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Bone sialoprotein: a multifunctional regulator of bone remodelling and tumour progression.

Bone sialoprotein (BSP) is a major non-collagenous protein of the bone extracellular matrix and an important regulator of bone formation and resorption. BSP is produced by bone cells and chondrocytes and present in the bone matrix, cells, dentin and cartilage. However, its aberrant expression in primary tumour tissues and the sera of cancer patients with metastases implicates BSP in tumour biology and progression. The Arg-Gly-Asp (RGD) motif of BSP may be crucial not only for the attachment of metastasising cells to the bone surface but also for tumour growth, survival and activity. This revie

Melatonin and Its Role in the Epithelial-to-Mesenchymal Transition (EMT) in Cancer.

The epithelial-to-mesenchymal transition (EMT) is a cell-biological program that occurs during the progression of several physiological processes and that can also take place during pathological situations such as carcinogenesis. The EMT program consists of the sequential activation of a number of intracellular signaling pathways aimed at driving epithelial cells toward the acquisition of a series of intermediate phenotypic states arrayed along the epithelial-mesenchymal axis. These phenotypic features include changes in the motility, conformation, polarity and functionality of cancer cells, u

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… Control of vascular morphogenesis and homeostasis through the angiopoietin-Tie system Nat. Rev. Mol. Cell Biol. 2009 10 165 177 10.1038/nrm2639 19234476 21. Fares J. Fares M.Y. Khachfe H.H. Salhab H.A. Fares Y. Molecular principles of metastasis: A hallmark of cancer revisited Signal Transduct. …

Nanotechnology and Matrix Metalloproteinases in Cancer Diagnosis and Treatment.

Cancer is still one of the leading causes of death worldwide. This great mortality is due to its late diagnosis when the disease is already at advanced stages. Although the efforts made to develop more effective treatments, around 90% of cancer deaths are due to metastasis that confers a systemic character to the disease. Likewise, matrix metalloproteinases (MMPs) are endopeptidases that participate in all the events of the metastatic process. MMPs' augmented concentrations and an increased enzymatic activity have been considered bad prognosis markers of the disease. Therefore, synthetic inhib

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… MMPs have an essential role in many cellular processes in physiological conditions such as blastocyst implantation, embryogenesis, morphogenesis, bone remodeling, wound healing, angiogenesis, aging, tissue repair, cell proliferation, differentiation, and migration due to their interaction with the extracellular …

Hyaluronic Acid as a Modern Approach in Anticancer Therapy-Review.

Hyaluronic acid (HA) is a linear polysaccharide and crucial component of the extracellular matrix (ECM), maintaining tissue hydration and tension. Moreover, HA contributes to embryonic development, healing, inflammation, and cancerogenesis. This review summarizes new research on the metabolism and interactions of HA with its binding proteins, known as hyaladherins (CD44, RHAMM), revealing the molecular basis for its distinct biological function in the development of cancer. The presence of HA on the surface of tumor cells is a sign of an adverse prognosis. The involvement of HA in malignancy h

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… Disruption of Hyaluronan Synthase-2 Abrogates Normal Cardiac Morphogenesis and Hyaluronan-Mediated Transformation of Epithelium to Mesenchyme J. Clin. Investig. 2000 106 349 360 10.1172/JCI10272 10930438 PMC314332 35. Laurent U.B.G. Reed R.K. Turnover of Hyaluronan in the Tissues Adv. Drug Deliv. …

Cancer of Unknown Primary: Challenges and Progress in Clinical Management.

Distant metastases are the main cause of cancer-related deaths in patients with advanced tumors. A standard diagnostic workup usually contains the identification of the tissue-of-origin of metastatic tumors, although under certain circumstances, it remains elusive. This disease setting is defined as cancer of unknown primary (CUP). Accounting for approximately 3-5% of all cancer diagnoses, CUPs are characterized by an aggressive clinical behavior and represent a real therapeutic challenge. The lack of determination of a tissue of origin precludes CUP patients from specific evidence-based thera

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… The transcription factor ttf-1 is expressed at the onset of thyroid and lung morphogenesis and in restricted regions of the foetal brain. Development. 1991;113:1093–1104. doi: 10.1242/dev.113.4.1093. 64. Goldstein N.S., Thomas M. …

Targeting cancer stem cells in drug discovery: Current state and future perspectives.

In recent decades, cancer stem cells (CSCs) have been increasingly identified in many malignancies. CSC-related signaling pathways and their functions provide new strategies for treating cancer. The aberrant activation of related signaling pathways (e.g., Wnt, Notch, and Hedgehog pathways) has been linked to multiple types of malignant tumors, which makes these pathways attractive targets for cancer therapy. CSCs display many characteristic features, such as self-renewal, differentiation, high tumorigenicity, and drug resistance. Therefore, there is an urgent need to develop new therapeutic st

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… Efficacy of Paclitaxel in Lung Adenocarcinoma Mol Cancer Ther 2017 16 2759 2769 28978720 10.1158/1535-7163.MCT-17-0439 PMC5716926 95 Krebs LT Xue Y Norton CR Shutter JR Maguire M Sundberg JP Gallahan D Closson V Kitajewski J Callahan R Smith GH Stark KL Gridley T Notch signaling is essential for vascular morphogenesis …

KSHV and cancer: understanding the oncogenic machinery for next-generation diagnostic tools and therapies.

Kaposi's sarcoma-associated herpesvirus (KSHV), or human herpesvirus 8 (HHV-8), is an oncogenic virus responsible for Kaposi's sarcoma (KS) and lymphoproliferative disorders like primary effusion lymphoma (PEL) and multicentric Castleman disease (MCD). This review explores KSHV's oncogenic mechanisms, focusing on its ability to manipulate host cell signaling, evade immune detection, and promote tumorigenesis through latent and lytic viral proteins. Key oncoproteins, such as LANA, vCyc, vFLIP, and vGPCR, activate cancer hallmarks, as sustained proliferation, immune evasion, angiogenesis, and re

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… HIV-1 protease enzyme plays a role in viral morphogenesis, and its inhibitors are potentially affective, but are followed by multiple severe adverse effects and resistance. …

Oncogenic influences of neurotrophin receptors: Shedding light on Trk biology.

During critical stages of neurodevelopment, tropomyosin receptor kinase receptors, encoded by NTRK genes, exhibit temporally driven differential peaks of expression to properly guide the establishment of the peripheral and central nervous systems. In addition, these neuronal systems exhibit non-canonical regulation of surrounding tissues, impacting organogenesis, homeostasis, plasticity, and regeneration. The same processes that guide neurodevelopment, such as differentiation, plasticity, and neuronal survival, are also hijacked in cancer, making the NTRK family an ideal candidate to study. Th

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… Astrocyte morphogenesis is dependent on BDNF signaling via astrocytic TrkB.T1. eLife 8, e44667. 10.7554/eLife.44667. 25. Geraghty AC, Gibson EM, Ghanem RA, Greene JJ, Ocampo A, Goldstein AK, Ni L, Yang T, Marton RM, Pas‚ ca SP, et al. (2019). …

Checking NEKs: Overcoming a Bottleneck in Human Diseases.

In previous years, several kinases, such as phosphoinositide 3-kinase (PI3K), mammalian target of rapamycin (mTOR), and extracellular-signal-regulated kinase (ERK), have been linked to important human diseases, although some kinase families remain neglected in terms of research, hiding their relevance to therapeutic approaches. Here, a review regarding the NEK family is presented, shedding light on important information related to NEKs and human diseases. NEKs are a large group of homologous kinases with related functions and structures that participate in several cellular processes such as th

Targeting Tumor Microenvironment for Cancer Therapy.

Cancer development is highly associated to the physiological state of the tumor microenvironment (TME). Despite the existing heterogeneity of tumors from the same or from different anatomical locations, common features can be found in the TME maturation of epithelial-derived tumors. Genetic alterations in tumor cells result in hyperplasia, uncontrolled growth, resistance to apoptosis, and metabolic shift towards anaerobic glycolysis (Warburg effect). These events create hypoxia, oxidative stress and acidosis within the TME triggering an adjustment of the extracellular matrix (ECM), a response

mTOR Cross-Talk in Cancer and Potential for Combination Therapy.

The mammalian Target of Rapamycin (mTOR) pathway plays an essential role in sensing and integrating a variety of exogenous cues to regulate cellular growth and metabolism, in both physiological and pathological conditions. mTOR functions through two functionally and structurally distinct multi-component complexes, mTORC1 and mTORC2, which interact with each other and with several elements of other signaling pathways. In the past few years, many new insights into mTOR function and regulation have been gained and extensive genetic and pharmacological studies in mice have enhanced our understandi

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… Moreover, mTOR inhibitors exert antiangiogenic effects by directly inhibiting endothelial cell functions, such as proliferation and morphogenesis [ 43 ]. …

Feline infectious peritonitis.

The article discusses feline infectious peritonitis (FIP), an important disease frequently seen in veterinary practice. FIP causes many problems to the veterinarian as it can be difficult to definitively diagnose the disease, as there is no effective treatment, and as prophylactic interventions are not very successful. Although intense research has created a lot of new knowledge about this disease in the last years, there are still many unanswered questions. The objective of this article is to review recent knowledge and to increase understanding of the complex pathogenesis of FIP.

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… Morphogenesis of a virus in cats with experimental feline infectious peritonitis Virology 41 1970 191 194 4986314 10.1016/0042-6822(70)90070-X PMC7131342 24 Holzworth J. Some important disorders of cats Cornell Vet 53 1963 157 160 13961523 25 O'Reilly K. Fishman B. Hitchcock L. …

Площадь метилирования ДНК клеток цереброспинальной жидкости в множестве склероза: исследование эпигеномной ассоциации.

Множественный склероз (MS) является хроническим воспалительным заболеванием центральной нервной системы, в которой метилация ДНК может увязывать генетические и экологические факторы риска. Methods: Мы профилировали содержание метилации ДНК по всему геному в клетках цереброспиновой жидкости (CSF) у людей с MS (pwMS) и совпадающими контрольными устройствами. Дифференцированные метилированные позиции (DMP) и регионы (DMR) были интегрированы с транскриптомными данными, аннотациями клеточного хроматина Т и анализом путей. Выражение гамма-протокадерина (ПХДГ) было оценено в первичных подмножествах C

Tumor angiogenesis as a target for dietary cancer prevention.

Between 2000 and 2050, the number of new cancer patients diagnosed annually is expected to double, with an accompanying increase in treatment costs of more than $80 billion over just the next decade. Efficacious strategies for cancer prevention will therefore be vital for improving patients' quality of life and reducing healthcare costs. Judah Folkman first proposed antiangiogenesis as a strategy for preventing dormant microtumors from progressing to invasive cancer. Although antiangiogenic drugs are now available for many advanced malignancies (colorectal, lung, breast, kidney, liver, brain,

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… These include (1) angiogenic growth factor production, release, and receptor activation, (2) degradation of vascular basement membrane, (3) endothelial proliferation, migration, and survival, (4) blood vessel sprouting and invasion, (5) tubular morphogenesis, (6) arterial-venous patterning, (7) vascular …

Role of lysophosphatidic acid and its receptors in health and disease: novel therapeutic strategies.

Lysophosphatidic acid (LPA) is an abundant bioactive phospholipid, with multiple functions both in development and in pathological conditions. Here, we review the literature about the differential signaling of LPA through its specific receptors, which makes this lipid a versatile signaling molecule. This differential signaling is important for understanding how this molecule can have such diverse effects during central nervous system development and angiogenesis; and also, how it can act as a powerful mediator of pathological conditions, such as neuropathic pain, neurodegenerative diseases, an

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… non-CNS endothelial cells have been elucidated, 114 only recently a study has focused on the role of LPA in different steps of CNS angiogenesis. 115 Analysis of inducible endothelial-specific Lpar4 / Lpar6 DKO retinas revealed a clear phenotype on retinal vascular expansion, tip cell, and sprouting morphogenesis …

Tumor biomarkers for diagnosis, prognosis and targeted therapy.

Tumor biomarkers, the substances which are produced by tumors or the body's responses to tumors during tumorigenesis and progression, have been demonstrated to possess critical and encouraging value in screening and early diagnosis, prognosis prediction, recurrence detection, and therapeutic efficacy monitoring of cancers. Over the past decades, continuous progress has been made in exploring and discovering novel, sensitive, specific, and accurate tumor biomarkers, which has significantly promoted personalized medicine and improved the outcomes of cancer patients, especially advances in molecu

Epigenetic Dysregulation in Neurodegeneration: The Role of Histone Deacetylases and Emerging Inhibitor Strategies.

Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD) are characterized by complex pathologies with progressive neurodegeneration, protein misfolding, oxidative stress, and persistent inflammation. Recent findings indicate the pivotal involvement of epigenetic disruption, particularly aberrant histone deacetylase (HDAC) activity, in disease initiation and progression. In the current review, we systematically discuss the mechanistic function of HDACs across all classes (I, IIa, IIb, III, and IV) in neurodegenerative disease mechanis

Double jeopardy: how BRCA2, TP53, and DNMT3A redefine the link between infertility and cancer risk.

BackgroundGermline mutations in genes governing DNA repair, cell cycle regulation, and epigenetic modification are now recognized as common etiological factors for both cancer predisposition and reproductive dysfunction. This reveals a profound intersection between reproductive biology and oncogenesis.MethodA systematic narrative review was conducted. The literature search spanned PubMed/MEDLINE, Scopus, and Web of Science using keywords and MeSH terms related to infertility phenotypes, cancer predisposition syndromes, and shared molecular mechanisms (e.g., DNA repair, epigenetics).OutcomesThe

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… Abnormal spermatogenesis (Hom) | Eischen (2016) ; Zalzali et al. (2018) ​ | Chek2 | Cell cycle checkpoint | No phenotypes reported | Bahassi el et al. (2009) Developmental Regulators | Wt1 | Gonadal development | Testis hypoplasia (Hom/het) | Wang et al. (2013) ; Chen et al. (2022b) ​ | Hoxb13 | Prostate morphogenesis …

Potential Protective Role Exerted by Secoiridoids from Olea europaea L. in Cancer, Cardiovascular, Neurodegenerative, Aging-Related, and Immunoinflammatory Diseases.

Iridoids, which have beneficial health properties, include a wide group of cyclopentane [c] pyran monoterpenoids present in plants and insects. The cleavage of the cyclopentane ring leads to secoiridoids. Mainly, secoiridoids have shown a variety of pharmacological effects including anti-diabetic, antioxidant, anti-inflammatory, immunosuppressive, neuroprotective, anti-cancer, and anti-obesity, which increase the interest of studying these types of bioactive compounds in depth. Secoiridoids are thoroughly distributed in several families of plants such as Oleaceae, Valerianaceae, Gentianaceae a

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… Margheri et al. also reported the effects of OL aglycone on capillary morphogenesis induced by MRC5 fibroblast "senescense associated secretory phenotype" and progenitor endothelial cells, establishing that this secoiridoid could modulate angiogenesis indirectly on senescent fibroblasts [ 158 ] ( Table …

The Anti-Cancer Effect of Polyphenols against Breast Cancer and Cancer Stem Cells: Molecular Mechanisms.

The high incidence of breast cancer in developed and developing countries, and its correlation to cancer-related deaths, has prompted concerned scientists to discover novel alternatives to deal with this challenge. In this review, we will provide a brief overview of polyphenol structures and classifications, as well as on the carcinogenic process. The biology of breast cancer cells will also be discussed. The molecular mechanisms involved in the anti-cancer activities of numerous polyphenols, against a wide range of breast cancer cells, in vitro and in vivo, will be explained in detail. The in

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… Modulation of the Epithelial Mesenchymal Transition (EMT) EMT is an intricate developmental process, in which special differentiated polarized epithelial cells undergo morphogenesis via loss of their differentiation characteristics, such as cell–cell adhesion, cell polarity, immotile status, and the …