Specific Antigen Research Articles

Non-Small Cell Lung Cancer Metastatic Without Oncogenic Alterations.

This overview provides a thorough review of current treatment approaches for first-line management of nononcogenic addicted non-small cell lung cancer. We also address pertinent clinical decision-making queries encountered in everyday practice, such as the optimal treatment strategy for PD-L1-high patients, predictive factors for response to immune checkpoint inhibitors (ICI) both in terms of patient and cancer characteristics, the potential benefits of dual checkpoint blockade, and the unresolved issue of safe discontinuation strategies for long-term responders. Around one in five patients falls into this latter category while the majority develop either primary or acquired resistance to ICI-based first-line therapy, necessitating effective subsequent lines of treatment. Docetaxel, with or without combination of antiangiogenic agents, serves as the backbone of treatment, although evidence in the post-ICI setting is limited. Given that an inflamed tumor microenvironment (TME) is crucial for ICI responses, targeting the TME in cases of acquired resistance alongside continued ICI administration appears rational, although clinical trials so far have failed to confirm this hypothesis. Antibody-drug conjugates have emerged as a promising treatment modality, offering the potential for reduced toxicity and improved efficacy by targeting specific cancer antigens. Moreover, several chemotherapy-free approaches are currently under investigation for treatment-naïve patients, including alternative ICI and drugs targeting epitopes on both cancer and immune cells.

Focal high-intensity focused ultrasound therapy for localized prostate cancer: An interim analysis of the multinational FASST study.

High-intensity focused ultrasound (HIFU) emerged as a novel approach for the treatment of localized prostate cancer (PCa). However, prospective studies on HIFU-related outcomes and predictors of treatment failure (TF) remain scarce. We conducted a multinational prospective cohort study among patients undergoing HIFU therapy for localized, low- to intermediate-risk PCa. Follow-up data on serial prostate specific antigen (PSA), multi-parametric magnetic resonance imaging (mpMRI), targeted/systematic biopsies, adverse events and functional outcomes were collected. The primary endpoint was TF, defined as histologically confirmed PCa requiring whole-gland salvage treatment. Uni- and multi-variable adjusted hazard ratios (HRs) were calculated using Cox proportional hazard regression models. At baseline, mean (standard deviation) age was 64.14 (7.19) years, with the majority of patients showing T-stage 1 (73.9%) and International Society of Urological Pathology grading system Grade 2 (58.8%). PSA nadir (median, 1.70 ng/mL) was reached after 6 months. Of all patients recruited, 16% had clinically significant PCa, as confirmed by biopsy, of which 13.4% had TF. Notably, T-stage and number of positive cores at initial biopsy were independent predictors of TF during follow-up (HR [95% CI] 1.27 [1.02-1.59] and 5.02 [1.80-14.03], respectively). Adverse events were minimal (17% and 8% early and late adverse events, respectively), with stable or improved functional outcomes in the majority of patients. This interim analysis of a multinational study on HIFU therapy for the management of low-to-intermediate-risk PCa reveals good functional outcomes, minimal adverse events and low incidence of TF over the short-term. Data on long-term outcomes, specifically as it relates to oncological outcomes, are awaited eagerly.

Do domain-specific protein language models outperform general models on immunology-related tasks?

Deciphering the antigen recognition capabilities by T-cell and B-cell receptors (antibodies) is essential for advancing our understanding of adaptive immune system responses. In recent years, the development of protein language models (PLMs) has facilitated the development of bioinformatic pipelines where complex amino acid sequences are transformed into vectorized embeddings, which are then applied to a range of downstream analytical tasks. With their success, we have witnessed the emergence of domain-specific PLMs tailored to specific proteins, such as immune receptors. Domain-specific models are often assumed to possess enhanced representation capabilities for targeted applications, however, this assumption has not been thoroughly evaluated. In this manuscript, we assess the efficacy of both generalist and domain-specific transformer-based embeddings in characterizing B and T-cell receptors. Specifically, we assess the accuracy of models that leverage these embeddings to predict antigen specificity and elucidate the evolutionary changes that B cells undergo during an immune response. We demonstrate that the prevailing notion of domain-specific models outperforming general models requires a more nuanced examination. We also observe remarkable differences between generalist and domain-specific PLMs, not only in terms of performance but also in the manner they encode information. Finally, we observe that the choice of the size and the embedding layer in PLMs are essential model hyperparameters in different tasks. Overall, our analyzes reveal the promising potential of PLMs in modeling protein function while providing insights into their information-handling capabilities. We also discuss the crucial factors that should be taken into account when selecting a PLM tailored to a particular task.

Sub-acute studies on the effects of trona consumption at varied low doses on male fertility and antioxidant properties using Wistar Rats

Geologically known as trona, evaporite, or locally known as greyish potash, akanwu, or kaun, it serves a multitude of purposes in Nigeria. These include, but are not limited to, softening legumes and flesh, augmenting the therapeutic attributes of herbal expectorant remedies, and reducing male libido or fertility. The unrestricted consumption and accessibility of this salt in the local markets of Anambra State, Nigeria, are due to its affordability and accessibility. Currently, there is no investigation into the comprehensive impact of potash's antioxidant properties at various low doses on male fertility. This led to a study that lasted for 28 days and involved rats weighing between 120 g and 140 g. The rats were separated into four groups, with each group consisting of seven rats. Group A was the control group, while groups B, C, and D were the test groups administered doses of 150 mg/kg, 300 mg/kg, and 450 mg/kg of potash, respectively. At the end of the study, the antioxidant properties of potash were tested. Prostate, gland, testis, and blood were collected and analyzed. Data was analyzed with the statistical social science (SPSS) version 27. Results were presented as mean ± standard deviation (SD). A one-way analysis of variance (ANOVA) was used to compare the mean values. Our study found a significant (p<0.05) dose dependent decrease in fertility hormones and semen parameters. Prostate specific antigen (PSA) increased dose-dependently compared to the control. Our findings indicate that trona is rich in antioxidants.

Resolution of RHCE Haplotype Ambiguities in Transfusion Settings

Red blood cell (RBC) transfusion, limited by patient alloimmunization, demands accurate blood group typing. The Rh system requires specific attention due to the limitations of serological phenotyping methods. Although these have been compensated for by molecular biology solutions, some RhCE ambiguities remain unresolved. The RHCE mRNA length is compatible with full-length analysis and haplotype discrimination, but the RHCE mRNA analyses reported so far are based on reticulocyte isolation and molecular biology protocols that are fastidious to implement in a routine context. We aim to present the most efficient reticulocyte isolation method, combined with an RT-PCR sequencing protocol that embraces the phasing of all haplotype configurations and identification of any allele. Two protocols were tested for reticulocyte isolation based either on their size/density properties or on their specific antigenicity. We show that the reticulocyte sorting method by antigen specificity from EDTA blood samples collected up to 48 h before processing is the most efficient and that the combination of an RHCE-specific RT-PCR followed by RHCE allele-specific sequencing enables analysis of cDNA RHCE haplotypes. All samples analyzed show full concordance between RHCE phenotype and haplotype sequencing. Two samples from the immunohematology laboratory with ambiguous results were successfully analyzed and resolved, one of them displaying a novel RHCE allele (RHCE*03 c.340C>T).

#1305 Analysis of clinicopathological characteristics of membranous nephropathy with concomitant malignancy and literature review

Abstract Background and Aims In recent years, the incidence of membranous nephropathy (MN) with malignancy has gradually increased, but the clinical and pathological characteristics of these patients are still unclear. Method Patients diagnosed with renal biopsy-proven MN and comorbid malignancy detected within 5 years before and after MN diagnosis were included. The control group were diagnosed with renal biopsy-proven IMN with no malignancy and no other clear secondary cause for MN. We present a comprehensive analysis of MN with concomitant malignancy in our cohort and literature review. Results A total of 19 MN patients with concomitant malignancy were evaluated at our center; among them, 13 (68.4%) were male, and the median age was 57.0 (45.0, 69.0) years. Malignancy occurred after the onset of renal disease in 61.1% of patients, with digestive system malignancy (36.8%) ranking as the predominant type. 8 (8/11) patients achieved either PR or CR during the follow-up period. Most patients had pathology typical of IMN. IF showed strong positivity for IgG (100%), whereas only 13 (68.4%) patients were positive for C3. IEM showed electron-dense deposits predominantly located in subepithelial. Specific MN antigen staining of renal tissues from 19 patients showed that the highest percentage was 68.4% (13/19) for PLA2R-only positivity followed by 15.8% (3/19) for THSD7A-only positivity. Specific MN antigen staining of malignant tissue was performed in 5 patients whose tumor samples were available. Only 2 patients expressed the same antigen on kidney and tumor. Screening 17 articles encompassing a total of 21 patients in whom MN-specific antigen staining was performed on both renal and tumor tissues simultaneously. Among these patients, 71.4% (15/21) were male, with a median age of 61.0 years (56.3, 72.8). In this cohort, malignancy was diagnosed before or simultaneously with MN in 15 patients (75.0%), with digestive system malignancy constituting the most prevalent comorbid malignancy, at 33.3%. Notably, THSD7A accounted for the highest proportion of MN antigens, at 66.7% (14/21); among these patients, 78.6% (11/14) also exhibited positive tumor THSD7A staining. Of the 21 patients, 72.2% (13/18) achieved CR or PR. No significant difference between the baseline characteristics was observed between the 19 patients from our center and 21 patients documented in the literature. Therefore, the clinicopathological data of these 40 patients were pooled and compared with 101 IMN patients without malignancy at our center. Compared to patients without malignancy, MN patients with malignancy were older at the time of renal biopsy (P = 0.017), had a lower eGFR (P = 0.035) and demonstrated a lower rate of CR or PR after treatment (P < 0.001). The rate of PLA2R positivity in the glomeruli of MN patients with concomitant malignancy was significantly lower (40.0% vs. 92.1%, P < 0.001), while the rate of THSD7A positivity was significantly higher (42.5% vs. 2.0%, P < 0.001). Renal tissue IgG subclass staining showed that the rate of IgG4 positivity was significantly decreased compared with that in IMN patients (59.3% vs. 90.1%, P < 0.001), and the rate of IgG2 positivity was significantly increased (36.0% vs. 16.5%, P = 0.033). Conclusion To conclude, malignancy screening should be more actively performed for MN patients presenting with the above characteristics.

#710 Rare manifestation of minimal change disease associated with prostate cancer

Abstract Background and Aims Prostate cancer is the most common malignancy in men. Secondary nephrotic syndrome as part of the paraneoplastic syndrome occurs in 11% of cases and is most often associated with membranous glomerulopathy. The association of minimal change disease (MCD) and prostate cancer is extremely rare, where only one case has been described in the available literature. Method We present the case of a 77-year-old patient who was admitted to the Transplantation-Nephrology Department of the University Hospital Martin with 3rd degree acute kidney injury and anasarca with fully developed nephrotic syndrome. Results During hospitalization, there was a gradual elevation of renal parameters and oliguria with the need for hemodialysis treatment. However, as part of the oncological screening, the level of prostate specific antigen was elevated (10.69 ng/l) with subsequent biopsy confirmed adenocarcinoma of the prostate in stage IIB (pT1cN0M0). Renal biopsy was performed with the finding of MCD, in light microscopy without pathological findings, with fully vital, normocellular glomeruli, without interstitial fibrosis and tubular damage, immunofluorescence without significant findings, in the electron microscope, pedicel podocyte fusions were present. Despite the generally valid recommendations for the treatment of prostate cancer of the given stage and age of the patient (follow-up), antiandrogen therapy was started in cooperation with the urologist along with the treatment of MCD with corticosteroids at a dose of 1 mg/kg. The patient experienced a significant improvement in renal parameters with the onset of diuresis without the need for dialysis treatment. Conclusion In the reported case, we describe a rare form of MCD associated with prostate cancer and a rare manifestation in the form of renal failure and the need for dialysis treatment with subsequent complete restitution of renal functions after KS treatment and antiandrogen treatment of the underlying oncological disease.

The effect of unusual presentation on delayed diagnosis of prostate cancer: a case series

BackgroundEarly diagnosis of prostate cancer is key to achieving a cure and its proper management leads to a good prognosis. In Ghana a large percentage of patients present with advanced disease and unusual presentations in these patients result in greater delay in the diagnosis thus worsening the outcomes.Case presentationWe present three African males with advanced prostate cancer who had delayed diagnosis. The first patient, a 64 year old male presented with ascites of 2 years duration with weight loss and no lower urinary tract symptoms, the second, a 69 year old man with end stage renal failure of 6 months duration and was receiving dialysis, the third case, an 87 year old man was managed for pulmonary tuberculosis after he presented with chronic cough and lower urinary tract symptoms. All patients eventually had a prostate specific antigen done which were elevated. Further investigations including prostate biopsies, abdominopelvic CT scans for case 1, abdominopelvic ultrasound, prostate biopsies and blood urea and electrolytes for case 2, prostate biopsies, chest and lumbosacral showed a diagnosis of metastatic prostate carcinoma, and all patients were managed with androgen deprivation. The second patient received additional radiotherapy.ConclusionA lack of knowledge of prostate cancer symptoms including unusual symptoms, can result in delayed diagnosis especially in regions of the world where a large number of patients present with advanced disease.

Epigenetics Meets CAR-T-Cell Therapy to Fight Cancer.

Based on the impressive success of Car-T-cell therapy in the treatment of hematological malignancies, a broad application for solid tumors also appears promising. However, some important hurdles need to be overcome. One of these is certainly the identification of specific target antigens on cancer cells. Hypomethylation is a characteristic epigenetic aberration in many tumor entities. Genome-wide screenings for consistent DNA hypomethylations in tumors enable the identification of aberrantly upregulated transcripts, which might result in cell surface proteins. Thus, this approach provides a new perspective for the discovery of potential new Car-T-cell target antigens for almost every tumor entity. First, we focus on this approach as a possible treatment for prostate cancer.

Adverse events associated with chimeric antigen receptor T-Cell therapy in ophthalmology: a narrative review

Chimeric antigen receptors are synthetically produced receptors engineered to engage with target cells with high specificity. These cells are created by inserting an artificial T-cell receptor into an immunoglobulin’s antigen-binding region, allowing the cells to combine and target specific antigens. The use of chimeric antigen receptor (CAR) T-cell therapy has been a remarkable achievement in the field of immunotherapy, particularly in the treatment of ophthalmic tumors like retinoblastoma and uveal melanoma. However, there are some documented side effects, such as cytokine release syndrome (CRS) and immunological effector cell-associated neurotoxicity syndrome (ICANS). Additionally, ocular side effects such as blurred vision, vision impairment, and intraocular infections are also concerning and require further evaluation. This review highlights the advances made in chimeric antigen receptor (CAR) immunotherapy, including its structure and manufacture, as well as relevant clinical discoveries and associated adverse effects. By identifying the gaps in current research, this analysis provides insights into potential strategies and solutions for addressing some of the most severe side effects.

Prostate Specific Membrane Antigen Expression in a Syngeneic Breast Cancer Mouse Model.

Prostate specific membrane antigen (PSMA) has been studied in human breast cancer (BCa) biopsies, however, lack of data on PSMA expression in mouse models impedes development of PSMA-targeted therapies, particularly in improving breast conserving surgery (BCS) margins. This study aimed to validate and characterize the expression of PSMA in murine BCa models, demonstrating that PSMA can be utilized to improve therapies and imaging techniques. Murine triple negative breast cancer 4T1 cells, and human cell lines, MDA-MB-231, MDA-MB-468, implanted into the mammary fat pads of BALB/c mice, were imaged by our PSMA targeted theranostic agent, PSMA-1-Pc413, and tumor to background ratios (TBR) were calculated to validate selective uptake. Immunohistochemistry was used to correlate PSMA expression in relation to CD31, an endothelial cell biomarker highlighting neovasculature. PSMA expression was also quantified by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR). Accumulation of PSMA-1-Pc413 was observed in 4T1 primary tumors and associated metastases. Average TBR of 4T1 tumors were calculated to be greater than 1.5-ratio at which tumor tissues can be distinguished from normal structures-at peak accumulation with the signal intensity in 4T1 tumors comparable to that in high PSMA expressing PC3-pip tumors. Extraction of 4T1 tumors and lung metastases followed by RT-PCR analysis and PSMA-CD31 co-staining shows that PSMA is consistently localized on tumor neovasculature with no expression in tumor cells and surrounding normal tissues. The selective uptake of PSMA-1-Pc413 in these cancer tissues as well as the characterization and validation of PSMA expression on neovasculature in this syngeneic 4T1 model emphasizes their potential for advancements in targeted therapies and imaging techniques for BCa. PSMA holds great promise as an oncogenic target for BCa and its associated metastases.

Immunoglobulin constant regions provide stabilization to the paratope and enforce epitope specificity.

Constant domains in antibody molecules at the level of the Fab (CH1 and CL) have long been considered to be simple scaffolding elements that physically separate the paratope-defining variable (V) region from the effector function-mediating constant (C) regions. However, due to recent findings that C domains of different isotypes can modulate the fine specificity encoded in the V region, elucidating the role of C domains in shaping the paratope and influencing specificity is a critical area of interest. To dissect the relative contributions of each C domain to this phenomenon, we generated antibody fragments with different C regions omitted, using a set of antibodies targeting capsular polysaccharide from the fungal pathogen, Cryptococcus neoformans. Antigen specificity mapping and functional activity measurements revealed that V region-only antibody fragments exhibited poly-specificity to antigenic variants and extending to recognition of self-antigens, while measurable hydrolytic activity of the capsule was greatly attenuated. To better understand the mechanistic origins of the remarkable loss of specificity that accompanies the removal of C domains from identical paratopes, we performed molecular dynamics simulations which revealed increased paratope plasticity in the scFv relative to the corresponding Fab. Together, our results and provide insight into how the remarkable specificity of immunoglobulins is governed and maintained at the level of the Fab through the enforcement of structural restrictions on the paratope by CH1 domains.

Does enzalutamide related PSMA upregulation affect outcomes of lutetium-177 PSMA radioligand therapy?

Enzalutamide is an antiandrogen drug used prior to lutetium-177 prostate specific membrane antigen (Lu-PSMA) radioligand therapy and has shown promising results for upregulating the PSMA expression on prostate cancer cells. In this study, we aim to compare prostate specific antigen (PSA) level changes in prostate cancer patients who received enzalutamide to those who did not. Prostate cancer patients who underwent Lu-PSMA between 2021 and 2023 were retrospectively included. Patients were grouped based on prior enzalutamide therapy: those who received enzalutamide (EZ+) for at least 14 days and those who did not (EZ-). PSA changes and F-18 DCFPyL SUV (Standardized Uptake Values) were compared. Thirty-seven patients were included, 18 EZ+ and 19 EZ-. The median age, Gleason score, and prior chemo/hormonal therapies were similar for EZ+ and EZ-, except for radium-223. Eleven patients (61%) in EZ+ and 13 patients (68%) in EZ- showed a decrease in PSA after the first cycle (p = 0.64). Four patients (22%) in EZ+ and seven patients (37%) in EZ- had more than 50% decrease in PSA after the first cycle (p = 0.33). The average percent decline at the end of the treatment was 23.3% in EZ+ and 50.4% in EZ- (p = 0.4). There was no difference in terms of lesion with highest SUVmax, mean SUV, total tumor volume or activity on pre-therapy PSMA imaging. Enzalutamide treatment prior to Lu-PSMA does not improve patient outcomes when applied remotely. Larger studies evaluating the combination therapies and the timing of enzalutamide are needed to assess its correlation with Lu-PSMA outcomes.

Prediction of Paratope-Epitope Pairs Using Convolutional Neural Networks.

Antibodies play a central role in the adaptive immune response of vertebrates through the specific recognition of exogenous or endogenous antigens. The rational design of antibodies has a wide range of biotechnological and medical applications, such as in disease diagnosis and treatment. However, there are currently no reliable methods for predicting the antibodies that recognize a specific antigen region (or epitope) and, conversely, epitopes that recognize the binding region of a given antibody (or paratope). To fill this gap, we developed ImaPEp, a machine learning-based tool for predicting the binding probability of paratope-epitope pairs, where the epitope and paratope patches were simplified into interacting two-dimensional patches, which were colored according to the values of selected features, and pixelated. The specific recognition of an epitope image by a paratope image was achieved by using a convolutional neural network-based model, which was trained on a set of two-dimensional paratope-epitope images derived from experimental structures of antibody-antigen complexes. Our method achieves good performances in terms of cross-validation with a balanced accuracy of 0.8. Finally, we showcase examples of application of ImaPep, including extensive screening of large libraries to identify paratope candidates that bind to a selected epitope, and rescoring and refining antibody-antigen docking poses.

Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography-Derived Radiomic Models in Prostate Cancer Prognostication.

The clinical integration of prostate membrane specific antigen (PSMA) positron emission tomography and computed tomography (PET/CT) scans represents potential for advanced data analysis techniques in prostate cancer (PC) prognostication. Among these tools is the use of radiomics, a computer-based method of extracting and quantitatively analyzing subvisual features in medical imaging. Within this context, the present review seeks to summarize the current literature on the use of PSMA PET/CT-derived radiomics in PC risk stratification. A stepwise literature search of publications from 2017 to 2023 was performed. Of 23 articles on PSMA PET/CT-derived prostate radiomics, PC diagnosis, prediction of biopsy Gleason score (GS), prediction of adverse pathology, and treatment outcomes were the primary endpoints of 4 (17.4%), 5 (21.7%), 7 (30.4%), and 7 (30.4%) studies, respectively. In predicting PC diagnosis, PSMA PET/CT-derived models performed well, with receiver operator characteristic curve area under the curve (ROC-AUC) values of 0.85-0.925. Similarly, in the prediction of biopsy and surgical pathology results, ROC-AUC values had ranges of 0.719-0.84 and 0.84-0.95, respectively. Finally, prediction of recurrence, progression, or survival following treatment was explored in nine studies, with ROC-AUC ranging 0.698-0.90. Of the 23 studies included in this review, 2 (8.7%) included external validation. While explorations of PSMA PET/CT-derived radiomic models are immature in follow-up and experience, these results represent great potential for future investigation and exploration. Prior to consideration for clinical use, however, rigorous validation in feature reproducibility and biologic validation of radiomic signatures must be prioritized.

Ultrasensitive Detection of Prostate Specific Antigen by an Unlabeled Fluorescence Aptasensor Based on the AIE Effect.

The accurate and sensitive detection of prostate specific antigen (PSA) is vital for the early diagnosis and treatment of prostate cancer. To this end, an unlabeled fluorescent aptasensor was constructed by using a novel Compound B {1,1'-(1,4-phenylene) bis(3-ethyl-1H-imidazol-3-ium) iodide} with aggregation-induced emission (AIE) activity as a fluorescence signal and NH2-Fe3O4 particle as an adsorption platform. Compound B could combine with prostate specific antigen aptamers (PSA-Apt) to form a PSA-Apt/B complex, which further generated the AIE effect. Then, PSA was added to the PSA-Apt/B solution. PSA combined with PSA-Apt/B to form the PSA-Apt/B/PSA complex. Next, NH2-Fe3O4 magnetic particles were added to the solution. Given that PSA-Apt/B/PSA would no longer combine with NH2-Fe3O4 magnetic particles, the PSA-Apt/B/PSA complex remained in the supernate after magnet separation, and the supernate showed strong fluorescence (I). When no PSA was added to the PSA-Apt/B solution, PSA-Apt/B could combine with NH2-Fe3O4 magnetic particles and would be sucked into the bottom of the test tube by magnet, and the supernate would show weak fluorescence (I0). Result showed that the difference between the above-mentioned two fluorescence values (∆I = I - I0) had an excellent linear relationship with the PSA concentration within the concentration range of 0.01-10ng/mL, and its limit of detection was 3pg/mL (S/N = 3). In addition, the sensor has high accuracy and can be directly used to test PSA in actual serum samples.

A novel model incorporating quantitative contrast-enhanced ultrasound into PI-RADSv2-based nomogram detecting clinically significant prostate cancer

The diagnostic accuracy of clinically significant prostate cancer (csPCa) of Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) is limited by subjectivity in result interpretation and the false positive results from certain similar anatomic structures. We aimed to establish a new model combining quantitative contrast-enhanced ultrasound, PI-RADSv2, clinical parameters to optimize the PI-RADSv2-based model. The analysis was conducted based on a data set of 151 patients from 2019 to 2022, multiple regression analysis showed that prostate specific antigen density, age, PI-RADSv2, quantitative parameters (rush time, wash-out area under the curve) were independent predictors. Based on these predictors, we established a new predictive model, the AUCs of the model were 0.910 and 0.879 in training and validation cohort, which were higher than those of PI-RADSv2-based model (0.865 and 0.821 in training and validation cohort). Net Reclassification Index analysis indicated that the new predictive model improved the classification of patients. Decision curve analysis showed that in most risk probabilities, the new predictive model improved the clinical utility of PI-RADSv2-based model. Generally, this new predictive model showed that quantitative parameters from contrast enhanced ultrasound could help to improve the diagnostic performance of PI-RADSv2 based model in detecting csPCa.

The impact of monoclonal antibodies in preventing antimicrobial resistance (AMR)

Monoclonal antibodies (mAbs) have transformed modern medicine through precision targeting and therapeutic efficacy. This summary summarises the development, applications, and comparative characteristics of mAbs in the context of antiviral medicines and antibiotic treatment durations. Monoclonal antibodies are designed to target specific antigens with great affinity and specificity, making them important for diagnostics and treatments. Anti-virulence mAbs, a type of mAb, target pathogen virulence factors rather than pathogens themselves, providing a promising technique for combating infectious diseases while limiting resistance development. When comparing the duration of antibiotic medication versus mAb treatment, mAbs frequently provide a shorter and more tailored therapeutic regimen. This can lead to better patient outcomes, less resistance, and a lower risk of side effects associated with long-term antibiotic usage. Antigen selection, hybridoma creation, antibody synthesis, purification, and characterization are all steps in the mAb development process, with advances like recombinant DNA technology improving efficiency and scalability.

Imaging and therapy in prostate cancer using PSMA radioligands.

Prostate specific membrane antigen (PSMA)-directed PET imaging has rapidly transformed prostate cancer workup over the past decade and paved the way for a theranostic approach using 177Lu-labelled PSMA radioligand therapy. This review gives an overview of the underlying principles behind PSMA as a target; the current use of PSMA PET in prostate cancer imaging and benefits compared to conventional imaging; and therapeutic applications including optimisation of patient selection. It also explores the evidence base of PSMA PET for other indications not in routine clinical use and the future of PSMA-directed radioligand therapy.

A phase 2, single-arm trial evaluating 131I-PSMA-1095 targeted radioligand therapy for metastatic castration-resistant prostate cancer.

Metastatic castration-resistant prostate cancer (mCRPC) remains uniformly lethal. Prostate specific membrane antigen (PSMA) is a transmembrane glycoprotein overexpressed in prostate cancer. 131I-PSMA-1095 (also known as 131I-MIP-1095) is a PSMA-targeted radioligand which selectively delivers therapeutic radiation to cancer cells and the tumor microenvironment. We conducted a single-arm, phase 2 trial to assess efficacy and tolerability of 131I-PSMA-1095 in mCRPC patients who had exhausted all lines of approved therapy. All patients underwent 18F-DCFPyL PET and 18F-FDG PET to determine PSMA-positive tumor volume, and patients with >50% PSMA-positive tumor volume were treated with up to four doses of 131I-PSMA-1095. The primary endpoint was the response rate of prostate specific antigen (PSA). Secondary endpoints included rates of radiographic response and adverse events. Overall and radiographic progression-free survival were also analyzed. Eleven patients were screened for inclusion and nine patients received 131I-PSMA-1095. The median baseline PSA was 162 µg/l, and six patients demonstrated a >50% PSA decrease. One patient demonstrated a confirmed radiographic response. Median overall survival was 10.3 months, and median progression-free survival was 5.4 months. Four patients experienced adverse events of grade 3 or higher, the most frequent being thrombocytopenia and anemia. 131I-PSMA-1095 is highly active against heavily-pretreated PSMA-positive mCRPC, significantly decreasing tumor burden as measured by PSA. Adverse events, mainly hematologic toxicity, were not infrequent, likely related to off-target irradiation. This hematologic toxicity, as well as a higher logistical burden associated with use, could represent relative disadvantages of 131I-PSMA-1095 compared to 177Lu-PSMA-617.