинические испытания, прилагаются постоянные усилия по изучению Талидомида в качестве лекарства от рака и подстрекательских заболеваний, таких, как ревматуидный артрит, проказа, и COVID-19. В рамках этого обзора основное внимание уделяется возможностям борьбы с воспалением путем повторного использования талидомида для лечения идиопатического фиброза легких (ИПФ). Статьи были найдены в базе данных Scopus, сортированы и рассмотрены отдельные статьи. Содержание включает в с

Conference Proceedings - 6th International Conference on Molecular Diagnostics and Biomarker Discovery (MDBD 2022): Building Resilience in Biomedical Research : Penang, Malaysia. 11-13 October 2022.

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Non-coding RNA in cancer drug resistance: Underlying mechanisms and clinical applications.

Cancer is one of the most frequently diagnosed malignant diseases worldwide, posing a serious, long-term threat to patients' health and life. Systemic chemotherapy remains the first-line therapeutic approach for recurrent or metastatic cancer patients after surgery, with the potential to effectively extend patient survival. However, the development of drug resistance seriously limits the clinical efficiency of chemotherapy and ultimately results in treatment failure and patient death. A large number of studies have shown that non-coding RNAs (ncRNAs), particularly microRNAs, long non-coding RN

The Cancer Antioxidant Regulation System in Therapeutic Resistance.

Antioxidants play a pivotal role in neutralizing reactive oxygen species (ROS), which are known to induce oxidative stress. In the context of cancer development, cancer cells adeptly maintain elevated levels of both ROS and antioxidants through a process termed "redox reprogramming". This balance optimizes the proliferative influence of ROS while simultaneously reducing the potential for ROS to cause damage to the cell. In some cases, the adapted antioxidant machinery can hamper the efficacy of treatments for neoplastic diseases, representing a significant facet of the resistance mechanisms ob

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… The NRF2 protein can also directly bind to the P21 promoter, thereby establishing a positive feedback loop that activates P21 expression and facilitates A549 cell survival under oxidative stress induced by H 2 O 2 [ 91 ]. … Recently, a supramolecular Pt(iv) prodrug nanoassembly delivery system containing the GGT inhibitor OU749 or NBDHEX was shown to maximize the therapeutic effect of platinum drugs in A549 cells by disrupting the redox balance [ 155 , 156 ]. …

Interplay of non-coding RNAs and approved antimetabolites such as gemcitabine and pemetrexed in mesothelioma.

Gemcitabine and pemetrexed are clinically approved antimetabolites for the therapy of mesothelioma diseases. These drugs are often applied in combination with platinum complexes and other drugs. The activity of antimetabolites depended on the expression levels of certain non-coding RNAs, in particular, of small microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). The development of tumor resistance towards antimetabolites was regulated by non-coding RNAs. An overview of the interplay between gemcitabine/pemetrexed antimetabolites and non-coding RNAs in mesothelioma is provided. Further to th

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… MiR-21 suppresses the anticancer activities of curcumin by targeting PTEN gene in human non-small cell lung cancer A549 cells Clin. Transl. Oncol. 16 2014 708 713 24293118 10.1007/s12094-013-1135-9 120 Pei C.-S. Wu H.-Y. Fan F.-T. Wu Y. Shen C.-S. Pan L.-Q. … Ginsenoside Rh2 mediates changes in the microRNA expression profile of human non-small cell lung cancer A549 cells Oncol. Rep. 29 2013 523 528 23152132 10.3892/or.2012.2136 162 Toden S. Okugawa Y. Buhrmann C. Nattamai D. Anguiano E. Baldwin N. Shakibaei M. Boland C.R. Goel A. …

Current Perspectives of the Applications of Polyphenols and Flavonoids in Cancer Therapy.

The development of anticancer therapies that involve natural drugs has undergone exponential growth in recent years. Among the natural compounds that produce beneficial effects on human health, polyphenols have shown potential therapeutic applications in cancer due to their protective functions in plants, their use as food additives, and their excellent antioxidant properties. The possibility of combining conventional drugs-which are usually more aggressive than natural compounds-with polyphenols offers very valuable advantages such as the building of more efficient anticancer therapies with l

Ten Years of Research on Fucoidan and Cancer: Focus on Its Antiangiogenic and Antimetastatic Effects.

Angiogenesis and metastasis represent two challenging targets to combat cancer development in the later stages of its progression. Numerous studies have indicated the important role of natural products in blocking tumor angiogenesis signaling pathways in several advanced tumors. In recent years, the marine polysaccharides fucoidans emerged as promising anticancer compounds showing potent antitumor activity in both in vitro and in vivo models of different types of cancers. The objective of this review is to focus on the antiangiogenic and antimetastatic activities of fucoidans with special emph

Modulation of angiogenesis with siRNA inhibitors for novel therapeutics.

Cancer and many other serious diseases are characterized by the uncontrolled growth of new blood vessels. Recently, RNA interference (RNAi) has reinvigorated the therapeutic prospects for inhibiting gene expression and promises many advantages over binding inhibitors, including high specificity, which is essential for targeted therapeutics. This article describes the latest developments using small-interfering RNA (siRNA) inhibitors to downregulate various angiogenic and tumor-associated factors, both in cell-culture assays and in animal disease models. The majority of research efforts are cur

Cannabidiol on the Path from the Lab to the Cancer Patient: Opportunities and Challenges.

Cannabidiol (CBD), a major non-psychotropic component of cannabis, is receiving growing attention as a potential anticancer agent. CBD suppresses the development of cancer in both in vitro (cancer cell culture) and in vivo (xenografts in immunodeficient mice) models. For critical evaluation of the advances of CBD on its path from laboratory research to practical application, in this review, we wish to call the attention of scientists and clinicians to the following issues: (a) the biological effects of CBD in cancer and healthy cells; (b) the anticancer effects of CBD in animal models and clin

MM-129 as a Novel Inhibitor Targeting PI3K/AKT/mTOR and PD-L1 in Colorectal Cancer.

Background and aimsThe purpose of the present study was to examine the pharmacodynamics features of MM-129 (1,2,4-triazine derivative) as a novel promising drug candidate against colon cancer.MethodsMM-129 was assessed for antitumor activity through an in vivo study on Cby.Cg-Foxn1nu/cmdb mice. The mechanistic studies investigated cellular affinity of a new 1,2,4-triazine derivative by measuring levels of intracellular/extracellular signal molecules participating in tumorigenesis.ResultsThe results revealed that MM-129 significantly reduced tumor growth in mice challenged with DLD-1 and HT-29

Current progress and mechanisms of bone metastasis in lung cancer: a narrative review.

Lung cancer is a kind of malignant tumor with rapid progression and poor prognosis. Distant metastasis has been the main cause of mortality among lung cancer patients. Bone is one of the most common sites. Among all lung cancer patients with bone metastasis, most of them are osteolytic metastasis. Some serious clinical consequences like bone pain, pathological fractures, spinal instability, spinal cord compression and hypercalcemia occur as well. Since the severity of bone metastasis in lung cancer, it is undoubtedly necessary to know how lung cancer spread to bone, how can we diagnose it and

Fatty acid synthase in chemoresistance: mechanisms and therapeutic opportunities.

Chemoresistance has been a major obstacle to the efficient treatment of cancer. Recently, targeting lipid metabolism has gained significant attention because of its roles not only in promoting cancer progression but also in inducing chemotherapy resistance. Fatty acid synthase (FAS) is the sole enzyme that is in charge of catalyzing the synthesis of palmitate, a long-chain lipid that is essential for membrane construction and post-translational modification in cell biology. Both FAS and its product, palmitate, have been validated as critical players in mediating or causing chemoresistance in c

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… In NSCLC A549 cells, FAS siRNA transfection could reduce the proliferation rate, migration and invasion ability through reducing ATP and lactic acid productions, suggesting a connection between fatty acid and glucose metabolism ( Chang et al., 2019 ). … More importantly, FAS siRNA treatment could inhibit tumor growth in the A549 cells xenograft mouse model ( Chang et al., 2019 ). …

Anti-cancer mechanisms of action of therapeutic alternating electric fields (tumor treating fields [TTFields]).

Despite improved survival outcomes across many cancer types, the prognosis remains grim for certain solid organ cancers including glioblastoma and pancreatic cancer. Invariably in these cancers, the control achieved by time-limited interventions such as traditional surgical resection, radiation therapy, and chemotherapy is short-lived. A new form of anti-cancer therapy called therapeutic alternating electric fields (AEFs) or tumor treating fields (TTFields) has been shown, either by itself or in combination with chemotherapy, to have anti-cancer effects that translate to improved survival outc