scholarly journals The Role of PARPs in Inflammation—and Metabolic—Related Diseases: Molecular Mechanisms and Beyond

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1047 ◽  
Author(s):  
Ke ◽  
Wang ◽  
Zhang ◽  
Zhong ◽  
Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cardiovascular Disease ◽  
Ovarian Cancer ◽  
Molecular Mechanisms ◽  
Parp Inhibition ◽  
Biological Processes ◽  
Post Translational Modification ◽  
Cancer Breast ◽  
Promising Strategy

Poly(ADP-ribosyl)ation (PARylation) is an essential post-translational modification catalyzed by poly(ADP-ribose) polymerase (PARP) enzymes. Poly(ADP-ribose) polymerase 1 (PARP1) is a well-characterized member of the PARP family. PARP1 plays a crucial role in multiple biological processes and PARP1 activation contributes to the development of various inflammatory and malignant disorders, including lung inflammatory disorders, cardiovascular disease, ovarian cancer, breast cancer, and diabetes. In this review, we will focus on the role and molecular mechanisms of PARPs enzymes in inflammation- and metabolic-related diseases. Specifically, we discuss the molecular mechanisms and signaling pathways that PARP1 is associated with in the regulation of pathogenesis. Recently, increasing evidence suggests that PARP inhibition is a promising strategy for intervention of some diseases. Thus, our in-depth understanding of the mechanism of how PARPs are activated and how their signaling downstream effecters can provide more potential therapeutic targets for the treatment of the related diseases in the future is crucial.

scholarly journals The Emerging Role of Extracellular Vesicles in Endocrine Resistant Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1160
Author(s):  
Giusi La Camera ◽  
Luca Gelsomino ◽  
Amanda Caruso ◽  
Salvatore Panza ◽  
Ines Barone ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Extracellular Vesicles ◽  
Molecular Mechanisms ◽  
Endocrine Resistance ◽  
Disease Recurrence ◽  
Estrogen Receptor Α ◽  
Research Area ◽  
Tumor Evolution

Breast cancer is the most common solid malignancy diagnosed in females worldwide, and approximately 70% of these tumors express estrogen receptor α (ERα), the main biomarker of endocrine therapy. Unfortunately, despite the use of long-term anti-hormone adjuvant treatment, which has significantly reduced patient mortality, resistance to the endocrine treatments often develops, leading to disease recurrence and limiting clinical benefits. Emerging evidence indicates that extracellular vesicles (EVs), nanosized particles that are released by all cell types and responsible for local and systemic intercellular communications, might represent a newly identified mechanism underlying endocrine resistance. Unraveling the role of EVs, released by transformed cells during the tumor evolution under endocrine therapy, is still an open question in the cancer research area and the molecular mechanisms involved should be better defined to discover alternative therapeutic approaches to overcome resistance. In this review, we will provide an overview of recent findings on the involvement of EVs in sustaining hormonal resistance in breast cancer and discuss opportunities for their potential use as biomarkers to monitor the therapeutic response and disease progression.

scholarly journals miR-146a is a significant brake on autoimmunity, myeloproliferation, and cancer in mice

2011 ◽  
Vol 208 (6) ◽  
pp. 1189-1201 ◽  
Author(s):  
Mark P. Boldin ◽  
Konstantin D. Taganov ◽  
Dinesh S. Rao ◽  
Lili Yang ◽  
Jimmy L. Zhao ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Immune Cell ◽  
Myeloid Cell ◽  
Genetically Engineered ◽  
Biological Processes ◽  
Targeted Deletion ◽  
Genetically Engineered Mice ◽  
Immune Defects ◽  
Molecular Brake

Excessive or inappropriate activation of the immune system can be deleterious to the organism, warranting multiple molecular mechanisms to control and properly terminate immune responses. MicroRNAs (miRNAs), ∼22-nt-long noncoding RNAs, have recently emerged as key posttranscriptional regulators, controlling diverse biological processes, including responses to non-self. In this study, we examine the biological role of miR-146a using genetically engineered mice and show that targeted deletion of this gene, whose expression is strongly up-regulated after immune cell maturation and/or activation, results in several immune defects. Collectively, our findings suggest that miR-146a plays a key role as a molecular brake on inflammation, myeloid cell proliferation, and oncogenic transformation.

scholarly journals Predictors of risk-reducing surgery intentions following genetic counseling for hereditary breast and ovarian cancer

2018 ◽  
Vol 10 (2) ◽  
pp. 337-346 ◽  
Author(s):  
Mary Kathleen Ladd ◽  
Beth N Peshkin ◽  
Leigha Senter ◽  
Shari Baldinger ◽  
Claudine Isaacs ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Genetic Counseling ◽  
Cancer Risk ◽  
Prophylactic Surgery ◽  
Ovarian Cancer Risk ◽  
Breast And Ovarian Cancer ◽  
Affective Factors ◽  
Risk Reducing

Abstract Risk-reducing mastectomy (RRM) and salpingo-oophorectomy (RRSO) are increasingly used to reduce breast and ovarian cancer risk following BRCA1/BRCA2 testing. However, little is known about how genetic counseling influences decisions about these surgeries. Although previous studies have examined intentions prior to counseling, few have examined RRM and RRSO intentions in the critical window between genetic counseling and test result disclosure. Previous research has indicated that intentions at this time point predict subsequent uptake of surgery, suggesting that much decision-making has taken place prior to result disclosure. This period may be a critical time to better understand the drivers of prophylactic surgery intentions. The aim of this study was to examine predictors of RRM and RRSO intentions. We hypothesized that variables from the Health Belief Model would predict intentions, and we also examined the role of affective factors. Participants were 187 women, age 21–75, who received genetic counseling for hereditary breast and ovarian cancer. We utilized multiple logistic regression to identify independent predictors of intentions. 49.2% and 61.3% of participants reported intentions for RRM and RRSO, respectively. Variables associated with RRM intentions include: newly diagnosed with breast cancer (OR = 3.63, 95% CI = 1.20–11.04), perceived breast cancer risk (OR = 1.46, 95% CI = 1.17–1.81), perceived pros (OR = 1.79, 95% CI = 1.38–2.32) and cons of RRM (OR = 0.81, 95% CI = 0.65–0.996), and decision conflict (OR = 0.80, 95% CI = 0.66–0.98). Variables associated with RRSO intentions include: proband status (OR = 0.28, 95% CI = 0.09–0.89), perceived pros (OR = 1.35, 95% CI = 1.11–1.63) and cons of RRSO (OR = 0.72, 95% CI = 0.59–0.89), and ambiguity aversion (OR = 0.79, 95% CI = 0.65–0.95). These data provide support for the role of genetic counseling in fostering informed decisions about risk management, and suggest that the role of uncertainty should be explored further.

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.

scholarly journals Anticancer Applications and Pharmacological Properties of Piperidine and Piperine: A Comprehensive Review on Molecular Mechanisms and Therapeutic Perspectives

2022 ◽  
Vol 12 ◽  
Author(s):  
Sicon Mitra ◽  
Uttpal Anand ◽  
Niraj Kumar Jha ◽  
Mahipal S. Shekhawat ◽  
Suchismita Chatterjee Saha ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Lung Cancer ◽  
Ovarian Cancer ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Black Pepper ◽  
Piper Nigrum ◽  
Molecular Formula ◽  
Cycle Arrest

Piperine and piperidine are the two major alkaloids extracted from black pepper (Piper nigrum); piperidine is a heterocyclic moiety that has the molecular formula (CH2)5NH. Over the years, many therapeutic properties including anticancer potential of these two compounds have been observed. Piperine has therapeutic potential against cancers such as breast cancer, ovarian cancer, gastric cancer, gliomal cancer, lung cancer, oral squamous, chronic pancreatitis, prostate cancer, rectal cancer, cervical cancer, and leukemia. Whereas, piperidine acts as a potential clinical agent against cancers, such as breast cancer, prostate cancer, colon cancer, lung cancer, and ovarian cancer, when treated alone or in combination with some novel drugs. Several crucial signalling pathways essential for the establishment of cancers such as STAT-3, NF-κB, PI3k/Aκt, JNK/p38-MAPK, TGF-ß/SMAD, Smac/DIABLO, p-IκB etc., are regulated by these two phytochemicals. Both of these phytochemicals lead to inhibition of cell migration and help in cell cycle arrest to inhibit survivability of cancer cells. The current review highlights the pharmaceutical relevance of both piperine and piperidine against different types of cancers.

scholarly journals The Evolving Role of Ferroptosis in Breast Cancer: Translational Implications Present and Future

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4576
Author(s):  
Hung-Yu Lin ◽  
Hui-Wen Ho ◽  
Yen-Hsiang Chang ◽  
Chun-Jui Wei ◽  
Pei-Yi Chu
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Drug Resistant ◽  
Therapeutic Targeting ◽  
The Past ◽  
Regulated Cell Death ◽  
Common Malignancy

Breast cancer (BC) is the most common malignancy among women worldwide. The discovery of regulated cell death processes has enabled advances in the treatment of BC. In the past decade, ferroptosis, a new form of iron-dependent regulated cell death caused by excessive lipid peroxidation has been implicated in the development and therapeutic responses of BC. Intriguingly, the induction of ferroptosis acts to suppress conventional therapy-resistant cells, and to potentiate the effects of immunotherapy. As such, pharmacological or genetic modulation targeting ferroptosis holds great potential for the treatment of drug-resistant cancers. In this review, we present a critical analysis of the current understanding of the molecular mechanisms and regulatory networks involved in ferroptosis, the potential physiological functions of ferroptosis in tumor suppression, its potential in therapeutic targeting, and explore recent advances in the development of therapeutic strategies for BC.

scholarly journals Role of Main RNA Methylation in Hepatocellular Carcinoma: N6-Methyladenosine, 5-Methylcytosine, and N1-Methyladenosine

2021 ◽  
Vol 9 ◽  
Author(s):  
Yating Xu ◽  
Menggang Zhang ◽  
Qiyao Zhang ◽  
Xiao Yu ◽  
Zongzong Sun ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cellular Differentiation ◽  
Molecular Mechanisms ◽  
Gene Sequence ◽  
Epigenetic Modification ◽  
Biological Processes ◽  
Biological Functions ◽  
Rna Detection ◽  
Rna Methylation

RNA methylation is considered a significant epigenetic modification, a process that does not alter gene sequence but may play a necessary role in multiple biological processes, such as gene expression, genome editing, and cellular differentiation. With advances in RNA detection, various forms of RNA methylation can be found, including N6-methyladenosine (m6A), N1-methyladenosine (m1A), and 5-methylcytosine (m5C). Emerging reports confirm that dysregulation of RNA methylation gives rise to a variety of human diseases, particularly hepatocellular carcinoma. We will summarize essential regulators of RNA methylation and biological functions of these modifications in coding and noncoding RNAs. In conclusion, we highlight complex molecular mechanisms of m6A, m5C, and m1A associated with hepatocellular carcinoma and hope this review might provide therapeutic potent of RNA methylation to clinical research.

The functional role of oncogenic lncRNA BCAR4 for cancer outcome

2021 ◽  
Vol 27 ◽  
Author(s):  
Bei Wang ◽  
Wen Xu ◽  
Yuxuan Cai ◽  
Kai Liu ◽  
Jiacheng Wu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gastric Cancer ◽  
Molecular Mechanisms ◽  
Clinical Value ◽  
Non Coding Rna ◽  
Entry Points ◽  
Multiple Processes ◽  
Cancer Outcome ◽  
Long Non Coding Rna

Background: Long non-coding RNA (lncRNA) breast cancer anti-estrogen resistance 4 (BCAR4) is a characterized oncogenic lncRNA in different cancers. This review is dedicated to summarize various molecular mechanisms of BCAR4 and demonstrate that the biological functions exerted by BCAR4 are good entry points for therapy. Methods: The molecular mechanism of BCAR4 acting on tumors is summarized by reviewing PubMed. Results: The expression of lncRNA BCAR4 is abnormally increased in all kinds of tumors, including colorectal cancer, prostate cancer, bladder cancer, gastric cancer, chondrosarcoma, glioma, breast cancer, glioma, gastric cancer, liver cancer, cervical cancer, lung cancer, etc. Besides, BCAR4 mediates multiple processes involved in carcinogenesis, including proliferation, invasion, anti-apoptosis, migration. Conclusion: BCAR4 may show great clinical value in this direction as a therapeutic cancer target.

scholarly journals Counteracting Chemoresistance with Metformin in Breast Cancers: Targeting Cancer Stem Cells

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2482
Author(s):  
Samson Mathews Samuel ◽  
Elizabeth Varghese ◽  
Lenka Koklesová ◽  
Alena Líšková ◽  
Peter Kubatka ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Acquired Resistance ◽  
Breast Cancers ◽  
Intrinsic Resistance ◽  
Mesenchymal Transition ◽  
Cancer Breast

Despite the leaps and bounds in achieving success in the management and treatment of breast cancers through surgery, chemotherapy, and radiotherapy, breast cancer remains the most frequently occurring cancer in women and the most common cause of cancer-related deaths among women. Systemic therapeutic approaches, such as chemotherapy, although beneficial in treating and curing breast cancer subjects with localized breast tumors, tend to fail in metastatic cases of the disease due to (a) an acquired resistance to the chemotherapeutic drug and (b) the development of intrinsic resistance to therapy. The existence of cancer stem cells (CSCs) plays a crucial role in both acquired and intrinsic chemoresistance. CSCs are less abundant than terminally differentiated cancer cells and confer chemoresistance through a unique altered metabolism and capability to evade the immune response system. Furthermore, CSCs possess active DNA repair systems, transporters that support multidrug resistance (MDR), advanced detoxification processes, and the ability to self-renew and differentiate into tumor progenitor cells, thereby supporting cancer invasion, metastasis, and recurrence/relapse. Hence, current research is focusing on targeting CSCs to overcome resistance and improve the efficacy of the treatment and management of breast cancer. Studies revealed that metformin (1, 1-dimethylbiguanide), a widely used anti-hyperglycemic agent, sensitizes tumor response to various chemotherapeutic drugs. Metformin selectively targets CSCs and improves the hypoxic microenvironment, suppresses the tumor metastasis and inflammation, as well as regulates the metabolic programming, induces apoptosis, and reverses epithelial–mesenchymal transition and MDR. Here, we discuss cancer (breast cancer) and chemoresistance, the molecular mechanisms of chemoresistance in breast cancers, and metformin as a chemo-sensitizing/re-sensitizing agent, with a particular focus on breast CSCs as a critical contributing factor to acquired and intrinsic chemoresistance. The review outlines the prospects and directions for a better understanding and re-purposing of metformin as an anti-cancer/chemo-sensitizing drug in the treatment of breast cancer. It intends to provide a rationale for the use of metformin as a combinatory therapy in a clinical setting.

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