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Current Rheumatology Reviews 2020Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, which is characterized by the hyperplasia of synovial tissue. Survivin is a member of the...
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, which is characterized by the hyperplasia of synovial tissue. Survivin is a member of the inhibitor of apoptosis protein family, which facilitates the formation of functional T-cell receptor and differentiation of memory T cells. Survivin plays an important role in the expression of major histocompatibility complex molecules and mature dendritic cells, which play the main role in the etiology of RA. This systematic review was conducted to investigate the evidence on the role of survivin as a diagnostic and predictive value in RA patients. All published articles related to the subject of interest and published up to 30 March 2018 were searched in three databases, including Google Scholar, PubMed, and Web of Science. After a detailed evaluation of the full-text version of the papers, 23 articles were entered into the study. The elevation of survivin in the preclinical phase of RA and its association with anti-cyclic citrullinated peptide (CCP) antibodies suggested it as a predictor of RA. Recently, survivin has been introduced as the biomarker of joint damage and poor response to antirheumatic treatment in RA patients. Based on the evidence, survivin level had high specificity and sensitivity in the diagnosis of RA patients. The results of the reviewed studies demonstrated that a positive survivin level was associated with the presence of anti-CCP antibodies.
Topics: Arthritis, Rheumatoid; Autoantibodies; Biomarkers; Humans; Predictive Value of Tests; Survivin
PubMed: 31951186
DOI: 10.2174/1573397116666200116095039 -
BioMed Research International 2022Endometrial cancer (EC) is one of the most common gynecologic malignancy, mostly in postmenopausal women. The gold standard treatment for EC is surgery, but in the early... (Review)
Review
BACKGROUND
Endometrial cancer (EC) is one of the most common gynecologic malignancy, mostly in postmenopausal women. The gold standard treatment for EC is surgery, but in the early stages, it is possible to opt for conservative treatment. In the last decade, different clinical and pathological markers have been studied to identify women who respond to conservative treatment. A lot of immunohistochemical markers have been evaluated to predict response to progestin treatment, even if their usefulness is still unclear; the prognosis of this neoplasm depends on tumor stage, and a specific therapeutic protocol is set according to the stage of the disease.
OBJECTIVE
(1) To provide an overview of the conservative management of Stage 1A Grade (G) 2 endometrioid EC (FIGO) and the oncological and reproductive outcomes related; (2) to describe the molecular alterations before and after progestin therapy in patients undergoing conservative treatment.
MATERIALS AND METHODS
A systematic computerized search of the literature was performed in the main electronic databases (MEDLINE, Embase, Web of Science, PubMed, and Cochrane Library), from 2010 to September 2021, in order to evaluate the oncological and reproductive outcomes in patients with G2 stage IA EC who ask for fertility-sparing treatment. The expression of several immunohistochemical markers was evaluated in pretreatment phase and during the follow-up in relation to response to hormonal therapy. Only scientific publications in English were included. The risk of bias assessment was performed. Review authors' judgments were categorized as "low risk," "high risk," or "unclear risk" of bias.
RESULTS
Twelve articles were included in the study: 7 observational studies and 5 case series/reports. Eighty-four patients who took progestins (megestrol acetate, medroxyprogesterone acetate, and/or levonorgestrel-releasing intrauterine devices) were analyzed. The publication bias analysis turned out to be "low." 54/84 patients had a complete response, 23/84 patients underwent radical surgery, and 20/84 had a relapse after conservative treatment. Twenty-two patients had a pregnancy. The length of follow-up was variable, from 6 to 142 months according to the different studies analyzed. Several clinical and pathological markers have been studied to identify women who do not respond to conservative treatment: PR and ER were the most studied predictive markers, in particular PR appeared as the most promising; MMR, SPAG9, Ki67, and Nrf2-survivin pathway provided good results with a significant association with a good response to progestin therapy. However, no reliable predictive markers are currently available to be used in clinical practice.
CONCLUSIONS
The conservative treatment may be an option for patients with stage IA G2 EEC who desire to preserve their fertility. The immunohistochemical markers evaluation looks promising in predicting response to conservative treatment. Further large series and randomized clinical trials are needed to confirm these results.
Topics: Adaptor Proteins, Signal Transducing; Antineoplastic Agents, Hormonal; Carcinoma, Endometrioid; Endometrial Neoplasms; Female; Fertility Preservation; Humans; Ki-67 Antigen; Levonorgestrel; Medroxyprogesterone Acetate; Megestrol Acetate; NF-E2-Related Factor 2; Neoplasm Recurrence, Local; Pregnancy; Progestins; Survivin
PubMed: 36203482
DOI: 10.1155/2022/4070368 -
Diagnostics (Basel, Switzerland) Jan 2023Neurogenic lower urinary tract dysfunction requires lifelong surveillance and management for the perseveration of patients' quality of life and the prevention of... (Review)
Review
BACKGROUND
Neurogenic lower urinary tract dysfunction requires lifelong surveillance and management for the perseveration of patients' quality of life and the prevention of significant morbidity and mortality. Urine biomarkers are an attractive noninvasive method of surveillance for these patients. The aim of this systematic review is to search for and critically appraise studies that investigate the clinical usefulness of urine biomarkers in the management of neurogenic lower urinary tract dysfunction (NLUTD) in adults.
METHODS
This review was conducted according to PRISMA and MOOSE guidelines. Search strategy included PubMed, CENTRAL, and Scopus (until October 2022). Studies investigating potential urine biomarkers for the management of adults with NLUTD were included.
RESULTS
Fifteen studies fulfilled the criteria. To date, a variety of different urine molecules have been investigated for the diagnosis and management of neurogenic overactive bladder and detrusor overactivity (nerve growth factor, brain-derived neurotrophic factor, prostaglandin E2, prostaglandin F2α, transformation growth factor β-1, tissue inhibitor metalloproteinase-2, matrix metalloproteinase-2, substance P, microRNA), diagnosis of vesicoureteral reflux (exosomal vitronectin), urinary tract infection (neutrophil gelatinase-associated lipocalin, interleukin 6) and bladder cancer screening (cytology, BTA stat, survivin) in neurological patients.
CONCLUSION
Further studies are needed to specify the utility of each molecule in the management algorithm of adult NLUTD.
PubMed: 36766573
DOI: 10.3390/diagnostics13030468 -
Pathology, Research and Practice May 2024Malignant pleural mesothelioma (MPM) poses diagnostic challenges due to its resemblance to benign pleural pathologies and different histological subtypes. Several... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Malignant pleural mesothelioma (MPM) poses diagnostic challenges due to its resemblance to benign pleural pathologies and different histological subtypes. Several immunohistochemistry markers have been employed to aid in accurate diagnosis.
METHODS
The present systematic review and meta-analysis aimed to assess the diagnostic performance of various immunohistochemistry markers in malignant pleural mesothelioma diagnosis and its histological subtypes. Following the PRISMA guidelines, we systematically searched the literature for articles on using different immunohistochemical markers in MPM and its histological subtypes. EMBASE, LILACS, MEDLINE, and Virtual Health Library were searched for studies published up to August 2023. We used the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies) criteria to assess the quality of the included articles. Meta-analyses were performed to determine prevalence using a random-effects model.
RESULTS
103 studies met the inclusion criteria, comprising a diverse range of immunohistochemistry markers. EMA and desmin-loss exhibited high sensitivity (96% and 92%, respectively) in distinguishing malignant pleural mesothelioma from benign pleural pathologies. Specificity was notably high for both BAP1-loss and survivin expression at 100%. Subtype-specific analyses demonstrated that EMA and HEG1 were sensitive markers for epithelioid mesothelioma, while GLUT1 showed high sensitivity for sarcomatoid mesothelioma. In cases comparing epithelioid mesothelioma and lung adenocarcinoma, CAM5.2 and calretinin displayed high sensitivity, while WT1 and BAP1-loss demonstrated exceptional specificity for malignant epithelioid mesothelioma. In the case of sarcomatoid mesothelioma and sarcomatoid lung carcinoma, GATA3 exhibited the most heightened sensitivity, while GATA3 and D2-40 displayed the best specificity for sarcomatoid malignant mesothelioma diagnosis.
CONCLUSION
Immunohistochemistry markers are essential in accurately diagnosing malignant pleural mesothelioma and its histological subtypes. This systematic review and meta-analysis provide a comprehensive insight into the diagnostic performance of these markers, facilitating their potential clinical utility in the discrimination of malignant pleural mesothelioma from other pleural pathologies and the differentiation of malignant pleural mesothelioma subtypes.
Topics: Humans; Mesothelioma, Malignant; Biomarkers, Tumor; Immunohistochemistry; Pleural Neoplasms; Lung Neoplasms; Diagnosis, Differential
PubMed: 38603842
DOI: 10.1016/j.prp.2024.155276 -
Frontiers in Veterinary Science 2020Canine and human bladder cancer present similar anatomical, morphological, and molecular characteristics, and dogs can be considered a model for human bladder cancer....
Canine and human bladder cancer present similar anatomical, morphological, and molecular characteristics, and dogs can be considered a model for human bladder cancer. However, the veterinary literature lacks information regarding cross-validation analysis between human and canine large-scale data. Therefore, this research aimed to perform a meta-analysis of the canine literature on bladder cancer, identifying genes and proteins previously evaluated in these studies. In addition, we also performed a cross-validation of the canine transcriptome data and the human data from The Cancer Genome Atlas (TCGA) to identify potential markers for both species. The meta-analysis was performed using the following indexing terms: "bladder" AND "carcinoma" AND "dog" in different international databases, and 385 manuscripts were identified in our initial search. Then, several inclusion criteria were applied, and only 25 studies met these criteria. Among these studies, five presented transcriptome data, and 20 evaluated only isolated genes or proteins. Regarding the studies involving isolated protein analysis, the HER-2 protein was the most studied (3/20), followed by TAG-72 (2/20), COX-2 (2/20), survivin (2/20), and CK7 (2/20), and the remaining nine studies evaluated one isolated protein each. Regarding the cross-validation analysis of human and canine transcriptome data, we identified 35 dysregulated genes, including , and . Our results demonstrate that the canine literature on bladder cancer previously focused on the evaluation of isolated markers with no association with patient survival. This limitation may be related to the lack of a homogenous protocol for treating patients and the lack of follow-up during treatment. In addition, the lack of information regarding tumor muscle invasion can be considered an important limitation when comparing human and canine bladder tumors. Our analysis involving canine and human transcriptome data provided several genes with the potential to be markers for both human and canine bladder tumors, and these genes should be considered for future studies on canine bladder cancer.
PubMed: 33304937
DOI: 10.3389/fvets.2020.558978 -
Journal of Molecular Histology Jun 2024The prevalence of TNBC in India is higher compared to western countries. There is a multitude of biomarkers associated with different clinical outcomes of TNBC with... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The prevalence of TNBC in India is higher compared to western countries. There is a multitude of biomarkers associated with different clinical outcomes of TNBC with contradictory reports. Identification of a set of specific biomarkers from the very many number of proteins reported in the literature to predict prognosis of TNBC is an urgent clinical need.
METHODOLOGY
A systematic review of key molecular biomarkers in cohort studies that have been investigated for their role in breast cancer prognosis was conducted. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology was followed. A meta-analysis was used to evaluate their pooled hazard ratio (HR) and the corresponding 95% confidence interval (95% CI) statistically. Immunohistochemical characterization of the meta-analyzed markers were performed in a cohort of 200 retrospective TNBC and 100 non TNBC patient tissues. Kaplan-Meier plot were used to evaluate disease free survival (DFS), and overall survival (OS). Cox regression models were used to evaluate predictors of DFS and OS.
RESULTS
Using a meta-analytical approach, we consolidated the biomarker signatures associated with survival outcomes in breast cancers. The promising markers that emerged for the prediction of DFS and OS included E-Cadherin, Survivin, p53, MTA1, HIF1A, CD133, Vimentin and CK5/6. Evaluation of these markers in tumor tissue revealed that subcellular localization of p53, MTA1 and HIF1A had a significant association in predicting TNBC prognosis. Kaplan Meier plot revealed that p53 (OS p = 0.007, DFS p = 0.004), HIF 1 A (OS p = 0.054, DFS p = 0.009) and MTA1 (OS p = 0.043, DFS = p = 0.001) expression in the primary tumor tissue were found to be significantly correlated with poor OS and DFS, whereas expression of Survivin (DFS p = 0.024) and E Cadherin (DFS p = 0.027) correlated with DFS alone in TNBC. Univariate analysis revealed that p53, HIF1A and MTA1 could be independent prognostic markers.
CONCLUSION
Our study suggests cytoplasmic over expression of HIF1A, nuclear over expression of MTA1 and mutated p53 in the primary tumor tissue of TNBC have significance as markers predicting survival of TNBC patients.
Topics: Humans; Triple Negative Breast Neoplasms; Tumor Suppressor Protein p53; Repressor Proteins; Biomarkers, Tumor; Female; Trans-Activators; Hypoxia-Inducible Factor 1, alpha Subunit; Histone Deacetylases; Prognosis; Kaplan-Meier Estimate
PubMed: 38613589
DOI: 10.1007/s10735-024-10190-9 -
Pharmacological Research May 2020During the latest decades, the interest on the effectiveness of natural compounds and their impact on human health constantly increased, especially on those...
During the latest decades, the interest on the effectiveness of natural compounds and their impact on human health constantly increased, especially on those demonstrating to be effective on cancer. Molecules coming from nature are currently used in chemotherapy like Taxol, Vincristine or Vinblastine, and several other natural substances have been showed to be active in reducing cancer cell progression and migration. Among them, astaxanthin, a xanthophyll red colored carotenoid, displayed different biological activities including, antinflammatory, antioxidant, proapoptotic, and anticancer effects. It can induce apoptosis through downregulation of antiapoptotic protein (Bcl-2, p-Bad, and survivin) expression and upregulation of proapoptotic ones (Bax/Bad and PARP). Thanks to these mechanisms, it can exert anticancer effects towards colorectal cancer, melanoma, or gastric carcinoma cell lines. Moreover, it possesses antiproliferative activity in many experimental models and enhances the effectiveness of conventional chemotherapic drugs on tumor cells underling its potential future use. This review provides an overview of the current knowledge on the anticancer potential of astaxanthin by modulating several molecular targets. While it has been clearly demonstrated its multitarget activity in the prevention and regression of malignant cells in in vitro or in preclinical investigations, further clinical studies are needed to assess its real potential as anticancer in humans.
Topics: Animals; Antineoplastic Agents; Apoptosis; Cell Cycle Checkpoints; Humans; Neoplasms; Xanthophylls
PubMed: 32057895
DOI: 10.1016/j.phrs.2020.104689 -
The International Journal of Biological... Dec 2019Colorectal cancer is a very common cancer worldwide. Serum tumor-associated autoantibodies (TAAbs), especially the anti-p53 autoantibody, may be promising biomarkers to... (Meta-Analysis)
Meta-Analysis
Colorectal cancer is a very common cancer worldwide. Serum tumor-associated autoantibodies (TAAbs), especially the anti-p53 autoantibody, may be promising biomarkers to detect early-stage colorectal cancer. This study aimed to identify all known autoantibodies and their value in colorectal cancer diagnosis, as well as exploring the underlying connections and mechanisms through a bioinformatics analysis. Databases were used to select available articles of TAAbs in colorectal cancer. In a meta-analysis of the anti-p53 autoantibody, the diagnostic odds ratio and area under the curve (AUC) of the summary receiver-operating characteristic (SROC) curve were calculated using Stata 12.0 and Meta-Disc 1.4. We identified 73 articles including 199 single autoantibodies and 42 multiple autoantibodies. The maximum value of Youden's index was 0.76, combining c-MYC, p53, cyclin B1, p62, Koc, IMP1, and survivin. The diagnostic odds ratio for anti-p53 autoantibody at all stages was 10.86 (95% CI 8.40, 14.06) with low heterogeneity (I = 40.3%) and the AUC of the SROC curve was 0.82. For the anti-p53 autoantibody in early-stage colorectal cancer, the diagnostic odds ratio was 4.82 (95% CI 2.95, 7.87) with heterogeneity (I = 7.9%) and the AUC of the SROC curve was 0.72. Eighty-seven autoantibodies were selected for bioinformatics analyses. We found that the most enriched functional terms and protein-protein interactions may relate to the mechanism of autoantibody generation. In summary, our study summarized the diagnostic value of TAAbs in colorectal cancer, either as single molecules or in combination. Bioinformatics analyses may be a new approach to explore the mechanism of autoantibody generation.
Topics: Autoantibodies; Biomarkers, Tumor; Colorectal Neoplasms; Computational Biology; Humans
PubMed: 31588830
DOI: 10.1177/1724600819880906 -
Acta Obstetricia Et Gynecologica... Sep 2019Progestogens are widely used for the conservative treatment of endometrial hyperplasia and early endometrial cancer. Nevertheless, they do not achieve the regression in...
INTRODUCTION
Progestogens are widely used for the conservative treatment of endometrial hyperplasia and early endometrial cancer. Nevertheless, they do not achieve the regression in all cases. Although several immunohistochemical markers have been assessed to predict the response to treatment, their usefulness is still unclear. We aimed to analyze the usefulness of each immunohistochemical marker studied in predicting the response to progestogens in endometrial hyperplasia and early endometrial cancer.
MATERIAL AND METHODS
Electronic databases were searched for relevant articles from January 2000 to June 2018. All studies assessing the association of immunohistochemical markers with the outcome of the progestogen-based therapy in endometrial hyperplasia and early endometrial cancer were included. The expression of immunohistochemical markers in pretreatment phase and changes of expression during the follow-up were evaluated in relation to response to therapy and relapse.
RESULTS
Twenty-seven studies with 1360 women were included in the systematic review; 43 immunohistochemical markers were assessed. The most studied predictive markers in the pretreatment phase were progesterone and estrogen receptors, although with conflicting results; their isoforms, and in particular progesterone receptor B, appeared more promising. Further studies are needed to confirm the usefulness of mismatch repair proteins, Dusp6, GRP78 and PTEN combined with other molecules such as phospho-AKT or phospho-mTOR. In the follow-up phase, Nrf2 and survivin showed the stronger evidence; a role may also be played by Bcl2 and Ki67. Further studies are necessary for Fas, NCoR, AKR1C1, HE4, PAX2 and SPAG9.
CONCLUSIONS
Several immunohistochemical markers might be helpful in predicting the response to conservative treatment of endometrial hyperplasia and early endometrial cancer on pretreatment and follow-up specimens. Further studies are needed to confirm their usefulness and possibly integrate them in a predictive immunohistochemical panel.
Topics: Biomarkers, Tumor; Conservative Treatment; Endometrial Hyperplasia; Endometrial Neoplasms; Endoplasmic Reticulum Chaperone BiP; Female; Humans; Immunohistochemistry; Predictive Value of Tests; Progestins
PubMed: 30793281
DOI: 10.1111/aogs.13587