NeoplasmaPub Date : 2024-04-01DOI: 10.4149/neo_2024_240328N140
Katarina Gercakova, Martina Poturnajova, Silvia Tyciakova, Ingeborg Rezuchova, Miroslava Matuskova
{"title":"Mouse models for cancer research - current state and the perspective.","authors":"Katarina Gercakova, Martina Poturnajova, Silvia Tyciakova, Ingeborg Rezuchova, Miroslava Matuskova","doi":"10.4149/neo_2024_240328N140","DOIUrl":"10.4149/neo_2024_240328N140","url":null,"abstract":"<p><p>Cancer is one of the leading causes of death worldwide. We still do not understand all the details of carcinogenesis, and effective treatment is lacking for many oncological diseases. Animal models provide an irreplaceable tool to observe the growth and spreading of neoplastic cells in an environment of living organisms, to test the efficacy of cancer treatment, side effects, and toxicity, and to study the tumor microenvironment. Mice are the most often used model organisms because of their easy handling, short reproductive period, multiple strains, and complete DNA sequencing. An ideal model should accurately recapitulate each step of tumor development. Recent techniques have established models that enable the study of different aspects of cancer, but choosing a particular model depends on the application of output data. This article aimed to review induced, transplantable, and engineered mice and highlight their significance for recent and future cancer research.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"71 2","pages":"99-116"},"PeriodicalIF":3.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141066013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NeoplasmaPub Date : 2024-04-01DOI: 10.4149/neo_2024_231219N652
Silvia Fecikova, Lucia Csaderova, Petra Belvoncikova, Barbora Puzderova, Kamila Bernatova, Tomas Talac, Jaromir Pastorek, Monika Barathova
{"title":"Can hypoxia marker carbonic anhydrase IX serve as a potential new diagnostic marker and therapeutic target of non-small cell lung cancer?","authors":"Silvia Fecikova, Lucia Csaderova, Petra Belvoncikova, Barbora Puzderova, Kamila Bernatova, Tomas Talac, Jaromir Pastorek, Monika Barathova","doi":"10.4149/neo_2024_231219N652","DOIUrl":"10.4149/neo_2024_231219N652","url":null,"abstract":"<p><p>Lung cancer represents the leading cause of cancer-related deaths. Non-small cell lung cancer (NSCLC), the most common form of lung cancer, is a molecularly heterogeneous disease with intratumoral heterogeneity and a significant mutational burden associated with clinical outcome. Tumor microenvironment (TME) plays a fundamental role in the initiation and progression of primary de novo lung cancer and significantly influences the response of tumor cells to therapy. Hypoxia, an integral part of the tumor microenvironment and a serious clinical phenomenon, is associated with increased genetic instability and a more aggressive phenotype of NSCLC, which correlates with the risk of metastasis. Low oxygen concentration influences all components of TME including the immune microenvironment. Hypoxia-inducible pathway activated in response to low oxygen supply mediates the expression of genes important for the adaptation of tumor cells to microenvironmental changes. A highly active transmembrane hypoxia-induced metalloenzyme - carbonic anhydrase IX (CAIX), as a part of transport metabolon, contributes to the maintenance of intracellular pH within physiological values and to the acidification of the extracellular space. CAIX supports cell migration and invasion and plays an important role in NSCLC tumor tissue and pleural effusion. Due to its high expression, it also represents a potential diagnostic differential biomarker and therapeutic target in NSCLC. To test new potential targeted therapeutic compounds, suitable models are required that more faithfully simulate tumor tissue, TME components, and spatial architecture.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"71 2","pages":"123-142"},"PeriodicalIF":3.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141066006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NeoplasmaPub Date : 2024-04-01DOI: 10.4149/neo_2024_231209N633
Vesna Bišof, Andrija Katić, Majana Soče, Marina Vidović, Jelena Viculin, Stjepko Pleština, Eduard Vrdoljak
{"title":"Impact of the number of therapy lines on survival in advanced gastric and esophagogastric adenocarcinoma - a real-world retrospective analysis from Croatia.","authors":"Vesna Bišof, Andrija Katić, Majana Soče, Marina Vidović, Jelena Viculin, Stjepko Pleština, Eduard Vrdoljak","doi":"10.4149/neo_2024_231209N633","DOIUrl":"https://doi.org/10.4149/neo_2024_231209N633","url":null,"abstract":"<p><p>The aim of the study was to conduct a retrospective database analysis to understand the current treatment patterns and outcomes to plan potential improvements in therapy delivery and patient selection. The electronic patient medical records of 225 patients with advanced gastric and esophagogastric adenocarcinoma treated at two Croatian high-volume tertiary centers from January 2018 to December 2021 were analyzed. Patients ineligible for chemotherapy (66 of 291, 22.7%) due to poor general condition or co-morbidities were not included in the study. The median overall survival (OS) for the whole cohort was 11.0 months (95% confidence interval (CI) 9.7-12.0). Of the 225 patients who received first-line therapy, 47.6%, 16.9%, and 3.1% received second-, third-, and fourth-line therapy, respectively. Survival correlated significantly with the number of treatment lines received (p<0.001), with a median OS from diagnosis of 7.8 (95% CI 6.6-9.4), 12.0 (95% CI 10.0-14.0), and 20.0 months (95% CI 18.0-23.0) for patients receiving 1, 2, and ≥3 lines of treatment, respectively. This study confirmed the positive impact of the number of chemotherapy lines on OS. This highlights the importance of the ratio of patients receiving multiple lines of therapy as well as the availability of new and effective drugs in real-life clinical practice. The selection of optimal therapy for each patient in the first-line therapy is important because a significant number of patients do not receive second-line therapy.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"71 2","pages":"201-208"},"PeriodicalIF":3.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141066011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NeoplasmaPub Date : 2024-04-01DOI: 10.4149/neo_2024_240116N24
Li Liang, Jin Wang, Tao Guo, Lijun Huang, Yanping Wu, Rui Xu, Tong Huang, Binghua Ma
{"title":"Calreticulin regulates the expression of MMP14 and ADAR1 through EIF2AK2 signaling to promote the proliferation and progression of malignant melanoma cells.","authors":"Li Liang, Jin Wang, Tao Guo, Lijun Huang, Yanping Wu, Rui Xu, Tong Huang, Binghua Ma","doi":"10.4149/neo_2024_240116N24","DOIUrl":"10.4149/neo_2024_240116N24","url":null,"abstract":"<p><p>It has been demonstrated that calreticulin (CALR) is expressed abnormally in various tumors and is involved in the occurrence and development of tumors. In this study, CALR and EIF2AK2 expression was measured in the clinical specimens of 39 patients with melanoma. Then, we constructed knockdown and overexpression cell models of CALR and EIF2AK2 and used wound healing and Transwell assays to observe cell migration and invasion. Apoptosis, EDU, and ROS assays were used to measure cell apoptosis and proliferation, as well as ROS levels. The effect of CALR on endoplasmic reticulum stress was detected using endoplasmic reticulum fluorescent probes. Western blotting was used to detect protein levels of CALR, EIF2AK2, ADAR1, and MMP14. The results indicated that CALR and EIF2AK2 expression levels were significantly higher in human melanoma tissues than in adjacent non-tumor tissue. In addition, we found a correlation between CALR and the expression of EIF2AK2 and MMP14, and the experimental results indicated that overexpression of CALR significantly upregulated the expression of EIF2AK2, MMP14, and ADAR1, while knockdown of CALR inhibited their expression. Notably, the knockdown of EIF2AK2 in the CALR overexpression group blocked the upregulation of MMP14 and ADAR1 expression by CALR, and the knockdown of both CALR and EIF2AK2 significantly inhibited MMP14 and ADAR1 expression. In conclusion, CALR and EIF2AK2 play a promoting role in melanoma progression, and knockdown of CALR and EIF2AK2 may be an effective anti-tumor target, and its mechanism may be through MMP14, ADAR1 signaling.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"71 2","pages":"180-192"},"PeriodicalIF":2.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141065977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Nanocomposite hydrogels in skin cancer medicine.","authors":"Lucia Balintova, Michaela Blazickova, Monika Sramkova","doi":"10.4149/neo_2024_240315N118","DOIUrl":"10.4149/neo_2024_240315N118","url":null,"abstract":"<p><p>Skin cancer is one of the most common malignancies in white populations. The therapy strategy is important in skin cancer treatment, depending on several criteria such as stage, size, and localization. Removal of cancerous tissue following anticancer therapeutic administration is considered as gold standard in skin cancer treatment. However, annually rising drug resistance, local inflammation, and ineffective treatment result in a reduction in the effectiveness of the patient's treatment. Nanotechnology has emerged as a prospective in the field of skin cancer medicine, offering innovative, promising solutions for therapeutic procedures and targeted drug delivery. Different nanomaterials are investigated for their potential in skin cancer treatment. Nanohydrogels as a hybrid material, have gained considerable attention due to their unique biomedical and pharmaceutical properties, such as biocompatibility, high water content, and tunable physicochemical characteristics. The principal problem with common skin melanoma chemotherapy is the strong side effects because therapeutics used for treatment do not distinguish cancer cells from healthy cells. Nanohydrogels, as a new-generation, versatile system with the possession of dual characteristics of hydrogels and nanoparticles have shown great potential in targeted delivery in cancer therapy thanks to the possibility of their various modifications, and by that overcome problems with side effects of treatment. This scientific review provides an analysis of the current state of research on nanohydrogels in skin cancer medicine, highlighting their design principles, synthesis methods, and applications in drug delivery, imaging, and combination therapies.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"71 2","pages":"153-163"},"PeriodicalIF":3.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141066016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NeoplasmaPub Date : 2024-04-01DOI: 10.4149/neo_2024_240207N58
Eva Lukáčová, Ondrej Pös, Eva Túryová, Tatiana Hurtová, Zuzana Hanzlíková, Tomáš Szemes, Tatiana Burjanivová
{"title":"Copy number variations in malignant melanoma: genomic regions, biomarkers, and therapeutic targets.","authors":"Eva Lukáčová, Ondrej Pös, Eva Túryová, Tatiana Hurtová, Zuzana Hanzlíková, Tomáš Szemes, Tatiana Burjanivová","doi":"10.4149/neo_2024_240207N58","DOIUrl":"10.4149/neo_2024_240207N58","url":null,"abstract":"<p><p>Malignant melanoma is a skin tumor arising from melanocytes, occurring mostly in predisposed individuals. Melanomas are frequently present with copy number variations (CNVs), i.e., gains or losses of specific DNA regions that have provided immense potential for disease diagnosis and classification. The methodology of CNV detection has revolutionized in past decades, and current high throughput technologies enable us to analyze the entire spectrum of CNV alterations at the whole genome scale. Thus, identifying novel CNV biomarkers and evaluating their applicability in biomedicine are becoming increasingly important. The aim of this review was to summarize copy number changes occurring in malignant melanomas. We made an overview of specific genes and chromosomal locations affected in sporadic and familial melanoma and also of known germline alterations in melanoma-prone families. We summarized genomic regions aberrant in malignant melanoma and highlighted those frequently discussed in the literature, suggesting 7q, 11q, 12q, 9p, and 1q, but also others, as the most affected ones.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"71 2","pages":"143-152"},"PeriodicalIF":3.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141066009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NeoplasmaPub Date : 2024-04-01DOI: 10.4149/neo_2024_240321N127
Jana Lapinova, Miroslav Balaz, Lucia Balazova, Lucia Csaderova, Tereza Golias, Miriam Zatovicova, Joerg Heeren, Silvia Pastorekova, Martina Takacova
{"title":"Unlocking the paracrine crosstalk: adipocyte-derived factors affect carbonic anhydrase IX expression in colon and breast cancer cells.","authors":"Jana Lapinova, Miroslav Balaz, Lucia Balazova, Lucia Csaderova, Tereza Golias, Miriam Zatovicova, Joerg Heeren, Silvia Pastorekova, Martina Takacova","doi":"10.4149/neo_2024_240321N127","DOIUrl":"10.4149/neo_2024_240321N127","url":null,"abstract":"<p><p>Obesity is a major public health concern because it increases the risk of several diseases, including cancer. Crosstalk between obesity and cancer seems to be very complex, and the interaction between adipocytes and cancer cells leads to changes in adipocytes' function and their paracrine signaling, promoting a microenvironment that supports tumor growth. Carbonic anhydrase IX (CA IX) is a tumor-associated enzyme that not only participates in pH regulation but also facilitates metabolic reprogramming and supports the migration, invasion, and metastasis of cancer cells. In addition, CA IX expression, predominantly regulated via hypoxia-inducible factor (HIF-1), serves as a surrogate marker of hypoxia. In this study, we investigated the impact of adipocytes and adipocyte-derived factors on the expression of CA IX in colon and breast cancer cells. We observed increased expression of CA9 mRNA as well as CA IX protein in the presence of adipocytes and adipocyte-derived conditioned medium. Moreover, we confirmed that adipocytes affect the hypoxia signaling pathway and that the increased CA IX expression results from adipocyte-mediated induction of HIF-1α. Furthermore, we demonstrated that adipocyte-mediated upregulation of CA IX leads to increased migration and decreased adhesion of colon cancer cells. Finally, we brought experimental evidence that adipocytes, and more specifically leptin, upregulate CA IX expression in cancer cells and consequently promote tumor progression.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"71 2","pages":"164-179"},"PeriodicalIF":2.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141066053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NeoplasmaPub Date : 2024-04-01DOI: 10.4149/neo_2024_231222N658
Michaela Blažíčková, Mária Bučková, Katarína Kozics
{"title":"Characterization of the effects of thymol derivatives on colorectal cancer spheroids.","authors":"Michaela Blažíčková, Mária Bučková, Katarína Kozics","doi":"10.4149/neo_2024_231222N658","DOIUrl":"https://doi.org/10.4149/neo_2024_231222N658","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is one of the most commonly diagnosed malignancies with a high mortality rate. In the last few years, attention has been focused on substances of natural origin with anticancer activity. One such substance is thymol and its derivatives, which have been shown to have an antitumor effect also against CRC cells. In our study, we focused on determining the biological and antibacterial effects of thymol and thymol derivatives. Analyses were performed on a 3D model of human colon carcinoma cell lines (HCT-116 and HT-29) - spheroids. The cytotoxic (MTT assay) and genotoxic effect (comet assay) of thymol and derivatives: acetic acid thymol ester and thymol ß-D-glucoside were determined. ROS levels (ROS-Glo™ H2O2 Assay) and total antioxidant status (Randox TAS Assay) were also monitored. Last but not least, we also detected the effect of the derivatives using a disk diffusion assay and determined the number of colonies on the plates on selected bacteria such as Lacticaseibacillus rhamnosus, Lactiplantibacillus plantarum, Lacticaseibacillus paracasei, Lactobacillus brevis, Lactobacillus pentosus and Weizmannia coagulans. The derivatives did not show a significant inhibitory effect on the growth of LAB bacteria (lactic acid bacteria) in contrast to thymol. Overall, thymol derivatives are cytotoxic, genotoxic and increase ROS levels. Among the derivatives tested, acetic acid thymol ester (IC50 ~ 0.2 μg/ml) was more effective. The second derivative tested (thymol β-D-glucoside) was effective at higher concentrations than thymol. Our research confirmed that thymol derivatives have a toxic effect on the 3D model of intestinal tumor cells, while they do not have a toxic effect on selected intestinal bacteria. Thus, they could bring new significance to the prevention or treatment of CRC.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"71 2","pages":"193-200"},"PeriodicalIF":3.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141066008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NeoplasmaPub Date : 2024-04-01DOI: 10.4149/neo_2024_240208N59
Dajana Vanova, Michal Andrezal, Jana Jakubechova, Ursula Altanerova, Cestmir Altaner
{"title":"Participation of suicide gene extracellular vesicles in metastasis prevention.","authors":"Dajana Vanova, Michal Andrezal, Jana Jakubechova, Ursula Altanerova, Cestmir Altaner","doi":"10.4149/neo_2024_240208N59","DOIUrl":"10.4149/neo_2024_240208N59","url":null,"abstract":"<p><p>The incidence of distant metastases is associated with most cancer-related mortalities. Extracellular vesicles (EVs), secreted from tumors and cancer-associated fibroblasts, are involved in the metastatic process mediating their organotropism through their involvement in the pre-metastatic niche formation. We have been developing suicide gene therapy mediated by EVs secreted from mesenchymal stem/ stromal cells, tumor cells, and cancer-associated fibroblasts. Suicide gene EVs conjugated with prodrug are tumor tropic, penetrate tumor cells, and kill them by intracellular conversion of nontoxic prodrug to an efficient anti-cancer drug. Here, we discuss findings regarding the possibility of using suicide gene EVs as a novel therapeutic approach for metastases, via pre-metastatic niche modification. The suicide gene EVs provide a future perspective for metastasis prevention.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"71 2","pages":"117-122"},"PeriodicalIF":3.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141066043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"USP36 plays an oncogenic role in colorectal cancer cells.","authors":"Lixiong Luo, Yijiang Li, Rongjie Huang, Ling Li, Chuncai Wu, Qunzhang Zeng","doi":"10.4149/neo_2023_230629N339","DOIUrl":"10.4149/neo_2023_230629N339","url":null,"abstract":"<p><p>Cancer stem cells (CSCs) have emerged as crucial contributors to tumor relapse and chemoresistance, making them promising targets for treating cancers like colorectal cancer (CRC). However, the mechanisms governing CSC maintenance in CRC remain poorly characterized. In this study, we investigated the potential role of ubiquitin-specific protease 36 (USP36) in CRC. Our bioinformatic analysis revealed a significant upregulation of USP36 expression in CRC, and high USP36 levels were associated with poor prognosis in CRC patients. Furthermore, we observed an increase in USP36 expression in CRC cell lines. Knockdown of USP36 resulted in reduced viability, cell cycle arrest, increased apoptosis, and impaired migration and invasion in CRC cells. Additionally, the colony formation and sphere formation ability, as well as the expression of stem cell markers and pluripotent transcription factors, were substantially reduced in USP36-deficient CRC cells. These findings emphasize the role of USP36 as an oncogene in CRC, highlighting its potential as a therapeutic target for the treatment of CRC.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":" ","pages":"13-21"},"PeriodicalIF":3.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139432786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}