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Critical Reviews in Oncology/hematology Jun 2023The treatment of locally advanced rectal cancer often consists of neoadjuvant chemoradiotherapy followed by surgery. However, approximately 15% of patients show no... (Review)
Review
BACKGROUND AND AIMS
The treatment of locally advanced rectal cancer often consists of neoadjuvant chemoradiotherapy followed by surgery. However, approximately 15% of patients show no response to this neoadjuvant chemoradiotherapy. This systematic review aimed to identify biomarkers of innate radioresistant rectal cancer.
METHOD
Through a systematic literature search, 125 papers were included and analyzed using ROBINS-I, a Cochrane risk of bias tool for non-randomized studies of interventions. Both statistically significant and nonsignificant biomarkers were identified. Biomarkers mentioned more than once in the results or biomarkers with a low or moderate risk of bias were included as the final results.
RESULTS
Thirteen unique biomarkers, three genetic signatures, one specific pathway, and two combinations of two or four biomarkers were identified. In particular, the connection between HMGCS2, COASY, and PI3K-pathway seems promising. Future scientific research should focus on further validating these genetic resistance markers.
Topics: Humans; Phosphatidylinositol 3-Kinases; Chemoradiotherapy; Rectal Neoplasms; Neoadjuvant Therapy; Biomarkers, Tumor; Treatment Outcome; Neoplasm Staging
PubMed: 37059272
DOI: 10.1016/j.critrevonc.2023.103991 -
Clinical and Experimental Immunology Jul 2021Cytotoxic T lymphocyte antigen 4 (CTLA-4) haploinsufficiency (CHAI) and lipopolysaccharide-responsive beige-like anchor (LRBA) deficiency (LATAIE) are newly identified... (Review)
Review
Cytotoxic T lymphocyte antigen 4 (CTLA-4) haploinsufficiency (CHAI) and lipopolysaccharide-responsive beige-like anchor (LRBA) deficiency (LATAIE) are newly identified inborn errors of immunity with shared molecular pathomechanisms and clinical manifestations. In this review, we aimed to provide differential comparisons regarding demographic, clinical, immunological and molecular characteristics between these two similar conditions. A literature search was conducted in PubMed, Web of Science and Scopus databases and included studies were systematically evaluated. Overall, 434 (222 CHAI and 212 LATAIE) patients were found in 101 eligible studies. The CHAI patients were mainly reported from North America and western Europe, while LATAIE patients were predominantly from Asian countries. In CHAI, positive familial history (P < 0·001) and in LATAIE, consanguineous parents (P < 0·001) were more common. In CHAI patients the rates of granulomas (P < 0·001), malignancies (P = 0·001), atopy (P = 0·001), cutaneous disorders (P < 0·001) and neurological (P = 0·002) disorders were higher, while LATAIE patients were more commonly complicated with life-threatening infections (P = 0·002), pneumonia (P = 0·006), ear, nose and throat disorders (P < 0·001), organomegaly (P = 0·023), autoimmune enteropathy (P = 0·038) and growth failure (P < 0·001). Normal lymphocyte subsets and immunoglobulins except low serum levels of CD9 B cells (14·0 versus 38·4%, P < 0·001), natural killer (NK) cells (21 versus 41·1%, P < 0·001), immunoglobulin (Ig)G (46·9 versus 41·1%, P = 0·291) and IgA (54·5 versus 44·7%, P = 0·076) were found in the majority of CHAI and LATAIE patients, respectively. The most frequent biological immunosuppressive agents prescribed for CHAI and LATAIE patients were rituximab and abatacept, respectively. Further investigations into the best conditioning and treatment regimens pre- and post-transplantation are required to improve the survival rate of transplanted CHAI and LATAIE patients.
Topics: Adaptor Proteins, Signal Transducing; CTLA-4 Antigen; Haploinsufficiency; Humans; Immunoglobulins; Immunosuppressive Agents; Lymphocytes
PubMed: 33788257
DOI: 10.1111/cei.13600 -
The Cochrane Database of Systematic... Nov 2016Among pediatric patients, newborns are at highest risk of developing thromboembolism. Neonatal thromboembolic (TE) events may consist of both venous and arterial... (Review)
Review
BACKGROUND
Among pediatric patients, newborns are at highest risk of developing thromboembolism. Neonatal thromboembolic (TE) events may consist of both venous and arterial thromboses and often iatrogenic complications (eg, central catheterization). Treatment guidelines for pediatric patients with TE events most often are extrapolated from the literature regarding adults. Options for the management of neonatal TE events include expectant management; nitroglycerin ointment; thrombolytic therapy or anticoagulant therapy, or a combination of the two; and surgery. Since the 1990s, low molecular weight heparin (LMWH) has become the neonatal anticoagulant of choice. Reasons for its appeal include predictable dose response, no need for venous access, and limited monitoring requirements. The overall major complication rate is around 5%. Whether preterm infants are at increased risk is unclear. No data are available on the frequency of osteoporosis, heparin-induced thrombocytopenia (HIT), or other hypersensitivity reactions in children and neonates exposed to LMWH.
OBJECTIVES
To assess whether heparin treatment (both unfractionated heparin [UFH] and LMWH) reduces mortality and morbidity rates in preterm and term newborn infants with diagnosed thrombosis. The intervention is compared with placebo or no treatment. Also, to assess the safety of heparin therapy (both UFH and LMWH) for potential harms.Subgroup analyses were planned to examine gestational age, birth weight, mode of thrombus diagnosis, presence of a central line, positive family history for genetic disorders (thrombophilia, deficiency of protein S and protein C, methylenetetrahydrofolate reductase [MTHFR] mutation), route of heparin administration, type of heparin used, and location of thrombus (see "Subgroup analysis and investigation of heterogeneity").
SEARCH METHODS
We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 4), MEDLINE via PubMed (1966 to May 9, 2016), Embase (1980 to May 9, 2016), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to May 9, 2016). We searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomized controlled trials and quasi-randomized trials.
SELECTION CRITERIA
Randomized, quasi-randomized, and cluster-randomized controlled trials comparing heparin versus placebo or no treatment in preterm and term neonates with a diagnosis of thrombosis.
DATA COLLECTION AND ANALYSIS
We used the standard methods of the Cochrane Neonatal Review Group. Two review authors independently assessed studies identified by the search strategy for inclusion.
MAIN RESULTS
Our search strategy yielded 1160 references. Two review authors independently assessed all references for inclusion. We found no completed studies and no ongoing trials for inclusion.
AUTHORS' CONCLUSIONS
We found no studies that met our inclusion criteria and no evidence from randomized controlled trials to recommend or refute the use of heparin for treatment of neonates with thrombosis.
Topics: Anticoagulants; Heparin; Heparin, Low-Molecular-Weight; Humans; Infant, Newborn; Thrombosis
PubMed: 27820879
DOI: 10.1002/14651858.CD012185.pub2 -
Autoimmunity Reviews Mar 2021Regulatory T cells (Tregs) are a subset of T cells responsible for the regulation of immune responses, thereby maintaining immune homeostasis and providing immune... (Review)
Review
Regulatory T cells (Tregs) are a subset of T cells responsible for the regulation of immune responses, thereby maintaining immune homeostasis and providing immune tolerance to both self and non-self-antigens. An increasing number of studies revealed Treg numbers and functions in a variety of autoimmune diseases. Treg deficiency can cause the development of several autoimmune skin diseases including vitiligo, alopecia areata, pemphigoid and pemphigus, psoriasis, and systemic sclerosis. Many clinical trials have been performed for autoimmune conditions using polyclonal Tregs, but efficiency can be significantly improved using antigen-specific Tregs engineered using T cell receptor (TCR) or chimeric antigen receptor (CAR) constructs. In this review, we systematically reviewed altered frequencies, impaired functions, and phenotypic features of Tregs in autoimmune skin conditions. We also summarized new advances in TCR and CAR based antigen-specific Tregs tested both in animal models and in clinics. The advantages and limitations of each approach were carefully discussed emphasizing possible clinical relevance to patients with autoimmune skin diseases. Moreover, we have reviewed potential approaches for engineering antigen-specific Tregs, and strategies for overcoming possible hurdles in clinical applications. Thereby, antigen-specific Tregs can be infused using autologous adoptive cell transfer to restore Treg numbers and to provide local immune tolerance for autoimmune skin disorders.
Topics: Animals; Autoimmune Diseases; Humans; Immune Tolerance; Receptors, Antigen, T-Cell; Skin Diseases; T-Lymphocytes, Regulatory
PubMed: 33476816
DOI: 10.1016/j.autrev.2021.102761 -
Chinese Medicine 2018Rhizoma coptidis has been used in China for thousands of years with the functions of heating dampness and purging fire detoxification. But the underlying molecular... (Review)
Review
Rhizoma coptidis has been used in China for thousands of years with the functions of heating dampness and purging fire detoxification. But the underlying molecular mechanisms of Rhizoma coptidis are still far from being fully elucidated. Alkaloids, especially berberine, coptisine and palmatine, are responsible for multiple pharmacological effects of Rhizoma coptidis. In this review, we studied on the effects and molecular mechanisms of Rhizoma coptidis on NF-κB/MAPK/PI3K-Akt/AMPK/ERS and oxidative stress pathways. Then we summarized the mechanisms of these alkaloid components of Rhizoma coptidis on cardiovascular and cerebrovascular diseases, diabetes and diabetic complications. Evidence presented in this review implicated that Rhizoma coptidis exerted beneficial effects on various diseases by regulation of NF-κB/MAPK/PI3K-Akt/AMPK/ERS and oxidative stress pathways, which support the clinical application of Rhizoma coptidis and offer references for future researches.
PubMed: 29930696
DOI: 10.1186/s13020-018-0184-y -
International Journal of Molecular... Oct 2023Bisphenols such as bisphenol A (BPA), S (BPS), C (BPC), F (BPF), AF (BPAF), tetrabromobisphenol, nonylphenol, and octylphenol are plasticizers used worldwide to... (Meta-Analysis)
Meta-Analysis Review
Bisphenols such as bisphenol A (BPA), S (BPS), C (BPC), F (BPF), AF (BPAF), tetrabromobisphenol, nonylphenol, and octylphenol are plasticizers used worldwide to manufacture daily-use articles. Exposure to these compounds is related to many pathologies of public health importance, such as infertility. Using a protector compound against the reproductive toxicological effects of bisphenols is of scientific interest. Melatonin and vitamins have been tested, but the results are not conclusive. To this end, this systematic review and meta-analysis compared the response of reproductive variables to melatonin and vitamin administration as protectors against damage caused by bisphenols. We search for controlled studies of male rats exposed to bisphenols to induce alterations in reproduction, with at least one intervention group receiving melatonin or vitamins (B, C, or E). Also, molecular docking simulations were performed between the androgen (AR) and estrogen receptors (ER), melatonin, and vitamins. About 1234 records were initially found; finally, 13 studies were qualified for review and meta-analysis. Melatonin plus bisphenol improves sperm concentration and viability of sperm and increases testosterone serum levels compared with control groups; however, groups receiving vitamins plus bisphenols had lower sperm concentration, total testis weight, and testosterone serum levels than the control. In the docking analysis, vitamin E had the highest negative MolDock score, representing the best binding affinity with AR and ER, compared with other vitamins and melatonin in the docking. Our findings suggest that vitamins could act as an endocrine disruptor, and melatonin is most effective in protecting against the toxic effects of bisphenols.
Topics: Male; Rats; Animals; Melatonin; Vitamins; Molecular Docking Simulation; Semen; Benzhydryl Compounds; Reproduction; Receptors, Estrogen; Vitamin A; Vitamin K; Testosterone; Endocrine Disruptors
PubMed: 37834378
DOI: 10.3390/ijms241914930 -
Current Oncology (Toronto, Ont.) Sep 2023Serous epithelial ovarian cancer, classified as either high-grade (90%) or low-grade (10%), varies in molecular, histological, and clinicopathological presentation.... (Review)
Review
Serous epithelial ovarian cancer, classified as either high-grade (90%) or low-grade (10%), varies in molecular, histological, and clinicopathological presentation. Low-grade serous ovarian cancer (LGSOC) is a rare histologic subtype that lacks disease-specific evidence-based treatment regimens. However, LGSOC is relatively chemo-resistant and has a poor response to traditional treatments. Alternative treatments, including biologic therapies such as bevacizumab, have shown some activity in LGSOC. Thus, the objective of this systematic review is to determine the effect and safety of bevacizumab in the treatment of LGSOC. Following PRISMA guidelines, Medline ALL, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Embase all from the OvidSP platform, ClinicalTrials.gov, International Clinical Trials Registry Platform, International Standard Randomised Controlled Trial Number Registry were searched from inception to February 2022. Articles describing bevacizumab use in patients with LGSOC were included. Article screening, data extraction, and critical appraisal of included studies were completed by two independent reviewers. The effect of bevacizumab on the overall response rate, progression-free survival, overall survival, and adverse effects were summarized. The literature search identified 3064 articles, 6 of which were included in this study. A total of 153 patients were analyzed; the majority had stage IIIC cancer (56.2%). The overall median response rate reported in the studies was 47.5%. Overall, bevacizumab is a promising treatment for LGSOC, with response rates higher than traditional treatment modalities such as conventional chemotherapy, and is often overlooked as a treatment tool. A prospective clinical trial evaluating the use of bevacizumab in LGSOC is necessary to provide greater evidence and support these findings.
Topics: Humans; Female; Bevacizumab; Prospective Studies; Carcinoma, Ovarian Epithelial; Cystadenocarcinoma, Serous; Peritoneal Neoplasms; Ovarian Neoplasms
PubMed: 37754507
DOI: 10.3390/curroncol30090592 -
Biomedicines Dec 2022Lafora disease (LD) is a neurodegenerative condition characterized by the accumulation of polyglucosan bodies (PBs) throughout the brain. Alongside metabolic and... (Review)
Review
BACKGROUND
Lafora disease (LD) is a neurodegenerative condition characterized by the accumulation of polyglucosan bodies (PBs) throughout the brain. Alongside metabolic and molecular alterations, neuroinflammation has emerged as another key histopathological feature of LD.
METHODS
To investigate the role of astrocytes and microglia in LD, we performed a systematic review according to the PRISMA statement. PubMed, Scopus, and Web-of-Science database searches were performed independently by two reviewers.
RESULTS
Thirty-five studies analyzing the relationship of astrocytes and microglia with LD and/or the effects of anti-inflammatory treatments in LD animal models were identified and included in the review. Although LD has long been dominated by a neuronocentric view, a growing body of evidence suggests a role of glial cells in the disease, starting with the finding that these cells accumulate PBs. We discuss the potential meaning of glial PB accumulations, the likely factors activating glial cells, and the possible contribution of glial cells to LD neurodegeneration and epilepsy.
CONCLUSIONS
Given the evidence for the role of neuroinflammation in LD, future studies should consider glial cells as a potential therapeutic target for modifying/delaying LD progression; however, it should be kept in mind that these cells can potentially assume multiple reactive phenotypes, which could influence the therapeutic response.
PubMed: 36551859
DOI: 10.3390/biomedicines10123103 -
Cancer Treatment Reviews Apr 2023The anti-tumor activity of WEE1 inhibitors (WEE1i) in gynecological malignancies has recently been demonstrated in clinical trials and its rationale is based on... (Review)
Review
INTRODUCTION
The anti-tumor activity of WEE1 inhibitors (WEE1i) in gynecological malignancies has recently been demonstrated in clinical trials and its rationale is based on biological/molecular features of gynecological cancers. With this systematic review, we aim to outline the clinical development and current evidence regarding the efficacy and safety of these targeted agents in in this patient group.
METHODS
Systematic literature review of trials including patients with gynecological cancers treated with a WEE1i. The primary objective was to summarize the efficacy of WEE1i in gynecological malignancies regarding objective response rate (ORR), clinical benefit rate (CBR), overall survival (OS) and progression-free survival (PFS). Secondary objectives included toxicity profile, Maximum Tolerated Dose (MTD), pharmacokinetics, drug-drug interactions and exploratory objectives such as biomarkers for response.
RESULTS
26 records were included for data extraction. Almost all trials used the first-in-class WEE1i adavosertib; one conference abstract reported about Zn-c3. The majority of the trials included diverse solid tumors (n = 16). Six records reported efficacy results of WEE1i in gynecological malignancies (n = 6). Objective response rates of adavosertib monotherapy or in combination with chemotherapy ranged between 23% and 43% in these trials. Median PFS ranged from 3.0 to 9.9 months. The most common adverse events were bone marrow suppression, gastrointestinal toxicities and fatigue. Mainly alterations in cell cycle regulator genes TP53 and CCNE1 were potential predictors of response.
CONCLUSION
This report summarizes encouraging clinical development of WEE1i in gynecological cancers and considers its application in future studies. Biomarker-driven patient selection might be essential to increase the response rates.
Topics: Female; Humans; Genital Neoplasms, Female; Antineoplastic Agents; Protein-Tyrosine Kinases; Cell Cycle Proteins
PubMed: 36893690
DOI: 10.1016/j.ctrv.2023.102531 -
RMD Open Mar 2023Type I interferons (IFN-I) contribute to a broad range of rheumatic and musculoskeletal diseases (RMDs). Compelling evidence suggests that the measurement of IFN-I...
Association between type I interferon pathway activation and clinical outcomes in rheumatic and musculoskeletal diseases: a systematic literature review informing EULAR points to consider.
BACKGROUND
Type I interferons (IFN-I) contribute to a broad range of rheumatic and musculoskeletal diseases (RMDs). Compelling evidence suggests that the measurement of IFN-I pathway activation may have clinical value. Although several IFN-I pathway assays have been proposed, the exact clinical applications are unclear. We summarise the evidence on the potential clinical utility of assays measuring IFN-I pathway activation.
METHODS
A systematic literature review was conducted across three databases to evaluate the use of IFN-I assays in diagnosis and monitor disease activity, prognosis, response to treatment and responsiveness to change in several RMDs.
RESULTS
Of 366 screened, 276 studies were selected that reported the use of assays reflecting IFN-I pathway activation for disease diagnosis (n=188), assessment of disease activity (n=122), prognosis (n=20), response to treatment (n=23) and assay responsiveness (n=59). Immunoassays, quantitative PCR (qPCR) and microarrays were reported most frequently, while systemic lupus erythematosus (SLE), rheumatoid arthritis, myositis, systemic sclerosis and primary Sjögren's syndrome were the most studied RMDs. The literature demonstrated significant heterogeneity in techniques, analytical conditions, risk of bias and application in diseases. Inadequate study designs and technical heterogeneity were the main limitations. IFN-I pathway activation was associated with disease activity and flare occurrence in SLE, but their incremental value was uncertain. IFN-I pathway activation may predict response to IFN-I targeting therapies and may predict response to different treatments.
CONCLUSIONS
Evidence indicates potential clinical value of assays measuring IFN-I pathway activation in several RMDs, but assay harmonisation and clinical validation are urged. This review informs the EULAR points to consider for the measurement and reporting of IFN-I pathway assays.
Topics: Humans; Interferon Type I; Musculoskeletal Diseases; Myositis; Lupus Erythematosus, Systemic
PubMed: 36882218
DOI: 10.1136/rmdopen-2022-002864