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Parasites revive hope for cancer therapy.

Parasites have attained a life-long stigma of being detrimental organisms with deleterious outcomes. Yet, recently, a creditable twist was verified that can dramatically change our perception of those parasites from being a source of misery to millions of people to a useful anti-cancerous tool. Various parasites have shown promise to combat cancer in different experimental models, including colorectal, lung, and breast cancers, among others. Helminths and protozoan parasites, as well as their derivatives such as Echinococcus granulosus protein KI-1, Toxoplasma gondii GRA15II, and Trypanosoma c

Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies.

Metastatic dissemination of solid tumors, a leading cause of cancer-related mortality, underscores the urgent need for enhanced insights into the molecular and cellular mechanisms underlying metastasis, chemoresistance, and the mechanistic backgrounds of individuals whose cancers are prone to migration. The most prevalent signaling cascade governed by multi-kinase inhibitors is the mitogen-activated protein kinase (MAPK) pathway, encompassing the RAS-RAF-MAPK kinase (MEK)-extracellular signal-related kinase (ERK) pathway. RAF kinase is a primary mediator of the MAPK pathway, responsible for th

A Review on the Molecular Mechanisms of Action of Natural Products in Preventing Bone Diseases.

The drugs used for treating bone diseases (BDs), at present, elicit hazardous side effects that include certain types of cancers and strokes, hence the ongoing quest for the discovery of alternatives with little or no side effects. Natural products (NPs), mainly of plant origin, have shown compelling promise in the treatments of BDs, with little or no side effects. However, the paucity in knowledge of the mechanisms behind their activities on bone remodeling has remained a hindrance to NPs' adoption. This review discusses the pathological development of some BDs, the NP-targeted components, an

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… Therefore, β-catenin builds up in the cytosol, and is transported into the nucleus where it binds to its promoter regions, TCF and LEF, to stimulate the transcription of target genes such as the RUNX2 gene, C-myc, cyclin D1, and c-jun. … Notably, albiflorin ( 34 ) and paeoniflorin ( 35 ) isolated from Paeonia lactiflora enhanced OBG in MC3T3-E1 cells by upregulating the mRNA expression of Wnt (Wnt10b), β-catenin (ctnnb1), LRP5, LRP6, Dvl2, and cyclin D1 (Ccnd1) [ 144 ], suggesting the involvement of BMP2-Wnt/β-catenin signaling pathway …

Transforming tumor microenvironments: nanotechnology and gene therapy in cellular signaling and epigenetic insight into chemo-resistance.

Chemoresistance remains the primary cause of cancer treatment failure, yet current understanding remains fragmented across isolated mechanistic studies. This review provides a unified framework linking tumor microenvironment (TME) signaling, epigenetic reprogramming, and nanotherapeutic intervention as an integrated axis driving and potentially reversing chemoresistance. We systematically examine how TME components: hypoxia (HIF-1α pathway), acidosis, cancer-associated fibroblasts (TGF-β/PDGF signaling), and immune cells (NF-κB-mediated immunosuppression) activate signaling cascades that direc

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… The NF-κB pathway is another central player that is a stress-responsive transcription factor that induces genes involved in cell survival (cMyc, Cyclin D1), drug efflux pumps, and cytokines. … Similarly, TNFα from macrophages activates NF-κB in cancer cells; NF-κB then induces targets such as cFLIP, BclxL, and Cyclin D1, which blunt the efficacy of chemotherapy [ 63 ]. …

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

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… Concurrently, phosphorylated ERK suppresses GSK-3β-mediated β-catenin degradation, facilitating its nuclear translocation and transcriptional activation of downstream targets such as c-myc and cyclin D1. …

MicroRNAs in B-cells: from normal differentiation to treatment of malignancies.

MicroRNAs (miRNAs) are small non-coding RNAs that play important post-transcriptional regulatory roles in a wide range of biological processes. They are fundamental to the normal development of cells, and evidence suggests that the deregulation of specific miRNAs is involved in malignant transformation due to their function as oncogenes or tumor suppressors. We know that miRNAs are involved in the development of normal B-cells and that different B-cell subsets express specific miRNA profiles according to their degree of differentiation. B-cell-derived malignancies contain transcription signatu

Leukemias in the Context of Rheumatoid Arthritis: Shared Pathways and Clinical Perspectives.

Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by systemic inflammation, progressive joint destruction, and increased risk of malignancies, particularly hematological cancers such as leukemias. RA patients appear to have a higher incidence of leukemias, suggesting a possible association between the two conditions. This association is driven by shared pathogenic mechanisms, including chronic inflammation, immune dysregulation, and genetic predispositions. Pro-inflammatory cytokines, notably tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6), play a crucial ro

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… The phosphorylated STAT3 (pSTAT3) forms dimers that translocate to the nucleus, promoting transcription of genes involved in cell survival, proliferation, and inflammation, including Mcl-1, Bcl-xL, c-Myc, Cyclin D1/D2, and Survivin. …

Long-Term Clinical Outcomes of Optimizing Combination Therapy for Primary Pulmonary Mucosa-Associated Lymphoid Tissue Lymphoma: A Retrospective Study.

INTRODUCTION: Pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma progresses with advancing disease stage. However, no standard treatment approach has been established. This single-center retrospective study evaluated clinical and radiological characteristics, treatment modalities, and long-term prognosis of pulmonary MALT lymphoma. METHODS: The study included 42 patients diagnosed with pulmonary MALT lymphoma between October 2004 and July 2019. Primary therapeutic modalities were determined using modified Ann Arbor staging. Therapeutic response was evaluated via computed tomography a

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… In all patients, immunohistochemical staining was positive for CD20 and CD79a, and levels of CD5, CD10, CD23, cyclin D1, and Ki-67 were also evaluated to exclude patients with other types of low-grade lymphoma. …

Serum interleukin-6 and C-reactive protein are associated with survival in melanoma patients receiving immune checkpoint inhibition.

BackgroundInflammatory mediators, including acute phase reactants and cytokines, have been reported to be associated with clinical efficacy in patients with melanoma and other cancers receiving immune checkpoint inhibitors (ICI). Analyses of patient sera from three large phase II/III randomized ICI trials, one of which included a chemotherapy arm, were performed to assess whether baseline levels of C-reactive protein (CRP), interleukin-6 (IL-6) or neutrophil/lymphocyte (N/L) ratios were prognostic or predictive.Patients and methodsBaseline and on-treatment sera were analyzed by multiplex prote

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… IL-6 induces tumor cell expression of STAT3 and its downstream target genes, which encode proteins that can drive tumor proliferation like cyclin D1 and/or survival like the BCL2-like protein 1 (BCL-xL). …

CeRNA Expression Profiling Identifies KIT-Related circRNA-miRNA-mRNA Networks in Gastrointestinal Stromal Tumour.

Gastrointestinal stromal tumours (GISTs) are the most common human sarcomas and are typically located in the stomach or small intestine. Although circular RNAs (circRNAs) reportedly play vital roles in tumour oncogenesis and progression, the molecular basis of the aggressive tumour biology of these circRNAs in GISTs remains unclear. In this study, we applied SBC ceRNA microarrays to screen for tumour-specific circRNA profiles in GISTs and identified that a total of 5,770 circRNAs and 1,815 mRNAs were differentially expressed in GISTs. Three significantly differential circRNAs (circ_0069765, ci

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… The overexpression of miR-149 increased the drug sensitivity of cancer cells and inhibited the EMT through the FOXM1/cyclin D1/MMP2 axis ( Ke et al., 2013 ; Xu et al., 2015 ; Sun et al., 2018 ). …

Screening of traditional Chinese medicine monomers as ribonucleotide reductase M2 inhibitors for tumor treatment.

BackgroundRibonucleotide reductase (RR) is a key enzyme in tumor proliferation, especially its subunit-RRM2. Although there are multiple therapeutics for tumors, they all have certain limitations. Given their advantages, traditional Chinese medicine (TCM) monomers have become an important source of anti-tumor drugs. Therefore, screening and analysis of TCM monomers with RRM2 inhibition can provide a reference for further anti-tumor drug development.AimTo screen and analyze potential anti-tumor TCM monomers with a good binding capacity to RRM2.MethodsThe Gene Expression Profiling Interactive An

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… Currently, some studies suggest that daphnetin also has an inhibitory effect on tumor growth, with the mechanisms of action including downregulating Cyclin D1 expression in breast cancer (MCF-7 cell line), inducing G2/M and S phase arrest in hepatoma cells (SMMC-7721 cell line), suppressing the Akt/NF-κB …

Clinical Utility of Selinexor/Dexamethasone in Patients with Relapsed or Refractory Multiple Myeloma: A Review of Current Evidence and Patient Selection.

Multiple myeloma (MM) is one the most common hematological malignancies, and despite the survival prolongation offered by proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs) and anti-CD38 monoclonal antibodies, the need for novel agents is prominent. Selinexor is a first-in-class, oral, selective inhibitor of exportin-1 (XPO1), a vital protein for the exportation of more than 200 tumor suppressor proteins from the nucleus. Both in solid tumors and hematologic malignancies, selinexor-mediated inhibition of nucleus export seems to effectively lead to cancer cell death. Selinexor in combi

Aberration of miRNAs Expression in Leukocytes from Sporadic Amyotrophic Lateral Sclerosis.

BACKGROUND: Accumulating evidence indicates that miRNAs play an important role in the development of amyotrophic lateral sclerosis (ALS). Most of previous studies on miRNA dysregulation in ALS focused on the alterative expression in ALS animal model or in limited samples from European patients with ALS. In the present study, the miRNA expression profiles were investigated in Chinese ALS patients to explore leukocytes miRNAs as a potential biomarker for the diagnosis of ALS. METHODS: We analyzed the expression profiles of 1733 human mature miRNAs using microarray technology in leukocytes obtai

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… MicroRNA-193b represses cell proliferation and regulates cyclin D1 in melanoma. Am. J. Pathol. 176, 2520–2529. 10.2353/ajpath.2010.091061 Chen X., Feng W., Huang R., Guo X., Chen Y., Zheng Z., et al. (2014). Evidence for peripheral immune activation in amyotrophic lateral sclerosis. J. Neurol. …

Chemistry and Pharmacology of Fluorinated Drugs Approved by the FDA (2016-2022).

Fluorine is characterized by high electronegativity and small atomic size, which provide this molecule with the unique property of augmenting the potency, selectivity, metabolic stability, and pharmacokinetics of drugs. Fluorine (F) substitution has been extensively explored in drug research as a means of improving biological activity and enhancing chemical or metabolic stability. Selective F substitution onto a therapeutic or diagnostic drug candidate can enhance several pharmacokinetic and physicochemical properties such as metabolic stability and membrane permeation. The increased binding a

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… Name | Structure | Mode of Action | References Abemaciclib | | CDK4/cyclin D1 complex inhibitor | [ 70 ] Alpelisib | | Phosphatidylinositol 3-kinase (PI3K) inhibitor | [ 71 ] Atogepant | | CGRP receptor antagonist | [ 72 ] Apalutamide | | Androgen receptor inhibitor | [ 73 ] Asciminib | | ABL/BCR–ABL1 …

Targeting the p53 signaling pathway in cancers: Molecular mechanisms and clinical studies.

Tumor suppressor p53 can transcriptionally activate downstream genes in response to stress, and then regulate the cell cycle, DNA repair, metabolism, angiogenesis, apoptosis, and other biological responses. p53 has seven functional domains and 12 splice isoforms, and different domains and subtypes play different roles. The activation and inactivation of p53 are finely regulated and are associated with phosphorylation/acetylation modification and ubiquitination modification, respectively. Abnormal activation of p53 is closely related to the occurrence and development of cancer. While targeted t

Biosynthesis of anticancer phytochemical compounds and their chemistry.

Cancer is a severe health issue, and cancer cases are rising yearly. New anticancer drugs have been developed as our understanding of the molecular mechanisms behind diverse solid tumors, and metastatic malignancies have increased. Plant-derived phytochemical compounds target different oncogenes, tumor suppressor genes, protein channels, immune cells, protein channels, and pumps, which have attracted much attention for treating cancer in preclinical studies. Despite the anticancer capabilities of these phytochemical compounds, systemic toxicity, medication resistance, and limited absorption re

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… Curcumin inhibits the cell cycle in colorectal cancer by upregulating caspases and downregulating cyclin D1 and cyclin D3. …

Homoharringtonine: updated insights into its efficacy in hematological malignancies, diverse cancers and other biomedical applications.

HHT has emerged as a notable compound in the realm of cancer treatment, particularly for hematological malignancies. Its multifaceted pharmacological properties extend beyond traditional applications, warranting an extensive review of its mechanisms and efficacy. This review aims to synthesize comprehensive insights into the efficacy of HHT in treating hematological malignancies, diverse cancers, and other biomedical applications. It focuses on elucidating the molecular mechanisms, therapeutic potential, and broader applications of HHT. A comprehensive search for peer-reviewed papers was condu

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… HHT's anti-leukemic mechanism involves inhibiting the translation process by affecting the A site in the ribosome, leading to rapid loss of several short-lived proteins crucial for cell survival, such as myeloid cell leukemia (MCL)-1, cyclin D1, the pro-oncoprotein c-Myc, and the X-linked inhibitor of … Subsequent studies have focused on elucidating the efficacy of omacetaxine; these investigations revealed that OM can induce the rapid degradation (in less than 4 h) of several short-lived proteins crucial for cancer cell survival, such as Mcl-1, Cyclin D1, c-Myc, XIAP, β-Catenin, and the long isoform …

The Multifaceted Roles of Myrrha in the Treatment of Breast Cancer: Potential Therapeutic Targets and Promises.

BackgroundBreast cancer is a critical threat to human health, and effective targeted agents showing lower systemic toxicity are still lacking. Therefore, exploring new potent therapeutic candidates with a broader safety margin is warranted. Alternative medicine, which has historically been used in traditional Chinese medicine, has played an increasingly prominent role in this area of research. This study introduces Commiphora myrrha (or myrrh) as a potential therapeutic candidate for treating breast cancer patients. Myrrh bioactive extracts have been used traditionally for decades to treat num

Cutting edge of immune response and immunosuppressants in allogeneic and xenogeneic islet transplantation.

As an effective treatment for diabetes, islet transplantation has garnered significant attention and research in recent years. However, immune rejection and the toxicity of immunosuppressive drugs remain critical factors influencing the success of islet transplantation. While immunosuppressants are essential in reducing immune rejection reactions and can significantly improve the survival rate of islet transplants, improper use of these drugs can markedly increase mortality rates following transplantation. Additionally, the current availability of islet organ donations fails to meet the demand

Dual targeting of protein translation and nuclear protein export results in enhanced antimyeloma effects.

Selinexor (KPT-330) is a small molecule inhibitor of XPO1, which mediates the transport of tumor suppressor proteins, oncogene messenger RNAs, and other proteins involved in governing cell growthfrom the cell nucleus to the cytoplasm. It is overexpressed in many cancer types. Because eukaryotic translation initiator factor 4E (eIF4E) plays a critical role in protein translation in cancer cells in multiple myeloma (MM), we evaluated the effectiveness of combined inhibition of protein translation and nuclear export in MM. Selinexor, an inhibitor of nuclear protein export, dose-dependently decrea

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… Multiple cancers, including MM, display elevated levels of translation initiation factors, 47 , 48 and eIF4E’s overexpression induces malignant transformation and drug resistance. 49 Furthermore, several eIF4E targets are upregulated in MM, including MMP9, Bcl-2, Bcl-XL, survivin, cyclin D1, c-MYC, and …