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Molecular Research and Treatment of Urologic Cancer

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (31 March 2024) | Viewed by 6726

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Special Issue Editor

Dr. Hironobu Yamashita

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Guest Editor

Department of Pathology and Laboratory Medicine, The Pennsylvania State University, Hershey, PA 17033, USA
Interests: transcription factor; extracellular matrix; tumor plasticity; tumor heterogeneity; matrix proteases; urological cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Urologic cancers comprise bladder and kidney (renal) cancers, which are commonly found in both men and women, and prostate and testicular cancers, which are specifically observed in men. Similar to other cancers, urologic cancers also exhibit tumor heterogeneity, resulting in differences in morphology, gene expression, proliferation, metabolism, aggressiveness, and drug resistance. Finally, tumor heterogeneity causes the failure of cancer therapy, including chemotherapy and immunotherapy targeting immune checkpoint molecules (PD-1/PD-L1). Therefore, it is highly important to elucidate the molecular mechanisms behind this event in urologic cancers.

This Special Issue of the International Journal of Molecular Sciences encourages authors to submit original and review articles focusing on elucidating the molecular mechanisms of the differences between tumor progression and drug resistance, and additionally, new predictive and prognostic biomarkers in the tumor heterogeneity of urologic cancers.

Dr. Hironobu Yamashita
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

bladder cancer
renal cancer
prostate cancer
tumor heterogeneity
immunotherapy
tumor progression
tumor microenvironment
gene expression
urologic cancer
metastasis

Published Papers (6 papers)

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Research

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22 pages, 9637 KiB

Open AccessArticle

Analysis of the Gene Networks and Pathways Correlated with Tissue Differentiation in Prostate Cancer

by Alexandru Filippi, Justin Aurelian and Maria-Magdalena Mocanu

Int. J. Mol. Sci. 2024, 25(7), 3626; https://doi.org/10.3390/ijms25073626 - 24 Mar 2024

Viewed by 935

Abstract

Prostate cancer (PCa) is the most prevalent non-cutaneous cancer in men. Early PCa detection has been made possible by the adoption of screening methods based on the serum prostate-specific antigen and Gleason score (GS). The aim of this study was to correlate gene expression with the differentiation level of prostate adenocarcinomas, as indicated by GS. We used data from The Cancer Genome Atlas (TCGA) and included 497 prostate cancer patients, 52 of which also had normal tissue sample sequencing data. Gene ontology analysis revealed that higher GSs were associated with greater responses to DNA damage, telomere lengthening, and cell division. Positive correlation was found with transcription factor activator of the adenovirus gene E2 (E2F) and avian myelocytomatosis viral homolog (MYC) targets, G2M checkpoints, DNA repair, and mitotic spindles. Immune cell deconvolution revealed high M0 macrophage counts and an increase in M2 macrophages dependent on the GS. The molecular pathways most correlated with GSs were cell cycle, RNA transport, and calcium signaling (depleted). A combinatorial approach identified a set of eight genes able to differentiate by k-Nearest Neighbors (kNN) between normal tissues, low-Gleason tissues, and high-Gleason tissues with high accuracy. In conclusion, our study could be a step forward to better understanding the link between gene expression and PCa progression and aggressiveness. Full article

(This article belongs to the Special Issue Molecular Research and Treatment of Urologic Cancer)

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13 pages, 2599 KiB

Open AccessArticle

Elevated Plasma Concentration of 4-Pyridone-3-carboxamide-1-β-D-ribonucleoside (4PYR) Highlights Malignancy of Renal Cell Carcinoma

by Agata Jedrzejewska, Patrycja Jablonska, Teresa Gawlik-Jakubczak, Mateusz Czajkowski, Patrycja Maszka, Paulina Mierzejewska, Ryszard T. Smolenski and Ewa M. Slominska

Int. J. Mol. Sci. 2024, 25(4), 2359; https://doi.org/10.3390/ijms25042359 - 17 Feb 2024

Viewed by 787

Abstract

Nicotinamide (NA) derivatives play crucial roles in various biological processes, such as inflammation, regulation of the cell cycle, and DNA repair. Recently, we proposed that 4-pyridone-3-carboxamide-1-β-D-ribonucleoside (4PYR), an unusual derivative of NA, could be classified as an oncometabolite in bladder, breast, and lung cancer. In this study, we investigated the relations between NA metabolism and the progression, recurrence, metastasis, and survival of patients diagnosed with different histological subtypes of renal cell carcinoma (RCC). We identified alterations in plasma NA metabolism, particularly in the clear cell RCC (ccRCC) subtype, compared to papillary RCC, chromophobe RCC, and oncocytoma. Patients with ccRCC also exhibited larger tumor sizes and elevated levels of diagnostic serum biomarkers, such as hsCRP concentration and ALP activity, which were positively correlated with the plasma 4PYR. Notably, 4PYR levels were elevated in advanced stages of ccRCC cancer and were associated with a highly aggressive phenotype of ccRCC. Additionally, elevated concentrations of 4PYR were related to a higher likelihood of mortality, recurrence, and particularly metastasis in ccRCC. These findings are consistent with other studies, suggesting that NA metabolism is accelerated in RCC, leading to abnormal concentrations of 4PYR. This supports the concept of 4PYR as an oncometabolite and a potential prognostic factor in the ccRCC subtype. Full article

(This article belongs to the Special Issue Molecular Research and Treatment of Urologic Cancer)

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14 pages, 18099 KiB

Open AccessArticle

The Expression of Alamandine Receptor MrgD in Clear Cell Renal Cell Carcinoma Is Associated with a Worse Prognosis and Unfavorable Response to Antiangiogenic Therapy

by Gorka Larrinaga, Asier Valdivia, Inés Arrieta-Aguirre, Jon Danel Solano-Iturri, Aitziber Ugalde-Olano, Ana Loizaga-Iriarte, Aida Santos-Martín, Amparo Pérez-Fernández, Javier C. Angulo and José I. López

Int. J. Mol. Sci. 2024, 25(3), 1499; https://doi.org/10.3390/ijms25031499 - 25 Jan 2024

Viewed by 850

Abstract

Renal cell carcinoma (RCC) ranks among the most prevalent malignancies in Western countries, marked by its notable heterogeneity, which contributes to an unpredictable clinical trajectory. The insufficiency of dependable biomarkers adds complexity to assessing this tumor progression. Imbalances of several components of the intrarenal renin–angiotensin system (iRAS) significantly impact patient prognoses and responses to first-line immunotherapies. In this study, we analyzed the immunohistochemical expression of the Mas-related G-protein-coupled receptor D (MrgD), which recognizes the novel RAS peptide alamandine (ALA), in a series of 87 clear cell renal cell (CCRCCs), 19 papillary (PRCC), 7 chromophobe (ChRCC) renal cell carcinomas, and 11 renal oncocytomas (RO). MrgD was expressed in all the renal tumor subtypes, with a higher mean staining intensity in the PRCCs, ChRCCs, and ROs. A high expression of MrgD at the tumor center and at the infiltrative front of CCRCC tissues was significantly associated with a high histological grade, large tumor diameter, local invasion, and locoregional node and distant metastasis. Patients with worse 5-year cancer-specific survival and a poorer response to antiangiogenic tyrosine-kinase inhibitors (TKIs) showed higher MrgD expression at the center of their primary tumors. These findings suggest a possible role of MrgD in renal carcinogenetic processes. Further studies are necessary to unveil its potential as a novel biomarker for CCRCC prognosis and response to frontline therapies. Full article

(This article belongs to the Special Issue Molecular Research and Treatment of Urologic Cancer)

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15 pages, 2962 KiB

Open AccessArticle

ERVK13-1/miR-873-5p/GNMT Axis Promotes Metastatic Potential in Human Bladder Cancer though Sarcosine Production

by Shingo Kishi, Shiori Mori, Rina Fujiwara-Tani, Ruiko Ogata, Rika Sasaki, Ayaka Ikemoto, Kei Goto, Takamitsu Sasaki, Makito Miyake, Satoru Sasagawa, Masashi Kawaichi, Yi Luo, Ujjal Kumar Bhawal, Kiyohide Fujimoto, Hidemitsu Nakagawa and Hiroki Kuniyasu

Int. J. Mol. Sci. 2023, 24(22), 16367; https://doi.org/10.3390/ijms242216367 - 15 Nov 2023

Cited by 1 | Viewed by 955

Abstract

N-methyl-glycine (sarcosine) is known to promote metastatic potential in some cancers; however, its effects on bladder cancer are unclear. T24 cells derived from invasive cancer highly expressed GNMT, and S-adenosyl methionine (SAM) treatment increased sarcosine production, promoting proliferation, invasion, anti-apoptotic survival, sphere formation, and drug resistance. In contrast, RT4 cells derived from non-invasive cancers expressed low GNMT, and SAM treatment did not produce sarcosine and did not promote malignant phenotypes. In T24 cells, the expression of miR-873-5p, which suppresses GNMT expression, was suppressed, and the expression of ERVK13-1, which sponges miR-873-5p, was increased. The growth of subcutaneous tumors, lung metastasis, and intratumoral GNMT expression in SAM-treated nude mice was suppressed in T24 cells with ERVK13-1 knockdown but promoted in RT4 cells treated with miR-873-5p inhibitor. An increase in mouse urinary sarcosine levels was observed to correlate with tumor weight. Immunostaining of 86 human bladder cancer cases showed that GNMT expression was higher in cases with muscle invasion and metastasis. Additionally, urinary sarcosine concentrations increased in cases of muscle invasion. Notably, urinary sarcosine concentration may serve as a marker for muscle invasion in bladder cancer; however, further investigation is necessitated. Full article

(This article belongs to the Special Issue Molecular Research and Treatment of Urologic Cancer)

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15 pages, 6741 KiB

Open AccessArticle

The Effect of Photosensitizer Metalation Incorporated into Arene–Ruthenium Assemblies on Prostate Cancer

by Lucie Paulus, Manuel Gallardo-Villagrán, Claire Carrion, Catherine Ouk, Frédérique Martin, Bruno Therrien, David Yannick Léger and Bertrand Liagre

Int. J. Mol. Sci. 2023, 24(17), 13614; https://doi.org/10.3390/ijms241713614 - 2 Sep 2023

Cited by 2 | Viewed by 1184

Abstract

Prostate cancer is the second most common cancer for men and a major health issue. Despite treatments, a lot of side effects are observed. Photodynamic therapy is a non-invasive method that uses photosensitizers and light to induce cell death through the intramolecular generation of reactive oxygen species, having almost no side effects. However, some of the PSs used in PDT show inherent low solubility in biological media, and accordingly, functionalization or vectorization is needed to ensure internalization. To this end, we have used arene–ruthenium cages in order to deliver PSs to cancer cells. These metalla-assemblies can host PSs inside their cavity or be constructed with PS building blocks. In this study, we wanted to determine if the addition of metals (Mg, Co, Zn) in the center of these PSs plays a role. Our results show that most of the compounds induce cytotoxic effects on DU 145 and PC-3 human prostate cancer cells. Localization by fluorescence confirms the internalization of the assemblies in the cytoplasm. An analysis of apoptotic processes shows a cleavage of pro-caspase-3 and poly-ADP-ribose polymerase, thus leading to a strong induction of DNA fragmentation. Finally, the presence of metals in the PS decreases PDT’s effect and can even annihilate it. Full article

(This article belongs to the Special Issue Molecular Research and Treatment of Urologic Cancer)

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Review

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13 pages, 1049 KiB

Open AccessReview

Mini-Review: Current Bladder Cancer Treatment—The Need for Improvement

by Emily Gill and Claire M. Perks

Int. J. Mol. Sci. 2024, 25(3), 1557; https://doi.org/10.3390/ijms25031557 - 26 Jan 2024

Cited by 1 | Viewed by 1460

Abstract

Bladder cancer is the tenth most common cancer and is a significant burden on health care services worldwide, as it is one of the most costly cancers to treat per patient. This expense is due to the extensive treatment and follow-ups that occur with costly and invasive procedures. Improvement in both treatment options and the quality of life these interventions offer has not progressed at the rates of other cancers, and new alternatives are desperately needed to ease the burden. A more modern approach needs to be taken, with urinary biomarkers being a positive step in making treatments more patient-friendly, but there is still a long way to go to make these widely available and of a comparable standard to the current treatment options. New targets to hit the major signalling pathways that are upregulated in bladder cancer, such as the PI3K/AkT/mTOR pathway, are urgently needed, with only one drug approved so far, Erdafitinib. Immune checkpoint inhibitors also hold promise, with both PD-1 and CDLA-4 antibody therapies approved for use. They effectively block ligand/receptor binding to block the immune checkpoint used by tumour cells. Other avenues must be explored, including drug repurposing and novel biomarkers, which have revolutionised this area in other cancers. Full article

(This article belongs to the Special Issue Molecular Research and Treatment of Urologic Cancer)

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