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Enhanced sialylation of bone marrow mesenchymal stromal cells contributes to immune remodeling through macrophage polarization in multiple myeloma patients.

INTRODUCTION: In multiple myeloma (MM), the immune system is disrupted, partly due to tumor-modified bone marrow mesenchymal stromal cells (BM-MSCs). These MSCs show altered glycosylation, including increased sialylation, which may promote immune evasion through Siglec interactions. METHODS: We quantified sialic acids and Siglec ligands on healthy donors-, MM-, T-MM-(treated multiple myeloma) and MGUS (monoclonal gammopathy of undetermined significance)-MSCs, and examined how different culture conditions (myeloma coculture, conditioned medium, hypoxia, inflammation, 3D culture) affect MSC gly

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… Previous studies have produced context-dependent effects of hypoxia on sialylation: Nawafley et al. observed increased expression of Siglec-7 ligands in a sub-population of K562 cells ( 71 ) under hypoxic stress, whereas Peng et al. reported reduced sialylation in breast cancer cells exposed to hypoxic …

The therapeutic potential of colchicine in oncology studies: from structural modification and targeted delivery to clinical management.

Colchicine, a classical microtubule-targeting agent (MTA), exhibits remarkable anti-tumor potential, but its clinical translation is severely restricted by a narrow therapeutic window, systemic off-target toxicity, and complex pharmacokinetic vulnerabilities. Driven by the objective of "toxicity reduction and efficacy enhancement," this review comprehensively summarizes colchicine's multidimensional translational research. First, precise chemical modifications of its tricyclic scaffold and multi-site synergistic strategies are analyzed, exploring structure-activity relationship (SAR) mechanism

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… Exploring C10 modifications to overcome multidrug resistance (MDR) and metabolic vulnerabilities, Yang et al. demonstrated that 10-methylaminocolchicine (compound 14) achieved a GI 50 of 5.0 ± 3.2 nM in K562 cells, roughly doubling the parent colchicine’s efficacy (10.7 ± 5.1 nM). …

Amiloride ameliorates muscle wasting in cancer cachexia through inhibiting tumor-derived exosome release.

BACKGROUND: Cancer cachexia (CAC) reduces patient survival and quality of life. Developments of efficient therapeutic strategies are required for the CAC treatments. This long-term process could be shortened by the drug-repositioning approach which exploits old drugs approved for non-cachexia disease. Amiloride, a diuretic drug, is clinically used for treatments of hypertension and edema due to heart failure. Here, we explored the effects of the amiloride treatment for ameliorating muscle wasting in murine models of cancer cachexia. METHODS: The CT26 and LLC tumor cells were subcutaneously in

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… Savina A Furlán M Vidal M Colombo MI Exosome release is regulated by a calcium-dependent mechanism in K562 cells J Biol Chem. 2003 278 22 20083 20090 10.1074/jbc.M301642200 12639953 46. …

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

Cancer Chemoprevention: A Strategic Approach Using Phytochemicals.

Cancer chemoprevention approaches are aimed at preventing, delaying, or suppressing tumor incidence using synthetic or natural bioactive agents. Mechanistically, chemopreventive agents also aid in mitigating cancer development, either by impeding DNA damage or by blocking the division of premalignant cells with DNA damage. Several pre-clinical studies have substantiated the benefits of using various dietary components as chemopreventives in cancer therapy. The incessant rise in the number of cancer cases globally is an issue of major concern. The excessive toxicity and chemoresistance associat

Mucosal-Associated Invariant T Cells Display Diminished Effector Capacity in Oesophageal Adenocarcinoma.

Oesophageal adenocarcinoma (OAC) is an aggressive malignancy with poor prognosis, and incidence is increasing rapidly in the Western world. Mucosal-associated invariant T (MAIT) cells recognize bacterial metabolites and kill infected cells, yet their role in OAC is unknown. We aimed to elucidate the role of MAIT cells during cancer development by characterizing the frequency, phenotype, and function of MAIT cells in human blood and tissues, from OAC and its pre-malignant inflammatory condition Barrett's oesophagus (BO). Blood and tissues were phenotyped by flow cytometry and conditioned media

Involvement of multiple myeloma cell-derived exosomes in osteoclast differentiation.

Bone disease is the most frequent complication in multiple myeloma (MM) resulting in osteolytic lesions, bone pain, hypercalcemia and renal failure. In MM bone disease the perfect balance between bone-resorbing osteoclasts (OCs) and bone-forming osteoblasts (OBs) activity is lost in favour of OCs, thus resulting in skeletal disorders. Since exosomes have been described for their functional role in cancer progression, we here investigate whether MM cell-derived exosomes may be involved in OCs differentiation. We show that MM cells produce exosomes which are actively internalized by Raw264.7 cel

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… The exosome pathway in K562 cells is regulated by Rab11. J Cell Sci. 2002;115:2505–2515. doi: 10.1242/jcs.115.12.2505. 25. Szymczyk KH, Freeman TA, Adams CS, Srinivas V, Steinbeck MJ. Active caspase-3 is required for osteoclast differentiation. …

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

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… Similar results were reported in another study indicating that EPA (40, 60, and 120 μM) can induce apoptosis in HL-60 cells but not in K562 cells independent of any of its effects on DNA fragmentation [ 38 ]. …

Contemporary Perspectives on the Warburg Effect Inhibition in Cancer Therapy.

In the 1920s, Otto Warburg observed the phenomenon of altered glucose metabolism in cancer cells. Although the initial hypothesis suggested that the alteration resulted from mitochondrial damage, multiple studies of the subject revealed a precise, multistage process rather than a random pattern. The phenomenon of aerobic glycolysis emerges not only from mitochondrial abnormalities common in cancer cells, but also results from metabolic reprogramming beneficial for their sustenance. The Warburg effect enables metabolic adaptation of cancer cells to grow and proliferate, simultaneously enabling

The progression of HMGB1-induced autophagy in cancer biology.

Autophagy is an important process of cellular degradation and has been proven to contribute to tumorigenesis. High-mobility group box 1 (HMGB1) is an abundant nonhistone protein that has been widely reported to play a central role in the induction of autophagy. In nucleus, HMGB1 upregulates the expression of HSP27 to induce autophagy. In cytoplasm, the Beclin-1/PI3K-III complex can be activated by HMGB1 to promote autophagy. Extracellular HMGB1 binds to the receptor for advanced glycation end products to induce autophagy. Recent studies have shown that HMGB1-induced autophagy exerts multiple f

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… Influence of HMGB1/MAPK/m-TOR signaling pathway on cell autophagy and chemotherapy resistance in K562 cells. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2016;41(10):1016–1023. doi: 10.11817/j.issn.1672-7347.2016.10.002. 47. Dajon M, Iribarren K, Cremer I. …

Exploration of the Use of Natural Compounds in Combination with Chemotherapy Drugs for Tumor Treatment.

Currently, chemotherapy is the main treatment for tumors, but there are still problems such as unsatisfactory chemotherapy results, susceptibility to drug resistance, and serious adverse effects. Natural compounds have numerous pharmacological activities which are important sources of drug discovery for tumor treatment. The combination of chemotherapeutic drugs and natural compounds is gradually becoming an important strategy and development direction for tumor treatment. In this paper, we described the role of natural compounds in combination with chemotherapeutic drugs in synergizing, reduci

Bisphosphonate-Based Conjugates and Derivatives as Potential Therapeutic Agents in Osteoporosis, Bone Cancer and Metastatic Bone Cancer.

Metastatic bone cancer occurs in every type of cancer but is prevalent in lung, breast, and prostate cancers. These metastases can cause extensive morbidity, including a range of skeletal-related events, often painful and linked with substantial hospital resource usage. The treatment used is a combination of chemotherapy and surgery. However, anticancer drugs are still limited due to severe side effects, drug resistance, poor blood supply, and non-specific drug uptake, necessitating high toxic doses. Bisphosphonates are the main class of drugs utilized to inhibit metastatic bone cancer. It is

The Power of Extracellular Vesicles in Myeloproliferative Neoplasms: "Crafting" a Microenvironment That Matters.

Myeloproliferative Neoplasms (MPN) are acquired clonal disorders of the hematopoietic stem cells and include Essential Thrombocythemia, Polycythemia Vera and Myelofibrosis. MPN are characterized by mutations in three driver genes (JAK2, CALR and MPL) and by a state of chronic inflammation. Notably, MPN patients experience increased risk of thrombosis, disease progression, second neoplasia and evolution to acute leukemia. Extracellular vesicles (EVs) are a heterogeneous population of microparticles with a role in cell-cell communication. The EV-mediated cross-talk occurs via the trafficking of

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… Of note, circDAP3 is able to inhibit the megakaryocytic differentiation of K562 cells. …

Targeting Eukaryotic Elongation Factor 1A: How Small-Molecule Inhibitors Suppress Tumor Growth via Diverse Pathways.

Eukaryotic elongation factor 1A (eEF1A), the second most abundant intracellular protein, not only plays a key role in peptide elongation, but is also capable of numerous moonlighting functions. Within malignant cells, eEF1A is by no means a neutral bystander but instead actively participates in oncogenic transformations via a myriad of molecular pathways. Thus far, a broad range of small-molecule inhibitors have been identified, which, despite their structural diversity, suppress tumor growth by targeting eEF1A. Interestingly, just as eEF1A enables its oncogenic potential far beyond boosting p

Targeted synthesis of a trimethoxyphenyltetrahydropyrimidine analogue designed as a DNA intercalator: in silico, multi-spectroscopic, thermodynamic, and in vitro approaches.

Based on the rational design of DNA intercalators and Topo-II inhibitors and taking into consideration the main pharmacophoric features of doxorubicin (Dox) as a reference standard, we theoretically designed novel substituted tetrahydropyrimidine analogues (T1-35). The designed analogues (T1-35) were investigated for their inhibitory potential towards the hybrid DNA and Topo-II target receptor using molecular docking. Interestingly, the theoretically designed analogue T30 with a 3,4,5-trimethoxy phenyl side chain was found to be the superior candidate, achieving a binding score of -7.06 kcal m

Epigenetic regulation in hematopoiesis and its implications in the targeted therapy of hematologic malignancies.

Hematologic malignancies are one of the most common cancers, and the incidence has been rising in recent decades. The clinical and molecular features of hematologic malignancies are highly heterogenous, and some hematologic malignancies are incurable, challenging the treatment, and prognosis of the patients. However, hematopoiesis and oncogenesis of hematologic malignancies are profoundly affected by epigenetic regulation. Studies have found that methylation-related mutations, abnormal methylation profiles of DNA, and abnormal histone deacetylase expression are recurrent in leukemia and lympho

Apoptotic Pathway as the Therapeutic Target for Anticancer Traditional Chinese Medicines.

Cancer is a leading cause of morbidity and mortality worldwide. Apoptosis is a process of programmed cell death and it plays a vital role in human development and tissue homeostasis. Mounting evidence indicates that apoptosis is closely related to the survival of cancer and it has emerged as a key target for the discovery and development of novel anticancer drugs. Various studies indicate that targeting the apoptotic signaling pathway by anticancer drugs is an important mechanism in cancer therapy. Therefore, numerous novel anticancer agents have been discovered and developed from traditional

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… Additional studies also showed that oridonin could inhibit cell growth and induce apoptosis in cervical cancer HeLa, gallbladder cancer SGC996 and NOZ, and leukemia K562 cells via alteration of the Bcl-2/Bax ratio with decreased expression of Bcl-2 and increased expression of Bax in mitochondria ( Zhang …

Involvement of the Opioid Peptide Family in Cancer Progression.

Peptides mediate cancer progression favoring the mitogenesis, migration, and invasion of tumor cells, promoting metastasis and anti-apoptotic mechanisms, and facilitating angiogenesis/lymphangiogenesis. Tumor cells overexpress peptide receptors, crucial targets for developing specific treatments against cancer cells using peptide receptor antagonists and promoting apoptosis in tumor cells. Opioids exert an antitumoral effect, whereas others promote tumor growth and metastasis. This review updates the findings regarding the involvement of opioid peptides (enkephalins, endorphins, and dynorphins

Current State of Human Gene Therapy: Approved Products and Vectors.

In the realm of gene therapy, a pivotal moment arrived with Paul Berg's groundbreaking identification of the first recombinant DNA in 1972. This achievement set the stage for future breakthroughs. Conditions once considered undefeatable, like melanoma, pancreatic cancer, and a host of other ailments, are now being addressed at their root cause-the genetic level. Presently, the gene therapy landscape stands adorned with 22 approved in vivo and ex vivo products, including IMLYGIC, LUXTURNA, Zolgensma, Spinraza, Patisiran, and many more. In this comprehensive exploration, we delve into a rich ass

Prospects for γδ T cells and chimeric antigen receptor γδ T cells in cancer immunotherapy.

γδ T cells, a type of specialized T cell, differ from alpha-beta T cells due to the presence of γ and δ chain surface T cell receptors. These receptors allow them to directly recognize and bind antigenic molecules without the requirement of attachment to MHC or APC antigen presentation. Given their intrinsic properties and functional versatility, γδ T cells are under intensive investigation as carriers for chimeric antigen receptor (CAR) in the context of cancer therapy. In this regard, γδ CAR-T cells have demonstrated great potential to overcome the limitations of antigen recognition with the