Breast Cancer in Art Painting

Breast cancer is an emotive cancer. It is a disease that affects a visible sexual organ and it is the commonest single cause of death of women between 40 and 60 years of age. Nevertheless, this type of cancer was infrequently depicted in art paintings. In this article the themes from the breast cancer in famous art paintings are discussed

RT-PCR Analysis of TOPBP1 Gene Expression in Hereditary Breast Cancer

Hereditary predisposition to breast cancer determined in large part by loss of function mutations in one of two genes BRCA1 and BRCA2. Besides BRCA1 and BRCA2 other genes are also likely to be involved in hereditary predisposition to breast cancer. TopBP1 protein is involved in DNA replication, DNA damage checkpoint response and transcriptional regulation. Expression of TopBP1 gene at the mRNA level was analyzed by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) in 94 samples of hereditary breast cancer. Analysis of TopBP1 mRNA level showed that expression of TopBP1 is significantly downregulated in poorly differentiated breast cancer (grade III according Bloom-Richardson system (P<0.05)

Ekspresja genów kodujących enzymy związane z O-GlcNAcylacją w rakach błony śluzowej trzonu macicy: korelacja z parametrami kliniczno-patologicznymi

Objectives: O-GlcNAcylation is an abundant modification of cellular proteins which consist of single N-acetylglucosamine residues attached by O-linkage to serine or threonine residues. Abnormal O-GlcNAcylation seems to be a feature of malignant cancer cells. The aim of the present study was to determine the relationship between the expression of genes encoding O-GlcNAc cycling enzymes (OGT and MGEA5) and clinicopathological parameters of endometrial carcinomas. Materials and methods: The mRNA expression levels of O-GlcNAc cycling enzymes in series of 76 samples of endometrial carcinoma were studied by real time RT-PCR method. Results: The OGT and MGEA5 mRNA expression was significantly higher in tumors of higher histological grade than in well-differentiated tumors. Statistically significant association was found between OGT and MGEA5 mRNA expression and depth of myometrial invasion. Both OGT and MGEA5 expression profiles showed no significant association with the clinical stage of endometrial cancer. Conclusion: O-GlcNAcylation may be an important regulatory modification involved in endometrial cancer pathogenesis but the actual significance of this modification for endometrial cancer progression needs to be investigated further.Cel pracy: O-GlcNAcylacja jest powszechną modyfikacją białek komórkowych polegającą na przyłączeniu wiązaniem O-glikozydowym pojedynczych reszt N-acetyloglukozoaminy do reszt seryny i treoniny. Zaburzenia O-GlcNAcylacji wydają się być istotną cechą związaną z agresywnością komórek nowotworowych. Celem prezentowanej pracy było określenie zależności pomiędzy ekspresją genów kodujących enzymy związane z O-GlcNAcylacją białek a kliniczno-patologicznymi parametrami raka błony śluzowej trzonu macicy. Materiał i metody: Poziom ekspresji mRNA enzymów analizowano techniką real time RT-PCR w 76 preparatach raków błony śluzowej trzonu macicy. Wyniki: Nowotwory o wyższym stopniu złośliwości histologicznej wykazywały wyższą ekspresję mRNA dla OGT i MGEA5 w porównaniu z rakami dobrze zróżnicowanymi. Stwierdzono również istotną statystycznie zależność pomiędzy ekspresją badanych genów a głębokością naciekania mięśniówki macicy. Nie stwierdzono natomiast zależności pomiędzy ekspresją mRNA OGT i MGEA5 a stopniem klinicznego zaawansowania nowotworu. Wniosek: Wydaje się, że O-GlcNAcylacja może być ważną regulatorową modyfikacją włączoną w patogenezę raka błony śluzowej trzonu macicy ale dokładne określenie jej roli w progresji tego nowotworu wymaga dalszych badań

Molecular basis of gynecological oncology – TopBP1 protein and its participation in the transcription process

Breast and ovarian cancer are among the most common malignancies of women in the world. About 5 – 10% of the cases are considered familial. Germline mutations in the BRCA1 and BRCA2 genes are strong predictors of breast and/or ovarian cancer development. However, currently known susceptibility genes including BRCA1, BRCA2, ATM, Chk2, PALB2, and BRIP1 explain less than 25% of familial breast and/ovarian cancers. Other genes, such as TopBP1 are also likely to be involved in hereditary predisposition to breast and/or ovarian cancer. TopBP1 protein displays structural and functional similarities with BRCA1, and these two proteins have been suggested to function partially in the same cellular processes. TopBP1 protein is involved in DNA repair and cell cycle checkpoint control. Moreover, TopBP1 interacts with transcription factors, such as E2F1, p53, Miz-1, HPV16 E2, and regulates their activity

Metallothionein 2A genetic polymorphisms and risk of ductal breast cancer

Metallothioneins (MTs) are a family of metal binding proteins that play an important role in cellular processes such as proliferation and apoptosis. Metallothionein 2A is the most expressed MT isoform in the breast cells. A number of studies have demonstrated increased MT2A expression in various human tumors, including breast cancer. We carried out an association study to examine whether MT2A gene polymorphisms are associated with risk of breast cancer. Information on lifestyle risk factors was collected via a self-administered questionnaire. Genotyping was conducted using polymerase chain reaction–restriction fragment length polymorphism technique. Three single nucleotide polymorphisms (SNP) rs28366003, rs1610216 and rs10636 were genotyped in 534 breast cancer cases and 556 population controls. One SNP in MT2A (rs28366003) showed a positive association with breast cancer. Compared with homozygous common allele carriers, heterozygous for the G variant [odds ratio (OR) = 1.92, 95 % confidence interval (CI):1.28–2.81, p trend <0.01; the OR assuming a dominant model 1.93 (95 % CI: 1.29–2.89, p dominant <0.02) after adjustment for age, family history, smoking status, BMI, menarche, parity, menopausal status and use of contraceptive and menopausal hormones] had a significantly increased risk of breast cancer in Polish population, as well as women with haplotypes, including variant allele of rs28366003 SNP (OR = 1.58, CI: 0.41–6.33, p global = 0.03). Our data suggest that the rs28366003 SNP in MT2A is associated with risk of breast cancer in Polish population.This work was supported, in part, by the statutory fund for the Department of Cytobiochemistry, University of Łód

Molekularne podstawy ginekologii onkologicznej – białko TopBP1 jako strażnik integralności genomu

Breast cancer is the most common malignancy in women. Its estimated annual incidence is about one million cases worldwide. A number of risk factor have been identified, among them early menarche, late menopause, nulliparity and positive family history. Moreover, a number of highly penetrant breast and ovarian cancer susceptibility genes, such as BRCA1 and BRCA2, have been identified. Recent findings suggest TopBP1 to be a breast and ovarian cancer susceptibility gene. Moreover, TopBP1 protein may be an important prognostic marker of breast cancer. TopBP1 protein is involved in DNA replication, mitosis and meiosis, as well as DNA repair. Deregulation of these processes may have pathological implications in cancer.Rak piersi jest najczęściej występującym nowotworem u kobiet. Rocznie na świecie notuje się około miliona nowych zachorowań. Zidentyfikowano liczne czynniki ryzyka raka piersi, do których zalicza się wczesny wiek pierwszej miesiączki, późny wiek menopauzy, niezachodzenie w ciążę oraz przypadki raka piersi u najbliższych krewnych.Ponadto zidentyfikowano liczne geny wysokiej penetracji, których mutacje wpływają na ryzyko zachorowania na raka piersi i jajnika. Do genów tych zalicza się przede wszystkim BRCA1 i BRCA2. Ostatnie wyniki badań sugerują, że również gen TopBP1 może wpływać na ryzyko wystąpienia raka piersi i jajnika, jak również może stanowić istotny czynnik prognostyczny dla złośliwych nowotworów piersi. Białko TopBP1 uczestniczy w wielu istotnych procesach komórkowych, w tym w replikacji DNA, w mitozie i mejozie, a także w naprawie uszkodzeń DNA. Zaburzenia tych procesów mogą mieć bezpośredni lub pośredni wpływ na proces transformacji nowotworowej

The expression of SOCS1 and TLR4-NFkappaB pathway molecules in neoplastic cells as potential biomarker for the aggressive tumor phenotype in laryngeal carcinoma.

Suppressor of cytokine signaling 1 (SOCS1) is the key regulator of cytokine-mediated innate and adaptive immunity. One of the molecular mechanisms of SOCS1 is connected with inhibition of TLR4-NFkappaB pathway. The relationships among these molecules in laryngeal carcinoma are not exactly known. In this preliminary study we focused on their special activity and role in regulation of development and progression of laryngeal carcinoma. To investigate NFkappaB (p65 subunit) nuclear and cytoplasmic expression in 45 tumor samples of advanced laryngeal carcinoma IHC staining was performed. To determine the mRNA expression levels of TLR4, IRAK1, TRAF6 and SOCS1 in isolated neoplasm cells and non-cancerous adjacent mucosa epithelial cells RT-PCR was used. The invasiveness of laryngeal carcinomas was evaluated according to tumor front grading, TFG, which included tumor-related features (cytoplasmic differentiation, nuclear polymorphism, number of mitoses) and adjacent stroma-related characteristics of the peripheral edge of tumor infiltration (mode of infiltration, depth of invasion and plasmalymphocytic infiltration). The relationships between pT, pN status, the histological G grade, certain clinicopathological characteristics as well as postoperative observation time and the mRNA expression of the molecules mentioned earlier were investigated. Significant differences of TLR4-NFkappaB pathway molecules and SOCS1 mRNA expression in laryngeal tumor cells and normal adjacent mucosa cells as well as significant interconnections of TLR4, SOCS1 and NFkappaB(p65) in isolated tumor cells were obtained. This preliminary study demonstrated that the expression of SOCS1 and TLR4-NFkappaB pathway molecules had a strong association with the aggressiveness of laryngeal carcinoma. Positive relationships of TRAF6 in tumor margin cells with the histological grade and the mode of tumor invasion as well as the TFG total score were highlighted. Significant positive correlations were found between the TLR4 in tumor central cells and the TFG total score. Negative relationships of SOCS1 in tumor central cells with the histological grade were also noted. Significant positive correlations were found between the cytoplasmic NFkappaB(p65) and the mode of invasion as well as TFG total score. Our findings confirmed the importance of SOCS1 and TLR4-NFkappaB pathway molecules as potential biomarkers for assessment of the aggressive tumor phenotype in laryngeal carcinoma

Ekspresja genów kodujących E-kadherynę i β1-integrynę w nowotworach błony śluzowej trzonu macicy

Objectives: The metastatic ability of tumors is characteristic for malignant neoplasms and constitutes the main cause of therapeutics failures. Metastasis formation involves the sequence of processes such as proteolytic degradation of the basement membrane, migration, intravasation, extravasation, proliferation and angiogenesis. Cadherins and integrins are groups of proteins directly involved in these processes. In the present study we analyzed the mRNA expression of CDH1 and ITGB1 genes by real-time polymerase chain reaction (RT-PCR). The study included 106 endometrial carcinomas. CDH1 and ITGB1 mRNA expression was found in all of the studied samples. Generally, the CDH1 and ITGB1 mRNA expression was significantly higher in well-differentiated rather than poorly differentiated tumors. Materials and methods: The mRNA expression levels of CDH1 and ITGB1 in series of 83 samples of endometrial carcinoma were studied by real time RT-PCR method. Statistical analysis of the obtained results was performed. Results: CDH1 and ITGB1 gene expression was observed in all examined tissues and was correlated with cancer malignancy (G). In high grade malignant tumors (G1), CDH1 and ITGB1 gene expression was the highest, in G2 and G3 tumors the expression of both genes was gradually lowering. Moreover, the statistically significant correlation between CDH1 and ITGB1 gene expression was observed. (Spearman test, r=0.29, pCel pracy: Powstawanie przerzutów jest nieodłączną cechą nowotworów złośliwych, a także przyczyną wielu niepowodzeń terapeutycznych. Proces ten jest sekwencją następujących po sobie zjawisk takich jak, proteolityczna degradacja błon plazmatycznych, migracja komórek, proliferacja i neowaskularyzacja. Do grup białek bezpośrednio zaangażowanych w wymienione powyżej procesy należą między innymi, kadheryny oraz integryny. Celem przeprowadzonych badań była ocena ekspresji genów kodujących E-kadherynę (CDH1) i β1-integrynę (ITGB1) w nowotworach błony śluzowej trzonu macicy oraz korelacja uzyskanych wyników z danymi kliniczno-patologicznymi. Materiał i metody: Materiał użyty do badań stanowiło 106 preparatów raka błony śluzowej trzonu macicy. W preparatach tych oznaczono ekspresję CDH1 i ITGB1 na poziomie mRNA metodą real-time PCR. Wyniki badań zostały poddane analizie statystycznej. Wyniki: Ekspresję genów CDH1 oraz ITGB1 stwierdzono we wszystkich badanych preparatach i była ona znamiennie statystycznie skorelowana ze stopniem złośliwości nowotworu. W nowotworach o wysokim stopniu zrożnicowania komórkowego (G1) była najwyższa, natomiast wartość jej obniżała się wraz ze wzrostem stopnia złośliwości nowotworu, w przypadku obu analizowanych genów. Stwierdzono także występowanie istotnej statystycznie korelacji między ekspresją CDH1 i ITGB1 (test rang Spearmana, r=0,29,