5 research outputs found
Pathological Complete Remission in Young Colon Cancer Patient with a Large Liver Metastasis after FOLFOX-4/Bevacizumab Treatment ā A Case Report
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BRCA1/2 mutation screening in high-risk breast/ovarian cancer families and sporadic cancer patient surveilling for hidden high-risk families
Background: The estimated ratio of hereditary breast/ovarian cancer (HBOC) based on family history is 1.5% in Latvia. This is significantly lower than the European average of 5-10%. Molecular markers like mutations and SNPs can help distinguish HBOC patients in the sporadic breast and ovarian cancer group.Methods: 50 patients diagnosed with HBOC in the Latvian Cancer Registry from January 2005 to December 2008 were screened for BRCA1 founder mutation-negatives and subjected to targeted resequencing of BRCA1 and BRCA2 genes. The newly found mutations were screened for in the breast and ovarian cancer group of 1075 patients by Real Time-PCR/HRM analysis and RFLP.Results: Four BRCA2 mutations including three novel BRCA2 frameshift mutations and one previously known BRCA2 frameshift mutation and one BRCA1 splicing mutation were identified. Two of the BRCA2 mutations were found in a group of consecutive breast cancer patients with a frequency of 0.51% and 0.38%.Conclusions: Molecular screening of sequential cancer patients is an important tool to identify HBOC families.publishersversionPeer reviewe
Mikro-RNS ekspresija kÄ prognostisks rÄdÄ«tÄjs krÅ«ts vÄža attÄ«stÄ«bai. Promocijas darba kopsavilkums
The Doctoral Thesis is elaborated in RÄ«ga StradiÅÅ” University, Institute of Oncology. Defence: at the public session of the Doctoral Committee of Medicine on 12 October 2015 at 15.00 in Hippocrates Lecture Theatre, Dzirciema Street 16, RÄ«ga StradiÅÅ” University.Breast cancer is the most wide spread tumor and the most frequent cause of death among women worldwide. Breast cancer is clinically, morphologically and genetically diverse disease therefore the outcome of the disease and treatment is dependent on the molecular heterogeneity of the disease. Breast cancer can be subdivided in several different molecular subtypes and this classification algorithm in the clinical practice is used to evaluate the pace of the disease and possible outcome. This algorithm has been used for more than 10 years already, thought this algorithm is not enough informative to predict the pace and the outcome of the disease. Hence in clinical practice new ā more informative biomarkers are required. One of such potential biomarker could be microRNAs ā non-coding small RNA molecules that have the ability to regulate gene expression post-transcriptionally, and they are involved in the cell differentiation, growth, and apoptosis. In tumors, microRNA expression is changed, and there is a correlation between the changed expression and clinical features of the disease MicroRNAs can act either as tumor inducers or tumor suppressors, and either are up-regulated or down-regulated. The TN breast cancer patients harboring the BRCA1 gene mutation at the time of the diagnosis are younger, have smaller tumor size, and have significantly better recurrence-free and disease-specific survival than TN breast cancer patients with no mutations in the BRCA1 gene. This study attempt to associate altered expression levels of some microRNAs (miR-10b, miR-21, miR-29a miR-31, and miR-214) in TNH and TNS cancer tissues to disease specific survival. In this study different gene expression profiles between TNH and TNS breast cancer tissues were evaluated as well. Four microRNAs (miR-10b, miR-21, miR-31, and miR-214) showed higher expression level in sporadic tissues than in hereditary ones; however only miR-214 was significantly higher. The triple-negative breast cancer patients with high level of miR-214 showed worse disease-specific survival than those with low level. In addition, 20 differently expressed gene were found between TNH and TNS breast cancer tissues. Moreover, three of those genes: C12ORF23, C1ORF19, and AMMECR1L are regulated by the miR-21 and miR-214.The thesis was co-funded by the ESF project: āSupport for Doctoral Students Mastering the Study Programme and Acquisition of a Scientific Degree in RÄ«ga StradiÅÅ” Universityā
MicroRNA Expression as a Prognostic Indicator for Breast Cancer Development. Doctoral Thesis
Promocijas darbs izstrÄdÄts: RSU, OnkoloÄ£ijas institÅ«tÄ. AizstÄvÄÅ”ana: 2015. gada 12. oktobrÄ« plkst. 15.00 RÄ«gas StradiÅa universitÄtes MedicÄ«nas promocijas padomes atklÄtÄ sÄdÄ RÄ«gÄ, Dzirciema ielÄ 16, HipokrÄta auditorijÄ.KrÅ«ts vÄzis ir viena no visbiežÄk izplatÄ«tÄkajÄm ļaundabÄ«go audzÄju formÄm un visbiežÄkais nÄves cÄlonis sievietÄm visÄ pasaulÄ. KrÅ«ts vÄzis ir klÄ«niski, morfoloÄ£iski un Ä£enÄtiski heterogÄna slimÄ«ba un tÄ attÄ«stÄ«bas gaita, atbildes reakcija uz terapiju, terapeitiskÄs blaknes un iznÄkums vistieÅ”ÄkajÄ veidÄ ir atkarÄ«gs no tÄ heterogÄnÄs dabas. KrÅ«ts vÄzi iedala vairÄkos apakÅ”tipos un klÄ«niskajÄ praksÄ Å”o klasificÄÅ”anas algoritmu izmanto, lai izvÄrtÄtu iespÄjamo slimÄ«bas attÄ«stÄ«bas virzÄ«bu un izvÄlÄtos optimÄlÄko terapeitisko stratÄÄ£iju, taÄu Å”is algoritms nav pietiekoÅ”i informatÄ«vs, lai prognozÄtu slimÄ«bas attÄ«stÄ«bas virzÄ«bu, tÄpÄc klÄ«niskajÄ praksÄ ir nepiecieÅ”ami jauni prognostiski un predikatÄ«vi marÄ·ieri. Vieni no Å”Ädiem marÄ·ierim ir mikroRNS ā 18 lÄ«dz 25 nukleotÄ«dus garas nekodÄjoÅ”as molekulas, kas regulÄ gÄnu ekspresiju post- transkripcijas lÄ«menÄ«. Å Ä«s molekulas ir iesaistÄ«tas tÄdos kritiskos Ŕūnas procesos kÄ diferenciÄcijÄ, augÅ”anÄ un apoptozÄ, lÄ«dz ar to tÄm ir nozÄ«mÄ«ga loma audzÄja attÄ«stÄ«bÄ. TurklÄt izmainÄ«ta mikroRNS ekspresija korelÄ ar audzÄja klÄ«niskÄm un patofizioloÄ£iskajÄm raksturiezÄ«mÄm. MikroRNS var rÄ«koties lÄ«dzÄ«gi kÄ audzÄju supresori vai onkogÄni un to ekspresiju atrod paaugstinÄtu, vai arÄ« samazinÄtu. TrÄ«skÄrÅ”i negatÄ«vas pÄrmantotas (TNH) krÅ«ts vÄža pacientes, kuras ir BRCA1 gÄna mutÄcijas nÄsÄtÄjas, diagnozes brÄ«dÄ« ir jaunÄkas, ar mazÄkiem audzÄja izmÄriem un tÄm novÄro labÄku krÅ«ts vÄža specifisko un kopÄjo dzÄ«vildzi kÄ trÄ«skÄrÅ”i negatÄ«vÄm sporÄdiskÄm (TNS) krÅ«ts vÄža pacientÄm ā bez BRCA1 gÄna mutÄcijas. Å Ä« pÄtÄ«juma mÄrÄ·is bija atrast saistÄ«bu starp izmainÄ«tu mikroRNS (miR-10b, miR-21, miR-29a, miR-31 un mir-214) ekspresiju TNH un TNS krÅ«ts vÄža audos un kopÄjo dzÄ«vildzi. Lai izskaidrotu atŔķirÄ«gu mikroRNS ekspresiju TNH un TNS krÅ«ts vÄža audos, veica gÄnu ekspresijas profila analÄ«zi. Äetriem mikroRNS (miR-10b, miR-21, miR-31 un miR-214) ekspresija bija augstÄka TNS kÄ TNH krÅ«ts vÄža audos, lai gan statistiskÄs ticamÄ«bas slieksni sasniedza tikai miR-214. TurklÄt krÅ«ts vÄža pacientÄm ar augstu miR-214 ekspresiju audzÄja audos bija sliktÄka kopÄjÄ dzÄ«vildze kÄ pacientÄm ar zemu miR-214 ekspresiju. Starp TNH un TNS krÅ«ts vÄža grupu atrada 20 atŔķirÄ«gi ekspresÄtus gÄnus, turklÄt trÄ«s no atrastajiem gÄniem: C12ORF23, C1ORF19 un AMMECR1L regulÄ miR-21 un miR-214 ekspresiju.Promocijas darbs veikts ar Eiropas SociÄlÄ fonda projekta āAtbalsts doktorantiem studiju programmas apguvei un zinÄtniskÄ grÄda ieguvei RÄ«gas StradiÅa universitÄtÄā finansiÄlu atbalstu
High expression of miR-214 is associated with a worse disease-specific survival of the triple-negative breast cancer patients
Publisher Copyright: Ā© Kalniete et al.; licensee BioMed Central.Background: Hereditary triple-negative breast cancer patients have better recurrence-free survival than triple-negative sporadic ones. High expression of some of the miRNAs is related to worse overall and disease-free survival of triple-negative breast cancer patients. The attempt to associate expression level of some miRNA in triple-negative hereditary and sporadic breast cancers to disease specific survival was performed in this study. Material and methods: Study group was made of 18 triple-negative breast cancer patients harboring the BRCA1 gene mutations and 32 triple-negative sporadic breast cancer patients. Quantitative amount of mir-10b, mir-21, mir-29a, mir-31, and mir-214 by real-time PCR was assessed. The disease-specific survival in relation of high and low levels of some of the miRNAs was analyzed using Log-rank (Mantel-Cox) test. Results: MiR-214 showed significantly higher expression level in sporadic tissues than in hereditary ones (p=0.0005). Triple-negative breast cancer patients with high level of miR-214 showed significantly worse disease-specific survival than patients with low level (p=0.0314). Conclusions: Our finding suggests that miR-214 possibly could be used as a potential prognostic biomarker for triple-negative breast cancer patients.Peer reviewe