Pub Date : 2021-01-01DOI: 10.35248/2157-2518.21.12.360
Keiji Kuwabara, H. Ichihara, Y. Matsumoto
Hybrid Liposomes (HL25) composed of 90 mol% L-a-Dimyristoylphosphatidylcholine (DMPC) and 10 mol% polyoxyethylene(25) dodecyl ethers (C12(EO)25) were found to fuse and accumulate in the cell membranes of human brain tumor, glioblastoma, (U-87MG) cells and inhibit their growth. HL25 induced apoptosis in U-87MG cells via the release of AIF under a caspase-independent pathway. HL25 inhibited tumor enlargement in orthotopic graft mouse models of glioblastoma after crossing the blood-brain barrier.
由90 mol% l -a-二myristoylphosphatidycholine (DMPC)和10 mol%聚氧乙烯(25)十二烷基醚(C12(EO)25)组成的杂种脂质体(HL25)在人脑肿瘤、胶质母细胞瘤(U-87MG)细胞的细胞膜中融合积累，抑制其生长。HL25通过caspase非依赖性途径释放AIF诱导U-87MG细胞凋亡。HL25在穿过血脑屏障后抑制胶质母细胞瘤原位移植小鼠模型的肿瘤增大。
{"title":"Novel Therapy with Hybrid Liposomes for Orthotopic Graft Mouse Models of Glioblastoma","authors":"Keiji Kuwabara, H. Ichihara, Y. Matsumoto","doi":"10.35248/2157-2518.21.12.360","DOIUrl":"https://doi.org/10.35248/2157-2518.21.12.360","url":null,"abstract":"Hybrid Liposomes (HL25) composed of 90 mol% L-a-Dimyristoylphosphatidylcholine (DMPC) and 10 mol% polyoxyethylene(25) dodecyl ethers (C12(EO)25) were found to fuse and accumulate in the cell membranes of human brain tumor, glioblastoma, (U-87MG) cells and inhibit their growth. HL25 induced apoptosis in U-87MG cells via the release of AIF under a caspase-independent pathway. HL25 inhibited tumor enlargement in orthotopic graft mouse models of glioblastoma after crossing the blood-brain barrier.","PeriodicalId":15209,"journal":{"name":"Journal of carcinogenesis & mutagenesis","volume":"42 1","pages":"1-5"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80597287","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}
Pub Date : 2021-01-01DOI: 10.35248/2157-2518.21.S19.002
L. Agius
The promotional antigenicity profiles exhibited by proliferating tumor cells allows for a permissive microenvironment as projected by immature DC. It is within redefined milieu of chemokine reactivity that redistribution of antigenic stimuli allow for projected modulations of the integral immune systems as proposed by the redefined ch emokine reactivity. It is the simple juxtaposition of multiple range of antigenicity that perforce allows for immune tolerance and permissiveness to emerge. The recharacterization of such antigenicity is recharacterization of inherent component pathway reactivity as indeed projected chemokine redistribution within profiles of the immune response to proliferating tumor cell beds.
{"title":"Incongruent Biology of Redistributed Chemokine Action in Carcinogenesis","authors":"L. Agius","doi":"10.35248/2157-2518.21.S19.002","DOIUrl":"https://doi.org/10.35248/2157-2518.21.S19.002","url":null,"abstract":"The promotional antigenicity profiles exhibited by proliferating tumor cells allows for a permissive microenvironment as projected by immature DC. It is within redefined milieu of chemokine reactivity that redistribution of antigenic stimuli allow for projected modulations of the integral immune systems as proposed by the redefined ch emokine reactivity. It is the simple juxtaposition of multiple range of antigenicity that perforce allows for immune tolerance and permissiveness to emerge. The recharacterization of such antigenicity is recharacterization of inherent component pathway reactivity as indeed projected chemokine redistribution within profiles of the immune response to proliferating tumor cell beds.","PeriodicalId":15209,"journal":{"name":"Journal of carcinogenesis & mutagenesis","volume":"98 1","pages":"1-3"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76667696","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}
Pub Date : 2021-01-01DOI: 10.35248/2157-2518.21.12.364
Keiji Kuwabara, H. Ichihara, Y. Matsumoto
The inhibitory effects of trehalose liposomes (TL) composed of α-D-glycopyranosyl-α-D-glucopyranoside monomyristate and L-α-dimyristoylphosphatidylcholine on the growth of human glioblastoma (U-87MG) cells were evaluated. Induction of apoptosis was observed after fusion and accumulation of TL in U-87MG cell membranes. Increased membrane fluidity of U-87MG cells treated with TL was observed. TL caused apoptosis in U-87MG cells through the activation of mitochondria and apoptosis-inducing factor via a caspase-independent pathway. Tumor weights markedly decreased in orthotopic graft mouse models of glioblastoma (U-87MG) after intravenous administration of TL compared with those in the control group.
{"title":"Trehalose Liposomes Inhibit the Growth of Glioblastoma Cell In vitro and In vivo","authors":"Keiji Kuwabara, H. Ichihara, Y. Matsumoto","doi":"10.35248/2157-2518.21.12.364","DOIUrl":"https://doi.org/10.35248/2157-2518.21.12.364","url":null,"abstract":"The inhibitory effects of trehalose liposomes (TL) composed of α-D-glycopyranosyl-α-D-glucopyranoside monomyristate and L-α-dimyristoylphosphatidylcholine on the growth of human glioblastoma (U-87MG) cells were evaluated. Induction of apoptosis was observed after fusion and accumulation of TL in U-87MG cell membranes. Increased membrane fluidity of U-87MG cells treated with TL was observed. TL caused apoptosis in U-87MG cells through the activation of mitochondria and apoptosis-inducing factor via a caspase-independent pathway. Tumor weights markedly decreased in orthotopic graft mouse models of glioblastoma (U-87MG) after intravenous administration of TL compared with those in the control group.","PeriodicalId":15209,"journal":{"name":"Journal of carcinogenesis & mutagenesis","volume":"161 1","pages":"1-5"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80178073","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}
Pub Date : 2021-01-01DOI: 10.35248/2157-2518.21.S17.001
K. Fujioka
Non-Alcoholic Fatty Liver Disease (NAFLD) is the common liver disease worldwide because of the increasing rates in parallel to obesity and Type 2 Diabetes Mellitus (T2DM). Mechanically, lipid accumulation and insulin resistance serve as the first hit, second hit is considered as inflammation and fibrosis in NAFLD. NAFLD is attributed to liverrelated morbidity and mortality, there is also growing evidence that NAFLD is a multisystem disease and is associated with hepatic (hepatocellular carcinoma: HCC) and extrahepatic (Cardiovascular Disease: CVD, Coronary Artery Disease: CAD, and Chronic Kidney Disease: CKD) diseases. The author previously suggested that an association between chronic liver disease (NAFLD/NASH and chronic hepatitis C virus infection: HCV infection) and systemic atherosclerosis may be present due to the presence of the inflammation as a common pathway. In this article, the current genetic advances of NAFLD/NASH-related HCC including PNPLA3, TM6SF2, GCKR, MBOAT7, HSD17B13, and the combined effect of these variants along with characteristic clinical manifestation have been reviewed. NAFLDs clinically predispose to occur non-cirrhotic NAFLD-HCC. The study of polygenic risk scores may be attributed to the stratification of the risk of the NAFLD/NASH-related HCC in the near feature. On the basis of the characteristic clinical and genetic evidences, the author suggests that the risk stratification of the medium/high risk in NAFLD-related HCC, especially non-cirrhotic HCC may contribute to the prevention, prediction, and surveillance.
{"title":"Current Genetic Advances in NAFLD/NASH: Related Hepatocellular Carcinoma Along with Characteristic Clinical Manifestation","authors":"K. Fujioka","doi":"10.35248/2157-2518.21.S17.001","DOIUrl":"https://doi.org/10.35248/2157-2518.21.S17.001","url":null,"abstract":"Non-Alcoholic Fatty Liver Disease (NAFLD) is the common liver disease worldwide because of the increasing rates in parallel to obesity and Type 2 Diabetes Mellitus (T2DM). Mechanically, lipid accumulation and insulin resistance serve as the first hit, second hit is considered as inflammation and fibrosis in NAFLD. NAFLD is attributed to liverrelated morbidity and mortality, there is also growing evidence that NAFLD is a multisystem disease and is associated with hepatic (hepatocellular carcinoma: HCC) and extrahepatic (Cardiovascular Disease: CVD, Coronary Artery Disease: CAD, and Chronic Kidney Disease: CKD) diseases. The author previously suggested that an association between chronic liver disease (NAFLD/NASH and chronic hepatitis C virus infection: HCV infection) and systemic atherosclerosis may be present due to the presence of the inflammation as a common pathway. In this article, the current genetic advances of NAFLD/NASH-related HCC including PNPLA3, TM6SF2, GCKR, MBOAT7, HSD17B13, and the combined effect of these variants along with characteristic clinical manifestation have been reviewed. NAFLDs clinically predispose to occur non-cirrhotic NAFLD-HCC. The study of polygenic risk scores may be attributed to the stratification of the risk of the NAFLD/NASH-related HCC in the near feature. On the basis of the characteristic clinical and genetic evidences, the author suggests that the risk stratification of the medium/high risk in NAFLD-related HCC, especially non-cirrhotic HCC may contribute to the prevention, prediction, and surveillance.","PeriodicalId":15209,"journal":{"name":"Journal of carcinogenesis & mutagenesis","volume":"44 1","pages":"1-5"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87534087","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}
Pub Date : 2021-01-01DOI: 10.35248/2157-2518.21.12.366
V. Zaichick
The aim of this exploratory study was to examine the content of Bromine (Br), Calcium (Ca), Chlorine (Cl), Iodine (I), Potassium (K), Magnesium (Mg), Manganese (Mn), and Sodium (Na) in the normal and adenomatous Thyroid (TA). Thyroid tissue levels of eight Chemical Elements (ChE) were prospectively evaluated in 19 patients with TA and 105 healthy inhabitants. Measurements were performed using non-destructive instrumental neutron activation analysis with high resolution spectrometry of short-lived radionuclides. Tissue samples were divided into two portions. One was used for morphological study while the other was intended for ChE analysis. A reduced content of I and Mg, as well as an elevated content of Br, Cl and Na in TA in comparison with normal thyroid was found. The study showed that the adenomatous transformation was accompanied by considerable changes in ChE contents of affected thyroid tissue.
{"title":"Evaluation of Bromine, Calcium, Chlorine, Iodine, Potassium, Magnesium, Manganese, and Sodium Content in the Thyroid Adenomas using Neutron Activation Analysis","authors":"V. Zaichick","doi":"10.35248/2157-2518.21.12.366","DOIUrl":"https://doi.org/10.35248/2157-2518.21.12.366","url":null,"abstract":"The aim of this exploratory study was to examine the content of Bromine (Br), Calcium (Ca), Chlorine (Cl), Iodine (I), Potassium (K), Magnesium (Mg), Manganese (Mn), and Sodium (Na) in the normal and adenomatous Thyroid (TA). Thyroid tissue levels of eight Chemical Elements (ChE) were prospectively evaluated in 19 patients with TA and 105 healthy inhabitants. Measurements were performed using non-destructive instrumental neutron activation analysis with high resolution spectrometry of short-lived radionuclides. Tissue samples were divided into two portions. One was used for morphological study while the other was intended for ChE analysis. A reduced content of I and Mg, as well as an elevated content of Br, Cl and Na in TA in comparison with normal thyroid was found. The study showed that the adenomatous transformation was accompanied by considerable changes in ChE contents of affected thyroid tissue.","PeriodicalId":15209,"journal":{"name":"Journal of carcinogenesis & mutagenesis","volume":"64 1","pages":"1-8"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88393771","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}
Pub Date : 2021-01-01DOI: 10.35248/2157-2518.21.12.365
Naimur Rehman
This study aims to assess the quality parameters of Clopidogrel tablets from different manufacturers available in the Bangladeshi market. Clopidogrel is a potent antiplatelet and antithrombotic drug. Clopidogrel has been approved and marketed globally with the primary indication being to reduce atherosclerotic events in patients with several comorbid conditions due to stroke, myocardial infarction and cardiovascular disease. The aim and the objective of our present study are to evaluate the quality parameters of some marketed Clopidogrel tablet and to compare the parameters among them. To assess the quality, three different marketed Clopidogrel 75 mg tablet are selected and invitro dissolution test, potency, disintegration time are carried out. Other general quality parameters of these tablets like weight variation, hardness, friability are also determined according to established protocols. All the brands comply the requirements of United State Pharmacopoeia as they show acceptable weight variation range. Friability of all brands is less than 1%. No significant differences are found in disintegration time as they disintegrate within 15 minutes. In case of dissolution profile all brands show better dissolution time as they release more than 75% of drug in 45 minutes. The hardness of one brand is within the range 40-60N. The limitation of the potency must be within 95- 105%. All three brands meet this specification. This study suggests that most commercially available Clopidogrel tablets in Bangladesh maintain the quality and comply with the USP specifications which are essential for better therapeutic activity of this antiplatelet drug.
{"title":"Comparative Quality Evaluation of Different Brands of Clopidogrel Tablet Available in Bangladesh","authors":"Naimur Rehman","doi":"10.35248/2157-2518.21.12.365","DOIUrl":"https://doi.org/10.35248/2157-2518.21.12.365","url":null,"abstract":"This study aims to assess the quality parameters of Clopidogrel tablets from different manufacturers available in the Bangladeshi market. Clopidogrel is a potent antiplatelet and antithrombotic drug. Clopidogrel has been approved and marketed globally with the primary indication being to reduce atherosclerotic events in patients with several comorbid conditions due to stroke, myocardial infarction and cardiovascular disease. The aim and the objective of our present study are to evaluate the quality parameters of some marketed Clopidogrel tablet and to compare the parameters among them. To assess the quality, three different marketed Clopidogrel 75 mg tablet are selected and invitro dissolution test, potency, disintegration time are carried out. Other general quality parameters of these tablets like weight variation, hardness, friability are also determined according to established protocols. All the brands comply the requirements of United State Pharmacopoeia as they show acceptable weight variation range. Friability of all brands is less than 1%. No significant differences are found in disintegration time as they disintegrate within 15 minutes. In case of dissolution profile all brands show better dissolution time as they release more than 75% of drug in 45 minutes. The hardness of one brand is within the range 40-60N. The limitation of the potency must be within 95- 105%. All three brands meet this specification. This study suggests that most commercially available Clopidogrel tablets in Bangladesh maintain the quality and comply with the USP specifications which are essential for better therapeutic activity of this antiplatelet drug.","PeriodicalId":15209,"journal":{"name":"Journal of carcinogenesis & mutagenesis","volume":"12 1","pages":"1-9"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86626060","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}
Pub Date : 2021-01-01DOI: 10.35248/2157-2518.21.S18.002
R. Solomon
{"title":"Calm Therapy in Managing Cancer Treatment","authors":"R. Solomon","doi":"10.35248/2157-2518.21.S18.002","DOIUrl":"https://doi.org/10.35248/2157-2518.21.S18.002","url":null,"abstract":"","PeriodicalId":15209,"journal":{"name":"Journal of carcinogenesis & mutagenesis","volume":"33 1","pages":"1-1"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76635878","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}
Pub Date : 2021-01-01DOI: 10.35248/2157-2518.21.12.358
Michael J. González, P. Biava, Alondra P Toro, J. Olalde, J. R. Mir, A. Massari
Exosomes are vesicles that carry nanoparticles that play important roles in cell-to-cell communication. They are currently being tested for their potential as therapeutic agents for various degenerative diseases including cancer. This is due to the rationale that these nanoparticles can transfer informational biomolecules, and subsequentially cause metabolic and physiological changes. Also, these vesicles can be used as a drug delivery system and be very effective at reducing toxicity and increasing bioavailability of therapeutic molecules and drugs. Exosomes were first thought as a waste cell product. Current research, has demonstrated that these particles can serve as cancer biomarkers, modulate the immune system, cause re-differentiation in cancer cells, and apoptosis. This review emphasizes on particular capabilities of specific exosomes that can potentially be used for cancer therapy, especially as an informational reprogramming therapy for malignant cells.
{"title":"Exosomes and Cancer: The Bio Informational Reprogramming Therapy for Malignant Cells","authors":"Michael J. González, P. Biava, Alondra P Toro, J. Olalde, J. R. Mir, A. Massari","doi":"10.35248/2157-2518.21.12.358","DOIUrl":"https://doi.org/10.35248/2157-2518.21.12.358","url":null,"abstract":"Exosomes are vesicles that carry nanoparticles that play important roles in cell-to-cell communication. They are currently being tested for their potential as therapeutic agents for various degenerative diseases including cancer. This is due to the rationale that these nanoparticles can transfer informational biomolecules, and subsequentially cause metabolic and physiological changes. Also, these vesicles can be used as a drug delivery system and be very effective at reducing toxicity and increasing bioavailability of therapeutic molecules and drugs. Exosomes were first thought as a waste cell product. Current research, has demonstrated that these particles can serve as cancer biomarkers, modulate the immune system, cause re-differentiation in cancer cells, and apoptosis. This review emphasizes on particular capabilities of specific exosomes that can potentially be used for cancer therapy, especially as an informational reprogramming therapy for malignant cells.","PeriodicalId":15209,"journal":{"name":"Journal of carcinogenesis & mutagenesis","volume":"164 1","pages":"1-6"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86313726","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}
Pub Date : 2021-01-01DOI: 10.35248/2157-2518.21.S18.E001
J. George
{"title":"A Brief Note on Cancer Immunology","authors":"J. George","doi":"10.35248/2157-2518.21.S18.E001","DOIUrl":"https://doi.org/10.35248/2157-2518.21.S18.E001","url":null,"abstract":"","PeriodicalId":15209,"journal":{"name":"Journal of carcinogenesis & mutagenesis","volume":"9 1","pages":"1-1"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81968062","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}
Pub Date : 2021-01-01DOI: 10.35248/2157-2518.21.12.361
J. Balbuena, J. Castresana, J. Petriz
The objective of this work focuses on determining whether there are tumor cells with the Side Population phenotype in cell lines derived from astrocytomas, and if they are sensitive to hypoxia conditions and to the combination of temozolomide with inhibitors of sonic hedgehog pathway (cyclopamine) and of MGMT (O6 -benzylguanine). Cytometry studies were performed to separate the SP cell fraction in all cell lines. The proportion of SP cells was directly proportional to the degree of malignancy of the astrocytoma. The cells showed characteristics of tumor stem cells, such as a greater capacity for self-renewal, and constituted an independent or partially overlapping population with the population of CD133+ cancer stem cells. SP cells were highly resistant to temozolomide, while tumor cells that did not display tumor stem cell properties appeared to be more sensitive. The sonic hedgehog pathway caused resistance to temozolomide, but its inhibition with cyclopamine increased the cytotoxic effects of temozolomide, preferentially in populations not enriched for tumor stem cells of the Side Population. Chemoresistance was often independent of MGMT expression. O6 -benzylguanine was not always capable of increasing the sensitivity to temozolomide in tumor stem cells of the Side Population and in hypoxia. ABCG2 was the transporter predominantly expressed in tumor stem cell populations of the Side Population in high-grade astrocytomas, whereas MDR1 expressed more in non-tumor stem cell populations, and in tumor cells in lower-grade astrocytomas. ABCG2 might be responsible for acquired resistance during treatment with temozolomide.
{"title":"The Role of Side Population Cells and Hypoxia in Resistance to Chemotherapy in Astrocytoma Cell Lines","authors":"J. Balbuena, J. Castresana, J. Petriz","doi":"10.35248/2157-2518.21.12.361","DOIUrl":"https://doi.org/10.35248/2157-2518.21.12.361","url":null,"abstract":"The objective of this work focuses on determining whether there are tumor cells with the Side Population phenotype in cell lines derived from astrocytomas, and if they are sensitive to hypoxia conditions and to the combination of temozolomide with inhibitors of sonic hedgehog pathway (cyclopamine) and of MGMT (O6 -benzylguanine). Cytometry studies were performed to separate the SP cell fraction in all cell lines. The proportion of SP cells was directly proportional to the degree of malignancy of the astrocytoma. The cells showed characteristics of tumor stem cells, such as a greater capacity for self-renewal, and constituted an independent or partially overlapping population with the population of CD133+ cancer stem cells. SP cells were highly resistant to temozolomide, while tumor cells that did not display tumor stem cell properties appeared to be more sensitive. The sonic hedgehog pathway caused resistance to temozolomide, but its inhibition with cyclopamine increased the cytotoxic effects of temozolomide, preferentially in populations not enriched for tumor stem cells of the Side Population. Chemoresistance was often independent of MGMT expression. O6 -benzylguanine was not always capable of increasing the sensitivity to temozolomide in tumor stem cells of the Side Population and in hypoxia. ABCG2 was the transporter predominantly expressed in tumor stem cell populations of the Side Population in high-grade astrocytomas, whereas MDR1 expressed more in non-tumor stem cell populations, and in tumor cells in lower-grade astrocytomas. ABCG2 might be responsible for acquired resistance during treatment with temozolomide.","PeriodicalId":15209,"journal":{"name":"Journal of carcinogenesis & mutagenesis","volume":"40 1","pages":"1-20"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86382314","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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