23 research outputs found

    Breast Cancer in the Setting of HIV

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    Oncogenesis in immunocompromised patients occurs due to a number of factors including reduced immune surveillance or other viral pathogens. Breast cancer, unlike other non-AIDS-defining cancers, does not appear associated and has rarely been reported. We describe a case with evidence of immune reactivity around the tumor, but not in the tumor itself

    Expression of Cancer/Testis genes in ductal carcinoma in situ and benign lesions of the breast

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    ABSTRACT: Cancer/testis (CT) genes represent a unique class of genes, which are expressed by germ cells, normally silenced in somatic cells, but activated in various cancers. CT proteins can elicit spontaneous immune responses in cancer patients and this feature makes them attractive targets for immunotherapy-based approaches. We have previously reported that CTs are relatively commonly expressed in estrogen receptor (ER) negative, high risk carcinomas. In this study, we examined the expression of selected CT genes in ductal carcinoma in situ (DCIS), lobular carcinoma in situ (LCIS) and benign proliferative lesions of the breast. ER negative DCIS were found to be associated with significant CT gene expression together with HER2 positivity and a marked stromal immune respons

    Zinc isotopic compositions of breast cancer tissue

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    This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. https://creativecommons.org/licenses/by-nc-nd/3.0/ The attached file is the published version of the article.An early diagnostic biomarker for breast cancer is essential to improve outcome. High precision isotopic analysis, originating in Earth sciences, can detect very small shifts in metal pathways. For the first time, the natural intrinsic Zn isotopic compositions of various tissues in breast cancer patients and controls were determined. Breast cancer tumours were found to have a significantly lighter Zn isotopic composition than the blood, serum and healthy breast tissue in both groups. The Zn isotopic lightness in tumours suggests that sulphur rich metallothionein dominates the isotopic selectivity of a breast tissue cell, rather than Zn-specific proteins. This reveals a possible mechanism of Zn delivery to Zn-sequestering vesicles by metallothionein, and is supported by a similar signature observed in the copper isotopic compositions of one breast cancer patient. This change in intrinsic isotopic compositions due to cancer has the potential to provide a novel early biomarker for breast cancer.This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. https://creativecommons.org/licenses/by-nc-nd/3.0/ The attached file is the published version of the article

    Expression of CDK7, cyclin H and MAT1 is elevated in breast cancer and is prognostic in estrogen receptor- positive breast cancer

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    Purpose: CDK-activation kinase (CAK) is required for the regulation of the cell-cycle and is a trimeric complex consisting of Cyclin Dependent Kinase 7 (CDK7), Cyclin H and the accessory protein, MAT1. CDK7 also plays a critical role in regulating transcription, primarily by phosphorylating RNA polymerase II, as well as transcription factors such as estrogen receptor-α (ER). Deregulation of cell cycle and transcriptional control are general features of tumor cells, highlighting the potential for the use of CDK7 inhibitors as novel cancer therapeutics. Experimental Design: mRNA and protein expression of CDK7 and its essential co-factors cyclinH and MAT1, were evaluated in breast cancer samples to determine if their levels are altered in cancer. Immunohistochemical staining of >900 breast cancers was used to determine the association with clinicopathological features and patient outcome. Results: We show that expression of CDK7, cyclinH and MAT1 are all closely linked at the mRNA and protein level and their expression is elevated in breast cancer compared with the normal breast tissue. Intriguingly, CDK7 expression was inversely proportional to tumour grade and size and outcome analysis showed an association between CAK levels and better outcome. Moreover, CDK7 expression was positively associated with ER expression and in particular with phosphorylation of ER at serine 118, a site important for ER transcriptional activity. Conclusions: Expression of components of the CAK complex, CDK7, MAT1 and Cyclin H are elevated in breast cancer and correlates with ER. Like ERα , CDK7 expression is inversely proportional to poor prognostic factors and survival

    A Case Matched Gender Comparison Transcriptomic Screen Identifies eIF4E and eIF5 as Potential Prognostic and Tractable Biomarkers in Male Breast Cancer

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    Purpose: Breast cancer (BC) affects both genders, but is understudied in men. Although still rare, male BC is being diagnosed more frequently. Treatments are wholly informed by clinical studies conducted in women, based on assumptions that underlying biology is similar. Experimental design: A transcriptomic investigation of male and female BC was performed, confirming transcriptomic data in silico. Biomarkers were immunohistochemically assessed in 697 MBCs (n=477, training; n=220, validation set) and quantified in pre- and post-treatment samples from a male BC patient receiving Everolimus and PI3K/mTOR inhibitor. Results: Gender-specific gene expression patterns were identified. eIF transcripts were up-regulated in MBC. eIF4E and eIF5 were negatively prognostic for overall survival alone (Log rank; p=0.013; HR=1.77, 1.12-2.8 and p=0.035; HR=1.68, 1.03-2.74, respectively), or when co-expressed (p=0.01; HR=2.66, 1.26-5.63), confirmed in the validation set. This remained upon multivariate Cox regression analysis (eIF4E p=0.016; HR 2.38 (1.18-4.8), eIF5 p=0.022; HR 2.55 (1.14-5.7); co-expression p=0.001; HR=7.04 (2.22-22.26)). Marked reduction in eIF4E and eIF5 expression was seen post BEZ235/Everolimus, with extended survival. Conclusions: Translational initiation pathway inhibition could be of clinical utility in male BC patients overexpressing eIF4E and eIF5. With mTOR inhibitors which target this pathway now in the clinic, these biomarkers may represent new targets for therapeutic intervention, although further independent validation is required

    Kematian Manusia Sebagai Inspirasi Dalam Seni Grafis

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    Kematian adalah suatu peristiwa yang paling hebat yang pasti akan terjadi atas diri manusia, melupakan mati atau tidak mengingat mati adalah suatu sikap yang tidak bertanggungjawab dari sudut pandang Islam. Semua manusia akan menemui kematian dalam hidupnya, ini adalah suatu kenyataan yang terjadi pada manusia. Maka persiapan menghadapi kematian menjadi penting dipertimbangkan untuk mendapatkan kebahagiaan dunia dan akhirat. Dalam kesenian, pesan-pesan agama, hubungan antara seni dan religi saling jalin menjalin sepanjang sejarah kehidupan manusia. Seni selalu hadir dalam setiap peradaban Islam, seperti, masjisd Nabawi di Madinah al Munawwarah yang sangat indah, atau penyampaian melalui lukisan “Arasbaque” dan karya seni lainnya. Konsep perwujudan dengan bentuk Tengkorak dan anatomi kerangka tulang manusia sebagai simbol yang dapat mewakili ide tentang kematian manusia, dipadu dengan objek pendukung lain dimaksudkan agar ilustrasi yang ingin dicapai dapat tersampaikan pesan dan makna ke dalam karya seni grafis. Dengan menggunakan teknik cetak saring atau serigrafi dalam visualisasinya dapat mendukung atau menghasilkan perwujudan karya yang maksimal sesuai dengan cita rasa, fantasi pengalaman estetis, dan kemampuan artistik yang diinginkan. Semua yang terjadi dari proses pembuatan karya seni Tugas Akhir ini merupakan respon atau tanggapan penulis terhadap seluruh permasalahan yang penulis alami dan amati atas realita yang terjadi di lingkungan sekitar. Penulis mencoba merefleksikan pengalaman pribadi penulis ke dalam karya-karya tugas akhir ini

    Pleomorphic Invasive Ductal Carcinoma of the Breast in a Patient with Huntington’s Disease

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    A pleomorphic invasive ductal carcinoma developed in a patient with Huntington’s disease. The tumour showed marked nuclear pleomorphism and contained large number of bizarre tumour giant cells and abundant abnormal mitoses. Tumour cells showed nuclear vesicles and inclusions similar to those described in nuclei of neural cells in patients with Huntington’s disease. The case suggests that, in some patients, tumour morphology may reflect specific individual features
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