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Frontiers in Immunology 2022Lung cancer is a disease with remarkable heterogeneity. A deep understanding of the tumor microenvironment (TME) offers potential therapeutic strategies against this... (Review)
Review
Lung cancer is a disease with remarkable heterogeneity. A deep understanding of the tumor microenvironment (TME) offers potential therapeutic strategies against this malignant disease. More and more attention has been paid to the roles of macrophages in the TME. This article briefly summarizes the origin of macrophages, the mutual regulation between anti-tumoral immunity and pro-tumoral statuses derived from macrophage polarization, and the therapeutic opportunities targeting alternately activated macrophages (AAM)-type macrophage polarization. Among them, cellular components including T cells, as well as acellular components represented by IL-4 and IL-13 are key regulators driving the polarization of AAM macrophages. Novel treatments targeting macrophage-associated mechanisms are mainly divided into small molecule inhibitors, monoclonal antibodies, and other therapies to re-acclimate AMM macrophages. Finally, we paid special attention to an immunosuppressive subgroup of macrophages with T cell immunoglobulin and mucin domain-3 (TIM-3) expression. Based on cellular interactions with cancer cells, TIM3+ macrophages facilitate the proliferation and progression of cancer cells, yet this process exposes targets blocking the ligand-receptor recognition. To sum up, this is a systematic review on the mechanism of tumor-associated macrophages (TAM) polarization, therapeutic strategies and the biological functions of Tim-3 positive macrophages that aims to provide new insights into the pathogenesis and treatment of lung cancer.
Topics: Humans; Hepatitis A Virus Cellular Receptor 2; Lung Neoplasms; Macrophages; Tumor Microenvironment; Tumor-Associated Macrophages
PubMed: 36439090
DOI: 10.3389/fimmu.2022.1007812 -
Caries Research 2022Salivary proteins play an important role in repairing mechanisms of damaged tissues and the maintenance of oral health. However, there is a dearth of information in the...
Salivary proteins play an important role in repairing mechanisms of damaged tissues and the maintenance of oral health. However, there is a dearth of information in the literature regarding the concentrations of salivary proteins in caries-free (CF) and caries-active (CA) subjects. Hence, this systematic review was conducted to update our previous systematic review published in 2013 that aimed to assess the association between caries and salivary proteins by comparing CF and CA individuals. Thereby, evaluating the possibility of whether salivary proteins can be regarded as biomarkers for caries. An extensive search of studies was conducted using PubMed, EMBASE, Clarivate Analytics' Web of Science, and Elsevier's Scopus between July 2012 and January 2022, without any language restriction. Manual searching in Google Scholar and evaluation of bibliographies of the included studies were also undertaken. The Newcastle-Ottawa Scale was used to assess the risk of bias (RoB) within the included studies. Of 22 included studies, 1,551 human subjects (range: 30-213 participants) were recruited, of which 848 individuals (54.7%) were CA and 703 (45.3%) were CF. Regarding the utilization of DMFT as the caries index, high variability was observed across different articles. A statistically significant increase in the salivary levels of alpha-amylase, acidic proline-rich protein-1, histatin-5, lactoperoxidase, and mucin-1 was found in CA patients, while the salivary levels of carbonic anhydrase 6, proteinase-3, and statherin were observed to be significantly increased in CF subjects. Conflicting results were found regarding the salivary levels of immunoglobulin A and total proteins among CA and CF subjects. The included studies were categorized as low RoB (n = 15), medium RoB (n = 4), and high RoB (n = 3). Due to significant heterogeneity among the included studies, no meta-analysis could be performed. In conclusion, the salivary levels of protein(s) might be a useful biomarker for caries diagnosis, especially alpha-amylase, acidic proline-rich protein-1, histatin-5, lactoperoxidase, mucin-1, carbonic anhydrase 6, proteinase-3, and statherin. However, their diagnostic value must be verified by large-scale prospective studies.
Topics: Humans; Mucin-1; Dental Caries; Histatins; Lactoperoxidase; Prospective Studies; Salivary Proteins and Peptides; Biomarkers; Proline; alpha-Amylases; Peptide Hydrolases
PubMed: 36116431
DOI: 10.1159/000526942 -
Fish & Shellfish Immunology Nov 2022Nanoparticles-based treatments is of utmost importance for aquaculture. In this scenario, chitosan-based nanoparticles have been proposed due to the properties of... (Review)
Review
Nanoparticles-based treatments is of utmost importance for aquaculture. In this scenario, chitosan-based nanoparticles have been proposed due to the properties of chitosan, which include mucoadhesiveness. Nevertheless, pivotal parameters of chitosan, such as degree of acetylation and molecular weight, are commonly underestimated in the available literature despite the influence they seem to have on the properties of chitosan-based nanoparticles. In this systematic review, the immunomodulator capacity of chitosan nanoparticles used as mucosal vaccines on teleost fish has been evaluated paying special attention to the chitosan properties. Four databases were used for literature search, yielding 486 documents, from which 14 meet the inclusion criteria. Only 21% of the available studies reported properly chitosan properties, which should be improved in future works to generate reproducible data as well as valuable information. To the best of our knowledge, this work objectively compares for the first time, by quantifying the mg of chitosan/g of fish applied in each study, the chitosan nanoparticle preparation and doses applied to fish, as well as the effects of the treatments applied on fish immune status.
Topics: Adjuvants, Immunologic; Animals; Chitosan; Immunity, Mucosal; Nanoparticles; Vaccines
PubMed: 36038102
DOI: 10.1016/j.fsi.2022.08.030 -
Experimental and Therapeutic Medicine Sep 2022The gallbladder undergoes different types of pathologies, ranging from inflammatory to preneoplasia and finally to malignant lesions. Gallbladder carcinoma can be highly...
The gallbladder undergoes different types of pathologies, ranging from inflammatory to preneoplasia and finally to malignant lesions. Gallbladder carcinoma can be highly invasive, and it is known that chronic inflammation of the gallbladder can lead to preneoplastic abnormalities and subsequently malignant phenotypes. Gallbladder neoplasia has a low incidence but is associated with a very poor prognosis. An early diagnosis is therefore extremely important in order to improve the prognosis of patients. Immunohistochemical markers of the mucin family can distinguish between different types of gallbladder lesions. Mucins are glycoproteins that can be attached to threonine residues that are -glycosylated (due to the hydroxyl group of this amino acid). Mucins are divided into two types: those that bind to the membrane, such as MUC1, and those that form gels or are secreted, such as MUC5AC. Various alterations in mucin expression have been revealed to be associated with the development of neoplasia, as they modulate cell growth, karyokinetic transformation, dedifferentiation, adhesion, invasion and immune surveillance. p53 is a tumor suppressor gene and is linked to the development of different types of neoplasia. The incidence of the p53 gene is variable in the pathophysiology of gallbladder cancer. Several studies have revealed an incidence of ~50% of the p53 gene in gallbladder tumors. Studying the immunohistochemical profile of mucins and the presence of different gene mutations in neoplastic lesions of the gallbladder and surrounding mucosa may contribute to the understanding of the pathophysiology of the disease and the mechanisms involved in tumor development, allowing the identification of patients at increased risk of developing neoplasia, thus leading to improved management.
PubMed: 35949333
DOI: 10.3892/etm.2022.11541 -
Frontiers in Oncology 2022Goblet cell adenocarcinoma (GCA) of the appendix is a rare and aggressive tumour with varying nomenclature and classification systems. This has led to heterogeneity in...
BACKGROUND
Goblet cell adenocarcinoma (GCA) of the appendix is a rare and aggressive tumour with varying nomenclature and classification systems. This has led to heterogeneity in published data, and there is a lack of consensus on incidence, survival, and management.
METHODS
We provide an overview of GCA with a comprehensive systematic review using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology and a retrospective analysis of all cases recorded in the English National Cancer Registration and Analysis Service database between 1995 and 2018. The Kaplan-Meier estimator was used to calculate overall survival, and Cox proportional hazards regression was used to identify prognostic factors.
RESULTS
The systematic review demonstrated an incidence of 0.05-0.3 per 100,000 per year among North American registry studies. The 1-, 3-, and 5-year survival rate was 95.5%, 85.9%-87.6%, and 76.0%-80.6%, respectively. Age, stage, and grade were identified as prognostic factors for survival. Our analysis included 1,225 cases. Age-standardised incidence was 0.0335 per year in 1995 and gradually rose to 0.158 per year in 2018. The 1-, 3-, and 5-year survival rate was 90.0% [95% confidence interval (95% CI): 85.4-94.0], 76.0% (95% CI: 73.8-80.9), and 68.6% (95% CI: 65.9-72.2), respectively. On univariate Cox regression analyses, female sex, stage, and grade were associated with worse overall survival. On multivariate analysis, only stage remained a statistically significant prognostic factor.
CONCLUSIONS
GCA of the appendix is rare, but incidence is increasing. We report a lower incidence and survival than North American registry studies. Higher stage was associated with decreased survival. Further prospective studies are required to establish optimal management.
PubMed: 35903705
DOI: 10.3389/fonc.2022.915028 -
Medicina (Kaunas, Lithuania) Jul 2022Pancreatic cystic lesions (PCLs) are frequently incidental findings. The prevalence of PCLs is increasing, mainly due to advancements in imaging techniques, but also... (Review)
Review
Pancreatic cystic lesions (PCLs) are frequently incidental findings. The prevalence of PCLs is increasing, mainly due to advancements in imaging techniques, but also because of the aging of the population. PCLs comprise challenging clinical problems, as their manifestations vary from benign to malignant lesions. Therefore, the recognition of PCLs is achieved through a complex diagnostic and surveillance process, which in turn is usually long-term, invasive, and expensive. Despite the progress made in the identification of novel biomarkers in the cystic fluid that also support the differentiation of PCLs, their application in clinical practice is limited. We conducted a systematic review of the literature published in two databases, Pubmed and Embase, on biochemical biomarkers in PCLs that may be applied in the diagnostic algorithms of PCLs. Eleven studies on intracystic glucose, twenty studies on intracystic carcinoembryonic antigen (CEA), and eighteen studies on other biomarkers were identified. Low levels of intracystic glucose had high sensitivity and specificity in the differentiation between mucinous and non-mucinous cystic neoplasms. CEA and glucose are the most widely studied fluid biochemical markers in pancreatic cystic lesions. Glucose has better diagnostic accuracy than CEA. Other biochemical biomarkers require further research.
Topics: Biomarkers, Tumor; Carcinoembryonic Antigen; Diagnosis, Differential; Glucose; Humans; Pancreatic Cyst; Pancreatic Neoplasms
PubMed: 35893110
DOI: 10.3390/medicina58080994 -
Pancreatology : Official Journal of the... Nov 2022Pancreatic cancer has a dismal prognosis. So far, imaging has been proven incapable of establishing an early enough diagnosis. Thus, biomarkers are urgently needed for... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Pancreatic cancer has a dismal prognosis. So far, imaging has been proven incapable of establishing an early enough diagnosis. Thus, biomarkers are urgently needed for early detection and improved survival. Our aim was to evaluate the pooled diagnostic performance of DNA alterations in pancreatic juice.
METHODS
A systematic literature search was performed in EMBASE, MEDLINE Ovid, Cochrane CENTRAL and Web of Science for studies concerning the diagnostic performance of DNA alterations in pancreatic juice to differentiate patients with high-grade dysplasia or pancreatic cancer from controls. Study quality was assessed using QUADAS-2. The pooled prevalence, sensitivity, specificity and diagnostic odds ratio were calculated.
RESULTS
Studies mostly concerned cell-free DNA mutations (32 studies: 939 cases, 1678 controls) and methylation patterns (14 studies: 579 cases, 467 controls). KRAS, TP53, CDKN2A, GNAS and SMAD4 mutations were evaluated most. Of these, TP53 had the highest diagnostic performance with a pooled sensitivity of 42% (95% CI: 31-54%), specificity of 98% (95%-CI: 92%-100%) and diagnostic odds ratio of 36 (95% CI: 9-133). Of DNA methylation patterns, hypermethylation of CDKN2A, NPTX2 and ppENK were studied most. Hypermethylation of NPTX2 performed best with a sensitivity of 39-70% and specificity of 94-100% for distinguishing pancreatic cancer from controls.
CONCLUSIONS
This meta-analysis shows that, in pancreatic juice, the presence of distinct DNA mutations (TP53, SMAD4 or CDKN2A) and NPTX2 hypermethylation have a high specificity (close to 100%) for the presence of high-grade dysplasia or pancreatic cancer. However, the sensitivity of these DNA alterations is poor to moderate, yet may increase if they are combined in a panel.
Topics: Humans; Biomarkers, Tumor; Carcinoma, Pancreatic Ductal; Early Detection of Cancer; Mutation; Pancreatic Juice; Pancreatic Neoplasms
PubMed: 35864067
DOI: 10.1016/j.pan.2022.06.260 -
Frontiers in Oncology 2022Early detection of synchronous colorectal peritoneal metastases (CPMs) is difficult due to the absence of typical symptoms and the low accuracy of imaging examinations....
BACKGROUND
Early detection of synchronous colorectal peritoneal metastases (CPMs) is difficult due to the absence of typical symptoms and the low accuracy of imaging examinations. Increasing the knowledge of the risk factors for synchronous CPM may be essential for early diagnosis and improving their management. This study aimed to identify the risk factors for synchronous CPM.
METHOD
The study was registered at PROSPERO (CRD42020198548). The PubMed, Embase and Cochrane Library databases were searched for studies comparing the clinicopathological and molecular features between patients with or without synchronous CPM. The pooled data were assessed by a random-effects model.
RESULTS
Twenty-five studies were included. A synchronous CPM was positively associated with female sex (OR 1.299; 1.118 to 1.509; P = 0.001), PROK1/PROKR2-positivity (OR 2.244; 1.031 to 4.884; P = 0.042), right-sided colon cancer (OR 2.468; 2.050 to 2.970; P < 0.001), poorly differentiated grade (OR 2.560; 1.537 to 4.265; P < 0.001), BRAF mutation (OR 2.586; 1.674 to 3.994; P < 0.001), mucinous adenocarcinoma (OR 3.565; 2.095 to 6.064; P < 0.001), signet-ring cell carcinoma (OR 4.480; 1.836 to 10.933; P = 0.001), N1-2 (OR 5.665; 3.628 to 8.848; P < 0.001), T4 (OR 12.331; 7.734 to 19.660; P < 0.001) and elevated serum CA19-9 (OR 12.868; 5.196 to 31.867; P < 0.001).
CONCLUSIONS
These evidence-based risk factors are indicators that could predict the presence of synchronous CPMs and can improve their management.
SYSTEMATIC REVIEW REGISTRATION
www.crd.york.ac.uk/prospero, identifier: CRD42020198548.
PubMed: 35795042
DOI: 10.3389/fonc.2022.885504 -
European Journal of Surgical Oncology :... Oct 2022Postoperative adjuvant chemotherapy followed surgery is the standard management for localized advanced colorectal carcinoma (CRC). Mucinous adenocarcinoma (MAC) is a... (Meta-Analysis)
Meta-Analysis Review
Mucinous histology is associated with poor prognosis in locally advanced colorectal adenocarcinoma treated with postoperative first-line adjuvant chemotherapy: A systematic review and meta-analysis.
PURPOSE
Postoperative adjuvant chemotherapy followed surgery is the standard management for localized advanced colorectal carcinoma (CRC). Mucinous adenocarcinoma (MAC) is a peculiar histological subtype of CRC, but the prognosis of MAC patients is controversial. The objective of this study is to assess the implication of MAC in survival of patients treated with surgery and firs-line adjuvant chemotherapy.
METHODS
Studies describing outcomes for advanced MAC and non-specific adenocarcinoma (AC) of CRC patients treated with first-line postoperative adjuvant chemotherapy followed surgery were searched in PubMed, Embase, Medline, EBSCO, Wiley, and Cochrane Library (January 1963-August 2021). Hazard ratios (HRs) of overall survival (OS), disease-free survival (DFS) and cancer-specific survival (CSS) for MAC to AC were extracted. Random-effects model was used for calculating the pooled HRs and 95% confidence interval (CI).
RESULTS
This meta-analysis is comprised of 8 studies involving a total of 124,303 CRC patients treated with first-line adjuvant chemotherapy followed surgery. The pooled HR for MAC was 1.23 (95% CI, 1.07-1.41, p < 0.01, I = 80%), and the DFS (HR, 2.95, 95% CI, 1.22-7.14) of MAC patients were significantly poorer than AC patients. Similar results were also observed in stage III and FOLFOX regimen subgroups.
CONCLUSION
MAC was a risk factor for prognosis of localized advanced CRC patients treated with postoperative first-line adjuvant chemotherapy. Thus, the role of first-line adjuvant chemotherapy regimens should be further studied in these MAC patients.
Topics: Humans; Colorectal Neoplasms; Adenocarcinoma; Chemotherapy, Adjuvant; Adenocarcinoma, Mucinous; Prognosis
PubMed: 35768312
DOI: 10.1016/j.ejso.2022.06.024 -
PloS One 2022The role of biomarkers in the early diagnosis and prognosis prediction of tumors has been paid more and more attention by researchers. Mucins are markers that have been... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The role of biomarkers in the early diagnosis and prognosis prediction of tumors has been paid more and more attention by researchers. Mucins are markers that have been found to have an abnormal expression in many tumors in recent years, which have been proved to have a predictive effect on the prognosis of tumors such as cholangiocarcinoma and colon cancer. However, whether it can predict the prognosis of pancreatic cancer remains unknown. The purpose of our study is to investigate whether the mucins and their subtypes are related to the prognosis of patients with pancreatic cancer.
METHODS
We systematically searched the Pubmed, Embase, and Cochrane Library for all eligible studies on the relationship between mucin and the prognosis of patients with pancreatic cancer up to November 2021. We used R 4.12 to calculate the combined risk ratio (HR) and 95% confidence interval (CI). For studies that did not provide HR values, we used scientific methods to calculate their values as accurately as possible. We used fixed effect model due to low heterogeneity. Subgroup analysis and sensitivity analysis were used to study heterogeneity. The funnel plot and Egger test were used to test whether the publication bias existed. The trim and filling method were used to evaluate the impact of publication bias on the results of the study.
RESULTS
A total of 18 studies were included in this meta-analysis, including 4 subtypes of mucin family members and 1643 patients. There was a slight heterogeneity between studies (I2 = 24.4%, P = 0.14). Meta-analysis showed that MUC4 (HR = 2.04, 95%CI 1.21;3.45), MUC16 (HR = 2.10, 95%CI 1.31;3.37), and whole mucin (HR = 1.32, 95%CI 1.07;1.63). The expression level was negatively correlated with the prognosis of pancreatic cancer patients, MUC1 (HR = 1.09, 95%CI 0.77;1.54), MUC5 (HR = 1.03, 95%CI 0.47;2.25) The expression level was not related to the prognosis of pancreatic cancer patients.
CONCLUSION
The meta-analysis demonstrated that the overall expression level of mucin and the expression levels of MUC4 and MUC16 were important prognostic predictors for pancreatic cancer patients. MUC1 and MUC5 had no predictive value for the prognosis of pancreatic cancer patients. Future studies should validate these and other promising biomarkers.
TRIAL REGISTRATION
PROSPERO registration number is CRD42021291962. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021291962.
Topics: Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Biomarkers; Early Detection of Cancer; Humans; Mucins; Pancreatic Neoplasms; Prognosis
PubMed: 35709153
DOI: 10.1371/journal.pone.0269612