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Frontiers in Cardiovascular Medicine 2024Although the adverse effects of atrial fibrillation (AF) on cancers have been well reported, the relationship between the AF and the adverse outcomes in prostate cancer...
PURPOSE
Although the adverse effects of atrial fibrillation (AF) on cancers have been well reported, the relationship between the AF and the adverse outcomes in prostate cancer (PC) remains inconclusive. This study aimed to explore the prevalence of AF and evaluate the relationship between AF and clinical outcomes in PC patients.
METHODS
Patients diagnosed with PC between 2008 and 2017 were identified from the National Inpatient Sample database. The trends in AF prevalence were compared among PC patients and their subgroups. Multivariable regression models were used to assess the associations between AF and in-hospital mortality, length of hospital stay, total cost, and other clinical outcomes.
RESULTS
256,239 PC hospitalizations were identified; 41,356 (83.8%) had no AF and 214,883 (16.2%) had AF. AF prevalence increased from 14.0% in 2008 to 20.1% in 2017 ( < .001). In-hospital mortality in PC inpatients with AF increased from 5.1% in 2008 to 8.1% in 2017 ( < .001). AF was associated with adverse clinical outcomes, such as in-hospital mortality, congestive heart failure, pulmonary circulation disorders, renal failure, fluid and electrolyte disorders, cardiogenic shock, higher total cost, and longer length of hospital stay.
CONCLUSIONS
The prevalence of AF among inpatients with PC increased from 2008 to 2017. AF was associated with poor prognosis and higher health resource utilization. Better management strategies for patients with comorbid PC and AF, particularly in older individuals, are required.
PubMed: 38638883
DOI: 10.3389/fcvm.2024.1382166 -
Translational Andrology and Urology Mar 2024Prostate cancer (PCa) is the second most common male cancer in the United States. Although new drugs have recently been approved, clinical challenges remain, notably the... (Review)
Review
BACKGROUND AND OBJECTIVE
Prostate cancer (PCa) is the second most common male cancer in the United States. Although new drugs have recently been approved, clinical challenges remain, notably the precise detection and prognostic implications of drug-resistant PCa. Extracellular vesicles (EVs), nanoscale lipid membrane vesicles, are actively secreted into the extracellular milieu by a variety of cell types. Over the past decade, interest in EVs has grown, and emerging evidence suggests that EVs play pivotal roles in cancer biology. In this review, we would like to summarize recent reports on EVs in PCa and discuss the potential clinical applications.
METHODS
We performed a non-systematic literature review using the PubMed database to identify articles specifically related to EVs and PCa management.
KEY CONTENT AND FINDINGS
EVs contain pathogenic components, such as proteins, DNA fragments, mRNA, non-coding RNA, and lipids, all of which can trigger intercellular signaling within tumor microenvironments. Thereby, EVs exert significant effects on several stages of cancer progression, influencing the immune system, angiogenesis, and the establishment of pre-metastatic niches. Furthermore, as EVs are encapsulated, their contents are stable in bodily fluids, and thus EVs have recently attracted attention as a novel kind of liquid biopsy.
CONCLUSIONS
We have summarized recent research on how EVs may aid PCa management. To date, we have discovered only the tip of the iceberg. We anticipate that further research will yield innovative therapeutic modalities, thereby aiding all PCa patients.
PubMed: 38590964
DOI: 10.21037/tau-23-533 -
Journal of Proteome Research May 2024Biofluids contain molecules in circulation and from nearby organs that can be indicative of disease states. Characterizing the proteome of biofluids with DIA-MS is an...
Biofluids contain molecules in circulation and from nearby organs that can be indicative of disease states. Characterizing the proteome of biofluids with DIA-MS is an emerging area of interest for biomarker discovery; yet, there is limited consensus on DIA-MS data analysis approaches for analyzing large numbers of biofluids. To evaluate various DIA-MS workflows, we collected urine from a clinically heterogeneous cohort of prostate cancer patients and acquired data in DDA and DIA scan modes. We then searched the DIA data against urine spectral libraries generated using common library generation approaches or a library-free method. We show that DIA-MS doubles the sample throughput compared to standard DDA-MS with minimal losses to peptide detection. We further demonstrate that using a sample-specific spectral library generated from individual urines maximizes peptide detection compared to a library-free approach, a pan-human library, or libraries generated from pooled, fractionated urines. Adding urine subproteomes, such as the urinary extracellular vesicular proteome, to the urine spectral library further improves the detection of prostate proteins in unfractionated urine. Altogether, we present an optimized DIA-MS workflow and provide several high-quality, comprehensive prostate cancer urine spectral libraries that can streamline future biomarker discovery studies of prostate cancer using DIA-MS.
Topics: Humans; Male; Prostatic Neoplasms; Proteome; Proteomics; Prostate; Peptide Library; Biomarkers, Tumor; Tandem Mass Spectrometry; Workflow
PubMed: 38580319
DOI: 10.1021/acs.jproteome.4c00009 -
Annals of Medicine and Surgery (2012) Apr 2024Guillain-Barre syndrome (GBS) has been found to have some interesting association with vaccinations. This paper mainly focuses on exploring different associations... (Review)
Review
BACKGROUND AND OBJECTIVE
Guillain-Barre syndrome (GBS) has been found to have some interesting association with vaccinations. This paper mainly focuses on exploring different associations between COVID-19 vaccination and GBS.
METHODS
Electronic databases such as PubMed, Google Scholar, Cochrane, and Embase were searched using MESH terms for case reports published till 1 August 2023 from which 70 case reports were documented involving 103 individuals from 23 different countries.
RESULT AND DISCUSSION
The case reports were from a wide range of individuals aged from 13 to 87 years with an average age of 53±20 interquartile range years along with male predominance. The average time between receiving the vaccine and the onset of symptoms was 13.08±2.14 days. Prominent clinical features included back pain, facial diplegia, weakness, and paraesthesia whereas the main diagnostic studies were cerebrospinal fluid (CSF) analysis and electromagnetic studies. The principal diagnostic clue was albumin-cytological dissociation in CSF while being negative for anti-ganglioside antibodies or SARS-CoV-2. Available treatment options consisted of intravenous immunoglobulin and Plasmapheresis. Patients with comorbidities such as diabetes mellitus, hypertension, dyslipidemia, permanent atrial fibrillation, hypothyroidism, Hashimoto's thyroiditis, Chronic Obstructive Pulmonary Disease, asthma, osteoporosis, migraine, rheumatoid arthritis, osteoarthritis, ulcerative colitis, coeliac disease, seizures, bipolar disorder, endometriosis, multiple sclerosis, bell's palsy, squamous cell carcinoma, prostate cancer were included in our study.
CONCLUSION
Overall, this review evaluated innovative and clinically relevant associations between COVID-19 vaccination and GBS. Understanding of this uncommon potential side effect of COVID-19 vaccination is crucial for prompt diagnosis and appropriate treatment. Importantly, GBS should not be considered a contraindication to vaccination. This underscores the importance of ongoing research to enhance the safety and efficacy of COVID-19 vaccination efforts.
PubMed: 38576928
DOI: 10.1097/MS9.0000000000001915 -
Tumour Biology : the Journal of the... 2024Tumor markers (TMs) are a heterogeneous group of molecules used in the diagnosis, prognosis and follow-up of cancer patients. During neoplastic differentiation, cells... (Review)
Review
BACKGROUND
Tumor markers (TMs) are a heterogeneous group of molecules used in the diagnosis, prognosis and follow-up of cancer patients. During neoplastic differentiation, cells can either directly synthesize or induce the synthesis of TMs, and the release of these molecules into the bloodstream allows their quantification in biological fluids. Although very small concentrations of TMs are usually present in the serum or plasma of healthy subjects, increased concentrations may also be found in the presence of benign diseases or due to technical interference, producing false positive results.
MATERIAL AND METHODS AND RESULTS
Our review analyses the causes of false positives described between January 1970 to February 2023 for the TMs most frequently used in clinical practice: α-fetoprotein (AFP), β2-microglobulin (β2-M), cancer antigen 15-3 (CA 15-3), cancer antigen CA 19-9 (CA 19-9), cancer antigen CA 72-4 (CA 72-4), cancer antigen 125 (CA 125), carcinoembryonic antigen (CEA), chromogranin A (CgA), choriogonadotropin (hCG), cytokeratin 19 fragment (CYFRA 21-1), neuron-specific enolase (NSE), human epididymis protein 4 (HE4), serum HER2 (sHER2), squamous cell carcinoma antigen (SCCA), protein induced by vitamin K absence-II (PIVKA-II), Pro-gastrin-releasing peptide (Pro-GRP), prostate-specific antigen (PSA), Protein S-100 (S-100) and thyroglobulin (Tg). A total of 247 references were included.
CONCLUSIONS
A better understanding of pathophysiological processes and other conditions that affect the concentration of TMs might improve the interpretation of results and their clinical application.
Topics: Male; Humans; Biomarkers, Tumor; Lung Neoplasms; Antigens, Neoplasm; Keratin-19; Carcinoembryonic Antigen; Prostate-Specific Antigen; Phosphopyruvate Hydratase; CA-125 Antigen
PubMed: 38517826
DOI: 10.3233/TUB-220023 -
The association between zinc and prostate cancer development: A systematic review and meta-analysis.PloS One 2024Prostate cancer is affecting males globally, with several complications. Zinc can play roles in cancers. We aimed to clarify the association between zinc levels or... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Prostate cancer is affecting males globally, with several complications. Zinc can play roles in cancers. We aimed to clarify the association between zinc levels or intake with prostate cancer development.
METHODS
We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science until May 1, 2023. We included case-controls and cross-sectionals that measured zinc level and/or intake in patients with prostate cancer or cohorts that evaluated the association between zinc and prostate cancer development. Studies that did not have a healthy control group were excluded. Joanna Briggs Institute was used for quality assessment. Publication bias was evaluated using Egger's and Begg's tests and funnel plot.
RESULTS
Overall, 52 studies (n = 44 case controls, n = 4 cohorts, and n = 4 cross sectionals) with a total number of 163909 participants were included. Serum (standardized mean difference (SMD): -1.11; 95% confidence interval (CI): -1.67, -0.56), hair (SMD: -1.31; 95% CI: -2.19, -0.44), and prostatic fluid or tissue zinc levels (SMD: -3.70; 95% CI: -4.90, -2.49) were significantly lower in prostate cancer patients. There were no significant differences in nail zinc level and zinc intake between those with prostate cancer and healthy controls. There was no publication bias except for serum and hair zinc levels based on Begg's and Egger's tests, respectively. The mean risk of bias scores were 4.61 in case-controls, eight in cohorts, and seven in cross-sectionals.
CONCLUSIONS
Overall, high zinc levels might have a protective role in prostate cancer, which can be used as a therapeutic or preventive intervention. Future large-scale studies are needed to confirm the association.
Topics: Male; Humans; Zinc; Prostatic Neoplasms; Health Status; Nutritional Status; PubMed
PubMed: 38507438
DOI: 10.1371/journal.pone.0299398 -
Molecules (Basel, Switzerland) Feb 2024Bitespiramycin, has been shown to have a therapeutic effect against respiratory tract inflammation, including a potential effect against COVID-19. A current clinical...
Bitespiramycin, has been shown to have a therapeutic effect against respiratory tract inflammation, including a potential effect against COVID-19. A current clinical trial in China showed that bitespiramycin was an effective treatment for severe pneumonia and intracranial infection. However, there is lack of an analytical method to elucidate the distribution of bitespiramycin. In this study, a highly sensitive, rapid and reliable UPLC-MS/MS method was developed to comprehensively characterize the bitespiramycin distribution in various bio-samples, which is significantly improved upon the published work. A rapid sample preparation method was developed by using -butanol as the solvent to extract bitespiramycin from different bio-samples. The extract was then directly analyzed by UPLC-MS/MS coupled with an alkaline-resistant column after centrifugation which avoids the time-consuming concentration process under nitrogen and redissolution. The method was employed to accurately quantify bitespiramycin and its metabolites in rat plasma, tissues, and human cerebrospinal fluid. Notably, the presence of bitespiramycin and its metabolites was identified for the first time in various rat organs including brain, testis, bladder and prostate as well as in human cerebrospinal fluid. This newly developed approach shows great promise for drug distribution assays including other antibiotics and can help elucidate the ADME of bitespiramycin.
Topics: Male; Rats; Humans; Animals; Chromatography, Liquid; Liquid Chromatography-Mass Spectrometry; Tandem Mass Spectrometry; Spiramycin; Chromatography, High Pressure Liquid
PubMed: 38474552
DOI: 10.3390/molecules29051037 -
BMC Cancer Mar 2024Liquid biopsy can detect circulating cancer cells or tumor cell-derived DNA at various stages of cancer. The fluid from these biopsies contains extracellular vesicles... (Review)
Review
Liquid biopsy can detect circulating cancer cells or tumor cell-derived DNA at various stages of cancer. The fluid from these biopsies contains extracellular vesicles (EVs), such as apoptotic bodies, microvesicles, exomeres, and exosomes. Exosomes contain proteins and nucleic acids (DNA/RNA) that can modify the microenvironment and promote cancer progression, playing significant roles in cancer pathology. Clinically, the proteins and nucleic acids within the exosomes from liquid biopsies can be biomarkers for the detection and prognosis of cancer. We review EVs protein and miRNA biomarkers identified for select cancers, specifically melanoma, glioma, breast, pancreatic, hepatic, cervical, prostate colon, and some hematological malignancies. Overall, this review demonstrates that EV biomolecules have great potential to expand the diagnostic and prognostic biomarkers used in Oncology; ultimately, EVs could lead to earlier detection and novel therapeutic targets. Clinical implicationsEVs represent a new paradigm in cancer diagnostics and therapeutics. The potential use of exosomal contents as biomarkers for diagnostic and prognostic indicators may facilitate cancer management. Non-invasive liquid biopsy is helpful, especially when the tumor is difficult to reach, such as in pancreatic adenocarcinoma. Moreover, another advantage of using minimally invasive liquid biopsy is that monitoring becomes more manageable. Identifying tumor-derived exosomal proteins and microRNAs would allow a more personalized approach to detecting cancer and improving treatment.
Topics: Male; Humans; Adenocarcinoma; Pancreatic Neoplasms; Extracellular Vesicles; Exosomes; MicroRNAs; Biomarkers; DNA; Biomarkers, Tumor; Tumor Microenvironment
PubMed: 38454346
DOI: 10.1186/s12885-024-11819-4 -
Cancer Cell International Feb 2024Cancer chemoresistance is a problematic dilemma that significantly restrains numerous cancer management protocols. It can promote cancer recurrence, spreading of cancer,... (Review)
Review
Cancer chemoresistance is a problematic dilemma that significantly restrains numerous cancer management protocols. It can promote cancer recurrence, spreading of cancer, and finally, mortality. Accordingly, enhancing the responsiveness of cancer cells towards chemotherapies could be a vital approach to overcoming cancer chemoresistance. Tumour cells express a high level of sphingosine kinase-1 (SphK1), which acts as a protooncogenic factor and is responsible for the synthesis of sphingosine-1 phosphate (S1P). S1P is released through a Human ATP-binding cassette (ABC) transporter to interact with other phosphosphingolipids components in the interstitial fluid in the tumor microenvironment (TME), provoking communication, progression, invasion, and tumor metastasis. Also, S1P is associated with several impacts, including anti-apoptotic behavior, metastasis, mesenchymal transition (EMT), angiogenesis, and chemotherapy resistance. Recent reports addressed high levels of S1P in several carcinomas, including ovarian, prostate, colorectal, breast, and HCC. Therefore, targeting the S1P/SphK signaling pathway is an emerging therapeutic approach to efficiently attenuate chemoresistance. In this review, we comprehensively discussed S1P functions, metabolism, transport, and signaling. Also, through a bioinformatic framework, we pointed out the alterations of SphK1 gene expression within different cancers with their impact on patient survival, and we demonstrated the protein-protein network of SphK1, elaborating its sparse roles. Furthermore, we made emphasis on different machineries of cancer resistance and the tight link with S1P. We evaluated all publicly available SphK1 inhibitors and their inhibition activity using molecular docking and how SphK1 inhibitors reduce the production of S1P and might reduce chemoresistance, an approach that might be vital in the course of cancer treatment and prognosis.
PubMed: 38419070
DOI: 10.1186/s12935-024-03221-8 -
Bioengineering (Basel, Switzerland) Jan 2024Whole-Body Diffusion-Weighted Imaging (WBDWI) is an established technique for staging and evaluating treatment response in patients with multiple myeloma (MM) and...
Deep Learning for Delineation of the Spinal Canal in Whole-Body Diffusion-Weighted Imaging: Normalising Inter- and Intra-Patient Intensity Signal in Multi-Centre Datasets.
BACKGROUND
Whole-Body Diffusion-Weighted Imaging (WBDWI) is an established technique for staging and evaluating treatment response in patients with multiple myeloma (MM) and advanced prostate cancer (APC). However, WBDWI scans show inter- and intra-patient intensity signal variability. This variability poses challenges in accurately quantifying bone disease, tracking changes over follow-up scans, and developing automated tools for bone lesion delineation. Here, we propose a novel automated pipeline for inter-station, inter-scan image signal standardisation on WBDWI that utilizes robust segmentation of the spinal canal through deep learning.
METHODS
We trained and validated a supervised 2D U-Net model to automatically delineate the spinal canal (both the spinal cord and surrounding cerebrospinal fluid, CSF) in an initial cohort of 40 patients who underwent WBDWI for treatment response evaluation (80 scans in total). Expert-validated contours were used as the target standard. The algorithm was further semi-quantitatively validated on four additional datasets (three internal, one external, 207 scans total) by comparing the distributions of average apparent diffusion coefficient (ADC) and volume of the spinal cord derived from a two-component Gaussian mixture model of segmented regions. Our pipeline subsequently standardises WBDWI signal intensity through two stages: (i) normalisation of signal between imaging stations within each patient through histogram equalisation of slices acquired on either side of the station gap, and (ii) inter-scan normalisation through histogram equalisation of the signal derived within segmented spinal canal regions. This approach was semi-quantitatively validated in all scans available to the study (N = 287).
RESULTS
The test dice score, precision, and recall of the spinal canal segmentation model were all above 0.87 when compared to manual delineation. The average ADC for the spinal cord (1.7 × 10 mm/s) showed no significant difference from the manual contours. Furthermore, no significant differences were found between the average ADC values of the spinal cord across the additional four datasets. The signal-normalised, high-b-value images were visualised using a fixed contrast window level and demonstrated qualitatively better signal homogeneity across scans than scans that were not signal-normalised.
CONCLUSION
Our proposed intensity signal WBDWI normalisation pipeline successfully harmonises intensity values across multi-centre cohorts. The computational time required is less than 10 s, preserving contrast-to-noise and signal-to-noise ratios in axial diffusion-weighted images. Importantly, no changes to the clinical MRI protocol are expected, and there is no need for additional reference MRI data or follow-up scans.
PubMed: 38391616
DOI: 10.3390/bioengineering11020130