Publications by authors named "Katerina Bouchalova"

13 Publications

  • Page 1 of 1

Predictive and Prognostic Value of DNA Damage Response Associated Kinases in Solid Tumors.

Front Oncol 2020 3;10:581217. Epub 2020 Nov 3.

Department of Medical Oncology and Haematology, Cantonal Hospital, St. Gallen, Switzerland.

Dysfunctional DNA repair with subsequent genome instability and high mutational burden represents a major hallmark of cancer. In established malignant tumors, increased DNA repair capacity mediates resistance to DNA-damaging therapeutics, including cytotoxic drugs, radiotherapy, and selected small molecules including inhibitors of poly (ADP-ribose) polymerase (PARP), Ataxia Telangiectasia Mutated (ATM), ataxia telangiectasia and Rad3-related protein (ATR), and Wee1 kinase (Wee1). In addition, DNA repair deficiency is not only associated with sensitivity to selected anticancer drugs, but also with increased mutagenicity and increased neoantigen load on tumor cells, resulting in increased immunogenicity and improved response to CTLA4- or PD-(L)1 targeting monoclonal antibodies. DNA damage response (DDR) is composed of complex signalling pathways, including the sensing of the DNA damage, signal transduction, cellular response pathways to DNA damage, and activation of DNA repair. DNA double strand breaks (DSBs) are the most dangerous form of DNA damage. Tumor cells are characterised by frequent accumulation of DSBs caused by either endogenous replication stress or the impact of cancer treatment, most prominently chemotherapy and radiotherapy. Therefore, response of cancer cells to DSBs represents a crucial mechanism for how tumors respond to systemic treatment or radiotherapy, and how resistance develops. Ample clinical evidence supports the importance of DDR associated kinases as predictive and prognostic biomarkers in cancer patients. The ATM-CHK2 and ATR-CHK1-WEE1 pathways initiate DNA DSB repair. In the current review, we focus on major DDR associated kinases including ATM, ATR, CHK1, CHK2, and WEE1, and discuss their potential prognostic and predictive value in solid malignancies.
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http://dx.doi.org/10.3389/fonc.2020.581217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670868PMC
November 2020

Free triiodothyronine/free thyroxine (FT3/FT4) ratio is strongly associated with insulin resistance in euthyroid and hypothyroid adults: a cross-sectional study.

Endokrynol Pol 2021 30;72(1):8-13. Epub 2020 Oct 30.

Ambulance Prof. MUDr. Karla Martiníka DrSc. s.r.o, Hradec Králové, Czech Republic.

Introduction: Insulin resistance (IR) is a key and early pathogenetic mechanism of cardiometabolic diseases with huge potential if detected early and mitigated, for lowering the burden of the disease. Available data are conflicting to what extent adult thyroid dysfunction is associated with IR. Therefore, we aimed to investigate the association and to identify which thyroid parameters are predictors of IR.

Material And Methods: After undergoing basic anthropometric and biochemical studies including thyroid hormones, oral glucose tolerance test (OGTT), and insulin, 1425 middle-aged individuals were divided into three groups according to thyroid parameters: overt hypothyroidism (OH), subclinical hypothyroidism (SH), and euthyroidism (EU).

Results: The homeostasis model assessment of IR (HOMA-IR), fasting insulin, and two-hour glucose levels of OGTT showed a steady, yet insignificant, increase from EU through SH to OH. The strongest noted correlations were those of insulin levels with free triiodothyronine/free thyroxine (FT3/FT4) ratio (r = 0.206, p < 0.001) and FT3 (r = 0.205, p < 0.001). Also in the case of HOMA-IR, the only statistically significant correlations were observed for FT3 (r = 0.181, p < 0.001) and the FT3/FT4 ratio (r = 0.165, p < 0.001). Among other thyroid hormones, linear logistic regression proved the FT3/FT4 ratio as the only significant predictor of HOMA-IR (linear coefficient = 5.26, p = 0.027) and insulin levels (linear coefficient = 18.01, p = 0.023), respectively. Thyroid-stimulating hormone was not associated with IR in either correlation or regression analysis.

Conclusions: The FT3/FT4 ratio should be more emphasised in the diagnosis and treatment of thyroid disorders. Patients could benefit from a pharmacological reduction of the FT3/FT4 ratio, potentially leading to a decrease in insulin resistance, and thus a corresponding decrease in the risk of the cardiometabolic diseases.
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http://dx.doi.org/10.5603/EP.a2020.0066DOI Listing
October 2020

Risks and protective factors for triple negative breast cancer with a focus on micronutrients and infections.

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2018 Jun 15;162(2):83-89. Epub 2018 May 15.

Department of Preventive Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc, Czech Republic.

Triple negative breast cancer (TNBC) is an aggressive form of breast cancer (BC) with a poor prognosis. Second, patients cannot benefit from targeted therapy, except for those with BRCA1/2 mutations, for whom poly (ADP-ribose) polymerase (PARP) inhibition therapy using olaparib has recently been approved. As global priorities continue to be epidemiological analysis of BC risk factors and early diagnosis, this review focuses on the risks and protective factors associated with TNBC. A PubMed keyword search for new knowledge on the risks and protective factors for TNBC was carried out. We also found statistical information from current online databases concerning the estimated incidence, prevalence and mortality worldwide of this cancer. Traditional risk factors for BC and TNBC are those related to reproduction such as the age of menarche, age of first birth, parity, breastfeeding and age at menopause. Attention needs to be paid to familial BC, weight control, alcohol consumption and regular physical activity. Epidemiological studies on TNBC provide evidence for protective factors such as regular consumption of soya, seafood, green tea, folic acid and vitamin D. Potential risk factors may include night work and viral infectious agents like human papillomavirus (HPV) and Epstein-Barr virus (EBV). Droplet digital methylation-specific PCR (ddMSP) is a possible new screening method for detection of BC including TNBC. Further research is necessary to validate these new factors.
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http://dx.doi.org/10.5507/bp.2018.014DOI Listing
June 2018

Ultrafast Online SPE-MS/MS Method for Quantification of 3 Tyrosine Kinase Inhibitors in Human Plasma.

Ther Drug Monit 2016 08;38(4):516-24

*Laboratory of Metabolomics, Institute of Molecular and Translational Medicine; †Laboratory of Inherited Metabolic Disorders; ‡Department of Hemato-Oncology; §Laboratory of Experimental Medicine, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University in Olomouc; and ¶Department of Clinical Biochemistry, University Hospital Olomouc, Czech Republic.

Background: With an increasing number of cancer patients receiving tyrosine kinase inhibitors (TKIs), therapeutic drug monitoring of these molecules is becoming more widespread today. It is mainly based on liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) methods with typical run times of several minutes. In an online solid phase extraction-MS/MS (SPE-MS/MS) system, the chromatography column is replaced with a reusable solid phase extraction (SPE) cartridge and the analysis time is shortened to less than half a minute. The aim of this study was to develop such a method and test the performance of this high-throughput system in the analysis of imatinib (IMA), nilotinib (NIL), and lapatinib (LAP) in human plasma.

Methods: Samples were prepared by simple protein precipitation with methanol containing deuterated internal standards. After centrifugation, the supernatant was diluted 10 fold with a mixture of methanol and water (1:1). A C4 cartridge was used for SPE and the analytes were eluted by acetonitrile. All the analytes were measured within a wide calibration range (50-5000 ng/mL for nilotinib and imatinib, 100-10,000 ng/mL for lapatinib). The method was compared with the LC-MS/MS method by the analysis of 176 clinical samples.

Results: Intraday and interday inaccuracies within 15% and a coefficient of variation less than 15% were achieved for all the TKIs that were measured. Even though the matrix effects were higher in comparison with LC-MS/MS methods, their effect on the performance of the method was eliminated by the usage of deuterated internal standards. The total run time of the new method was 29 seconds for one analysis and the results were fully comparable with LC-MS/MS.

Conclusions: Routine clinical practice requiring high-throughput methods for therapeutic drug monitoring of TKIs may benefit from the online SPE-MS/MS method that provides fast, low-cost analysis, and results that are comparable with conventional methods.
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http://dx.doi.org/10.1097/FTD.0000000000000309DOI Listing
August 2016

Frequency of chromosome 17 polysomy in relation to CEP17 copy number in a large breast cancer cohort.

Genes Chromosomes Cancer 2016 May 5;55(5):409-17. Epub 2016 Feb 5.

Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University and University Hospital in Olomouc, Hnevotinska 5, 775 15 Olomouc, the Czech Republic.

Eligibility to anti-HER2 therapy for breast tumors strictly depends on demonstrating HER2 overexpression (by immunohistochemistry) or HER2 gene amplification by in situ hybridization (ISH), usually defined by the ratio of HER2 gene to chromosome 17 centromere (CEP17) copies. However, the CEP17 copy number increase (CNI) has been proven responsible for misleading HER2 FISH results and recent small cohort studies suggest that chromosome 17 polysomy is actually very rare. Here we investigated by FISH the frequency of true chromosome 17 polysomy in a consecutive cohort of 5,477 invasive breast cancer patients. We evaluated and selected the LSI 17p11.2 probe for chromosome 17 enumeration on a training cohort of 67 breast cancer samples (CEP17 ≥ 2.5). LSI 17p11.2 was used in the 297/5,477 patients from the validation cohort displaying CEP17 CNI (CEP17 ≥ 3.0). Using HER2/17p11.2 scoring criteria, 37.3%/1.5% patients initially classified as equivocal/non-amplified were reclassified as amplified. For a more accurate assessment of chromosome 17 and ploidy in the samples, we tested six markers located on chromosome 17 and centromeric regions of chromosome 8 (CEP8) and 11 (CEP11) in 67 patients with CEP17 and LSI 17p11.2 CNI. True polysomy (hyperdiploidy) according to these markers was found in 0.48% of cases (24/5,020). CEP8 and CEP11 CNI (≥3.0) was more frequent in the hyperdiploid than CEP17 non-polysomic group (55.6% vs. 6.1% and 25% vs. 2.3%, respectively). Our results suggest that chromosome 17 polysomy is a rare event found in <1% breast cancer cases and that polysomy of other chromosomes frequently occurs with chromosome 17 polysomy.
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http://dx.doi.org/10.1002/gcc.22337DOI Listing
May 2016

BCL2 is an independent predictor of outcome in basal-like triple-negative breast cancers treated with adjuvant anthracycline-based chemotherapy.

Tumour Biol 2015 Jun 24;36(6):4243-52. Epub 2015 Jan 24.

Laboratory of Experimental Medicine, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Hnevotinska 5, 775 15, Olomouc, Czech Republic,

Neither targeted therapies nor predictors for chemotherapy sensitivity are available for triple-negative breast cancer (TNBC). Our study included 187 patients with TNBC, 164 of whom were treated with anthracycline-based adjuvant chemotherapy. Eleven molecular biomarkers were analyzed. BCL2, epidermal growth factor receptor (EGFR), MYC, TOP2A, and Ki-67 protein expression was evaluated by immunohistochemistry. The status of the EGFR, MYC, and TOP2A genes and chromosomes 7, 8, and 17 was assessed using fluorescence in situ hybridization. High BCL2 expression predicted poor relapse-free survival (RFS) in patients treated with anthracycline-based adjuvant chemotherapy (p = 0.035), poor breast cancer-specific survival (BCSS) (p = 0.048), and a trend to poor overall survival (OS) (p = 0.085). High levels of BCL2 expression predicted poor OS in basal-like (BL) TNBC patients treated with adjuvant anthracycline-based regimens (log-rank p = 0.033, hazard ratio (HR) 3.04, 95 % confidence interval (CI) 1.04-8.91) and a trend to poor RFS (log-rank p = 0.079) and poor BCSS (log-rank p = 0.056). Multivariate analysis showed that BCL2 status, tumor size, and nodal status all had independent predictive significance for RFS (p = 0.005, p = 0.091, p = 0.003, respectively; likelihood ratio test for the whole model, p = 0.003), BCSS (p = 0.012, p = 0.077, p = 0.01, respectively; likelihood ratio test for the whole model, p = 0.016), and OS (p = 0.008, p = 0.004, p = 0.004, respectively; likelihood ratio test for the whole model, p = 0.0006). Similarly, multivariate analysis for BL TNBC showed BCL2, tumor size, and nodal status all had independent predictive significance for RFS (likelihood ratio test for the whole model, p = 0.00125), BCSS (p = 0.00035), and OS (p = 0.00063). High EGFR expression was associated with poor BCSS (p = 0.039) in patients treated with anthracycline-based adjuvant chemotherapy. Patients who underwent anthracycline-based adjuvant chemotherapy and exhibited CMYC amplification had a trend to worse BCSS (p = 0.066). In conclusion, high BCL2 expression is a significant independent predictor of poor outcome in TNBC patients treated with anthracycline-based adjuvant chemotherapy, and this is the first study showing the BCL2 prediction in BL TNBC. BCL2 expression analysis could facilitate decision making on adjuvant treatment in TNBC patients.
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http://dx.doi.org/10.1007/s13277-015-3061-7DOI Listing
June 2015

Triple negative breast cancer - BCL2 in prognosis and prediction. Review.

Curr Drug Targets 2014 ;15(12):1166-75

Laboratory of Experimental Medicine, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University and University Hospital Olomouc, Hnevotinska 5, 775 15, Olomouc, Czech Republic.

Background: Breast cancer (BC), the most frequent malignancy in women worldwide, is currently diagnosed in about 1.4 million female patients annually. Approximately 10-20% of BC is represented by triple negative breast cancer (TNBC) which is aggressive, the prognosis is poor and patients cannot benefit from targeted treatment based on hormonal or HER2 receptors. For this reason, search for markers that can predict the efficacy of chemotherapy in TNBC is a priority.

Methods And Results: This review focuses on BCL2 protein as a prognostic marker in TNBC and its potential as a predictor of sensitivity to chemotherapy.

Conclusion: BCL2 protein expression is a positive prognostic factor in BC. Better survival of patients with BCL2 positivity (BCL2+) has been explained by the correlation with estrogen receptor positive (ER+) status. BCL2+ is however not simply a surrogate marker for ER+. Moreover, BCL2 protein expression is also a positive prognostic marker in the TNBC subgroup. We and others show, that low BCL2 expression was associated with good outcome of TNBC patients treated with both adjuvant and neoadjuvant anthracycline-based chemotherapy. On the other hand, recent studies have shown that a subset of TNBC patients may benefit from the classical adjuvant CMF (cyclophosphamide, methotrexate, 5-fluorouracil) regimen. Given the heterogeneity of TNBC there is an urgent need to find and validate the sensitivity predictors to these regimens making them usable in clinical practice. BCL2 enrichment has been described in the mesenchymal stem-like (MSL) TNBC subgroup.
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http://dx.doi.org/10.2174/1389450115666141106151143DOI Listing
July 2015

The role of cancer-associated fibroblasts, solid stress and other microenvironmental factors in tumor progression and therapy resistance.

Cancer Cell Int 2014 16;14:41. Epub 2014 May 16.

Laboratory of Molecular Pathology, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.

Tumors are not merely masses of neoplastic cells but complex tissues composed of cellular and noncellular elements. This review provides recent data on the main components of a dynamic system, such as carcinoma associated fibroblasts that change the extracellular matrix (ECM) topology, induce stemness and promote metastasis-initiating cells. Altered production and characteristics of collagen, hyaluronan and other ECM proteins induce increased matrix stiffness. Stiffness along with tumor growth-induced solid stress and increased interstitial fluid pressure contribute to tumor progression and therapy resistance. Second, the role of immune cells, cytokines and chemokines is outlined. We discuss other noncellular characteristics of the tumor microenvironment such as hypoxia and extracellular pH in relation to neoangiogenesis. Overall, full understanding of the events driving the interactions between tumor cells and their environment is of crucial importance in overcoming treatment resistance and improving patient outcome.
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http://dx.doi.org/10.1186/1475-2867-14-41DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4038849PMC
June 2014

High lapatinib plasma levels in breast cancer patients: risk or benefit?

Tumori 2012 Jan-Feb;98(1):162-5

Laboratory of Experimental Medicine, Institute of Molecular and Translational Medicine, Palacky University and University Hospital Olomouc, Olomouc, Czech Republic.

Aims And Background: Lapatinib is a tyrosine kinase inhibitor targeting epidermal growth factor receptors 1 (EGFR/HER1) and 2 (HER2) used in the treatment of patients with HER2-positive breast cancer. The aim of the present study was to determine lapatinib plasma levels in breast cancer patients treated with lapatinib plus capecitabine.

Patients And Methods: We assessed lapatinib plasma levels in blood samples from 21 breast cancer patients treated with lapatinib plus capecitabine using the standard regimen in an expanded access program. Liquid chromatography tandem mass spectrometry was used for measuring lapatinib plasma concentrations. The validated method was applied for measurement of 55 plasma samples.

Results: The median lapatinib plasma level was 5.09 μg/mL, with large interindividual differences. Patients of lower weight tended to have higher lapatinib plasma levels (Spearman correlation coefficient R = -0.435, P = 0.055). One patient's lapatinib plasma levels were markedly higher than those of the others, with a median level of 11.25 μg/mL and repeatedly exceeding 7.80 μg/mL. The treatment was terminated after 8 months when hyperbilirubinemia occurred.

Conclusions: The lapatinib plasma levels reported here are twice as high as the clinically effective steady-state geometric mean maximum concentration. We conclude that increased lapatinib body levels occur when patients are in a nonfasting state at the time of drug intake and when lapatinib doses are not adjusted to low body weight or weight loss during treatment. In Europe, dose adjustments are not recommended in the case of hepatic function impairment. Thus, attention should be paid to changes in liver function test results in clinical practice, especially in patients of small stature and weight, given the risk of high plasma concentrations. Prospective lapatinib plasma level assessment in treated patients might be useful to confirm or refute the possible correlation of high lapatinib plasma levels with hepatic and/or other toxicities.
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http://dx.doi.org/10.1700/1053.11516DOI Listing
July 2012

Collagen triple helix repeat containing 1 protein, periostin and versican in primary and metastatic breast cancer: an immunohistochemical study.

J Clin Pathol 2011 Nov 8;64(11):977-82. Epub 2011 Jul 8.

Department of Clinical and Molecular Pathology, Laboratory of Molecular Pathology, Institute of Molecular and Translational Medicine, Palacky University and University Hospital, Olomouc, Czech Republic.

Background: Collagen triple helix repeat containing 1 (CTHRC1) affects Wnt signalling, collagen deposition and bone formation. It is an extracellular matrix protein which is also abnormally expressed in the tumour microenvironment. CTHRC1 has not been studied in breast cancer by immunohistochemistry.

Aims: To examine expression of CTHRC1 together with periostin and versican in breast cancer patients and investigate its association with clinicopathological characteristics.

Methods: The formalin-fixed paraffin-embedded tissues of 173 invasive carcinomas (classified into WHO histotypes and luminal, triple negative and Her2 subtypes), as well as normal tissues, precursor lesions and metastatic lymph nodes were stained by relevant antibodies, assessed semiquantitatively by histoscore and statistically evaluated.

Results: Expression of CTHRC1, versican and periostin was significantly higher in breast cancer than in normal tissue or precursor lesions. CTHRC1 stromal expression was enhanced in triple negative cases and also in patients with bone metastasis. Periostin expression was high in primary tumours, in particular triple negative ones, and also in their lymph node metastases. Cox regression analysis showed that in patients with high periostin, the risk of bone metastases increased with increased CTHRC1 expression.

Conclusions: CTHRC1 and periostin play important roles in breast cancer progression. These preliminary results show that combined evaluation of CTHRC1 and periostin could serve as a potential marker for breast cancer bone metastasis; the other observations contribute to the description of the tumour microenvironment, with implications for lymph node and bone metastasis.
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http://dx.doi.org/10.1136/jclinpath-2011-200106DOI Listing
November 2011

Lapatinib in breast cancer - the predictive significance of HER1 (EGFR), HER2, PTEN and PIK3CA genes and lapatinib plasma level assessment.

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2010 Dec;154(4):281-8

Laboratory of Experimental Medicine, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Czech Republic.

Background: Breast cancer treatment trends are currently based on tailored therapies using tumor and patient biomarkers. Lapatinib is the first dual inhibitor of HER1 (EGFR, ErbB1) and HER2 (ErbB2, Neu) tyrosine kinases to be used in clinical practice. However, only HER2 is currently used for therapy indications and new predictors for the treatment with lapatinib are sought.

Methods And Results: This minireview focuses on lapatinib and its role in breast cancer treatment. Preclinical and clinical studies as well as pharmacological characteristics are briefly reviewed while the focus is on efficacy assessment including predictive factors for therapy outcome.

Conclusion: Lapatinib (Tykerb/Tyverb) was Food and Drug Administration (FDA) approved in 2007 for use in combination with capecitabine for the treatment of HER2-positive advanced or metastatic breast cancer in patients who had received previous treatment (including anthracycline, taxane and trastuzumab containing regimens) and in 2010 for use in combination with letrozole for postmenopausal women with hormonal receptor positive and HER2- positive metastatic breast cancer. In contrast to trastuzumab (Herceptin), lapatinib is orally administered and it targets both HER2 and HER1 receptors. As a synthetic and oral tyrosine kinase inhibitor (TKI), it is convenient, cheaper and easier to produce than monoclonal antibodies. The recommended dosage is not dependent on body weight either. Lapatinib plasma level measurement could be an approach to tailored therapy for further optimizing the dose and prolonging this efficient therapy. New lapatinib response predictors are being evaluated. At this time, only HER2 amplification/overexpression is used to choose lapatinib therapy candidates. Further studies on concurrent HER1 fluorescent in situ hybridization (FISH)/immunohistochemistry (IHC) assessment and/or microarray analyses may produce new data on the predictive role of the HER1 (EGFR) gene/protein. PTEN loss and PIK3CA gene mutations are other markers that may predict lapatinib poor response.
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http://dx.doi.org/10.5507/bp.2010.043DOI Listing
December 2010

Triple negative breast cancer--current status and prospective targeted treatment based on HER1 (EGFR), TOP2A and C-MYC gene assessment.

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2009 Mar;153(1):13-7

Department of Paediatrics, Faculty of Medicine and Dentistry, Laboratory of Experimental Medicine, Palacky University and University Hospital, Olomouc, Czech Republic.

Background: Every year about one million women worldwide are diagnosed with breast cancer which is the most common malignancy in female. Of these, triple negative breast carcinoma represents 10-17 %. Triple negative breast carcinomas, characterized by estrogen, progesterone and HER2 receptor negativity are very aggressive tumours with poor prognosis. Individualized treatment (tailored therapy) based on molecular biology markers of tumor and patient is the trend in clinical practice these days. However, molecular targets and predictors for the treatment of triple negative breast carcinoma do not currently exist.

Methods And Results: This minireview focuses on biomarkers (HER1/EGFR, TOP2A and C-MYC genes) that may predict the response of triple negative breast carcinoma patients to chemotherapy and/or targeted biological treatment with a summary of current knowledge about them.

Conclusion: HER1 belonging to the HER family of receptors plays an important role in cell proliferation, migration and protection against apoptosis. HER1 protein could be targeted by monoclonal antibodies and/or tyrosine kinase inhibitors (TKIs). Given signal pathway complexity and HER family member cooperation, it may be better to simultaneously target a number of these receptors (e.g. HER1/HER2 by lapatinib). Thus, HER1 assessment could reveal a particular breast cancer patient group with probably good response to HER1 targeted therapy. TOP2A gene, encoding topoisomerase II alpha (target for anthracyclines) is predictive of response to anthracycline therapy. TOP2A aberrations (amplification, deletion) are found in up to approximately 30-90 % of HER2 amplified breast cancer and amplifications are more common than deletions. Recent publications describe TOP2A amplification also in 2.7-8.8 % HER2 nonamplified breast cancers. Patients with a pathologic complete response to anthracycline based neoadjuvant chemotherapy had a good overall prognosis regardless of molecular subtype of breast cancer. These results suggest that particularly tumors with a complete pathological response to anthracyclines could have TOP2A amplification. C-MYC encodes nuclear DNA binding proteins that regulate proliferation and apoptosis; amplification is associated with poor prognosis and hormonally negative breast carcinoma.
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http://dx.doi.org/10.5507/bp.2009.002DOI Listing
March 2009

A duplication dup(4)(q28q35.2) de novo in a newborn.

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2006 Jul;150(1):113-6

Institute of Biology and Medical Genetics, General Faculty Hospital and The 1st Faculty of Medicine, Charles University, Prague 2, Czech Republic.

We report here a case of a newborn with hypotrophy and somatic stigmatization: microcephaly, facial dysmorphism, heart defect and immunodeficiency syndrome. The proband's karyotype was 46,XY,dup(4)(q28q35.2) de novo with chromosomal breaks in 4% of metaphases. We demonstrate the usefulness of a combination of physical examination, classical cytogenetics, FISH and PCR techniques in order to establish correct diagnosis because of overlap of some clinical and cytogenetic features of Nijmegen breakage syndrome (NBS) and duplication 4q in our patient. Although FISH technique detected translocation t(14q;21q) in 4 metaphases, deletion 657del5 in exon 6 of the NBS1 gene associated with NBS in Slavic population was not confirmed. We compare in this report similarity of the clinical picture of our patient, NBS cases and other patients carrying a duplication of the distal part of 4q as described in the literature.
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http://dx.doi.org/10.5507/bp.2006.016DOI Listing
July 2006
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