K. Linowiecka, Olga Urbanowska-Domańska, Jolanta Guz, M. Foksinski
Alterations in DNA methylation may cause disturbances in regulation of gene expression, including drug metabolism and distribution. Moreover, many cancers, including breast cancer, are characterized by DNA hypomethylation and a decreased 5-hydroxymethylcytosine level. The abnormal cell growth found in breast carcinoma might be the result of impaired up-regulation of breast cancer receptors. Receptors’ expression in breast cancer determines clinical outcome, and it is possible that they lead to different DNA methylation patterns. Excessive steroid exposure can affect DNA methylation by promoting demethylation of CpG islands in promoter regions of genes, and hence may have an impact on promotion and progression of breast cancer cells. Tamoxifen, as a leading drug in breast cancer hormone therapy, has an ability to act like estrogen or antiestrogen depending on the type and localization of the breast cancer receptor. Further studies are needed to determine whether tamoxifen, similarly to steroids, may evoke changes in methylation pattern.
{"title":"The potential influence of breast cancer estrogen receptors’ distribution on active DNA demethylation","authors":"K. Linowiecka, Olga Urbanowska-Domańska, Jolanta Guz, M. Foksinski","doi":"10.5114/wo.2019.85200","DOIUrl":"https://doi.org/10.5114/wo.2019.85200","url":null,"abstract":"Alterations in DNA methylation may cause disturbances in regulation of gene expression, including drug metabolism and distribution. Moreover, many cancers, including breast cancer, are characterized by DNA hypomethylation and a decreased 5-hydroxymethylcytosine level. The abnormal cell growth found in breast carcinoma might be the result of impaired up-regulation of breast cancer receptors. Receptors’ expression in breast cancer determines clinical outcome, and it is possible that they lead to different DNA methylation patterns. Excessive steroid exposure can affect DNA methylation by promoting demethylation of CpG islands in promoter regions of genes, and hence may have an impact on promotion and progression of breast cancer cells. Tamoxifen, as a leading drug in breast cancer hormone therapy, has an ability to act like estrogen or antiestrogen depending on the type and localization of the breast cancer receptor. Further studies are needed to determine whether tamoxifen, similarly to steroids, may evoke changes in methylation pattern.","PeriodicalId":10652,"journal":{"name":"Contemporary Oncology","volume":"45 1","pages":"74 - 80"},"PeriodicalIF":0.0,"publicationDate":"2019-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80791125","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}
M. Toossi, M. Ghorbani, A. Rostami, M. Khosroabadi, S. Khademi, C. Knaup
Aim of the study The 57Co radioisotope has recently been proposed as a hypothetical brachytherapy source due to its high specific activity, appropriate half-life (272 days) and medium energy photons (114.17 keV on average). In this study, Task Group No. 43 dosimetric parameters were calculated and reported for a hypothetical 57Co source. Material and methods A hypothetical 57Co source was simulated in MCNPX, consisting of an active cylinder with 3.5 mm length and 0.6 mm radius encapsulated in a stainless steel capsule. Three photon energies were utilized (136 keV [10.68%], 122 keV [85.60%], 14 keV [9.16%]) for the 57Co source. Air kerma strength, dose rate constant, radial dose function, anisotropy function, and isodose curves for the source were calculated and compared to the corresponding data for a 192Ir source. Results The results are presented as tables and figures. Air kerma strength per 1 mCi activity for the 57Co source was 0.46 cGyh–1 cm 2 mCi–1. The dose rate constant for the 57Co source was determined to be 1.215 cGyh–1U–1. The radial dose function for the 57Co source has an increasing trend due to multiple scattering of low energy photons. The anisotropy function for the 57Co source at various distances from the source is more isotropic than the 192Ir source. Conclusions The 57Co source has advantages over 192Ir due to its lower energy photons, longer half-life, higher dose rate constant and more isotropic anisotropic function. However, the 192Ir source has a higher initial air kerma strength and more uniform radial dose function. These properties make 57Co a suitable source for use in brachytherapy applications.
{"title":"Comparison of the hypothetical 57Co brachytherapy source with the 192Ir source","authors":"M. Toossi, M. Ghorbani, A. Rostami, M. Khosroabadi, S. Khademi, C. Knaup","doi":"10.5114/wo.2016.61854","DOIUrl":"https://doi.org/10.5114/wo.2016.61854","url":null,"abstract":"Aim of the study The 57Co radioisotope has recently been proposed as a hypothetical brachytherapy source due to its high specific activity, appropriate half-life (272 days) and medium energy photons (114.17 keV on average). In this study, Task Group No. 43 dosimetric parameters were calculated and reported for a hypothetical 57Co source. Material and methods A hypothetical 57Co source was simulated in MCNPX, consisting of an active cylinder with 3.5 mm length and 0.6 mm radius encapsulated in a stainless steel capsule. Three photon energies were utilized (136 keV [10.68%], 122 keV [85.60%], 14 keV [9.16%]) for the 57Co source. Air kerma strength, dose rate constant, radial dose function, anisotropy function, and isodose curves for the source were calculated and compared to the corresponding data for a 192Ir source. Results The results are presented as tables and figures. Air kerma strength per 1 mCi activity for the 57Co source was 0.46 cGyh–1 cm 2 mCi–1. The dose rate constant for the 57Co source was determined to be 1.215 cGyh–1U–1. The radial dose function for the 57Co source has an increasing trend due to multiple scattering of low energy photons. The anisotropy function for the 57Co source at various distances from the source is more isotropic than the 192Ir source. Conclusions The 57Co source has advantages over 192Ir due to its lower energy photons, longer half-life, higher dose rate constant and more isotropic anisotropic function. However, the 192Ir source has a higher initial air kerma strength and more uniform radial dose function. These properties make 57Co a suitable source for use in brachytherapy applications.","PeriodicalId":10652,"journal":{"name":"Contemporary Oncology","volume":"38 1","pages":"327 - 334"},"PeriodicalIF":0.0,"publicationDate":"2016-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87391032","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}
Aim of the study A recent breast cancer genome-wide association study (GWAS) identified single-nucleotide polymorphism (SNP) rs2046210 on 6q25.1 showing a strong association with breast cancer risk. Numerous association studies have been conducted to investigate the relationship between this polymorphism and breast cancer risk in various populations. There have been conflicting reports about the association of this locus with breast cancer risk in different ethnic groups. For the first time, this study has investigated the association of rs2046210 SNP with breast cancer risk in Iranian Azari-Turkish women in North West Iran. Material and methods In this study 192 breast cancer subjects and 186 healthy controls were genotyped using Taqman SNP genotyping assays for different SNP rs2046210 alleles. Results No significant association between rs2046210 SNP alleles and the risk of breast cancer was detected in Iranian Azari-Turkish women. Conclusions The data suggests that rs2046210SNP does not play a role in the aetiology of breast cancer in the Iranian Azari-Turkish population, and it indicates possible genetic differences for breast cancer between different population ancestries. Our result is an important contribution to the literature about genetic susceptibility for breast cancer in Asian populations. Additional studies are required to confirm our findings.
{"title":"Evaluation of a newly discovered breast cancer susceptibility locus at 6q25.1 in Iranian Azari-Turkish women","authors":"Ziba Garehdaghchi, S. Derakhshan, M. Khaniani","doi":"10.5114/wo.2016.61851","DOIUrl":"https://doi.org/10.5114/wo.2016.61851","url":null,"abstract":"Aim of the study A recent breast cancer genome-wide association study (GWAS) identified single-nucleotide polymorphism (SNP) rs2046210 on 6q25.1 showing a strong association with breast cancer risk. Numerous association studies have been conducted to investigate the relationship between this polymorphism and breast cancer risk in various populations. There have been conflicting reports about the association of this locus with breast cancer risk in different ethnic groups. For the first time, this study has investigated the association of rs2046210 SNP with breast cancer risk in Iranian Azari-Turkish women in North West Iran. Material and methods In this study 192 breast cancer subjects and 186 healthy controls were genotyped using Taqman SNP genotyping assays for different SNP rs2046210 alleles. Results No significant association between rs2046210 SNP alleles and the risk of breast cancer was detected in Iranian Azari-Turkish women. Conclusions The data suggests that rs2046210SNP does not play a role in the aetiology of breast cancer in the Iranian Azari-Turkish population, and it indicates possible genetic differences for breast cancer between different population ancestries. Our result is an important contribution to the literature about genetic susceptibility for breast cancer in Asian populations. Additional studies are required to confirm our findings.","PeriodicalId":10652,"journal":{"name":"Contemporary Oncology","volume":"6 1","pages":"308 - 310"},"PeriodicalIF":0.0,"publicationDate":"2016-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85370977","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}
M. Brzozowa-Zasada, A. Piecuch, Anna Dittfeld, Ł. Mielańczyk, M. Michalski, G. Wyrobiec, M. Harabin-Słowińska, J. Kurek, R. Wojnicz
Notch signalling is an evolutionarily conserved signalling pathway, which plays a significant role in a wide array of cellular processes including proliferation, differentiation, and apoptosis. Nevertheless, it must be noted that Notch is a binary cell fate determinant, and its overexpression has been described as oncogenic in a broad range of human malignancies. This finding led to interest in therapeutically targeting this pathway especially by the use of GSIs, which block the cleavage of Notch at the cell membrane and inhibit release of the transcriptionally active NotchIC subunit. Preclinical cancer models have clearly demonstrated that GSIs suppress the growth of such malignancies as pancreatic, breast, and lung cancer; however, GSI treatment in vivo is associated with side effects, especially those within the gastrointestinal tract. Although intensive studies are associated with the role of γ-secretase in pathological states, it should be pointed out that this complex impacts on proteolytic cleavages of around 55 membrane proteins. Therefore, it is clear that GSIs are highly non-specific and additional drugs must be designed, which will more specifically target components of the Notch signalling.
{"title":"Notch signalling pathway as an oncogenic factor involved in cancer development","authors":"M. Brzozowa-Zasada, A. Piecuch, Anna Dittfeld, Ł. Mielańczyk, M. Michalski, G. Wyrobiec, M. Harabin-Słowińska, J. Kurek, R. Wojnicz","doi":"10.5114/wo.2016.61845","DOIUrl":"https://doi.org/10.5114/wo.2016.61845","url":null,"abstract":"Notch signalling is an evolutionarily conserved signalling pathway, which plays a significant role in a wide array of cellular processes including proliferation, differentiation, and apoptosis. Nevertheless, it must be noted that Notch is a binary cell fate determinant, and its overexpression has been described as oncogenic in a broad range of human malignancies. This finding led to interest in therapeutically targeting this pathway especially by the use of GSIs, which block the cleavage of Notch at the cell membrane and inhibit release of the transcriptionally active NotchIC subunit. Preclinical cancer models have clearly demonstrated that GSIs suppress the growth of such malignancies as pancreatic, breast, and lung cancer; however, GSI treatment in vivo is associated with side effects, especially those within the gastrointestinal tract. Although intensive studies are associated with the role of γ-secretase in pathological states, it should be pointed out that this complex impacts on proteolytic cleavages of around 55 membrane proteins. Therefore, it is clear that GSIs are highly non-specific and additional drugs must be designed, which will more specifically target components of the Notch signalling.","PeriodicalId":10652,"journal":{"name":"Contemporary Oncology","volume":"70 1","pages":"267 - 272"},"PeriodicalIF":0.0,"publicationDate":"2016-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88533664","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}
Salivary gland tumours are a group of lesions whose heterogeneity of biological and pathological features is widely reflected in the molecular aspect. This is demonstrated by an increasing number of studies in the field of genetics of these tumours. The aim of this study was to collect the most significant scientific reports on the cytogenetic and molecular data concerning these tumours, which might facilitate the identification of potential biomarkers and therapeutic targets. The analysis covered 71 papers included in the PubMed database. We focused on the most common tumours, such as pleomorphic adenoma, Warthin tumour, mucoepidermoid carcinoma, and others. The aim of this study is to present current knowledge about widely explored genotypic alterations (such as PLAG1 gene in pleomorphic adenoma or MECT1 gene in mucoepidermoid carcinoma), and also about rare markers, like Mena or SOX10 protein, which might also be associated with tumourigenesis and carcinogenesis of these tumours.
{"title":"Particular aspects in the cytogenetics and molecular biology of salivary gland tumours – current review of reports","authors":"Aleksandra Ochal-Choińska, E. Osuch-Wójcikiewicz","doi":"10.5114/wo.2016.61847","DOIUrl":"https://doi.org/10.5114/wo.2016.61847","url":null,"abstract":"Salivary gland tumours are a group of lesions whose heterogeneity of biological and pathological features is widely reflected in the molecular aspect. This is demonstrated by an increasing number of studies in the field of genetics of these tumours. The aim of this study was to collect the most significant scientific reports on the cytogenetic and molecular data concerning these tumours, which might facilitate the identification of potential biomarkers and therapeutic targets. The analysis covered 71 papers included in the PubMed database. We focused on the most common tumours, such as pleomorphic adenoma, Warthin tumour, mucoepidermoid carcinoma, and others. The aim of this study is to present current knowledge about widely explored genotypic alterations (such as PLAG1 gene in pleomorphic adenoma or MECT1 gene in mucoepidermoid carcinoma), and also about rare markers, like Mena or SOX10 protein, which might also be associated with tumourigenesis and carcinogenesis of these tumours.","PeriodicalId":10652,"journal":{"name":"Contemporary Oncology","volume":"46 1","pages":"281 - 286"},"PeriodicalIF":0.0,"publicationDate":"2016-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87776117","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}
Aim of the study Determining the role of PET/CT imaging in the evaluation of treatment efficacy in primary mediastinal B-cell lymphoma (PMBCL). Material and methods Retrospective analysis of seven PMBCL patients, treated at the University Hospital in Krakow, with interim PET/CT after the third course of chemo-immunotherapy.The analysis was based on the calculation of exact tumour volume and metabolic activity, compared with initial values (directly after diagnosis). Results Patients (five females, two males, average age 26.2 years, range 18–40 years), in clinical stage IIBX at diagnosis, were treated with eight cycles of R-CHOP-14 regimen, with radiotherapy consolidation (7/7) and central nervous system prophylaxis (6/7). The observed decrease in tumour volume between the initial staging and the interim PET ranged 72–89%. The mean ΔSUVmax reduction between initial (when available) and interim PET was 87% (range 84–89%). In 3/7 cases in the interim PET/CT, the uptake of the tumour was higher than the liver (Deauville Criteria score 4–5), and in 4/7 it was lower than the liver but higher than mediastinal blood pool structures (score 3 according to Deauville Criteria). After a median follow-up of 58 months – OS and EFS is 100%. Conclusions The excellent clinical outcome in the study group corresponds with very good metabolic and volumetric response in the interim PET. The ΔSUVmax seems to be easier in implementation and has a more significant impact than other measurements.
{"title":"Primary mediastinal B-cell lymphoma – metabolic and anatomical features in 18FDG-PET/CT and response to therapy","authors":"A. Kocurek, B. Małkowski, A. Giza, W. Jurczak","doi":"10.5114/wo.2016.61849","DOIUrl":"https://doi.org/10.5114/wo.2016.61849","url":null,"abstract":"Aim of the study Determining the role of PET/CT imaging in the evaluation of treatment efficacy in primary mediastinal B-cell lymphoma (PMBCL). Material and methods Retrospective analysis of seven PMBCL patients, treated at the University Hospital in Krakow, with interim PET/CT after the third course of chemo-immunotherapy.The analysis was based on the calculation of exact tumour volume and metabolic activity, compared with initial values (directly after diagnosis). Results Patients (five females, two males, average age 26.2 years, range 18–40 years), in clinical stage IIBX at diagnosis, were treated with eight cycles of R-CHOP-14 regimen, with radiotherapy consolidation (7/7) and central nervous system prophylaxis (6/7). The observed decrease in tumour volume between the initial staging and the interim PET ranged 72–89%. The mean ΔSUVmax reduction between initial (when available) and interim PET was 87% (range 84–89%). In 3/7 cases in the interim PET/CT, the uptake of the tumour was higher than the liver (Deauville Criteria score 4–5), and in 4/7 it was lower than the liver but higher than mediastinal blood pool structures (score 3 according to Deauville Criteria). After a median follow-up of 58 months – OS and EFS is 100%. Conclusions The excellent clinical outcome in the study group corresponds with very good metabolic and volumetric response in the interim PET. The ΔSUVmax seems to be easier in implementation and has a more significant impact than other measurements.","PeriodicalId":10652,"journal":{"name":"Contemporary Oncology","volume":"29 1","pages":"297 - 301"},"PeriodicalIF":0.0,"publicationDate":"2016-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78232116","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}
Aim of the study The purpose of this retrospective study is to evaluate the clinicopathological features and treatment results of male breast cancer presented to our tertiary referral center. Material and methods Between January 1998 and December 2005, a total of 39 men with breast cancer treated at Alexandria Main University Hospital and their medical records were reviewed. Results The median age of patients was 59 years. Only 3 (7.7%) patients had positive family history. All patients presented by breast swellings that were associated with axillary mass in about one third of them. Around 80% had hormone receptor positive (estrogen and/or progesterone receptors). Two third of patients had advanced T-stage (T3 and T4). Left sided breast cancer occurred in 51.3%. Infiltrating ductal carcinoma was the most common type of histology encountered and grade 2 was the predominant grade of tumor. Modified radical mastectomy was the most common (87.2%) type of surgery done followed by chemotherapy for 32 patients and loco-regional radiotherapy for 20 patients. Tamoxifen was administered in 31 patients. Distant relapse occurred in 7 patients (17.9%) and local recurrence occurred in 2 patients (5.1%). The 5-year disease-free survival (DFS) was 82% and the 5-year overall survival (OS) rate was 84%. Only negative axillary lymph node and positive hormone receptor status were significantly associated with favorable DFS and OS. T-stage, grade of tumor and type of chemotherapy given had no statistically significant impact on either DFS or OS. Conclusions Male breast cancer is still under-investigated and further researches are warranted.
{"title":"Male breast cancer: a clinicopathological study of an Egyptian population (Alexandria experience)","authors":"M. Soliman, M. Hetnał","doi":"10.5114/wo.2016.61855","DOIUrl":"https://doi.org/10.5114/wo.2016.61855","url":null,"abstract":"Aim of the study The purpose of this retrospective study is to evaluate the clinicopathological features and treatment results of male breast cancer presented to our tertiary referral center. Material and methods Between January 1998 and December 2005, a total of 39 men with breast cancer treated at Alexandria Main University Hospital and their medical records were reviewed. Results The median age of patients was 59 years. Only 3 (7.7%) patients had positive family history. All patients presented by breast swellings that were associated with axillary mass in about one third of them. Around 80% had hormone receptor positive (estrogen and/or progesterone receptors). Two third of patients had advanced T-stage (T3 and T4). Left sided breast cancer occurred in 51.3%. Infiltrating ductal carcinoma was the most common type of histology encountered and grade 2 was the predominant grade of tumor. Modified radical mastectomy was the most common (87.2%) type of surgery done followed by chemotherapy for 32 patients and loco-regional radiotherapy for 20 patients. Tamoxifen was administered in 31 patients. Distant relapse occurred in 7 patients (17.9%) and local recurrence occurred in 2 patients (5.1%). The 5-year disease-free survival (DFS) was 82% and the 5-year overall survival (OS) rate was 84%. Only negative axillary lymph node and positive hormone receptor status were significantly associated with favorable DFS and OS. T-stage, grade of tumor and type of chemotherapy given had no statistically significant impact on either DFS or OS. Conclusions Male breast cancer is still under-investigated and further researches are warranted.","PeriodicalId":10652,"journal":{"name":"Contemporary Oncology","volume":"14 1","pages":"335 - 340"},"PeriodicalIF":0.0,"publicationDate":"2016-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75498066","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}
Chi Pan, Shanshan Weng, Yin Duan, L. Ding, Su-zhan Zhang, Jian-jin Huang
Aim of the study Many studies have shown that interferon-α (IFN-α) enhances the antiproliferative effect of gefitinib in some solid tumours. We aimed to determine the effect of combining IFN-α with gefitinib in human non-small cell lung cancer (NSCLC) cell lines (A549, H1299, HCC827) with different EGFR and K-Ras gene statuses. Material and methods An MTT assay was used to assess cell proliferation. Apoptosis was detected by an Annexin V/propidium iodide assay using flow cytometry, and western blotting was used to determine the expression of epidermal growth factor receptor/phosphorylated epidermal growth factor receptor (EGFR/p-EGFR) and signal transducers and activators of transcription 3/phosphorylated signal transducers and activators of transcription 3 (STAT3/p-STAT3). Results There was an additive interaction when gefitinib was combined with IFN-α in all cell lines; however, there was antagonism when gefitinib followed IFN-α pretreatment in three cell lines. Notably, IFN-α pretreatment significantly reduced the gefitinib sensitivity of HCC827 cells. Surprisingly, while IFN-α inhibited STAT3 phosphorylation in cell lines, gefitinib could do so. Conclusions The results might confirm the hypothesis that IFN-α induces gefitinib sensitivity of NSCLC, and IFN-α inhibits phosphorylation of STAT3, which may be dependent on EGFR signal activation playing a role in the reduction of gefitinib sensitivity after IFN-α treatment in NSCLC cell lines.
{"title":"Interferon-α reduces the gefitinib sensitivity of human non-small cell lung cancer","authors":"Chi Pan, Shanshan Weng, Yin Duan, L. Ding, Su-zhan Zhang, Jian-jin Huang","doi":"10.5114/wo.2016.61853","DOIUrl":"https://doi.org/10.5114/wo.2016.61853","url":null,"abstract":"Aim of the study Many studies have shown that interferon-α (IFN-α) enhances the antiproliferative effect of gefitinib in some solid tumours. We aimed to determine the effect of combining IFN-α with gefitinib in human non-small cell lung cancer (NSCLC) cell lines (A549, H1299, HCC827) with different EGFR and K-Ras gene statuses. Material and methods An MTT assay was used to assess cell proliferation. Apoptosis was detected by an Annexin V/propidium iodide assay using flow cytometry, and western blotting was used to determine the expression of epidermal growth factor receptor/phosphorylated epidermal growth factor receptor (EGFR/p-EGFR) and signal transducers and activators of transcription 3/phosphorylated signal transducers and activators of transcription 3 (STAT3/p-STAT3). Results There was an additive interaction when gefitinib was combined with IFN-α in all cell lines; however, there was antagonism when gefitinib followed IFN-α pretreatment in three cell lines. Notably, IFN-α pretreatment significantly reduced the gefitinib sensitivity of HCC827 cells. Surprisingly, while IFN-α inhibited STAT3 phosphorylation in cell lines, gefitinib could do so. Conclusions The results might confirm the hypothesis that IFN-α induces gefitinib sensitivity of NSCLC, and IFN-α inhibits phosphorylation of STAT3, which may be dependent on EGFR signal activation playing a role in the reduction of gefitinib sensitivity after IFN-α treatment in NSCLC cell lines.","PeriodicalId":10652,"journal":{"name":"Contemporary Oncology","volume":"71 1","pages":"320 - 326"},"PeriodicalIF":0.0,"publicationDate":"2016-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77113901","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}
Edyta Ulińska, Katarzyna Mycko, Elżbieta Sałacińska-Łoś, A. Pastorczak, A. Siwicka, W. Młynarski, M. Matysiak
Aim of the study To characterise expression of mTOR (mammalian target of rapamycin) in childhood B-cell acute lymphoblastic leukaemia (ALL), and to evaluate a possible link between mTOR and clinical characteristics. Material and methods The examined group consisted of 21 consecutive patients, aged 1–18 years, diagnosed with B-cell ALL in 2010, and 10 relapsed B-cell ALL patients diagnosed for the first time between 2009 and 2011, who developed relapse before 2014. All subjects were treated in the Department of Paediatric Haematology and Oncology of the Medical University of Warsaw according to the ALL-IC BFM 2002 Protocol. We evaluated mTOR and phospho-mTOR expression by immunohistochemistry using rabbit monoclonal antibodies. Results mTOR expression was found to be significantly associated with the risk of relapse and was more frequent in ALL recurrence. No significant relationship was detected between mTOR expression and other features of high-risk disease in paediatric ALL. Conclusions mTOR activity could be considered a high-risk feature in paediatric B-cell ALL. Expression of mTOR kinase is observed remarkably more frequently in disease recurrence than at first diagnosis, indicating higher proliferative and survival potential of leukaemic cells in relapse. Routine analysis of mTOR activity could be performed to select patients that may potentially benefit from mTOR inhibitors (MTI) treatment.
研究目的:研究mTOR(哺乳动物雷帕霉素靶蛋白)在儿童b细胞急性淋巴细胞白血病(ALL)中的表达，并评估mTOR与临床特征之间的可能联系。材料与方法实验组包括21例2010年诊断为b细胞ALL的连续患者，年龄1-18岁，以及10例2009 - 2011年首次诊断，2014年之前复发的b细胞ALL患者。所有受试者在华沙医科大学儿科血液学和肿瘤学系根据All - ic BFM 2002年议定书进行治疗。我们利用兔单克隆抗体免疫组化检测mTOR和磷酸化mTOR的表达。结果mTOR表达与ALL复发风险显著相关，在ALL复发中更为常见。未发现mTOR表达与儿科ALL高危疾病的其他特征有显著关系。结论mTOR活性可被认为是儿童b细胞ALL的高危特征。mTOR激酶的表达在疾病复发时比首次诊断时更为频繁，这表明复发时白血病细胞的增殖和生存潜力更高。可以对mTOR活性进行常规分析，以选择可能从mTOR抑制剂(MTI)治疗中获益的患者。
{"title":"Impact of mTOR expression on clinical outcome in paediatric patients with B-cell acute lymphoblastic leukaemia – preliminary report","authors":"Edyta Ulińska, Katarzyna Mycko, Elżbieta Sałacińska-Łoś, A. Pastorczak, A. Siwicka, W. Młynarski, M. Matysiak","doi":"10.5114/wo.2016.61848","DOIUrl":"https://doi.org/10.5114/wo.2016.61848","url":null,"abstract":"Aim of the study To characterise expression of mTOR (mammalian target of rapamycin) in childhood B-cell acute lymphoblastic leukaemia (ALL), and to evaluate a possible link between mTOR and clinical characteristics. Material and methods The examined group consisted of 21 consecutive patients, aged 1–18 years, diagnosed with B-cell ALL in 2010, and 10 relapsed B-cell ALL patients diagnosed for the first time between 2009 and 2011, who developed relapse before 2014. All subjects were treated in the Department of Paediatric Haematology and Oncology of the Medical University of Warsaw according to the ALL-IC BFM 2002 Protocol. We evaluated mTOR and phospho-mTOR expression by immunohistochemistry using rabbit monoclonal antibodies. Results mTOR expression was found to be significantly associated with the risk of relapse and was more frequent in ALL recurrence. No significant relationship was detected between mTOR expression and other features of high-risk disease in paediatric ALL. Conclusions mTOR activity could be considered a high-risk feature in paediatric B-cell ALL. Expression of mTOR kinase is observed remarkably more frequently in disease recurrence than at first diagnosis, indicating higher proliferative and survival potential of leukaemic cells in relapse. Routine analysis of mTOR activity could be performed to select patients that may potentially benefit from mTOR inhibitors (MTI) treatment.","PeriodicalId":10652,"journal":{"name":"Contemporary Oncology","volume":"20 1","pages":"291 - 296"},"PeriodicalIF":0.0,"publicationDate":"2016-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81538111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Poletajew, R. Biernacki, P. Buraczyński, J. Chojnacki, S. Czarniecki, D. Gajewska, T. Pohaba, J. Sondka, M. Skrzypczyk, T. Suchojad, D. Wojtkowiak, B. Zaforemski, Ł. Zapała, A. Zemła, P. Radziszewski
A potential reason for poor survival among patients with muscle-invasive bladder cancer (MIBC) in Poland is initial disqualification from curative treatment due to advanced stage of the disease or low performance status. The aim of this study was to describe patterns of care in patients with newly diagnosed MIBC. This is a multicentre retrospective cohort study involving 296 consecutive patients with primary histologically diagnosed MIBC. Therapeutic decisions and potentially underlying clinical factors were analysed. Full clinical data was available for 285 patients. One hundred and sixty-four (57.5%) patients were qualified for radical cystectomy (RC), 32 (11.2%) patients for a second step of transurethral resection of the bladder tumour (TURBT) intentionally followed by systemic chemotherapy, four (1.4%) patients after complete TURBT were qualified for adjuvant intravesical chemotherapy only, while the remaining 85 (29.8%) patients were qualified for palliative treatment in the form of chemotherapy and/or radiotherapy and/or best supportive care. Patients disqualified from curative treatment were older (78 vs. 69 years, p < 0.02), had lower BMI values (24.5 vs. 25.7 kg/m2, p < 0.02), lower haemoglobin concentration (11.6 vs. 12.9 mg/l, p < 0.02), declared lower rate of nicotine abuse (50.5% vs. 72.1%, p < 0.02), and had a shorter time interval between first symptom and diagnosis (30 vs. 60 days, p = 0.02). As the majority of Polish patients with primary MIBC receive curative treatment, the stage of the disease alone seems not to be the leading cause of poor survival. However, appropriateness of qualification for RC and treatment quality needs to be assessed for final conclusion on the factors influencing outcomes of treatment in Poland.
波兰肌肉浸润性膀胱癌(MIBC)患者生存率低的一个潜在原因是，由于疾病晚期或表现不佳，患者最初无法接受根治性治疗。本研究的目的是描述新诊断的MIBC患者的护理模式。这是一项多中心回顾性队列研究，涉及296例连续的原发性组织学诊断为MIBC的患者。分析了治疗决定和潜在的临床因素。285例患者有完整的临床资料。164例(57.5%)患者适合根治性膀胱切除术(RC)， 32例(11.2%)患者适合经尿道膀胱肿瘤切除术(TURBT)的第二步，随后进行全身化疗，4例(1.4%)患者在完全TURBT后仅适合辅助膀胱化疗，而其余85例(29.8%)患者适合姑息治疗，包括化疗和/或放疗和/或最佳支持治疗。不能获得根治性治疗的患者年龄较大(78 vs 69岁，p < 0.02)， BMI值较低(24.5 vs. 25.7 kg/m2, p < 0.02)，血红蛋白浓度较低(11.6 vs. 12.9 mg/l, p < 0.02)，尼古丁滥用率较低(50.5% vs. 72.1%， p < 0.02)，首次症状和诊断之间的时间间隔较短(30 vs. 60天，p = 0.02)。由于大多数波兰原发性MIBC患者接受了治愈性治疗，疾病的分期似乎不是导致生存率低的主要原因。然而，需要评估RC资格的适当性和治疗质量，以最终得出影响波兰治疗结果的因素的结论。
{"title":"Patterns of care in patients with muscle-invasive bladder cancer – a retrospective cohort study","authors":"S. Poletajew, R. Biernacki, P. Buraczyński, J. Chojnacki, S. Czarniecki, D. Gajewska, T. Pohaba, J. Sondka, M. Skrzypczyk, T. Suchojad, D. Wojtkowiak, B. Zaforemski, Ł. Zapała, A. Zemła, P. Radziszewski","doi":"10.5114/wo.2016.61857","DOIUrl":"https://doi.org/10.5114/wo.2016.61857","url":null,"abstract":"A potential reason for poor survival among patients with muscle-invasive bladder cancer (MIBC) in Poland is initial disqualification from curative treatment due to advanced stage of the disease or low performance status. The aim of this study was to describe patterns of care in patients with newly diagnosed MIBC. This is a multicentre retrospective cohort study involving 296 consecutive patients with primary histologically diagnosed MIBC. Therapeutic decisions and potentially underlying clinical factors were analysed. Full clinical data was available for 285 patients. One hundred and sixty-four (57.5%) patients were qualified for radical cystectomy (RC), 32 (11.2%) patients for a second step of transurethral resection of the bladder tumour (TURBT) intentionally followed by systemic chemotherapy, four (1.4%) patients after complete TURBT were qualified for adjuvant intravesical chemotherapy only, while the remaining 85 (29.8%) patients were qualified for palliative treatment in the form of chemotherapy and/or radiotherapy and/or best supportive care. Patients disqualified from curative treatment were older (78 vs. 69 years, p < 0.02), had lower BMI values (24.5 vs. 25.7 kg/m2, p < 0.02), lower haemoglobin concentration (11.6 vs. 12.9 mg/l, p < 0.02), declared lower rate of nicotine abuse (50.5% vs. 72.1%, p < 0.02), and had a shorter time interval between first symptom and diagnosis (30 vs. 60 days, p = 0.02). As the majority of Polish patients with primary MIBC receive curative treatment, the stage of the disease alone seems not to be the leading cause of poor survival. However, appropriateness of qualification for RC and treatment quality needs to be assessed for final conclusion on the factors influencing outcomes of treatment in Poland.","PeriodicalId":10652,"journal":{"name":"Contemporary Oncology","volume":"1 1","pages":"341 - 343"},"PeriodicalIF":0.0,"publicationDate":"2016-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89274851","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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