Pub Date : 2023-08-01DOI: 10.4149/neo_2023_230526N287
Viktor Bielik, Ivan Hric, Sabína Šmahová, Miriam Tkačiková, Veronika Hlaváčová, Libuša Nechalová, Simona Ugrayová, Alexandra Kolenová
Gut microbial dysbiosis persists months after intensive cancer treatment in children and adolescents. This prospective study compared the intestinal microbiome of children 1-3 years after completion of Berlin-Frankfurt-Münster protocol (BFM)-based pediatric ALL (PALL) treatment and healthy controls. To induce a favorable shift in the bacterial composition of the intestines in PALL with gut microbiome disruptions, 8 weeks of physical activity and probiotic consumption were used. Blood analyses and 16S rRNA sequencing for the gut microbiome were performed on 16 pediatric cases and 16 healthy controls. Significant differences in bacterial diversity were found between pre- and post-intervention, respectively (Shannon index, 3.22±0.45 vs. 3.47±0.24, p=0.04; Simpson index, 0.10±0.05 vs. 0.06±0.02, p=0.02; and Chao1 index, 693.88±238.58 vs. 794.23±116.34, p=0.04). Furthermore, the increase in the relative abundance of Lactobacillus casei (5.04E-03±1.62E-02 vs. 2.92E-02±5.03E-02, p=0.04) and the increase in some strains of Veillonella, a bacterial genus recently linked to improved physical fitness, were identified. Promisingly, the exercise program combined with dairy probiotics increased bacterial richness and diversity.
{"title":"The effect of physical exercise and dairy probiotics (Lactobacillus casei) on gut microbiome in childhood cancer survivors.","authors":"Viktor Bielik, Ivan Hric, Sabína Šmahová, Miriam Tkačiková, Veronika Hlaváčová, Libuša Nechalová, Simona Ugrayová, Alexandra Kolenová","doi":"10.4149/neo_2023_230526N287","DOIUrl":"https://doi.org/10.4149/neo_2023_230526N287","url":null,"abstract":"<p><p>Gut microbial dysbiosis persists months after intensive cancer treatment in children and adolescents. This prospective study compared the intestinal microbiome of children 1-3 years after completion of Berlin-Frankfurt-Münster protocol (BFM)-based pediatric ALL (PALL) treatment and healthy controls. To induce a favorable shift in the bacterial composition of the intestines in PALL with gut microbiome disruptions, 8 weeks of physical activity and probiotic consumption were used. Blood analyses and 16S rRNA sequencing for the gut microbiome were performed on 16 pediatric cases and 16 healthy controls. Significant differences in bacterial diversity were found between pre- and post-intervention, respectively (Shannon index, 3.22±0.45 vs. 3.47±0.24, p=0.04; Simpson index, 0.10±0.05 vs. 0.06±0.02, p=0.02; and Chao1 index, 693.88±238.58 vs. 794.23±116.34, p=0.04). Furthermore, the increase in the relative abundance of Lactobacillus casei (5.04E-03±1.62E-02 vs. 2.92E-02±5.03E-02, p=0.04) and the increase in some strains of Veillonella, a bacterial genus recently linked to improved physical fitness, were identified. Promisingly, the exercise program combined with dairy probiotics increased bacterial richness and diversity.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"70 4","pages":"588-596"},"PeriodicalIF":3.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41167490","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}
Pub Date : 2023-08-01DOI: 10.4149/neo_2023_230413N206
Dongbo Chen, Xiangxun Chen, Lei Xu, Yichun Wang, Liyang Zhu, Mei Kang
Although a phase II clinical trial confirmed that camrelizumab combined with apatinib is effective in patients with hepatocellular carcinoma (HCC), we generally lack data on the results of this regimen in real-world clinical practice. In this study, the efficacy and safety of camrelizumab combined with apatinib in the treatment of patients with HCC were re-evaluated. Data from 86 patients with HCC were collected and combinatorically treated with camrelizumab and apatinib at the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China. The objective remission rate and disease control rate were 25.6% and 72.1%, respectively. The median progression-free survival was 5 months (95% CI 3.7-6.3 months), and the median overall survival time was 19.0 months (95% CI 16.9-21.1 months). The 12- and 18-month survival rates were 70.9% and 54.2%, respectively. The most common grade 3-4 adverse events were hypertension (24.4%), thrombocytopenia (16.3%), and hyperbilirubinemia (9.3%). Multivariate regression analysis showed that operation history was an independent risk factor for overall survival.
{"title":"Camrelizumab combined with apatinib in the treatment of patients with hepatocellular carcinoma: a real-world assessment.","authors":"Dongbo Chen, Xiangxun Chen, Lei Xu, Yichun Wang, Liyang Zhu, Mei Kang","doi":"10.4149/neo_2023_230413N206","DOIUrl":"https://doi.org/10.4149/neo_2023_230413N206","url":null,"abstract":"<p><p>Although a phase II clinical trial confirmed that camrelizumab combined with apatinib is effective in patients with hepatocellular carcinoma (HCC), we generally lack data on the results of this regimen in real-world clinical practice. In this study, the efficacy and safety of camrelizumab combined with apatinib in the treatment of patients with HCC were re-evaluated. Data from 86 patients with HCC were collected and combinatorically treated with camrelizumab and apatinib at the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China. The objective remission rate and disease control rate were 25.6% and 72.1%, respectively. The median progression-free survival was 5 months (95% CI 3.7-6.3 months), and the median overall survival time was 19.0 months (95% CI 16.9-21.1 months). The 12- and 18-month survival rates were 70.9% and 54.2%, respectively. The most common grade 3-4 adverse events were hypertension (24.4%), thrombocytopenia (16.3%), and hyperbilirubinemia (9.3%). Multivariate regression analysis showed that operation history was an independent risk factor for overall survival.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"70 4","pages":"580-587"},"PeriodicalIF":3.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41138236","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}
Pub Date : 2023-08-01DOI: 10.4149/neo_2023_230806N411
Danica Ivovič, Pavlína Kabelíková, Dana Jurkovičová
Protein phosphatase 2A (PP2A) is a major serine/threonine phosphatase considered a potent tumor suppressor that critically regulates diverse cellular processes, including cell cycle progression, apoptosis, or DNA repair. PP2A is typically downregulated in cancers but mechanisms for its inactivation in human cancers are poorly understood. PP2A represents a family of more than 60 phosphatases. According to cellular context, each heterotrimeric PP2A holoenzyme exerts a unique role in cancer, and PP2A isoforms can act either as tumor suppressors or as promoters. Due to wide structural diversity, PP2A has been considered undruggable. However, increasing knowledge predisposes PP2A diversity to therapeutical targeting for the treatment of a broad range of cancer pathologies, including drug resistance or cloaking immune surveillance. In this review, we discuss the regulatory role of PP2A in cancer, its regulation by microRNA and hypoxia, its contribution to therapy resistance development, and the therapeutic potential of direct and indirect targeting, or combinatory administration with other anti-cancer drugs to improve cancer treatment outcomes.
{"title":"Unraveling the complexity: A comprehensive analysis of the PP2A in cancer and its potential for novel targeted therapies.","authors":"Danica Ivovič, Pavlína Kabelíková, Dana Jurkovičová","doi":"10.4149/neo_2023_230806N411","DOIUrl":"10.4149/neo_2023_230806N411","url":null,"abstract":"<p><p>Protein phosphatase 2A (PP2A) is a major serine/threonine phosphatase considered a potent tumor suppressor that critically regulates diverse cellular processes, including cell cycle progression, apoptosis, or DNA repair. PP2A is typically downregulated in cancers but mechanisms for its inactivation in human cancers are poorly understood. PP2A represents a family of more than 60 phosphatases. According to cellular context, each heterotrimeric PP2A holoenzyme exerts a unique role in cancer, and PP2A isoforms can act either as tumor suppressors or as promoters. Due to wide structural diversity, PP2A has been considered undruggable. However, increasing knowledge predisposes PP2A diversity to therapeutical targeting for the treatment of a broad range of cancer pathologies, including drug resistance or cloaking immune surveillance. In this review, we discuss the regulatory role of PP2A in cancer, its regulation by microRNA and hypoxia, its contribution to therapy resistance development, and the therapeutic potential of direct and indirect targeting, or combinatory administration with other anti-cancer drugs to improve cancer treatment outcomes.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"70 4","pages":"485-499"},"PeriodicalIF":3.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41159356","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}
Glioma is a highly aggressive primary malignant tumor. Migration-inducing gene-7 (Mig-7) is closely related to tumor invasion and metastasis. However, the detailed molecular mechanism of Mig-7-mediated promotion of glioma cell invasion requires further investigation. Therefore, this study aimed to investigate the molecular mechanism by which Mig-7 promotes invasion and growth of glioma tumor cells. After collecting 65 glioma tissues and 16 non-tumor tissues, the expression difference of Mig-7 between tumor tissues and non-tumor tissues was analyzed. The molecular mechanism of Mig-7 in tumor cells was investigated by knockdown or overexpression of Mig-7 in U87MG cells. Specifically, the expression levels of mitogen-activated protein kinase (MAPK) signaling pathway-related molecules were detected in cells that knocked down Mig-7. MTT, Transwell, and three-dimensional cell culture assays were used to detect the survival, migration, invasion, and tube formation of U87MG cells that overexpressed Mig-7 were treated with the MAPK signaling pathway inhibitors (SP600125, SCH772984, and SB202190). The effect of Mig-7 on the tumorigenic ability of U87MG cells was investigated by subcutaneous tumorigenic experiment in nude mice. The corresponding results indicated that Mig-7 expression was significantly higher in glioma tissues and cell lines compared to that in non-neoplastic brain tissues and normal glial cell lines. In U87MG cells, downregulation or overexpression of Mig-7 inhibited or promoted the expression of MMP-2, MMP-9, LAMC2, EphA2, and VE-cadherin, and phosphorylation levels of ERK1/2, JNK, and p38. Mig-7 overexpression promoted migration, invasion, cell viability, and tube formation, which were reversed by the MAPK signaling pathway inhibitors. Mig-7 overexpression promoted subcutaneous tumor growth in mice and upregulated the phosphorylation levels of ERK1/2, JNK, and p38 and the expression of Ki-67. These effects of Mig-7 overexpression were reversed by MAPK pathway inhibitors. Overall, these results suggest that Mig-7 may be a novel biomarker and potential therapeutic target for glioma, with the MAPK pathway playing a key role in the corresponding Mig-7 mechanism of action.
{"title":"Migration-inducing gene-7 promotes glioma cell proliferation and invasiveness via activating the MAPK signaling pathway.","authors":"Zhigang Pan, Chunhui Chen, Xinyue Huang, Yu Xiong, Xiaodong Kang, Jianfeng Zhou, Xiumei Guo, Shuni Zheng, Cui'e Wang, Feng Zheng, Weipeng Hu","doi":"10.4149/neo_2023_230307N121","DOIUrl":"https://doi.org/10.4149/neo_2023_230307N121","url":null,"abstract":"<p><p>Glioma is a highly aggressive primary malignant tumor. Migration-inducing gene-7 (Mig-7) is closely related to tumor invasion and metastasis. However, the detailed molecular mechanism of Mig-7-mediated promotion of glioma cell invasion requires further investigation. Therefore, this study aimed to investigate the molecular mechanism by which Mig-7 promotes invasion and growth of glioma tumor cells. After collecting 65 glioma tissues and 16 non-tumor tissues, the expression difference of Mig-7 between tumor tissues and non-tumor tissues was analyzed. The molecular mechanism of Mig-7 in tumor cells was investigated by knockdown or overexpression of Mig-7 in U87MG cells. Specifically, the expression levels of mitogen-activated protein kinase (MAPK) signaling pathway-related molecules were detected in cells that knocked down Mig-7. MTT, Transwell, and three-dimensional cell culture assays were used to detect the survival, migration, invasion, and tube formation of U87MG cells that overexpressed Mig-7 were treated with the MAPK signaling pathway inhibitors (SP600125, SCH772984, and SB202190). The effect of Mig-7 on the tumorigenic ability of U87MG cells was investigated by subcutaneous tumorigenic experiment in nude mice. The corresponding results indicated that Mig-7 expression was significantly higher in glioma tissues and cell lines compared to that in non-neoplastic brain tissues and normal glial cell lines. In U87MG cells, downregulation or overexpression of Mig-7 inhibited or promoted the expression of MMP-2, MMP-9, LAMC2, EphA2, and VE-cadherin, and phosphorylation levels of ERK1/2, JNK, and p38. Mig-7 overexpression promoted migration, invasion, cell viability, and tube formation, which were reversed by the MAPK signaling pathway inhibitors. Mig-7 overexpression promoted subcutaneous tumor growth in mice and upregulated the phosphorylation levels of ERK1/2, JNK, and p38 and the expression of Ki-67. These effects of Mig-7 overexpression were reversed by MAPK pathway inhibitors. Overall, these results suggest that Mig-7 may be a novel biomarker and potential therapeutic target for glioma, with the MAPK pathway playing a key role in the corresponding Mig-7 mechanism of action.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"70 4","pages":"534-544"},"PeriodicalIF":3.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41167489","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}
Pub Date : 2023-08-01DOI: 10.4149/neo_2023_230404N185
Jana Plava, Lenka Trnkova, Peter Makovicky, Michal Mego, Svetlana Miklikova, Lucia Kucerova
Breast cancer metastases are the main reason for women´s highest cancer mortality. Even though tumor cell dissemination via circulating tumor cells (CTC) released from the primary site is a very ineffective process, distant metastases appear in 46% of triple-negative breast cancer (TNBC) patients corresponding to the disease aggressiveness. Laboratory models for functional testing which mimic the spread of metastatic cells are needed for efficient investigation of the underlying mechanisms and therapeutic intervention. Here, we describe novel isogenic variants LMC3 and CTC3 of human TNBC cell line MDA-MB-231 that were derived by repeated injection of tumor cells into the tail vein of immunodeficient mice and subsequent selection of metastatic cells from lung metastases. These variants have increased migration potential, altered expression profiles, and elevated tumorigenic potential. Moreover, cell line CTC3 readily produces metastases in the lungs and bone marrow and detectable viable circulating tumor cells in the blood. This model enables rapid and cost-efficient strategies for biomarker exploration and novel intervention approaches to limit the CTC presence in the blood and hence tumor dissemination.
{"title":"Novel model of triple-negative breast cancer produces viable circulating tumor cells and rapid lung metastasis for functional testing in vivo.","authors":"Jana Plava, Lenka Trnkova, Peter Makovicky, Michal Mego, Svetlana Miklikova, Lucia Kucerova","doi":"10.4149/neo_2023_230404N185","DOIUrl":"https://doi.org/10.4149/neo_2023_230404N185","url":null,"abstract":"<p><p>Breast cancer metastases are the main reason for women´s highest cancer mortality. Even though tumor cell dissemination via circulating tumor cells (CTC) released from the primary site is a very ineffective process, distant metastases appear in 46% of triple-negative breast cancer (TNBC) patients corresponding to the disease aggressiveness. Laboratory models for functional testing which mimic the spread of metastatic cells are needed for efficient investigation of the underlying mechanisms and therapeutic intervention. Here, we describe novel isogenic variants LMC3 and CTC3 of human TNBC cell line MDA-MB-231 that were derived by repeated injection of tumor cells into the tail vein of immunodeficient mice and subsequent selection of metastatic cells from lung metastases. These variants have increased migration potential, altered expression profiles, and elevated tumorigenic potential. Moreover, cell line CTC3 readily produces metastases in the lungs and bone marrow and detectable viable circulating tumor cells in the blood. This model enables rapid and cost-efficient strategies for biomarker exploration and novel intervention approaches to limit the CTC presence in the blood and hence tumor dissemination.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"70 4","pages":"514-525"},"PeriodicalIF":3.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41122091","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}
Pub Date : 2023-08-01DOI: 10.4149/neo_2023_230405N186
Vladimira Sadlonova, Alena Mazurakova, Lenka Koklesova, Nora Malinovska, Marian Grendar, Elena Novakova, Peter Kubatka
The purpose of this study was to assess the potential effects of Rhus coriaria L. (sumac) and of Cinnamomum zeylanicum L. bark on the selected serum cytokines as possible serum tumor markers - interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α) in the rat model of mammary carcinogenesis. R. coriaria and C. zeylanicum bark were used as the chemopreventive-therapeutic agents taken by rats in the powder form in the diet at two different concentrations during the entire period of two experiments carried out separately: lower concentration 1 g/kg - 0.1% and higher concentration 10 g/kg - 1%. The serum levels of cytokines of IL-6, IL-10, and TNF-α were determined using an enzyme-linked immunosorbent assay. In the first experiment treated with R. coriaria, a significant decrease in serum levels of IL-6 and TNF-α was present at higher concentrations compared to the chemoprevention-free control group. R. coriaria at lower concentrations non-significantly reduced the serum levels of IL-6 and TNF-α when compared to controls. A significant decrease in serum levels of TNF-α was present at higher concentrations compared to lower concentrations. The significant effect of R. coriaria on the serum levels of IL-10 was not observed. In the second experiment treated with C. zeylanicum bark, a significant decrease in serum levels of IL-6 was observed in lower and higher concentrations compared to the chemoprevention-free control group. C. zeylanicum bark non-significantly reduced the serum levels of TNF-α and had no effect on the serum levels of IL-10. In conclusion, R. coriaria and C. zeylanicum bark demonstrated significant anti-inflammatory effects by analyzing the selected serum cytokine levels in the rat breast carcinoma model. Observed anti-inflammatory effects of both plant-natural substances were associated with their anticancer activities in rats.
{"title":"The effects of Rhus coriaria L. (sumac) and Cinnamomum zeylanicum L. bark on serum cytokine levels in rat mammary carcinogenesis.","authors":"Vladimira Sadlonova, Alena Mazurakova, Lenka Koklesova, Nora Malinovska, Marian Grendar, Elena Novakova, Peter Kubatka","doi":"10.4149/neo_2023_230405N186","DOIUrl":"https://doi.org/10.4149/neo_2023_230405N186","url":null,"abstract":"<p><p>The purpose of this study was to assess the potential effects of Rhus coriaria L. (sumac) and of Cinnamomum zeylanicum L. bark on the selected serum cytokines as possible serum tumor markers - interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α) in the rat model of mammary carcinogenesis. R. coriaria and C. zeylanicum bark were used as the chemopreventive-therapeutic agents taken by rats in the powder form in the diet at two different concentrations during the entire period of two experiments carried out separately: lower concentration 1 g/kg - 0.1% and higher concentration 10 g/kg - 1%. The serum levels of cytokines of IL-6, IL-10, and TNF-α were determined using an enzyme-linked immunosorbent assay. In the first experiment treated with R. coriaria, a significant decrease in serum levels of IL-6 and TNF-α was present at higher concentrations compared to the chemoprevention-free control group. R. coriaria at lower concentrations non-significantly reduced the serum levels of IL-6 and TNF-α when compared to controls. A significant decrease in serum levels of TNF-α was present at higher concentrations compared to lower concentrations. The significant effect of R. coriaria on the serum levels of IL-10 was not observed. In the second experiment treated with C. zeylanicum bark, a significant decrease in serum levels of IL-6 was observed in lower and higher concentrations compared to the chemoprevention-free control group. C. zeylanicum bark non-significantly reduced the serum levels of TNF-α and had no effect on the serum levels of IL-10. In conclusion, R. coriaria and C. zeylanicum bark demonstrated significant anti-inflammatory effects by analyzing the selected serum cytokine levels in the rat breast carcinoma model. Observed anti-inflammatory effects of both plant-natural substances were associated with their anticancer activities in rats.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"70 4","pages":"545-554"},"PeriodicalIF":3.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41166471","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}
Long noncoding RNAs (lncRNAs) play important roles in the progression of human cancer. It is reported that lncRNA plasmacytoma variant translocation 1 (PVT1) is involved in colorectal cancer (CRC), however, the underlying mechanism remains to be explored deeply, especially by in vivo models. In the present study, bioinformatics analysis showed that the expression level of PVT1 was upregulated in CRC tissues and highly associated with poor prognosis of CRC patients. In cultured CRC cells, knockdown of PVT1 inhibited cell proliferation and migration of CRC cells, while overexpression of PVT1 promoted the progression of CRC cells. In zebrafish xenografts, the silencing of PVT1 also suppressed the growth and metastasis of CRC cells. For mechanism studies, the binding relationships among PVT1, miR-24-3p, and Neuropilin 1 (NRP1) were predicted by starBase firstly. The luciferase reporter assays verified that PVT1 and NRP1 could bind with miR-24-3p directly. Further studies showed miR-24-3p negatively regulated the progression of CRC cells, the inhibition of miR-24-3p counteracted the repression effects of CRC progression when knocking down PVT1. In addition, the expression of NRP1 was regulated by PVT1, and NRP1 overexpression could partially rescue the inhibition effects of CRC progression when knocking down PVT1 in vitro and in vivo. Our study reveals that PVT1 promotes the proliferation and metastasis of CRC via regulating the miR-24-3p/NRP1 axis, which provides a prognosis biomarker and a potential therapeutic target for CRC patients.
{"title":"Long noncoding RNA PVT1 predicts poor prognosis and promotes the progression of colorectal cancer through the miR-24-3p/NRP1 axis in zebrafish xenografts.","authors":"Hailin Yin, Shanye Gu, Guiqin Li, Hanxu Yu, Xishan Zhang, Yangsong Zuo","doi":"10.4149/neo_2023_221208N1169","DOIUrl":"https://doi.org/10.4149/neo_2023_221208N1169","url":null,"abstract":"<p><p>Long noncoding RNAs (lncRNAs) play important roles in the progression of human cancer. It is reported that lncRNA plasmacytoma variant translocation 1 (PVT1) is involved in colorectal cancer (CRC), however, the underlying mechanism remains to be explored deeply, especially by in vivo models. In the present study, bioinformatics analysis showed that the expression level of PVT1 was upregulated in CRC tissues and highly associated with poor prognosis of CRC patients. In cultured CRC cells, knockdown of PVT1 inhibited cell proliferation and migration of CRC cells, while overexpression of PVT1 promoted the progression of CRC cells. In zebrafish xenografts, the silencing of PVT1 also suppressed the growth and metastasis of CRC cells. For mechanism studies, the binding relationships among PVT1, miR-24-3p, and Neuropilin 1 (NRP1) were predicted by starBase firstly. The luciferase reporter assays verified that PVT1 and NRP1 could bind with miR-24-3p directly. Further studies showed miR-24-3p negatively regulated the progression of CRC cells, the inhibition of miR-24-3p counteracted the repression effects of CRC progression when knocking down PVT1. In addition, the expression of NRP1 was regulated by PVT1, and NRP1 overexpression could partially rescue the inhibition effects of CRC progression when knocking down PVT1 in vitro and in vivo. Our study reveals that PVT1 promotes the proliferation and metastasis of CRC via regulating the miR-24-3p/NRP1 axis, which provides a prognosis biomarker and a potential therapeutic target for CRC patients.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"70 4","pages":"500-513"},"PeriodicalIF":3.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41167488","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}
Pub Date : 2023-06-01DOI: 10.4149/neo_2023_230525N283
Kristina Jakic, Michal Selc, Radka Macova, Antonia Kurillova, Libor Kvitek, Ales Panacek, Andrea Babelova
Silver nanoparticles (AgNPs) exhibit unique physicochemical properties, making these nanomaterials attractive for various medical applications. Among them, AgNPs have shown great potential in the treatment of cancer by inducing apoptosis in cancer cells, inhibiting tumor growth, and enhancing the efficacy of conventional cancer treatments such as chemotherapy and radiation therapy. Despite the promising therapeutical advantage of AgNPs, there are several challenges that need to be addressed. One of the most important is AgNPs' toxicity, which in case of treatment might be extended to non-cancerous cells and tissues. In our study, we therefore investigated the effects of spherical AgNPs with the silver core size of 10, 30, and 45 nm coated with polyacrylic acid (PAA-AgNPs) in an in vitro model using cancer (A549) and non-cancer (HEL299) cells. We estimated the impact of these nanoparticles on cell viability, cell proliferation, and cell actin cytoskeleton remodeling. Moreover, changes in the expression of TNFA, IL-10, FN1, and SOD1 mRNA induced by PAA-AgNPs were determined. Our results suggest that the smallest (10 nm) PAA-AgNPs are the most effective in apoptosis induction, however, they are also the most toxic from the three AgNPs types to both, cancer and non-cancer cells, while bigger (30 and 45 nm) PAA-AgNPs showed fewer undesirable effects in these pulmonary cells.
{"title":"Effects of different-sized silver nanoparticles on morphological and functional alterations in lung cancer and non-cancer lung cells.","authors":"Kristina Jakic, Michal Selc, Radka Macova, Antonia Kurillova, Libor Kvitek, Ales Panacek, Andrea Babelova","doi":"10.4149/neo_2023_230525N283","DOIUrl":"https://doi.org/10.4149/neo_2023_230525N283","url":null,"abstract":"<p><p>Silver nanoparticles (AgNPs) exhibit unique physicochemical properties, making these nanomaterials attractive for various medical applications. Among them, AgNPs have shown great potential in the treatment of cancer by inducing apoptosis in cancer cells, inhibiting tumor growth, and enhancing the efficacy of conventional cancer treatments such as chemotherapy and radiation therapy. Despite the promising therapeutical advantage of AgNPs, there are several challenges that need to be addressed. One of the most important is AgNPs' toxicity, which in case of treatment might be extended to non-cancerous cells and tissues. In our study, we therefore investigated the effects of spherical AgNPs with the silver core size of 10, 30, and 45 nm coated with polyacrylic acid (PAA-AgNPs) in an in vitro model using cancer (A549) and non-cancer (HEL299) cells. We estimated the impact of these nanoparticles on cell viability, cell proliferation, and cell actin cytoskeleton remodeling. Moreover, changes in the expression of TNFA, IL-10, FN1, and SOD1 mRNA induced by PAA-AgNPs were determined. Our results suggest that the smallest (10 nm) PAA-AgNPs are the most effective in apoptosis induction, however, they are also the most toxic from the three AgNPs types to both, cancer and non-cancer cells, while bigger (30 and 45 nm) PAA-AgNPs showed fewer undesirable effects in these pulmonary cells.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"70 3","pages":"390-401"},"PeriodicalIF":3.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9873637","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}
Pub Date : 2023-06-01DOI: 10.4149/neo_2023_230418N216
Miroslav Tibensky, Filip Blasko, Peter Vargovic, Jana Jakubikova, Dana Cholujova, Jana Jakubechova, Boris Mravec
Experimental and clinical data have shown that the nervous system can significantly stimulate the initiation and progression of melanoma. In support of this, approaches that reduce the transmission of signals from peripheral nerves to effector tissues reduce the recurrence of melanoma. Therefore, we investigated the effect of topical application of the local anesthetic Pliaglis (7% lidocaine and 7% tetracaine) on the growth of melanoma induced by intradermal application of B16F0 cells in mice without treatment and in mice treated with the anti-PD-1 antibody. We found that application of Pliaglis to melanoma significantly reduced its growth and this effect was even pronounced in mice treated with the anti-PD-1 antibody. To determine the mechanisms and pathways responsible for the observed effect, the in vitro effect of incubating melanoma cells with lidocaine and/or tetracaine and the in vivo gene expression of cancer and immune-related factors, percentage of immune cells, gene expression of selected neurotransmitter receptors and nerve growth factors in melanoma tissue were studied. We found that lidocaine and tetracaine significantly reduced the viability of B16F0 cells in vitro. In mice with melanoma, Pliaglis potentiated the effect of anti-PD-1 antibody on gene expression of COX-2, IL-1β, IL-6, CCL11, F4/80, CD206, and NCR1. In addition, Pliaglis increased the gene expression of α9nACHR and 5-HT2a receptors and decreased the gene expression of nerve growth factor receptor (p75NTR) and p53. We also observed Pliaglis-mediated changes in myeloid populations. Topical application of this local anesthetic cream decreased the CD11b+Gr1- population and increased the CD11b+Gr1high population. Our data suggest that Pliaglis reduces melanoma growth through a direct effect on melanoma cells as well as through modulation of the immune response. The involvement of nervous system-related signaling in the inhibitory effect of Pliaglis on melanoma is inconclusive from our data.
{"title":"Topical application of local anesthetics to melanoma increases the efficacy of anti-PD-1 therapy.","authors":"Miroslav Tibensky, Filip Blasko, Peter Vargovic, Jana Jakubikova, Dana Cholujova, Jana Jakubechova, Boris Mravec","doi":"10.4149/neo_2023_230418N216","DOIUrl":"https://doi.org/10.4149/neo_2023_230418N216","url":null,"abstract":"<p><p>Experimental and clinical data have shown that the nervous system can significantly stimulate the initiation and progression of melanoma. In support of this, approaches that reduce the transmission of signals from peripheral nerves to effector tissues reduce the recurrence of melanoma. Therefore, we investigated the effect of topical application of the local anesthetic Pliaglis (7% lidocaine and 7% tetracaine) on the growth of melanoma induced by intradermal application of B16F0 cells in mice without treatment and in mice treated with the anti-PD-1 antibody. We found that application of Pliaglis to melanoma significantly reduced its growth and this effect was even pronounced in mice treated with the anti-PD-1 antibody. To determine the mechanisms and pathways responsible for the observed effect, the in vitro effect of incubating melanoma cells with lidocaine and/or tetracaine and the in vivo gene expression of cancer and immune-related factors, percentage of immune cells, gene expression of selected neurotransmitter receptors and nerve growth factors in melanoma tissue were studied. We found that lidocaine and tetracaine significantly reduced the viability of B16F0 cells in vitro. In mice with melanoma, Pliaglis potentiated the effect of anti-PD-1 antibody on gene expression of COX-2, IL-1β, IL-6, CCL11, F4/80, CD206, and NCR1. In addition, Pliaglis increased the gene expression of α9nACHR and 5-HT2a receptors and decreased the gene expression of nerve growth factor receptor (p75NTR) and p53. We also observed Pliaglis-mediated changes in myeloid populations. Topical application of this local anesthetic cream decreased the CD11b+Gr1- population and increased the CD11b+Gr1high population. Our data suggest that Pliaglis reduces melanoma growth through a direct effect on melanoma cells as well as through modulation of the immune response. The involvement of nervous system-related signaling in the inhibitory effect of Pliaglis on melanoma is inconclusive from our data.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"70 3","pages":"375-389"},"PeriodicalIF":3.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9880258","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}
Pub Date : 2023-06-01DOI: 10.4149/neo_2023_230117N34
Li Wang, Hua-Tao Quan, Jie Wang, Tian-Ci Tang, Yi Li, Xin-Mao Song
In sinonasal squamous cell carcinoma (SNSCC), the prognostic relevance of p16INK4a (p16) expression has been reported rarely. This study aims to examine the immunohistochemical expression of p16 and investigate the possibility of p16 as a prognostic factor for SNSCC. The medical records of 173 individuals with SNSCC between 2010 and 2022 were retrospectively reviewed. The researchers examined patients' demographics, p16 status, staging, tumor histological subtypes, treatment details, recurrence, metastasis, and survival outcomes. p16 was found in 22.0% (38/173) of SNSCC patients, and there was no difference between inverted papilloma-SNSCC (19.6%) and de novo SNSCC (23.0%). p16 status did not correlate with all the cases' age, gender, clinical stage, or therapy features. p16-positive patients had a considerably superior 5-year overall survival (OS) rate (80.7% vs. 57.5%, p=0.039) and a slight tendency in progression-free survival (PFS) rate (68.1% vs. 52.0%, p=0.15), except in stage T4b cases. In maxillary sinus lesions, p16-positive SNSCC had a better 5-year OS (87.4% vs. 49.2%, p=0.03) rate and PFS (79.1% vs. 40.7%, p=0.01) rate than p16-negative SNSCC. Among patients without skull base involvement (82.9% vs. 57.7%, p=0.037) or orbital invasion (86.9% vs. 57.3%, p=0.02), p16-positive SNSCC confers benefits in OS rates more than p16-negative SNSCC. Immunohistochemical p16 expression may be a predictive predictor in individuals with maxillary sinus SCC, non-T4b stage, without skull base involvement, and without orbital invasion.
在鼻窦鳞状细胞癌(SNSCC)中,p16INK4a (p16)表达与预后的相关性很少报道。本研究旨在检测p16的免疫组织化学表达,并探讨p16作为SNSCC预后因素的可能性。本文回顾性分析了2010年至2022年间173例SNSCC患者的医疗记录。研究人员检查了患者的人口统计学、p16状态、分期、肿瘤组织学亚型、治疗细节、复发、转移和生存结果。在22.0%(38/173)的SNSCC患者中发现p16,倒置乳头状瘤-SNSCC(19.6%)和新生SNSCC(23.0%)之间无差异。P16状态与所有病例的年龄、性别、临床分期或治疗特征无关。除T4b期患者外,p16阳性患者的5年总生存率(OS)显著高于其他患者(80.7% vs. 57.5%, p=0.039),无进展生存率(PFS)有轻微趋势(68.1% vs. 52.0%, p=0.15)。在上颌窦病变中,p16阳性SNSCC的5年OS(87.4%比49.2%,p=0.03)率和PFS(79.1%比40.7%,p=0.01)率均优于p16阴性SNSCC。在未侵犯颅底(82.9% vs. 57.7%, p=0.037)或侵犯眶部(86.9% vs. 57.3%, p=0.02)的患者中,p16阳性SNSCC的OS率高于p16阴性SNSCC。免疫组织化学p16的表达可能是上颌窦SCC,非t4b期,无颅底受损伤,无眼眶侵犯的预测指标。
{"title":"Immunohistochemical p16 expression in the prognosis of patients with sinonasal squamous cell carcinoma.","authors":"Li Wang, Hua-Tao Quan, Jie Wang, Tian-Ci Tang, Yi Li, Xin-Mao Song","doi":"10.4149/neo_2023_230117N34","DOIUrl":"https://doi.org/10.4149/neo_2023_230117N34","url":null,"abstract":"<p><p>In sinonasal squamous cell carcinoma (SNSCC), the prognostic relevance of p16INK4a (p16) expression has been reported rarely. This study aims to examine the immunohistochemical expression of p16 and investigate the possibility of p16 as a prognostic factor for SNSCC. The medical records of 173 individuals with SNSCC between 2010 and 2022 were retrospectively reviewed. The researchers examined patients' demographics, p16 status, staging, tumor histological subtypes, treatment details, recurrence, metastasis, and survival outcomes. p16 was found in 22.0% (38/173) of SNSCC patients, and there was no difference between inverted papilloma-SNSCC (19.6%) and de novo SNSCC (23.0%). p16 status did not correlate with all the cases' age, gender, clinical stage, or therapy features. p16-positive patients had a considerably superior 5-year overall survival (OS) rate (80.7% vs. 57.5%, p=0.039) and a slight tendency in progression-free survival (PFS) rate (68.1% vs. 52.0%, p=0.15), except in stage T4b cases. In maxillary sinus lesions, p16-positive SNSCC had a better 5-year OS (87.4% vs. 49.2%, p=0.03) rate and PFS (79.1% vs. 40.7%, p=0.01) rate than p16-negative SNSCC. Among patients without skull base involvement (82.9% vs. 57.7%, p=0.037) or orbital invasion (86.9% vs. 57.3%, p=0.02), p16-positive SNSCC confers benefits in OS rates more than p16-negative SNSCC. Immunohistochemical p16 expression may be a predictive predictor in individuals with maxillary sinus SCC, non-T4b stage, without skull base involvement, and without orbital invasion.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"70 3","pages":"451-457"},"PeriodicalIF":3.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9880264","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}