Antigen Levels Research Articles

Prevalence of SPOP and IDH Gene Mutations in Prostate Cancer in a Jordanian Population.

Speckle-type POZ (SPOP) is described as an essential tumor suppressor factor in gastric cancer, colorectal cancer, and prostate cancer (PCa). SPOP gene mutations were reported in primary human PCa. Isocitrate dehydrogenase-1 (IDH1) oncogene mutations were detected in gliomas, acute myeloid leukemia, some benign and malignant cartilaginous tumors, and only 1% of PCa. This study aimed to investigate the prevalence of mutations of SPOP and IDH1 genes in PCa in the Jordanian population. One hundred formalin-fixed paraffin-embedded tissue samples were collected from patients diagnosed with prostate adenocarcinoma. The obtained specimens were subjected to genomic DNA extraction, PCR amplification, and direct sequencing of exons 4, 5, 6, and 7 of the SPOP gene and exon 6 of the IDH1 gene. SPOP gene mutations were found in 17% of PCa cases, while no mutation was detected in the screened exon 6 of the IDH1 gene. Clinicopathological data demonstrated a strong correlation between prostate-specific antigen (PSA) levels and both Gleason score (GS) and the International Society of Urological Pathology (ISUP) grade group (GG). There was no significant correlation between PSA levels and age (p = 0.816) nor there were significant associations for SPOP mutational status with age (p = 0.659), PSA levels (p = 0.395), GS (p = 0.259), and ISUP GG (p = 0.424) in the tested population. The study found a strong correlation between PSA levels and both GS and ISUP GG. It also identified a high frequency (17%) of SPOP gene mutations in Jordanian Arab PCa patients, mainly in exon 7. No IDH1 mutations were detected in exon 6.

Biochemical response to neoadjuvant androgen deprivation therapy before radiation therapy and the risk of death in patients with unfavorable-risk prostate cancer: A secondary analysis of a randomized clinical trial.

A prostate-specific antigen (PSA) level >0.5 ng/mL after 9 to 10 weeks of neoadjuvant androgen deprivation therapy and before radiation therapy (RT) was associated with an increased PSA-failure risk; however, the impact on all-cause mortality (ACM) risk after adjusting for serum testosterone level remains unknown. From 2005 to 2015, 350 patients with localized, unfavorable-risk prostate cancer (PC) were randomly assigned to receive androgen deprivation therapy and RT plus docetaxel vs standard of care (SOC) with androgen deprivation therapy and RT. Multivariable Cox regression analyses were used to assess whether a significant association existed between PSA (continuous and categorized as ≤0.5 vs>0.5 ng/mL) measured at 9 to 10 weeks after randomization and ACM risk, adjusting for known PC prognostic factors and baseline testosterone level. After a median follow-up of 10.23 years (interquartile range: 8.07-11.41), 85 patients died (25.30%), 41 from PC (48.24%). PSA level at 9 to 10 weeks after randomization was significantly associated with increased risk of ACM when analyzed as a continuous (adjusted hazard ratio, 1.16; 95% CI, 1.04-1.30; p=.008) or categorical covariate (>0.5 vs≤0.5 ng/mL; adjusted hazard ratio, 1.88; 95% CI, 1.12-3.17; p=.02) after adjusting for covariates. This study validates that a PSA level >0.5 ng/mL after neoadjuvant androgen deprivation therapy and before RT is prognostic and significantly associated with an increased ACM risk. Patients achieving this endpoint should be considered for enrollment in future randomized trials evaluating the impact of treatment escalation on ACM using a prerandomization stratification by age or validated comorbidity metrics.

Osteoblast-derived exosomal miR-140-3p targets ACER2 and increases the progression of prostate cancer via the AKT/mTOR pathway-mediated inhibition of autophagy.

Advanced prostate cancer (aPCa) often results in bone metastases (BM). However, the mechanism underlying its progression and metastasis to bones remains unclear. Therefore, we examined whether exosomal miR-140-3p affects prostate cancer (PCa) progression. We obtained from cell lines, clinical data analyses, and animal models consistently provide important evidence. Patients with PCa having BM had higher miR-140-3p expression in their serum exosomes than those without BM. Clinical investigations have manifested that the exosomal miR-140-3p overexpression connects with serum prostate-specific antigen (PSA) levels and Gleason grade in patients with PCa. Osteoblast-derived exosomal miR-140-3p targeting ACER2 activates the AKT/mTOR pathway invitro, inhibits autophagy, and promotes PCa cell proliferation, invasion, and migration. miR-140-3p significantly increased tumorigenesis and metastasis of LNCaP invitro. Bone metastatic PCa tissues exhibited elevated levels of miR-140-3p, p-GSK3, p-mTOR, p62, p-AKT (S473), and p-AKT (T308) contrasted with non-BM tissues. Moreover, their expression was intensified in the metastatic bone tissues. However, ACER2 and LC3 II showed opposite expression patterns. Based on our study outcomes, the evidence suggests that osteoblast-derived miR-140-3p inhibition of autophagy through the AKT/mTOR pathway is involved in PCa progression. Osteoblast-secreted exosomal miR-140-3p activates the AKT/mTOR pathway by targeting ACER2, inhibiting autophagy, and promoting the progression of PCa cells invitro. Moreover, miR-140-3p induces the progression and metastasis of PCa invivo.

Significance of the modified global leadership initiative on malnutrition (GLIM) criteria malcondition for patients with biliary tract cancer.

This study investigated the significance of the Global Leadership Initiative on Malnutrition (GLIM) for patients with resected biliary tract cancers. The subjects of this retrospective analysis were 114 patients who underwent radical surgery for cholangiocarcinoma between 2018 and 2023. We analyzed both handgrip force and skeletal muscle area and classified patients as having GLIM malnutrition or modified GLIM malcondition. We also evaluated clinicopathological factors, short-term outcomes, and prognoses. The GLIM criteria identified 47 patients (41.2%) with malnutrition and 13 patients (11.4%) with modified GLIM malcondition. Overall survival (P = 0.009) and recurrence-free survival (P = 0.016) were significantly different between the well-nourished and malnourished patients according to the GLIM criteria. Furthermore, modified GLIM criteria malcondition was a significant prognostic factor for both recurrence-free and overall survival (P = 0.002 and P < 0.001, respectively). Multivariate analysis identified a higher carcinoembryonic antigen level and modified GLIM malcondition as predictors of overall and recurrence-free survival. Pathological stage ≥ III was also a predictor of recurrence-free survival. On comparing the prognoses of modified GLIM malcondition and GLIM malnutrition using the Akaike Information Criteria, the modified GLIM malcondition was identified as a stronger prognostic factor. A modified GLIM malcondition can be a highly useful prognostic marker for patients with resected biliary tract cancer.

Comparative Analysis of C4d Deposition with The Severity, Laboratory Results and Histopathologic Scores in Lupus Nephritis

Background: Lupus nephritis (LN) is a serious complication of systemic lupus erythematosus (SLE) and evident in 60% of patients. Complement system and its product, complement component 4 degradation (C4d), plays an important role in the pathogenesis of LN. The aim is to determine the prognostic value of C4d detection in different classes of LN and correlation with laboratory results and histopathologic activity score. Methods: Thirty-five patients with LN were collected between January to September 2023. Blood levels of anti-nuclear antigens (ANA), anti-double stranded DNA antibody (Anti-dsDNA), C3, C4, and 24hr urine protein were measured. Renal tissue biopsy was examined regarding glomerular C4d antibody immunohistochemical staining and Classes of LN according to International society of nephrology/Renal Pathology Society (ISN/RPS). Results: Glomerular C4d was expressed in 40% of LN patients and was significantly correlated with urinary protein excretion (p=0.001) and Anti-dsDNA antibody (P=0.048), but not with LN classes or activity score or low complements. Conclusions: Glomerular C4d deposition of LN does not indicate the present disease activity but may help to identify a subset of patients with worse renal prognosis, providing insights about the therapeutic approaches for SLE with LN. Keywords: Lupus nephriti, glomerular C4d, proteinuria, Anti-double stranded DNA Antibody.

CEA-Induced PI3K/AKT Pathway Activation through the Binding of CEA to KRT1 Contributes to Oxaliplatin Resistance in Gastric Cancer

BackgroundThe serum level of carcinoembryonic antigen (CEA) has prognostic value in patients with gastric cancer (GC) receiving oxaliplatin-based chemotherapy. As the molecular functions of CEA are increasingly uncovered, its role in regulating oxaliplatin resistance in GC attracts attention. MethodsThe survival analysis adopted the KaplanMeier method. Effects of CEA on proliferative capacity were investigated using CCK8, colony formation, and xenograft assays. Oxaliplatin sensitivity was identified through IC50 detection, apoptosis analysis, comet assay, organoid culture model, and xenograft assay. Multi-omics approaches were utilized to explore CEA’s downstream effects. The binding of CEA to KRT1 was confirmed through proteomic analysis and Co-IP, GST pull-down, and immunofluorescence colocalization assays. Furthermore, small molecule inhibitors were identified using virtual screening and surface plasmon resonance. ResultsStarting from clinical data, we confirmed that CEA demonstrated superior ability to predict the prognosis of patients with GC who received oxaliplatin-based chemotherapy, particularly in predicting recurrence-free survival based on serum CEA level. In vitro and in vivo experiments revealed CEAhigh GC cells presented increased proliferative capacity and decreased oxaliplatin sensitivity. The resistance phenotype was transmitted through secreted CEA. Multi-omics analysis revealed that CEA activated the PI3K/AKT pathway by binding to KRT1, leading to oxaliplatin resistance. Finally, the small molecule inhibitor evacetrapib, which competitively inhibits the CEA-KRT1 interaction, was identified and validated in vitro. ConclusionsIn summary, the CEA-KRT1-PI3K/AKT axis regulates oxaliplatin sensitivity in GC cells. Treatment with small molecule inhibitors such as evacetrapib to inhibit this interaction constitutes a novel therapeutic strategy.

Salvage local treatment for recurrent prostate cancer after focal therapy: A systematic review and meta-analysis

ObjectivesTo evaluate the role of salvage local treatment in managing recurrent PCa following FT, focusing on oncological and functional outcomes. MethodsA systematic review and meta-analysis were performed following the PRISMA framework. A comprehensive literature search using the PubMed/MEDLINE and EMBASE databases was performed until July 2023. Eligible studies included patients with clinically localised PCa initially treated with FT, who experienced relapse during surveillance and subsequently underwent salvage radical prostatectomy (sRP), salvage external beam radiation therapy (sEBRT) or salvage focal therapy (sFT). The primary endpoint was the biochemical recurrence rate post-salvage treatment. The secondary endpoints were functional outcomes, including urinary incontinence and erectile dysfunction rates. ResultsIn 26 retrospective studies including 990 patients, the overall pooled biochemical recurrence rate postsalvage treatment was 26%. The subgroup analysis revealed a biochemical recurrence rate of 20%, 22%, and 42% after sRP, sEBRT, and sFT, respectively. The overall pooled rate of urinary incontinence was 20%. Salvage FT had the lowest prevalence of urinary incontinence, followed by sRP and sEBRT. The overall pooled rate of erectile dysfunction was 43%. Salvage RP had the highest prevalence of erectile dysfunction, followed by sFT and sEBRT. Substantial heterogeneity was observed among the studies, primarily due to different sample sizes. Meta-regression analysis revealed no to low contributions of salvage treatment modalities, extent of ablation, age, prostatic specific antigen level before salvage treatment, proportion of patients with Gleason score ≥7 at recurrence, and time between the primary and salvage therapies to heterogeneity. ConclusionSalvage local treatment for recurrent PCa after FT is feasible, and it provides acceptable oncological and functional outcomes. Among all treatment modalities, sRP and sEBRT appeared to have the lowest biochemical recurrence rates, whereas sFT was associated with improved functional outcomes.

Cancer detection in patients with prostate-specific antigen levels within the grey zone: can synthetic magnetic resonance imaging aid in the differentiation between prostate cancer and noncancerous lesions?

Cancer detection in patients with prostate-specific antigen levels within the grey zone: can synthetic magnetic resonance imaging aid in the differentiation between prostate cancer and noncancerous lesions?

Clinically significant prostate cancer detection rate in biopsy-naïve patients with mpMRI and microultrasound topographically discordant lesions: A single-center retrospective analysis

Introduction and objectivesMultiparametric magnetic resonance imaging (mpMRI) has improved the detection of clinically significant prostate cancer (csPCa), and microultrasound (micro-US) shows promise in enhancing detection rates. We compared mpMRI-guided targeted biopsy (MTBx) and micro–US-guided targeted biopsy (micro–US-TBx) in biopsy-naïve patients with discordant lesions at micro-US and mpMRI to detect csPCa (grade group ≥2) and clinically insignificant PCa (ciPCa; grade group 1) and assessed the role of nontargeted systematic biopsy (SBx). Material and MethodsWe analyzed 178 biopsy-naive men with suspected PCa and discordant lesions at mpMRI and micro-US. All patients underwent mpMRI followed by micro-US, the latter being performed immediately before the biopsy. Imaging findings were interpreted blindly, followed by targeted and SBx. Median age was 63 years (IQR, 57–70), median prostate-specific antigen level was 7 ng/mL (IQR, 5–9 ng/mL), and median prostate volume was 49 cm^3 (IQR, 35–64 cm^3). Overall, 86/178 (48%) patients were diagnosed with PCa, 51/178 (29%) with csPCa. ResultsMicro-USTBx detected csPCa in 36/178 men (20%; 95% CI: 26–46), and MTBx detected csPCa in 28/178 men (16%; 95% CI: 36–50), resulting in a -8% difference (95% CI: −10, 4; P = 0.022) and a relative detection rate of 0.043. Micro-USTBx detected ciPCa in 9/178 men (5%; 95% CI: 3, 15), while MTBx detected ciPCa in 12/178 men (7%; 95% CI: 5, 20), resulting in a −3% difference (95% CI: −2 to 4; P = 0.2) and a relative detection rate of 0.1. SBx detected ciPCa in 29 (16%) men. mpMRI plus micro-US detected csPCa in 51/178 men, with no additional cases with the addition of SBx. Similarly, MTBx plus micro-USTBx plus SBx detected ciPCa in 35/178 men (20%; 95% CI: 18, 37) compared to 9 (5%) in the micro-US pathway (P = 0.002) and 14/178 (8%; 95% CI: 6, 26) in the mpMRI plus micro-US pathway (P = 0.004). ConclusionsIn conclusion, a combined micro-US/mpMRI approach could characterize primary disease in biopsy-naïve patients with discordant lesions, potentially avoiding SBx. Further studies are needed to validate our findings and assess micro-US's role in reducing unnecessary biopsies.

Percutaneous radiofrequency ablation of liver metastases from colorectal cancer: Development of a prognostic score to predict overall survival

PurposeTo develop a model for pretreatment prediction of overall survival (OS) after radiofrequency ablation (RFA) for colorectal liver metastasis (CRLM). MethodThis retrospective study included 491 patients (median age, 61 years; 348 men) who underwent percutaneous RFA for CRLM between 2000 and 2021. The Kaplan–Meier method was used to estimate OS rates. Independent factors affecting OS were investigated using multivariable Cox regression analysis. Risk scores were assigned to the risk factors and pretreatment prediction models were created using the risk factors. ResultsAfter RFA, the 5-, 10-, and 20-year OS rates were 44 %, 31 %, and 24 %, respectively, and the median OS was 46 months. Multivariate Cox regression analysis showed that a largest tumor size ≥ 2 cm (P<0.001), positive nodal status of primary tumor (P<0.001), carcinoembryonic antigen level > 30 ng/mL (P=0.049), multiple tumors (P=0.008), and T4 stage of the primary tumor (P=0.029) were independently associated with OS. In patients with a single CRLM, tumor diameter (P<0.001), positive nodal status of primary tumor (P=0.001), disease-free interval <12 months (P=0.045), and subcapsular location (P=0.03) were risk factors affecting OS. According to our prediction models, which included the aforementioned risk factors, OS rates progressively decreased as the risk scores increased, with significantly different OS rates between contiguous groups (P<0.001). ConclusionsOur prediction models can be used as a prognostic stratification tool in patients with CRLM, and can help select those candidates who will benefit most from RFA.

Effect of Elderberry (Sambucus nigra L.) Extract Intake on Normalizing Testosterone Concentration in Testosterone Deficiency Syndrome Rat Model Through Regulation of 17β-HSD, 5α-Reductase, and CYP19A1 Expression

Background/Objectives. Men experience Leydig cell and mitochondrial dysfunction due to the accumulation of reactive oxygen species during aging, leading to hormonal imbalances in the body. This results in symptoms of testosterone deficiency syndrome (TDS) as testosterone levels decline. Consequently, there is a growing need for alternative therapies, such as phytotherapy, to regulate testosterone secretion. Methods. In this study, we evaluated the potential of elderberry extract powder (KSB191) as a functional ingredient for improving TDS by analyzing its mechanism in regulating testosterone imbalance. The major compounds of KSB191 were rutin and fructose–leucine, and the efficacy of KSB191 was confirmed by observing increases in total testosterone, free testosterone, and sperm motility in an aged rat model with decreased testosterone levels. Additionally, we assessed safety by analyzing levels of prostate-specific antigen, alanine aminotransferase, aspartate aminotransferase, and creatinine. Results. To confirm the effectiveness of KSB191 in increasing testosterone synthesis and inhibiting its breakdown, we analyzed the expression levels of genes related to testosterone synthesis and degradation in the testis tissue. KSB191 not only increases the expression levels of enzymes (3β-HSD, CYP17A1, and 17β-HSD) that catalyze testosterone synthesis in Leydig cells, but also reduces the expression of enzymes (5α-reductase and CYP19A1) that degrade testosterone, thereby enhancing testosterone production in the body. Conclusions. KSB191 is predicted to be a novel functional ingredient that acts on Leydig cells and increases testosterone synthesis (particularly, the increase in free testosterone), ultimately alleviating the symptoms of TDS.

Early Experience of the Single-Port Robotic Transvesical Radical Prostatectomy: Case Series

Purpose: This study evaluated the feasibility and safety of single-port transvesical robotic radical prostatectomy.Materials and Methods: Four patients underwent a transvesical robotic radical prostatectomy using a singleport robotic system. The procedure involved a 2.5-cm suprapubic incision to access the anterior bladder wall, which was incised by approximately 2 cm. Utilizing a floating-docking technique.Results: All surgeries were successfully completed without the need for additional ports or open conversion. Intraoperative complications were not observed. The median (interquartile range, IQR) console time was 159 (96–198) minutes. The median (IQR) estimated blood loss was 350 (300–700) mL. The median (IQR) duration for Foley catheter removal and patient discharge postsurgery was 7.5 (6–10) days. None of the patients experienced total incontinence after Foley catheter removal, and at 1-month postsurgery, all patients used only a safety pad. Pathology revealed positive surgical margins in 2 patients (both with pT3a and pT3b), with one of these patients having a persistent prostate-specific antigen level of 0.48 ng/mL at 1-month postsurgery. Additionally, 2 patients experienced gross hematuria within 2-week postdischarge.Conclusion: This series demonstrates that single-port robotic transvesical radical prostatectomy is a feasible procedure with favorable perioperative functional outcomes. This offers the advantage of rapid continence recovery without oncological disadvantages.

Predicting solitary pulmonary lesions in breast cancer patients using 18fluorodeoxyglucose-positron emission tomography/computed tomography combined with clinicopathological characteristics

BackgroundSolitary pulmonary nodules (SPNs) remain difficult to diagnose for clinical therapeutic purposes in patients with a history of breast cancer. This study try to investigate the value of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) combined with clinicopathological predictors for the differential diagnosis of SPNs in breast cancer patients.MethodsOne hundred and twenty breast cancer patients with newly detected SPNs were enrolled in the study and divided into a primary lung cancer (PLC) group and a breast cancer metastasis (BCM) group. The clinicopathological characteristics as well as metabolic and morphological characteristics on 18F-FDG-PET/CT images of 120 patients were retrospectively reviewed. The differences of clinicopathological and 18F-FDG-PET/CT characteristics between the two groups were analyzed, and multivariate analyses for the diagnosis of SPNs were performed.ResultsClinicopathological terms of carcinoembryonic antigen (CEA) and CA15-3 levels exhibited significant differences between PLC and BCM groups (P = 0.005 and P = 0.001, respectively). Metabolic characteristics of 18F-FDG-PET/CT images included FDG uptake, SUVmax of SPNs, hilar and/or mediastinal lymph node metastasis, SUVmax of hilar and/or mediastinal lymph node, and extrapulmonary metastasis showed significant differences between PLC and BCM groups (P = 0.004, P < 0.001, P = 0.01, P = 0.032 and P = 0.023, respectively). The lobulation sign, spicule sign, and pleural indentation sign were identified as statistically different morphological features of PLC in CT images (all P < 0.001). Among these, the SUVmax of SPNs, lobulation sign, and pleural indentation sign were valuable predictive factors for accurate diagnosis of SPNs in breast cancer patients.Conclusions18F-FDG-PET/CT combined with serum tumor markers are valuable for the diagnosis of SPNs in breast cancer patients.

Use of a Pathomics Nomogram to Predict Postoperative Liver Metastasis in Patients with Stage III Colorectal Cancer.

Approximately 25% of patients with stage III colorectal cancer experience liver metastasis after radical resection; however, there is currently a lack of methods to predict liver metastasis. This study aims to develop and validate a pathomics nomogram to predict liver metastasis in patients with stage III colorectal cancer. A total of 318 enrolled patients were divided into three cohorts: a training cohort (n=139), a validation cohort (n=69), and an external cohort (n=110). A competitive risk nomogram was established by the pathomics signature and clinicopathological characteristics and assessed by calibration, discrimination, and clinical usefulness. A significant correlation between the pathomics signature and liver metastasis in stage III colorectal cancer was found. Multivariate Fine-Gray analysis indicated that preoperative carcinoembryonic antigen level, postoperative chemotherapy, and pathomics signature were independent predictors of liver metastasis. A competitive risk nomogram was developed to predict liver metastasis in patients with stage III colorectal cancer. The predicting nomogram shows good discrimination and calibration, with C-indexes of 0.811 (95% confidence interval [CI] 0.651-0.971), 0.759 (95% CI 0.531-0.987), and 0.845 (95% CI 0.641-0.999), with area under the receiver operating characteristic (AUROC) curves at 5 years of 0.833 (95% CI 0.742-0.925), 0.760 (95% CI 0.652-0.893), and 0.812 (95% CI 0.692-0.931) in the training, validation, and external cohorts, respectively. Compared with the clinicopathological nomogram, the nomogram combined with the pathomics signature had better performance (AUROC 0.823 [95% CI 0.764-0.881] vs. 0.678 [95% CI 0.606-0.751]; p<0.001). The pathomics signature is a predictive indicator for liver metastasis in patients with stage III colorectal cancer, and the integrated nomogram can be used to predict liver metastasis better than the clinicopathological nomogram alone.

Lymph node metastasis risk factors in T2 colorectal cancer.

This study evaluates risk factors for lymph node metastasis (LNM) in T2 colorectal cancer to refine patient selection for endoscopic resection. We reviewed records from consecutive patients who had undergone curative surgical resection of T2 colorectal cancerat our institution in Japan between April 2001 and December 2021. Data on conventional clinicopathologic variables were retrieved from the pathology reports at the time of surgery. The clinicopathological features included patient age, sex, tumor diameter, morphology, tumor location, lymphatic invasion, vascular invasion, tumor differentiation, carcinoembryonic antigen and carbohydrate antigen 19-9 levels, number of lymph node dissections, presence of adenoma component, and LNM. Among the patients (338 men, 320 women), 170 (25.8%) exhibited LNM. Multivariate logistic regression identified three independent risk factors for LNM: lymphatic invasion (odds ratio [OR], 32.6; 95% confidence interval [CI], 17.3-61.4; p < 0.0001), female sex (OR, 1.70; 95% CI, 1.10-2.62; p = 0.02), and elevated carcinoembryonic antigen levels (OR, 2.56; 95% CI, 1.10-5.96; p = 0.03). Lymphatic invasion, female sex, and high carcinoembryonic antigen levels significantly increase the risk of LNM in T2 colorectal cancer.

Epidemiologic study on prostate cancer in Sudanese men across African ethnic groups

This study sought to investigate the demographic and clinical characteristics of Sudanese men diagnosed with prostate cancer (PCa) to highlight differences in diagnosis among the three major ethnolinguistic groups. A total of 532 patients with confirmed PCa diagnosis through biopsy were enrolled from six medical centers in Sudan. The majority of patients, comprising 84.2% (448/532), were diagnosed with advanced-stage disease, with a Grade group above 3. There were no discernible differences in PCa aggressiveness among the ethnolinguistic groups. However, higher levels of prostate-specific antigen (PSA) were observed in the Niger-Congo group, where 55.2% had PSA values exceeding 50 ng/ml. Patients from this group were also diagnosed at a younger age. In contrast, 90.5% of Afro-Asiatic patients are over 60 years old. Further analysis conducted within an age-matched subgroup of patients (n = 273) revealed a higher incidence of perineural invasion in the Afro-Asiatic group. This research represents the first investigation of PCa across different African ethnic groups and associates a higher incidence of perineural invasion with a specific ethnic group. While recent efforts have been made to establish African-relevant risk models to mitigate PCa health disparities, there remains a need for further investigation into genetically distinct populations within the African continent.

Spatial Transcriptomic Profiling to Characterize the Nature of Peripheral- Versus Transition-zone Prostate Cancer

Background and objectiveProstate cancer (PC) in the transition zone (TZ) has better prognosis than peripheral-zone (PZ) PC despite higher prostate-specific antigen (PSA) in patients with TZ tumors. Our aim was to characterize molecular differences between TZ and PZ tumors and their clinical implications. MethodsWe performed spatial whole-transcriptome analyses of 50 regions of interest (ROIs) from three patients with PZ and/or TZ PC. ROIs were selected on the basis of SYTO13, pan-cytokeratin, smooth muscle actin, and CD45 markers. Downstream analyses of the transcriptomics data included differential gene expression and Molecular Signatures Database cancer hallmark analysis for pathway enrichment. Survival analyses were performed in The Cancer Genome Atlas (TCGA) prostate data set. Key findings and limitationsWe analyzed Gleason grade 4 (10 ROIs) and grade 5 (10 ROIs) tumors from the PZ, and grade 3 (10 ROIs), grade 4 (11 ROIs), and grade 5 (1 ROI) tumors from the TZ. We observed distinct gene expression profiles between PZ (n = 20) and TZ (n = 22) tumors. TZ ROIs exhibited enrichment of androgen response signaling (ARS; false discovery rate <5%) and a higher androgen subscore of the genomic prostate score (p < 0.001), regardless of grade and the epithelial, stromal, or immune component of the region. Genes underexpressed in PZ tumors, including ARS genes, were associated with poorer progression-free survival in the TCGA data set (n = 451; p < 0.05). Conclusions and clinical implicationsOur results demonstrate higher ARS in TZ tumors than in PZ tumors, explaining the higher PSA and better prognosis for TZ tumors. Further studies are needed to integrate zonal location in diagnostic and treatment algorithms for PC. Patient summaryWe looked at the biological explanation for higher PSA (prostate-specific antigen) levels in blood for cancers found in different zones of the prostate. We found that genes involved in androgen response signaling may explain the higher PSA often seen for tumors in the transition zone than for tumors in the peripheral zone of the prostate. These findings may inform how we diagnose and treat prostate cancer.

A nomogram for predicting lymphovascular invasion in lung adenocarcinoma: a retrospective study

BackgroudLymphovascular invasion (LVI) was histological factor that was closely related to prognosis of lung adenocarcinoma (LAC).The primary aim was to investigate the value of a nomogram incorporating clinical and computed tomography (CT) factors to predict LVI in LAC, and validating the predictive efficacy of a clinical model for LVI in patients with lung adenocarcinoma with lesions ≤ 3 cm.MethodsA total of 450 patients with LAC were retrospectively enrolled. Clinical data and CT features were analyzed to identify independent predictors of LVI. A nomogram incorporating the independent predictors of LVI was built. The performance of the nomogram was evaluated by assessing its discriminative ability and clinical utility.We took 321 patients with tumours ≤ 3 cm in diameter to continue constructing the clinical prediction model, which was labelled subgroup clinical model.ResultsCarcinoembryonic antigen (CEA) level, maximum tumor diameter, spiculation, and vacuole sign were independent predictors of LVI. The LVI prediction nomogram showed good discrimination in the training set [area under the curve (AUC), 0.800] and the test set (AUC, 0.790), the subgroup clinical model also owned the stable predictive efficacy for preoperative prediction of LVI in lung adenocarcinoma patients, and both training and test set AUC reached 0.740.ConclusionsThe nomogram developed in this study could predict the risk of LVI in LAC patients, facilitate individualized risk-stratification, and help inform treatment decision-makin, and the subgroup clinical model also had good predictive performance for lung cancer patients with lesion ≤ 3 cm in diameter.

A fully humanized von Willebrand disease type 1 mouse model as unique platform to investigate novel therapeutic options.

Patients suffering from von Willebrand disease (VWD) have reduced quality-of-life despite current treatment options. Moreover, innovation in VWD therapeutic strategies has essentially stalled and available treatments have remained unchanged for decades. Therefore, there is an unmet need to develop new therapeutic strategies for VWD-patients, especially for the large portion of those with VWD-type 1. Due to species differences, the available VWD murine models are not suitable for preclinical studies, making it difficult to test new therapeutic approaches in vivo. With this in mind, we generated mice selectively expressing human von Willebrand factor (VWF) and human GPIbα. Because this fully humanized model was found to express low VWF (12%) and FVIII (40%) levels with normal multimer profile and activity/antigen ratio, we repositioned it as a VWD-type 1 model (hVWD1 mice). In depth characterization of this model confirmed VWD-type 1 features with a decrease in platelet adhesion and thrombus formation in vitro. In vivo, a moderate bleeding phenotype was observed which was corrected upon the administration of recombinant-VWF or upon histamine-induced release of endothelial VWF. In search for new therapeutic options for VWD, we designed a bispecific single-domain antibody that bridges VWF to albumin (KB-V13A12). Remarkably, a single subcutaneous administration of KB-V13A12 coincided with a sustained 2-fold increase in VWF antigen levels for up to 10 days and normalized haemostasis in a tail-clip model in hVWD1 mice. We have developed a unique humanized mouse model for VWD-type 1 and a promising new therapeutic that corrected haemostasis in these mice.

18F]PSMA-1007 PET for biochemical recurrence of prostate cancer, a comparison with [18F]Fluciclovine.

The objective of this study was to compare the detection rates of [18F]PSMA-1007 and [18F]Fluciclovine in early biochemical recurrence (BCR) of prostate cancer, i.e. with low prostate-specific antigen (PSA) levels (0.2-5.0µg/L). This was a prospective, single-center (Radboudumc; Nijmegen, The Netherlands), comparative phase II diagnostic imaging study (NCT04239742). The main inclusion criteria were histologically proven adenocarcinoma of the prostate, BCR after radical treatment with two consecutive (rising) PSA values (0.2-5.0µg/L). Patients underwent both [18F]PSMA-1007 PET/CT and [18F]Fluciclovine PET/CT within two weeks. Both scans were blindly scored by three independent nuclear medicine physicians. Hereafter, a result per scan and region was generated by consensus. The primary outcome was to compare the detection rate on a patient and region level. Secondary objectives were to determine detection rate stratified for PSA value, inter-reader agreement, and SUV measurements. For lesion confirmation a composite reference score was established using follow-up data. Data of fifty patients were included, median age of 71 (IQR: 67-74) years and median PSA value of 0.38 (IQR: 0.30-1.55) µg/L. Detection rates were 68% (34/50) for [18F]PSMA-1007 and 42% (21/50) for [18F]Fluciclovine on a patient level (p < 0.001). Detection rates stratified for PSA value of [18F]PSMA-1007 in comparison with [18F]Fluciclovine were for PSA 0.2-0.5µg/L; 60.7% versus 25.0% (p = 0.002); and for PSA ≥ 0.5µg/L; 77.3% versus 63.6% (p = 0.250). There was a trend for higher inter-reader agreement with [18F]PSMA-1007. SUVmax (p < 0.001) was significantly higher for [18F]PSMA-1007 in comparison to [18F]Fluciclovine. In patients with early BCR of prostate cancer after radical surgery or radiotherapy, [18F]PSMA-1007 demonstrated a significantly higher detection rate than [18F]Fluciclovine. This is particularly relevant since earlier and more accurate detection of a BCR can guide salvage therapy into a tailored strategy which may improve outcomes. ClinicalTrials.gov, NCT04239742. Registered 02 January 2020, https://clinicaltrials.gov/study/NCT04239742 .