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Topic Review
Proteoglycans in the hormone-dependent cancers
The tumor microenvironment (TME) exhibits unique characteristics that differ among various tumor types. It is composed of cancerous, non-cancerous, stromal, and immune cells that are surrounded and supported by components of the extracellular matrix (ECM). Therefore, the interactions among cancer cells, stromal cells, and components of the ECM determine cancer progression and response to therapy. Proteoglycans (PGs), hybrid molecules consisting of a protein core to which sulfated glycosaminoglycan chains are bound, are significant components of the ECM that are implicated in all phases of tumorigenesis. These molecules, secreted by both the stroma and cancer cells, are crucial signaling mediators that modulate the vital cellular pathways implicated in gene expression, phenotypic versatility, and response to therapy in specific tumor types. Specific inputs from the endocrine and immune systems are some of the characteristics of hormone-dependent cancer pathogenesis. Notably, the mechanisms involved in various aspects of cancer progression are executed in the ECM niche of the TME, and its' PG components crucially mediate these processes including cancer metastasis, angiogenesis, immunobiology, autophagy, and response to therapy. Hormone-dependent cancers exhibit high morbidity and mortality. In spite of advances in therapy, the treatment  of hormone-dependent cancers remains an unmet health need. The tumor microenvironment (TME) exhibits unique characteristics that differ among various tumor types. It is composed of cancerous, non-cancerous, stromal, and immune cells that are surrounded and supported by components of the extracellular matrix (ECM). Therefore, the interactions among cancer cells, stromal cells, and components of the ECM determine cancer progression and response to therapy. Proteoglycans (PGs), hybrid molecules consisting of a protein core to which sulfated glycosaminoglycan chains are bound, are significant components of the ECM that are implicated in all phases of tumorigenesis. These molecules, secreted by both the stroma and cancer cells, are crucial signaling mediators that modulate the vital cellular pathways implicated in gene expression, phenotypic versatility, and response to therapy in specific tumor types. A plethora of deregulated signaling pathways contributes to the growth, dissemination, and angiogenesis of hormone-dependent cancers. Specific inputs from the endocrine and immune systems are some of the characteristics of hormone-dependent cancer pathogenesis. Importantly, the mechanisms involved in various aspects of cancer progression are executed in the ECM niche of the TME, and the PG components crucially mediate these processes.
  • 1.5K
  • 31 Aug 2020
Topic Review
The Fra-1/AP-1 Oncoprotein
Among components of the AP-1 complex, the FOS-family transcription factor Fra-1, encoded by FOSL1, has emerged as a prominent therapeutic target. Fra-1 is overexpressed in most solid tumors, in response to the BRAF-MAPK, Wnt-beta-catenin, Hippo-YAP, IL-6-Stat3, and other major oncogenic pathways. In vitro functional analyses, validated in onco-mouse models and corroborated by prognostic correlations, show that Fra-1-containing dimers control tumor growth and disease progression. Fra-1 participates in key mechanisms of cancer cell invasion, Epithelial-to-Mesenchymal Transition, and metastatic spreading, by driving the expression of EMT-inducing transcription factors, cytokines, and microRNAs.
  • 1.5K
  • 06 May 2023
Topic Review
ROS in the Tumor Microenvironment
Reactive oxygen species (ROS) are important signaling molecules in cancer. The level of ROS will determine physiological effects. While high levels of ROS can cause damage to tissues and cell death, low levels of ROS can have a proliferative effect. ROS are produced by tumor cells but also cellular components that make up the tumor microenvironment (TME).
  • 1.5K
  • 19 Aug 2021
Topic Review
Oncolytic Virotherapy
Some non-pathogenic viruses that do not cause serious illness in humans can efficiently target and kill cancer cells and may be considered candidates for cancer treatment with virotherapy. However, many cancer cells are protected from viruses. An important goal of personalized cancer treatment is to identify viruses that can kill a certain type of cancer cells. To this end, researchers investigate expression patterns of cell entry receptors, which viruses use to bind to and enter host cells.
  • 1.5K
  • 22 Dec 2020
Topic Review
Glioblastoma Organoids
Glioblastoma (GB) is the most lethal primary adult brain tumor. The great number of mutations involved and the aggressiveness of glioblastoma render this type of cancer especially difficult to investigate. Moreover, the lack of reliable GB models, together with its considerable clinical heterogeneity, has impaired a comprehensive investigation of the mechanisms that lead to tumorigenesis, cancer progression, and response to treatments. To address this problem, cerebral organoids have emerged as promising tools to investigate brain biology and to recapitulates the major steps involved in glioblastoma tumorigenesis. Here we exemplify relevant aspects of 3D models of glioblastoma, with a specific focus on organoids and their involvement in basic and translational research.
  • 1.5K
  • 25 Nov 2020
Topic Review
Syndecans and Pancreatic Ductal Adenocarcinoma
Pancreatic Ductal Adenocarcinoma (PDAC) is a fatal disease with poor prognosis because pa-tients rarely express symptoms in initial stages, which prevents early detection and diagnosis. Syndecans, a subfamily of proteoglycans, are involved in many physiological processes includ-ing cell proliferation, adhesion, and migration. Syndecans are physiologically found in many cell types and their interactions with other macromolecules enhance many pathways. In particu-lar, extracellular matrix components, growth factors, and integrins collect the majority of syndecans associations acting as biochemical, physical, and mechanical transducers. Syndecans are transmembrane glycoproteins, but occasionally their extracellular domain can be released from the cell surface by the action of matrix metalloproteinases, converting them into soluble molecules that are capable of binding distant molecules such as extracellular matrix (ECM) components, growth factor receptors, and integrins from other cells.
  • 1.5K
  • 02 Mar 2021
Topic Review
Neutrophil
Neutrophils represent about 50–70% of all white blood cells in the human circulation and are widely recognized as the first line of defense in infectious disease. However, neutrophils also have a clear modulatory role in human diseases such as cancer, respiratory disease, and autoimmunity. Infections and/or any inflammatory signals trigger a rapid influx of neutrophils from the peripheral blood to the inflammatory site, where they can utilize a broad variety of effector functions to.  Neutrophils are well known phagocytic cells, engulfing microorganisms or in case of bigger targets, such as cancer cells, taking “bites” of the membrane in a process called ‘trogocytosis’. Moreover, neutrophils are armed with granules that are loaded with proteases and inflammatory mediators  that are released upon activation. In addition, during a so called ‘oxidative burst’ neutrophils release high levels of  reactive oxygen species (ROS), which can trigger cell death of the target cell. Finally, neutrophils can entrap foreign materials in so called ‘neutrophil extracellular traps’ (NETs), which are mainly composed of neutrophil DNA and Granular contents. The effector functions of neutrophils can be triggered by antibodies that activate  neutrophils by binding to Fc-receptors (FcRs), leading to antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). Although neutrophils are mainly involved in innate immunity, neutrophils contribute to adaptive immune responses. 
  • 1.5K
  • 05 Jan 2021
Topic Review
Natural Blockers of PD-1/PD-L1 Interaction
The limited treatment options for triple-negative breast cancer with brain metastasis (TNBC-BM) have left the door of further drug development for these patients wide open. Although immunotherapy via monoclonal antibodies has shown some promising results in several cancers including TNBC, it cannot be considered the most effective treatment for brain metastasis. This is due to the protective role of the blood–brain barrier (BBB) which limits the entrance of most drugs, especially the bulky ones such as antibodies, to the brain. For a drug to traverse the BBB via passive diffusion, various physicochemical properties should be considered. 
  • 1.5K
  • 11 Jan 2023
Topic Review
Gastroesophageal Adenocarcinoma
The World Health Organization (WHO) classified gastric cancer into tubular, papillary, mucinous, poorly cohesive (including Lauren diffuse type), and mixed variants. 
  • 1.5K
  • 20 Jul 2022
Topic Review
Group 2 Innate Lymphoid Cells
Group 2 Innate Lymphoid Cells (ILC2s) belong to the family of helper ILCs which provide host defense against infectious agents, participate in inflammatory responses and mediate lymphoid organogenesis and tissue repair, mainly at the skin and mucosal level. Based on their transcriptional, phenotypic and functional profile, ILC2s mirror the features of the adaptive CD4+ Th2 cell subset, both contributing to the so-called type 2 immune response. Similar to other ILCs, ILC2s are rapidly activated by signals deriving from tissue and/or other tissue-resident immune cells. The biologic activity of ILCs needs to be tightly regulated in order to prevent them from contributing to severe inflammation and damage in several organs. Indeed, ILC2s display both enhancing and regulatory roles in several pathophysiological conditions, including tumors.
  • 1.5K
  • 29 Apr 2021
Topic Review
Microfluidic Systems and Breast Cancer Metastasis
Microfluidic devices are useful tools in studying biological phenomena involving fluid flow, thin tissue culture, and cell mobility; each of these aspects make microfluidic techniques attractive for studying human breast cancer, which is the most commonly occurring cancer in women and the second most common cancer overall worldwide.
  • 1.5K
  • 15 Feb 2022
Topic Review
Vitamin D arrests cell cycling
Vitamin D is a steroid hormone crucial for bone mineral metabolism. In addition, vitamin D has pleiotropic actions in the body, including anti-cancer actions. These anti-cancer properties observed within in vitro studies frequently report the reduction of cell proliferation by direct alteration of cell cycle regulators which induce cell cycle arrest. The most recurrent reported mode of cell cycle arrest by vitamin D is at the G1/G0 phase of the cell cycle. This arrest is mediated by p21 and p27 upregulation, which results in suppression of cyclin D and E activity which leads to G1/G0 arrest. In addition, vitamin D treatments within in vitro cell lines have observed a reduced C-MYC expression and increased retinoblastoma protein levels that also result in G1/G0 arrest.
  • 1.5K
  • 16 Dec 2020
Topic Review
WNT Signalling in Dental Pathologies
Great efforts have been made over the past decades to discover new therapeutic targets for a big variety of human pathologies. Most of the studies dealing with severe pathological conditions such as cancers and tissue malformations are focused on the role of either widely recognized master controlling genes such as ras and myc or pivotal components of key signalling pathways, among which Wnt and Notch. However, these genes and molecules are fundamental for paired embryogenesis as well as for tissue and organ homeostasis and regeneration, where they regulate cell proliferation, migration, differentiation and apoptosis. The precise timing and localization of their activation are important to ensure the appropriate cellular functions in physiological conditions. Thus, their indiscriminate targeting is not desirable, due to both the high risk of severe side effects and the certainty of broad phenotypic consequences. On the contrary, optimal therapeutic targets should be selected based on their tissue, time and pathology specific roles. Here, we suggest a paradigmatic example of such target molecules that could be represented by the Wnt/b-catenin signalling components Bcl9 and Bcl9l. 
  • 1.5K
  • 05 Nov 2020
Topic Review
Electric Fields for Cancers Treatment
The biological impact of exogenous, alternating electric fields (AEFs) and direct-current electric fields has a long history of study, ranging from effects on embryonic development to influences on wound healing. Tumor treating fields (TTFields) is a form of alternating electric fields (AEF) therapy that is delivered to the tumor via electrodes placed on the skin.
  • 1.5K
  • 16 Jun 2021
Topic Review
Epigenetics and pancreatic cancer progression
Due to the lack of diagnostic biomarkers and high resistance to treatment, pancreatic ductal adenocarcinoma (PDAC) represents one of the most lethal solid tumors with poor survival. Moreover, the metastatic potential of PDAC is extremely high and tumors spread mainly through lymphatic and blood vessels. Although genetic modifications are well defined in PDAC, the role of epigenetics regulations, which secure dynamic response to environmental stimuli, has only recently been recognized. Epigenomic studies revealed that epigenetic changes in oncogenes and tumor suppressor genes were associated with epithelial-mesenchymal transition (EMT) which is responsible for the invasive phenotype of cancer cells and therefore, their metastatic potential. 
  • 1.5K
  • 18 Jan 2021
Topic Review
Spermine in Prostate Cancer
Spermine, a member of polyamines, exists in all organisms and is essential for normal cell growth and function. It is highly expressed in the prostate compared with other organs and is detectable in urine, tissue, expressed prostatic secretions, and erythrocyte. A significant reduction of spermine level was observed in prostate cancer (PCa) tissue compared with benign prostate tissue, and the level of urinary spermine was also significantly lower in men with PCa. Decreased spermine level may be used as an indicator of malignant phenotype transformation from normal to malignant tissue in prostate.
  • 1.5K
  • 25 May 2021
Topic Review
Cryptosporidium and Colon Cancer
The number of cancers attributable to infectious agents represents over 20% of the global cancer burden. The intracellular parasite Cryptosporidium is currently considered one of the major causes of mild and severe diarrhea worldwide. However, less attention has been paid to its tumorigenic potential despite  the high exposure of humans and animals to this ubiquitous parasite and the large number of epidemiological and experimental studies revealing the link between cancer and the presence of this parasite. 
  • 1.5K
  • 13 Dec 2020
Topic Review
Inhibitors Targeting the 80S ribosome
Protein biosynthesis is a vital process for all kingdoms of life. The ribosome is the massive ribonucleoprotein machinery that reads the genetic code, in the form of messenger RNA (mRNA), to produce proteins. The mechanism of translation is tightly regulated to ensure that cell growth is well sustained. In bacteria, the ribosome is a major target of inhibitors, as demonstrated by the high number of small molecules identified to bind to it. In eukaryotes, the design of ribosome inhibitors may be used as a therapy to treat cancer cells, which exhibit higher proliferation rates compared to healthy ones. 
  • 1.5K
  • 28 Sep 2021
Topic Review
Superficial Spindle Cell Mesenchymal Tumors
Superficial spindle cell mesenchymal tumors form a diverse group of lesions with benign and malignant entities that are often very similar clinically and/or histologically. In children, the patient’s age; the lesion site; the presentation as a mass, nodule, or plaque; and the location in the dermis or subcutis are important features that will guide the dermatologist and the pathologist.
  • 1.5K
  • 02 Oct 2021
Topic Review
Benign Prostatic Hyperplasia
The apoptosis machinery is a promising target against benign prostatic hyperplasia (BPH). Inhibitors of apoptosis proteins (IAPs) modulate apoptosis by direct inhibition of caspases. Serenoa Repens (SeR) may be combined with other natural compounds such as Lycopene (Ly) and Selenium (Se) to maximize its therapeutic activity in BPH. We investigated the effects of SeR, Se and Ly, alone or in association, on the expression of four IAPs, cIAP-1, cIAP-2, NAIP and survivin in rats with experimental testosterone-dependent BPH. Moreover, caspase-3, interleukin-6 (IL-6) and prostate specific membrane antigen (PSMA) have been evaluated. Rats were administered, daily, with testosterone propionate (3 mg/kg/sc) or its vehicle for 14 days. Testosterone injected animals (BPH) were randomized to receive vehicle, SeR (25 mg/kg/sc), Se (3 mg/kg/sc), Ly (1 mg/kg/sc) or the SeR-Se-Ly association for 14 days. Animals were sacrificed and prostate removed for analysis. BPH animals treated with vehicle showed unchanged expression of cIAP-1 and cIAP-2 and increased expression of NAIP, survivin, caspase-3, IL-6 and PSMA levels when compared with sham animals. Immunofluorescence studies confirmed the enhanced expression of NAIP and survivin with a characteristic pattern of cellular localization. SeR-Se-Ly association showed the highest efficacy in reawakening apoptosis; additionally, this therapeutic cocktail significantly reduced IL-6 and PSMA levels. The administration of SeR, Se and Ly significantly blunted prostate overweight and growth; moreover, the SeR-Se-Ly association was most effective in reducing prostate enlargement and growth by 43.3% in treated animals. The results indicate that IAPs may represent interesting targets for drug therapy of BPH.
  • 1.5K
  • 01 Nov 2020
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