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Histochemistry and Cell Biology Jul 2020Molecular pathology allows the identification of causative agents in infectious diseases and detection of biomarkers important for prediction of disease susceptibility,...
Molecular pathology allows the identification of causative agents in infectious diseases and detection of biomarkers important for prediction of disease susceptibility, diagnosis and personalized therapy. Accordingly, nucleic acid-based methods have gained a special role in clinical laboratories particularly to evaluate solid and hematological tumors. Extraction of nucleic acids is commonly performed in microdissected formalin-fixed paraffin-embedded (FFPE) or cytological samples that had been previously evaluated through the use of hematoxylin and eosin (H&E) or Papanicolau (Pap) stains, respectively. Although the effect of both stains on nucleic acids integrity has been explored by several authors, the results are not consistent and require further examination. Accordingly, the goal of this review was to assess the influence of H&E and Pap stains on DNA and RNA integrity and to address the mechanism by which each staining compromises molecular based-analysis. The analyzed studies demonstrate that H&E- and Pap-staining result in low DNA recovery and some degree of DNA fragmentation. Additionally, it is concluded that hemalum inhibits PCR by interfering with DNA extraction, preventing DNA polymerase attachment and possibly by rescuing divalent cations. Accordingly, proper sample purification and adjustment of PCR conditions are of key importance to achieve satisfactory results by PCR in H&E- and Pap-stained samples. Furthermore, although H&E results in RNA fragmentation, it is possible to perform expression analysis in H&E-stained frozen sections, using RNase-free conditions, low amounts of hematoxylin and a rapid protocol from sample collection to RNA analysis. It The effect of Pap-staining on RNA integrity remains to be determined.
Topics: Animals; DNA; Eosine Yellowish-(YS); Hematoxylin; Humans; Papanicolaou Test; Paraffin Embedding; Polymerase Chain Reaction; RNA; Staining and Labeling
PubMed: 32372108
DOI: 10.1007/s00418-020-01882-w -
Environmental Research Feb 2023Endocrine disrupting chemicals (EDCs) are exogenous substances recognised as relevant tumourigenic chemicals. Studies show that even EDCs which were long abolished are... (Review)
Review
INTRODUCTION
Endocrine disrupting chemicals (EDCs) are exogenous substances recognised as relevant tumourigenic chemicals. Studies show that even EDCs which were long abolished are still contributing to the increasing incidence of neoplasia.
AIM
To investigate the association between human exposure to EDCs and the risk of endocrine-related tumours: breast, prostate, thyroid, uterus, testis, and ovary.
METHODS
A systematic review using PubMed, Scopus, and Embase was conducted, searching for original observational studies published between 1980 and 2020, approaching EDCs exposure and endocrine tumourigenic risk in humans. We comprised neoplasia of six endocrine organs. We included all the studies on EDCs reporting tumour odds ratio, risk ratio, or hazard ratio. Study levels of confidence and risk of bias were accessed applying accredited guidelines. Human-made accidents and natural EDCs were not considered in the present study.
RESULTS
Our search returned 3271 papers. After duplicate removal and screening, only 237 papers were included (corresponding to 268 records). EDCs were grouped from the most frequently (pesticides) to the least frequently studied (salts). The most tumourigenic EDC groups were phthalates (63%), heavy metals (54%), particulate matter (47%), and pesticides (46%). Pesticides group comprised the highest number of retrieved studies (n = 133). Increased neoplasia risk was found in 43-67% of the studies, with a lower value for ovary (43%) and a higher value for thyroid (67%).
CONCLUSIONS
The innovative nature of our review comes from including human studies of six endocrine-related neoplasia aiming to understand the contribution of specific EDCs groups to each organ's tumourigenesis. Thyroid was the organ presenting the highest cancer risk after EDC exposure which may explain the increasing thyroid cancer incidence. However, detailed and controlled works reporting the effects of EDCs are scarce, probably justifying conflicting results. Multinational and multicentric human studies with biochemical analysis are needed to achieve stronger and concordant evidence.
Topics: Male; Female; Humans; Endocrine Disruptors; Endocrine System; Pesticides; Testis; Metals, Heavy
PubMed: 36460069
DOI: 10.1016/j.envres.2022.114869 -
International Journal of Molecular... Nov 2023One of the most complex and challenging developments at the beginning of the third millennium is the alarming increase in demographic aging, mainly-but not... (Review)
Review
One of the most complex and challenging developments at the beginning of the third millennium is the alarming increase in demographic aging, mainly-but not exclusively-affecting developed countries. This reality results in one of the harsh medical, social, and economic consequences: the continuously increasing number of people with dementia, including Alzheimer's disease (AD), which accounts for up to 80% of all such types of pathology. Its large and progressive disabling potential, which eventually leads to death, therefore represents an important public health matter, especially because there is no known cure for this disease. Consequently, periodic reappraisals of different therapeutic possibilities are necessary. For this purpose, we conducted this systematic literature review investigating nonpharmacological interventions for AD, including their currently known cellular and molecular action bases. This endeavor was based on the PRISMA method, by which we selected 116 eligible articles published during the last year. Because of the unfortunate lack of effective treatments for AD, it is necessary to enhance efforts toward identifying and improving various therapeutic and rehabilitative approaches, as well as related prophylactic measures.
Topics: Humans; Alzheimer Disease; Amyloid beta-Peptides; tau Proteins
PubMed: 38003723
DOI: 10.3390/ijms242216533 -
Comprehensive characterisation of acinar cystic transformation of the pancreas: a systematic review.Journal of Clinical Pathology Nov 2023Acinar cystic transformation (ACT) of the pancreas is a rare pancreatic cystic lesion. Owing to its rarity, comprehensive histomolecular characterisation of this entity...
AIMS
Acinar cystic transformation (ACT) of the pancreas is a rare pancreatic cystic lesion. Owing to its rarity, comprehensive histomolecular characterisation of this entity is still lacking. We aim to perform a systematic review on this controversial entity.
METHODS
We searched PubMed, SCOPUS and Embase through May 2023 to identify all studies on ACTs. Clinicopathological, immunohistochemical (IHC) and molecular data have been extracted and analysed.
RESULTS
Overall, there were 121 cases of ACTs in the literature. ACT had a female predominance (65.3% of patients), and a mean size of 4.8 cm. ACT was more often unifocal (71.9%) and multiloculate (61.2%). Histologically, the cysts were lined by an acinar epithelium, sometimes harbouring ductal-like areas (18.2%). In five cases (4.1%), an intralesional pancreatic intraepithelial neoplasia (PanIN) was reported. Preoperative diagnosis is challenging. After surgical resection, all patients were alive and disease free during follow-up except one patient who developed a second ACT after resection. By IHC, all lesions were positive for acinar markers; cytokeratin 7 and 8/18/19 were usually positive, and Ki-67 was invariably ≤3%. At the molecular level, three cases demonstrated genetic alterations: one showed multiple chromosomal gains, and other two harboured somatic mutations of and genes (one mutation per case).
CONCLUSIONS
Globally considered, our findings demonstrated that ACT is a benign entity, without the need of surgical resection with the exception of symptomatic lesions. The rare occurrence of intracystic PanINs and driver mutations suggest considering follow-up if a preoperative diagnosis of ACT can be made.
Topics: Humans; Female; Male; Pancreas; Pancreatic Neoplasms; Pancreatic Cyst; Carcinoma in Situ; Carcinoma, Pancreatic Ductal
PubMed: 37643836
DOI: 10.1136/jcp-2023-209103 -
Clinical and Molecular Hepatology Apr 2023Hepatocellular carcinoma (HCC) is one of the most common and deadly cancers worldwide and is characterized by complex molecular carcinogenesis. Neuropilins (NRPs) NRP1... (Review)
Review
Hepatocellular carcinoma (HCC) is one of the most common and deadly cancers worldwide and is characterized by complex molecular carcinogenesis. Neuropilins (NRPs) NRP1 and NRP2 are the receptors of multiple proteins involved in key signaling pathways associated with tumor progression. We aimed to systematically review all the available findings on their role in HCC. We searched the Scopus, Web of Science (WOS), PubMed, Cochrane and Embase databases for articles evaluating NRPs in preclinical or clinical HCC models. This study was registered in PROSPERO (CRD42022349774) and include 49 studies. Multiple cellular and molecular processes have been associated with one or both NRPs, indicating that they are potential diagnostic and prognostic biomarkers in HCC patients. Mainly NRP1 has been shown to promote tumor cell survival and progression by modulating several signaling pathways. NRPs mainly regulate angiogenesis, invasion and migration and have shown to induce invasion and metastasis. They also regulate the immune response and tumor microenvironment, showing a crucial interplay with the hypoxia response and microRNAs in HCC. Altogether, NRP1 and NRP2 are potential biomarkers and therapeutic targets, providing novel insight into the clinical landscape of HCC patients.
Topics: Humans; Carcinoma, Hepatocellular; Neuropilins; Liver Neoplasms; Signal Transduction; Biomarkers; Biomarkers, Tumor; Tumor Microenvironment
PubMed: 36726054
DOI: 10.3350/cmh.2022.0425 -
PloS One 2021Xerosis cutis or dry skin is a highly prevalent dermatological disorder especially in the elderly and in patients with underlying health conditions. In the past decades,...
BACKGROUND
Xerosis cutis or dry skin is a highly prevalent dermatological disorder especially in the elderly and in patients with underlying health conditions. In the past decades, numerous molecular markers have been investigated for their association with the occurrence or severity of skin dryness. The aim of this review was to summarize the molecular markers used in xerosis cutis research and to describe possible associations with different dry skin etiologies.
METHODS
We conducted a systematic review of molecular markers of xerosis cutis caused by internal or systemic changes. References published between 1990 and September 2020 were searched using 'MEDLINE', 'EMBASE' and 'Biological abstracts' databases. Study results were summarized and analyzed descriptively. The review protocol was registered in PROSPERO database (CRD42020214173).
RESULTS
A total of 21 study reports describing 72 molecules were identified including lipids, natural moisturizing factors (NMFs), proteins including cytokines and metabolites or metabolic products. Most frequently reported markers were ceramides, total free fatty acids, triglycerides and selected components of NMFs. Thirty-one markers were reported only once. Although, associations of these molecular markers with skin dryness were described, reports of unclear and/or no association were also frequent for nearly every marker.
CONCLUSION
An unexpectedly high number of various molecules to quantify xerosis cutis was found. There is substantial heterogeneity regarding molecular marker selection, tissue sampling and laboratory analyses. Empirical evidence is also heterogeneous regarding possible associations with dry skin. Total free fatty acids, total ceramide, ceramide (NP), ceramide (NS), triglyceride, total free amino acids and serine seem to be relevant, but the association with dry skin is inconsistent. Although the quantification of molecular markers plays an important role in characterizing biological processes, pathogenic processes or pharmacologic responses, it is currently unclear which molecules work best in xerosis cutis.
Topics: Biomarkers; Ceramides; Connective Tissue Diseases; Epidermis; Fatty Acids, Nonesterified; Humans; Lipids; Skin; Skin Diseases; Skin Diseases, Eczematous; Skin Physiological Phenomena
PubMed: 34914754
DOI: 10.1371/journal.pone.0261253 -
Journal of Human Genetics May 2015Mutations in APP, PSEN1 and PSEN2 as the genetic causes of familial Alzheimer's disease (FAD) have been found in various ethnic populations. A substantial number of FAD... (Meta-Analysis)
Meta-Analysis Review
Mutations in APP, PSEN1 and PSEN2 as the genetic causes of familial Alzheimer's disease (FAD) have been found in various ethnic populations. A substantial number of FAD pedigrees with mutations have been reported in the Japanese population; however, it remains unclear whether the genetic and clinical features of FAD in the Japanese population differ from those in other populations. To address this issue, we conducted a systematic review and meta-analysis of Japanese FAD and frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) by literature search. Using this analysis, we identified 39 different PSEN1 mutations in 140 patients, 5 APP mutations in 35 patients and 16 MAPT mutations in 84 patients. There was no PSEN2 mutation among Japanese patients. The age at onset in Japanese FAD patients with PSEN1 mutations was significantly younger than that in patients with APP mutations. Kaplan-Meier analysis revealed that patients with MAPT mutations showed a shorter survival than patients with PSEN1 or APP mutations. Patients with mutations in different genes exhibit characteristic clinical presentations, suggesting that mutations in causative genes may modify the clinical presentations. By collecting and cataloging genetic and clinical information on Japanese FAD and FTDP-17, we developed an original database designated as Japanese Familial Alzheimer's Disease Database, which is accessible at http://alzdb.bri.niigata-u.ac.jp/.
Topics: Age of Onset; Alzheimer Disease; Chromosomes, Human, Pair 17; Frontotemporal Dementia; Genetic Predisposition to Disease; Humans; Mutation
PubMed: 25694106
DOI: 10.1038/jhg.2015.15 -
Pharmacology & Therapeutics Jan 2024The treatment of interstitial lung diseases, including idiopathic pulmonary fibrosis (IPF), remains challenging as current available antifibrotic agents are not... (Review)
Review
The treatment of interstitial lung diseases, including idiopathic pulmonary fibrosis (IPF), remains challenging as current available antifibrotic agents are not effective in halting disease progression. Connective tissue growth factor (CTGF), also known as cellular communication factor 2 (CCN2), is a member of the CCN family of proteins that regulates cell signaling through cell surface receptors such as integrins, the activity of cytokines/growth factors, and the turnover of extracellular matrix (ECM) proteins. Accumulating evidence indicates that CTGF plays a crucial role in promoting lung fibrosis through multiple processes, including inducing transdifferentiation of fibroblasts to myofibroblasts, epithelial-mesenchymal transition (EMT), and cooperating with other fibrotic mediators such as TGF-β. Increased expression of CTGF has been observed in fibrotic lungs and inhibiting CTGF signaling has been shown to suppress lung fibrosis in several animal models. Thus, the CTGF signaling pathway is emerging as a potential therapeutic target in IPF and other pulmonary fibrotic conditions. This review provides a comprehensive overview of the current evidence on the pathogenic role of CTGF in pulmonary fibrosis and discusses the current therapeutic agents targeting CTGF using a systematic review approach.
Topics: Animals; Connective Tissue Growth Factor; Fibrosis; Fibroblasts; Transforming Growth Factor beta; Idiopathic Pulmonary Fibrosis; Transforming Growth Factor beta1; Lung
PubMed: 38103794
DOI: 10.1016/j.pharmthera.2023.108578 -
World Journal of Gastroenterology Aug 2016Epithelial-to-mesenchymal transition (EMT) is defined as the transformation of an epithelial cell into a spindle cell with the loss of membrane E-cadherin expression and... (Review)
Review
Epithelial-to-mesenchymal transition (EMT) is defined as the transformation of an epithelial cell into a spindle cell with the loss of membrane E-cadherin expression and the gain of mesenchymal markers positivity. In the field of colorectal cancer (CRC), first data about EMT was published in 1995 and more than 400 papers had been written up to March 2016. Most of them are focused on the molecular pathways and experimentally-proved chemoresistance. In the present article, an update in the field of EMT in CRC based on the review of the literature and personal experience of the authors is presented. The information about the molecular and immunohistochemical (IHC) particularities of these processes and their possible role in the prognosis of CRC were also up-dated. This article focuses on the IHC quantification of the EMT, the immunoprofile of tumor buds and on the relation between EMT, angiogenesis, and stem cells activation. The EMT-induced chemoresistance vs chemotherapy- or radiotherapy-induced EMT and cellular senescence was also synthesized for both conventional and targeted therapy. As a future perspective, the EMT-angiogenesis-stemness link could be used as a possible valuable parameter for clinical follow-up and targeted therapeutic oncologic management of patients with CRC. Association of dexamethasone and angiotensin converting enzyme inhibitors combined with conventional chemotherapies could have clinical benefits in patients with CRC. The main conclusion is that, although many studies have been published, the EMT features are still incompletely elucidated and newly discovered EMT markers provide confusing data in understanding this complicated process, which might have significant clinical impact.
Topics: Colorectal Neoplasms; Epithelial-Mesenchymal Transition; Humans; Immunohistochemistry; Neoplasm Metastasis; Neovascularization, Physiologic
PubMed: 27570416
DOI: 10.3748/wjg.v22.i30.6764 -
International Journal of Gynaecology... Jul 2022The TCGA molecular groups of endometrial carcinoma are "POLE-mutated" (POLEmut), "microsatellite-instable/mismatch repair-deficient" (MSI/MMRd),... (Review)
Review
BACKGROUND
The TCGA molecular groups of endometrial carcinoma are "POLE-mutated" (POLEmut), "microsatellite-instable/mismatch repair-deficient" (MSI/MMRd), "TP53-mutated/p53-abnormal" (TP53mut/p53abn), and "no specific molecular profile" (NSMP).
OBJECTIVE
Prognostic assessment of the TCGA groups in uterine carcinosarcoma (UCS).
SEARCH STRATEGY
Systematic review from January 2000 to January 2021.
SELECTION CRITERIA
Studies assessing the TCGA groups in UCS.
DATA COLLECTION AND ANALYSIS
Progression-free survival (PFS) and overall survival (OS) were assessed by Kaplan-Meier and Cox analyses (reference: TP53mut/p53abn group) and compared with endometrioid and serous carcinomas (original TCGA cohort), with a significant P < 0.050.
MAIN RESULTS
Five studies with 263 UCS were included. Compared with TP53mut/p53abn UCS, MSI/MMRd UCS showed significantly better PFS (P < 0.001) but similar OS (P = 0.788), whereas NSMP UCS showed similar PFS (P = 0.936) and OS (P = 0.240). Compared with their endometrioid/serous counterparts, NSMP and TP53mut/p53abn UCS showed significantly worse PFS (P < 0.001 and P = 0.004) and OS (P < 0.001 and P < 0.001), while MSI/MMRd UCS showed similar PFS (P = 0.595) but significantly worse OS (P < 0.001). The POLEmut group showed neither recurrences nor deaths in both the UCS and the endometrioid/serous carcinoma cohorts.
CONCLUSION
POLEmut UCS show excellent prognosis, whereas TP53mut/p53abn and NSMP UCS show a prognosis even worse than that of TP53mut/p53abn endometrioid/serous carcinomas. The prognosis of MSI/MMRd UCS remains to be defined.
Topics: Carcinoma, Endometrioid; Carcinosarcoma; Endometrial Neoplasms; Female; Humans; Prognosis; Uterine Neoplasms
PubMed: 34536971
DOI: 10.1002/ijgo.13937