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Article ; Online: Ubiquitin-Specific Proteases as Potential Therapeutic Targets in Bladder Cancer—In Vitro Evaluation of Degrasyn and PR-619 Activity Using Human and Canine Models

Łukasz Nowak / Wojciech Krajewski / Ewa Dejnaka / Bartosz Małkiewicz / Tomasz Szydełko / Aleksandra Pawlak

Biomedicines, Vol 11, Iss 759, p

2023 Volume 759

Abstract: Background: The inhibition of ubiquitin-specific proteases (USPs) is a novel and promising direction in the development of molecularly targeted therapies in oncology. The aim of the present study was to examine whether Degrasyn could be a potential ... ...

Abstract	Background: The inhibition of ubiquitin-specific proteases (USPs) is a novel and promising direction in the development of molecularly targeted therapies in oncology. The aim of the present study was to examine whether Degrasyn could be a potential therapeutic agent against bladder cancer (BC). Also, we aimed to determine whether Degrasyn is more effective in terms of anti-cancer activity compared to the non-selective DUB inhibitor PR-619. To facilitate the translational value of the obtained results, our experiments were performed using both human and canine in vitro models of BC. Methods: Human T24 (urothelial grade III BC) and SV-HUC-1 (non-tumorigenic urothelial cell line), as well as canine K9TCC-PU-NK and RDSVS-TCC1 (both derived from invasive grade III urothelial bladder tumors) cell lines, were used in the present study. Cell proliferation was determined using the MTT assay and Ki-67 proliferation assay, and the level of apoptosis induced by Degrasyn and PR-619 was evaluated by Annexin V-FITC staining and caspase 3/7 activation assay. Western blot was used to assess DNA damage and key proteins involved in apoptosis. Results: Degrasyn inhibited the proliferation of all BC cell lines in a concentration- and time-dependent manner. Lower concentrations of Degrasyn were more potent against human and canine BC cell lines compared to PR-619. Degrasyn induced caspase-dependent apoptosis and triggered DNA damage. PR-619 did not show a significant pro-apoptotic effect. Conclusions: Our results demonstrate that Degrasyn significantly impairs the growth of in vitro models of human and canine BC. Selective USP inhibition with Degrasyn seems to be more effective in reducing BC cell proliferation and inducing apoptosis and DNA damage than non-selective USP inhibition with PR-619.
Keywords	bladder cancer ; urothelial carcinoma ; ubiquitin-specific proteases ; Degrasyn ; PR-619 ; Biology (General) ; QH301-705.5
Subject code	616
Language	English
Publishing date	2023-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Characteristics and Applications of Canine In Vitro Models of Bladder Cancer in Veterinary Medicine

Łukasz Nowak / Wojciech Krajewski / Bartosz Małkiewicz / Tomasz Szydełko / Aleksandra Pawlak

Animals, Vol 12, Iss 516, p

An Up-to-Date Mini Review

2022 Volume 516

Abstract: Bladder cancer (BC) constitutes approximately 2% of all spontaneously occurring cancers in dogs. It is characterized by a devastating clinical course in most cases, which emphasizes a constant need for the development of novel methods of disease ... ...

Abstract	Bladder cancer (BC) constitutes approximately 2% of all spontaneously occurring cancers in dogs. It is characterized by a devastating clinical course in most cases, which emphasizes a constant need for the development of novel methods of disease characterization and treatment. Over the past years, advances in cell engineering have resulted in the development of various canine in vitro models of BC, emerging as complements for in vivo research. In this article, we aimed to review the available data on existing in vitro models of canine BC, focusing primarily on their characteristics, applications in veterinary medicine, as well as advantages and disadvantages. The most commonly used in vitro models of canine BC comprise immortalized cell lines grown as adherent monolayers. They provide an unlimited supply of research material, however, they do not faithfully reflect the conditions prevailing in vivo, since the spatial cellular interactions are lost. The importance of the three-dimensional (3D) features of solid tumors in relation to carcinogenesis or drug response process has resulted in the development of the first canine 3D models of BC available for in vitro research. So far, results obtained with in vitro and in vivo research should be interpreted together. With the constantly growing complexity of in vitro models of BC cancer, animal-based research might be reduced in the future.
Keywords	canine ; bladder ; urothelial cancer ; in vitro model ; Veterinary medicine ; SF600-1100 ; Zoology ; QL1-991
Language	English
Publishing date	2022-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Novel Histopathological Biomarkers in Prostate Cancer

Paweł Kiełb / Kamil Kowalczyk / Adam Gurwin / Łukasz Nowak / Wojciech Krajewski / Roman Sosnowski / Tomasz Szydełko / Bartosz Małkiewicz

Biomedicines, Vol 11, Iss 1552, p

Implications and Perspectives

2023 Volume 1552

Abstract: Prostate cancer (PCa) is the second most frequently diagnosed cancer in men. Despite the significant progress in cancer diagnosis and treatment over the last few years, the approach to disease detection and therapy still does not include ... ...

Abstract	Prostate cancer (PCa) is the second most frequently diagnosed cancer in men. Despite the significant progress in cancer diagnosis and treatment over the last few years, the approach to disease detection and therapy still does not include histopathological biomarkers. The dissemination of PCa is strictly related to the creation of a premetastatic niche, which can be detected by altered levels of specific biomarkers. To date, the risk factors for biochemical recurrence include lymph node status, prostate-specific antigen (PSA), PSA density (PSAD), body mass index (BMI), pathological Gleason score, seminal vesicle invasion, extraprostatic extension, and intraductal carcinoma. In the future, biomarkers might represent another prognostic factor, as discussed in many studies. In this review, we focus on histopathological biomarkers (particularly CD169 macrophages, neuropilin-1, cofilin-1, interleukin-17, signal transducer and activator of transcription protein 3 (STAT3), LIM domain kinase 1 (LIMK1), CD15, AMACR, prostate-specific membrane antigen (PSMA), Appl1, Sortilin, Syndecan-1, and p63) and their potential application in decision making regarding the prognosis and treatment of PCa patients. We refer to studies that found a correlation between the levels of biomarkers and tumor characteristics as well as clinical outcomes. We also hypothesize about the potential use of histopathological markers as a target for novel immunotherapeutic drugs or targeted radionuclide therapy, which may be used as adjuvant therapy in the future.
Keywords	prostate cancer ; prognostic markers ; IL-17 ; STAT3 ; NRP1 ; LIMK1 ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2023-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Pain reduction methods during transurethral cystoscopy

Jan Łaszkiewicz / Wojciech Krajewski / Mateusz Łuczak / Joanna Chorbińska / Łukasz Nowak / Klaudia Bardowska / Romuald Zdrojowy

Contemporary Oncology, Vol 25, Iss 2, Pp 80-

2021 Volume 87

Abstract: Transurethral cystoscopy (CS) is a common urological procedure, performed mostly for diagnostic but also for therapeutic purposes. Although CS is generally well tolerated, some patients describe the pain related to the procedure as high or even “ ... ...

Abstract	Transurethral cystoscopy (CS) is a common urological procedure, performed mostly for diagnostic but also for therapeutic purposes. Although CS is generally well tolerated, some patients describe the pain related to the procedure as high or even “unbearable”. As a result, many patients fear and avoid both primary and/or follow-up cystoscopies. This may lead to uncontrolled progression of neoplastic disease. Therefore, it is crucial to maximally increase the comfort of the patient and to implement safe and effective analgesia before the procedure. Providing the patients with appropriate care during CS can encourage them to comply with diagnostic schedules and improve their prognosis. The aim of this review is to analyze the available literature on various methods of pain reduction during transurethral CS. The PubMed electronic database limited to English articles published until January 2021 was used in the process. Meta-analyses, systematic reviews, randomized controlled trials, clinical trials, prospective randomized studies, multicenter comparisons, reviews and retrospective comparisons were used. As a result, 65 articles were included in this review.
Keywords	cystoscopy ; pain reduction ; transurethral cystoscopy ; rigid cystoscopy ; flexible cystoscopy ; Medicine ; R
Subject code	610
Language	English
Publishing date	2021-05-01T00:00:00Z
Publisher	Termedia Publishing House
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Clinical Characteristics of Itch in Renal Transplant Recipients

Piotr K. Krajewski / Piotr Olczyk / Magdalena Krajewska / Wojciech Krajewski / Jacek C. Szepietowski

Frontiers in Medicine, Vol

2021 Volume 7

Abstract: Background: Chronic itch is the most common symptom in dermatology. End-stage renal disease-associated chronic itch (ESRDCI) is a common burden affecting up to 35% of patients treated with hemodialysis. Kidney transplant (KTx) is believed to be the best ... ...

Abstract	Background: Chronic itch is the most common symptom in dermatology. End-stage renal disease-associated chronic itch (ESRDCI) is a common burden affecting up to 35% of patients treated with hemodialysis. Kidney transplant (KTx) is believed to be the best renal replacement therapy leading to the elimination of ESRDCI. The study was undertaken to characterize and assess the prevalence of itch among patients after renal transplantation.Methods: Between October 2019 and January 2020, we analyzed the data of 197 patients comprising 121 males (61.4%) and 76 females (38.6%) and aged 54.5 ± 13.6 years. The data collection was performed with a specially designed questionnaire. Level of itch after renal transplantation was assessed with the use of a Numeral Rating Scale, a Visual Rating Scale, and 4-Item Itch Questionnaire. Moreover, the previous 3 days of itching were evaluated.Results: The patients suffered from chronic renal disease for 20.2 ± 12.3 years, with a mean time of pre-transplant dialysis of 2.6 ± 2.4 years and a mean time after the KTx of 8.0 ± 6.5 years. The itch was present in 38.6% of the patients during the hemodialysis, and in 73.7% of cases, the itch ceased completely after the successful transplantation. Moreover, only 2.63% of the cases had no improvement. Nevertheless, the itch was reported in 42 (21.3%) renal transplant recipients (RTR), and in 22 (52.4%) cases, the itch appeared after transplantation. The majority of patients suffering from itch were women (54.8%). Itch in the last 3 days was reported in 21 patients. The itch's severity was assessed with a numerical rating scale (NRS), with the worst severity measured at 6 ± 2.2 points indicating moderate itch. In most cases (57.1%), itch affected multiple body areas. Extremities (50%) and the back (50%) were among the most frequently affected areas. The sensation had a mostly short duration and was most frequently reported in the evening. Only eight patients suffered for the whole day. Hot water was the most frequently reported (16.7%) alleviating ...
Keywords	renal transplant ; itch ; chronic kidney disease ; ESRDCI ; renal transplant recipients ; Medicine (General) ; R5-920
Subject code	616
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Acute kidney injury secondary to urinary tract infection in kidney transplant recipients

Tomasz Królicki / Klaudia Bardowska / Tobiasz Kudla / Anna Królicka / Krzysztof Letachowicz / Oktawia Mazanowska / Wojciech Krajewski / Paweł Poznański / Magdalena Krajewska / Dorota Kamińska

Scientific Reports, Vol 12, Iss 1, Pp 1-

2022 Volume 14

Abstract: Abstract Acute kidney injury (AKI) in kidney transplant recipients (KTRs) is a common, yet poorly investigated, complication of urinary tract infections (UTI) and urosepsis. A retrospective comparative analysis was performed, recruiting 101 KTRs with ... ...

Abstract	Abstract Acute kidney injury (AKI) in kidney transplant recipients (KTRs) is a common, yet poorly investigated, complication of urinary tract infections (UTI) and urosepsis. A retrospective comparative analysis was performed, recruiting 101 KTRs with urosepsis, 100 KTRs with UTI, and 100 KTRs without history of UTI or sepsis. The incidences of AKI in the urosepsis and UTI groups were 75.2% and 41%, respectively. The urosepsis group has also presented with a significantly higher prevalence of AKI stage 2 and 3 than the UTI group. The rates of recovery from AKI stages 1, 2 and 3, were 75,6%, 55% and 26.1%, respectively. Factors independently associated with renal recovery from AKI were: AKI severity grade (AKI stage 2 with OR = 0.25 and AKI stage 3 with OR = 0.1), transfusion of red blood cells (RBC) (OR = 0.22), and the use of steroid bolus in the acute phase of treatment (OR = 4). The septic status (urosepsis vs UTI) did not influence the rates of renal recovery from AKI after adjustment for the remaining variables. The dominant cause of RBC transfusions in the whole population was upper GI-bleeding. In multivariable analyses, the occurrence of AKI was also independently associated with a greater decline of eGFR at 1-year post-discharge and with a greater risk of graft loss. In KTRs with both urosepsis and UTI, the occurrence of AKI portends poor transplantation outcomes. The local transfusion policy, modulation of immunosuppression and stress ulcer prophylaxis (which is not routinely administered in KTRs) in the acute setting may be modifiable factors that significantly impact long-term transplantation outcomes.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2022-06-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: High-Intensity Focused-Ultrasound Focal Therapy Versus Laparoscopic Radical Prostatectomy

Łukasz Nyk / Wojciech Michalak / Stanisław Szempliński / Rafał Woźniak / Bartłomiej Zagożdżon / Wojciech Krajewski / Piotr Kryst / Hubert Kamecki / Sławomir Poletajew

Journal of Personalized Medicine, Vol 12, Iss 251, p

A Comparison of Oncological and Functional Outcomes in Low- and Intermediate-Risk Prostate Cancer Patients

2022 Volume 251

Abstract: To compare oncological and functional outcomes of high-intensity focused-ultrasound (HIFU) focal therapy (FT) versus laparoscopic radical prostatectomy (LRP) in patients treated for low- or intermediate-risk prostate cancer (PCa), we retrospectively ... ...

Abstract	To compare oncological and functional outcomes of high-intensity focused-ultrasound (HIFU) focal therapy (FT) versus laparoscopic radical prostatectomy (LRP) in patients treated for low- or intermediate-risk prostate cancer (PCa), we retrospectively analyzed data of consecutive patients comprising 30 men, who underwent HIFU-FT, and 96 men who underwent LRP, in an academic center. Oncological outcomes were assessed based on the follow-up prostate-specific antigen values. We used the International Index of Erectile Function short form score to assess erectile function (EF). Urinary continence status was defined based on the number of pads used per day. Median follow-up was 12.5 and 19.1 months in the LRP and HIFU-FT groups, respectively. The effects were computed after propensity score matching and expressed as average treatment effect (ATE). Compared to LRP, HIFU-FT was associated with increased risk of treatment failure (ATE 0.103–0.164, depending on definition, p < 0.01) and lower risk of urinary incontinence (ATE −0.808 at 12 months, p < 0.01). Risk of erectile dysfunction was higher in the LRP group (ATE 5.092, p < 0.01). Our results demonstrate that HIFU-FT may be a reasonable treatment option in selected PCa patients, willing to preserve their EF and urinary continence yet accepting a higher risk of treatment failure.
Keywords	prostate cancer ; focal therapy ; high-intensity focused-ultrasound ; urinary incontinence ; erectile dysfunction ; Medicine ; R
Subject code	610
Language	English
Publishing date	2022-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Interleukin 17 and Its Involvement in Renal Cell Carcinoma

Michał Jarocki / Julia Karska / Szymon Kowalski / Paweł Kiełb / Łukasz Nowak / Wojciech Krajewski / Jolanta Saczko / Julita Kulbacka / Tomasz Szydełko / Bartosz Małkiewicz

Journal of Clinical Medicine, Vol 11, Iss 4973, p

2022 Volume 4973

Abstract: Nowadays, molecular and immunological research is essential for the better understanding of tumor cells pathophysiology. The increasing number of neoplasms has been taken under ‘the molecular magnifying glass’ and, therefore, it is possible to discover ... ...

Abstract	Nowadays, molecular and immunological research is essential for the better understanding of tumor cells pathophysiology. The increasing number of neoplasms has been taken under ‘the molecular magnifying glass’ and, therefore, it is possible to discover complex relationships between the cytophysiology and immune system action. An example could be renal cell carcinoma (RCC) which has deep interactions with immune mediators such as Interleukin 17 (IL-17)—an inflammatory cytokine reacting to tissue damage and external pathogens. RCC is one of the most fatal urological cancers because of its often late diagnosis and poor susceptibility to therapies. IL-17 and its relationship with tumors is extremely complex and constitutes a recent topic for numerous studies. What is worth highlighting is IL-17’s dual character in cancer development—it could be pro- as well as anti-tumorigenic. The aim of this review is to summarize the newest data considering multiple connections between IL-17 and RCC.
Keywords	interleukin-17 ; renal cell carcinoma ; immunotherapy ; inflammation ; tumor microenvironment ; tumor development ; Medicine ; R
Subject code	616
Language	English
Publishing date	2022-08-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Utility of Lymphadenectomy in Prostate Cancer

Bartosz Małkiewicz / Paweł Kiełb / Jakub Karwacki / Róża Czerwińska / Paulina Długosz / Artur Lemiński / Łukasz Nowak / Wojciech Krajewski / Tomasz Szydełko

Journal of Clinical Medicine, Vol 11, Iss 2343, p

Where Do We Stand?

2022 Volume 2343

Abstract: The purpose of this review is to summarize the current knowledge on lymph node dissection (LND) in prostate cancer (PCa) patients undergoing radical prostatectomy (RP). Despite a growing body of evidence, the utility and therapeutic and prognostic value ... ...

Abstract	The purpose of this review is to summarize the current knowledge on lymph node dissection (LND) in prostate cancer (PCa) patients undergoing radical prostatectomy (RP). Despite a growing body of evidence, the utility and therapeutic and prognostic value of such an approach, as well as the optimal extent of LND, remain unsolved issues. Although LND is the most accurate staging procedure, the direct therapeutic effect is still not evident from the current literature, which limits the possibility of establishing clear recommendations. This indicates the need for further robust and adequately designed high-quality clinical trials.
Keywords	prostate cancer ; lymph node dissection ; lymphadenectomy ; radical prostatectomy ; Medicine ; R
Language	English
Publishing date	2022-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Diagnostic Performance of Preoperative Choline-PET/CT in Patients Undergoing Salvage Lymph Node Dissection for Recurrent Prostate Cancer

Łukasz Nyk / Hubert Kamecki / Wojciech Krajewski / Bartosz Małkiewicz / Tomasz Szydełko / Markiian Kubis / Marcin Słojewski / Piotr Kryst / Sławomir Poletajew / Wojciech Malewski

Tomography, Vol 8, Iss 89, Pp 1090-

A Multicenter Experience

2022 Volume 1096

Abstract: We aimed to retrospectively analyze consecutive prostate cancer patients diagnosed with biochemical or clinical recurrence after local treatment with curative intent, with no evidence of distant metastases, who underwent positron emission tomography/ ... ...

Abstract	We aimed to retrospectively analyze consecutive prostate cancer patients diagnosed with biochemical or clinical recurrence after local treatment with curative intent, with no evidence of distant metastases, who underwent positron emission tomography/computed tomography (PET/CT) with choline followed by salvage lymph node dissection (SLND) in three academic centers between 2013 and 2020. A total of 27 men were included in the analyses. Sensitivity, specificity, positive and negative predictive values, and accuracy of choline-PET/CT in predicting pathology-proven lymph node involvement were 75%, 43%, 79%, 38% and 67% on per-patient and 70%, 86%, 80%, 78%, and 79% on per-site analyses, respectively, with the differences in specificity and NPV between per-patient and per-site analyses being statistically significant ( p = 0.03 and 0.04, respectively). The study provides further insight into the role of preoperative choline-PET/CT in patients undergoing SLND for recurrent PC.
Keywords	positron emission tomography computed tomography ; prostatic neoplasms ; salvage therapy ; predictive value of tests ; sensitivity and specificity ; Computer applications to medicine. Medical informatics ; R858-859.7
Subject code	610
Language	English
Publishing date	2022-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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