scholarly journals Prognostic Role of Androgen Receptor Expression in HER2+ Breast Carcinoma Subtypes

Biomedicines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 164
Author(s):  
Sandra Orrù ◽  
Emanuele Pascariello ◽  
Giovanni Sotgiu ◽  
Daniela Piras ◽  
Laura Saderi ◽  
...  
Keyword(s):  
Tumor Size ◽  
Molecular Mechanisms ◽  
Histological Grade ◽  
Receptor Expression ◽  
Immunohistochemical Method ◽  
Prognostic Impact ◽  
Her2 Breast Cancer ◽  
High Prevalence ◽  
Expression Evaluation

HER2+ breast cancer (BC) is an aggressive subtype representing a genetically and biologically heterogeneous group of tumors resulting in variable prognosis and treatment response to HER2-targeted therapies according to estrogen (ER) and progesterone receptor (PR) expression. The relationship with androgen receptors (AR), a member of the steroid hormone’s family, is unwell known in BC. The present study aims to evaluate the prognostic impact of AR expression in HER2+ BC subtypes. A total of 695 BCs were selected and reviewed, AR, ER, PR and HER2 expression in tumor cells were examined by immunohistochemical method, and the SISH method was used in case of HER2 with equivocal immunohistochemical score (2+). A high prevalence of AR expression (91.5%) in BC HER+ was observed, with minimal differences between luminal and non-luminal tumor. According to steroid receptor expression, tumors were classified in four subgroups, including BC luminal and non-luminal HER2+ expressing or not AR. The luminal BC HER2 + AR+ was associated with lower histological grade, lower tumor size, higher PR expression and lower HER2 intensity of expression (2+). Also, the non-luminal tumors AR+ showed lower tumor size and lower prognostic stage but frequently higher grade and higher HER2 intensity of expression (3+). These findings should suggest a different progression of luminal and non-luminal tumors, both expressing AR, and allow us to speculate that the molecular mechanisms of AR, involved in the biology of BC HER2 + AR+, differ in relation to ER and PR expression. Moreover, AR expression may be a useful predictor of prognosis for overall survival (OS) in HER2+ BC subtypes. Our findings suggest that AR expression evaluation in clinical practice could be utilized in clinical oncology to establish different aggressiveness in BC HER2+ subtypes.

scholarly journals Polypeptide-GalNAc-Transferase-13 Shows Prognostic Impact in Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5616
Author(s):  
Eugenia Fernandez ◽  
Luis Ubillos ◽  
Nabila Elgul ◽  
María Florencia Festari ◽  
Daniel Mazal ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Nodes ◽  
Cancer Biology ◽  
Molecular Mechanisms ◽  
Health Concern ◽  
Breast Cancer Cell Lines ◽  
Prognostic Impact ◽  
Metastatic Lymph Nodes ◽  
Metastatic Lymph

Breast cancer is a public health concern and is currently the fifth cause of mortality worldwide. Identification of different biological subtypes is essential for clinical management; therefore, the role of pathologists is essential and useful tools for immunohistochemistry diagnosis are needed. Polypeptide-GalNAc-transferases are emerging novel biomarkers related to cancer behavior and GalNAc-T13, correlated with aggressiveness in some tumors, is an interesting candidate. Few monoclonal antibodies reacting with native proteins, and not affected by fixation and paraffin embedding, have been reported. The aim of this work was to develop a useful monoclonal antibody anti-GalNAc-T13 and to assess its potential significance in breast cancer diagnosis. We evaluated 6 human breast cancer cell lines, 338 primary breast tumors and 48 metastatic lymph nodes and looked for clinical significance correlating GalNAc-T13 expression with patients’ clinical features and survival. We found high GalNAc-T13 expression in 43.8% of the cases and observed a significant higher expression in metastatic lymph nodes, correlating with worse overall survival. We hypothesized several possible molecular mechanisms and their implications. We conclude that GalNAc-T13 may be a novel biomarker in breast cancer, useful for routine pathological diagnosis. Elucidation of molecular mechanisms related to aggressiveness should contribute to understand the role of GalNAc-T13 in breast cancer biology.

Biological mechanisms that trigger breast cancer (BC) tumor progression are molecular subtype dependent

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 10581-10581 ◽  
Author(s):  
C. Sotiriou ◽  
C. Desmedt ◽  
B. Haibe-Kains ◽  
A. Harris ◽  
D. Larsimont ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
Clinical Outcome ◽  
Tumor Size ◽  
Tumor Invasion ◽  
Molecular Mechanisms ◽  
Molecular Subtypes ◽  
Proliferation Index ◽  
P Value ◽  
Prognostic Impact

10581 Background: We have recently developed several gene expression indices related to hallmarks of breast cancer involving various biological processes such as tumor invasion, impairment of immune response, sustained angiogenesis, evasion of apoptosis and self- sufficiency in growth signal, and investigated their impact on clinical outcome. Here, we aim to refine our biological understanding and the prognostic impact of these indices according to the previously described molecular subtypes based on the estrogen (ER) and ERBB2 receptors. Methods: Each of these indices were developed in a series of 581 BC samples and then computed on several publicly available microarray studies totaling over 2100 BC patients. Multivariate analyses were used to study the dependency patterns between these indices, the molecular subtypes and their impact on survival. Results: ER-/ERBB2- and ERBB2+ subgroups were significantly associated with high expression levels of the proliferation, tumor invasion, angiogenesis and immune response indices. Multivariate analysis showed that in the ER+/ERBB2- subgroup, only tumor size and the proliferation and tumor invasion indices were significantly associated with clinical outcome, with the proliferation index having the largest HR and most significant p-value (HR 3.25; CI 2.31–4.56; p=1.2 10-11). In contrast, in the ER-/ERBB2- subgroup, only tumor size (HR 2.08; CI 1.14–3.81; p=0.01) and immune response index (HR 0.66; CI 0.46–0.95; p=0.02) were associated with prognosis whereas in the ERBB2+ tumors only nodal status (HR 3.40; CI 0.96–12.10; p=0.05) and tumor invasion index (HR 3.03; CI 1.32–6.95; p=0.009) showed significant association with survival. Of interest, proliferation index lost its significance as almost all ER- /ERBB2- and ERBB2 + tumors showed high proliferation levels. Conclusions: Although proliferation seems to be the strongest parameter predicting clinical outcome in ER+/ERBB2- subtype, immune response and tumor invasion appear to be the main molecular mechanisms associated with prognosis in the ER-/ERBB2- and ERBB2+ subgroups respectively. Defining these clinico-genomic models in the specific molecular subgroups will be the key to success for personalized medicine. No significant financial relationships to disclose.

scholarly journals lncRNA SNHG15 Induced by SOX12 Promotes the Tumorigenic Properties and Chemoresistance in Cervical Cancer via the miR-4735-3p/HIF1a Pathway

2022 ◽  
Vol 2022 ◽  
pp. 1-15
Author(s):  
Jiang Yang ◽  
Mei Yang ◽  
Huabing Lv ◽  
Min Zhou ◽  
Xiaogang Mao ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Molecular Mechanisms ◽  
Therapeutic Strategies ◽  
Luciferase Reporter ◽  
Major Health ◽  
Tumor Tissues ◽  
High Prevalence ◽  
Reporter Assays

Cervical cancer (CC) is one of the most common malignancies in females, with high prevalence and mortality globally. Despite advances in diagnosis and therapeutic strategies developed in recent years, CC is still a major health burden worldwide. The molecular mechanisms underlying the development of CC need to be understood. In this study, we aimed to demonstrate the role of lncRNA SNHG15 in CC progression. Using qRT-PCR, we determined that lncRNA SNHG15 is highly expressed in CC tumor tissues and cells. lncRNA SNHG15 knockdown also reduces the tumorigenic properties of CC in vitro, as determined using the MTT, EdU, flow cytometry, and transwell assays. Using bioinformatics analysis, RNA pull-down, ChIP, and luciferase reporter assays, we verified the molecular mechanisms of lncRNA SNHG15 in CC progression and found that lncRNA SNHG15 expression in CC cells is transcriptionally regulated by SOX12; moreover, lncRNA SNHG15 promotes CC progression via the miR-4735-3p/HIF1a axis. This study can provide a potential target for CC diagnosis or therapeutic strategies in the future.

scholarly journals The role of the AR/ER ratio in ER-positive breast cancer patients

2018 ◽  
Vol 25 (3) ◽  
pp. 163-172 ◽  
Author(s):  
Nelson Rangel ◽  
Milena Rondon-Lagos ◽  
Laura Annaratone ◽  
Simona Osella-Abate ◽  
Jasna Metovic ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Histological Grade ◽  
Molecular Characteristics ◽  
Prognostic Impact ◽  
Breast Cancer Patients ◽  
Disease Free Interval ◽  
Hazard Ratios ◽  
Er Positive ◽  
Independent Marker

The significance of androgen receptor (AR) in breast cancer (BC) management is not fully defined, and it is still ambiguous how the level of AR expression influences oestrogen receptor-positive (ER+) tumours. The aim of the present study was to analyse the prognostic impact of AR/ER ratio, evaluated by immunohistochemistry (IHC), correlating this value with clinical, pathological and molecular characteristics. We retrospectively selected a cohort of 402 ER+BC patients. On each tumour, IHC analyses for AR, ER, PgR, HER2 and Ki67 were performed and AR+ cases were used to calculate the AR/ER value. A cut-off of ≥2 was selected using receiver-operating characteristic (ROC) curve analyses. RNA from 19 cases with AR/ER≥2 was extracted and used for Prosigna-PAM50 assays. Tumours with AR/ER≥2 (6%) showed more frequent metastatic lymph nodes, larger size, higher histological grade and lower PgR levels than cases with AR/ER<2. Multivariate analysis confirmed that patients with AR/ER≥2 had worse disease-free interval (DFI) and disease-specific survival (DSS) (hazard ratios (HR) = 4.96 for DFI and HR = 8.69 for DSS, bothP ≤ 0.004). According to the Prosigna-PAM50 assay, 63% (12/19) of these cases resulted in intermediate or high risk of recurrence categories. Additionally, although all samples were positive for ER assessed by IHC, the molecular test assigned 47.4% (9/19) of BCs to intrinsic non-luminal subtypes. In conclusion, the AR/ER ratio ≥2 identifies a subgroup of patients with aggressive biological features and may represent an additional independent marker of worse BC prognosis. Moreover, the Prosigna-PAM50 results indicate that a significant number of cases with AR/ER≥2 could be non-luminal tumours.

scholarly journals Leptin and Cancer: Updated Functional Roles in Carcinogenesis, Therapeutic Niches, and Developments

2021 ◽  
Vol 22 (6) ◽  
pp. 2870
Author(s):  
Tsung-Chieh Lin ◽  
Michael Hsiao
Keyword(s):  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Leptin Receptor ◽  
Biological Effects ◽  
Prognostic Significance ◽  
Cell Types ◽  
Receptor Expression ◽  
Specific Cell ◽  
Signaling Axis

Leptin is an obesity-associated adipokine that is known to regulate energy metabolism and reproduction and to control appetite via the leptin receptor. Recent work has identified specific cell types other than adipocytes that harbor leptin and leptin receptor expression, particularly in cancers and tumor microenvironments, and characterized the role of this signaling axis in cancer progression. Furthermore, the prognostic significance of leptin in various types of cancer and the ability to noninvasively detect leptin levels in serum samples have attracted attention for potential clinical applications. Emerging findings have demonstrated the direct and indirect biological effects of leptin in regulating cancer proliferation, metastasis, angiogenesis and chemoresistance, warranting the exploration of the underlying molecular mechanisms to develop a novel therapeutic strategy. In this review article, we summarize and integrate transcriptome and clinical data from cancer patients together with the recent findings related to the leptin signaling axis in the aforementioned malignant phenotypes. In addition, a comprehensive analysis of leptin and leptin receptor distribution in a pancancer panel and in individual cell types of specific organs at the single-cell level is presented, identifying those sites that are prone to leptin-mediated tumorigenesis. Our results shed light on the role of leptin in cancer and provide guidance and potential directions for further research for scientists in this field.

scholarly journals HIF1α in aortic aneurysms and beyond

2017 ◽  
Vol 131 (7) ◽  
pp. 621-623
Author(s):  
Tomoki Hashimoto ◽  
Victor Rizzo
Keyword(s):  
Vessel Wall ◽  
Molecular Mechanisms ◽  
Hypoxia Inducible Factor ◽  
Aortic Aneurysms ◽  
Endogenous Inhibitors ◽  
Abdominal Aortic ◽  
High Prevalence ◽  
Basic Studies ◽  
New Discovery

Abdominal aortic aneurysm (AAA) is a permanent expansion of the vessel wall with a high prevalence in those 65 years of age and older. Aneurysms are prone to dissection and rupture that carry a mortality rate of over 85%. Currently, surgical repair is the only option to treat this disease. The need to intervene prior to these events has set off a flurry of basic studies in an effort to understand the cellular and molecular mechanisms that govern AAA formation, progression and rupture. In the present study, the role of myeloid cells in contributing to AAA development has been confirmed. More specifically, the transcription factor, hypoxia-inducible factor-1α (HIF1α), was demonstrated to be a necessary component for regulating the expression of extracellular matrix modifying enzymes and their endogenous inhibitors in these cells. This new discovery may lead to therapeutic targets to prohibit the degradation and weakening of the vessel wall with the hope of limiting AAA formation and/or growth.

scholarly journals CHRONIC ENDOMETRITIS AS A СAUSE OF DISORDERS OF THE FEMALE REPRODUCTIVE FUNCTION

2015 ◽  
pp. 9-16
Author(s):  
Yu. A. Lyzikova
Keyword(s):  
Risk Factors ◽  
Reproductive Function ◽  
Receptor Expression ◽  
Immunohistochemical Method ◽  
Main Role ◽  
Reproductive Disorders ◽  
Local Immunity ◽  
Chronic Endometritis ◽  
Inflammatory Processes

The review deals with the main role of chronic endometritis in the genesis of disorders of the female reproductive function and reveals the etiologic risk factors for the development and starting mechanism of chronic inflammatory processes in the endometrium, features of the pathogenesis and clinical picture of chronic endometritis. The work shows the importance of diagnosis of chronic endometritis with immunohistochemical method, reasonability of immunohistochemical research for the assessment of receptor expression and expressiveness of local immunity in the endometrium, the necessity of detection of fertility alpha-2-microglobulin (AMGF) protein for prediction of reproductive disorders.

Processes exacerbating apoptosis in non-alcoholic steatohepatitis

2019 ◽  
Vol 133 (22) ◽  
pp. 2245-2264 ◽  
Author(s):  
Marta B. Afonso ◽  
Rui E. Castro ◽  
Cecília M. P. Rodrigues
Keyword(s):  
Molecular Mechanisms ◽  
Health Concern ◽  
Alcoholic Fatty Liver ◽  
Intrinsic Signals ◽  
Alcoholic Steatohepatitis ◽  
Significant Public Health Concern ◽  
High Prevalence ◽  
Significant Public Health ◽  
Alcoholic Fatty Liver Disease

Abstract Non-alcoholic fatty liver disease (NAFLD) is a significant public health concern, owing to its high prevalence, progressive nature and lack of effective medical therapies. NAFLD is a complex and multifactorial disease involving the progressive and concerted action of factors that contribute to the development of liver inflammation and eventually fibrosis. Here, we summarize fundamental molecular mechanisms underlying the pathogenesis of non-alcoholic steatohepatitis (NASH), how they are interrelated and possible translation to clinical applications. We focus on processes triggering and exacerbating apoptotic signalling in the liver of NAFLD patients and their metabolic and pathological implications. Indeed, liver injury and inflammation are cardinal histopathological features of NASH, a duo in which derailment of apoptosis is of paramount importance. In turn, the liver houses a very high number of mitochondria, crucial metabolic unifiers of both extrinsic and intrinsic signals that converge in apoptosis activation. The role of lifestyle options is also dissected, highlighting the management of modifiable risk factors, such as obesity and harmful alcohol consumption, influencing apoptosis signalling in the liver and ultimately NAFLD progression. Integrating NAFLD-associated pathologic mechanisms in the cell death context could provide clues for a more profound understating of the disease and pave the way for novel rational therapies.

Endometriosis: disease pathophysiology and the role of prostaglandins

2007 ◽  
Vol 9 (2) ◽  
pp. 1-20 ◽  
Author(s):  
Meng-Hsing Wu ◽  
Yutaka Shoji ◽  
Pei-Chin Chuang ◽  
Shaw-Jenq Tsai
Keyword(s):  
Chronic Pelvic Pain ◽  
Molecular Mechanisms ◽  
Modern Society ◽  
Reproductive Age ◽  
Health Concern ◽  
Public Health Concern ◽  
Reproductive Age Women ◽  
High Prevalence

Endometriosis is considered to be a polygenic disease with a complex, multifactorial aetiology that affects about 10% of women in the reproductive age. Women with endometriosis have symptoms that include chronic pelvic pain, dysmenorrhoea and dyspareunia, significantly reducing their quality of life. Endometriosis is also the primary cause of infertility in women, with the prevalence rate ranging from 20% to 50%. The high prevalence and severe outcomes of this disease have made it a major public health concern in modern society. Currently, the mechanism(s) responsible for the initiation and promotion of this disease remains obscure. In this review, we focus on the expression, regulation and action of prostaglandins in the cellular and molecular mechanisms that contribute to the development and/or maintenance of endometriosis.

scholarly journals The Role of Glucocorticoid Receptor Signaling in Bladder Cancer Progression

Cancers ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 484 ◽  
Author(s):  
Hiroki Ide ◽  
Satoshi Inoue ◽  
Hiroshi Miyamoto
Keyword(s):  
Bladder Cancer ◽  
Glucocorticoid Receptor ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Receptor Expression ◽  
Receptor Signaling ◽  
Castration Resistant Prostate Cancer ◽  
And Function

Previous preclinical studies have indicated that the activation of glucocorticoid receptor signaling results in inhibition of the growth of various types of tumors. Indeed, several glucocorticoids, such as dexamethasone and prednisone, have been prescribed for the treatment of, for example, hematological malignancies and castration-resistant prostate cancer. By contrast, the role of glucocorticoid-mediated glucocorticoid receptor signaling in the progression of bladder cancer remains far from being fully understood. Nonetheless, emerging evidence implies its unique functions in urothelial cancer cells. Moreover, the levels of glucocorticoid receptor expression have been documented to significantly associate with the prognosis of patients with bladder cancer. This review summarizes the available data suggesting the involvement of glucocorticoid-mediated glucocorticoid receptor signaling in urothelial tumor outgrowth and highlights the potential underlying molecular mechanisms. The molecules/pathways that contribute to modulating glucocorticoid receptor activity and function in bladder cancer cells are also discussed.

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