Rare myxoid liposarcoma metastasis to the interventricular septum of the heart

AbstractLiposarcomas are malignant tumors of the soft tissue. Myxoid liposarcoma is the second most common subtype of these tumors in adults. It accounts for approximately 20% of all malignant soft tissue tumors [1,2]. Peak of its incidence occurs between 40 to 60 years of age with relatively indolent clinical course Matsumoto et al. (2007) [3], Cho et al. (2010) [4], Faiman et al. (2005) [5]. Typical localizations of myxoid liposarcoma comprise limbs, particularly thighs with a tendency to metastasize into extrapulmonary sites such as retroperitoneum, mediastinum, bones. Cardiac metastases are extremely rare.We present a case of a 36-year-old man with a history of recurrent myxoid liposarcoma. Primary location was in the left popliteal area. After extirpation of the tumor, metastatic tumor was subsequently revealed in the right axilla. Each surgical extirpation was followed by radiation therapy and brachytherapy. Cardiac metastasis was accidentally diagnosed with PET/CT during the staging process. The patient was asymptomatic and was admitted to our institution for further diagnostics and treatment. After confirmation of its location, the tumor was excised. Histological examination revealed myxoid liposarcoma

The role of cytochromes P450 and aldo-keto reductases in prognosis of breast carcinoma patients

Metabolism of anticancer drugs affects their antitumor effects. This study has investigated the associations of gene expression of enzymes metabolizing anticancer drugs with therapy response and survival of breast carcinoma patients.Gene expression of 13 aldo-keto reductases (AKRs), carbonyl reductase 1, and 10 cytochromes P450 (CYPs) was assessed using quantitative real-time polymerase chain reaction in tumors and paired adjacent nonneoplastic tissues from 68 posttreatment breast carcinoma patients. Eleven candidate genes were then evaluated in an independent series of 50 pretreatment patients. Protein expression of the most significant genes was confirmed by immunoblotting.AKR1A1 was significantly overexpressed and AKR1C1-4, KCNAB1, CYP2C19, CYP3A4, and CYP3A5 downregulated in tumors compared with control nonneoplastic tissues after correction for multiple testing. Significant association of CYP2B6 transcript levels in tumors with expression of hormonal receptors was found in the posttreatment set and replicated in the pretreatment set of patients. Significantly higher intratumoral levels of AKR1C1, AKR1C2, or CYP2W1 were found in responders to neoadjuvant chemotherapy compared with nonresponders. Patients with high AKR7A3 or CYP2B6 levels in the pretreatment set had significantly longer disease-free survival than patients with low levels. Protein products of AKR1C1, AKR1C2, AKR7A3, CYP3A4, and carbonyl reductase (CBR1) were found in tumors and those of AKR1C1, AKR7A3, and CBR1 correlated with their transcript levels. Small interfering RNA-directed knockdown of AKR1C2 or vector-mediated upregulation of CYP3A4 in MDA-MB-231 model cell line had no effect on cell proliferation after paclitaxel treatment in vitro.Prognostic and predictive roles of drug-metabolizing enzymes strikingly differ between posttreatment and pretreatment breast carcinoma patients. Mechanisms of action of AKR1C2, AKR7A3, CYP2B6, CYP3A4, and CBR1 should continue to be further followed in breast carcinoma patients and models.13-25222J, GACR, Czech Science FoundationCzech Science Foundation [13-25222J]; Internal Grant Agency of the Czech Ministry of Health [NT/14055-3

Non-Coding Polymorphisms in Nucleotide Binding Domain 1 in <i>ABCC1</i> Gene Associate with Transcript Level and Survival of Patients with Breast Cancer

<div><p>Objectives</p><p>ATP-Binding Cassette (ABC) transporters may cause treatment failure by transporting of anticancer drugs outside of the tumor cells. Multidrug resistance-associated protein 1 coded by the <i>ABCC1</i> gene has recently been suggested as a potential prognostic marker in breast cancer patients. This study aimed to explore tagged haplotype covering nucleotide binding domain 1 of <i>ABCC1</i> in relation with corresponding transcript levels in tissues and clinical phenotype of breast cancer patients.</p><p>Methods</p><p>The distribution of twelve <i>ABCC1</i> polymorphisms was assessed by direct sequencing in peripheral blood DNA (n = 540).</p><p>Results</p><p>Tumors from carriers of the wild type genotype in rs35623 or rs35628 exhibited significantly lower levels of ABCC1 transcript than those from carriers of the minor allele (p = 0.003 and p = 0.004, respectively). The ABCC1 transcript levels significantly increased in the order CT-GT>CC-GT>CC-GG for the predicted rs35626-rs4148351 diplotype. Chemotherapy-treated patients carrying the T allele in rs4148353 had longer disease-free survival than those with the GG genotype (p = 0.043). On the other hand, hormonal therapy-treated patients with the AA genotype in rs35628 had significantly longer disease-free survival than carriers of the G allele (p = 0.012).</p><p>Conclusions</p><p>Taken together, our study shows that genetic variability in the nucleotide binding domain 1 has a significant impact on the ABCC1 transcript level in the target tissue and may modify survival of breast cancer patients.</p></div

Haplotype analysis of <i>ABCC1</i> SNPs.

<p>Figure indicates linkage disequilibrium plot (A) and three blocks comprising of SNP diplotypes (B) predicted from experimental data obtained in the present study. The likelihood of linkage of two tested SNPs increases from white to red color (A). Population frequency of diplotypes and connections from one diplotype block to the next one are shown (B). Analysis was performed by HaploView v4.2 program.</p

Distribution of <i>ABCC1</i> diplotypes predicted by HaploView v4.2.

<p>Numbers of patients with combinations of diplotypes presented.</p><p>The most frequent diplotypes used for statistical analyses in bold.</p

Schematic representation of functional domains of ABCC1.

<p>Figure depicts functional domains of ABCC1 protein (A) and important structural motifs within NBD1 (B). Data modified from NCBI’s Conserved Domain Database (CDD) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0101740#pone.0101740-MarchlerBauer1" target="_blank">[49]</a>.</p

Significant associations of <i>ABCC1</i> polymorphisms with expression levels.

<p>All SNPs and frequent diplotypes were analyzed but to retain concise style only significant associations are reported.</p><p>Footnotes:</p><p>*Analyzed by Mann-Whitney test. The higher is the rank the lower is the normalized expression ABCC1/reference genes.</p>#<p>Result passed FDR analysis for multiple testing <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0101740#pone.0101740-Benjamini1" target="_blank">[29]</a>.</p