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Communications Biology Jun 2024Studying cellular mechanoresponses during cancer metastasis is limited by sample variation or complex protocols that current techniques require. Metastasis is governed...
Studying cellular mechanoresponses during cancer metastasis is limited by sample variation or complex protocols that current techniques require. Metastasis is governed by mechanotransduction, whereby cells translate external stimuli, such as circulatory fluid shear stress (FSS), into biochemical cues. We present high-throughput, semi-automated methods to expose cells to FSS using the VIAFLO96 multichannel pipetting device custom-fitted with 22 G needles, increasing the maximum FSS 94-fold from the unmodified tips. Specifically, we develop protocols to semi-automatically stain live samples and to fix, permeabilize, and intracellularly process cells for flow cytometry analysis. Our first model system confirmed that the pro-apoptotic effects of TRAIL therapeutics in prostate cancer cells can be enhanced via FSS-induced Piezo1 activation. Our second system implements this multiplex methodology to show that FSS exposure (290 dyn cm) increases activation of murine bone marrow-derived dendritic cells. These methodologies greatly improve the mechanobiology workflow, offering a high-throughput, multiplex approach.
Topics: Mechanotransduction, Cellular; Animals; Humans; Mice; Prostatic Neoplasms; Male; Dendritic Cells; Cell Line, Tumor; High-Throughput Screening Assays; Stress, Mechanical; TNF-Related Apoptosis-Inducing Ligand; Flow Cytometry; Ion Channels
PubMed: 38824207
DOI: 10.1038/s42003-024-06327-x -
European Urology Oncology May 2024Metastatic prostate cancer (mPCa) harbors genomic alterations that may predict targeted therapy efficacy. These alterations can be identified not only in tissue but also... (Review)
Review
BACKGROUND AND OBJECTIVE
Metastatic prostate cancer (mPCa) harbors genomic alterations that may predict targeted therapy efficacy. These alterations can be identified not only in tissue but also directly in biologic fluids (ie, liquid biopsies), mainly blood. Liquid biopsies may represent a safer and less invasive alternative for monitoring patients treated for mPCa. Current research focuses on the description and validation of novel predictive biomarkers to improve precision medicine in mPCa. Our aim was to systematically review the current evidence on liquid biopsy biomarkers for predicting treatment response in mPCa.
METHODS
We systematically searched Medline, Web of Science, and evidence-based websites for publications on circulating biomarkers in mPCa between March 2013 and February 2024 for review. Endpoints were: prediction of overall survival, biochemical or radiographic progression-free survival after treatment (chemotherapy, androgen deprivation therapy, androgen receptor pathway inhibitors [ARPIs], immunotherapy, or PARP inhibitors [PARPIs]). For each biomarker, the level of evidence (LOE) for clinical validity was attributed: LOE IA and IB, high level of evidence; LOE IIB and IIC, intermediate level; and LOE IIIC and LOE IV-VD, weak level.
KEY FINDINGS AND LIMITATIONS
The predictive value of each biomarker for the response to several therapies was evaluated in both metastatic hormone-sensitive (mHSPC) and castration-resistant prostate cancer (mCRPC). In patients with mCRPC, BRCA1/2 or ATM mutations predicted response to ARPIs (LOE IB) and PARPIs (LOE IIB), while AR-V7 transcripts or AR-V7 protein levels in circulating tumor cells (CTCs) predicted response to ARPIs and taxanes (LOE IB). CTC quantification predicted response to cabazitaxel, abiraterone, and radium-223 (LOE IIB), while TP53 alterations predicted response to Lu prostate-specific membrane antigen radioligand treatment (LOE IIB). AR copy number in circulating tumor DNA before the first treatment line and before subsequent lines predicted response to docetaxel, cabazitaxel, and ARPIs (LOE IIB). In mHSPC, DNA damage in lymphocytes was predictive of the response to radium-223 (LOE IIB).
CONCLUSIONS AND CLINICAL IMPLICATIONS
BRCA1/2, ATM, and AR alterations detected in liquid biopsies may help clinicians in management of patients with mPCa. The other circulating biomarkers did not reach the LOE required for routine clinical use and should be validated in prospective independent studies.
PATIENT SUMMARY
We reviewed studies assessing the value of biomarkers in blood or urine for management of metastatic prostate cancer. The evidence indicates that some biomarkers could help in selecting patients eligible for specific treatments.
PubMed: 38824003
DOI: 10.1016/j.euo.2024.05.003 -
Current Pharmaceutical Design May 2024Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths worldwide. There may be more than a million instances of hepatocellular carcinoma...
Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths worldwide. There may be more than a million instances of hepatocellular carcinoma by 2025, making it a persistent concern for global health. The most common form of hepatocellular carcinoma accounts for more than 90% of cases. There is no known cure for hepatocellular carcinoma, which is usually detected late in life. Unlike most other common malignancies, such as lung, prostate, and breast cancers, where mortality rates are declining, rates of death are rising by around 2-3% every year. It is extremely difficult to diagnose hepatocellular carcinoma in its early stages. Alpha-fetoprotein serology studies and ultrasonography (US) monitoring were historically the primary methods for early detection of hepatocellular cancer. However, the sensitivity or specificity of ultrasonography/alpha-fetoprotein (US/AFP) is not high enough to detect hepatocellular carcinoma in its early stages. Alpha-fetoprotein, or AFP, is an amino acid that is normally produced by the liver or yolk sac of an embryonic baby. In adults, AFP levels are typically modest. Adults with high levels of AFP have been associated with several illnesses, the most well-known of which are certain types of cancer. It is still possible to diagnose hepatocellular carcinoma early because of current technological advancements. We address the advancements in the diagnosis of hepatocellular carcinoma in this article, with a focus on new imaging techniques and diagnostic markers for early-stage tumor identification.
PubMed: 38797901
DOI: 10.2174/0113816128298875240321073907 -
Medicina (Kaunas, Lithuania) Apr 2024: Transurethral urologic surgeries frequently lead to hypothermia due to bladder irrigation. Prewarming in the preoperative holding area can reduce the risk of... (Randomized Controlled Trial)
Randomized Controlled Trial
: Transurethral urologic surgeries frequently lead to hypothermia due to bladder irrigation. Prewarming in the preoperative holding area can reduce the risk of hypothermia but disrupts surgical workflow, preventing it from being of practical use. This study explored whether early intraoperative warming during induction of anesthesia, known as peri-induction warming, using a forced-air warming device combined with warmed intravenous fluid could prevent intraoperative hypothermia. : Fifty patients scheduled for transurethral resection of the bladder (TURB) or prostate (TURP) were enrolled and were randomly allocated to either the peri-induction warming or control group. The peri-induction warming group underwent whole-body warming during anesthesia induction using a forced-air warming device and was administered warmed intravenous fluid during surgery. In contrast, the control group was covered with a cotton blanket during anesthesia induction and received room-temperature intravenous fluid during surgery. Core temperature was measured upon entrance to the operating room (T), immediately after induction of anesthesia (T), and in 10 min intervals until the end of the operation (T). The incidence of intraoperative hypothermia, change in core temperature (T-T), core temperature drop rate (T-T/[duration of anesthesia]), postoperative shivering, and postoperative thermal comfort were assessed. : The incidence of intraoperative hypothermia did not differ significantly between the two groups. However, the peri-induction warming group exhibited significantly less change in core temperature (0.61 ± 0.3 °C vs. 0.93 ± 0.4 °C, = 0.002) and a slower core temperature drop rate (0.009 ± 0.005 °C/min vs. 0.013 ± 0.004 °C/min, = 0.013) than the control group. The peri-induction warming group also reported higher thermal comfort scores ( = 0.041) and less need for postoperative warming ( = 0.034) compared to the control group. : Brief peri-induction warming combined with warmed intravenous fluid was insufficient to prevent intraoperative hypothermia in patients undergoing urologic surgery. However, it improved patient thermal comfort and mitigated the absolute amount and rate of temperature drop.
Topics: Humans; Male; Hypothermia; Anesthesia, General; Aged; Middle Aged; Female; Urologic Surgical Procedures; Intraoperative Complications
PubMed: 38792930
DOI: 10.3390/medicina60050747 -
Urology May 2024To assess the role of intraprostatic injection of tranexamic acid (TXA) in reducing blood loss during transurethral resection of the prostate (TURP).
OBJECTIVE
To assess the role of intraprostatic injection of tranexamic acid (TXA) in reducing blood loss during transurethral resection of the prostate (TURP).
METHODS
We conducted a randomized, controlled, double-blind trial involving 60 patients with benign prostatic hyperplasia aged 50-85years, undergoing monopolar TURP. Patients' prostatic weights ranged from 50 to 80 g. They were divided equally into two groups: group I received an intraprostatic injection of 1 g of TXA (Cyklokapron) dissolved in 50 mL of 0.9 % saline at multiple sites, while group II (control) received a 60 mL saline injection. Comprehensive clinical assessments and standard laboratory tests, including screenings for TXA hypersensitivity, were performed for all patients.
RESULTS
Group I exhibited significantly lower intraoperative blood loss and hemoglobin concentration in irrigation fluid immediately postsurgery and at the 6-hour postoperative mark compared to group II (P < .05). Coagulation parameters-activated partial thromboplastin time, prothrombin time, fibrinogen level, and thrombin clotting time-showed no significant differences between the groups preoperatively or at 6 and 24 hours postoperatively. No thromboembolic events or other complications were reported in either group.
CONCLUSION
The intraprostatic injection of TXA during monopolar TURP is safe, with minimal adverse effects, and effectively reduces blood loss.
REGISTRATION
The study was registered on ClinicalTrials.gov No (ID: NCT05913466).
PubMed: 38788904
DOI: 10.1016/j.urology.2024.05.015 -
International Braz J Urol : Official... May 2024Robot-assisted radical prostatectomy (RARP) has become a popular surgical approach for localized prostate cancer due to its favorable oncological and functional...
INTRODUCTION
Robot-assisted radical prostatectomy (RARP) has become a popular surgical approach for localized prostate cancer due to its favorable oncological and functional outcomes, as well as lower morbidity. In cases of intermediate- and high-risk prostate cancer, bilateral pelvic lymphadenectomy (PLND) is recommended as an adjunct to RARP (1-3). Despite its benefits, PLND can lead to surgical complications, with postoperative lymphocele formation being the most common. Most postoperative lymphoceles are clinically insignificant with variable incidence, reaching up to 60% of cases 4. However, a small percentage of patients 2-8% may experience symptomatic lymphoceles (SL), which can cause significant morbidity (4, 5).
SURGICAL TECHNIQUE
We perform our RARP technique with our standard approach in all patients (6). After vesicourethral anastomosis a modified PF created to prevent symptomatic lymphocele. We start by suturing the peritoneal fold on the right side, medially to the vas deferens, followed by a similar stitch on the left side to approximate the edges in the midline. A running suture bunches the bladder peritoneum from both sides, passing through the pubic bone periosteum to secure it in place (7). This approach keeps the lateral pelvic gutters open for lymphatic drainage, while allowing fluid drainage from the true pelvis into the abdomen. A pelvic ultrasound was done for all patients at 6 weeks post operative, and additional clinical follow-up was carried out at 3 months following surgery.
CONSIDERATIONS
We have demonstrated a modified technique of peritoneal flap (PBFB) with an initial decrease in postoperative symptomatic lymphoceles, the technique is feasible, safe, does not add significant morbidity, and does not require a learning curve.
PubMed: 38787614
DOI: 10.1590/S1677-5538.IBJU.2024.0278 -
Cell Reports. Medicine Jun 2024Molecular phenotypic variations in metabolites offer the promise of rapid profiling of physiological and pathological states for diagnosis, monitoring, and prognosis....
Molecular phenotypic variations in metabolites offer the promise of rapid profiling of physiological and pathological states for diagnosis, monitoring, and prognosis. Since present methods are expensive, time-consuming, and still not sensitive enough, there is an urgent need for approaches that can interrogate complex biological fluids at a system-wide level. Here, we introduce hyperspectral surface-enhanced Raman spectroscopy (SERS) to profile microliters of biofluidic metabolite extraction in 15 min with a spectral set, SERSome, that can be used to describe the structures and functions of various molecules produced in the biofluid at a specific time via SERS characteristics. The metabolite differences of various biofluids, including cell culture medium and human serum, are successfully profiled, showing a diagnosis accuracy of 80.8% on the internal test set and 73% on the external validation set for prostate cancer, discovering potential biomarkers, and predicting the tissue-level pathological aggressiveness. SERSomes offer a promising methodology for metabolic phenotyping.
Topics: Humans; Prostatic Neoplasms; Spectrum Analysis, Raman; Male; Phenotype; Metabolomics; Metabolome; Biomarkers, Tumor; Cell Line, Tumor
PubMed: 38776910
DOI: 10.1016/j.xcrm.2024.101579 -
Magnetic Resonance in Medicine May 2024Prostate tissue has a complex microstructure, mainly composed of epithelial and stromal cells, and of extracellular (acinar-luminal) spaces. Diffusion-weighted MR...
PURPOSE
Prostate tissue has a complex microstructure, mainly composed of epithelial and stromal cells, and of extracellular (acinar-luminal) spaces. Diffusion-weighted MR spectroscopy (DW-MRS) is ideally suited to explore complex microstructure in vivo with metabolites selectively distributed in different subspaces. To date, this technique has been applied to brain and muscle. This study presents the development and pioneering utilization of H-DW-MRS in the prostate, accompanied by in vitro studies to support interpretations of in vivo findings.
METHODS
Nine healthy volunteers underwent a prostate MR examination (mean age, 56 years; range, 31-66). Metabolic complexation was studied in vitro using solutions with major compounds found in prostatic fluid of the lumen. DW-MRS was performed at 3 T with a non-water-suppressed single-voxel sequence with metabolite-cycling to concurrently measure metabolite and water signals. The water signal was used in postprocessing as a reference in a motion-compensation scheme. The spectra were fitted simultaneously in the spectral and diffusion-weighting dimensions. Apparent diffusion coefficients (ADCs) were derived by fitting signal decays that were assumed to be mono-exponential for metabolites and biexponential for water.
RESULTS
DW-MRS of the prostate revealed relatively low ADCs for Cho and Cr compounds, aligning with their intracellular location and higher ADCs for citrate and spermine supporting their luminal origin. In vitro assessments of the ADCs of citrate and spermine demonstrated their complex formation and protein binding. Tissue concentrations of MRS-detectable metabolites were as expected for the voxel location.
CONCLUSIONS
This work successfully demonstrates the feasibility of H-DW-MRS of the prostate and its potential for providing valuable microstructural information.
PubMed: 38775024
DOI: 10.1002/mrm.30141 -
Cureus Apr 2024We report a rare case of a 59-year-old male with a history of metastatic prostate cancer presenting with acute onset dyspnea due to extensive bilateral pleural...
We report a rare case of a 59-year-old male with a history of metastatic prostate cancer presenting with acute onset dyspnea due to extensive bilateral pleural effusions. This case highlights the rarity of metastatic prostate cancer with pleural involvement and underscores the importance of accurate diagnosis using cytopathology and immunohistochemical staining.
PubMed: 38765351
DOI: 10.7759/cureus.58597 -
P. gingivalis in oral-prostate axis exacerbates benign prostatic hyperplasia via IL-6/IL-6R pathway.Military Medical Research May 2024Benign prostatic hyperplasia (BPH) is the most common disease in elderly men. There is increasing evidence that periodontitis increases the risk of BPH, but the specific...
BACKGROUND
Benign prostatic hyperplasia (BPH) is the most common disease in elderly men. There is increasing evidence that periodontitis increases the risk of BPH, but the specific mechanism remains unclear. This study aimed to explore the role and mechanism of the key periodontal pathogen Porphyromonas gingivalis (P. gingivalis) in the development of BPH.
METHODS
The subgingival plaque (Sp) and prostatic fluid (Pf) of patients with BPH concurrent periodontitis were extracted and cultured for 16S rDNA sequencing. Ligature-induced periodontitis, testosterone-induced BPH and the composite models in rats were established. The P. gingivalis and its toxic factor P. gingivalis lipopolysaccharide (P.g-LPS) were injected into the ventral lobe of prostate in rats to simulate its colonization of prostate. P.g-LPS was used to construct the prostate cell infection model for mechanism exploration.
RESULTS
P. gingivalis, Streptococcus oralis, Capnocytophaga ochracea and other oral pathogens were simultaneously detected in the Pf and Sp of patients with BPH concurrent periodontitis, and the average relative abundance of P. gingivalis was found to be the highest. P. gingivalis was detected in both Pf and Sp in 62.5% of patients. Simultaneous periodontitis and BPH synergistically aggravated prostate histological changes. P. gingivalis and P.g-LPS infection could induce obvious hyperplasia of the prostate epithelium and stroma (epithelial thickness was 2.97- and 3.08-fold that of control group, respectively), and increase of collagen fibrosis (3.81- and 5.02-fold that of control group, respectively). P. gingivalis infection promoted prostate cell proliferation, inhibited apoptosis, and upregulated the expression of inflammatory cytokines interleukin-6 (IL-6; 4.47-fold), interleukin-6 receptor-α (IL-6Rα; 5.74-fold) and glycoprotein 130 (gp130; 4.47-fold) in prostatic tissue. P.g-LPS could significantly inhibit cell apoptosis, promote mitosis and proliferation of cells. P.g-LPS activates the Akt pathway through IL-6/IL-6Rα/gp130 complex, which destroys the imbalance between proliferation and apoptosis of prostate cells, induces BPH.
CONCLUSION
P. gingivalis was abundant in the Pf of patients with BPH concurrent periodontitis. P. gingivalis infection can promote BPH, which may affect the progression of BPH via inflammation and the Akt signaling pathway.
Topics: Male; Prostatic Hyperplasia; Porphyromonas gingivalis; Rats; Humans; Animals; Interleukin-6; Receptors, Interleukin-6; Prostate; Periodontitis; Aged; Middle Aged; Rats, Sprague-Dawley; Disease Models, Animal; Signal Transduction
PubMed: 38764065
DOI: 10.1186/s40779-024-00533-8