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[Mathematical and computational methods to model chemotherapy- induced resistance]. [数学和计算方法模拟化疗引起的耐药]。
Magyar onkologia Pub Date : 2021-06-03 Epub Date: 2021-05-11
Dániel Kiss, Anna Lovrics, Gergely Szakács, András Füredi, Levente Kovács, Dániel Drexler
{"title":"[Mathematical and computational methods to model chemotherapy- induced resistance].","authors":"Dániel Kiss,&nbsp;Anna Lovrics,&nbsp;Gergely Szakács,&nbsp;András Füredi,&nbsp;Levente Kovács,&nbsp;Dániel Drexler","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Chemotherapy plays an important role in the treatment of cancer. While clinical chemotherapy protocols can lead to remission in some patients, in many cases tumor progression occurs despite continued treatment. In the present study we summarize mathematical approaches to model tumor growth and response to treatment, focusing on anticancer therapy resistance. We present results obtained at the recently founded Cybermedical Competence Center at Óbuda University, focusing on the development of a new therapy optimization concept that aims to optimize traditional chemotherapy.</p>","PeriodicalId":18175,"journal":{"name":"Magyar onkologia","volume":"65 2","pages":"167-175"},"PeriodicalIF":0.0,"publicationDate":"2021-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39057860","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}
引用次数: 0
[Single cell mass cytometric comparison of human H1975 lung and MDA-MD-231 breast adenocarcinoma cellular models]. [人H1975肺和MDA-MD-231乳腺腺癌细胞模型的单细胞大量细胞术比较]。
Magyar onkologia Pub Date : 2021-06-03 Epub Date: 2021-04-28
Patrícia Neuperger, G László Puskás, János Gábor Szebeni
{"title":"[Single cell mass cytometric comparison of human H1975 lung and MDA-MD-231 breast adenocarcinoma cellular models].","authors":"Patrícia Neuperger,&nbsp;G László Puskás,&nbsp;János Gábor Szebeni","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The most frequent cancer types are lung and breast cancer in the Western world. However, the prognosis of breast cancer patients shows an improved tendency, while lung cancer types remained with high mortality. Intratumor heterogeneity (ITH) frequently leads to the failure of treatments, so there is an unmet need revealing ITH at single cell resolution. Our aim was to study female-derived human H1975 lung and MDA-MB-231 triple-negative breast cancer adenocarcinoma cell line models using single cell mass cytometry. Nine of thirteen carcinoma markers showed significant differences in the percentage of cells. Our current work shed light on the intra- and inter cell line heterogeneity still preserved in the studied, widely-used adenocarcinoma laboratory models.</p>","PeriodicalId":18175,"journal":{"name":"Magyar onkologia","volume":"65 2","pages":"129-138"},"PeriodicalIF":0.0,"publicationDate":"2021-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39009148","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}
引用次数: 0
[And what about doctors? Associations between spontaneous chromosomal aberrations and cancer morbidity in healthcare workers]. 那医生呢?自发性染色体畸变与卫生保健工作者癌症发病率之间的关系。
Magyar onkologia Pub Date : 2021-06-03 Epub Date: 2021-04-05
Gyöngyi Farkas, Zsuzsa S Kocsis, Gábor Székely, Mária Dobozi, Csaba Polgár, Zsolt Jurányi
{"title":"[And what about doctors? Associations between spontaneous chromosomal aberrations and cancer morbidity in healthcare workers].","authors":"Gyöngyi Farkas,&nbsp;Zsuzsa S Kocsis,&nbsp;Gábor Székely,&nbsp;Mária Dobozi,&nbsp;Csaba Polgár,&nbsp;Zsolt Jurányi","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Healthcare workers may be occupationally exposed to low dose rate radiation or different chemicals during their work. There are strong associations between the increased frequency of spontaneous chromosomal aberrations in blood lymphocytes and the risk of cancer. Cytogenetic tests were conducted on 1240 healthy medical workers and cancer incidence was followed up between 1997-2018. Both structural and numerical chromosome aberrations were evaluated and the results were compared taking into account gender, age, and smoking. The frequency of aberrant cells was significantly higher in smoker males than in non-smokers (p=0.009). Within the same study period, there was no significant difference in chromosome aberrations between the potentially exposed group of workers and the control group. Among 82 cancer cases (6.6%) the most common tumors were breast (16), colon (12), lung (7) and thyroid gland cancers (7). Our analysis showed 7.3% cancer occurrence among smokers compared to 6.2% among non-smokers. These results suggest that in our cases cytogenetic effects of smoking are more deleterious than occupational exposures.</p>","PeriodicalId":18175,"journal":{"name":"Magyar onkologia","volume":"65 2","pages":"141-148"},"PeriodicalIF":0.0,"publicationDate":"2021-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39073430","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}
引用次数: 0
[EGFR protein is a negative prognostic and predictive factor in wild-type RAS colorectal cancer]. [EGFR蛋白是野生型RAS结直肠癌的阴性预后和预测因素]。
Magyar onkologia Pub Date : 2021-06-03 Epub Date: 2021-05-16
Andrea Uhlyarik, Violetta Piurkó, Zsuzsanna Pápai, Erzsébet Rásó, Erika Lahm, Edina Kiss, Márta Sikter, József Vachaja, Laura Vízkeleti, István Kenessey, József Tímár
{"title":"[EGFR protein is a negative prognostic and predictive factor in wild-type RAS colorectal cancer].","authors":"Andrea Uhlyarik,&nbsp;Violetta Piurkó,&nbsp;Zsuzsanna Pápai,&nbsp;Erzsébet Rásó,&nbsp;Erika Lahm,&nbsp;Edina Kiss,&nbsp;Márta Sikter,&nbsp;József Vachaja,&nbsp;Laura Vízkeleti,&nbsp;István Kenessey,&nbsp;József Tímár","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Negative predictive markers of the anti-EGFR antibody therapies are RAS or BRAF mutations, while left sidedness can be considered as a positive predictor. Here we analyzed 97 wild type RAS metastatic colorectal cancers looking for the prognostic and predictive roles of EGFR protein expression. We found that right-sided colorectal cancers are characterized by significantly higher EGFR protein expression as compared to left-sided ones, irrespective of the primary or metastatic tissue analysis. Furthermore, tumors with multiple organ involvement are characterized by significantly higher EGFR protein expression as compared to single organ ones. In the homogenous cetuximab treated cohort (n=90) we have found that lower than the applied EGFR protein expression cut-off was associated with favorable survival. In the multivariate analysis only sidedness proved to be a strong independent predictor, however sidedness is an EGFR-dependent predictor of anti-EGFR therapy.</p>","PeriodicalId":18175,"journal":{"name":"Magyar onkologia","volume":"65 2","pages":"121-127"},"PeriodicalIF":0.0,"publicationDate":"2021-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39073429","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}
引用次数: 0
[Predictive relevance of KRAS mutational status in bone metastatic lung adenocarcinoma treated with bisphosphonate therapy]. [KRAS突变状态与双膦酸盐治疗骨转移性肺腺癌的预测相关性]。
Magyar onkologia Pub Date : 2021-06-03 Epub Date: 2021-05-08
Péter Radeczky, Zsolt Megyesfalvi, János Fillinger, Viktória László, Erzsébet Rásó, Judit Moldvay, Erzsébet Schlegl, Tamás Barbai, Krisztina Bogos, József Tímár, Ferenc Rényi-Vámos, Balázs Hegedűs, Balázs Döme
{"title":"[Predictive relevance of KRAS mutational status in bone metastatic lung adenocarcinoma treated with bisphosphonate therapy].","authors":"Péter Radeczky,&nbsp;Zsolt Megyesfalvi,&nbsp;János Fillinger,&nbsp;Viktória László,&nbsp;Erzsébet Rásó,&nbsp;Judit Moldvay,&nbsp;Erzsébet Schlegl,&nbsp;Tamás Barbai,&nbsp;Krisztina Bogos,&nbsp;József Tímár,&nbsp;Ferenc Rényi-Vámos,&nbsp;Balázs Hegedűs,&nbsp;Balázs Döme","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The therapeutic impact of KRAS mutations remains controversial in bone metastatic lung adenocarcinoma (LADC). Therefore, our aim was to investigate the effects of KRAS mutational status on overall survival (OS) in these patients according to bisphosphonate therapy (BTx) and radiation therapy (RTx). In total, 134 LADC patients diagnosed with simultaneous bone metastasis were included in this study. The results of the univariate (p=0.008) and multivariate (p=0.004) survival analyses indicated that KRAS mutation is a negative prognostic factor. Both BTx and RTx can increase the OS with a pronounced benefit for patients with KRAS wild-type tumors. Importantly, the concomitant use of BTx and RTx might increase the OS irrespective of KRAS status compared to BTx or RTx alone. In summary, our results might contribute to the development of new therapeutic approaches with regards to KRAS mutational status in bone metastatic LADC.</p>","PeriodicalId":18175,"journal":{"name":"Magyar onkologia","volume":"65 2","pages":"103-111"},"PeriodicalIF":0.0,"publicationDate":"2021-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39073427","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}
引用次数: 0
[Application of Asn-Gly-Arg sequence based cyclic peptides for targeted tumor therapy]. [Asn-Gly-Arg序列环肽在肿瘤靶向治疗中的应用]。
Magyar onkologia Pub Date : 2021-06-03 Epub Date: 2021-05-15
Gábor Mező, Andrea Tripodi Angelo Pierluigi, Ivan Ranđelovič, Nóra Kata Enyedi, Beáta Biri-Kovács, József Tóvári
{"title":"[Application of Asn-Gly-Arg sequence based cyclic peptides for targeted tumor therapy].","authors":"Gábor Mező,&nbsp;Andrea Tripodi Angelo Pierluigi,&nbsp;Ivan Ranđelovič,&nbsp;Nóra Kata Enyedi,&nbsp;Beáta Biri-Kovács,&nbsp;József Tóvári","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The in vivo antitumor effect of two NGR sequence containing peptide-daunomycin conjugates was studied on CD13+ Kaposi's sarcoma s.c. tumor model on SCID mice, and on orthotopically developed CD13- HT-29 colon adenocarcinoma SCID mouse model. Both tumor types were positive for integrins. Significant tumor growth inhibition was observed on both tumor types by the treatment with the conjugates (Dau=Aoa-GFLGK(cyclo[KNGRE]-GG)-NH2 (1) and Dau=Aoa-GFLGK(cyclo[NleNGRE]-GG)-NH2 (2)). KS conjugate 1 with rather stable construct was more potent in tumor growth inhibition that might be explained by the CD13 receptor recognition of NGR sequence. In contrast, conjugate 2 that has propensity to rearrange isoAsp derivative showed significantly higher inhibition on CD13- HT-29 tumor model that is related to the integrin binding of isoDGR sequence. Next to the low toxic side effect of the conjugates in comparison with the free daunomycin, the positive efficiency of the conjugates was detected by the lower proliferation index and lower neovascularization of the tumor tissue.</p>","PeriodicalId":18175,"journal":{"name":"Magyar onkologia","volume":"65 2","pages":"113-120"},"PeriodicalIF":0.0,"publicationDate":"2021-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39073428","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}
引用次数: 0
[Consequences of extracellular alterations of EGFR on cetuximab therapy in HNSCC]. [细胞外EGFR改变对西妥昔单抗治疗HNSCC的影响]。
Magyar onkologia Pub Date : 2021-06-03 Epub Date: 2021-05-12
Mihály Cserepes, Györgyi A Nelhűbel, Mónika Meilinger-Dobra, Sára Eszter Surguta, Erzsébet Rásó, Andrea Ladányi, István Kenessey, Árpád Szöőr, György Vereb, Éva Remenár, József Tóvári
{"title":"[Consequences of extracellular alterations of EGFR on cetuximab therapy in HNSCC].","authors":"Mihály Cserepes,&nbsp;Györgyi A Nelhűbel,&nbsp;Mónika Meilinger-Dobra,&nbsp;Sára Eszter Surguta,&nbsp;Erzsébet Rásó,&nbsp;Andrea Ladányi,&nbsp;István Kenessey,&nbsp;Árpád Szöőr,&nbsp;György Vereb,&nbsp;Éva Remenár,&nbsp;József Tóvári","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Head and neck squamous cell carcinomas (HNSCC) take many lifes worldwide. Patients with recurrent/metastatic disease receive combination chemotherapy containing anti-EGFR antibody cetuximab. However, resistance often hurdles therapy. The mechanism is yet to unveil, although EGFR extracellular alterations and activity of c-Met signaling were accused. We investigated the effects of EGFR-vIII and EGFR-R521K on cetuximab efficacy in HNSCC in cellular, xenograft, and clinical setup. Furthermore, we investigated the efficacy of c-Met inhibition in HNSCC in vitro and in vivo. We showed that EGFR-vIII is very rare in HNSCC, while the common R521K polymorphism abolishes antibody-dependent cellular cytotoxicity and in vivo antitumor effect of cetuximab. This selectivity was not reflected in immunophenotype or survival data of HNSCC patients, suggesting a more complex mechanism behind. Interestingly, c-Met inhibitor SU11274 was more effective in cetuximab-resistant, EGFR R521K heterozygous cells and xenografts, raising the possible importance of simultaneous targeting of the two receptors.</p>","PeriodicalId":18175,"journal":{"name":"Magyar onkologia","volume":"65 2","pages":"188-195"},"PeriodicalIF":0.0,"publicationDate":"2021-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39057862","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}
引用次数: 0
[Development of novel treatment strategies for drug resistant cancer]. [耐药癌症新治疗策略的发展]。
Magyar onkologia Pub Date : 2021-06-03 Epub Date: 2021-05-09
Flóra Vajda, Eszter Bajtai, Balázs Gombos, Edina Karai, Lilla Hámori, Gergely Szakács, András Füredi
{"title":"[Development of novel treatment strategies for drug resistant cancer].","authors":"Flóra Vajda,&nbsp;Eszter Bajtai,&nbsp;Balázs Gombos,&nbsp;Edina Karai,&nbsp;Lilla Hámori,&nbsp;Gergely Szakács,&nbsp;András Füredi","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>There are about 14 million new cancer cases and 8 million deaths every year. Every second man and one in every three women will get cancer during their lifetimes. Following decades of steady increase, death rates have stabilized due to increased awareness and prevention, early detection, and the emergence of more effective therapy. Yet despite all the advances cancer remains a major killer. Despite improved therapies, nearly all current treatments face the same problem: for many patients, they ultimately stop working. Therapy resistance is the ultimate challenge facing cancer researchers and patients today. In this review we present an overview of the most important resistance mechanisms, discussing progress in therapies designed to prevent or overcome anticancer therapy resistance. Finally, we present recent findings from our own laboratory on the development of new experimental models and new therapeutic approaches to combat multidrug resistant cancer.</p>","PeriodicalId":18175,"journal":{"name":"Magyar onkologia","volume":"65 2","pages":"176-187"},"PeriodicalIF":0.0,"publicationDate":"2021-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39057861","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}
引用次数: 0
[Molecular background of BRAF inhibitor induced resistance in BRAFV600E mutant melanoma cell lines]. [BRAF抑制剂诱导BRAFV600E突变黑色素瘤细胞系耐药的分子背景]。
Magyar onkologia Pub Date : 2021-06-03 Epub Date: 2021-05-18
István Szász, Viktória Koroknai, Laura Vízkeleti, Margit Balázs
{"title":"[Molecular background of BRAF inhibitor induced resistance in BRAFV600E mutant melanoma cell lines].","authors":"István Szász,&nbsp;Viktória Koroknai,&nbsp;Laura Vízkeleti,&nbsp;Margit Balázs","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Target-specific inhibition of the BRAFV600E mutant protein has been a major breakthrough in the treatment of metastatic cutaneous melanoma. However, the success of therapies is significantly overshadowed by the development of resistance. Understanding the molecular mechanisms associated with acquired resistance is an important step to increase the effectiveness of melanoma treatment. Our aim was to elucidate the molecular differences underlying the development of drug resistance using a mutant BRAF protein inhibitor (vemurafenib analogue: PLX4720) in BRAFV600E mutant melanoma cell lines. We developed four BRAF inhibitor-resistant cell lines and examined the effect of BRAF inhibitor \"withdrawal\" on cell division. ArrayCGH was used to define genetic, and Affymetrix HumanGene 1.0 microarray to monitor gene expression alterations between the sensitive and resistant cell lines. Protein expression was determined using Proteome Profiler Human XL Oncology Array. We found that withdrawal of the inhibitor reduces cell proliferation in the resistant cells. The invasive potential of the resistant cells increased. Using genomic and proteomic methods we described new molecular alterations associated with acquired resistance.</p>","PeriodicalId":18175,"journal":{"name":"Magyar onkologia","volume":"65 2","pages":"149-156"},"PeriodicalIF":0.0,"publicationDate":"2021-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39073431","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}
引用次数: 0
[Dosimetric analysis of LINAC based stereotactic irradiation of brain tumours in CIRS SHANE phantom]. [基于LINAC立体定向照射CIRS SHANE幻象脑肿瘤的剂量学分析]。
Magyar onkologia Pub Date : 2021-03-17 Epub Date: 2020-07-17
Dalma Mihály, Barbara Melles-Bencsik, Tamás Pócza, Gábor Kontra, Tibor Major, András Bajcsay, Csaba Polgár, Csilla Pesznyák
{"title":"[Dosimetric analysis of LINAC based stereotactic irradiation of brain tumours in CIRS SHANE phantom].","authors":"Dalma Mihály,&nbsp;Barbara Melles-Bencsik,&nbsp;Tamás Pócza,&nbsp;Gábor Kontra,&nbsp;Tibor Major,&nbsp;András Bajcsay,&nbsp;Csaba Polgár,&nbsp;Csilla Pesznyák","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The aim of the study was to compare the different stereotactic treatment plans and dose calculation algorithms for small targets with film dosimetry in anthropomorphic phantom. Treatment plans were prepared for multiple targets with single setup isocenter. Plans for three different irradiation techniques were generated using conformal arc with four non-coplanar arcs, RapidArc with two coplanar full arcs and RapidArc with four non-coplanar arcs in the Varian Eclipse v13.7.16 TPS. Conformal arc and RapidArc plans were calculated using AAA, Acuros XBDm and XBDw algorithms. Conformity index, gradient index and dose maximum were calculated for all PTVs. All measurements were made on the Varian TrueBeam linear accelerator. Comparison between computed and measured dose distributions was performed with gamma evaluation criteria of 3%, 3 mm; 3%, 1 mm and 2%, 2 mm. According to our results, the Eclipse AAA and AXB algorithms provide accurate dose distributions for homogeneous cranial irradiation.</p>","PeriodicalId":18175,"journal":{"name":"Magyar onkologia","volume":"65 1","pages":"23-29"},"PeriodicalIF":0.0,"publicationDate":"2021-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25487150","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}
引用次数: 0
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