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Biomedicines
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The Biomarkers for the Diagnosis, Prognosis and Treatments Response in...
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The Biomarkers for the Diagnosis, Prognosis and Treatments Response in Digestive Disorders

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 10956

Special Issue Editors

Dr. Alessandro Coppola

E-Mail Website
Guest Editor
General Surgery Unit, Surgery Center, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy
Interests: hepatobiliary-pancreatic surgery and cancers; abdominal surgical oncology; liver and pancreatic benign and chronic diseases
Special Issues, Collections and Topics in MDPI journals
Dr. Michele Fiore

E-Mail Website
Guest Editor
Radiation Oncology, Campus Bio-Medico University, 00128 Rome, Italy
Interests: pancreatic neoplasms; head and neck neoplasms; clinical dosimetry; special techniques - modulated intensity radiation therapy, stereotaxy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The management of cancer involves the use of biomarkers from diagnosis to follow up, exceeding the effectiveness of therapeutic radio-chemotherapy or surgical treatments. In addition, in patients with digestive disorders, biomarkers have a crucial role in the fight against this deathful disease.

The role of this Special Issue is to report the most recent knowledge regarding the relationship between biomarkers and digestive disorders. Furthermore, much attention will be paid to the contributions that highlight the potential role that markers may play in guiding therapeutic decisions (e.g., to start neoadjuvant treatments or not) in the treatment of digestive disorders.

Another interesting aspect is the role of markers in precancerous diseases and in aiding the early diagnosis of digestive disorders, as they appear to improve survival in these cases.

Finally, the use of markers as a tool for evaluating the effect of neoadjuvant, surgical and adjuvant treatments on the response to therapy, as well as their role in the follow up, will be discussed.

You are kindly invited to share your knowledge, purposes, and recent advances in digestive disorders, focused on biomarkers, in this Special Issue of Biomedicines.

Dr. Alessandro Coppola
Dr. Michele Fiore
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • digestive disorders
  • oncological markers
  • treatment response
  • cancer prognosis
  • new molecular markers
  • early diagnosis

Published Papers (6 papers)

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Research

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16 pages, 4931 KiB  
Article
Co-Expression of Chromatin Assembly Factor 1 Subunit A and Proliferating Cell Nuclear Antigen Is a Prognostic Biomarker of Esophageal Cancer
by Bing Wen, Dan-Xia Deng, Lian-Di Liao, Zhi-Da Zhang, Ya-Qi Zheng, Ke Dong, Li-Yan Xu and En-Min Li
Biomedicines 2023, 11(4), 1184; https://doi.org/10.3390/biomedicines11041184 - 16 Apr 2023
Viewed by 1209
Abstract
(1) Background: Esophageal cancer (EC) is an important global health challenge. Due to the lack of necessary biomarkers and therapeutic targets, the survival of EC patients is poor. The EC proteomic data of 124 patients recently published by our group provides a database [...] Read more.
(1) Background: Esophageal cancer (EC) is an important global health challenge. Due to the lack of necessary biomarkers and therapeutic targets, the survival of EC patients is poor. The EC proteomic data of 124 patients recently published by our group provides a database for research in this field. (2) Methods: Bioinformatics analysis was used to identify DNA replication and repair-related proteins in EC. Proximity ligation assay, colony formation assay, DNA fiber assay, and flow cytometry were used to study the effects of related proteins on EC cells. Kaplan–Meier survival analysis was used to evaluate the relationship between gene expression and the survival time of EC patients. (3) Results: Chromatin assembly factor 1 subunit A (CHAF1A) was highly correlated with proliferating cell nuclear antigen (PCNA) expression in EC. CHAF1A and PCNA colocalized in the nucleus of EC cells. Compared with the knockdown of CHAF1A or PCNA alone, the double knockdown of CHAF1A and PCNA could significantly inhibit EC cell proliferation. Mechanistically, CHAF1A and PCNA synergistically accelerated DNA replication and promoted S-phase progression. EC patients with high expression of both CHAF1A and PCNA had a worse survival rate. (4) Conclusion: we identify CHAF1A and PCNA as key cell cycle-related proteins leading to the malignant progression of EC, and these proteins could serve as important prognostic biomarkers and targets for EC. Full article
(This article belongs to the Special Issue The Biomarkers for the Diagnosis, Prognosis and Treatments Response in Digestive Disorders)
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8 pages, 481 KiB  
Article
Endoscopic Surveillance of Esophageal Atresia Population according to ESPGHAN-NASPGHAN 2016 Guidelines: Incidence of Eosinophilic Esophagitis and New Histological Findings
by Francesca Maestri, Anna Morandi, Martina Ichino, Giorgio Fava, Giacomo Cavallaro, Ernesto Leva and Francesco Macchini
Biomedicines 2022, 10(11), 2836; https://doi.org/10.3390/biomedicines10112836 - 07 Nov 2022
Viewed by 1307
Abstract
Follow-up of children born with esophageal atresia (EA) is mandatory due to high incidence of comorbidities. We evaluated endoscopic findings at follow-up of EA patients performed at our Centre according to ESPGHAN-NASPGHAN 2016 guidelines. A retrospective observational study was performed using data from [...] Read more.
Follow-up of children born with esophageal atresia (EA) is mandatory due to high incidence of comorbidities. We evaluated endoscopic findings at follow-up of EA patients performed at our Centre according to ESPGHAN-NASPGHAN 2016 guidelines. A retrospective observational study was performed using data from January 2016 to January 2021. We included EA patients (age range: 1–18 years) who were offered a program of endoscopic and histological high gastrointestinal (GI) tract examinations as per ESPGHAN-NASPGHAN 2016 guidelines. Clinical, surgical, auxological, endoscopic, and histological data were reviewed; variables as polyhydramnios, EA type, surgical type, enteral feeding introduction age, growth data, and symptoms were correlated to endoscopic and histological findings. The population included 75 patients (47 males), with mean age of 5 ± 4 years. In 40/75 (53.3%) patients, we recorded oral feeding problems, and upper gastrointestinal or respiratory symptoms suspicious of gastroesophageal reflux. Eosinophilic esophagitis (EoE) incidence was 9/75 (12%), significantly higher than in general population (p < 0.0001), and 10/75 (13.3%) presented non-specific duodenal mucosal lesions. EoE represents a frequent comorbidity of EA, as previously known. EA is also burdened by high, never-described incidence of non-specific duodenal mucosal lesions. Embedding high GI tract biopsies in EA endoscopic follow-up should be mandatory from pediatric age. Full article
(This article belongs to the Special Issue The Biomarkers for the Diagnosis, Prognosis and Treatments Response in Digestive Disorders)
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26 pages, 3672 KiB  
Article
Characterization of Mesothelin Glycosylation in Pancreatic Cancer: Decreased Core Fucosylated Glycoforms in Pancreatic Cancer Patients’ Sera
by Adrià Duran, Pedro E. Guerrero, Maria Rosa Ortiz, Dúnia Pérez del Campo, Ernesto Castro, Adelaida Garcia-Velasco, Esther Fort, Rafael de Llorens, Radka Saldova, Esther Llop and Rosa Peracaula
Biomedicines 2022, 10(8), 1942; https://doi.org/10.3390/biomedicines10081942 - 10 Aug 2022
Cited by 1 | Viewed by 2142
Abstract
Currently, there are no reliable biomarkers for the diagnosis of pancreatic cancer (PaC). Glycoproteomic approaches that analyze the glycan determinants on specific glycoproteins have proven useful to develop more specific cancer biomarkers than the corresponding protein levels. In PaC, mesothelin (MSLN) is a [...] Read more.
Currently, there are no reliable biomarkers for the diagnosis of pancreatic cancer (PaC). Glycoproteomic approaches that analyze the glycan determinants on specific glycoproteins have proven useful to develop more specific cancer biomarkers than the corresponding protein levels. In PaC, mesothelin (MSLN) is a neo-expressed glycoprotein. MSLN glycosylation has not been described and could be altered in PaC. In this work, we aimed to characterize MSLN glycans from PaC cells and serum samples to assess their potential usefulness as PaC biomarkers. First, we analyzed MSLN glycans from PaC cell lines and then we developed an enzyme-linked lectin assay to measure core fucosylated-MSLN (Cf-MSLN) glycoforms. MSLN glycans from PaC cells were analyzed by glycan sequencing and through Western blotting with lectins. All of the cell lines secreted MSLN, with its three N-glycosylation sites occupied by complex-type N-glycans, which were mainly α2,3-sialylated, core fucosylated and highly branched. The Cf-MSLN glycoforms were quantified on PaC serum samples, and compared with MSLN protein levels. The Cf-MSLN was significantly decreased in PaC patients compared to control sera, while no differences were detected by using MSLN protein levels. In conclusion, Cf-MSLN glycoforms were differently expressed in PaC, which opens the way to further investigate their usefulness as PaC biomarkers. Full article
(This article belongs to the Special Issue The Biomarkers for the Diagnosis, Prognosis and Treatments Response in Digestive Disorders)
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15 pages, 1389 KiB  
Article
High Arterial Lactate Levels after Hepatic Resection Are Associated with Low Oxygen Delivery and Predict Severe Postoperative Complications
by Rita Gaspari, Luciana Teofili, Francesco Ardito, Enrica Adducci, Maria Vellone, Caterina Mele, Nicoletta Orlando, Tiziana Iacobucci, Massimo Antonelli and Felice Giuliante
Biomedicines 2022, 10(5), 1108; https://doi.org/10.3390/biomedicines10051108 - 10 May 2022
Viewed by 1472
Abstract
High End-Surgery Arterial Lactate Concentration (ES-ALC) predicts poor outcome after hepatectomy. The aim of this study was to identify intraoperative hemodynamic parameters predicting high ES-ALC during elective liver resection. Patients who underwent liver resection between 2017 and 2018, under FloTrac/EV1000TM hemodynamic monitoring, [...] Read more.
High End-Surgery Arterial Lactate Concentration (ES-ALC) predicts poor outcome after hepatectomy. The aim of this study was to identify intraoperative hemodynamic parameters predicting high ES-ALC during elective liver resection. Patients who underwent liver resection between 2017 and 2018, under FloTrac/EV1000TM hemodynamic monitoring, were included. The ES-ALC cutoff best predicting severe postoperative complications was identified. Association between high ES-ALC and preoperative and intraoperative variables was assessed. 108 patients were included; 90-day mortality was 0.9% and severe morbidity 14.8%. ES-ALC cutoff best discriminating severe complications was 5.05 mmol/L. Patients with ES-ALC > 5.0 mmol/L had a relative risk of severe complications of 2.8% (p = 0.004). High ES-ALC patients had longer surgery and ischemia duration, larger blood losses and higher requirements of fluids and blood transfusions. During surgery, hemoglobin concentration and oxygen delivery (DO2) decreased more significantly in patients with high ES-ALC, although they had similar values of stroke volume and cardiac output to those of other patients. At multivariate analysis, surgery duration and lowest recorded DO2 value were the strongest predictors of high ES-ALC. ES-ALC > 5.0 mmol/L in elective liver resection predicts postoperative morbidity and is essentially driven by the impaired DO2. Timely correction of blood losses might prevent the ES-ALC increase. Full article
(This article belongs to the Special Issue The Biomarkers for the Diagnosis, Prognosis and Treatments Response in Digestive Disorders)
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14 pages, 34007 KiB  
Article
Evaluation of AIF-1 (Allograft Inflammatory Factor-1) as a Biomarker of Crohn’s Disease Severity
by Luis G. Guijarro, David Cano-Martínez, M. Val Toledo-Lobo, Lidia Ruiz-Llorente, María Chaparro, Iván Guerra, Marisa Iborra, José Luis Cabriada, Luis Bujanda, Carlos Taxonera, Valle García-Sánchez, Ignacio Marín-Jiménez, Manuel Barreiro-de Acosta, Isabel Vera, María Dolores Martín-Arranz, Francisco Mesonero, Laura Sempere, Fernando Gomollón, Joaquín Hinojosa, Sofía Zoullas, Jorge Monserrat, Cesar Menor-Salvan, Melchor Alvarez-Mon, Javier P. Gisbert, Miguel A. Ortega and Borja Hernández-Breijoadd Show full author list remove Hide full author list
Biomedicines 2022, 10(3), 727; https://doi.org/10.3390/biomedicines10030727 - 21 Mar 2022
Cited by 5 | Viewed by 2417
Abstract
Background: Recently, increased tissue levels of AIF-1 have been shown in experimental colitis, supporting its role in intestinal inflammation. Therefore, we studied the levels of AIF-1 in Crohn’s disease (CD). Methods: This study included 33 patients with CD (14 men and 19 women) [...] Read more.
Background: Recently, increased tissue levels of AIF-1 have been shown in experimental colitis, supporting its role in intestinal inflammation. Therefore, we studied the levels of AIF-1 in Crohn’s disease (CD). Methods: This study included 33 patients with CD (14 men and 19 women) who participated in the PREDICROHN project, a prospective multicenter study of the Spanish Group of Inflammatory bowel disease (GETECCU). Results: This article demonstrates declines with respect to baseline levels of serum AIF-1 in Crohn’s disease (CD) patients after 14 weeks of treatment with anti-TNFs. Furthermore, in patients with active CD (HB ≥ 5), serum AIF-1 levels were significantly higher than those in patients without activity (HB ≤ 4). The study of serum AIF-1 in the same cohort, revealed an area under the ROC curve (AUC) value of AUC = 0.66 (p = 0.014), while for the CRP (C-reactive protein), (AUC) value of 0.69 (p = 0.0066), indicating a similar ability to classify CD patients by their severity. However, the combination of data on serum levels of AIF-1 and CRP improves the predictive ability of these analyses for classifying CD patients as active (HB ≥ 5) or inactive (HB ≤ 4). When we used the odds ratio (OR) formula, we observed that patients with CRP > 5 mg/L or AIF-1 > 200 pg/mL or both conditions were 13 times more likely to show HB ≥ 5 (active CD) than were those with both markers below these thresholds. Conclusion: The development of an algorithm that includes serum levels of AIF-1 and CRP could be useful for assessing Crohn’s disease severity. Full article
(This article belongs to the Special Issue The Biomarkers for the Diagnosis, Prognosis and Treatments Response in Digestive Disorders)
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Review

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12 pages, 274 KiB  
Review
Role of CA 19.9 in the Management of Resectable Pancreatic Cancer: State of the Art and Future Perspectives
by Alessandro Coppola, Vincenzo La Vaccara, Tommaso Farolfi, Michele Fiore, Roberto Cammarata, Sara Ramella, Roberto Coppola and Damiano Caputo
Biomedicines 2022, 10(9), 2091; https://doi.org/10.3390/biomedicines10092091 - 26 Aug 2022
Cited by 10 | Viewed by 1417
Abstract
Background: Surgery still represents the gold standard of treatment for resectable pancreatic ductal adenocarcinoma (PDAC). Neoadjuvant treatments (NAT), currently proposed for borderline and locally advanced PDACs, are gaining momentum even in resectable tumors due to the recent interesting concept of “biological resectability”. In [...] Read more.
Background: Surgery still represents the gold standard of treatment for resectable pancreatic ductal adenocarcinoma (PDAC). Neoadjuvant treatments (NAT), currently proposed for borderline and locally advanced PDACs, are gaining momentum even in resectable tumors due to the recent interesting concept of “biological resectability”. In this scenario, CA 19.9 is having increasing importance in preoperative staging and in the choice of therapeutic strategies. We aimed to assess the state of the art and to highlight the future perspectives of CA 19.9 use in the management of patients with resectable pancreatic cancer. Methods: A PubMed database search of articles published up to December 2021 has been carried out. Results: Elevated pre-operative levels of CA 19.9 have been associated with reduced overall survival, nodal involvement, and margin status positivity after surgery. These abilities of CA 19.9 increase when combined with radiological or different biological criteria. Unfortunately, due to strong limitations of previously published articles, CA 19.9 alone cannot be yet considered as a key player in resectable pancreatic cancer patient management. Conclusion: The potential of CA 19.9 must be fully explored in order to standardize its role in the “biological staging” of patients with resectable pancreatic cancer. Full article
(This article belongs to the Special Issue The Biomarkers for the Diagnosis, Prognosis and Treatments Response in Digestive Disorders)
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