HIF-1α Is a Rational Target for Future Ovarian Cancer Therapies

Ovarian cancer is the eighth most commonly diagnosed cancer among women worldwide. Even with the development of novel drugs, nearly one-half of the patients with ovarian cancer die within five years of diagnosis. These situations indicate the need for novel therapeutic agents for ovarian cancer. Increasing evidence has shown that hypoxia-inducible factor-1α(HIF-1α) plays an important role in promoting malignant cell chemoresistance, tumour metastasis, angiogenesis, immunosuppression and intercellular interactions. The unique microenvironment, crosstalk and/or interaction between cells and other characteristics of ovarian cancer can influence therapeutic efficiency or promote the disease progression. Inhibition of the expression or activity of HIF-1α can directly or indirectly enhance the therapeutic responsiveness of tumour cells. Therefore, it is reasonable to consider HIF-1α as a potential therapeutic target for ovarian cancer. In this paper, we summarize the latest research on the role of HIF-1α and molecules which can inhibit HIF-1α expression directly or indirectly in ovarian cancer, and drug clinical trials about the HIF-1α inhibitors in ovarian cancer or other solid malignant tumours.

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Leucine-Rich Repeat Kinase 2 in Parkinson’s Disease: Updated from Pathogenesis to Potential Therapeutic Target

European Neurology ◽

10.1159/000488938 ◽

2018 ◽

Vol 79 (5-6) ◽

pp. 256-265 ◽

Cited By ~ 9

Author(s):

Jinhua Chen ◽

Ying Chen ◽

Jiali Pu

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Significant Role ◽

Dopaminergic Neurons ◽

Recent Progress ◽

Therapeutic Agents ◽

Leucine Rich Repeat ◽

Potential Therapeutic Target ◽

Genetic And Environmental Factors

Background: Parkinson’s disease (PD) is characterized by the selective loss of dopaminergic neurons in the midbrain. The pathogenesis of PD is not fully understood but is likely caused by a combination of genetic and environmental factors. Several genes are associated with the onset and progression of familial PD. There is increasing evidence that leucine-rich repeat kinase 2 (LRRK2) plays a significant role in PD pathophysiology. Summary: Many studies have been conducted to elucidate the functions of LRRK2 and identify effective LRRK2 inhibitors for PD treatment. In this review, we discuss the role of LRRK2 in PD and recent progress in the use of LRRK2 inhibitors as therapeutic agents. Key Messages: LRRK2 plays a significant role in the pathophysiology of PD, and pharmacological inhibition of LRRK2 has become one of the most promising potential therapies for PD. Further research is warranted to determine the functions of LRRK2 and expand the applications of LRRK2 inhibitors in PD treatment.

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Downregulation of hypoxia-inducible factor-1α contributes to impaired megakaryopoiesis in immune thrombocytopenia

Thrombosis and Haemostasis ◽

10.1160/th17-03-0155 ◽

2017 ◽

Vol 117 (10) ◽

pp. 1875-1886 ◽

Cited By ~ 3

Author(s):

Tingting Pan ◽

Qi Wang ◽

Li Zhu ◽

Jiaqian Qi ◽

Tao You ◽

...

Keyword(s):

Cell Size ◽

Immune Thrombocytopenia ◽

Hypoxia Inducible Factor ◽

Potential Therapeutic Target ◽

Platelet Destruction ◽

Haematopoietic Stem Cells ◽

Healthy Donors ◽

High Ploidy ◽

Supplementary Material

SummaryImpaired megakaryocyte maturation and exaggerated platelet destruction play a pivotal role in the pathogenesis of immune thrombocytopenia (ITP). Previous studies have shown that HIF-1α promotes the homing and engraftment of haematopoietic stem cells (HSCs), thereby stimulating HSC differentiation. However, whether HIF-1α plays a role in megakaryocytic maturation and platelet destruction in ITP remains elusive. Using enzyme-linked immunosorbent assays (ELISAs), we demonstrated that there were lower HIF-1α levels in the bone marrow (BM) of ITP patients than in that of healthy donors and patients with chemotherapy-related thrombocytopenia. Subjects with lower megakaryocyte (<100/slide) and platelet (<30 × 109/L) counts exhibited significantly decreased BM HIF-1α levels, compared to those with higher megakaryocyte (≥100/slide) and platelet (≥30 × 109/L) counts. To test whether HIF-1α regulates megakaryopoiesis and platelet production, megakaryocytes derived from mouse BM cells were treated with an HIF-1α activator (IOX-2; 50 µM) or inhibitor (PX-478; 50 µM). PX-478 significantly decreased HIF-1α expression, cell size, and the populations of CD41-positive and high-ploidy cells. Importantly, to evaluate the role of HIF-1α as a potential therapeutic target in ITP, mouse BM cells were incubated with plasma from ITP patients in the presence or absence of IOX-2. IOX-2 significantly attenuated the ITP plasma-induced decrease in cell size as well as the proportions of CD41-positive and high-ploidy cells. In addition, IOX-2 increased the number of megakaryocytes from mouse BM cells treated with ITP plasma. Our findings indicate that decreased HIF-1α may contribute to impaired megakaryopoiesis in ITP, and HIF-1α may provide a potential therapy for ITP patients.Supplementary Material to this article is available online at www.thrombosis-online.com.

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Role of Molecular Agents and Targeted Therapy in Clinical Trials for Women With Ovarian Cancer

International Journal of Gynecological Cancer ◽

10.1097/igc.0b013e31821b2669 ◽

2011 ◽

Vol 21 (4) ◽

pp. 763-770 ◽

Cited By ~ 21

Author(s):

Jonathan A. Ledermann ◽

Christian Marth ◽

Mark S. Carey ◽

Michael Birrer ◽

David D.L. Bowtell ◽

...

Keyword(s):

Ovarian Cancer ◽

Clinical Trials ◽

Targeted Therapy ◽

Predictive Biomarkers ◽

Therapeutic Agents ◽

Careful Consideration ◽

Consensus Conference ◽

Molecular Pathways ◽

New Agents

There is now a greater understanding of the molecular pathways in ovarian cancer, and using this knowledge, a large number of new therapeutic agents can be tested. The success of these drugs will depend on selecting drugs that target known key dysfunctional molecular pathways. To make best use of these compounds, prognostic and predictive biomarkers need to be identified. Novel methods of assessment such as functional imaging need to be developed as additional biological end points to evaluate these therapies. Promising antitumor activity has been observed with some drugs, and careful consideration is needed to determine in what circumstances new agents, such as antiangiogenic compounds, could be considered as a standard therapy. These areas were discussed at the 4th Ovarian Cancer Consensus Conference.

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Potential role of the HOXD8 transcription factor in cisplatin resistance and tumour metastasis in advanced epithelial ovarian cancer

Scientific Reports ◽

10.1038/s41598-018-31030-3 ◽

2018 ◽

Vol 8 (1) ◽

Cited By ~ 5

Author(s):

PengMing Sun ◽

YiYi Song ◽

DaBin Liu ◽

GuiFen Liu ◽

XiaoDan Mao ◽

...

Keyword(s):

Ovarian Cancer ◽

Transcription Factor ◽

Epithelial Ovarian Cancer ◽

Potential Role ◽

Cisplatin Resistance ◽

Tumour Metastasis ◽

Advanced Epithelial Ovarian Cancer

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CUZD1 and Anti-CUZD1 Antibodies as Markers of Cancer and Inflammatory Bowel Diseases

Clinical and Developmental Immunology ◽

10.1155/2013/968041 ◽

2013 ◽

Vol 2013 ◽

pp. 1-11 ◽

Cited By ~ 7

Author(s):

Christos Liaskos ◽

Eirini I. Rigopoulou ◽

Timoklia Orfanidou ◽

Dimitrios P. Bogdanos ◽

Christos N. Papandreou

Keyword(s):

Ovarian Cancer ◽

Pancreatic Cancer ◽

Inflammatory Bowel Diseases ◽

Serum Levels ◽

Malignant Tumours ◽

Autoimmune Attack ◽

Frequent Event ◽

Bowel Diseases ◽

Inflammatory Bowel

CUZD1, the CUB, and zona pellucida-like domains-containing protein 1, is a newly identified antigen of pancreatic autoantibodies (PAB) giving a reticulogranular pattern in patients with inflammatory bowel diseases, and in particular Crohn’s disease. The exact mechanisms by which this pancreatic antigen becomes the target of IBD-specific pancreatic autoantibodies are unclear. At the same time, evolving data strongly support a role for CUZD1 in carcinogenesis. HumanCUZD1is mapped at chromosome 10q26.13 and the loss of this region is a frequent event in various malignant tumours. mRNA overexpression of CUZD1 has been noted in ovarian cancer and serum levels of CUZD1 are elevated in women with ovarian cancer and patients suffering from pancreatic cancer. CUZD1 appears to be one of the relatively few biomarkers that serve as both cancer biomarker and autoantigen of autoantibodies in an autoimmune disease unrelated to cancerous organs. This review discusses the role of CUZD1 in cancer and autoimmunity. We anticipate that a better understanding of the function of CUZD1 will help us to understand how it becomes the focus of an autoimmune attack specifically targeting the intestine and its enigmatic role in carcinogenesis.

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Macrophage Function and the Role of GSK3

International Journal of Molecular Sciences ◽

10.3390/ijms22042206 ◽

2021 ◽

Vol 22 (4) ◽

pp. 2206

Author(s):

Sarvatit Patel ◽

Geoff H. Werstuck

Keyword(s):

Metabolic Disorders ◽

Glycogen Synthase ◽

Cell Metabolism ◽

Glycogen Synthase Kinase 3 ◽

Immune Functions ◽

Potential Therapeutic Target ◽

Macrophage Function ◽

Novel Drugs ◽

Complex Variety

Macrophages are present in nearly all vertebrate tissues, where they respond to a complex variety of regulatory signals to coordinate immune functions involved in tissue development, metabolism, homeostasis, and repair. Glycogen synthase kinase 3 (GSK3) is a ubiquitously expressed protein kinase that plays important roles in multiple pathways involved in cell metabolism. Dysregulation of GSK3 has been implicated in several prevalent metabolic disorders, and recent findings have highlighted the importance of GSK3 activity in the regulation of macrophages, especially with respect to the initiation of specific pathologies. This makes GSK3 a potential therapeutic target for the development of novel drugs to modulate immunometabolic responses. Here, we summarize recent findings that have contributed to our understanding of how GSK3 regulates macrophage function, and we discuss the role of GSK3 in the development of metabolic disorders and diseases.

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The current role of gemcitabine in ovarian cancer

Seminars in Oncology ◽

10.1053/sonc.2001.24368 ◽

2001 ◽

Vol 28 (2D) ◽

pp. 18-24

Author(s):

Robert F. Ozols

Keyword(s):

Ovarian Cancer ◽

Current Role

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Role of Hypoxia Inducible Factor (HIF) and NADPH oxidases in regulation of Kv channels in pulmonary artery smooth muscle cells

Pneumologie ◽

10.1055/s-2008-1074194 ◽

2008 ◽

Vol 62 (S 2) ◽

Author(s):

M Mittal ◽

M Roth ◽

R Schermuly ◽

HA Ghofrani ◽

W Seeger ◽

...

Keyword(s):

Smooth Muscle ◽

Pulmonary Artery ◽

Smooth Muscle Cells ◽

Hypoxia Inducible Factor ◽

Muscle Cells ◽

Nadph Oxidases ◽

Kv Channels ◽

Pulmonary Artery Smooth Muscle

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ROLE OF LIPID PROFILE IN OVARIAN CARCINOMA PATIENTS

International Journal of Medical and Biomedical Studies ◽

10.32553/ijmbs.v3i8.501 ◽

2019 ◽

Vol 3 (8) ◽

Author(s):

Dr. Manisha ◽

Dr. Ruchi Jindal

Keyword(s):

Ovarian Cancer ◽

Lipid Profile ◽

Cancer Patients ◽

Ovarian Tumor ◽

Ovarian Cancer Risk ◽

Low Level ◽

Medical College ◽

Group I ◽

History Of

Background: The term "ovarian cancer" includes several different types of cancer that arise from cells of the ovary, most commonly, tumors arise from the epithelium or lining cells of the ovary. Ovarian cancer risk is positively associated with higher consumption of dietary cholesterol and eggs, and inversely associated with a higher intake of vegetables. High consumption of fats may increase circulating estrogen levels, thus increasing the possibility of cell damage and proliferation that is responsible for cancerous growth. Material & Methods: The present study was conducted at Geetanjali Medical College and Hospital, Udaipur (Rajasthan). Total 100 cases (females) attending the obstetrics and gynecology department for some gynecological and other problem were selected for this study between the age of 40-60 years, who were attending cancer centre at GEETANJALI MEDICAL COLLEGE AND HOSPITAL, Udaipur (Rajasthan). GROUP I: - It consisted of healthy females control subjects (n=50) .By routine examination and tests, we ensured that all the subjects were healthy and there were no signs and symptoms or history of ovarian tumor and diseases GROUP II: - It consisted of ovarian cancer females subjects (n=50) with a history of ovarian tumor. Results: Higher level of cholesterol, LDL, VLDL and low level of HDL are found in ovarian cancer patients. Conclusion: The present study we highlights the importance and role of serum lipid profile in diagnosis, prognosis and recurrence of the disease. The study shows that serum level of cholesterol, LDL, VLDL was elevated in patients of ovarian cancer while low level of HDL are found in ovarian cancer patients. Key words: lipid profile, ovarian cancer.

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