-
Cancer Metastasis Reviews Mar 2023Pseudomyxoma peritonei (PMP) is a rare, progressive, slowly growing neoplastic condition which is poorly understood, with a 5-year progression-free survival rate as low... (Review)
Review
Pseudomyxoma peritonei (PMP) is a rare, progressive, slowly growing neoplastic condition which is poorly understood, with a 5-year progression-free survival rate as low as 48%. PMP is most commonly caused by appendiceal mucinous neoplasms (AMN), and understanding their genetic biology and pathogenicity may allow for the development of better novel systemic treatments to target key deleterious mutations and the implicated pathways. The primary aim of this systematic review was to identify the genetic profile of histologically confirmed human PMP or AMN samples. The secondary aim was to identify whether genetic marks could be used to predict patient survival. Ovid EMBASE, Ovid MEDLINE, PubMed, and Web of Science were searched to identify studies investigating the genetic profile of histologically-confirmed human PMP or AMN samples. We review findings of 46 studies totalling 2181 tumour samples. The most frequently identified somatic gene mutations in patients with PMP included KRAS (38-100%), GNAS (17-100%), and TP53 (5-23%); however, there were conflicting results of their effect on survival. Three studies identified molecular subtypes based on gene expression profiles classifying patients into oncogene-enriched, immune-enriched, and mixed molecular subtypes with prognostic value. This review summarises the current literature surrounding genetic aberrations in PMP and AMNs and their potential utility for targeted therapy. Given the recent advances in clinical trials to directly target KRAS and GNAS mutations in other cancers, we propose a rationale to explore these mutations in future pre-clinical studies in PMP with a view for a future clinical trial.
Topics: Humans; Pseudomyxoma Peritonei; Peritoneal Neoplasms; Appendiceal Neoplasms; Genetic Profile; Proto-Oncogene Proteins p21(ras)
PubMed: 36723696
DOI: 10.1007/s10555-023-10088-0 -
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 -
International Journal of Medical... 2023The members of the transmembrane emp24 domain-containing protein (TMED) family are summarized in human as four subfamilies, α (TMED 4, 9), β (TMED 2), γ (TMED1, 3, 5,... (Review)
Review
The members of the transmembrane emp24 domain-containing protein (TMED) family are summarized in human as four subfamilies, α (TMED 4, 9), β (TMED 2), γ (TMED1, 3, 5, 6, 7) and δ (TMED 10), with a total of nine members, which are important regulators of intracellular protein transport and are involved in normal embryonic development, as well as in the pathogenic processes of many human diseases. Here we systematically review the composition, structure and function of TMED family members, and describe the progress of TMED family in human diseases, including malignancies (head and neck tumors, lung cancer, breast cancer, ovarian cancer, endometrial cancer, gastrointestinal tumors, urological tumors, osteosarcomas, etc.), immune responses, diabetes, neurodegenerative diseases, and nonalcoholic fatty liver disease, dilated cardiomyopathy, mucin 1 nephropathy (MKD), and desiccation syndrome (SS). Finally, we discuss and prospect the potential of TMED for disease prognosis prediction and therapeutic targeting, with a view to laying the foundation for therapeutic research based on TMED family causative genes.
Topics: Pregnancy; Female; Humans; Membrane Proteins; Protein Transport; Non-alcoholic Fatty Liver Disease; Vesicular Transport Proteins
PubMed: 37928880
DOI: 10.7150/ijms.87272 -
JAMA Network Open Jun 2023Randomized clinical trials examining the effectiveness of neoadjuvant chemotherapy (NACT) for advanced ovarian cancer predominantly included patients with high-grade... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Randomized clinical trials examining the effectiveness of neoadjuvant chemotherapy (NACT) for advanced ovarian cancer predominantly included patients with high-grade serous carcinomas. The use and outcomes of NACT in less common epithelial carcinomas are understudied.
OBJECTIVE
To investigate the uptake and survival outcomes in treatment with NACT for less common histologic subtypes of epithelial ovarian cancer.
DESIGN, SETTING, AND PARTICIPANTS
A retrospective cohort study and systematic literature review with meta-analysis was conducted using the National Cancer Database from 2006 to 2017 and the National Cancer Institute's Surveillance, Epidemiology, and End Results Program from 2006 to 2019. Data analysis was performed from July 2022 to April 2023. The evaluation included patients with stage III to IV ovarian cancer with clear cell, mucinous, or low-grade serous histologic subtypes who received multimodal treatment with surgery and chemotherapy.
EXPOSURES
Exposure assignment per the sequence of treatment: primary debulking surgery (PDS) followed by chemotherapy (PDS group) or NACT followed by interval surgery (NACT group).
MAIN OUTCOMES AND MEASURES
Temporal trends and characteristics of NACT use were assessed using multivariable analysis, and overall survival (OS) was assessed with the inverse probability of treatment weighting propensity score.
RESULTS
A total of 3880 patients were examined in the National Cancer Database including 1829 women (median age, 56 [IQR, 49-63] years) with clear cell, 1156 women (median age, 53 [IQR, 42-64] years) with low-grade serous, and 895 women (median age, 57 [IQR, 48-66] years) with mucinous carcinomas. NACT use increased in patients with clear cell (from 10.2% to 16.2%, 58.8% relative increase; P < .001 for trend) or low-grade serous (from 7.7% to 14.2%, 84.4% relative increase; P = .007 for trend) carcinoma during the study period. This association remained consistent in multivariable analysis. NACT use also increased, but nonsignificantly, in mucinous carcinomas (from 8.6% to 13.9%, 61.6% relative increase; P = .07 for trend). Across the 3 histologic subtypes, older age and stage IV disease were independently associated with NACT use. In a propensity score-weighted model, the NACT and PDS groups had comparable OS for clear cell (4-year rates, 31.4% vs 37.7%; hazard ratio [HR], 1.12; 95% CI, 0.95-1.33) and mucinous (27.0% vs 26.7%; HR, 0.90; 95% CI, 0.68-1.19) carcinomas. For patients with low-grade serous carcinoma, NACT was associated with decreased OS compared with PDS (4-year rates, 56.4% vs 81.0%; HR, 2.12; 95% CI, 1.55-2.90). Increasing NACT use and histologic subtype-specific survival association were also found in the Surveillance, Epidemiology, and End Results Program cohort (n = 1447). A meta-analysis of 4 studies, including the current study, observed similar OS associations for clear cell (HR, 1.13; 95% CI, 0.96-1.34; 2 studies), mucinous (HR, 0.93; 95% CI, 0.71-1.21; 2 studies), and low-grade serous (HR, 2.11; 95% CI, 1.63-2.74; 3 studies) carcinomas.
CONCLUSIONS AND RELEVANCE
Despite the lack of data on outcomes of NACT among patients with less common carcinomas, this study noted that NACT use for advanced disease has gradually increased in the US. Primary chemotherapy for advanced-stage, low-grade serous ovarian cancer may be associated with worse survival compared with PDS.
Topics: Female; Humans; Middle Aged; Adenocarcinoma, Mucinous; Carcinoma, Ovarian Epithelial; Chemotherapy, Adjuvant; Cystadenocarcinoma, Serous; Neoadjuvant Therapy; Neoplasm Staging; Ovarian Neoplasms; Peritoneal Neoplasms; Retrospective Studies; Adult; Aged
PubMed: 37326992
DOI: 10.1001/jamanetworkopen.2023.18602 -
Skin Appendage Disorders May 2022Hematohidrosis and hemolacria are 2 conditions surrounded in religiousness, mysticism, and supernatural superstitions. While the mechanism is still unclear, these cases...
INTRODUCTION
Hematohidrosis and hemolacria are 2 conditions surrounded in religiousness, mysticism, and supernatural superstitions. While the mechanism is still unclear, these cases have amazed physicians for centuries.
METHODS
We performed a systematic review in PubMed from 2000 to mid-2021 accounting for 75 studies from which we included 60 cases in 53 articles which were described.
RESULTS
The median age of apparition was 24 years with the youngest case being 12 and the oldest 81. Some of the diseases were secondary to other causes such as hemangiomas and other neoplasias or epistaxis episodes. Most of the cases have been reported in India and the USA; most of them correspond to hemolacria alone (51.6%).
DISCUSSION
We have stated the basics of the substances involved in the coagulation process that have been described as genetically altered in some patients such as mucins, metalloproteinases, and fibrinogen, as well as propose a mechanism that can explain the signs of this particular entity and approach to its treatment as well as provide the first trichoscopy image of a patient with hemolacria.
PubMed: 35707284
DOI: 10.1159/000520648 -
Frontiers in Oncology 2024Early-onset colorectal cancer (CRC), defined as diagnosis before age 50, has increased in recent decades. Although more often diagnosed at advanced stage, associations...
BACKGROUND
Early-onset colorectal cancer (CRC), defined as diagnosis before age 50, has increased in recent decades. Although more often diagnosed at advanced stage, associations with other histological and molecular markers that impact prognosis and treatment remain to be clarified. We conducted a systematic review and meta-analysis concerning the prevalence of prognostic and predictive tumor markers for early- vs. late-onset CRC, including oncogene mutations, microsatellite instability (MSI), and emerging markers including immune cells and the consensus molecular subtypes.
METHODS
We systematically searched PubMed for original research articles published between April 2013-January 2024. Included studies compared the prevalence of tumor markers in early- vs. late-onset CRC. A meta-analysis was completed and summary odds ratios (ORs) with 95% confidence intervals (CIs) were obtained from a random effects model via inverse variance weighting. A sensitivity analysis was completed to restrict the meta-analysis to studies that excluded individuals with Lynch syndrome, a hereditary condition that influences the distribution of tumor markers for early-onset CRC.
RESULTS
In total, 149 articles were identified. Tumors from early-onset CRC are less likely to include mutations in (OR, 95% CI: 0.91, 0.85-0.98), (0.63, 0.51-0.78), (0.70, 0.58-0.84), and (0.88, 0.78-1.00) but more likely to include mutations in (1.68, 1.04-2.73) and (1.34, 1.24-1.45). After limiting to studies that excluded Lynch syndrome, the associations between early-onset CRC and (0.77, 0.64-0.92) and mutation (0.81, 0.67-0.97) were attenuated, while an inverse association with mutation was also observed (0.88, 0.78-0.99). Early-onset tumors are less likely to develop along the CpG Island Methylator Phenotype pathway (0.24, 0.10-0.57), but more likely to possess adverse histological features including high tumor grade (1.20, 1.15-1.25), and mucinous (1.22, 1.16-1.27) or signet ring histology (2.32, 2.08-2.57). A positive association with MSI status (1.31, 1.11-1.56) was also identified. Associations with immune markers and the consensus molecular subtypes are inconsistent.
DISCUSSION
A lower prevalence of mutations in and is consistent with extended survival and superior response to targeted therapies for metastatic disease. Conversely, early-onset CRC is associated with aggressive histological subtypes and and mutations, which may serve as therapeutic targets.
PubMed: 38737895
DOI: 10.3389/fonc.2024.1349572 -
Cancer Reports (Hoboken, N.J.) Nov 2022Excess weight is convincingly associated with several cancers, but the association with ovarian cancer is insufficiently clarified, in particular regarding subgroups... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Excess weight is convincingly associated with several cancers, but the association with ovarian cancer is insufficiently clarified, in particular regarding subgroups defined by menopausal status and ovarian cancer histologic type.
AIMS
We carried out a comprehensive systematic review and meta-analysis of overweight and obesity in relation to ovarian cancer with focus on different subgroups.
METHODS AND RESULTS
We searched PubMed and Web of Science for relevant cohort and case-control studies published from inception to June 2021 in English language and using a clear definition of overweight and obesity. We combined maximally adjusted risk estimates using a random effects model. We analyzed data from 15 cohort and 26 case-control studies, including 28 471 ovarian cancer cases. The relative risk of ovarian cancer for overweight and obesity was 1.06 (95% confidence interval [CI] = 1.00-1.12) and 1.19 (95% CI = 1.11-1.28), respectively. Among premenopausal women, increased ovarian cancer risk was noted for overweight (RR 1.34; 95% CI = 1.03-1.75) and obesity (RR 1.51; 95% CI = 1.21-1.88). By comparison, among postmenopausal women no statistically significant association was found for overweight (RR 1.00; 95% CI 0.87-1.14) and obesity (RR1.03; 95% CI = 0.82-1.31). Increased risk was found for mucinous (RR 1.44; 95% CI = 1.03-2.01) and clear cell (RR 1.82; 95% CI = 1.11-2.99) ovarian cancer subtypes, but not for serous (RR1.12; 95% CI = 0.84-1.50;) and endometroid subtypes (RR1.24; 95% CI =0.96-1.60).
CONCLUSIONS
Obesity is associated with increased ovarian cancer risk. That relation is largely due to a positive association between adiposity and ovarian cancer among premenopausal but not postmenopausal women and among cases with mucinous and clear cell but not serous or endometrioid histology.
Topics: Female; Humans; Overweight; Risk Factors; Carcinoma, Ovarian Epithelial; Ovarian Neoplasms; Obesity
PubMed: 35384414
DOI: 10.1002/cnr2.1618 -
Brazilian Oral Research Jun 2017Dental caries is an oral pathology associated with both lifestyle and genetic factors. The caries process can be influenced by salivary composition, which includes ions... (Review)
Review
Dental caries is an oral pathology associated with both lifestyle and genetic factors. The caries process can be influenced by salivary composition, which includes ions and proteins. Studies have described associations between salivary protein polymorphisms and dental caries experience, while others have shown no association with salivary proteins genetic variability. The aim of this study is to assess the influence of salivary protein polymorphisms on the risk of dental caries by means of a systematic review of the current literature. An electronic search was performed in PubMed, Scopus, and Virtual Health Library. The following search terms were used: "dental caries susceptibility," "dental caries," "polymorphism, genetics," "saliva," "proteins," and "peptides." Related MeSH headings and free terms were included. The inclusion criteria comprised clinical investigations of subjects with and without caries. After application of these eligibility criteria, the selected articles were qualified by assessing their methodological quality. Initially, 338 articles were identified from the electronic databases after exclusion of duplicates. Exclusion criteria eliminated 322 articles, and 16 remained for evaluation. Eleven articles found a consistent association between salivary protein polymorphisms and risk of dental caries, for proteins related to antimicrobial activity (beta defensin 1 and lysozyme-like protein), pH control (carbonic anhydrase VI), and bacterial colonization/adhesion (lactotransferrin, mucin, and proline-rich protein Db). This systematic review demonstrated an association between genetic polymorphisms and risk of dental caries for most of the salivary proteins.
Topics: DMF Index; Dental Caries; Dental Caries Susceptibility; Female; Genetic Association Studies; Genetic Markers; Humans; Male; Polymorphism, Genetic; Risk Factors; Salivary Proteins and Peptides
PubMed: 28591238
DOI: 10.1590/1807-3107BOR-2017.vol31.0041 -
Gynecologic Oncology Reports May 2019True primary mucinous ovarian carcinomas are rarer than originally thought and their clinical behavior and treatment response are different than more common epithelial... (Review)
Review
True primary mucinous ovarian carcinomas are rarer than originally thought and their clinical behavior and treatment response are different than more common epithelial ovarian carcinomas. Secondary ovarian neoplasms often mimic the clinical and histological features of mucinous ovarian cancer making their diagnosis, and therefore treatment, more difficult. Misdiagnosis can have a significant impact on both treatment and prognosis. The majority of these secondary ovarian neoplasms arise from the gastrointestinal tract, with mucinous histology often of pancreaticobiliary origin. Our study objective was to review current evidence distinguishing pancreaticobiliary ovarian metastasis from primary mucinous ovarian carcinoma. We utilized a PubMed search using MeSH terms and selected articles were reviewed, synthesized and summarized. Thirty-nine articles were included in the review. The clinical, gross, histological and immunohistochemical features distinguishing primary mucinous ovarian carcinomas from pancreaticobiliary ovarian metastasis were identified. Compared to primary mucinous ovarian carcinoma, metastatic pancreaticobiliary tumors are more often bilateral, <10 cm, have irregular external surface and surface implants, display an infiltrative pattern of invasion and stain for MUC1 and CK17. Primary ovarian mucinous tumors rarely (<3%) have signet ring cells or involvement of the hilum. Metastatic mucinous tumors mimic their primary mucinous ovarian counterparts and their clinical and histopathological features overlap in many ways. However, these metastatic tumors have features that can help differentiate them from primary mucinous carcinoma. With a high index of suspicion and knowledge of the reviewed features, distinguishing these tumors will continue to become easier.
PubMed: 30997376
DOI: 10.1016/j.gore.2019.03.012 -
Infection and Drug Resistance 2022Antigen-presenting cells recognize respiratory syncytial virus antigens, and produce cytokines and chemokines that act on immune cells. Dendritic cells play the main... (Review)
Review
Antigen-presenting cells recognize respiratory syncytial virus antigens, and produce cytokines and chemokines that act on immune cells. Dendritic cells play the main role in inflammatory cytokine responses. Similarly, alveolar macrophages produce IFN-β, IFN-α, TNF-α, IL-6, CXCL10, and CCL3, while alternatively activated macrophages differentiate at the late phase, and require IL-13 or IL-4 cytokines. Furthermore, activated NKT cells secrete IL-13 and IL-4 that cause lung epithelial, endothelial and fibroblasts to secrete eotaxin that enhances the recruitment of eosinophil to the lung. CD8 and CD4T cells infection by the virus decreases the IFN-γ and IL-2 production. Despite this, both are involved in terminating virus replication. CD8T cells produce a larger amount of IFN-γ than CD4T cells, and CD8T cells activated under type 2 conditions produce IL-4, down regulating CD8 expression, granzyme and IFN-γ production. Antiviral inhibitors inhibit biological functions of viral proteins. Some of them directly target the virus replication machinery and are effective at later stages of infection; while others inhibit F protein dependent fusion and syncytium formation. TMC353121 reduces inflammatory cytokines, TNF-α, IL-6, and IL-1β and chemokines, KC, IP-10, MCP and MIP1-α. EDP-938 inhibits viral nucleoprotein (N), while GRP-156784 blocks the activity of respiratory syncytial virus ribonucleic acid (RNA) polymerase. PC786 inhibits non-structural protein 1 (NS-1) gene, RANTES transcripts, virus-induced CCL5, IL-6, and mucin increase. In general, it is an immune reaction that is blamed for the disease severity and pathogenesis in respiratory syncytial virus infection. Anti-viral inhibitors not only inhibit viral entry and replication, but also may reduce inflammatory cytokines and chemokines. Many respiratory syncytial virus inhibitors are proposed; however, only palivizumab and ribavirin are approved for prophylaxis and treatment, respectively. Hence, this review is focused on immunity cell responses to respiratory syncytial virus and the role of antiviral inhibitors.
PubMed: 36540102
DOI: 10.2147/IDR.S387479