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The Journal of Clinical Endocrinology... Oct 2023Tumor-induced osteomalacia (TIO) due to fibroblast growth factor 23 (FGF23) overexpression is becoming recognized in patients with malignancy. The condition may be... (Meta-Analysis)
Meta-Analysis
CONTEXT
Tumor-induced osteomalacia (TIO) due to fibroblast growth factor 23 (FGF23) overexpression is becoming recognized in patients with malignancy. The condition may be underdiagnosed, with a scarce medical literature.
OBJECTIVE
To perform a meta-analysis of case reports to allow a better understanding of malignant TIO and its clinical implications.
METHODS
Full texts were selected according to strict inclusion criteria. All case reports were included where patients had hypophosphatemia, malignant TIO, and FGF23 blood levels. Thirty-two of 275 eligible studies (n = 34 patients) met inclusion criteria. A list of desired data was extracted and graded for methodological quality.
RESULTS
Prostate adenocarcinoma (n = 9) were the most tumors reported. Twenty-five of 34 patients had a metastatic disease and a poor clinical outcome was reported for 15 of 28 patients. The median levels of blood phosphate and C-terminal FGF23 (cFGF23) were 0.40 mmol/L and 788.5 RU/mL, respectively. For most of patients, blood PTH was elevated or within range, and calcitriol levels were inappropriately low or normal. Alkaline phosphatase concentrations were increased for 20 of 22 patients. The cFGF23 values were significantly higher for patients with a poor clinical outcome when compared to other patients (1685 vs 357.5 RU/mL). In case of prostate cancer, cFGF23 levels were significantly lower (429.4 RU/mL) than for other malignancies (1007.5 RU/mL).
CONCLUSION
We report for the first time a detailed description of the clinical and biological characteristics of malignant TIO. In this context, FGF23 blood measurement would be of value for the diagnostic workup, prognostication, and follow-up of patients.
Topics: Humans; Male; Calcitriol; Fibroblast Growth Factors; Hypophosphatemia; Osteomalacia; Paraneoplastic Syndromes; Case Reports as Topic
PubMed: 37235783
DOI: 10.1210/clinem/dgad297 -
Journal of Oral and Maxillofacial... 2023Odontogenic keratocyst (OKC) is an aggressive odontogenic lesion that has been the subject of continuous dispute about its biological activity and classification.... (Review)
Review
Odontogenic keratocyst (OKC) is an aggressive odontogenic lesion that has been the subject of continuous dispute about its biological activity and classification. 'Numerous studies are being conducted to see how much more or lower expression of the tumour-suppressing p53 protein is in the odontogenic cyst than in the dentigerous cyst (DC) or ameloblastic tumours. The aim was to find immunohistochemistry studies reporting on OKCs, DCs and ameloblastomas (AMBs); we searched MEDLINE, WEB of Science and SCOPUS. Effects may be shown to exist when the risk difference (RD) between lesions overexpressing and those without the p53 protein was a value of less than 0.05. A total of 129 records were returned in the first hit. After the elimination of duplicates, there were 89 items, of which 18 were deemed eligible for inclusion. According to a meta-analysis of 13 studies including OKCs, DCs and AMB, the chance of p53 expression in OKCs is assessed to be 23 per cent higher ( = 0.003) than in DCs, whereas the probability is predicted to be 4 per cent lower ( = 0.028) than in AMBs. OKCs appear to act more like cancers than odontogenic sores as far as p53 articulation, and the order of this illness into the keratocystic odontogenic tumour (KCOT) ought to be rethought.
PubMed: 37234299
DOI: 10.4103/jomfp.jomfp_58_22 -
Annals of Medicine Dec 2023We performed an umbrella meta-analysis to explore the factors that influence the efficacy of immune checkpoint inhibitor (ICI) therapy. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
We performed an umbrella meta-analysis to explore the factors that influence the efficacy of immune checkpoint inhibitor (ICI) therapy.
MATERIALS AND METHODS
We systematically searched three databases (PubMed, Web of Science and Embase) up to 20 February 2023. Extracting the effect size and 95% confidence intervals for overall survival (OS), progression-free survival (PFS) and the objective response rate (ORR).
RESULTS
A total of 65 articles were included. We identified the following factors that benefit ICI therapy: smoking status (PFS: 0.72 [0.62, 0.84], < .001), chemotherapy (PFS: 0.68 [0.58, 0.79], < .001), expression of programmed cell death ligand 1(PD-L1) (≥1%, ≥5%, or ≥10%) (≥1%: 0.76 [0.71,0.82], < .001; ≥5%: 0.62 [0.52, 0.74], < .001; ≥10%: 0.42 [0.30, 0.59], < .001). We also identified three adverse factors: epidermal growth factor receptor mutations (OS: 1.57 [1.06, 2.32], = .02), with liver metastases (OS: 1.16 [1.02,1.32], = .02) and antibiotics (OS: 3.13 [1.25,7.84], < .001; PFS: 2.54 [1.38, 4.68], = .003).
CONCLUSION
The results of this umbrella meta-analysis first supported pre-existing understandings of the relationship between beneficial and adverse factors with the efficacy of ICI therapy. In addition, the overexpression of PD-L1 may adversely affect patients.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; B7-H1 Antigen; Immune Checkpoint Inhibitors; Antineoplastic Agents, Immunological; Randomized Controlled Trials as Topic
PubMed: 37212453
DOI: 10.1080/07853890.2023.2215543 -
Critical Reviews in Oncology/hematology Jul 2023Head and neck cancer (HNC) is a growing disease, affecting more than 700.000 cases per year and ranking as the sixth most prevalent type of cancer worldwide. The... (Meta-Analysis)
Meta-Analysis Review
Head and neck cancer (HNC) is a growing disease, affecting more than 700.000 cases per year and ranking as the sixth most prevalent type of cancer worldwide. The impossibility of properly entering into apoptosis directly influences uncontrolled growth and consequently tumor development and progression. Bcl-2 emerged as a key regulator in the balance between cell apoptosis and proliferation in apoptosis machinery. This systematic review and meta-analysis aimed to review all published studies investigating changes in Bcl-2 protein expression assessed by immunohistochemistry (IHC) and related to prognostic and survival values of patients with HNC. After applying the inclusion and exclusion factors, we reached the number of 20 articles included in the meta-analysis. The random-effect pooled HR (CI95%) value of OS related to Bcl-2 IHC expression in tissues from HNC patients was 1.80 (CI95% 1.21-2.67) (p 0.0001) and DFS was 1.90 (CI95% 1.26-2.86 (p 0.0001). The OS value for the specific oral cavity tumors was 1.89 (1.34-2.67), while in the larynx it was 1.77 (0.62-5.06), and the DFS in the pharynx was 2.02 (1.46-2.79). The univariate and multivariate analyses of OS were respectively 1.43 (1.11-1.86) and 1.88 (1.12-3.16), while in DFS it was 1.70 (0.95-3.03) and 2.08 (1.55-2.80). The OS considering a low cut-off for Bcl-2 positivity was 1.19 (0.60-2.37) and DFS was 1.48 (0.91-2.41), while studies with a high cut-off demonstrated OS of 2.28 (1.47-3.52) and DFS of 2.77 (1.74-4.40). Our meta-analysis demonstrates that Bcl-2 protein overexpression can result in worse LNM, OS, and DFS in patients with HNC, however, it is not a reliable conclusion, due to the wide divergences between the original studies and the fact that many studies have a very high range of confidence and also a high risk of bias.
Topics: Humans; Biomarkers, Tumor; Prognosis; Head and Neck Neoplasms
PubMed: 37210016
DOI: 10.1016/j.critrevonc.2023.104021 -
Archives of Gerontology and Geriatrics Oct 2023Cellular senescence (CS) is a permanent arrest of cell growth and exit of the cell cycle. It is an important tumor suppression mechanism and has a key role in wound... (Review)
Review
Cellular senescence (CS) is a permanent arrest of cell growth and exit of the cell cycle. It is an important tumor suppression mechanism and has a key role in wound healing, tissue regeneration, and prevention of tissue fibrosis. Despite the short-term benefits of CS, accumulation of senescent cells has deleterious effects and is associated with several pathological age-related phenotypes. As Heat Shock Proteins (HSP) are associated with cyto-protection, their role in longevity and CS became a research interest. However, an overview of the relationship between HSP and CS in humans still lacks in the literature. To provide an overview of the current state of the literature, this systematic review focused on the role of HSP in the development of CS in humans. PubMed, Web of Science and Embase were systematically screened for studies on the relationship between HSP and CS in humans. A total of 14 articles were eligible for inclusion. The heterogeneity and lack of numerical reporting of outcomes obstructed the conduction of a meta-analysis. The results consistently show that HSP depletion results in increased CS, while overexpression of HSP decreases CS, whether in cancer, fibroblasts, or stem cell lines. This systematic review summarized the literature on the prospective role of HSP in the development of CS in humans.
Topics: Humans; Cellular Senescence; Heat-Shock Proteins; Longevity; Neoplasms
PubMed: 37207540
DOI: 10.1016/j.archger.2023.105057 -
Journal of Clinical Pathology Jul 2023The prognostic role of CD274 (programmed cell death ligand 1 (PD-L1)) overexpression has been examined in many studies. However, the results are controversial and... (Meta-Analysis)
Meta-Analysis
AIM
The prognostic role of CD274 (programmed cell death ligand 1 (PD-L1)) overexpression has been examined in many studies. However, the results are controversial and conflicting. The present study aims to investigate the potential role of CD274 (PD-L1) immunohistochemical overexpression as a prognostic marker in malignant tumours.
METHODS
We searched PubMed, Embase and Web of Science from inception to December 2021 to identify potentially eligible studies. The pooled HRs with 95% CIs were calculated to identify the association between CD274 (PD-L1) overexpression and overall survival (OS), cancer-specific survival, disease-free survival, recurrence-free survival and progression-free survival in 10 lethal malignant tumours. Heterogeneity and publication bias were also analysed.
RESULTS
The study included 57 322 patients from 250 eligible studies (241 articles). The meta-analysis by tumour type using multivariate HR revealed worse OS in non-small cell lung cancer (HR 1.41, 95% CI 1.19 to 1.68), hepatocellular carcinoma (HR 1.75, 95% CI 1.11 to 2.74), pancreatic cancer (HR 1.84, 95% CI 1.12 to 3.02), renal cell carcinoma (HR 1.55, 95% CI 1.12 to 2.14) and colorectal cancer (HR 1.46, 95% CI 1.14 to 1.88). Estimated HRs showed associations between CD274 (PD-L1) overexpression and worse prognosis across different types of tumours in various survival endpoints, but no inverse correlation was identified. The heterogeneity for most of the pooled results was high.
CONCLUSIONS
This large meta-analysis suggests that CD274 (PD-L1) overexpression is a potential biomarker for multiple types of cancers. However, further studies are needed to reduce high heterogeneity.
PROSPERO REGISTRATION NUMBER
CRD42022296801.
Topics: Humans; B7-H1 Antigen; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Prognosis; Liver Neoplasms; Kidney Neoplasms
PubMed: 37130750
DOI: 10.1136/jcp-2023-208848 -
Expert Review of Anticancer Therapy Jun 2023Targeting HER2 has led to a revolution in therapy for cancers such as breast and gastric cancer, HER2 amplification is rarer (just 2-6%) in colorectal cancer (CRC) and...
INTRODUCTION
Targeting HER2 has led to a revolution in therapy for cancers such as breast and gastric cancer, HER2 amplification is rarer (just 2-6%) in colorectal cancer (CRC) and efforts to target this receptor have lagged. Despite recent FDA approval for the first directed therapy combination for HER2 amplified metastatic CRC, the EMA has not yet authorized any such treatment and this represents a persistent unmet need in Europe and beyond. Here, we review data from trials targeting HER2 amplification, the latest target for CRC therapy.
AREAS COVERED
PubMed, Cochrane Library, EMBASE, and clinicaltrials.gov were reviewed systematically for possible manuscripts from inception to 1 July 2022. Results: A total of seven studies comprised of 284 locally advanced/mCRC patients receiving HER2 targeting agents were included in this systematic review. Most of the studies (n = 5) were non-randomized phase 2 trials, one phase 2/3 randomized controlled trial, and one phase 2a multiple-basket study. The outcomes consisted in the analysis of HER2 targeting agents and ORR, PFS, OS benefit, and toxicities of the therapy.
EXPERT OPINION
Anti-HER2 therapy exhibits a favorable toxicity profile compared with other targeted approaches; however, there is work to be done on optimizing patient selection and understanding resistance mechanisms.
Topics: Female; Humans; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Colonic Neoplasms; Colorectal Neoplasms; Receptor, ErbB-2; Rectal Neoplasms; Clinical Trials as Topic
PubMed: 37127555
DOI: 10.1080/14737140.2023.2207830 -
Clinical and Experimental Medicine Nov 2023Anti-human epidermal growth factor receptor-2 (anti-HER2) therapy has shown excellent efficacy in patients with HER2 overexpression and amplification. Although HER2... (Meta-Analysis)
Meta-Analysis Review
Anti-human epidermal growth factor receptor-2 (anti-HER2) therapy has shown excellent efficacy in patients with HER2 overexpression and amplification. Although HER2 mutations are rarely expressed in several cancers, when they occur, they can activate the HER2 signaling pathway. In recent years, studies have shown that anti-HER2 drugs have promising efficacy in patients with HER2 mutations. Based on keywords, we searched databases, such as PubMed, Embase, and Cochrane Library, and the main conference abstracts. We extracted data on objective response rate (ORR), clinical benefit rate (CBR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) from studies on the efficacy of anti-HER2 therapies in patients with HER2-mutated cancers, and analyzed grade 3 or higher adverse events (AEs). We included 19 single-arm clinical studies and 3 randomized controlled trials (RCTs), containing a total of 1017 patients with HER2 mutations, involving seven drugs and nine cancers, and 18 studies enrolled a high proportion of heavily pretreated patients who had received multiple lines of therapy. Our results showed pooled ORR and CBR of 25.0% (range, 3.8-72.7%; 95% CI, 18-32%) and 36.0% (range, 8.3-63.0%; 95% CI, 31-42%) for anti-HER2 therapy in HER2-mutated cancers. The pooled median PFS, OS, DOR were 4.89 (95% CI, 4.16-5.62), 12.78 (95% CI, 10.24-15.32), and 8.12 (95% CI, 6.48-9.75) months, respectively. In a subgroup analysis, we analyzed the ORR for different cancers, showing 27.0, 25.0, 23.0, and 16.0% for breast, lung, cervical, and biliary tract cancers, respectively. ORR analyses were performed for different drugs as monotherapy or in combination, showing 60.0% for trastuzumab deruxtecan (T-DXd), 31.0% for pyrotinib, 26.0% for neratinib combined with trastuzumab, 25.0% for neratinib combined with fulvestrant, 19.0% for trastuzumab combined with pertuzumab, and 16.0% for neratinib. In addition, we found that diarrhoea, neutropenia, and thrombocytopenia were the most common grade ≥ 3 AEs associated with anti-HER2 therapeutic agents. In this meta-analysis of heavily pretreated patients with HER2 mutations, anti-HER2 therapies, DS-8201 and trastuzumab emtansine, showed promising efficacy and activity. Anti-HER2 therapies showed different efficacies in different or the same cancer settings and all had a tolerable safety profile.
Topics: Humans; Female; Trastuzumab; Receptor, ErbB-2; Ado-Trastuzumab Emtansine; Neoplasms; Breast Neoplasms; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37120775
DOI: 10.1007/s10238-023-01072-7 -
Diagnostic Pathology Apr 2023Hypoxia is a characteristic of many solid tumours and an adverse prognostic factor for cancer therapy. Hypoxia results in upregulation of carbonic anhydrase IX (CAIX)... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Hypoxia is a characteristic of many solid tumours and an adverse prognostic factor for cancer therapy. Hypoxia results in upregulation of carbonic anhydrase IX (CAIX) expression, a pH-regulating enzyme. Many human tissue studies have examined the prognostic value of CAIX expression in breast cancer but have yielded inconsistent results. Therefore, a systematic review and meta-analysis was undertaken to assess the prognostic value of CAIX expression for breast cancer patients.
METHODS
The electronic databases were systematically searched to identify relevant papers. The clinical outcomes included disease-free survival (DFS), recurrence-free survival (RFS) and overall survival (OS) in breast cancer patients. Review Manager version 5.4 was employed to analysis data from 23 eligible studies (containing 8390 patients).
RESULTS
High CAIX expression was associated with poorer RFS [HR = 1.42, 95% CI (1.32-1.51), p < 0.00001], DFS [HR = 1.64, 95% CI (1.34-2.00), p < 0.00001], and OS [HR = 1.48, 95% CI (1.22-1.80), p < 0.0001]. Heterogeneity was observed across the studies. There was an effect of the CAIX antibody employed, scoring methods, and tumour localisation on CAIX expression.
CONCLUSION
CAIX overexpression was significantly associated with poorer RFS, DFS, and OS in breast cancer patients. However, further work in high quantity tissue cohorts is required to define the optimal methodological approach.
Topics: Humans; Female; Carbonic Anhydrase IX; Breast Neoplasms; Carbonic Anhydrases; Biomarkers, Tumor; Antigens, Neoplasm; Prognosis; Hypoxia
PubMed: 37061698
DOI: 10.1186/s13000-023-01325-9 -
International Journal of Molecular... Mar 2023Energy production by cancer is driven by accelerated glycolysis, independently of oxygen levels, which results in increased lactate production. Lactate is shuttled to... (Review)
Review
Energy production by cancer is driven by accelerated glycolysis, independently of oxygen levels, which results in increased lactate production. Lactate is shuttled to and from cancer cells via monocarboxylate transporters (MCTs). MCT1 works both as an importer and an extruder of lactate, being widely studied in recent years and generally associated with a cancer aggressiveness phenotype. The aim of this systematic review was to assess the prognostic value of MCT1 immunoexpression in different malignancies. Study collection was performed by searching nine different databases (PubMed, EMBASE, ScienceDirect, Scopus, Cochrane Library, Web of Science, OVID, TRIP and PsycINFO), using the keywords "cancer", "Monocarboxylate transporter 1", "SLC16A1" and "prognosis". Results showed that MCT1 is an indicator of poor prognosis and decreased survival for cancer patients in sixteen types of malignancies; associations between the transporter's overexpression and larger tumour sizes, higher disease stage/grade and metastasis occurrence were also frequently observed. Yet, MCT1 overexpression correlated with better outcomes in colorectal cancer, pancreatic ductal adenocarcinoma and non-small cell lung cancer patients. These results support the applicability of MCT1 as a biomarker of prognosis, although larger cohorts would be necessary to validate the overall role of MCT1 as an outcome predictor.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lactic Acid; Lung Neoplasms; Monocarboxylic Acid Transporters; Pancreatic Neoplasms; Prognosis; Symporters
PubMed: 36982217
DOI: 10.3390/ijms24065141