scholarly journals An Omics Perspective on Molecular Biomarkers for Diagnosis, Prognosis, and Therapeutics of Cholangiocarcinoma

2015 ◽  
Vol 2015 ◽  
pp. 1-16 ◽  
Author(s):  
Pattaya Seeree ◽  
Phorutai Pearngam ◽  
Supeecha Kumkate ◽  
Tavan Janvilisri
Keyword(s):  
Survival Rates ◽  
Underlying Mechanism ◽  
Diagnostic Biomarkers ◽  
Recent Advancement ◽  
Novel Biomarkers ◽  
Therapeutic Measures ◽  
Cellular Pathways ◽  
Biliary Tract Malignancy ◽  
Insight Into ◽  
Early Diagnostic

Cholangiocarcinoma (CCA) is an aggressive biliary tract malignancy arising from the epithelial bile duct. The lack of early diagnostic biomarkers as well as therapeutic measures results in severe outcomes and poor prognosis. Thus, effective early diagnostic, prognostic, and therapeutic biomarkers are required to improve the prognosis and prolong survival rates in CCA patients. Recent advancement in omics technologies combined with the integrative experimental and clinical validations has provided an insight into the underlying mechanism of CCA initiation and progression as well as clues towards novel biomarkers. This work highlights the discovery and validation of molecular markers in CCA identified through omics approaches. The possible roles of these molecules in various cellular pathways, which render CCA carcinogenesis and progression, will also be discussed. This paper can serve as a reference point for further investigations to yield deeper understanding in the complex feature of this disease, potentially leading to better approaches for diagnosis, prognosis, and therapeutics.

scholarly journals Biliary Strictures and Cholangiocarcinoma – Untangling a Diagnostic Conundrum

2021 ◽  
Vol 11 ◽  
Author(s):  
Alexander Ney ◽  
Andres Garcia-Sampedro ◽  
George Goodchild ◽  
Pilar Acedo ◽  
Giuseppe Fusai ◽  
...  
Keyword(s):  
Serum Markers ◽  
Biliary Strictures ◽  
Histological Techniques ◽  
Diagnostic Biomarkers ◽  
Non Invasive ◽  
Novel Biomarkers ◽  
Standard Serum ◽  
Biliary Tract Malignancy ◽  
Diagnostic Pathways ◽  
Disease Stages

Cholangiocarcinoma is an uncommon and highly aggressive biliary tract malignancy with few manifestations until late disease stages. Diagnosis is currently achieved through a combination of clinical, biochemical, radiological and histological techniques. A number of reported cancer biomarkers have the potential to be incorporated into diagnostic pathways, but all lack sufficient sensitivity and specificity limiting their possible use in screening and early diagnosis. The limitations of standard serum markers such as CA19-9, CA125 and CEA have driven researchers to identify multiple novel biomarkers, yet their clinical translation has been slow with a general requirement for further validation in larger patient cohorts. We review recent advances in the diagnostic pathway for suspected CCA as well as emerging diagnostic biomarkers for early detection, with a particular focus on non-invasive approaches.

scholarly journals Multi-omic profiling of lung and liver tumor microenvironments of metastatic pancreatic cancer reveals site-specific immune regulatory pathways

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Won Jin Ho ◽  
Rossin Erbe ◽  
Ludmila Danilova ◽  
Zaw Phyo ◽  
Emma Bigelow ◽  
...  
Keyword(s):  
Mouse Model ◽  
Primary Tumors ◽  
Regulatory Pathways ◽  
Tumor Microenvironments ◽  
Clinical Responses ◽  
Cellular Pathways ◽  
Autopsy Specimens ◽  
Rapid Autopsy ◽  
Insight Into ◽  
Systemic Therapies

Abstract Background The majority of pancreatic ductal adenocarcinomas (PDAC) are diagnosed at the metastatic stage, and standard therapies have limited activity with a dismal 5-year survival rate of only 8%. The liver and lung are the most common sites of PDAC metastasis, and each have been differentially associated with prognoses and responses to systemic therapies. A deeper understanding of the molecular and cellular landscape within the tumor microenvironment (TME) metastasis at these different sites is critical to informing future therapeutic strategies against metastatic PDAC. Results By leveraging combined mass cytometry, immunohistochemistry, and RNA sequencing, we identify key regulatory pathways that distinguish the liver and lung TMEs in a preclinical mouse model of metastatic PDAC. We demonstrate that the lung TME generally exhibits higher levels of immune infiltration, immune activation, and pro-immune signaling pathways, whereas multiple immune-suppressive pathways are emphasized in the liver TME. We then perform further validation of these preclinical findings in paired human lung and liver metastatic samples using immunohistochemistry from PDAC rapid autopsy specimens. Finally, in silico validation with transfer learning between our mouse model and TCGA datasets further demonstrates that many of the site-associated features are detectable even in the context of different primary tumors. Conclusions Determining the distinctive immune-suppressive features in multiple liver and lung TME datasets provides further insight into the tissue specificity of molecular and cellular pathways, suggesting a potential mechanism underlying the discordant clinical responses that are often observed in metastatic diseases.

scholarly journals Glycomic-Based Biomarkers for Ovarian Cancer: Advances and Challenges

Diagnostics ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 643
Author(s):  
Francis Mugeni Wanyama ◽  
Véronique Blanchard
Keyword(s):  
Ovarian Cancer ◽  
Survival Rates ◽  
Post Translational Modification ◽  
Diagnostic Biomarkers ◽  
Diagnostic Strategies ◽  
Delay In Diagnosis ◽  
Common Causes ◽  
New Biomarkers ◽  
Cure Rates ◽  
Developed World

Ovarian cancer remains one of the most common causes of death among gynecological malignancies afflicting women worldwide. Among the gynecological cancers, cervical and endometrial cancers confer the greatest burden to the developing and the developed world, respectively; however, the overall survival rates for patients with ovarian cancer are worse than the two aforementioned. The majority of patients with ovarian cancer are diagnosed at an advanced stage when cancer has metastasized to different body sites and the cure rates, including the five-year survival, are significantly diminished. The delay in diagnosis is due to the absence of or unspecific symptoms at the initial stages of cancer as well as a lack of effective screening and diagnostic biomarkers that can detect cancer at the early stages. This, therefore, provides an imperative to prospect for new biomarkers that will provide early diagnostic strategies allowing timely mitigative interventions. Glycosylation is a protein post-translational modification that is modified in cancer patients. In the current review, we document the state-of-the-art of blood-based glycomic biomarkers for early diagnosis of ovarian cancer and the technologies currently used in this endeavor.

scholarly journals Sex-Specific Differences in Extracellular Vesicle Protein Cargo in Synovial Fluid of Patients with Osteoarthritis

Life ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 337
Author(s):  
Ravindra Kolhe ◽  
Virgenal Owens ◽  
Ashok Sharma ◽  
Tae Jin Lee ◽  
Wenbo Zhi ◽  
...  
Keyword(s):  
Synovial Fluid ◽  
Protein Content ◽  
Extracellular Vesicle ◽  
Specific Protein ◽  
Paracrine Signaling ◽  
Age Related ◽  
Specific Manner ◽  
Inflammatory Processes ◽  
Novel Biomarkers ◽  
Cellular Pathways

Women are at a significantly higher risk of developing osteoarthritis (OA) compared to males. The pathogenesis of osteoarthritis (OA) in women is poorly understood. Extracellular vesicles (EVs) have been shown to play an essential role in numerous signaling processes during the pathogenesis of age-related diseases via paracrine signaling. Molecular profiling of the synovial fluid-derived EVs cargo in women may help in the discovery of novel biomarkers and therapeutics for the treatment of OA in women. Previously, we reported that synovial fluid-derived EV miRNA cargo differs in a sex-specific manner. This study aims to characterize synovial fluid-derived EV protein cargo in OA patients. Our data showed sex-specific EVs protein content in OA. We found haptoglobin, orosomucoid, and ceruloplasmin significantly up-regulated, whereas apolipoprotein down-regulated in female OA EVs. In males, we discovered β-2-glycoprotein, and complement component 5 proteins significantly up-regulated and Spt-Ada-Gcn5 acetyltransferase (SAGA)-associated factor 29 down-regulated in male OA EVs. Database for Annotation, Visualization, and Integrated Discovery (DAVID) and QuickGO analysis revealed OA-specific protein involvement in several biological, molecular, and cellular pathways, specifically in inflammatory processes. In conclusion, synovial fluid EV protein content is altered in a sex-specific manner with OA, explaining the increased prevalence and severity of OA in women.

Abstract WMP30: Circulating MicroRNAs as Potential Novel Diagnostic Biomarkers for Ruptured Intracranial Aneurysm

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Zhang Xin ◽  
Liu L Ping
Keyword(s):  
Intracranial Aneurysm ◽  
Target Genes ◽  
Bioinformatic Analysis ◽  
Aneurysm Rupture ◽  
Pathological Process ◽  
Differentially Expressed ◽  
Diagnostic Biomarkers ◽  
Ruptured Intracranial Aneurysm ◽  
Novel Biomarkers ◽  
Aneurysm Development

Background and Objective: MicroRNAs have been shown to regulate in several pathological process of intracranial aneurysms. The study aimed to estimate whether miRNAs have the potential to become novel biomarkers for intracranial aneurysm rupture. Materials and methods Forty-five ruptured intracranial aneurysm patients were enrolled according to the inclusion criteria, meanwhile thirty-five healthy individuals were recruited in this study. Differentially expressed plasma miRNA profiles were screened in five pairs of patients and controls in microarray study. Then validation was performed in the rest of the objects using quantitative real-time PCR assays. Results: Fourteen significantly changed miRNAs were screened out from patients with aneurysms compared with healthy controls. More than three thousand target genes related to these disregulated miRNAs were found and bioinformatic analysis revealed that these miRNA were involved in intracranial aneurysm development and rupture. Ultimately four miRNAs from screening profile and one supplementary miRNA were demonstrated to be significantly altered. Conclusion: We demonstrated that several miRNAs were differentially expressed among ruptured aneurysm patients and healthy participants, and plasma miRNAs may be novel diagnostic biomarkers in intracranial aneurysm rupture.

scholarly journals Identification of Potential Early Diagnostic Biomarkers of Sepsis

2021 ◽  
Vol Volume 14 ◽  
pp. 621-631
Author(s):  
Zhenhua Li ◽  
Bin Huang ◽  
Wenfeng Yi ◽  
Fei Wang ◽  
Shizhuang Wei ◽  
...  
Keyword(s):  
Diagnostic Biomarkers ◽  
Early Diagnostic

scholarly journals Nucleases as molecular targets for cancer diagnosis

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Alien Balian ◽  
Frank J. Hernandez
Keyword(s):  
Enzymatic Activity ◽  
Cancer Diagnosis ◽  
Essential Feature ◽  
Treatment Options ◽  
Cancer Biomarkers ◽  
Diagnostic Biomarkers ◽  
Early Cancer Diagnosis ◽  
Novel Biomarkers ◽  
Made In

AbstractEarly cancer diagnosis is a crucial element to improved treatment options and survival. Great research efforts have been made in the search for better performing cancer diagnostic biomarkers. However, the quest continues as novel biomarkers with high accuracy for an early diagnosis remain an unmet clinical need. Nucleases, which are enzymes capable of cleaving nucleic acids, have been long considered as potential cancer biomarkers. The implications of nucleases are key for biological functions, their presence in different cellular counterparts and catalytic activity led the enthusiasm towards investigating the role of nucleases as promising cancer biomarkers. However, the most essential feature of these proteins, which is their enzymatic activity, has not been fully exploited. This review discusses nucleases interrogated as cancer biomarkers, providing a glimpse of their physiological roles. Moreover, it highlights the potential of harnessing the enzymatic activity of cancer-associated nucleases as a novel diagnostic biomarker using nucleic acid probes as substrates.

scholarly journals Dissonant roles: the experience of Maori in cancer care.

2020 ◽  
Author(s):  
Kevin Dew ◽  
L Signal ◽  
C Davies ◽  
T Huia ◽  
C Hooper ◽  
...  
Keyword(s):  
Survival Rates ◽  
Quality Of Healthcare ◽  
Sick Role ◽  
Membership Categorization Analysis ◽  
Care Access ◽  
Aotearoa New Zealand ◽  
Membership Categorization ◽  
Alternative Approaches ◽  
Insight Into

© 2015 Elsevier Ltd. Indigenous peoples have poorer health outcomes than their non-indigenous counterparts and this applies to cancer outcomes for Maori in Aotearoa/New Zealand. Differential access to and quality of healthcare contributes to poorer survival rates for Maori. This research provides insight into some of the mechanisms that hinder and facilitate care access. Thirty four people who had undergone cancer treatment (19Maori and 15 non-Maori) were interviewed by two Maori researchers. The analysis of the interview transcripts was informed by membership categorization analysis. This form of analysis attends to the categories that are used and the activities and characteristics associated with those categories. From this analysis it is argued that the classical patient role, or sick role, inadequately captures the kind of role that some Maori take in relation to their healthcare. Maori can also have culturally specific family (whanau) influences and a greater draw towards alternative approaches to healthcare. Dissonant roles contribute to a different experience for Maori. A better understanding of the categories and roles that are relevant to those who have cancer provides opportunities to attenuate the monocultural impacts of healthcare.

scholarly journals Metabolic Activation and Covalent Protein Binding of Berberrubine: Insight into the Underlying Mechanism Related to Its Hepatotoxicity

2020 ◽  
Vol Volume 14 ◽  
pp. 4423-4438
Author(s):  
Kai Wang ◽  
Jinqiu Rao ◽  
Tingting Zhang ◽  
Qing Gao ◽  
Jichao Zhang ◽  
...  
Keyword(s):  
Protein Binding ◽  
Metabolic Activation ◽  
Underlying Mechanism ◽  
Covalent Protein Binding ◽  
Insight Into

scholarly journals Mechanism of riboregulation of p62 protein oligomerisation by vault RNA1-1 in selective autophagy

2021 ◽  
Author(s):  
Magdalena Buescher ◽  
Rastislav Horos ◽  
Kevin Haubrich ◽  
Nikolay Dobrev ◽  
Florence Baudin ◽  
...  
Keyword(s):  
Chemical Structure ◽  
Membrane Vesicles ◽  
Underlying Mechanism ◽  
Selective Autophagy ◽  
Ubiquitinated Proteins ◽  
Flexible Loop ◽  
Structure Probing ◽  
Molecular Determinants ◽  
Necessary And Sufficient ◽  
Insight Into

Macroautophagy ensures the clearance of intracellular substrates ranging from single ubiquitinated proteins to large proteotoxic aggregates and defective organelles. The selective autophagy receptor p62 binds these targets and recruits them to double-membrane vesicles, which fuse with lysosomes to degrade their content. We recently uncovered that p62 function is riboregulated by the small non-coding vault RNA1-1. Here, we present detailed insight into the underlying mechanism. We show that the PB1 domain and adjacent linker region of p62 (aa 1-122) are necessary and sufficient for specific vault RNA1-1 binding, and identify lysine 7 and arginine 21 as key hinges for p62 riboregulation. Chemical structure probing of vault RNA1-1 further reveals a central flexible loop within the RNA that mediates the specific p62 interaction. Our data define molecular determinants that govern mammalian autophagy via the p62-vault RNA1-1 riboregulatory pair.

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