W. Tomczak, Wojciech Krajewski, Joanna Chorbińska, Ł. Nowak, J. Łaszkiewicz, Katarzyna Grunwald, Adam Chełmoński, Szymon Pisarski, T. Szydełko
The persistence of high incidence and mortality rates associated with urologic cancers underscores the urgent need for effective and safe treatments. Conventional chemotherapy regimens are often limited by their high toxicity, the cancer’s drug resistance, and the challenge of managing independently evolving multifocal spread. In this context, a repurposing strategy is particularly enticing. It allows for the introduction of a drug with a known safety profile, thus significantly reducing the costs and time necessary to introduce a new treatment. Nitroxoline (NIT), a drug with a well-established pharmacokinetic profile known for over 50 years and utilised in treating uncomplicated urinary tract infections, has recently garnered attention for its potential oncologic applications. Given the pharmacokinetic properties of NIT, our focus was specifically on urologic cancers in which its excretion profile is most advantageous. We examined all available studies, demonstrating significant effectiveness of NIT in inhibiting angiogenesis, tissue invasion, metastasis formation, and counteracting multidrug resistance. The efficacy and mechanism of action of NIT were found to vary across different cell lines. The findings to date are promising, suggesting that NIT or its derivatives could play a role in oncology, although further research is necessary to fully understand its potential and applicability in cancer treatment.
{"title":"Application of nitroxoline in urologic oncology – a review of evidence","authors":"W. Tomczak, Wojciech Krajewski, Joanna Chorbińska, Ł. Nowak, J. Łaszkiewicz, Katarzyna Grunwald, Adam Chełmoński, Szymon Pisarski, T. Szydełko","doi":"10.5114/wo.2024.139584","DOIUrl":"https://doi.org/10.5114/wo.2024.139584","url":null,"abstract":"The persistence of high incidence and mortality rates associated with urologic cancers underscores the urgent need for effective and safe treatments. Conventional chemotherapy regimens are often limited by their high toxicity, the cancer’s drug resistance, and the challenge of managing independently evolving multifocal spread. In this context, a repurposing strategy is particularly enticing. It allows for the introduction of a drug with a known safety profile, thus significantly reducing the costs and time necessary to introduce a new treatment. Nitroxoline (NIT), a drug with a well-established pharmacokinetic profile known for over 50 years and utilised in treating uncomplicated urinary tract infections, has recently garnered attention for its potential oncologic applications. Given the pharmacokinetic properties of NIT, our focus was specifically on urologic cancers in which its excretion profile is most advantageous. We examined all available studies, demonstrating significant effectiveness of NIT in inhibiting angiogenesis, tissue invasion, metastasis formation, and counteracting multidrug resistance. The efficacy and mechanism of action of NIT were found to vary across different cell lines. The findings to date are promising, suggesting that NIT or its derivatives could play a role in oncology, although further research is necessary to fully understand its potential and applicability in cancer treatment.","PeriodicalId":10652,"journal":{"name":"Contemporary Oncology","volume":"115 23","pages":"1 - 8"},"PeriodicalIF":0.0,"publicationDate":"2024-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141124409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction Illness in the family is a new and difficult situation. Illness frequently causes radical changes both in patients’ lives and in their closest family situation. It often threatens currently performed tasks or values pursued by patients and those who support them. The aim of the study was to determine the relationship between the health condition of people supporting leukaemia patients, strategies for coping with stress, and the level of subjective resources. Material and methods The research involved 100 people supporting leukaemia patients. The methods used in the research included a standardised interview, CISS SES, SOC-29 and ISCL-STAI questionnaires, as well as Bryant’s perceived control of life questionnaire. Results The results show that the health of people supporting leukaemia patients is largely conditioned by emotion-focused style (β= –0.276, p = 0.007) and avoidant attachment style linked to social anxiety (β = 0.444, p = 0.012). As regards the resources, a significant negative health predictor in people supporting leukaemia patients is the anxious personality type (β = –0.375, p = 0.001), whereas a positive health predictor is the sen-se of support provided by others (β = 0.281, p = 0.001). Conclusions People supporting leukaemia patients point to the key role of the subjective resources possessed by an individual. Concentration on negative emotions and deficient resources, in particular the anxious personality, are definitely detrimental to health.
{"title":"Health and coping styles including resources of close family members supporting leukaemia patients","authors":"Anna Magda Kaczmarska-Tabor","doi":"10.5114/wo.2024.139486","DOIUrl":"https://doi.org/10.5114/wo.2024.139486","url":null,"abstract":"Introduction Illness in the family is a new and difficult situation. Illness frequently causes radical changes both in patients’ lives and in their closest family situation. It often threatens currently performed tasks or values pursued by patients and those who support them. The aim of the study was to determine the relationship between the health condition of people supporting leukaemia patients, strategies for coping with stress, and the level of subjective resources. Material and methods The research involved 100 people supporting leukaemia patients. The methods used in the research included a standardised interview, CISS SES, SOC-29 and ISCL-STAI questionnaires, as well as Bryant’s perceived control of life questionnaire. Results The results show that the health of people supporting leukaemia patients is largely conditioned by emotion-focused style (β= –0.276, p = 0.007) and avoidant attachment style linked to social anxiety (β = 0.444, p = 0.012). As regards the resources, a significant negative health predictor in people supporting leukaemia patients is the anxious personality type (β = –0.375, p = 0.001), whereas a positive health predictor is the sen-se of support provided by others (β = 0.281, p = 0.001). Conclusions People supporting leukaemia patients point to the key role of the subjective resources possessed by an individual. Concentration on negative emotions and deficient resources, in particular the anxious personality, are definitely detrimental to health.","PeriodicalId":10652,"journal":{"name":"Contemporary Oncology","volume":" 26","pages":"71 - 74"},"PeriodicalIF":0.0,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141128887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Asmaa Emad El-Din Mohammed Rashad, Mostafa Abdelwanis Mohamed Abdelaziz, Manar Abdulwaniss Mohammed Abdulaziz
Introduction Oral squamous cell carcinoma (OSCC) is one of the most common malignancies of the head and neck, which attracts much attention because of its increasing incidence and poor outcome. Coffee is one of the most popular beverages that are globally consumed. It consists of several phytochemical constituents, such as polyphenols, caffeine, and chlorogenic acid (CGA). Those constituents account for the potential effects on several diseases, including cancer. It has been reported that coffee exerts significant cytotoxicity against OSCC via inhibition of epidermal growth factor receptor tyrosine kinase (EGFR-TK) and up-regulation of apoptotic proteins, such as caspase-3 and caspase-9. The current study aims to measure the concentration of caffeine and CGA in 3 different types of coffee extracts, unroasted green coffee (GC), medium-roasted coffee (MRC), and decaffeinated coffee. Material and methods The cytotoxic effect against OSCC-25 cell lines was evaluated and correlated with the concentration of constituents in each extract. The mechanisms of cytotoxicity were also studied by assessing the effect of each extract on caspase-3 and caspase-9 levels, in addition to the inhibitory effect on EGFR-TK. Results It was found that the caffeine concentration was higher in MRC than in GC because of the roasting process. However, the concentration of caspase-3 and -9 and the inhibitory effect on EGFR-TK were much higher in GC than MRC-treated cells because of the higher concentration of CGA. Conclusions Decaffeinated coffee exerts lower cytotoxic effects because it was totally deprived of caffeine and CGA during the decaffeination process.
{"title":"The impact of altering the concentration of coffee constituents on their anticancer effect on oral squamous cell carcinoma cell line – in vitro study","authors":"Asmaa Emad El-Din Mohammed Rashad, Mostafa Abdelwanis Mohamed Abdelaziz, Manar Abdulwaniss Mohammed Abdulaziz","doi":"10.5114/wo.2024.139374","DOIUrl":"https://doi.org/10.5114/wo.2024.139374","url":null,"abstract":"Introduction Oral squamous cell carcinoma (OSCC) is one of the most common malignancies of the head and neck, which attracts much attention because of its increasing incidence and poor outcome. Coffee is one of the most popular beverages that are globally consumed. It consists of several phytochemical constituents, such as polyphenols, caffeine, and chlorogenic acid (CGA). Those constituents account for the potential effects on several diseases, including cancer. It has been reported that coffee exerts significant cytotoxicity against OSCC via inhibition of epidermal growth factor receptor tyrosine kinase (EGFR-TK) and up-regulation of apoptotic proteins, such as caspase-3 and caspase-9. The current study aims to measure the concentration of caffeine and CGA in 3 different types of coffee extracts, unroasted green coffee (GC), medium-roasted coffee (MRC), and decaffeinated coffee. Material and methods The cytotoxic effect against OSCC-25 cell lines was evaluated and correlated with the concentration of constituents in each extract. The mechanisms of cytotoxicity were also studied by assessing the effect of each extract on caspase-3 and caspase-9 levels, in addition to the inhibitory effect on EGFR-TK. Results It was found that the caffeine concentration was higher in MRC than in GC because of the roasting process. However, the concentration of caspase-3 and -9 and the inhibitory effect on EGFR-TK were much higher in GC than MRC-treated cells because of the higher concentration of CGA. Conclusions Decaffeinated coffee exerts lower cytotoxic effects because it was totally deprived of caffeine and CGA during the decaffeination process.","PeriodicalId":10652,"journal":{"name":"Contemporary Oncology","volume":" 5","pages":"63 - 70"},"PeriodicalIF":0.0,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141129839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Asmaa Abdullatif, Aziza E. Abdelrahman, Adel Bakry, Shimaa Gharieb, Mohamed S H Ramadan, Mohamed A. Wasfy, Abdelfatah H. Abdelwanis, Enas M. Fouad
Introduction Death in cervical cancer patients is usually due to invasion and metastasis due to the aggressive nature of the tumour. Therefore, it is critical to identify potent therapeutic targets and prognostic markers to detect high-risk patients. Material and methods We assessed the immunohistochemical expression of protein disulphide isomerase A3 (PDIA3) and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in 50 cases of cervical carcinoma, and we investigated their association with clinicopathological characteristics. Results High PDIA3 was detected in 50% of cases, and statistical analysis revealed a positive correlation between high PDAI3 expression and tumour grade (p < 0.001) and large tumour size (p = 0.010), depth of stromal invasion (p = 0.017), lymph-vascular invasion (p = 0.005), parametrial invasion (p < 0.001), nodal metastasis (p < 0.001), and higher International Federation of Gynaecology and Obstetrics stages (p < 0.001). Positive nuclear expression of p-STAT3 was detected in 44% of cases and showed significant association with histological grade (p = 0.036), tumour stage (p = 0.021), nodal metastasis (p = 0.020), and parametrial invasion (p = 0.045); statistical analysis of the patient’s survival data revealed that shorter overall survival and disease-free survival, S, were associated with high PDIA3 expression and positive p-STAT3 immunoexpression. Conclusions The high expression of PDIA3 and p-STAT3 was related to highly aggressive cervical carcinoma with poor prognosis, and high risk of recurrence after the standardised protocol of treatment. Hence, both PDIA3 and p-STAT3 could be considered as novel biomarkers for tumour progression and promising targets in the management of cervical carcinoma patients.
{"title":"Clinicopathological significance of protein disulphide isomerase A3 and phosphorylated signal transducer and activator of transcription 3 in cervical carcinoma","authors":"Asmaa Abdullatif, Aziza E. Abdelrahman, Adel Bakry, Shimaa Gharieb, Mohamed S H Ramadan, Mohamed A. Wasfy, Abdelfatah H. Abdelwanis, Enas M. Fouad","doi":"10.5114/wo.2024.139368","DOIUrl":"https://doi.org/10.5114/wo.2024.139368","url":null,"abstract":"Introduction Death in cervical cancer patients is usually due to invasion and metastasis due to the aggressive nature of the tumour. Therefore, it is critical to identify potent therapeutic targets and prognostic markers to detect high-risk patients. Material and methods We assessed the immunohistochemical expression of protein disulphide isomerase A3 (PDIA3) and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in 50 cases of cervical carcinoma, and we investigated their association with clinicopathological characteristics. Results High PDIA3 was detected in 50% of cases, and statistical analysis revealed a positive correlation between high PDAI3 expression and tumour grade (p < 0.001) and large tumour size (p = 0.010), depth of stromal invasion (p = 0.017), lymph-vascular invasion (p = 0.005), parametrial invasion (p < 0.001), nodal metastasis (p < 0.001), and higher International Federation of Gynaecology and Obstetrics stages (p < 0.001). Positive nuclear expression of p-STAT3 was detected in 44% of cases and showed significant association with histological grade (p = 0.036), tumour stage (p = 0.021), nodal metastasis (p = 0.020), and parametrial invasion (p = 0.045); statistical analysis of the patient’s survival data revealed that shorter overall survival and disease-free survival, S, were associated with high PDIA3 expression and positive p-STAT3 immunoexpression. Conclusions The high expression of PDIA3 and p-STAT3 was related to highly aggressive cervical carcinoma with poor prognosis, and high risk of recurrence after the standardised protocol of treatment. Hence, both PDIA3 and p-STAT3 could be considered as novel biomarkers for tumour progression and promising targets in the management of cervical carcinoma patients.","PeriodicalId":10652,"journal":{"name":"Contemporary Oncology","volume":" 31","pages":"51 - 62"},"PeriodicalIF":0.0,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141129779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aleksandra Ciarka, M. Kunc, M. Popęda, A. Łacko, Barbara Radecka, Marcin Braun, Joanna Pikiel, M. Litwiniuk, Katarzyna Pogoda, Ewa Iżycka-Świeszewska, Anna Zeller, Magdalena Niemira, R. Pęksa, Wojciech Biernat, Elżbieta Senkus
Introduction This study aimed to evaluate the impact of tumour-infiltrating lymphocytes (TILs) on the expression of immune-related genes and prognosis in single hormone receptor-positive breast cancer. Material and methods: Tumour-infiltrating lymphocytes were analysed according to the guidelines of the International TILs Working Group in a cohort of 206 patients with single hormone receptor-positive breast cancer. Of these, 44.7% were classified as ER+/PgR–/HER2–, 18.4% as ER+/PgR–/HER2+, 26.2% as ER–/PgR+/HER2–, and 10.7% as ER–/PgR+/HER2+. Moreover, in 52 samples the analysis of gene expression profiling was performed using nCounter technology. Results Most cases (74.3%) showed at least 1% of stromal TILs, with a median of 4%, mean of 16.3%, and interquartile range of 0–20%. ER–/PgR+ tumours displayed significantly higher TILs density than ER+/PgR– cases (p < 0.001, Wilcoxon test), regardless of HER2 status. The abundance of TILs was positively associated with ER–/PgR+ phenotype, higher Ki-67, and higher grade, but not with age, tumour size, or regional and distant metastases at diagnosis. Additionally, in ER+/PgR– subgroup higher TILs were associated with HER2-positive status. Stromal TILs > 5% were associated with better survival in the whole group, but this effect was less prominent in ER–/PgR+ patients. We identified 50 differentially expressed genes (DEGs) between single hormone receptor-positive breast tumours with high and low TILs, including 39 up-regulated and 11 down-regulated genes in the high TILs group. Conclusions The up-regulated expression of immune-related genes was consistent also among separately analysed single hormone receptor-positive groups (ER+/PgR– and ER–/PgR+).
{"title":"High tumour-infiltrating lymphocytes correlate with distinct gene expression profile and favourable survival in single hormone receptor-positive breast cancer","authors":"Aleksandra Ciarka, M. Kunc, M. Popęda, A. Łacko, Barbara Radecka, Marcin Braun, Joanna Pikiel, M. Litwiniuk, Katarzyna Pogoda, Ewa Iżycka-Świeszewska, Anna Zeller, Magdalena Niemira, R. Pęksa, Wojciech Biernat, Elżbieta Senkus","doi":"10.5114/wo.2024.139375","DOIUrl":"https://doi.org/10.5114/wo.2024.139375","url":null,"abstract":"Introduction This study aimed to evaluate the impact of tumour-infiltrating lymphocytes (TILs) on the expression of immune-related genes and prognosis in single hormone receptor-positive breast cancer. Material and methods: Tumour-infiltrating lymphocytes were analysed according to the guidelines of the International TILs Working Group in a cohort of 206 patients with single hormone receptor-positive breast cancer. Of these, 44.7% were classified as ER+/PgR–/HER2–, 18.4% as ER+/PgR–/HER2+, 26.2% as ER–/PgR+/HER2–, and 10.7% as ER–/PgR+/HER2+. Moreover, in 52 samples the analysis of gene expression profiling was performed using nCounter technology. Results Most cases (74.3%) showed at least 1% of stromal TILs, with a median of 4%, mean of 16.3%, and interquartile range of 0–20%. ER–/PgR+ tumours displayed significantly higher TILs density than ER+/PgR– cases (p < 0.001, Wilcoxon test), regardless of HER2 status. The abundance of TILs was positively associated with ER–/PgR+ phenotype, higher Ki-67, and higher grade, but not with age, tumour size, or regional and distant metastases at diagnosis. Additionally, in ER+/PgR– subgroup higher TILs were associated with HER2-positive status. Stromal TILs > 5% were associated with better survival in the whole group, but this effect was less prominent in ER–/PgR+ patients. We identified 50 differentially expressed genes (DEGs) between single hormone receptor-positive breast tumours with high and low TILs, including 39 up-regulated and 11 down-regulated genes in the high TILs group. Conclusions The up-regulated expression of immune-related genes was consistent also among separately analysed single hormone receptor-positive groups (ER+/PgR– and ER–/PgR+).","PeriodicalId":10652,"journal":{"name":"Contemporary Oncology","volume":" 2","pages":"75 - 83"},"PeriodicalIF":0.0,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141129808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Teh, Abozer Y. Elderdery, S. Rampal, S. Subbiah, P. Mok
Introduction Cutaneous squamous cell carcinoma (SCC) is the second most common form of skin malignancy, representing around 20% of all skin cancers. It is the main cause of death due to non-melanoma skin cancer every year. Metastatic cutaneous SCC is associated with poor prognosis in patients and warrants a more effective and specific approach such as disruption of genes associated with cancer metastasis. Material and methods Matrix metalloproteinases (MMPs) are enzymes involved in cancer progression and are regarded as major oncotargets. Among others, MMP9 plays critical roles in tumour progression, angiogenesis, and invasion of cutaneous SCC. We aimed to determine whether the MMP9 gene is a suitable gene target for anti-cancer therapy for cutaneous SCC. We performed clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9 transfection of guide RNA (gRNA) targeting the MMP9 gene into human cutaneous SCC cell line A431. Results Following CRISPR transfection treatment, the viability (p < 0.01) and migratory activities (p < 0.0001) of in vitro cutaneous SCC cells were found to be reduced significantly. The use of quantitative polymerase chain reaction (qPCR) also revealed downregulation of the mRNA expression levels of cancer-promoting genes TGF-β, FGF, PI3K, VEGF-A, and vimentin. Direct inhibition of the MMP9 gene was shown to decrease survivability and metastasis of cutaneous SCC cell line A431. Conclusions Our findings provided direct evidence that MMP9 is important in the viability, proliferation, and metastasis of cutaneous SCC cells. It serves as a positive foundation for future CRISPR-based targeted anti-cancer therapies in treating skin cancer and other forms of malignancies that involve MMPs as the key determinants.
{"title":"Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 transfection of guide RNA targeting on MMP9 as anti-cancer therapy in human cutaneous squamous cell carcinoma cell line A431","authors":"S. Teh, Abozer Y. Elderdery, S. Rampal, S. Subbiah, P. Mok","doi":"10.5114/wo.2023.135364","DOIUrl":"https://doi.org/10.5114/wo.2023.135364","url":null,"abstract":"Introduction Cutaneous squamous cell carcinoma (SCC) is the second most common form of skin malignancy, representing around 20% of all skin cancers. It is the main cause of death due to non-melanoma skin cancer every year. Metastatic cutaneous SCC is associated with poor prognosis in patients and warrants a more effective and specific approach such as disruption of genes associated with cancer metastasis. Material and methods Matrix metalloproteinases (MMPs) are enzymes involved in cancer progression and are regarded as major oncotargets. Among others, MMP9 plays critical roles in tumour progression, angiogenesis, and invasion of cutaneous SCC. We aimed to determine whether the MMP9 gene is a suitable gene target for anti-cancer therapy for cutaneous SCC. We performed clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9 transfection of guide RNA (gRNA) targeting the MMP9 gene into human cutaneous SCC cell line A431. Results Following CRISPR transfection treatment, the viability (p < 0.01) and migratory activities (p < 0.0001) of in vitro cutaneous SCC cells were found to be reduced significantly. The use of quantitative polymerase chain reaction (qPCR) also revealed downregulation of the mRNA expression levels of cancer-promoting genes TGF-β, FGF, PI3K, VEGF-A, and vimentin. Direct inhibition of the MMP9 gene was shown to decrease survivability and metastasis of cutaneous SCC cell line A431. Conclusions Our findings provided direct evidence that MMP9 is important in the viability, proliferation, and metastasis of cutaneous SCC cells. It serves as a positive foundation for future CRISPR-based targeted anti-cancer therapies in treating skin cancer and other forms of malignancies that involve MMPs as the key determinants.","PeriodicalId":10652,"journal":{"name":"Contemporary Oncology","volume":"10 10","pages":"255 - 262"},"PeriodicalIF":0.0,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139958036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
T. Milecki, Katarzyna Kluzek, Natalia Pstrąg, Andrzej Antczak, W. Cieślikowski, Mateusz Wichtowski, Ł. Kuncman, Z. Kwias, Joanna Wesoły
Introduction Assessment of renal tumour masses is based on conventional imaging studies (computer tomography or magnetic resonance), which does not allow characterisation of the histopathological type. Moreover, the prediction of prognosis in localised and metastatic renal cell carcinoma requires improvement as well. Analysis of circulating free DNA (cfDNA) in blood is one of the variants of liquid biopsy that may improve diagnostics and prognosis issues of patients with renal tumour masses suspected to be renal cell carcinoma. The aim of the study was to assess the diagnostic and prognostic role of preoperative cfDNA concentration in the plasma samples of clear cell renal cell carcinoma (ccRCC) patients. Material and methods The preoperative plasma cfDNA concentration was assessed in ccRCC patients (n = 46) and healthy individuals (control group) (n = 17). The circulating free DNA concentration was reflected by the 90 bp DNA fragments determined by real-time polymerase chain reaction. Results The median cfDNA concentration was significantly higher in ccRCC patients (n = 46) compared to the control g roup (n = 17) (2588 ±2554 copies/ml vs. 960 ±490 copies/ml, p < 0.01). In multivariate analysis, the preoperative plasma cfDNA concentration was the significant factor increasing the probability of ccRCC detection (OR: 1.003; 95% CI: 1.001–1.005). The median cfDNA concentration depended on the stage of ccRCC; it was higher in metastatic ccRCC patients (n = 11) compared to non-metastatic ccRCC patients (n = 35) (3619 ±4059 copies/ml vs. 2473 ±1378 copies/ml, p < 0.03). Kaplan-Meier survival analysis demon-strated that patients with high cfDNA values (above 2913 copies/ml) had significantly worse cancer-specific survival (HR: 4.5; 95% CI: 1.3–16.9, log-rank Mantel-Cox test p = 0.015). Conclusions Preoperative plasma cfDNA concentration has diagnostic and prognostic potential in ccRCC pa-tients.
导言：肾肿瘤肿块的评估基于传统的成像研究（计算机断层扫描或磁共振），无法确定组织病理学类型。此外，对局部和转移性肾细胞癌预后的预测也需要改进。血液中的循环游离 DNA（cfDNA）分析是液体活检的变体之一，可改善疑似肾细胞癌肾肿瘤肿块患者的诊断和预后问题。本研究旨在评估透明细胞肾细胞癌（ccRCC）患者术前血浆样本中 cfDNA 浓度的诊断和预后作用。材料和方法 评估了ccRCC患者（46人）和健康人（对照组）（17人）术前血浆中的cfDNA浓度。循环游离 DNA 浓度通过实时聚合酶链反应测定的 90 bp DNA 片段来反映。结果 与对照组（17 人）相比，ccRCC 患者（46 人）的 cfDNA 中位浓度明显更高（2588 ±2554 拷贝/毫升 vs. 960 ±490 拷贝/毫升，P <0.01）。在多变量分析中，术前血浆 cfDNA 浓度是增加发现 ccRCC 概率的重要因素（OR：1.003；95% CI：1.001-1.005）。中位cfDNA浓度取决于ccRCC的分期；与非转移性ccRCC患者（35人）相比，转移性ccRCC患者（11人）的中位cfDNA浓度更高（3619 ±4059 copies/ml vs. 2473 ±1378 copies/ml，P < 0.03）。Kaplan-Meier生存分析表明，cfDNA值高（超过2913拷贝/毫升）的患者癌症特异性生存率明显较低（HR：4.5；95% CI：1.3-16.9，对数秩Mantel-Cox检验p = 0.015）。结论 术前血浆 cfDNA 浓度对 ccRCC 患者具有诊断和预后潜力。
{"title":"Preoperative cell-free DNA concentration in plasma as a diagnostic and prognostic biomarker of clear cell renal cell carcinoma","authors":"T. Milecki, Katarzyna Kluzek, Natalia Pstrąg, Andrzej Antczak, W. Cieślikowski, Mateusz Wichtowski, Ł. Kuncman, Z. Kwias, Joanna Wesoły","doi":"10.5114/wo.2023.135366","DOIUrl":"https://doi.org/10.5114/wo.2023.135366","url":null,"abstract":"Introduction Assessment of renal tumour masses is based on conventional imaging studies (computer tomography or magnetic resonance), which does not allow characterisation of the histopathological type. Moreover, the prediction of prognosis in localised and metastatic renal cell carcinoma requires improvement as well. Analysis of circulating free DNA (cfDNA) in blood is one of the variants of liquid biopsy that may improve diagnostics and prognosis issues of patients with renal tumour masses suspected to be renal cell carcinoma. The aim of the study was to assess the diagnostic and prognostic role of preoperative cfDNA concentration in the plasma samples of clear cell renal cell carcinoma (ccRCC) patients. Material and methods The preoperative plasma cfDNA concentration was assessed in ccRCC patients (n = 46) and healthy individuals (control group) (n = 17). The circulating free DNA concentration was reflected by the 90 bp DNA fragments determined by real-time polymerase chain reaction. Results The median cfDNA concentration was significantly higher in ccRCC patients (n = 46) compared to the control g roup (n = 17) (2588 ±2554 copies/ml vs. 960 ±490 copies/ml, p < 0.01). In multivariate analysis, the preoperative plasma cfDNA concentration was the significant factor increasing the probability of ccRCC detection (OR: 1.003; 95% CI: 1.001–1.005). The median cfDNA concentration depended on the stage of ccRCC; it was higher in metastatic ccRCC patients (n = 11) compared to non-metastatic ccRCC patients (n = 35) (3619 ±4059 copies/ml vs. 2473 ±1378 copies/ml, p < 0.03). Kaplan-Meier survival analysis demon-strated that patients with high cfDNA values (above 2913 copies/ml) had significantly worse cancer-specific survival (HR: 4.5; 95% CI: 1.3–16.9, log-rank Mantel-Cox test p = 0.015). Conclusions Preoperative plasma cfDNA concentration has diagnostic and prognostic potential in ccRCC pa-tients.","PeriodicalId":10652,"journal":{"name":"Contemporary Oncology","volume":"8 7","pages":"284 - 291"},"PeriodicalIF":0.0,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139957888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Monika Adamska, Ewelina Kowal-Wiśniewska, Joanna Czerwinska-Rybak, K. Kiwerska, M. Barańska, Weronika Gronowska, Jagoda Loba, Katarzyna Brzeźniakiewicz-Janus, Ewa Wasilewska, Aleksandra Łanocha, M. Jarmuż-Szymczak, Lidia Gil
Introduction Lower-risk myelodysplastic neoplasms (LR-MDS) comprise the majority of MDS. Despite favourable prognoses, some patients remain at risk of rapid progression. We aimed to define the mutational profile of LR-MDS using next-generation sequencing (NGS), Sanger Sequencing (SSeq), and pyrosequencing. Material and methods Samples from 5 primary LR-MDS (67 exons of SF3B1, U2AF1, SRSF2, ZRSR2, TET2, ASXL1, DNMT3A, TP53, and RUNX1 genes) were subjected to NGS. Next, a genomic study was performed to test for the presence of identified DNA sequence variants on a larger group of LR-MDS patients (25 bone marrow [BM], 3 saliva [SAL], and one peripheral blood [PB] sample/s). Both SSeq (all selected DNA sequence variants) and pyrosequencing (9 selected DNA sequence variants) were performed. Results Next-generation sequencing results identified 13 DNA sequence variants in 7 genes, comprising 8 mutations in 6 genes (ASXL1, DNMT3A, RUNX1, SF3B1, TET2, ZRSR2) in LR-MDS. The presence of 8 DNA variants was detected in the expanded LR-MDS group using SSeq and pyrosequencing. Mutation acquisition was observed during LR-MDS progression. Four LR-MDS and one acute myeloid leukaemia myelodysplasia-related patient exhibited the presence of at least one mutation. ASXL1 and SF3B1 alterations were most commonly observed (2 patients). Five DNA sequence variants detected in BM (patients: 9, 13) were also present in SAL. Conclusions We suggest using NGS to determine the LR-MDS mutational profile at diagnosis and suspicion of disease progression. Moreover, PB and SAL molecular testing represent useful tools for monitoring LR-MDS at higher risk of progression. However, the results need to be confirmed in a larger group.
导言 低危骨髓增生异常肿瘤（LR-MDS）占 MDS 的大多数。尽管预后良好，但仍有部分患者面临病情快速进展的风险。我们旨在利用新一代测序（NGS）、桑格测序（SSeq）和热测序确定 LR-MDS 的突变谱。材料与方法 对来自 5 个原发性 LR-MDS 的样本（SF3B1、U2AF1、SRSF2、ZRSR2、TET2、ASXL1、DNMT3A、TP53 和 RUNX1 基因的 67 个外显子）进行了 NGS 测序。接下来，对更大范围的 LR-MDS 患者（25 份骨髓样本、3 份唾液样本和 1 份外周血样本）进行了基因组研究，以检测是否存在已确定的 DNA 序列变异。同时进行了 SSeq（所有选定的 DNA 序列变异）和热测序（9 个选定的 DNA 序列变异）。结果 下一代测序结果在 LR-MDS 中发现了 7 个基因中的 13 个 DNA 序列变异，包括 6 个基因（ASXL1、DNMT3A、RUNX1、SF3B1、TET2、ZRSR2）中的 8 个突变。利用 SSeq 和热测序技术，在扩大的 LR-MDS 组中检测到了 8 个 DNA 变异。在LR-MDS进展过程中观察到了突变的获得。四名LR-MDS患者和一名急性髓性白血病骨髓增生异常相关患者至少出现了一种突变。最常见的是 ASXL1 和 SF3B1 变异（2 名患者）。在 BM（患者：9、13）中检测到的 5 个 DNA 序列变异也出现在 SAL 中。结论 我们建议在诊断和怀疑疾病进展时使用 NGS 来确定 LR-MDS 的突变情况。此外，PB 和 SAL 分子检测是监测进展风险较高的 LR-MDS 的有用工具。然而，这些结果还需要在更大的群体中得到证实。
{"title":"Defining the mutational profile of lower-risk myelodysplastic neoplasm patients with respect to disease progression using next-generation sequencing and pyrosequencing","authors":"Monika Adamska, Ewelina Kowal-Wiśniewska, Joanna Czerwinska-Rybak, K. Kiwerska, M. Barańska, Weronika Gronowska, Jagoda Loba, Katarzyna Brzeźniakiewicz-Janus, Ewa Wasilewska, Aleksandra Łanocha, M. Jarmuż-Szymczak, Lidia Gil","doi":"10.5114/wo.2023.135365","DOIUrl":"https://doi.org/10.5114/wo.2023.135365","url":null,"abstract":"Introduction Lower-risk myelodysplastic neoplasms (LR-MDS) comprise the majority of MDS. Despite favourable prognoses, some patients remain at risk of rapid progression. We aimed to define the mutational profile of LR-MDS using next-generation sequencing (NGS), Sanger Sequencing (SSeq), and pyrosequencing. Material and methods Samples from 5 primary LR-MDS (67 exons of SF3B1, U2AF1, SRSF2, ZRSR2, TET2, ASXL1, DNMT3A, TP53, and RUNX1 genes) were subjected to NGS. Next, a genomic study was performed to test for the presence of identified DNA sequence variants on a larger group of LR-MDS patients (25 bone marrow [BM], 3 saliva [SAL], and one peripheral blood [PB] sample/s). Both SSeq (all selected DNA sequence variants) and pyrosequencing (9 selected DNA sequence variants) were performed. Results Next-generation sequencing results identified 13 DNA sequence variants in 7 genes, comprising 8 mutations in 6 genes (ASXL1, DNMT3A, RUNX1, SF3B1, TET2, ZRSR2) in LR-MDS. The presence of 8 DNA variants was detected in the expanded LR-MDS group using SSeq and pyrosequencing. Mutation acquisition was observed during LR-MDS progression. Four LR-MDS and one acute myeloid leukaemia myelodysplasia-related patient exhibited the presence of at least one mutation. ASXL1 and SF3B1 alterations were most commonly observed (2 patients). Five DNA sequence variants detected in BM (patients: 9, 13) were also present in SAL. Conclusions We suggest using NGS to determine the LR-MDS mutational profile at diagnosis and suspicion of disease progression. Moreover, PB and SAL molecular testing represent useful tools for monitoring LR-MDS at higher risk of progression. However, the results need to be confirmed in a larger group.","PeriodicalId":10652,"journal":{"name":"Contemporary Oncology","volume":"87 5","pages":"269 - 279"},"PeriodicalIF":0.0,"publicationDate":"2024-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139959627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bożena Sikora-Kupis, Piotr Domański, Weronika Fortuniak, Barbara Kruczyk, Szymon Staneta, Mateusz Piętak, Anna Mydlak, Tomasz Demkow, Paulina Dumnicka, Jakub Kucharz
Introduction Urothelial carcinoma is the most common type of urinary tract malignancy. Current treatment options, including platinum-based chemotherapy or immunotherapy, present significant challenges, ranging from limited efficacy to severe toxicities. Recent developments in antibody-drug conjugates (ADC), such as enfortumab vedotin (EV), promise to significantly improve overall survival. The study aims to evaluate the efficacy and tolerability of EV. In addition, we highlight the observed benefits of next-line treatment after progression. Material and methods This retrospective study involved 16 patients with advanced urothelial cancer treated with EV at the Department of Genitourinary Oncology, Maria Skłodowska- Curie National Research Institute of Oncology between November 2022 and November 2023. The study evaluated patients’ medical history, response to EV treatment, and side effects. Notably, the study included patients who had already exhausted standard treatment options and who were treated with EV through a rescue access procedure. Results Partial response was observed in 4 out of 9 (44%) patients with available imaging. Common terminology criteria for adverse events (AE) grade 3 and 4 were observed in 3 out of 16 patients, which subsequently required dose reduction. Conclusions Enfortumab vedotin demonstrates effectiveness in real-world settings in treating advanced urothelial cancer. Proper management of AE in experienced centres may further prolong survival. Personalized treatment and the development of new ADC represent the future for improved patient outcomes.
导言 尿路上皮癌是最常见的尿路恶性肿瘤。目前的治疗方案，包括铂类化疗或免疫疗法，都面临着巨大的挑战，既有有限的疗效，也有严重的毒性。抗体药物共轭物（ADC）的最新进展，如恩福单抗维多汀（EV），有望显著提高总生存率。本研究旨在评估EV的疗效和耐受性。此外，我们还强调了观察到的进展后进行下线治疗的益处。材料与方法 本项回顾性研究涉及2022年11月至2023年11月期间在玛丽亚-斯克沃多夫斯卡-居里国家肿瘤研究所泌尿生殖肿瘤部接受EV治疗的16例晚期尿路上皮癌患者。该研究评估了患者的病史、对 EV 治疗的反应和副作用。值得注意的是，研究对象包括已经用尽标准治疗方案并通过抢救性入路手术接受EV治疗的患者。结果 在9名有影像学资料的患者中，有4名（44%）观察到部分反应。16例患者中有3例出现了通用术语标准的3级和4级不良事件（AE），随后需要减少剂量。结论 恩福单抗维多汀在现实世界中治疗晚期尿路上皮癌效果显著。在有经验的中心对AE进行适当处理可进一步延长患者的生存期。个性化治疗和新型 ADC 的开发代表着改善患者预后的未来。
{"title":"First experience in treating advanced urothelial cancer with enfortumab vedotin. Single-centre retrospective study of patients qualified for a rescue access procedure","authors":"Bożena Sikora-Kupis, Piotr Domański, Weronika Fortuniak, Barbara Kruczyk, Szymon Staneta, Mateusz Piętak, Anna Mydlak, Tomasz Demkow, Paulina Dumnicka, Jakub Kucharz","doi":"10.5114/wo.2023.134751","DOIUrl":"https://doi.org/10.5114/wo.2023.134751","url":null,"abstract":"Introduction Urothelial carcinoma is the most common type of urinary tract malignancy. Current treatment options, including platinum-based chemotherapy or immunotherapy, present significant challenges, ranging from limited efficacy to severe toxicities. Recent developments in antibody-drug conjugates (ADC), such as enfortumab vedotin (EV), promise to significantly improve overall survival. The study aims to evaluate the efficacy and tolerability of EV. In addition, we highlight the observed benefits of next-line treatment after progression. Material and methods This retrospective study involved 16 patients with advanced urothelial cancer treated with EV at the Department of Genitourinary Oncology, Maria Skłodowska- Curie National Research Institute of Oncology between November 2022 and November 2023. The study evaluated patients’ medical history, response to EV treatment, and side effects. Notably, the study included patients who had already exhausted standard treatment options and who were treated with EV through a rescue access procedure. Results Partial response was observed in 4 out of 9 (44%) patients with available imaging. Common terminology criteria for adverse events (AE) grade 3 and 4 were observed in 3 out of 16 patients, which subsequently required dose reduction. Conclusions Enfortumab vedotin demonstrates effectiveness in real-world settings in treating advanced urothelial cancer. Proper management of AE in experienced centres may further prolong survival. Personalized treatment and the development of new ADC represent the future for improved patient outcomes.","PeriodicalId":10652,"journal":{"name":"Contemporary Oncology","volume":"54 3","pages":"224 - 229"},"PeriodicalIF":0.0,"publicationDate":"2024-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139964865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction The aim of this work is to detect and classify brain tumours using computational intelligence techniques on magnetic resonance imaging (MRI) images. Material and methods A dataset of 3264 MRI brain images consisting of 4 categories: unspecified glioma, meningioma, pituitary, and healthy brain, was used in this study. Twelve convolutional neural networks (GoogleNet, MobileNetV2, Xception, DesNet-BC, ResNet 50, SqueezeNet, ShuffleNet, VGG-16, AlexNet, Enet, EfficientB0, and MobileNetV2 with meta pseudo-labels) were used to classify gliomas, meningiomas, pituitary tumours, and healthy brains to find the most appropriate model. The experiments included image preprocessing and hyperparameter tuning. The performance of each neural network was evaluated based on accuracy, precision, recall, and F-measure for each type of brain tumour. Results The experimental results show that the MobileNetV2 convolutional neural network (CNN) model was able to diagnose brain tumours with 99% accuracy, 98% recall, and 99% F1 score. On the other hand, the validation data analysis shows that the CNN model GoogleNet has the highest accuracy (97%) among CNNs and seems to be the best choice for brain tumour classification. Conclusions The results of this work highlight the importance of artificial intelligence and machine learning for brain tumour prediction. Furthermore, this study achieved the highest accuracy in brain tumour classification to date, and it is also the only study to compare the performance of so many neural networks simultaneously.
{"title":"Brain tumour detection from magnetic resonance imaging using convolutional neural networks","authors":"Irene Rethemiotaki","doi":"10.5114/wo.2023.135320","DOIUrl":"https://doi.org/10.5114/wo.2023.135320","url":null,"abstract":"Introduction The aim of this work is to detect and classify brain tumours using computational intelligence techniques on magnetic resonance imaging (MRI) images. Material and methods A dataset of 3264 MRI brain images consisting of 4 categories: unspecified glioma, meningioma, pituitary, and healthy brain, was used in this study. Twelve convolutional neural networks (GoogleNet, MobileNetV2, Xception, DesNet-BC, ResNet 50, SqueezeNet, ShuffleNet, VGG-16, AlexNet, Enet, EfficientB0, and MobileNetV2 with meta pseudo-labels) were used to classify gliomas, meningiomas, pituitary tumours, and healthy brains to find the most appropriate model. The experiments included image preprocessing and hyperparameter tuning. The performance of each neural network was evaluated based on accuracy, precision, recall, and F-measure for each type of brain tumour. Results The experimental results show that the MobileNetV2 convolutional neural network (CNN) model was able to diagnose brain tumours with 99% accuracy, 98% recall, and 99% F1 score. On the other hand, the validation data analysis shows that the CNN model GoogleNet has the highest accuracy (97%) among CNNs and seems to be the best choice for brain tumour classification. Conclusions The results of this work highlight the importance of artificial intelligence and machine learning for brain tumour prediction. Furthermore, this study achieved the highest accuracy in brain tumour classification to date, and it is also the only study to compare the performance of so many neural networks simultaneously.","PeriodicalId":10652,"journal":{"name":"Contemporary Oncology","volume":"1 3","pages":"230 - 241"},"PeriodicalIF":0.0,"publicationDate":"2024-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139964694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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