Antigen Levels Research Articles

3D-printed model for resection of positive surgical margins in robot-assisted prostatectomy.

To improve precision of secondary resection (SR) after positive surgical margin (PSM) detection by frozen section (FS) during nerve-sparing (NS) robot-assisted radical prostatectomy (RARP) by employing a personalised three-dimensional (3D)-printed prostate model derived from pelvic magnetic resonance imaging (MRI). This model was used to mark positive surgical margins (PSM) and guide intraoperative SR during NS-RARP. Prospective multicentre cohort study with 100 patients undergoing NS-RARP between September 2018 and August 2021. Primary and secondary endpoints were the conversion rate of FS-identified PSM to a tumour-free margin and functional/oncological parameters within a 12-month follow-up, respectively. A PSM was identified in 23% of cases during FS, with a conversion to negative surgical margins (NSM) in 83% (19/23 cases) by model-guided SR. The tumour detection rate in SR specimens was 39% (nine of 23 cases). Among the 19 patients with converted margins, 18 (95%) achieved undetectable prostate-specific antigen levels 2 months postoperatively, with six (32%) having subsequent biochemical recurrence within 12 months. prostate-specific-membrane-antigen positron emission tomography computed tomography found one local recurrence, and five cases of metastatic disease. In converted patients, the baseline median five-item version of the International Index of Erectile Function score decreased by 16% after 1 year, with no significant difference compared to patients with primarily NSM. Limitations include the absence of a control group, the potential for false-negative FS results and limited accuracy of MRI. The integration of 3D-printed prostate models into NS-RARP has the potential to positively impact surgical outcomes by improving the precision of SR and optimising pathosurgical communication.

Comparative efficacy and safety of 180W XPS vs. 120 W HPS GreenLight laser therapy for benign prostatic hyperplasia: a systematic review and meta-analysis.

To compare the surgical and functional outcomes of the 120 W HPS and 180 W XPS GreenLight laser vaporization systems in the treatment of benign prostatic hyperplasia (BPH). In January 2024, a comprehensive search across PubMed, Cochrane Library, and EMBASE was conducted following PRISMA guidelines, registered under PROSPERO (CRD42024531176). Studies comparing 120 W and 180 W GreenLight lasers in BPH treatment were assessed for clinical outcomes. Eight studies were included. The 180 W XPS system improved operation time (MD: 12.70, 95% CI [5.29-20.11], p=0.0008), lasing duration (MD: 10.09, 95% CI [0.85-19.33], p=0.03), and catheterization duration (MD: 0.43, 95% CI [0.12-0.74], p=0.007). No significant differences in energy consumption, energy density, or length of hospital stay were found. Functional outcomes such as International Prostate Symptom Score and maximum urinary flow rate showed no significant differences, except in quality of life (MD: 0.43, 95% CI [0.06-0.80], p=0.02) and prostate-specific antigen levels (MD: -0.77, 95% CI [-1.28 to -0.25], p=0.003). The 180 W system exhibited a lower rate of overall (OR: 1.52, 95% CI [1.14-2.04], p=0.005) and minor complications (OR: 1.84, 95% CI [1.27-2.66], p=0.001), with no significant differences in major complications or other adverse events. The 180 W XPS system demonstrates enhanced efficiency and reduced complication rates, offering a favorable option for BPH treatment, particularly for larger prostates. Future studies should focus on randomized trials to confirm these findings and assess long-term outcomes.

Molecular characterization of human respiratory syncytial virus strains circulating among hospitalized children in Jordan

BackgroundHuman Respiratory Syncytial Virus (HRSV) is a primary cause of severe pediatric respiratory infections, particularly in infants and young children, often resulting in hospitalization. The virus possesses a high degree of mutagenic potential, contributing to significant antigenic diversity, which complicates immune responses and poses challenges for vaccine development and disease management. This study was conducted in Jordan from 2022 to 2023 to epidemiologically determine the prevalence and molecular characteristics of RSV.MethodsA total of 288 nasopharyngeal (NP) swabs were collected from hospitalized children at Prince Hamza Hospital, Amman, Jordan. All samples were screened for common viral and bacterial respiratory pathogens using PCR. A partial segment of the G gene of RSV was amplified for molecular characterization and phylogenetic tree analysis.ResultsViral and/or bacterial infection was identified in 71.9% (207/288) of the tested specimens. Among these, 35 samples (12.2%, 35/288) tested positive for RSV. Specific subgroup PCR analysis identified (25, 71.4%) RSV-A, (4, 11.4%) RSV-B, and (6, 17.1%) could not be identified using our set of primers. Phylogenetic tree analysis revealed that RSV-A ON1 and RSV-B BA9 genotype strains predominate in Jordan. We observed multiple substitutions in our studied sample which would drive variation in the level of antigenicity and pathogenicity of RSV. Glycosylation sites identified were consistent with previously reported studies.ConclusionThis study provides updated epidemiological data on the strains circulating in Amman, Jordan and their molecular characteristics. Continuous RSV surveillance informs vaccine development, guides public health interventions, and enables timely administration of prophylactic treatments, reducing the burden of RSV-related illness.

Bioinspired caffeic acid-laden milk protein-based nanoparticles targeting folate receptors for breast cancer treatment.

Breast cancer is the second leading cause of death worldwide. Conventional chemotherapeutic therapies lack the specific targeting effect toward the cancerous cells resulting in extensive side effects. Our current study endeavors to prepare novel bioinspired folic acid-functionalized caffeic acid (CA)-loaded casein nanoparticles (CS NPs) for curbing breast cancer. CA-CS NPs were prepared by simple coacervation method followed by lyophilization. Functionalized CS NPs were achieved using folic acid as the targeting moiety. Entire comparative characterization between unconjugated and conjugated NPs were implemented in terms of size, polydispersity index, surface charge, 1H-NMR, surface morphology, in-vitro drug release, sterilization, cytotoxicity, and animal studies. Conjugated NPs attained PS = 157.23 ± 2.64 nm, PDI = 0.309 ± 0.199, ZP = -25.53 ± 2.31 mV and IC50 = 40 ± 2.9 µg/ml. Significant reduction in the biochemical marker levels of Carcino-embryonic antigen, carbohydrate antigen 15-3, and malondialdehyde while increased superoxide dismutase levels were achieved in the tumor -induced rats treated by the conjugated NPs. Histopathological examinations showed great improvement in the mammary and necrotic regions. The present work paves the road of 'back to nature' approach in designing biocompatible bioinspired conjugated nanocarriers for the diagnosis and treatment of various diseases.

Diffuse Peritoneal Carcinomatosis of Prostate Cancer Unveiled by [89Zr]Zr-PSMA-617 PET/CT

Abstract We report an interesting case of a 64-year-old man with a history of radical prostatectomy for prostate cancer. The patient presented with steady increasing prostate-specific antigen levels, but with negative findings on previous multiple conventional prostate-specific membrane antigen (PSMA) PET/CT (with [68Ga]Ga-PSMA-11) and [18F]FDG PET/CT. A recently introduced PSMA tracer using long-lived 89Zr (half-life 3.3 days), [89Zr]Zr-PSMA-617, was administered in attempt to localize potential local recurrence or metastasis. [89Zr]Zr-PSMA-617 PET/CT clearly revealed diffuse peritoneal carcinomatosis and local recurrence of the prostate cancer, which were unidentified on previous conventional PET/CT scans. This case highly demonstrates the potential of PET imaging with the novel PSMA tracer [89Zr]Zr-PSMA-617.

Is prostate-specific antigen density superior than prostate-specific antigen kinetics and prostate volume in predicting clinically insignificant prostate cancer?

Objectives: In this study, we aimed to evaluate the parameters that could predict clinically insignificant prostate cancer (ciPCa) in men who underwent transrectal ultrasound (TRUS)-guided prostate biopsy. Methods: Data of patients who underwent transrectal prostate biopsy between January 2015 and November 2019 were examined retrospectively. Free/total PSA ratio (fPSA%), serum total and free prostate-specific antigen (PSA) levels, prostate volumes (PV) measured by ultrasonography, and PSA density (PSAD) values of the patients before biopsy were recorded. ciPCa patients were defined as patients with Gleason scores ≤6 and clinical stage ≤T2a (Group 1). The remaining patients (Gleason score >6 and clinical stage >T2a) were included in Group 2 (clinical significant prostate cancer (csPCa). The parameters examined before biopsy were compared between groups. Results: After performing the exclusion criteria, the study counts in 168 patients with the current data of total/free PSA levels, age, PV calculated by TRUS, rectal examination findings, and pathology reports. Group 1 consisted of 115 patients and Group 2 consisted of 53 patients. In the univariate analysis, PV, total PSA and PSAD were found significantly different between groups, while age, free PSA, and fPSA% showed no significant difference between the two groups. According to the results of the multivariate analysis, the independent predictor of ciPCa was determined to be PSAD while total PSA and PV were not independent predictors. Conclusion: PSAD was found to be superior to other PSA kinetics in predicting ciPCa.

Focal therapy using high-intensity focused ultrasound with intraoperative prostate compression for patients with localized prostate cancer: a multi-center prospective study with 7 year experience.

To evaluate clinical outcomes of focal therapy using high-intensity focused ultrasound (HIFU) with intraoperative prostate compression for patients with localized prostate cancer (PC). Patients were included if they had prostate specific antigen levels of ≤20 ng/mL and clinically significant PC (CSPC) within the left or right half, or upper or lower half of the prostate. CSPC was detected using magnetic resonance imaging-transrectal ultrasound fusion image-guided target biopsy and a 12-core systematic biopsy. Focal therapy using HIFU with intraoperative prostate compression was administered to lesions visible on the magnetic resonance imaging. Biochemical failure was defined by the Phoenix ASTRO definition. Pathological failure was defined as having CSPC in the biopsy at the time of biochemical failure. The patients (n = 240; median age, 69 years old; median prostate specific antigen level, 6.42 ng/mL) were divided according to the D'Amico risk classification into: 'low' (n = 51), 'intermediate' (n = 107), and 'high' (n = 82) groups. The biochemical and the pathological disease-free survival rates after a single treatment for the low-, intermediate-, and high-risk groups were 93.7% and 92.2%, 88.5% and 91.6%, and 84.8% and 86.6%, respectively. The radical or systematic treatment-free survival rates were 96.1%, 94.4%, and 95.1%, respectively. Median follow-up period was 48 months (range 24-84). The urinary and sexual function at 1 month post-treatment had deteriorated but returned to preoperative levels at 3 or 6 months after treatment. Focal therapy using HIFU with intraoperative prostate compression would improve medium-term oncological outcomes without the risk of functional deterioration.

The Discovery and Preclinical Profile of ALG-000184, a Prodrug of the Potent Hepatitis B Virus Capsid Assembly Modulator ALG-001075.

Chronic hepatitis B (CHB) represents a significant unmet medical need with few options beyond lifelong treatment with nucleoside analogues, which rarely leads to a functional cure. Novel agents that reduce levels of HBV DNA, RNA and other viral antigens could lead to better treatment outcomes. The capsid assembly modulator (CAM) class of compounds represents an important modality for chronic suppression and to improve functional cure rates, either alone or in combination. GLP-26 is a potent CAM, which in this work was optimized for potency, safety, and other drug-like properties leading to ALG-001075. ALG-001075 was further advanced through clinical development as the highly soluble prodrug ALG-000184. ALG-000184 is currently being explored in multiple clinical trials in HBV-infected subjects where unprecedented reductions in HBV DNA, RNA and other viral antigens have been observed, making ALG-000184 a promising candidate to become a cornerstone for future chronic suppressive and combination treatment regimens for CHB.

Affinity-tuned mesothelin CAR T cells demonstrate enhanced targeting specificity and reduced off-tumor toxicity.

The application of chimeric antigen receptor (CAR) T cell therapy in solid tumors is hindered by life-threatening toxicities resulting from on-target, off-tumor killing of nonmalignant cells that express low levels of the target antigen. Mesothelin (MSLN) has been identified as a target antigen for CAR T cell treatment of mesothelioma, lung, ovarian, and other cancers because of its high expression on tumor cells and limited expression on mesothelial cells. However, fatal off-tumor toxicity of high-affinity MSLN-targeting CAR T cells has been reported in multiple clinical trials. In this study, we constructed CARs using mutant variants of a single-domain nanobody that bind both human and mouse MSLN with a wide range of affinities and examined tumor responses and their toxicities from on-target, off-tumor interactions in mouse models. CAR T cells with low nanomolar affinity (equilibrium dissociation constant, KD) exhibited profound systemic expansion with no apparent infiltration into the tumor. With a gradual reduction of CAR affinity toward the micromolar KD, the expansion of CAR T cells became more restricted to tumors. Our preclinical studies demonstrated that high-affinity MSLN CARs were associated with fatal on-target, off-tumor toxicity and that affinity-tuned CARs rendered T cells more selective for MSLN-high tumors.

Results of treatment of patients 75 years or older with non-metastatic prostate cancer in real clinical practice

Aim. To evaluate the results of radical surgical treatment and radiotherapy in patients with non-metastatic prostate cancer at age ≥75 years.Materials and methods. The retrospective study included data from 151 patients ≥75 years with verified non-metastatic prostate cancer who underwent radical prostatectomy (RP) or external beam radiotherapy (EBRT). Median age was 81.0 (75.0–97.0) years. Median Charlson comorbidity index was 7 (4–12). Median baseline prostate specific antigen (PSA) level was 11.0 (1.8–172.0) ng/mL. Prostatic adenocarcinoma was verified (ISUP grade 4–5 – 30 (19.9 %)) in all patients. сТ category was сТ3–4 in 37 (24.5 %), cN1 category was diagnosed in 10 (6.6 %) patients. The groups of unfavorable intermediate, high and very high risk included 93 (61.6 %) patients. Radical treatmentwas performed in all cases: RP in 38 (25.2 %), EBRT in 113 (74.8 %) patients (109 (72.2 %) men completed EBRT). Adjuvant treatment was administered in 8 (21.1 %) patients who underwent surgery. In the EBRT group neoadjuvant androgen-deprivation therapy (ADT) was administered in 74 (65.5 %), adjuvant ADT in 79 (70.0 %) cases. Treatment groups were matched by the main characteristics (р >0.05 for all) excluding lower baseline PSA in the RP group (р = 0.013). Median follow-up was 46.2 (1.5–234.2) months for all patients.Results. RP complications were registered in 3 (7.8 %), EBRT complications – in 7 (6.2 %) patients. No serious or lethal adverse event was observed. Recurrences were diagnosed in 9 (23.7 %) patients after surgery and in 26 (23.9 %) of 109 patients who completed EBRT. In the total study population, 4-year recurrence-free, cancer-specific, overall, and cardiac-specific survival rates were 74.5; 96.3; 91.2 and 90.8 %, respectively. The only factor significantly decreasing overall survival was Charlson comorbidity index ³8 (р = 0.05). Significant decrease of recurrence-free survival was observed in the surgery group compared to the EBRT group (р = 0.032). It did not translate into decreased cancerspecific and overall survival (р >0.05 for all). There was no significant difference in cardiac-specific survival between the groups (р = 0.626). Significant unfavorable prognostic factors of recurrence-free survival in the EBRT group included сN1 category (р = 0.045), very high risk (р = 0.049), and EBRT dose.Conclusion. RP and EBRT in elderly patients with non-metastatic prostate cancer receiving treatment in real clinical practice have acceptable safety profile and provide effectiveness comparable to the historical data on patients not sampled by age. The optimal candidates for radical treatment are men with Charlson comorbidity index <8.

Clinical case of mantle cell lymphoma of the prostate

The article presents a clinical case of mantle cell lymphoma of the prostate in a 75-year-old man who was hospitalized in the Emergency Urological Department of the City Clinical Hospital No. 52 with gross hematuria through cystostomy tube. During examination the patient was found to have prostatomegaly (prostate volume 992 cm3), prostate-specific antigen level was 2.2 ng/mL. Immunohistochemical examination of prostate tissue after adenectomy indicates prostate damage due to mantle cell lymphoma.

Correlation of Cytokine Profiles with Prostate-Specific Antigen and Disease Grade in Prostate Cancer.

BACKGROUND The development and progression of prostate cancer are multistep processes involving several growth factors, hormones, and cytokines. This study aimed to measure the serum concentrations of different cytokines and determine their correlation with prostate-specific antigen (PSA) levels and disease grade in patients with prostate adenocarcinoma. MATERIAL AND METHODS This cross-sectional study was conducted from March 2023 to March 2024 at the Clinic of Oncology of the University Hospital Center in Mostar, Bosnia and Herzegovina. Altogether, 50 male patients with prostate adenocarcinoma were included, of whom 28 had no proven metastases (PC group) and 22 had metastatic disease (MPC group). Serum concentrations of total (tPSA), free (fPSA), and complexed (cPSA) PSA were determined using a chemiluminescent microparticle immunoassay, whereas serum concentrations of cytokines were measured using a flow cytometry bead-based assay. RESULTS The MPC group had higher serum tPSA, fPSA, and cPSA levels than the PC group. The PC group had significantly higher serum levels of monocyte chemotactic protein (MCP)-1 than the MPC group (P=0.008). In the PC group, serum levels of interleukin (IL)-10 significantly correlated with cPSA. In the MPC group, serum concentrations of IL-1ß, tumor necrosis factor (TNF)-alpha, and IL-23 significantly correlated with disease grade. CONCLUSIONS Our study emphasizes the importance of MCP-1 in the development of prostate cancer, while IL-10 was the only cytokine whose serum level significantly correlated with cPSA. Serum concentrations of IL-1ß, TNF-alpha, and IL-23 may serve as potential biomarkers for disease grade.

Analysis of the clinical characteristics of HBeAg-negative chronic HBV infection in indeterminate phase with a low viral load

Objective: To analyze the clinical characteristics of HBeAg-negative chronic hepatitis B virus (HBV) infection in indeterminate phase with a low viral load. Methods: One hundred and thirty-nine cases with persistent normal alanine aminotransferase (ALT) and HBeAg-negative chronic HBV infection with low viral load who visited the Department of Infectious Diseases of the Affiliated Hospital of Yan'an University from September 2013 to July 2021 were retrospectively collected. Patients were divided into low hepatitis B surface antigen (HBsAg) group (n=59) and high HBsAg group (n=80) according to the baseline hepatitis B surface antigen (HBsAg) level. The changes of various indicators at baseline and follow-up endpoints were analyzed between the two groups. The rate of HBsAg decrease ≥0.5 log10IU/ml, HBV DNA negative conversion rate, ALT persistently normal rate, and liver stiffness measurement (LSM) persistently normal rate at the end of the follow-up were compared. The t-test, or non-parametric Mann-Whitney U test, and Wilcoxon signed rank test were used for comparison of continuous data between the two groups. The χ2 test, or Fisher's exact probability method, was used for comparing count data between the two groups. Results: There were statistically significant differences in age, gender, and HBsAg at baseline, but there was no statistically significant difference in terms of family history of hepatitis B, follow-up time, anti-HBe, anti-HBc, HBV DNA, ALT, aspartate aminotransferase (AST), albumin (Alb), and LSM between the two groups. There were statistically significant differences in HBsAg, anti-HBc, and ALT levels before and after follow-up in the low HBsAg group, but no statistically significant differences in anti-HBe, HBV DNA, AST, Alb, and LSM levels. There were statistically significant differences in HBsAg and anti-HBc before and after follow-up in the high HBsAg group, but no statistically significant differences in anti-HBe, HBV DNA, ALT, AST, Alb, and LSM. A liver biopsy was performed in 66 patients during follow-up, and 27.27% of the patients had moderate liver damage. In the low HBsAg group, 45.76% of patients had a HBsAg decrease rate of ≥0.5 log10IU/ml, 10.17% of patients had HBV DNA negative conversion, 88.14% of patients had a persistently normal ALT, and 96.61% of patients had a persistently normal LSM at the end of follow-up. In the high HBsAg group, 3.75% of patients had a HBsAg decrease of ≥0.5 log10IU/ml, no patient had a HBV DNA negative conversion, 90% of patients had a persistently normal ALT, and 98.75% of patients had a persistently normal LSM. There were statistically significant differences in the HBsAg decrease rate (45.76% vs. 3.75%, χ2=32.975, P＜0.001) and HBV DNA negative conversion rate (10.17% vs. 0, χ2=6.219, P=0.013) between the two groups at the end of follow-up, but there were no statistically significant differences in the persistently normal ALT and LSM rates. Conclusion: The vast majority of patients with HBeAg-negative chronic HBV infection in the indeterminate phase with low viral load had persistent hypoviremia over the long term. Some patients have liver tissue damage and may progress to cirrhosis and liver cancer as a result of HBV DNA positivity, so antiviral treatment should be initiated in all.

Isorhamnetin Ameliorates Dopaminergic Neuronal Damage via Targeting FOSL1 to Activate AKT/mTOR in 6-OHDA-induced SH-SY5Y Cells.

Parkinson's disease (PD) is a chronic neurodegenerative disorder caused by loss of dopaminergic neurons in the substantia nigra compacta, which may result from mitochondrial dysfunction and oxidative stress. Isorhamnetin (Iso) has important anti-oxidative stress and anti-apoptotic effects, this study investigated the effects of Iso on PD in vitro and its underlying mechanisms using a model of 6-hydroxydopamine (6-OHDA)-induced SH-SY5Y cell damage. The results showed that Iso significantly ameliorated 6-OHDA-induced SH-SY5Y cell injury, including decreased cell viability, increased apoptosis and senescence, and oxidative stress injury. Senescence-associated β-galactosidase (SA-β) Staining, Western blot (WB) and immunofluorescence suggested that Iso significantly decreased the number of SA-β+ cells and the levels of senescence-associated proteins p21 and p16, and enhanced tyrosinehydroxylase level. Iso markedly reduced number of apoptotic cells and the levels of cleaved caspase-3 and BAX, as detected by CCK-8, flow cytometry and WB. The results of DCFH-DA, JC-1 staining, and the measurement of MDA and SOD content indicated that Iso elevated ROS generation and mitochondrial membrane potential, lowered MDA content and raised SOD level in the 6-OHDA group. In-depth investigation revealed that Iso activated the AKT/mTOR signal via reducing the expression level of Fos-like antigen (FOSL1), which further exerted the protective effect in SH-SY5Y cells. Overexpression of FOSL1 attenuated the effect of Iso by inhibiting the AKT/mTOR signaling pathway. Taken together, Iso protects against senescence, apoptotic, and oxidative stress injury by targeting FOSL1 to activate the AKT/ mTOR signaling pathway in 6-OHDA-induced SH-SY5Y cells, which may provide new insights for PD treatment.

Analysis of therapeutic effects and influencing factors of ICIs in lung-cancer patients.

The aim of this retrospective study was to analyze the efficacy and risk factors of immune checkpoint inhibitors (ICIs) in lung cancer patients. One hundred lung cancer patients who were treated in our hospital from May 2021 to May 2023 were selected as the study subjects and divided into chemotherapy group (n = 50) and ICIs group (n = 50), in which the chemotherapy group was given the combined treatment of vincristine and cisplatin (NP), while the ICIs group was given ICIs for treatment. The therapeutic effect and adverse reactions (hypertriglyceridemia, anemia, hypertension and hypoproteinemia) of the two groups were compared, and fasting venous blood was collected. The levels of carcinoembryonic antigen (CEA) and cancer antigen 199 (CA199) were compared between the two groups before and after treatment. According to the therapeutic effect, 100 patients with lung cancer were divided into complete remission (CR) + partial remission (PR) group (n = 52) and stable (SD) + progressive (PD) group (n = 48). The clinical data and pathologic data of the two groups were compared. The rates of objective effective rate (ORR) in chemotherapy group and ICIs group were 36.00% and 68.00% respectively, and the level of ORR in ICIs group was significantly higher than that in chemotherapy group, with statistical significance (P < 0.05). There was no significant difference in serum CEA and CA199 levels between the two groups before operation (P > 0.05). Three months after operation, the serum CEA and CA199 levels in ICIs group were significantly lower than those in chemotherapy group, and the difference was statistically significant (P < 0.05). The adverse reactions of hypertriglyceridemia, anemia, hypertension and hypoproteinemia in chemotherapy group and ICIs group during treatment were all grade 1-2, and the incidence of adverse reactions was similar between the two groups (P > 0.05). There was no significant difference in sex, age, anatomic position, pathologic type, smoking history and differentiation between the two groups (P > 0.05). In SD + PD group, the preoperative maximum tumor diameter > 4cm, tumor node metastasis (TNM) stage IV, lactate dehydrogenase (LDH) ≥ 183 U/L, and tumor volume ≥ 120m3 were significantly higher than those in CR + PR group, and the prognostic nutritional index (PNI) ≥ 41.8 and the proportion of ICIs were significantly lower than those in CR + PR group, with statistical significance (P < 0.05). Multifactorial logistic regression analysis showed that preoperative maximum tumor diameter > 4cm and LDH ≥ 183U/L were risk factors for poor lung cancer outcome, and PNI ≥ 41.8 and ICIs treatment were protective factors for poor lung cancer outcome (P < 0.05). ICIs is effective in the treatment of lung cancer, which can obviously reduce the tumor load and has high safety. In addition, the maximum tumor diameter and LDH are risk factors that affect the poor curative effect of lung cancer. High PNI level and ICIs treatment are helpful to improve the effect of lung cancer, and early monitoring is helpful to guide the treatment plan and evaluate the treatment effect.

Ablation of FAS confers allogeneic CD3- CAR T cells with resistance to rejection by T cells and natural killer cells.

Allogeneic chimaeric antigen receptor T cells (allo-CAR T cells) derived from healthy donors could provide rapid access to standardized and affordable batches of therapeutic cells if their rejection by the host's immune system is avoided. Here, by means of an in vivo genome-wide CRISPR knockout screen, we show that the deletion of Fas or B2m in allo- T cells increases their survival in immunocompetent mice. Human B2M- allo-CAR T cells become highly sensitive to rejection mediated by natural killer (NK) cells, whereas FAS- CAR T cells expressing normal levels of human leukocyte antigen I remain resistant to NK cells. CD3- FAS- CAR T cells outperformed CD3- B2M- CAR T cells in the control of leukaemia growth in mice under allogeneic pressure by T cells and NK cells. The partial protection of CD3- FAS- allo-CAR T cells from cellular rejection may improve the efficacy of allogeneic cellular therapies in patients with cancer.

Predictors of Recurrence After Curative Surgery for Stage I Colon Cancer: Retrospective Cohort Analysis of the Italian Society of Surgical Oncology Colorectal Cancer Network Collaborative Group

Objective: The aim of this study is to provide solid evidence to update the management of stage I colon cancer (CC) after surgery. Background: Given the low risk of recurrence of stage I CC, some international guidelines do not recommend intensive follow-up after surgery. However, data on the actual incidence, risk factors, and site of recurrences are scarce. Methods: This is a retrospective multicenter cohort study considering patients who underwent surgery at 25 Italian centers between 2010 and 2019, with a minimum follow-up of 24 months. A total of 1883 consecutive adult patients with stage I CC treated with curative surgery were considered, and 1611 fulfilled the inclusion criteria. The primary outcome was the rate of recurrence. Secondary outcomes included survival and risk factors for recurrence. Results: Eighty patients developed cancer recurrence (5.0%), of which 90% was systemic relapse. The event was more frequent in pT2 (6.0% vs 3.2%, P = 0.013), male patients (6.1% vs 3.6%, P = 0.021), in the presence of lymphovascular invasion (7.2% vs 3.6%, P = 0.01), and in cases of partial resection (11.1% vs 4.6%, P = 0.011). Also, preoperative carcinoembryonic antigen (P = 0.007) and tumor diameter (P &lt; 0.001) were higher in the group who relapsed. Most patients had isolated cancer recurrence (90%). Recurrences peaked between 10 and 18 months after surgery and declined over time. Adjusted Cox regression analysis identified tumor diameter, carcinoembryonic antigen level, lymphovascular invasion, male gender, and less than 12 analyzed lymph nodes as significant risk factors for worse recurrence-free survival. Conclusions: This study showed that a not negligible rate of stage I CC recur after curative surgery. Most relapses occur at a single site within the first 3 years after surgery. This evidence could be used to optimize postoperative follow-up.

Proportion of Gleason Score ≥8 Prostate Cancer on Biopsy and Tumor Aggressiveness in Matched Cohorts of East Asian and Non-East Asian Men.

Historically, Asia had a lower prostate cancer (PCa) incidence and mortality compared with Western countries, but the gap is narrowing. Paradoxically, Asians have been reported to present with more advanced disease though more favorable outcomes. Despite PCa becoming an emerging health priority in East Asia, our knowledge remains limited. We compared the prevalence of high-grade PCa on biopsy and disease progression after radical prostatectomy (RP) in East Asian men from Asia and non-East Asian men from Western countries. This retrospective cohort study included men who underwent prostate biopsy and RP at academic centers in Shanghai, China, and Toronto, Canada (2014-2019). The expanded RP cohort included East Asian men from Singapore (n=282) and non-East Asians from Paris (n=192). Primary endpoints included the proportion of men with Gleason score (GS) ≥8 on biopsy and metastasis-free survival (MFS) after RP for GS ≥8. Multivariable logistic regression and Cox proportional hazard models were performed. Propensity score matching was used to reduce imbalances between cohorts. PCa was found on biopsy in 2,343 of 4,905 (48%) East Asians and 2,317 of 3,482 (67%) non-East Asians (P<.001). Prostate-specific antigen (PSA) levels at presentation and the proportion of men with GS ≥8 were higher in East Asians than non-East Asians (12.4 vs 6.6 ng/mL and 15.0% vs 8.8%, respectively; both P<.001). On multivariable analysis, there was no difference in the proportion of men with GS ≥8 between matched cohorts with PSA <20 ng/mL (n=3,572; odds ratio, 1.05 [95% CI, 0.77-1.43]; P=.76). No difference in MFS was found after RP between matched cohorts (hazard ratio, 0.97 [95% CI, 0.55-1.70]; P=.92). This contemporary study demonstrates that East Asian men are equally as likely to harbor aggressive PCa on biopsy as non-East Asian men at PSA levels observed in screening programs, with no difference in disease aggressiveness after RP. The assumption that unfavorable PCa at diagnosis is more common but less aggressive in East Asians should be revisited and viewed in the context of the expected increase in the PCa burden worldwide.

Observations of the effectiveness, dosage, and prognosis of intensity-modulated radiation therapy under ultrasonic guidance for cervical cancer patients.

Volumetric modulated arc therapy (VMAT) guided by ultrasound is a novel radiation therapy technique that facilitates the delineation of the tumor target area under image guidance, enhancing the precision of radiation therapy and maximizing the protection of surrounding tissues. The objective of this paper is to investigate the effectiveness of VMAT under ultrasonic guidance for cervical cancer patients and its impact on radiotherapy dosage and prognosis. A retrospective analysis encompassed 128 instances of cervical cancer patients who were admitted to our medical facility between April 2019 and April 2021. The patients were categorized into an observation cohort and a control cohort, depending on variations in treatment modalities post-admission. The control group underwent conventional radiotherapy, whereas the observation group received VMAT guided by ultrasound. Clinical efficacy, average radiation dosages (in the radiotherapy target area, rectum, and bladder), radiotherapy-related toxicities during treatment, and one-year survival rates were compared between the two groups. Additionally, variances in pre- and post-treatment serum levels of squamous cell carcinoma antigen (SCC-Ag), carcinoembryonic antigen (CEA), and carbohydrate antigen 724 (CA724) were subjected to assessment. When compared to the control group (64.52%), the observation cohort's comprehensive effectiveness rate was considerably greater (80.30%). The observation group saw lower average radiation exposures and a reduction in the post-treatment concentrations of CEA, SCC-Ag, and CA724. The overall incidence of adverse effects from radiation treatment also declined. The observation group had a greater one-year survival rate (90.48%) than the control group (73.33%). When comparing the observation cohort to the control group, Kaplan-Meier survival analysis showed a significantly higher one-year survival rate (Log-Rank = 6.530, P= 0.011). VMAT guided by ultrasound for patients with cervical cancer demonstrates promising short- and long-term treatment outcomes. It also leads to improvements in serum CEA, SCC-Ag, and CA724 levels, as well as reductions in the average radiation dosages to the radiotherapy target area, rectum, and bladder. This approach warrants attention from clinicians in clinical practice.

Structure-Activity Relationships and Discovery of (S)-5-(tert-Butyl)-11-(difluoromethoxy)-9-methoxy-2-oxo-1,2,5,6-tetrahydropyrido[2',1':2,3]imidazo[4,5-h]quinoline-3-carboxylic Acid (AB-161), a Novel Orally Available and Liver-Centric HBV RNA Destabilizer.

Lowering hepatitis B surface antigen (HBsAg) levels from covalently closed circular DNA (cccDNA) and the integrated genome could reduce the persistence of hepatitis B virus (HBV) infection. Since HBV replication occurs in the liver and to ameliorate the peripheral neuropathy observed with a first-generation tricyclic 4-pyridone PAPD5/7 inhibitor (AB-452) having high systemic exposure, we focused on increasing the hepatocyte concentration and reducing plasma levels. Optimization of a novel series of PAPD5/7 inhibitors that decrease HBsAg levels led to the tetracyclic 2-pyridone AB-161, which was similarly potent to AB-452 in vitro and in vivo but showed dramatically higher rodent liver-to-plasma ratios. There were no neurobehavioral effects with AB-161 in dogs up to 45 mg/kg after 60 days, unlike with AB-452, where these were observed at lower doses by day 14. AB-161 was then advanced into 90-day GLP toxicology studies, where the improved neurotoxicity profile persisted, but reproductive issues emerged, leading to discontinuation.