scholarly journals Etiology and Pathogenesis of Epithelial Ovarian Cancer

2007 ◽  
Vol 23 (5-6) ◽  
pp. 367-376 ◽  
Author(s):  
Samuel C. Mok ◽  
Joseph Kwong ◽  
William R. Welch ◽  
Goli Samimi ◽  
Laurent Ozbun ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Molecular Mechanisms ◽  
Complex Disease ◽  
Critical Role ◽  
Epidemiological Studies ◽  
Genetic Studies ◽  
Genetic Changes ◽  
Disease Phenotypes ◽  
Stromal Microenvironment ◽  
Insight Into

Ovarian cancer is complex disease composed of different histological grades and types. However, the underlying molecular mechanisms involved in the development of different phenotypes remain largely unknown. Epidemiological studies identified multiple exogenous and endogenous risk factors for ovarian cancer development. Among them, an inflammatory stromal microenvironment seems to play a critical role in the initiation of the disease. The interaction between such a microenvironment, genetic polymorphisms, and different epithelial components such as endosalpingiosis, endometriosis, and ovarian inclusion cyst in the ovarian cortex may induce different genetic changes identified in the epithelial component of different histological types of ovarian tumors. Genetic studies on different histological grades and types provide insight into the pathogenetic pathways for the development of different disease phenotypes. However, the link between all these genetic changes and the etiological factors remains to be established.

Molecular Mechanisms of Complement System Proteins and Matrix Metalloproteinases in the Pathogenesis of Age-Related Macular Degeneration

2019 ◽  
Vol 19 (10) ◽  
pp. 705-718 ◽  
Author(s):  
Naima Mansoor ◽  
Fazli Wahid ◽  
Maleeha Azam ◽  
Khadim Shah ◽  
Anneke I. den Hollander ◽  
...  
Keyword(s):  
Matrix Metalloproteinases ◽  
Macular Degeneration ◽  
Complement System ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Age Related Macular Degeneration ◽  
Genetic Changes ◽  
Complement System Proteins ◽  
Age Related ◽  
Common Genetic Variants

: Age-related macular degeneration (AMD) is an eye disorder affecting predominantly the older people above the age of 50 years in which the macular region of the retina deteriorates, resulting in the loss of central vision. The key factors associated with the pathogenesis of AMD are age, smoking, dietary, and genetic risk factors. There are few associated and plausible genes involved in AMD pathogenesis. Common genetic variants (with a minor allele frequency of >5% in the population) near the complement genes explain 40–60% of the heritability of AMD. The complement system is a group of proteins that work together to destroy foreign invaders, trigger inflammation, and remove debris from cells and tissues. Genetic changes in and around several complement system genes, including the CFH, contribute to the formation of drusen and progression of AMD. Similarly, Matrix metalloproteinases (MMPs) that are normally involved in tissue remodeling also play a critical role in the pathogenesis of AMD. MMPs are involved in the degradation of cell debris and lipid deposits beneath retina but with age their functions get affected and result in the drusen formation, succeeding to macular degeneration. In this review, AMD pathology, existing knowledge about the normal and pathological role of complement system proteins and MMPs in the eye is reviewed. The scattered data of complement system proteins, MMPs, drusenogenesis, and lipofusogenesis have been gathered and discussed in detail. This might add new dimensions to the understanding of molecular mechanisms of AMD pathophysiology and might help in finding new therapeutic options for AMD.

scholarly journals Deciphering the Mounting Complexity of the p53 Regulatory Network in Correlation to Long Non-Coding RNAs (lncRNAs) in Ovarian Cancer

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 527 ◽  
Author(s):  
Sonali Pal ◽  
Manoj Garg ◽  
Amit Kumar Pandey
Keyword(s):  
Ovarian Cancer ◽  
Molecular Mechanisms ◽  
Human Cancer ◽  
Critical Role ◽  
Functional Characterization ◽  
Great Promise ◽  
Altered Expression ◽  
Disease Biology ◽  
Non Coding Rnas ◽  
Post Transcriptional Regulation

Amongst the various gynecological malignancies affecting female health globally, ovarian cancer is one of the predominant and lethal among all. The identification and functional characterization of long non-coding RNAs (lncRNAs) are made possible with the advent of RNA-seq and the advancement of computational logarithm in understanding human disease biology. LncRNAs can interact with deoxyribonucleic acid (DNA), ribonucleic acid (RNA), proteins and their combinations. Moreover, lncRNAs regulate orchestra of diverse functions including chromatin organization and transcriptional and post-transcriptional regulation. LncRNAs have conferred their critical role in key biological processes in human cancer including tumor initiation, proliferation, cell cycle, apoptosis, necroptosis, autophagy, and metastasis. The interwoven function of tumor-suppressor protein p53-linked lncRNAs in the ovarian cancer paradigm is of paramount importance. Several lncRNAs operate as p53 regulators or effectors and modulates a diverse array of functions either by participating in various signaling cascades or via interaction with different proteins. This review highlights the recent progress made in the identification of p53 associated lncRNAs while elucidating their molecular mechanisms behind the altered expression in ovarian cancer tumorigenesis. Moreover, the development of novel clinical and therapeutic strategies for targeting lncRNAs in human cancers harbors great promise.

Platelets in tissue repair: control of apoptosis and interactions with regenerative cells

Blood ◽  
2013 ◽  
Vol 122 (15) ◽  
pp. 2550-2554 ◽  
Author(s):  
Meinrad Gawaz ◽  
Sebastian Vogel
Keyword(s):  
Cell Survival ◽  
Tissue Repair ◽  
Molecular Mechanisms ◽  
Healing Process ◽  
Critical Role ◽  
Cellular Migration ◽  
Tissue Repair And Regeneration ◽  
Primary Hemostasis ◽  
Regenerative Cells ◽  
Insight Into

Abstract Besides mediating primary hemostasis and thrombosis, platelets play a critical role in tissue repair and regeneration. They regulate fundamental mechanisms involved in the healing process including cellular migration, proliferation, and angiogenesis. Control of apoptosis/cell survival and interaction with progenitor cells, which are clinically relevant but poorly understood aspects of platelets in tissue repair, will be highlighted in this review. Gaining deeper insight into the less well-characterized molecular mechanisms is necessary to develop new therapeutic platelet-based options.

scholarly journals Ovarian Surface Epithelium: Biology, Endocrinology, and Pathology*

2001 ◽  
Vol 22 (2) ◽  
pp. 255-288 ◽  
Author(s):  
Nelly Auersperg ◽  
Alice S. T. Wong ◽  
Kyung-Chul Choi ◽  
Sung Keun Kang ◽  
Peter C. K. Leung
Keyword(s):  
Ovarian Cancer ◽  
Molecular Mechanisms ◽  
Ovarian Surface Epithelium ◽  
Surface Epithelium ◽  
Neoplastic Progression ◽  
Ovarian Carcinomas ◽  
Genetic Changes ◽  
Ovarian Surface ◽  
Histological Characteristics ◽  
Epithelial Ovarian Carcinomas

Abstract The epithelial ovarian carcinomas, which make up more than 85% of human ovarian cancer, arise in the ovarian surface epithelium (OSE). The etiology and early events in the progression of these carcinomas are among the least understood of all major human malignancies because there are no appropriate animal models, and because methods to culture OSE have become available only recently. The objective of this article is to review the cellular and molecular mechanisms that underlie the control of normal and neoplastic OSE cell growth, differentiation, and expression of indicators of neoplastic progression. We begin with a brief discussion of the development of OSE, from embryonic to the adult. The pathological and genetic changes of OSE during neoplastic progression are next summarized. The histological characteristics of OSE cells in culture are also described. Finally, the potential involvement of hormones, growth factors, and cytokines is discussed in terms of their contribution to our understanding of the physiology of normal OSE and ovarian cancer development.

scholarly journals De novo transcriptome assembly of the Italian white truffle (Tuber magnatum Pico)

2018 ◽  
Author(s):  
Federico Vita ◽  
Amedeo Alpi ◽  
Edoardo Bertolini
Keyword(s):  
Molecular Mechanisms ◽  
De Novo ◽  
Transcriptome Assembly ◽  
Rna Seq ◽  
Genetic Studies ◽  
Protein Coding ◽  
Important Species ◽  
White Truffle ◽  
Tuber Magnatum ◽  
Insight Into

AbstractThe Italian white truffle (Tuber magnatum Pico) is a gastronomic delicacy that dominates the worldwide truffle market. Despite its importance, the genomic resources currently available for this species are still limited. Here we present the first de novo transcriptome assembly of T. magnatum. Illumina RNA-seq data were assembled using a single-k-mer approach into 22,932 transcripts with N50 of 1,524 bp. Our approach allowed to predict and annotate 12,367 putative protein coding sequences, reunited in 6,723 loci. In addition, we identified 2,581 gene-based SSR markers. This work provides the first publicly available reference transcriptome for genomics and genetic studies providing insight into the molecular mechanisms underlying the biology of this important species.

Molecular Mechanisms of Renal Magnesium Reabsorption

2021 ◽  
pp. ASN.2021010042
Author(s):  
David Ellison ◽  
Yujiro Maeoka ◽  
James McCormick
Keyword(s):  
Molecular Mechanisms ◽  
Narrow Range ◽  
Serum Magnesium ◽  
Critical Role ◽  
Cellular Processes ◽  
Magnesium Homeostasis ◽  
Life Threatening ◽  
Transepithelial Voltage ◽  
Paracellular Pathways ◽  
Insight Into

Magnesium is an essential cofactor in many cellular processes, and aberrations in magnesium homeostasis can have life-threatening consequences. The kidney plays a central role in maintaining serum magnesium within a narrow range (0.70 to 1.10 mmol/L). Along the proximal tubule and thick ascending limbs, magnesium reabsorption occurs via paracellular pathways. Members of the claudin family form the magnesium pores in these segments, and also regulate magnesium reabsorption by adjusting the transepithelial voltage that drives it. Along the distal convoluted tubule transcellular reabsorption via heteromeric TRPM6/7 channels predominates, though paracellular reabsorption may also occur. In this segment, the NaCl cotransporter plays a critical role in determining transcellular magnesium reabsorption. While the general machinery involved in renal magnesium reabsorption has been identified by studying genetic forms of magnesium imbalance, the mechanisms regulating it are poorly understood. This review discusses pathways of renal magnesium reabsorption by different segments of the nephron, emphasizing newer findings that provide insight into regulatory process, and outlining critical unanswered questions.

JNK- and Akt-mediated Puma expression in the apoptosis of cisplatin-resistant ovarian cancer cells

2012 ◽  
Vol 444 (2) ◽  
pp. 291-301 ◽  
Author(s):  
Zhiwei Zhao ◽  
Jingjing Wang ◽  
Jingsheng Tang ◽  
Xinyu Liu ◽  
Qian Zhong ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Nuclear Translocation ◽  
Critical Role ◽  
P53 Gene ◽  
Dominant Negative ◽  
Ovarian Cancer Cells ◽  
Puma Expression ◽  
Domain 3

BH3 (Bcl-2 homology domain 3)-only proteins have an important role in the cisplatin resistance of cells. However, the effect of BH3-only proteins on cisplatin-resistant ovarian cancer cells has not been thoroughly elucidated. Our results from the present study indicate that Puma plays a critical role in the apoptosis of chemo-resistant ovarian cancer cells treated with BetA (betulinic acid). The reduction of Puma expression inhibits Bax activation and apoptosis. However, p53 gene silencing has little effect on Puma activation. Further experiments demonstrated that Akt-mediated FoxO3a (forkhead box O3a) nuclear translocation and the JNK (c-Jun N-terminal kinase)/c-Jun pathway only partially trigger Puma induction and apoptosis, whereas dominant-negative c-Jun expression with FoxO3a reduction completely inhibits Puma expression and cell death. Furthermore, our results suggest that JNK regulates the Akt/FoxO3a signalling pathway. Therefore the dual effect of JNK can efficiently trigger Puma activation and apoptosis in chemoresistant cells. Taken together, our results demonstrate the role of Puma in BetA-induced apoptosis and the molecular mechanisms of Puma expression regulated by BetA during ovarian cancer cell apoptosis. Our findings suggest that the JNK-potentiated Akt/FoxO3a and JNK-mediated c-Jun pathways co-operatively trigger Puma expression, which determines the threshold for overcoming chemoresistance in ovarian cancer cells.

scholarly journals CircASH2L Promotes Ovarian Cancer Tumorigenesis, Angiogenesis, and Lymphangiogenesis by Regulating the miR-665/VEGFA Axis as a Competing Endogenous RNA

2020 ◽  
Vol 8 ◽  
Author(s):  
Jinxin Chen ◽  
Xiaocen Li ◽  
Lu Yang ◽  
Mengmeng Li ◽  
Ye Zhang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Gynecologic Cancer ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Ovarian Cancer Cells ◽  
Western Blots ◽  
The Impact

Ovarian cancer is the leading cause of gynecologic cancer-related deaths. Emerging research has revealed a close relationship between circular RNAs (circRNAs) and ovarian cancer development, metastasis, and prognosis. The objective of our research was to further explore the relationship between circASH2L and ovarian cancer. Quantitative real-time polymerase chain reaction was used to detect the differential expression of circRNAs between normal ovaries and ovarian cancer tissues. The impact of circASH2L on the proliferation, invasion, and tumorigenicity of ovarian cancer cells was evaluated using gain- and loss-of-function experiments. The molecular mechanisms of circASH2L function were investigated using bioinformatics analysis, RNA fluorescence in situ hybridization, western blots, and dual-luciferase reporter assays. The results showed that circASH2L was remarkably upregulated in ovarian cancer. The invasion and growth of ovarian cancer cells were suppressed by circASH2L knockdown in vitro, and downregulation of circASH2L restrained both angiogenesis and lymphangiogenesis of tumor xenografts in vivo. Furthermore, circASH2L was mostly distributed in the cytoplasm, where it competes with vascular endothelial growth factor A (VEGFA) for binding to miR-665. These findings indicate that circASH2L has an oncogenic function in ovarian cancer. In conclusion, circASH2L plays a critical role in regulating ovarian cancer cell tumorigenesis, angiogenesis, and lymphangiogenesis through the miR-665/VEGFA axis and, therefore, is a possible candidate target for ovarian cancer treatment.

Ovarian cancer and the evolution of subtype classifications using transcriptional profiling†

2019 ◽  
Vol 101 (3) ◽  
pp. 645-658 ◽  
Author(s):  
David P Cook ◽  
Barbara C Vanderhyden
Keyword(s):  
Ovarian Cancer ◽  
Molecular Mechanisms ◽  
Complex Disease ◽  
Transcriptional Profiling ◽  
Model Systems ◽  
Valuable Insight ◽  
Cancer Subtypes ◽  
Molecular Alterations ◽  
Spatially Resolved ◽  
Technological Advances

AbstractOvarian cancer is a complex disease with multiple subtypes, each having distinct histopathologies and variable responses to treatment. This review highlights the technological milestones and the studies that have applied them to change our definitions of ovarian cancer. Over the past 50 years, technologies such as microarrays and next-generation sequencing have led to the discovery of molecular alterations that define each of the ovarian cancer subtypes and has enabled further subclassification of the most common subtype, high-grade serous ovarian cancer (HGSOC). Improvements in mutational profiling have provided valuable insight, such as the ubiquity of TP53 mutations in HGSOC tumors. However, the information derived from these technological advances has also revealed the immense heterogeneity of this disease, from variation between patients to compositional differences within single masses. In looking forward, the emerging technologies for single-cell and spatially resolved transcriptomics will allow us to better understand the cellular composition and structure of tumors and how these contribute to the molecular subtypes. Attempts to incorporate the complexities ovarian cancer has resulted in increasing sophistication of model systems, and the increased precision in molecular profiling of ovarian cancers has already led to the introduction of inhibitors of poly (ADP-ribose) polymerases as a new class of treatments for ovarian cancer with DNA repair deficiencies. Future endeavors to define increasingly accurate classification strategies for ovarian cancer subtypes will allow for confident prediction of disease progression and provide important insight into potentially targetable molecular mechanisms specific to each subtype.

scholarly journals Human pancreatic islet 3D chromatin architecture provides insights into the genetics of type 2 diabetes

2018 ◽  
Author(s):  
Irene Miguel-Escalada ◽  
Silvia Bonàs-Guarch ◽  
Inês Cebola ◽  
Ponsa-Cobas Joan ◽  
Julen Mendieta-Esteban ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Genetic Studies ◽  
Chromatin Architecture ◽  
Genome Maps ◽  
3D Space ◽  
Dependent Activity ◽  
Insight Into

AbstractGenetic studies promise to provide insight into the molecular mechanisms underlying type 2 diabetes (T2D). Variants associated with T2D are often located in tissue-specific enhancer regions (enhancer clusters, stretch enhancers or super-enhancers). So far, such domains have been defined through clustering of enhancers in linear genome maps rather than in 3D-space. Furthermore, their target genes are generally unknown. We have now created promoter capture Hi-C maps in human pancreatic islets. This linked diabetes-associated enhancers with their target genes, often located hundreds of kilobases away. It further revealed sets of islet enhancers, super-enhancers and active promoters that form 3D higher-order hubs, some of which show coordinated glucose-dependent activity. Hub genetic variants impact the heritability of insulin secretion, and help identify individuals in whom genetic variation of islet function is important for T2D. Human islet 3D chromatin architecture thus provides a framework for interpretation of T2D GWAS signals.

Sign in / Sign up

Export Citation Format

Share Document