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Frontiers in Oncology 2022Cell Division Cycle Protein 20(CDC20) is reported to promote cancer initiation, progression and drug resistance in many preclinical models and is demonstrated in human...
BACKGROUND
Cell Division Cycle Protein 20(CDC20) is reported to promote cancer initiation, progression and drug resistance in many preclinical models and is demonstrated in human cancer tissues. However, the correlation between CDC20 and cancer patients' prognosis has not yet been systematically evaluated. Therefore, this present meta-analysis was performed to determine the prognostic value of CDC20 expression in various malignancy tumors.
METHODS
A thorough database search was performed in EMBASE, PubMed, Cochrane Library and Web of Science from inception to May 2022. Stata14.0 Software was used for the statistical analysis. The pooled hazard ratios(HRs) and their 95% confidence intervals (95% CIs) were used to analysis of overall survival (OS), recurrence-free survival (RFS), distant-metastasis free survival (DMFS). Qualities of the included literature were assessed by JBI Critical appraisal checklist. Egger's test was used to assess publication bias in the included studies.
RESULTS
Ten articles were selected, and 2342 cancer patients were enrolled. The cancer types include breast, colorectal, lung, gastric, oral, prostate, urothelial bladder cancer, and hepatocellular carcinoma. The result showed strong significant associations between high expression of CDC20 and endpoints: OS (HR 2.52, 95%CI 2.13-2.99; HR 2.05, 95% CI 1.50-2.82, respectively) in the multivariate analysis and in the univariate analysis. Also, high expression of CDC20 was significantly connected with poor RFS (HR 2.08, 95%CI 1.46-2.98) and poor DMFS (HR 4.49, 95%CI 1.57-12.85). The subgroup analysis was also performed, which revealed that CDC20 upregulated expression was related to poor OS in non-small cell lung cancer (HR 2.40, 95% CI 1.91-3.02).
CONCLUSIONS
This meta-analysis demonstrated that highly expressing CDC20 was associated with poor survival in human malignancy tumors. CDC20 may be a valuable prognostic predictive biomarker and a potential therapeutic target in various cancer parents.
PubMed: 36479068
DOI: 10.3389/fonc.2022.1017864 -
Frontiers in Endocrinology 2022Prostate cancer is a common malignancy affecting men worldwide. While the vast majority of newly diagnosed prostate cancers are categorized as adenocarcinomas, a...
Prostate cancer is a common malignancy affecting men worldwide. While the vast majority of newly diagnosed prostate cancers are categorized as adenocarcinomas, a spectrum of uncommon tumor types occur including those with small cell and neuroendocrine cell features. Benign neuroendocrine cells exist in the normal prostate microenvironment, and these cells may give rise to primary neuroendocrine carcinomas. However, the more common development of neuroendocrine prostate cancer is observed after therapeutics designed to repress the signaling program regulated by the androgen receptor which is active in the majority of localized and metastatic adenocarcinomas. Neuroendocrine tumors are identified through immunohistochemical staining for common markers including chromogranin A/B, synaptophysin and neuron specific enolase (NSE). These markers are also common to neuroendocrine tumors that arise in other tissues and organs such as the gastrointestinal tract, pancreas, lung and skin. Notably, neuroendocrine prostate cancer shares biochemical features with nerve cells, particularly functions involving the secretion of a variety of peptides and proteins. These secreted factors have the potential to exert local paracrine effects, and distant endocrine effects that may modulate tumor progression, invasion, and resistance to therapy. This review discusses the spectrum of factors derived from neuroendocrine prostate cancers and their potential to influence the pathophysiology of localized and metastatic prostate cancer.
Topics: Male; Humans; Prostate; Prostatic Neoplasms; Carcinoma, Neuroendocrine; Adenocarcinoma; Neuroendocrine Tumors; Tumor Microenvironment
PubMed: 36440195
DOI: 10.3389/fendo.2022.1012005 -
Clinical Genitourinary Cancer Feb 2023Adrenocortical carcinoma (ACC) is a very rare endocrine cancer and is associated with a poor prognosis. There is a paucity of randomized clinical trials for this rare... (Review)
Review
A Systematic Review of Published Clinical Trials in the Systemic Treatment of Adrenocortical Carcinoma: An Initiative Led on Behalf of the Global Society of Rare Genitourinary Tumors.
Adrenocortical carcinoma (ACC) is a very rare endocrine cancer and is associated with a poor prognosis. There is a paucity of randomized clinical trials for this rare disease. We aimed to perform a systematic review of the literature on systemic therapy options in different stages of ACC. A systematic review was performed using Pubmed and Embase databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A total of 24 trials of systemic therapy in the treatment of ACC were identified and included in this review. Only one clinical trial in the adjuvant setting was identified, the negative phase III trial ADIUVO, which tested mitotane in low to intermediate-risk ACC patients. In the treatment of advanced ACC, cisplatin-based chemotherapy was evaluated in small and non-randomized phase II trials, and response rates ranged from 21% to 53.5%. The phase III trial FIRM-ACT compared etoposide, doxorubicin, cisplatin, and mitotane versus treatment with streptozotocin and mitotane and showed no difference in OS, but higher RR and PFS were reported with the multi-drug regimen. Six clinical trials of immunotherapy and seven studies of targeted therapy in advanced ACC were included, with modest activity and no phase 3 trials were identified. Treatment recommendations of ACC are based on retrospective and small studies with limited systemic therapy options. International and multi-center collaboration is essential to expand clinical research and improve outcomes.
Topics: Humans; Adrenocortical Carcinoma; Mitotane; Adrenal Cortex Neoplasms; Cisplatin; Retrospective Studies; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36376169
DOI: 10.1016/j.clgc.2022.10.011 -
Urologic Oncology May 2023Due to possible synergistic effects, the combination of radiation therapy (RT) and immune checkpoint inhibitors (ICI) represents an interesting therapeutic option. An... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Due to possible synergistic effects, the combination of radiation therapy (RT) and immune checkpoint inhibitors (ICI) represents an interesting therapeutic option. An increasing number of clinical trials are ongoing to investigate this combination in genitourinary malignancies and the first results are available.
OBJECTIVES
To review and summarize available data on the combination of RT and ICI in genitourinary malignancies and update the evidence for this potential therapeutic approach.
EVIDENCE ACQUISITION
A study protocol was registered in the PROSPERO-Database. Terms of search were prostate cancer, bladder cancer, renal cell carcinoma, penile cancer, testicular cancer, radiotherapy, and immunotherapy in multiple literature databases and study registers. Clinical studies reporting on the combination treatment of RT and ICI were included. A systematic review of ongoing trials according to the PRISMA statement and a meta-analysis of available trials were performed.
EVIDENCE SYNTHESIS
Overall, 43 studies met the inclusion criteria examining the therapeutic effect of combined RT and ICI. For bladder cancer, renal cell carcinoma, prostate cancer, and penile cancer 28, 9, 5, and 1 trial could be identified, respectively. No study was found for testicular cancer. Three phases III trials were identified, all other trials were phase I or II. Twelve studies have been completed so far. The meta-analysis of available data indicates comparable toxicity of RT plus ICI vs. ICI alone for grade 3/4 AEs. Mature efficacy data is limited with interesting early results.
CONCLUSION
This article reviews the clinical trial landscape investigating RT and ICI in genitourinary malignancies. It provides an overview of ongoing trials and discusses available results. Actual data regarding efficacy is limited, while toxicities seem comparable to ICI alone. Especially in bladder and kidney cancer, further trial results might impact on the clinical use of the combination therapy.
Topics: Male; Humans; Carcinoma, Renal Cell; Testicular Neoplasms; Immunotherapy; Kidney Neoplasms; Urinary Bladder Neoplasms; Prostatic Neoplasms
PubMed: 36372634
DOI: 10.1016/j.urolonc.2022.10.009 -
Pharmaceuticals (Basel, Switzerland) Nov 2022Several studies proposed the use of positron emission tomography (PET) with Prostate-Specific Membrane Antigen (PSMA)-targeting radiopharmaceuticals in hepatocellular... (Review)
Review
Can PSMA-Targeting Radiopharmaceuticals Be Useful for Detecting Hepatocellular Carcinoma Using Positron Emission Tomography? An Updated Systematic Review and Meta-Analysis.
BACKGROUND
Several studies proposed the use of positron emission tomography (PET) with Prostate-Specific Membrane Antigen (PSMA)-targeting radiopharmaceuticals in hepatocellular carcinoma (HCC). Our aim is to calculate the detection rate (DR) of this examination in HCC with a meta-analysis.
METHODS
A comprehensive literature search of studies on the DR of PET/CT or PET/MRI with PSMA-targeting radiopharmaceuticals in HCC was performed. Original articles evaluating these imaging examinations both in newly diagnosed HCC patients and HCC patients with disease relapse were included. Pooled DR including 95% confidence intervals (95% CI) was calculated. Statistical heterogeneity was also assessed using the I test.
RESULTS
The meta-analysis of six selected studies (126 patients) provided a DR of 85.9% for PET imaging with PSMA-targeting radiopharmaceuticals in the diagnosis of HCC. Moderate statistical heterogeneity among the included studies was found (I = 56%).
CONCLUSIONS
The quantitative data provided demonstrate the high DR of PET/CT or PET/MRI with PSMA-targeting radiopharmaceuticals for HCC lesion detection. However, more studies are needed to confirm the promising role of PSMA-targeted PET in HCC.
PubMed: 36355540
DOI: 10.3390/ph15111368 -
Seminars in Oncology Oct 2022Multiple systemic immune-oncology (IO) combination therapies have demonstrated overall survival (OS) benefits in metastatic renal clear cell carcinoma (mRCC). However,... (Review)
Review
Multiple systemic immune-oncology (IO) combination therapies have demonstrated overall survival (OS) benefits in metastatic renal clear cell carcinoma (mRCC). However, the magnitude of benefits over time has not been compared in a structured fashion. To assess OS and progression free survival (PFS) efficacy as reflected by hazard ratios [HR]) according to the duration of follow-up over time for each of four IO combination therapies. A systematic PubMed (MEDLINE) literature review was performed (January, 1, 2016 to February, 20, 2022). Only phase III randomized clinical trials with proven OS benefit relative to sunitinib were included. These search criteria yielded four eligible RCTs: CheckMate 214 (nivolumab plus ipilimumab), Keynote 426 (pembrolizumab plus axitinib), CheckMate 9ER (nivolumab plus cabozantinib), CLEAR (lenvatinib plus pembrolizumab). OS and PFS HRs were tabulated for all four studies including all reported timepoints. Median follow-up ranged from 25-68 months for CheckMate 214 (5 timepoints), 13-43 months for Keynote 426 (3 timepoints), 18-33 months for CheckMate 9ER (3 timepoints) and 27-34 months for CLEAR (2 timepoints). Respective OS and PFS HRs were 0.68-0.72 and 0.98-0.86, 0.53-0.73 and 0.69-0.68, 0.60-0.70 and 0.51-0.56, 0.66-0.72 and 0.39-0.47 for CheckMate 214, Keynote 426, CheckMate 9ER and CLEAR. Regarding OS HRs virtually no change was recorded over time for CheckMate 214, but a decrease in magnitude occurred in the three IO-TKI remaining studies. Regarding PFS HRs, no benefit was recorded for CheckMate 214. Statistically significant benefit was recorded in the remaining IO-TKI studies. However, it also decreased with longer follow-up. It remains to be seen, whether further 'slippage' of efficacy will persist as the data matures further for all IO-TKI combinations.
Topics: Humans; Antineoplastic Agents; Carcinoma, Renal Cell; Kidney Neoplasms; Nivolumab; Sunitinib
PubMed: 36333148
DOI: 10.1053/j.seminoncol.2022.10.001 -
Iranian Journal of Public Health Dec 2021The tumor suppressor genes play a critical role in cellular and molecular mechanisms such as cell cycle processes, cell differentiation and apoptosis. Aberrant DNA... (Review)
Review
BACKGROUND
The tumor suppressor genes play a critical role in cellular and molecular mechanisms such as cell cycle processes, cell differentiation and apoptosis. Aberrant DNA methylation of tumor suppressor genes and subsequent gene expression changes have shown to be involved in the initiation and progression of various malignancies including thyroid malignancies. In this review, we investigated what is known about the impact of promoter hypermethylation on the key tumor suppressor genes known to be involved in cell growth and/or apoptosis of thyroid cancer.
METHODS
The most important databases were searched for research articles until June 2020 to identify reported tumor suppressor genes that are modulated by methylation modulation changes in thyroid carcinoma. Following the inclusion and exclusion criteria, 26 studies were reviewed using the full text to meet the inclusion and exclusion criteria.
RESULTS
The tumor suppressor genes reviewed here are suggestive biomarkers and potential targetable drugs. Inactivation of , , , and through aberrant epigenetic methylation could activate BRAF/MEK/ERK kinase pathways with potential clinical implications in thyroid cancer patients. and could suppress cell cycle and induce apoptosis in malignant cells. and could prevent angiogenesis and invasion through PIP3 pathway and arrest VEFG activity.
CONCLUSION
The methylation status of key genes in various types of thyroid malignancies could be used in early diagnosis as well as differentiation of malignant and benign thyroid. This is valuable in drug repurposing and discovering alternative treatments or preventions in thyroid cancer.
PubMed: 36317025
DOI: 10.18502/ijph.v50i12.7928 -
Frontiers in Physiology 2022Cancer is one of the top causes of death globally. Recently, microarray gene expression data has been used to aid in cancer's effective and early detection. The use of...
Cancer is one of the top causes of death globally. Recently, microarray gene expression data has been used to aid in cancer's effective and early detection. The use of DNA microarray technology to uncover information from the expression levels of thousands of genes has enormous promise. The DNA microarray technique can determine the levels of thousands of genes simultaneously in a single experiment. The analysis of gene expression is critical in many disciplines of biological study to obtain the necessary information. This study analyses all the research studies focused on optimizing gene selection for cancer detection using artificial intelligence. One of the most challenging issues is figuring out how to extract meaningful information from massive databases. Deep Learning architectures have performed efficiently in numerous sectors and are used to diagnose many other chronic diseases and to assist physicians in making medical decisions. In this study, we have evaluated the results of different optimizers on a RNA sequence dataset. The Deep learning algorithm proposed in the study classifies five different forms of cancer, including kidney renal clear cell carcinoma (KIRC), Breast Invasive Carcinoma (BRCA), lung adenocarcinoma (LUAD), Prostate Adenocarcinoma (PRAD) and Colon Adenocarcinoma (COAD). The performance of different optimizers like Stochastic gradient descent (SGD), Root Mean Squared Propagation (RMSProp), Adaptive Gradient Optimizer (AdaGrad), and Adaptive Momentum (AdaM). The experimental results gathered on the dataset affirm that AdaGrad and Adam. Also, the performance analysis has been done using different learning rates and decay rates. This study discusses current advancements in deep learning-based gene expression data analysis using optimized feature selection methods.
PubMed: 36246115
DOI: 10.3389/fphys.2022.952709 -
European Urology Oncology Dec 2022Use of three-dimensional (3D) guidance for nephron-sparing surgery (NSS) has increased in popularity, especially for laparoscopic and robotic approaches. Different 3D... (Meta-Analysis)
Meta-Analysis Review
CONTEXT
Use of three-dimensional (3D) guidance for nephron-sparing surgery (NSS) has increased in popularity, especially for laparoscopic and robotic approaches. Different 3D visualization modalities have been developed as promising new tools for surgical planning and intraoperative navigation.
OBJECTIVES
To summarize and evaluate the impact of 3D models on minimally invasive NSS in terms of perioperative, functional, and oncological outcomes.
EVIDENCE ACQUISITION
A systematic literature search was conducted in December 2021 using the Medline (PubMed), Embase (Ovid), Scopus, and Web of Science databases. The protocol was registered on PROSPERO (CRD42022300948). The search strategy used the PICOS (Population, Intervention, Comparison, Outcome, Study design) criteria and article selection was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The risk of bias and the quality of the articles included were assessed. A dedicated data extraction form was used to collect the data of interest. Meta-analysis was performed using the Mantel-Haenszel method for binary outcomes, with results summarized as the odds ratio (OR), and the inverse variance method for continuous data, with results reported as the mean difference (MD). All effect estimates are reported with the 95% confidence interval (CI) and p ≤ 0.05 was considered statistically significant. All analyses were performed using R software and the meta package.
EVIDENCE SYNTHESIS
The initial electronic search identified 450 papers, of which 17 met the inclusion criteria and were included in the analysis. Use of 3D technology led to a significant reduction in the global ischemia rate (OR 0.22, 95% CI 0.07-0.76; p = 0.02) and facilitated more frequent enucleation (OR 2.54, 95% CI 1.36-4.74; p < 0.01) and less frequent opening of the collecting system (OR 0.36, 95% CI 0.15-0.89; p = 0.03) and was associated with less blood loss (MD 23.1 ml, 95% CI 31.8-14.4; p < 0.01). 3D guidance for NSS was associated with a significant reduction in the transfusion rate (OR 0.20, 95% CI 0.07-0.56; p < 0.01). There were no significant differences in rates of conversion to radical nephrectomy, minor and major complications, change in glomerular filtration rate, or surgical margins (all p > 0.05).
CONCLUSIONS
3D guidance for NSS is associated with lower rates of detriment and surgical injury to the kidney. Specifically, a lower amount of nontumor renal parenchyma is exposed to ischemia or sacrificed during resection, and opening of the collecting system is less frequent. However, use of 3D technology does not lead to significant improvements in oncological or functional outcomes.
PATIENT SUMMARY
We reviewed the use of three-dimensional tools for minimally invasive surgery for partial removal of the kidney in patients with kidney cancer. The evidence suggests that these tools have benefits during surgery, but do not lead to significant improvements in cancer control or functional outcomes for patients.
Topics: Humans; Robotic Surgical Procedures; Treatment Outcome; Nephrectomy; Kidney Neoplasms; Carcinoma, Renal Cell
PubMed: 36216739
DOI: 10.1016/j.euo.2022.09.003 -
Frontiers in Nutrition 2022Clinical and preclinical studies suggested that certain mutagens occurring as a reaction of creatine, amino acids, and sugar during the high temperature of cooking meat...
BACKGROUND
Clinical and preclinical studies suggested that certain mutagens occurring as a reaction of creatine, amino acids, and sugar during the high temperature of cooking meat are involved in the pathogenesis of human cancer. Here we conducted a systematic review and meta-analysis to examine whether meat mutagens [PhIP, MeIQx, DiMeIQx, total HCA, and B(a)P] present a risk factor for human cancer.
METHODS
We searched the following databases for relevant articles published from inception to 10 Oct 2021 with no language restrictions: Pubmed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Baidu Academic, Zhejiang Digital Library. Two independent researchers screened all titles and obtained eligible texts for further screening. Independent data extraction was conducted, and meta-analysis was carried out using random-effects models to calculate the risk ratio of the meat mutagens exposure.
RESULTS
A total of 1,786,410 participants and 70,653 cancer cases were identified. Among these, there were 12 different types of cancer at various sites, i.e., breast, bladder, colorectal, colon, rectum, prostate, lung, Non-Hodgkin lymphoma, kidney, gastric, esophagus, pancreatic, hepatocellular carcinoma. Cancer risk was significantly increased by intake of PhIP (OR = 1.13;95% CI 1.07-1.21; < 0.001), MeIQx (OR = 1.14; 95% CI: 1.07-1.21; < 0.001), DiMeIQx (OR = 1.07; 95% CI: 1.01-1.13; = 0.013), total HCA (OR = 1.20; 95% CI: 1.03-1.38; = 0.016), and cancer risk was not significantly increased by intake of B(a)P (OR = 1.04; 95% CI: 0.98-1.10; = 0.206).
CONCLUSION
Meat mutagens of PhIP, MeIQx, DiMeIQx, and total HCA have a positive association with the risk of cancer.
SYSTEMATIC REVIEW REGISTRATION
[www.crd.york.ac.uk/prospero], identifier [CRD42022148856].
PubMed: 36211500
DOI: 10.3389/fnut.2022.962688