• cell-cycle inhibitors
• cyclin-dependent kinase 4/6 inhibitors
• prostate cancer
• targeted therapy

• actin
• actin filaments
• actin-binding protein
• cytoskeleton
• prostate cancer

• Androgen receptor
• Filamin A
• TNBC marker
• Triple negative breast cancer

• Humans
• Triple Negative Breast Neoplasms/drug therapy
• Triple Negative Breast Neoplasms/pathology
• Filamins/genetics

• benign prostatic hyperplasia
• clinical value
• inflammasomes
• prostate cancer
• tumor

• Nerve-growth factor
• Perineural invasion
• Prostate cancer
• Tumor microenvironment

• 2017EKMFTN_002 Ministry of Scientific and Technological Development, Higher Education and Information Society
• Progetto di Ricerca Finalizzata RF-2019-12368937 Regione Siciliana
• PATG.Rice.Base.GiovaniRicercatori2022.IDEA Università degli Studi della Campania Luigi Vanvitelli

• endocrine therapies
• altered metabolism
• cell specific effects
• mouse models
• steroid hormones
• tumor microenvironment

• Humans
• Male
• Androgens
• Prostatic Neoplasms/drug therapy
• Prostatic Neoplasms/metabolism
• Androgen Antagonists
• Estrogens/metabolism
• Gonadal Steroid Hormones/metabolism
• Orchiectomy

• PI3K inhibitors
• Vps34
• breast cancer
• cell growth
• cell migration
• invasiveness
• p110δ
• phosphoinositide 3-kinase (PI3K)
• signalling
• three-dimensional (3D) tumour spheroids

• Breast Neoplasms/metabolism
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Class III Phosphatidylinositol 3-Kinases/antagonists & inhibitors
• Class Ia Phosphatidylinositol 3-Kinase
• Female
• Humans
• MCF-7 Cells
• Phosphoinositide-3 Kinase Inhibitors/pharmacology
• Signal Transduction
• Triple Negative Breast Neoplasms/drug therapy
• Triple Negative Breast Neoplasms/metabolism

As a new and ubiquitous trace organic pollutant, endocrine-disrupting compounds (EDCs) can cause endocrine-disrupting effects on organisms even at low levels. However, little information is available on the resource and assessment of EDC risks in the water environment. The study area was selected based on the paucity of information on the pollution status of inland lakes. Wuhan has numerous and diverse types of lakes which receive micropollutants from different pathways. In this study, the spatial distribution, occurrence, quantity and ecological risks of EDCs in 12 lakes were investigated. Five EDCs, including 17-alpha-ethinylestradiol (17α-EE₂), estrone (E₁), β-estradiol (β-E₂), estriol (E₃) and bisphenol A (BPA) were detected in surface waters. The distribution of EDC content in the lakes was ordered as follows: exurban zone < suburban area < urban areas. The pollution sources in remote lakes mainly included agricultural and aquaculture wastewater, while those in suburban and urban areas included domestic or industrial wastewater. Areas with higher EDC content were frequently related to agricultural activities, aquaculture water or dense populations. Water quality parameters, including dissolved oxygen, pH and water temperature, were significantly related to the occurrence and distribution of EDCs in the lakes. Risk assessment demonstrated that the occurrence of EDCs posed minimum to medium risk to aquatic organisms in the lakes. The results showed that the lakes faced a threat hormone pollution though it was at lower doses and, thus, the ecological risk of EDCs should be considered in future environmental policies and decisions in China.

Androgen exerts its functions by binding with an androgen receptor (AR). It can activate many signaling pathways that are important to the progression of castration-resistant prostate cancer (CRPC). Here, we characterized the rapid proteomic changes seen at 5, 15, 30, and 60 min after the androgen treatment of VCaP cells via the tandem mass tag (TMT) labeling strategy. A total of 5529 proteins were successfully identified and quantified. Dynamic time profiling of protein expression patterns allowed us to identify five protein clusters involved in various stages of androgen-initiated signal transmission and processing. More details of protein functions and localization patterns, and our elucidation of an AR-interacting protein network, were obtained. Finally, we validated the expression level of AR-regulated proteins known to be significantly regulated in CRPC patients using the mouse xenograft model and patient samples. Our work offers a systematic analysis of the rapid proteomic changes induced by androgen and provides a global view of the molecular mechanisms underlying CRPC progression.

The tumour micro-environment (TME) plays a crucial role in the onset and progression of prostate cancer (PCa). Here we studied the potential of a selected panel of TME-markers to predict clinical recurrence (CLR) in PCa. Patient cohorts were matched for the presence or absence of CLR 5 years post-prostatectomy. Tissue micro-arrays (TMA) were composed with both prostate non-tumour (PNT) and PCa tissue and subsequently processed for immunohistochemistry (IHC). The IHC panel included markers for cancer activated fibroblasts (CAFs), blood vessels and steroid hormone receptors ((SHR): androgen receptor (AR), progesterone receptor (PR) and estrogen receptor (ER)). Stained slides were digitalised, selectively annotated and analysed for percentage of marker expression with standardized and validated image analysis algorithms. A univariable analysis identified several TME markers with significant impact on CR: expression of CD31 (vascular marker) in PNT stroma, expression of alpha smooth muscle actin (αSMA) in PCa stroma, and PR expression ratio between PCa stroma and PNT stroma. A multivariable model, which included CD31 expression (vascular marker) in PNT stroma and PR expression ratio between PCa stroma and PNT stroma, could significantly stratify patients for CLR, with the identification of a low risk and high-risk subgroup. If validated and confirmed in an independent prospective series, this subgroup might have clinical potential for PCa patient stratification.

• Actins/metabolism
• Aged
• Biomarkers, Tumor/metabolism
• Humans
• Male
• Middle Aged
• Neoplasm Recurrence, Local/metabolism
• Neoplasm Recurrence, Local/pathology
• Neoplasm Recurrence, Local/surgery
• Neoplasm Staging
• Platelet Endothelial Cell Adhesion Molecule-1/metabolism
• Prospective Studies
• Prostatectomy
• Prostatic Neoplasms/metabolism
• Prostatic Neoplasms/pathology
• Prostatic Neoplasms/surgery
• Receptors, Androgen/metabolism
• Receptors, Estrogen/metabolism
• Receptors, Progesterone/metabolism
• Tissue Array Analysis/methods
• Tumor Microenvironment

• CDK4/6 inhibitors
• combination therapy
• genomics
• metastatic castrate-resistant prostate cancer

• dietary flavonoids
• endocrine
• estrogenic
• flaxseeds
• health
• isoflavones
• lignans
• polyphenols
• soy
• stages of life

• Adult
• Child
• Diet
• Female
• Gonadal Steroid Hormones/metabolism
• Heart Disease Risk Factors
• Hormones/metabolism
• Humans
• Hypothyroidism/epidemiology
• Isoflavones/administration & dosage
• Isoflavones/adverse effects
• Lignans/administration & dosage
• Lignans/adverse effects
• Longevity/drug effects
• Male
• Non-alcoholic Fatty Liver Disease/epidemiology
• Phytoestrogens/administration & dosage
• Phytoestrogens/adverse effects
• Postmenopause/drug effects
• Pregnancy
• Premenopause/drug effects
• Glycine max
• Vegetables

• breast cancer
• chemotherapy neoadjuvant
• gene expression
• stromal cells

Breast cancer (BC) is the most common cancer among women, and current available therapies often have high success rates. Nevertheless, BC might acquire drug resistance and sometimes relapse. Current knowledge about the most aggressive forms of BC points to the role of specific cells with stem properties located within BC, the so-called “BC stem cells” (BCSCs). The role of BCSCs in cancer formation, growth, invasiveness, therapy resistance and tumor recurrence is becoming increasingly clear. The growth and metastatic properties of BCSCs are regulated by different pathways, which are only partially known. Sex steroid receptors (SSRs), which are involved in BC etiology and progression, promote BCSC proliferation, dedifferentiation and migration. However, in the literature, there is incomplete information about their roles. Particularly, there are contrasting conclusions about the expression and role of the classical BC hormonal biomarkers, such as estrogen receptor alpha (ERα), together with scant, albeit promising information concerning ER beta (ERβ) and androgen receptor (AR) properties that control different transduction pathways in BCSCs. In this review, we will discuss the role that SRs expressed in BCSCs play to BC progression and recurrence and how these findings have opened new therapeutic possibilities.

• Breast cancer
• Steroids
• Sex steroid receptors
• Cancer stem cells
• Therapeutic implications

Prostate cancer is the most prevalent non-skin cancer in men and is the leading cause of cancer-related death. Early detection of prostate cancer is largely determined by a widely used prostate specific antigen (PSA) blood test and biopsy is performed for definitive diagnosis. Prostate cancer is asymptomatic in the early stage of the disease, comprises of diverse clinico-pathologic and progression features, and is characterized by a large subset of the indolent cancer type. Therefore, it is critical to develop an individualized approach for early detection, disease stratification (indolent vs. aggressive), and prediction of treatment response for prostate cancer. There has been remarkable progress in prostate cancer biomarker discovery, largely through advancements in genomic technologies. A rich array of prostate cancer diagnostic and prognostic tests has emerged for serum (4K, phi), urine (Progensa, T2-ERG, ExoDx, SelectMDx), and tumor tissue (ConfirmMDx, Prolaris, Oncoytype DX, Decipher). The development of these assays has created new opportunities for improving prostate cancer diagnosis, prognosis, and treatment decisions. While opening exciting opportunities, these developments also pose unique challenges in terms of selecting and incorporating these assays into the continuum of prostate cancer patient care.

• diagnosis
• molecular biomarkers
• prognosis
• prostate cancer

• Akt
• CSF-2
• ERK1/2
• MSCs
• differentiation
• growth
• migration
• stemness

• biomarkers
• metabolites
• metabolomics
• profiling
• prostate cancer
• systematic review

• 22904 Cancer Research UK

• EMT
• apoptosis
• estrogens
• migration
• prostate cancer
• somatostatin analogs
• somatostatin receptors

• Ministero dell’Istruzione, dell’Università e della Ricerca

• Glioblastomas
• androgen receptor
• cell invasion
• cell migration
• cell proliferation
• testosterone

Prostate cancer is the most common cancer among men. Green tea consumption is reported to play an important role in the prevention of carcinogenesis in many types of malignancies, including prostate cancer; however, epidemiological studies show conflicting results regarding these anti-cancer effects. In recent years, in addition to prevention, many investigators have shown the efficacy and safety of green tea polyphenols and combination therapies with green tea extracts and anti-cancer agents in in vivo and in vitro studies. Furthermore, numerous studies have revealed the molecular mechanisms of the anti-cancer effects of green tea extracts. We believe that improved understanding of the detailed pathological roles at the molecular level is important to evaluate the prevention and treatment of prostate cancer. Therefore, in this review, we present current knowledge regarding the anti-cancer effects of green tea extracts in the prevention and treatment of prostate cancer, with a particular focus on the molecular mechanisms of action, such as influencing tumor growth, apoptosis, androgen receptor signaling, cell cycle, and various malignant behaviors. Finally, the future direction for the use of green tea extracts as treatment strategies in patients with prostate cancer is introduced.

• anti-cancer effects
• green tea
• molecular mechanism
• prostate cancer

Prostate cancer (PCa) is a major health problem in males. Metastasis-associated with lung adenocarcinoma transcript-1 (MALAT1), which is overexpressed in PCa tissue, is associated with physiological and pathological conditions of PCa. M2 macrophages are major immune cells abundant in the tumor microenvironment. However, it remains unknown whether M2 macrophages are involved in the effects or not, and molecular mechanisms of MALAT1 on PCa progression have not yet been comprehensively explored. Here we reported that, M2 macrophages (PMA/IL-4 treated THP1) induced MALAT1 expression in PCa cell lines. Knockdown MALAT1 expression level in PCa cell lines inhibited cellular proliferation, invasion, and tumor formation. Further mechanistic dissection revealed that M2 macrophages secreted IL-8 was sufficient to drive up MALAT1 expression level via activating STAT3 signaling pathway. Additional chromatin immunoprecipitation (ChIP) and luciferase reporter assays displayed that STAT3 could bind to the MALAT1 promoter region and transcriptionally stimulate the MALAT1 expression. In summary, our present study identified the IL-8/STAT3/MALAT1 axis as key regulators during prostate tumorigenesis and therefore demonstrated a new mechanism for the MALAT1 transcriptional regulation.

• IL-8
• M2 macrophage
• MALAT1
• STAT3
• prostate cancer

• androgen receptor
• breast cancer
• intracrinology
• non-genomic signaling
• steroids

The androgen receptor (AR) is a ligand-dependent transcription factor that promotes prostate cancer (PC) cell growth through control of target gene expression. This report suggests that Canopy FGF signaling regulator 2 (CNPY2) controls AR protein levels in PC cells. We found that AR was ubiquitinated by an E3 ubiquitin ligase, myosin regulatory light chain interacting protein (MYLIP) and then degraded through the ubiquitin-proteasome pathway. CNPY2 decreased the ubiquitination activity of MYLIP by inhibition of interaction between MYLIP and UBE2D1, an E2 ubiquitin ligase. CNPY2 up-regulated gene expression of AR target genes such as KLK3 gene which encodes the prostate specific antigen (PSA) and promoted cell growth of PC cells. The cell growth inhibition by CNPY2 knockdown was rescued by AR overexpression. Furthermore, positive correlation of expression levels between CNPY2 and AR/AR target genes was observed in tissue samples from human prostate cancer patients. Together, these results suggested that CNPY2 promoted cell growth of PC cells by inhibition of AR protein degradation through MYLIP-mediated AR ubiquitination.

• AR
• CNPY2
• MYLIP
• prostate cancer
• protein degradation

A major challenge in clinical management of prostate cancer (PC) is to limit tumor growth and prevent metastatic spreading. Considerable efforts have been made to discover new compounds for PC therapy and recent years have seen promising progress in this field. Pharmacological approaches have been designed to achieve benefits in PC treatment and avoid the negative side effects resulting from administration of antagonists or agonists or new drugs. Nonetheless, the currently available therapies frequently induce resistance and PC progresses toward castration-resistant forms that can be caused by the androgen receptor reactivation and/or mutations, or derangement of signaling pathways. Preclinical and clinical findings have also shown that other nuclear receptors are frequently altered in PC. In this review, we focus on the role of estradiol/estradiol receptor (ER) axis, which controls PC growth and progression. Selective targeting of ER subtypes (α or β) may be an attractive way to limit the growth and spreading of prostatic cancer cells.

• castrate resistant prostate cancer
• estradiol
• estradiol receptors
• new drugs
• prostate cancer

• Src
• TrkA
• cell cycle
• cytoskeleton changes
• filamin A

Prostate cancer is one of the most commonly diagnosed cancers in men, and androgen deprivation therapy still represents the primary treatment for prostate cancer patients. This approach, however, frequently fails and patients develop castration-resistant prostate cancer, which is almost untreatable.

Cancer cells are characterized by a hierarchical organization, and stem/progenitor cells are endowed with tumor-initiating activity. Accumulating evidence indicates that prostate cancer stem cells lack the androgen receptor and are, indeed, resistant to androgen deprivation therapy. In contrast, these cells express classical (α and/or β) and novel (GPR30) estrogen receptors, which may represent new putative targets in prostate cancer treatment.

In the present review, we discuss the still-debated mechanisms, both genomic and non-genomic, by which androgen and estradiol receptors (classical and novel) mediate the hormonal control of prostate cell stemness, transformation, and the continued growth of prostate cancer. Recent preclinical and clinical findings obtained using new androgen receptor antagonists, anti-estrogens, or compounds such as enhancers of androgen receptor degradation and peptides inhibiting non-genomic androgen functions are also presented. These new drugs will likely lead to significant advances in prostate cancer therapy.

• GPR30, stem cells
• androgen receptor
• estradiol receptors
• prostate cancer