Unique Breast Cancer Features Within the Vietnamese Population

BACKGROUND: Breast cancer is known to be a heterogeneous disease across women, and even within individual tumors. However, relatively little is known about heterogeneity across cultures. There has been some evidence to suggest that Asian women are more likely to have HER2+ breast cancer than their Caucasian counterparts. PURPOSE: The aim of this study was to further investigate the unique pattern of breast cancer incidence and subtype in the Vietnamese population. METHODS: We retrospectively collected data on all Vietnamese women diagnosed with invasive breast cancer at the Lester & Sue Smith Breast Center in Houston, Texas over a four year period. We recorded the subtype of breast cancer, tumor grade, age at diagnosis, and menopausal status for each woman. We then compared these characteristics between our population of Vietnamese breast cancer patients, and an ethnically diverse group of American women from the 2010 SEER registry. RESULTS: We discovered that 15 of 33 Vietnamese patients diagnosed in our breast center had HER2 over-expressing breast cancer, resulting in a 45% rate of HER2 positivity. Compared with the 2010 Surveillance, Epidemiology, and End Results (SEER) registry data that encompasses 28% of all US breast cancer patients diagnosed that year, regardless of race, the Smith Clinic Vietnamese cohort had a statistically significant higher rate of HER2+ breast cancer, with an odds ratio of 4.7 (45% vs. 15%, p CONCLUSIONS: Vietnamese breast cancer patients, especially those older than 50 years old, tend to have higher rates of HER2+ breast cancer than the general population. This unique pattern of breast cancer merits further study, as it may reflect a genetic mutation or environmental exposure which is more common among Vietnamese women

O Pasamontañas como espelho

The propose of this photo essay is to fully contemplate the paradoxical characteristic of the Zapatist indigenous faces covered by the pasamontañas. What do they allow us to uncover and what those insurgent stares can show us? As in a mirror – in which we can see them and, at the same time, see ourselves – what do we see? What other perspectives of the world can we perceive through the eyes on those dignified faces wich, for more than two decades, are between the fire and the words to buid processes of political and social autonomy? O ensaio fotográfico buscou contemplar a paradoxal característica dos rostos indígenas zapatistas cobertos pelos pasamontañas. O que permitem desvelar e para quais possibilidades apontam os olhares insurgentes? Como em um espelho - em que podemos enxergá-los e, concomitantemente, enxergar-nos - o que vemos? Que outros mundos podemos imaginar pelos olhos de rostos cobertos de dignidade, que há mais de duas décadas, entre o fogo e a palavra, constroem processos de autonomia política e social

The SOX11 transcription factor is a critical regulator of basal-like breast cancer growth, invasion, and basal-like gene expression.

Basal-like breast cancers (BLBCs) are aggressive breast cancers associated with poor survival. Defining the key drivers of BLBC growth will allow identification of molecules for targeted therapy. In this study, we performed a primary screen integrating multiple assays that compare transcription factor expression and activity in BLBC and non-BLBC at the RNA, DNA, and protein levels. This integrated screen identified 33 transcription factors that were elevated in BLBC in multiple assays comparing mRNA expression, DNA cis-element sequences, or protein DNA-binding activity. In a secondary screen to identify transcription factors critical for BLBC cell growth, 8 of the 33 candidate transcription factors (TFs) were found to be necessary for growth in at least two of three BLBC cell lines. Of these 8 transcription factors, SOX11 was the only transcription factor required for BLBC growth, but not for growth of non-BLBC cells. Our studies demonstrate that SOX11 is a critical regulator of multiple BLBC phenotypes, including growth, migration, invasion, and expression of signature BLBC genes. High SOX11 expression was also found to be an independent prognostic indicator of poor survival in women with breast cancer. These results identify SOX11 as a potential target for the treatment of BLBC, the most aggressive form of breast cancer

Keratin 6a marks mammary bipotential progenitor cells that can give rise to a unique tumor model resembling human normal-like breast cancer.

Progenitor cells are considered an important cell of origin of human malignancies. However, there has not been any single gene that can define mammary bipotential progenitor cells, and as such it has not been possible to use genetic methods to introduce oncogenic alterations into these cells in vivo to study tumorigenesis from them. Keratin 6a is expressed in a subset of mammary luminal epithelial cells and body cells of terminal end buds. By generating transgenic mice using the Keratin 6a (K6a) gene promoter to express tumor virus A (tva), which encodes the receptor for avian leukosis virus subgroup A (ALV/A), we provide direct evidence that K6a(+) cells are bipotential progenitor cells, and the first demonstration of a non-basal location for some biopotential progenitor cells. These K6a(+) cells were readily induced to form mammary tumors by intraductal injection of RCAS (an ALV/A-derived vector) carrying the gene encoding the polyoma middle T antigen. Tumors in this K6a-tva line were papillary and resembled the normal breast-like subtype of human breast cancer. This is the first model of this subtype of human tumors and thus may be useful for preclinical testing of targeted therapy for patients with normal-like breast cancer. These observations also provide direct in vivo evidence for the hypothesis that the cell of origin affects mammary tumor phenotypes

Untersuchungen zur Entblutezeit bei Rindern nach Bolzenschußbetäubung

At an abattoir there was investigated the visual detectable atony and the provoking of reactions in 545 cattles (127 bulls, 150 heifers, 268 cows) in the period between capitive bolt stun and cutting off of the carpus. In part 1, the complete atony of the carcass, especially of the tail, was used as the basis for the cutting off of the carpus, and there was a mild reaction in 9.8%, a strong reaction in 4.4%. Remarkably, the responsiveness of cows was high and long lasting as compared with bulls and heifers. With exception of 2 improper stunned animals, no animal reacted after 5 minutes. In part 2, reactions were provoked with a knife stabing in the pastern region. The frequency and intensity of reactions decreased in the course of time and increased ascending in the order bulls, heifers, cows. After 5 minutes there was only a weak reaction in one animal. In part 3, the progress of atony every minute was investigated. In almost all animals complete atony was achieved in five minutes, and predominantly identifiable at the tail or by outflowing of ruminal fluid. If an akinesia – as demanded in the German „Tierschutzschlachtverordnung (TierScHV)“ – was used as a precondition for the cutting off of the carpus, the number of animals with reactions greatly increased up to 30.8%. It is concluded that it is insufficient only to wait for an akinesia before cutting off of the carpus as the TierSchV demands. It is recommend to change the original term to „complete atony“ and to set a time limit of 5 minutes after sticking. The results were ascertained for bleeding by chest stab. Other bleeding methods presumably require higher values.In der vorliegenden Untersuchung wurden an einem Schlachthof 545 Rinder (127 Bullen, 150 Färsen, 268 Kühe) im Zeitraum zwischen Bolzenschuß und Absetzen des Karpus, hinsichtlich visuell wahrnehmbarer Erschlaffung und Auslösen von Reaktionen auf einen Reiz, analysiert. In Block 1 wurde die völlige Erschlaffung des Tierkörpers, besonders des Schwanzes, als Grundlage für das Absetzen der Vordergliedmaße genommen und es reagierten noch 9,8% der Tiere bzw. 4,4% in mittlerer bis starker Intensität. Auffallend war schon hier die relativ hohe und lang andauernde Reaktionsbereitschaft der Kühe im Gegensatz zu Bullen und Färsen. Nach 5 Minuten war, außer bei 2 fehlbetäubten Tieren, keine Reaktion auf das Absetzen mehr zu erkennen. Block 2 umfasste das Auslösen von Reaktionen mittels Messerstich in die Fesselbeuge. Es zeigte sich die mit fortschreitender Zeit abnehmende Reagibilität in Auftreten und Intensität. Auch hier zeigten sich die Unterschiede innerhalb der Kategorien, wonach aufsteigend in der Reihenfolge Bullen, Färsen, Kühe die Reaktionsbereitschaft und -stärke zunahm. Nach 5 Minuten reagierte nur noch ein Tier schwach. Die in Block 3 visuell in Erscheinung tretende Erschlaffung wurde in unterschiedlichen Zeitrastern festgehalten und war bei nahezu allen Tieren nach 5 Minuten abgeschlossen, und in erster Linie am Schwanz und Abfließen von Pansensaft zu erkennen. Die in dieser Reihe, bei einem Teil der Tiere, als Grundlage für den folgenden Arbeitsschritt herangezogene Bewegungslosigkeit, wie sie in der TierSchlV beschrieben ist, hatte ein starkes Ansteigen der Tiere mit Reaktionen zur Folge (30,8%). Anhand der durchgeführten Untersuchungen ist festzustellen, dass die Regelung in der TierSchlV, weitere Arbeitsschritte erst durchzuführen, wenn keine Bewegungen des Tieres mehr zu erkennen sind, nicht ausreicht. Es wird empfohlen den Wortlaut in "vollständige Erschlaffung" umzubenennen und eine Frist von mindestens 5 Minuten nach dem Entblutestich zu setzen. Diese Werte wurden für den Bruststich ermittelt, bei anderen Entblutearten ist möglicherweise mit höheren Werten zu rechnen

Analysis of phosphatases in ER-negative breast cancers identifies DUSP4 as a critical regulator of growth and invasion.

Estrogen receptor (ER)-negative cancers have a poor prognosis, and few targeted therapies are available for their treatment. Our previous analyses have identified potential kinase targets critical for the growth of ER-negative, progesterone receptor (PR)-negative and HER2-negative, or "triple-negative" breast cancer (TNBC). Because phosphatases regulate the function of kinase signaling pathways, in this study, we investigated whether phosphatases are also differentially expressed in ER-negative compared to those in ER-positive breast cancers. We compared RNA expression in 98 human breast cancers (56 ER-positive and 42 ER-negative) to identify phosphatases differentially expressed in ER-negative compared to those in ER-positive breast cancers. We then examined the effects of one selected phosphatase, dual specificity phosphatase 4 (DUSP4), on proliferation, cell growth, migration and invasion, and on signaling pathways using protein microarray analyses of 172 proteins, including phosphoproteins. We identified 48 phosphatase genes are significantly differentially expressed in ER-negative compared to those in ER-positive breast tumors. We discovered that 31 phosphatases were more highly expressed, while 11 were underexpressed specifically in ER-negative breast cancers. The DUSP4 gene is underexpressed in ER-negative breast cancer and is deleted in approximately 50 % of breast cancers. Induced DUSP4 expression suppresses both in vitro and in vivo growths of breast cancer cells. Our studies show that induced DUSP4 expression blocks the cell cycle at the G1/S checkpoint; inhibits ERK1/2, p38, JNK1, RB, and NFkB p65 phosphorylation; and inhibits invasiveness of TNBC cells. These results suggest that that DUSP4 is a critical regulator of the growth and invasion of triple-negative breast cancer cells

The SOX11 transcription factor is a critical regulator of basal-like breast cancer growth, invasion, and basal-like gene expression

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Bioelectrical impedance analysis in clinical practice: implications for hepatitis C therapy BIA and hepatitis C

<p>Abstract</p> <p>Background</p> <p>Body composition analysis using phase angle (PA), determined by bioelectrical impedance analysis (BIA), reflects tissue electrical properties and has prognostic value in liver cirrhosis. Objective of this prospective study was to investigate clinical use and prognostic value of BIA-derived phase angle and alterations in body composition for hepatitis C infection (HCV) following antiviral therapy.</p> <p>Methods</p> <p>37 consecutive patients with HCV infection were enrolled, BIA was performed, and PA was calculated from each pair of measurements. 22 HCV genotype 3 patients treated for 24 weeks and 15 genotype 1 patients treated for 48 weeks, were examined before and after antiviral treatment and compared to 10 untreated HCV patients at 0, 24, and 48 weeks. Basic laboratory data were correlated to body composition alterations.</p> <p>Results</p> <p>Significant reduction in body fat (BF: 24.2 ± 6.7 kg vs. 19.9 ± 6.6 kg, genotype1; 15.4 ± 10.9 kg vs. 13.2 ± 12.1 kg, genotype 3) and body cell mass (BCM: 27.3 ± 6.8 kg vs. 24.3 ± 7.2 kg, genotype1; 27.7 ± 8.8 kg vs. 24.6 ± 7.6 kg, genotype 3) was found following treatment. PA in genotype 3 patients was significantly lowered after antiviral treatment compared to initial measurements (5.9 ± 0.7° vs. 5.4 ± 0.8°). Total body water (TBW) was significantly decreased in treated patients with genotype 1 (41.4 ± 7.9 l vs. 40.8 ± 9.5 l). PA reduction was accompanied by flu-like syndromes, whereas TBW decline was more frequently associated with fatigue and cephalgia.</p> <p>Discussion</p> <p>BIA offers a sophisticated analysis of body composition including BF, BCM, and TBW for HCV patients following antiviral regimens. PA reduction was associated with increased adverse effects of the antiviral therapy allowing a more dynamic therapy application.</p