-
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 -
International Journal of Molecular... Apr 2022Temporal bone squamous cell carcinoma (TBSCC) is an uncommon malignancy with a poor prognosis in advanced cases. The dismal outcome of advanced TBSSC cases is largely...
Temporal bone squamous cell carcinoma (TBSCC) is an uncommon malignancy with a poor prognosis in advanced cases. The dismal outcome of advanced TBSSC cases is largely due to the cancer's local aggressiveness and the complex anatomy of this region, as well as to persistent pitfalls in diagnosis and treatment. Molecular changes occur in malignancies before any morphological changes become visible, and are responsible for the disease's clinical behavior. The main purpose of this critical systematic review is to assess the level of knowledge on the molecular markers involved in the biology, behavior, and prognosis of TBSCC. A search (updated to March 2022) was run in PubMed, Scopus, and Web of Science electronic databases without publication date limits for studies investigating molecular markers in cohorts of patients with primary TBSCC. The search terms used were: "temporal bone" OR "external auditory canal" OR "ear", AND "cancer" OR "carcinoma" OR "malignancy". We preliminarily decided not to consider series with less than five cases. Twenty-four case series of TBSCC were found in which different analytical techniques had been used to study the role of several biomarkers. In conclusion, only very limited information on the prognostic role of molecular markers in TBSCC are currently available; prospective, multi-institutional, international prognostic studies should be planned to identify the molecular markers involved in the clinical behavior and prognosis of TBSCC. A further, more ambitious goal would be to find targets for therapeutic agents able to improve disease-specific survival in patients with advanced TBSCC.
Topics: Biomarkers; Carcinogenesis; Carcinoma, Squamous Cell; Humans; Neoplasm Recurrence, Local; Prospective Studies; Retrospective Studies; Temporal Bone
PubMed: 35562926
DOI: 10.3390/ijms23094536 -
Insights Into Imaging Dec 2023Calcifications on mammography can be indicative of breast cancer, but the prognostic value of their appearance remains unclear. This systematic review and meta-analysis... (Review)
Review
BACKGROUND
Calcifications on mammography can be indicative of breast cancer, but the prognostic value of their appearance remains unclear. This systematic review and meta-analysis aimed to evaluate the association between mammographic calcification morphology descriptors (CMDs) and clinicopathological factors.
METHODS
A comprehensive literature search in Medline via Ovid, Embase.com, and Web of Science was conducted for articles published between 2000 and January 2022 that assessed the relationship between CMDs and clinicopathological factors, excluding case reports and review articles. The risk of bias and overall quality of evidence were evaluated using the QUIPS tool and GRADE. A random-effects model was used to synthesize the extracted data. This systematic review is reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA).
RESULTS
Among the 4715 articles reviewed, 29 met the inclusion criteria, reporting on 17 different clinicopathological factors in relation to CMDs. Heterogeneity between studies was present and the overall risk of bias was high, primarily due to small, inadequately described study populations. Meta-analysis demonstrated significant associations between fine linear calcifications and high-grade DCIS [pooled odds ratio (pOR), 4.92; 95% confidence interval (CI), 2.64-9.17], (comedo)necrosis (pOR, 3.46; 95% CI, 1.29-9.30), (micro)invasion (pOR, 1.53; 95% CI, 1.03-2.27), and a negative association with estrogen receptor positivity (pOR, 0.33; 95% CI, 0.12-0.89).
CONCLUSIONS
CMDs detected on mammography have prognostic value, but there is a high level of bias and variability between current studies. In order for CMDs to achieve clinical utility, standardization in reporting of CMDs is necessary.
CRITICAL RELEVANCE STATEMENT
Mammographic calcification morphology descriptors (CMDs) have prognostic value, but in order for CMDs to achieve clinical utility, standardization in reporting of CMDs is necessary.
SYSTEMATIC REVIEW REGISTRATION
CRD42022341599 KEY POINTS: • Mammographic calcifications can be indicative of breast cancer. • The prognostic value of mammographic calcifications is still unclear. • Specific mammographic calcification morphologies are related to lesion aggressiveness. • Variability between studies necessitates standardization in calcification evaluation to achieve clinical utility.
PubMed: 38051355
DOI: 10.1186/s13244-023-01529-z -
Head & Neck Sep 2023In this systematic review, we aimed to evaluate the clinicopathological profile of sclerosing polycystic adenoma (SPA). PubMed, Scopus, EMBASE, Lilacs, Web of Science,... (Review)
Review
In this systematic review, we aimed to evaluate the clinicopathological profile of sclerosing polycystic adenoma (SPA). PubMed, Scopus, EMBASE, Lilacs, Web of Science, and gray literature were searched to access cases of SPA in salivary glands. One hundred and thirty cases of SPA were found across 61 selected articles. SPA affected mainly the parotid gland of adults with a mean age of 44.6 years old, with a slight preference for females. The lesion was usually presented as a painless firm mass with a long period of evolution. Histologically, they are well-delimitated lesions composed of acinar and ductal elements with a variety of cytomorphologic features surrounded by a densely collagenized stroma. PI3K was the most common gene mutation related to SPA. SPA is a benign condition that mainly affects the parotid gland of female patients and it is usually treated by surgical resection with a good prognosis.
Topics: Adult; Humans; Female; Parotid Gland; Adenoma; Sclerosis
PubMed: 37403748
DOI: 10.1002/hed.27435 -
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 -
Diagnostics (Basel, Switzerland) May 2020The objective of this systematic review was to analyze the current state of the art of imaging-derived biomarkers predictive of genetic alterations and immunotherapy... (Review)
Review
The objective of this systematic review was to analyze the current state of the art of imaging-derived biomarkers predictive of genetic alterations and immunotherapy targets in lung cancer. We included original research studies reporting the development and validation of imaging feature-based models. The overall quality, the standard of reporting and the advancements towards clinical practice were assessed. Eighteen out of the 24 selected articles were classified as "high-quality" studies according to the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). The 18 "high-quality papers" adhered to Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis (TRIPOD) with a mean of 62.9%. The majority of "high-quality" studies (16/18) were classified as phase II. The most commonly used imaging predictors were radiomic features, followed by visual qualitative computed tomography (CT) features, convolutional neural network-based approaches and positron emission tomography (PET) parameters, all used alone or combined with clinicopathologic features. The majority (14/18) were focused on the prediction of epidermal growth factor receptor (EGFR) mutation. Thirty-five imaging-based models were built to predict the EGFR status. The model's performances ranged from weak (n = 5) to acceptable (n = 11), to excellent (n = 18) and outstanding (n = 1) in the validation set. Positive outcomes were also reported for the prediction of ALK rearrangement, ALK/ROS1/RET fusions and programmed cell death ligand 1 (PD-L1) expression. Despite the promising results in terms of predictive performance, image-based models, suffering from methodological bias, require further validation before replacing traditional molecular pathology testing.
PubMed: 32486314
DOI: 10.3390/diagnostics10060359 -
Biochemistry. Biokhimiia Jan 2024Mutations that disrupt the function of the DNA/RNA-binding protein FUS could cause amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. One of the... (Review)
Review
Mutations that disrupt the function of the DNA/RNA-binding protein FUS could cause amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. One of the key features in ALS pathogenesis is the formation of insoluble protein aggregates containing aberrant isoforms of the FUS protein in the cytoplasm of upper and lower motor neurons. Reproduction of human pathology in animal models is the main tool for studying FUS-associated pathology and searching for potential therapeutic agents for ALS treatment. In this review, we provide a systematic analysis of the role of FUS protein in ALS pathogenesis and an overview of the results of modelling FUS-proteinopathy in animals.
Topics: Animals; Humans; Amyotrophic Lateral Sclerosis; RNA-Binding Protein FUS; Motor Neurons; Cytoplasm; Mutation; Disease Models, Animal
PubMed: 38621743
DOI: 10.1134/S0006297924140037 -
Clinical Neurology and Neurosurgery Apr 2017Cerebral small vessel disease is considered hereditary in about 5% of patients and is characterized by lacunar infarcts and white matter hyperintensities on MRI. Several... (Review)
Review
Cerebral small vessel disease is considered hereditary in about 5% of patients and is characterized by lacunar infarcts and white matter hyperintensities on MRI. Several monogenic hereditary diseases causing cerebral small vessel disease and stroke have been identified. The purpose of this systematic review is to provide a guide for determining when to consider molecular genetic testing in patients presenting with small vessel disease and stroke. CADASIL, CARASIL, collagen type IV mutations (including PADMAL), retinal vasculopathy with cerebral leukodystrophy, Fabry disease, hereditary cerebral hemorrhage with amyloidosis, and forkhead box C1 mutations are described in terms of genetics, pathology, clinical manifestation, imaging, and diagnosis. These monogenic disorders are often characterized by early-age stroke, but also by migraine, mood disturbances, vascular dementia and often gait disturbances. Some also present with extra-cerebral manifestations such as microangiopathy of the eyes and kidneys. Many present with clinically recognizable syndromes. Investigations include a thorough family medical history, medical history, neurological examination, neuroimaging, often supplemented by specific examinations e.g of the of vision, retinal changes, as well as kidney and heart function. However molecular genetic analysis is the final gold standard of diagnosis. There are increasing numbers of reports on new monogenic syndromes causing cerebral small vessel disease. Genetic counseling is important. Enzyme replacement therapy is possible in Fabry disease, but treatment options remain overall very limited.
Topics: Alopecia; Animals; Brain; Cerebral Infarction; Cerebral Small Vessel Diseases; Humans; Leukoencephalopathies; Spinal Diseases; Stroke
PubMed: 28254515
DOI: 10.1016/j.clineuro.2017.02.015 -
Neuroradiology Feb 2015Neuroimaging techniques including structural magnetic resonance imaging (MRI) and functional positron emission tomography (PET) are useful in categorizing various... (Review)
Review
PURPOSE
Neuroimaging techniques including structural magnetic resonance imaging (MRI) and functional positron emission tomography (PET) are useful in categorizing various midbrain-hindbrain (MHB) malformations, both in allowing diagnosis and in helping to understand the developmental processes that were disturbed. Brain imaging phenotypes of numerous malformations are characteristic features that help in guiding the genetic testing in case of direct neuroimaging-genotype correlation or, at least, to differentiate among MHB malformations entities. The present review aims to provide the reader with an update of the use of neuroimaging applications in the fine analysis of MHB malformations, using a comprehensive, recently proposed developmental and genetic classification.
METHODS
We have performed an extensive systematic review of the literature, from the embryology main steps of MHB development through the malformations entities, with regard to their molecular and genetic basis, conventional MRI features, and other neuroimaging characteristics.
RESULTS
We discuss disorders in which imaging features are distinctive and how these features reflect the structural and functional impairment of the brain.
CONCLUSION
Recognition of specific MRI phenotypes, including advanced imaging features, is useful to recognize the MHB malformation entities, to suggest genetic investigations, and, eventually, to monitor the disease outcome after supportive therapies.
Topics: Humans; Magnetic Resonance Imaging; Mesencephalon; Nervous System Malformations; Neuroimaging; Rhombencephalon
PubMed: 25339235
DOI: 10.1007/s00234-014-1431-2 -
Journal of Biomedical Nanotechnology Mar 2016In preceding decades, different mechanisms have been proposed to "instruct" dendritic cells (DCs) to induce immune responses against tumor antigens (TAs), thus breaking... (Review)
Review
In preceding decades, different mechanisms have been proposed to "instruct" dendritic cells (DCs) to induce immune responses against tumor antigens (TAs), thus breaking immune tolerance. Immunotherapy has been, for the last two decades, an attractive and promising therapeutic approach to fight cancer. This review will approach the nature of the immune response during cancer development and its correlation with DC function, as well as cancer vaccine principles and limitations. An overview of several delivery strategies used for in vivo modulation of DCs and direct activation of T cells will be provided, highlighting their advantages, limitations, and optimization strategies. This manuscript also presents a critical and systematic review of recent clinical trials that are investigating the therapeutic effect of these approaches, discussing prognostic outcomes of combined-treatment modalities.
Topics: Animals; Dendritic Cells; Humans; Immunotherapy; Molecular Targeted Therapy; Nanoparticles; Neoplasms; Treatment Outcome
PubMed: 27280242
DOI: 10.1166/jbn.2016.2157