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  • 1
    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
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2662592-1
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  • 2
    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
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2720867-9
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  • 3
    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
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2720867-9
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  • 4
    In: Biomedicines, MDPI AG, Vol. 10, No. 11 ( 2022-10-23), p. 2673-
    Abstract: Despite significant developments in renal cell carcinoma (RCC) detection and molecular pathology, mortality has been steadily rising. Advanced RCC remains an incurable disease. Better clinical management tools, i.e., RCC biomarkers, have yet to emerge. Thymine-dimers (TDs) were traditionally considered photo-dependent pre-mutagenic lesions, occurring exclusively during ultra-violet light exposure. Non-oxidative, direct, and preferential byproducts of DNA photochemical reactions, TDs, have recently shown evidence regarding UVR-independent formation. In this study, we investigate, for the first time, TD expression within RCC tumor tissue and tumor-adjacent healthy renal parenchyma using a TD-targeted IHC monoclonal antibody, clone KTM53. Remarkably, out of the 54 RCCs evaluated, 77.8% showed nuclear TD-expression in RCC tumor tissue and 37% in the tumor-adjacent healthy renal parenchyma. A comprehensive report regarding quantitative/qualitative TD-targeted immunostaining was elaborated. Two main distribution models for TD expression within RCC tumor tissue were identified. Statistical analysis showed significant yet moderate correlations regarding TD-positivity in RCC tissue/tumor-adjacent healthy renal parenchyma and TNM stage at diagnosis/lymphatic dissemination, respectively, indicating possible prognostic relevance. We review possible explanations for UVR-independent TD formation and molecular implications regarding RCC carcinogenesis. Further rigorous molecular analysis is required in order to fully comprehend/validate the biological significance of this newly documented TD expression in RCC.
    Type of Medium: Online Resource
    ISSN: 2227-9059
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2720867-9
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