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  • 1
    Online Resource
    Online Resource
    Immunotherapy Applications for Thymine Dimers and WT1 Antigen in Renal Cancers: A Comparative Statistical Analysis
    MDPI AG ; 2024
    In:  Journal of Personalized Medicine Vol. 14, No. 6 ( 2024-05-23), p. 557-
    Details
    In: Journal of Personalized Medicine, MDPI AG, Vol. 14, No. 6 ( 2024-05-23), p. 557-
    Abstract: Renal cell carcinoma (RCC) remains incurable in advanced stages. Biomarkers have proven to be quite useful in cancer therapeutics. Herein, we provide a comparative/integrative statistical analysis of seminal immunohistochemistry (IHC) findings for Wilms’ Tumor 1 antigen (WT1) and thymine dimers (TDs), emerging as atypical, yet promising, potential biomarkers for RCCs. We assessed WT1/TD reactivity in adult RCC tumor cells, tumor microenvironment (TME), and tumor-adjacent healthy renal tissue (HRT). WT1 positivity was scarce and strictly nuclear in tumor cells, whereas TD-reactive tumor tissues were prevalent. We report statistically significant positive correlations between the density of reactive RCC cellularity and the intensity of nuclear staining for both biomarkers (WT1 − rho = 0.341, p-value = 0.036; TDs − rho = 0.379, p-value = 0.002). RCC stromal TME TD-positivity was much more frequent than WT1 reactivity, apparently proportional to that of the proper RCC cellularity and facilitated by extensive RCC inflammatory infiltration. TDs exhibited nuclear reactivity for most TME cell lines, while RCC TME WT1 expression was rare and inconsistent. In HRTs, TDs were entirely restricted to renal tubular cells, the likely cellular progenitor of most conventional RCC subtypes. In lieu of proper validation, these early findings have significant implications regarding the origins/biology of RCCs and may inform RCC therapeutics, both accounting for the high frequency of immunotherapy-permissive frameshift indels in RCCs, but also hinting at novel predictive clinical tools for WT1-targeted immunotherapy. Overall, the current study represents a meek yet hopefully significant step towards understanding the molecular biology and potential therapeutic targets of RCCs.
    Type of Medium: Online Resource
    ISSN: 2075-4426
    URL: Article
    DOI: 10.3390/jpm14060557
    Language: English
    Publisher: MDPI AG
    Publication Date: 2024
    detail.hit.zdb_id: 2662248-8
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  • 2
    Online Resource
    Online Resource
    Surgical Strategies for Renal Transplantation: A Pictorial Essay
    MDPI AG ; 2024
    In:  Journal of Clinical Medicine Vol. 13, No. 14 ( 2024-07-17), p. 4188-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 13, No. 14 ( 2024-07-17), p. 4188-
    Abstract: This pictorial essay aims to navigate through the complexities and challenges of renal transplantation (RT), by weaving together visual imagery with clinical insights within a comprehensive illustrative surgical guide. Herein, we provide a detailed visual exploration of the intricate anatomy and surgical processes necessary for both renal graft retrieval from the donor and also for an adequate implantation in the recipient. Regarding graft retrieval, after reviewing the relevant retroperitoneal surgical anatomy, and donor nephrectomy techniques, graft preservation and optimal backbench graft dissection principles were meticulously analyzed. Thereafter, the recipient surgical strategy for graft implantation was addressed, focusing on preoperative preparations, the site of implantation selection, exposure, operative bed dissection, graft revascularization, and urinary tract reconstruction. Careful donor and recipient selection, meticulous surgical execution, and rigorous postoperative management clearly hold a pivotal role in optimizing patient outcomes. Fostering a deeper understanding of the surgical nuances and clinical management practices that contribute to successful results post-RT, we hope to provide a useful practical tool for clinicians about to embark on the treacherous road of RT surgery. Innovative technologies and surgical practices that have already significantly improved the safety and effectiveness of RT stand testament to the importance of further scientific inquiry, conceptual developments, and clinical integration. Moving forward, it is essential that the medical community continues to refine these strategies and advocate for equitable access to transplantation, ensuring that advancements in the field translate into real-world benefits for all patients grappling with ESRD. The collaborative efforts of multidisciplinary teams are essential in addressing the complex clinical challenges associated with RT, with the ultimate goal of improving patient survival, enhancing graft longevity, and reducing healthcare disparities.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm13144188
    Language: English
    Publisher: MDPI AG
    Publication Date: 2024
    detail.hit.zdb_id: 2662592-1
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  • 3
    Online Resource
    Online Resource
    Rats, Neuregulins and Radical Prostatectomy: A Conceptual Overview
    MDPI AG ; 2023
    In:  Journal of Clinical Medicine Vol. 12, No. 6 ( 2023-03-13), p. 2208-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 12, No. 6 ( 2023-03-13), p. 2208-
    Abstract: In the contemporary era of early detection, with mostly curative initial treatment for prostate cancer (PC), mortality rates have significantly diminished. In addition, mean age at initial PC diagnosis has decreased. Despite technical advancements, the probability of erectile function (EF) recovery post radical prostatectomy (RP) has not significantly changed throughout the last decade. Due to virtually unavoidable intraoperative cavernous nerve (CN) lesions and operations with younger patients, post-RP erectile dysfunction (ED) has now begun affecting these younger patients. To address this pervasive limitation, a plethora of CN lesion animal model investigations have analyzed the use of systemic/local treatments for EF recovery post-RP. Most promisingly, neuregulins (NRGs) have demonstrated neurotrophic effects in both neurodegenerative disease and peripheral nerve injury models. Recently, glial growth factor 2 (GGF2) has demonstrated far superior, dose-dependent, neuroprotective/restorative effects in the CN injury rat model, as compared to previous therapeutic counterparts. Although potentially impactful, these initial findings remain limited and under-investigated. In an effort to aid clinicians, our paper reviews post-RP ED pathogenesis and currently available therapeutic tools. To stimulate further experimentation, a standardized preparation protocol and in-depth analysis of applications for the CN injury rat model is provided. Lastly, we report on NRGs, such as GGF2, and their potentially revolutionary clinical applications, in hopes of identifying relevant future research directions.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm12062208
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2662592-1
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  • 4
    Online Resource
    Online Resource
    Contemporary Clinical Definitions, Differential Diagnosis, and Novel Predictive Tools for Renal Cell Carcinoma
    MDPI AG ; 2022
    In:  Biomedicines Vol. 10, No. 11 ( 2022-11-14), p. 2926-
    Details
    In: Biomedicines, MDPI AG, Vol. 10, No. 11 ( 2022-11-14), p. 2926-
    Abstract: Despite significant progress regarding clinical detection/imaging evaluation modalities and genetic/molecular characterization of pathogenesis, advanced renal cell carcinoma (RCC) remains an incurable disease and overall RCC mortality has been steadily rising for decades. Concomitantly, clinical definitions have been greatly nuanced and refined. RCCs are currently viewed as a heterogeneous series of cancers, with the same anatomical origin, but fundamentally different metabolisms and clinical behaviors. Thus, RCC pathological diagnosis/subtyping guidelines have become increasingly intricate and cumbersome, routinely requiring ancillary studies, mainly immunohistochemistry. Meanwhile, RCC-associated-antigen targeted systemic therapy has been greatly diversified and emerging, novel clinical applications for RCC immunotherapy have already reported significant survival benefits, at least in the adjuvant setting. Even so, systemically disseminated RCCs still associate very poor clinical outcomes, with currently available therapeutic modalities only being able to prolong survival. In lack of a definitive cure for advanced RCCs, integration of the amounting scientific knowledge regarding RCC pathogenesis into RCC clinical management has been paramount for improving patient outcomes. The current review aims to offer an integrative perspective regarding contemporary RCC clinical definitions, proper RCC clinical work-up at initial diagnosis (semiology and multimodal imaging), RCC pathological evaluation, differential diagnosis/subtyping protocols, and novel clinical tools for RCC screening, risk stratification and therapeutic response prediction.
    Type of Medium: Online Resource
    ISSN: 2227-9059
    URL: Article
    DOI: 10.3390/biomedicines10112926
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2720867-9
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  • 5
    Online Resource
    Online Resource
    Evaluating Established Roles, Future Perspectives and Methodological Heterogeneity for Wilms’ Tumor 1 (WT1) Antigen Detection in Adult Renal Cell Carcinoma, Using a Novel N-Terminus Targeted Antibody (Clone WT49)
    MDPI AG ; 2022
    In:  Biomedicines Vol. 10, No. 4 ( 2022-04-15), p. 912-
    Details
    In: Biomedicines, MDPI AG, Vol. 10, No. 4 ( 2022-04-15), p. 912-
    Abstract: Renal cell carcinoma (RCC) is arguably the deadliest form of genitourinary malignancy and is nowadays viewed as a heterogeneous series of cancers, with the same origin but fundamentally different metabolisms and clinical behaviors. Immunohistochemistry (IHC) is increasingly necessary for RCC subtyping and definitive diagnosis. WT1 is a complex gene involved in carcinogenesis. To address reporting heterogeneity and WT1 IHC standardization, we used a recent N-terminus targeted monoclonal antibody (clone WT49) to evaluate WT1 protein expression in 56 adult RCC (aRCC) cases. This is the largest WT1 IHC investigation focusing exclusively on aRCCs and the first report on clone WT49 staining in aRCCs. We found seven (12.5%) positive cases, all clear cell RCCs, showing exclusively nuclear staining for WT1. We did not disregard cytoplasmic staining in any of the negative cases. Extratumoral fibroblasts, connecting tubules and intratumoral endothelial cells showed the same exclusively nuclear WT1 staining pattern. We reviewed WT1 expression patterns in aRCCs and the possible explanatory underlying metabolomics. For now, WT1 protein expression in aRCCs is insufficiently investigated, with significant discrepancies in the little data reported. Emerging WT1-targeted RCC immunotherapy will require adequate case selection and sustained efforts to standardize the quantification of tumor-associated antigens for aRCC and its many subtypes.
    Type of Medium: Online Resource
    ISSN: 2227-9059
    URL: Article
    DOI: 10.3390/biomedicines10040912
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2720867-9
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  • 6
    Online Resource
    Online Resource
    Contemporary Biomarkers for Renal Transplantation: A Narrative Overview
    MDPI AG ; 2023
    In:  Journal of Personalized Medicine Vol. 13, No. 8 ( 2023-07-31), p. 1216-
    Details
    In: Journal of Personalized Medicine, MDPI AG, Vol. 13, No. 8 ( 2023-07-31), p. 1216-
    Abstract: Renal transplantation (RT) is the preferred treatment for end-stage renal disease. However, clinical challenges persist, i.e., early detection of graft dysfunction, timely identification of rejection episodes, personalization of immunosuppressive therapy, and prediction of long-term graft survival. Biomarkers have emerged as valuable tools to address these challenges and revolutionize RT patient care. Our review synthesizes the existing scientific literature to highlight promising biomarkers, their biological characteristics, and their potential roles in enhancing clinical decision-making and patient outcomes. Emerging non-invasive biomarkers seemingly provide valuable insights into the immunopathology of nephron injury and allograft rejection. Moreover, we analyzed biomarkers with intra-nephron specificities, i.e., glomerular vs. tubular (proximal vs. distal), which can localize an injury in different nephron areas. Additionally, this paper provides a comprehensive analysis of the potential clinical applications of biomarkers in the prediction, detection, differential diagnosis and assessment of post-RT non-surgical allograft complications. Lastly, we focus on the pursuit of immune tolerance biomarkers, which aims to reclassify transplant recipients based on immune risk thresholds, guide personalized immunosuppression strategies, and ultimately identify patients for whom immunosuppression may safely be reduced. Further research, validation, standardization, and prospective studies are necessary to fully harness the clinical utility of RT biomarkers and guide the development of targeted therapies.
    Type of Medium: Online Resource
    ISSN: 2075-4426
    URL: Article
    DOI: 10.3390/jpm13081216
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2662248-8
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