scholarly journals Integration of global metabolomics and lipidomics approaches reveals the molecular mechanisms and the potential biomarkers for postoperative recurrence in early-stage cholangiocarcinoma

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Sureerat Padthaisong ◽  
Jutarop Phetcharaburanin ◽  
Poramate Klanrit ◽  
Jia V. Li ◽  
Nisana Namwat ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Early Stage ◽  
Survival Rates ◽  
Cancer Recurrence ◽  
Tca Cycle ◽  
Postoperative Recurrence ◽  
Lipid Uptake ◽  
Predictive Values ◽  
H Nmr ◽  
Potential Biomarker

Abstract Background Cholangiocarcioma (CCA) treatment is challenging because most of the patients are diagnosed when the disease is advanced, and cancer recurrence is the main problem after treatment, leading to low survival rates. Therefore, our understanding of the mechanism underlying CCA recurrence is essential in order to prevent CCA recurrence and improve patient outcomes. Methods We performed 1H-NMR and UPLC-MS-based metabolomics on the CCA serum. The differential metabolites were further analyzed using pathway analysis and potential biomarker identification. Results At an early stage, the metabolites involved in energy metabolisms, such as pyruvate metabolism, and the TCA cycle, are downregulated, while most lipids, including TGs, PCs, PEs, and PAs, are upregulated in recurrence patients. This metabolic feature has been described in cancer stem-like cell (CSC) metabolism. In addition, the CSC markers CD44v6 and CD44v8-10 are associated with CD36 (a protein involved in lipid uptake) as well as with recurrence-free survival. We also found that citrate, sarcosine, succinate, creatine, creatinine and pyruvate, and TGs have good predictive values for CCA recurrence. Conclusion Our study demonstrates the possible molecular mechanisms underlying CCA recurrence, and these may associate with the existence of CSCs. The metabolic change involved in the recurrence pathway might be used to determine biomarkers for predicting CCA recurrence.

scholarly journals Integration of Global Metabolomics and Lipidomics Approaches Reveals the Molecular Mechanisms and the Potential Biomarkers for Post-Operative Recurrence in Early Stage Cholangiocarcinoma

2020 ◽  
Author(s):  
Sureerat Padthaisong ◽  
Jutarop Phetcharaburanin ◽  
Poramate Klanrit ◽  
Jia V. Li ◽  
Nisana Namwat ◽  
...  
Keyword(s):  
Metabolic Profile ◽  
Molecular Mechanisms ◽  
Early Stage ◽  
Survival Rates ◽  
Recurrence Free Survival ◽  
Lipid Uptake ◽  
Major Health Problem ◽  
Predictive Values ◽  
Free Survival ◽  
Potential Biomarkers

Abstract Background: Cholangiocarcioma (CCA) is a major health problem for people in Thailand. The treatment is challenging because most of patients are diagnosed when the disease is advanced, and cancer recurrence is the main problem after treatment, leading to low survival rates. Therefore, our understanding of the mechanism underlying CCA recurrence is essential in order to prevent CCA recurrence and improve patient outcome. Methods: We performed 1H-NMR and UPLC-MS based-metabolomics on CCA serum. The differential metabolites were further analyzed using pathway analysis and potential biomarkers identification.Results: At an early stage, CCA patients with recurrence have a different metabolic profile compared with non-recurrence patients. In recurrence patients, the metabolites involved in energy metabolism, such as pyruvate metabolism and the TCA cycle, are down-regulated, while most lipids, including TGs, PCs, PEs and Pas, are up-regulated. This metabolic feature has been described in cancer stem-like cell (CSC) metabolism. Based on this, the correlation of putative CSC markers and proteins involved in identified pathways, together with recurrence-free survival was explored. The results revealed that the expression levels of the CSC markers CD44v6 and CD44v8-10 are associated with CD36 (a protein involved in lipid uptake) as well as with recurrence-free survival. Potential metabolic biomarkers were identified using ROC and Kaplan-Meier analyses. We found that citrate, sarcosine, succinate, creatine, creatinine and pyruvate and TGs have good predictive values for CCA recurrence and are associated with recurrence-free survival. Conclusions: These findings reveal an alteration of the metabolic profile associated with recurrence. These metabolic changes may be associated with the existence of CSCs that lead to CCA recurrence. Moreover, the alteration of metabolites was shown to provide suitable biomarkers for CCA recurrence. Therefore, the differential metabolites between patients with and without recurrence can be used as biomarkers for CCA recurrence.

scholarly journals Early alterations of neurovascular unit in the retina in mouse models of tauopathy

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Fan Xia ◽  
Yonju Ha ◽  
Shuizhen Shi ◽  
Yi Li ◽  
Shengguo Li ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Mouse Models ◽  
Molecular Mechanisms ◽  
Early Stage ◽  
Leukocyte Adhesion ◽  
Neurovascular Unit ◽  
Integrated Analysis ◽  
Therapeutic Effects ◽  
Retinal Ganglion ◽  
Potential Biomarker

AbstractThe retina, as the only visually accessible tissue in the central nervous system, has attracted significant attention for evaluating it as a biomarker for neurodegenerative diseases. Yet, most of studies focus on characterizing the loss of retinal ganglion cells (RGCs) and degeneration of their axons. There is no integrated analysis addressing temporal alterations of different retinal cells in the neurovascular unit (NVU) in particular retinal vessels. Here we assessed NVU changes in two mouse models of tauopathy, P301S and P301L transgenic mice overexpressing the human tau mutated gene, and evaluated the therapeutic effects of a tau oligomer monoclonal antibody (TOMA). We found that retinal edema and breakdown of blood–retina barrier were observed at the very early stage of tauopathy. Leukocyte adhesion/infiltration, and microglial recruitment/activation were constantly increased in the retinal ganglion cell layer of tau transgenic mice at different ages, while Müller cell gliosis was only detected in relatively older tau mice. Concomitantly, the number and function of RGCs progressively decreased during aging although they were not considerably altered in the very early stage of tauopathy. Moreover, intrinsically photosensitive RGCs appeared more sensitive to tauopathy. Remarkably, TOMA treatment in young tau transgenic mice significantly attenuated vascular leakage, inflammation and RGC loss. Our data provide compelling evidence that abnormal tau accumulation can lead to pathology in the retinal NVU, and vascular alterations occur more manifest and earlier than neurodegeneration in the retina. Oligomeric tau-targeted immunotherapy has the potential to treat tau-induced retinopathies. These data suggest that retinal NVU may serve as a potential biomarker for diagnosis and staging of tauopathy as well as a platform to study the molecular mechanisms of neurodegeneration.

scholarly journals Discovery and validation of novel protein markers in mucosa of portal hypertensive gastropathy

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ying Zhu ◽  
Wen Xu ◽  
Wei Hu ◽  
Fang Wang ◽  
Yan Zhou ◽  
...  
Keyword(s):  
Portal Hypertension ◽  
Gastric Mucosa ◽  
Molecular Mechanisms ◽  
Early Stage ◽  
Trial Registration ◽  
Portal Hypertensive Gastropathy ◽  
Protein Markers ◽  
Decompensated Liver Cirrhosis ◽  
Potential Biomarker ◽  
Normal Controls

Abstract Background Portal hypertension induced esophageal and gastric variceal bleeding is the main cause of death among patients of decompensated liver cirrhosis. Therefore, a standardized, biomarker-based test, to make an early-stage non-invasive risk assessment of portal hypertension, is highly desirable. However, no fit-for-purpose biomarkers have yet been identified. Methods We conducted a pilot study consisting of 5 portal hypertensive gastropathy (PHG) patients and 5 normal controls, sampling the gastric mucosa of normal controls and PHG patients before and after endoscopic cyanoacrylate injection, using label-free quantitative (LFQ) mass spectrometry, to identify potential biomarker candidates in gastric mucosa from PHG patients and normal controls. Then we further used parallel reaction monitoring (PRM) to verify the abundance of the targeted protein. Results LFQ analyses identified 423 significantly differentially expressed proteins. 17 proteins that significantly elevated in the gastric mucosa of PHG patients were further validated using PRM. Conclusions This is the first application of an LFQ-PRM workflow to identify and validate PHG–specific biomarkers in patient gastric mucosa samples. Our findings lay the foundation for comprehending the molecular mechanisms of PHG pathogenesis, and provide potential applications for useful biomarkers in early diagnosis and treatment. Trial registration and ethics approval: Trial registration was completed (ChiCTR2000029840) on February 25, 2020. Ethics Approvals were completed on July 17, 2017 (NYSZYYEC20180003) and February 15, 2020 (NYSZYYEC20200005).

scholarly journals MTA2 as a Potential Biomarker and Its Involvement in Metastatic Progression of Human Renal Cancer by miR-133b Targeting MMP-9

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1851 ◽  
Author(s):  
Yong-Syuan Chen ◽  
Tung-Wei Hung ◽  
Shih-Chi Su ◽  
Chia-Liang Lin ◽  
Shun-Fa Yang ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Survival Rates ◽  
The Cancer Genome Atlas ◽  
Metastatic Progression ◽  
Tumour Grade ◽  
Potential Biomarker ◽  
Cancer Genome Atlas ◽  
Metalloproteinase 9

Metastasis-associated protein 2 (MTA2) was previously known as a requirement to maintain malignant potentials in several human cancers. However, the role of MTA2 in the progression of renal cell carcinoma (RCC) has not yet been delineated. In this study, MTA2 expression was significantly increased in RCC tissues and cell lines. Increased MTA2 expression was significantly associated with tumour grade (p = 0.002) and was an independent prognostic factor for overall survival with a high RCC tumour grade. MTA2 knockdown inhibited the migration, invasion, and in vivo metastasis of RCC cells without effects on cell proliferation. Regarding molecular mechanisms, MTA2 knockdown reduced the activity, protein level, and mRNA expression of matrix metalloproteinase-9 (MMP-9) in RCC cells. Further analyses demonstrated that patients with lower miR-133b expression had poorer survival rates than those with higher expression from The Cancer Genome Atlas database. Moreover, miR-133b modulated the 3′untranslated region (UTR) of MMP-9 promoter activities and subsequently the migratory and invasive abilities of these dysregulated expressions of MTA2 in RCC cells. The inhibition of MTA2 could contribute to human RCC metastasis by regulating the expression of miR-133b targeting MMP-9 expression.

scholarly journals Discovery and Validation of Novel Protein Markers in Mucosa of Portal Hypertensive Gastropathy

2021 ◽  
Author(s):  
Ying Zhu ◽  
Wen Xu ◽  
Wei Hu ◽  
Fang Wang ◽  
Yan Zhou ◽  
...  
Keyword(s):  
Portal Hypertension ◽  
Gastric Mucosa ◽  
Molecular Mechanisms ◽  
Early Stage ◽  
Trial Registration ◽  
Portal Hypertensive Gastropathy ◽  
Protein Markers ◽  
Decompensated Liver Cirrhosis ◽  
Potential Biomarker ◽  
Normal Controls

Abstract Background: Portal hypertension induced esophageal and gastric varix bleeding is the main cause of death among patients of decompensated liver cirrhosis. Therefore, a standardized, biomarker-based test, to make an early-stage non-invasive risk assessment of portal hypertension, is highly desirable. However, no fit-for-purpose biomarkers have yet been identified. Methods: We conducted a pilot study consisting of 5 portal hypertensive gastropathy (PHG) patients and 5 normal controls, sampling the gastric mucosa of normal controls and PHG patients before and after endoscopic cyanoacrylate injection, using label-free quantitative (LFQ) mass spectrometry, to identify potential biomarker candidates in gastric mucosa from PHG patients and normal controls. Then we further used parallel reaction monitoring (PRM) to verify the abundance of the targeted protein. Results: LFQ analyses identified 423 significantly differentially expressed proteins. 17 protein that significantly elevated in the gastric mucosa of PHG patients were further validated using PRM. Conclusions: This is the first application of an LFQ-PRM workflow to identify and validate PHG–specific biomarkers in patient gastric mucosa samples. Our findings lay the foundation for comprehending the molecular mechanisms of PHG pathogenesis, and provide potential applications for useful biomarkers in early diagnosis and treatment.Trial Registration: Trial registration was completed (ChiCTR2000029840) on February 25, 2020.

scholarly journals Diagnostic and Prognostic Potential of AKR1B10 in Human Hepatocellular Carcinoma

Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 486 ◽  
Author(s):  
Johanna DiStefano ◽  
Bethany Davis
Keyword(s):  
Hepatocellular Carcinoma ◽  
Molecular Mechanisms ◽  
Early Stage ◽  
Acquired Resistance ◽  
Experimental Studies ◽  
Chemotherapeutic Agents ◽  
Clinical Value ◽  
Surgical Interventions ◽  
Diagnostic Measures ◽  
Potential Biomarker

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Although diagnostic measures and surgical interventions have improved in recent years, the five-year survival rate for patients with advanced HCC remains bleak—a reality that is largely attributable to an absence of early stage symptoms, lack of adequate diagnostic and prognostic biomarkers, and the common occurrence of acquired resistance to chemotherapeutic agents during HCC treatment. A limited understanding of the molecular mechanisms underlying HCC pathogenesis also presents a challenge for the development of specific and efficacious pharmacological strategies to treat, halt, or prevent progression to advanced stages. Over the past decade, aldo-keto reductase family 1 member 10 (AKR1B10) has emerged as a potential biomarker for the diagnosis and prognosis of HCC, and experimental studies have demonstrated roles for this enzyme in biological pathways underlying the development and progression of HCC and acquired resistance to chemotherapeutic agents used in the treatment of HCC. Here we provide an overview of studies supporting the diagnostic and prognostic utility of AKR1B10, summarize the experimental evidence linking AKR1B10 with HCC and the induction of chemoresistance, and discuss the clinical value of AKR1B10 as a potential target for HCC-directed drug development. We conclude that AKR1B10-based therapies in the clinical management of specific HCC subtypes warrant further investigation.

NOB1: A Potential Biomarker or Target in Cancer

2019 ◽  
Vol 20 (10) ◽  
pp. 1081-1089
Author(s):  
Weiwei Ke ◽  
Zaiming Lu ◽  
Xiangxuan Zhao
Keyword(s):  
Cancer Treatment ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Binding Protein ◽  
Tumor Development ◽  
Anticancer Therapy ◽  
Research Progress ◽  
Normal Tissues ◽  
Potential Biomarker

Human NIN1/RPN12 binding protein 1 homolog (NOB1), an RNA binding protein, is expressed ubiquitously in normal tissues such as the lung, liver, and spleen. Its core physiological function is to regulate protease activities and participate in maintaining RNA metabolism and stability. NOB1 is overexpressed in a variety of cancers, including pancreatic cancer, non-small cell lung cancer, ovarian cancer, prostate carcinoma, osteosarcoma, papillary thyroid carcinoma, colorectal cancer, and glioma. Although existing data indicate that NOB1 overexpression is associated with cancer growth, invasion, and poor prognosis, the molecular mechanisms behind these effects and its exact roles remain unclear. Several studies have confirmed that NOB1 is clinically relevant in different cancers, and further research at the molecular level will help evaluate the role of NOB1 in tumors. NOB1 has become an attractive target in anticancer therapy because it is overexpressed in many cancers and mediates different stages of tumor development. Elucidating the role of NOB1 in different signaling pathways as a potential cancer treatment will provide new ideas for existing cancer treatment methods. This review summarizes the research progress made into NOB1 in cancer in the past decade; this information provides valuable clues and theoretical guidance for future anticancer therapy by targeting NOB1.

Molecular Processes Involved in Pancreatic Cancer and Therapeutics

2020 ◽  
Vol 14 ◽  
Author(s):  
Subhajit Makar ◽  
Abhrajyoti Ghosh ◽  
Divya ◽  
Shalini Shivhare ◽  
Ashok Kumar ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Molecular Mechanisms ◽  
Early Stage ◽  
Locally Advanced ◽  
Therapeutic Strategies ◽  
Screening Methods ◽  
Pancreatic Cancer Cells ◽  
Systemic Treatments ◽  
Cancer Initiation ◽  
Novel Therapeutic Strategies

: Despite advances in the development of cytotoxic and targeted therapies, pancreatic adenocarcinoma (PAC) remains a significant cause of cancer mortality worldwide. It is also difficult to detect it at an early stage due to numbers of factors. Most of the patients are present with locally advanced or metastatic disease, which precludes curative resection. In the absence of effective screening methods, considerable efforts have been made to identify better systemic treatments during the past decade. This review describes the recent advances in molecular mechanisms involved in pancreatic cancer initiation, progression, and metastasis. Additionally, the importance of deregulated cellular signalling pathways and various cellular proteins as potential targets for developing novel therapeutic strategies against incurable forms of pancreatic cancer is reported. The emphasis is on the critical functions associated with growth factors and their receptors viz. c-MET/HGF, CTHRC1, TGF-β, JAK-STAT, cyclooxygenase pathway, WNT, CCK, MAPK-RAS-RAF, PI3K-AKT, Notch, src, IGF-1R, CDK2NA and chromatin regulation for the sustained growth, survival, and metastasis of pancreatic cancer cells. It also includes various therapeutic strategies viz. immunotherapy, surgical therapy, radiation therapy and chemotherapy.

scholarly journals The survival rates and risk factors of implants in the early stage: a retrospective study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yong Yang ◽  
Huiting Hu ◽  
Mianyan Zeng ◽  
Hongxing Chu ◽  
Zekun Gan ◽  
...  
Keyword(s):  
Risk Factors ◽  
Survival Rate ◽  
Dental Implants ◽  
Bone Quality ◽  
Early Stage ◽  
Survival Rates ◽  
Bone Augmentation ◽  
Early Survival ◽  
Immediate Implantation ◽  
Implant Length

Abstract Background Few large-sample studies in China have focused on the early survival of dental implants. The present study aimed to report the early survival rates of implants and determine the related influencing factors. Methods All patients receiving dental implants at our institution between 2006 and 2017 were included. The endpoint of the study was early survival rates of implants, according to gender, age, maxilla/mandible, dental position, bone augmentation, bone augmentation category, immediate implant, submerged implant category, implant diameter, implant length, implant torque, and other related factors. Initially, SPSS22.0 was used for statistical analysis. The Chi-square test was used to screen all factors, and those with p < 0.05 were further introduced into a multiple logistic regression model to illustrate the risk factors for early survival rates of implants. Results In this study, we included 1078 cases (601 males and 477 females) with 2053 implants. After implantation, 1974 implants were retained, and the early survival rate was 96.15%. Patients aged 30–60 years (OR  2.392), with Class I bone quality (OR  3.689), bone augmentation (OR  1.742), immediate implantation (OR  3.509), and implant length < 10 mm (OR  2.972), were said to possess risk factors conducive to early survival rates. Conclusions The early survival rate of implants in our cohort exceeded 96%, with risk factors including age, tooth position, bone quality, implant length, bone augmentation surgery, and immediate implantation. When the above factors coexist, implant placement should be treated carefully.

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