Breast Carcinoma; Human Epidermal Growth Factor Receptor-2 (HER-2) and Grading Correlation

Introduction: Overexpression of Human Epidermal Growth factor Receptor-2 (HER-2) is one of the most important prognostic and predictive factors of breast cancer, observed in 25% - 30% of breast carcinoma patients leading to poor prognosis and feasible anti HER-2 antibody drugs. The objective of this study was to evaluate the HER-2 frequency in target population and its correlation with histologic grade as well as tumor pathology, estrogen receptor (ER) and P53 in our patients. Methods: A total of 300 cases (all female) aged 24- 80 year, were randomly selected from patients who were admitted in two of the Tehran University of Medical Sciences affiliated centers (Emam Khomeini Cancer Institute and Shariati hospital) over a 2-year period (2013-2014). Assessment of tumors for HER-2, P53, ER, pathological type and histologic grade was performed. HER-2 over expression defined as three plus (+++) in immunohistochemistry (IHC). Results: The mean age was 49.6±11 years. HER-2 over expression was seen in 34% of the patients. Significant correlations were found between HER-2+, P53+ and high histologic grade and ER (PConclusion: Co-expression of several poor prognostic biomarkers in breast cancer (HER-2 +, P53 +, ER- , high grade) may predict more aggressive phenotype, worse disease and lower overall survival in these patients

Trafficking through COPII Stabilises Cell Polarity and Drives Secretion during Drosophila Epidermal Differentiation

BACKGROUND: The differentiation of an extracellular matrix (ECM) at the apical side of epithelial cells implies massive polarised secretion and membrane trafficking. An epithelial cell is hence engaged in coordinating secretion and cell polarity for a correct and efficient ECM formation. PRINCIPAL FINDINGS: We are studying the molecular mechanisms that Drosophila tracheal and epidermal cells deploy to form their specific apical ECM during differentiation. In this work we demonstrate that the two genetically identified factors haunted and ghost are essential for polarity maintenance, membrane topology as well as for secretion of the tracheal luminal matrix and the cuticle. We show that they code for the Drosophila COPII vesicle-coating components Sec23 and Sec24, respectively, that organise vesicle transport from the ER to the Golgi apparatus. CONCLUSION: Taken together, epithelial differentiation during Drosophila embryogenesis is a concerted action of ECM formation, plasma membrane remodelling and maintenance of cell polarity that all three rely mainly, if not absolutely, on the canonical secretory pathway from the ER over the Golgi apparatus to the plasma membrane. Our results indicate that COPII vesicles constitute a central hub for these processes

Diagnostiska test i Biologi för kartläggning av elevers förkunskaper in i gymnasieskolan

Syfte: Syftet med detta examensarbete är att kartlägga förkunskaperna i områdena fotosyntes, biologisk mångfald, växthusgaser, energi och hållbar utveckling, samt evolution och naturligt urval hos gymnasieelever som läser ämnet Biologi 1 på det naturvetenskapliga programmet på en gymnasieskola i västra Götaland. Syftet är också att utvärdera betydelsen av diagnostiska test för dessa elever och deras lärare. Avsikten är även att presentera möjliga förslag till att utnyttja resultaten av dessa test för att på bästa sätt kunna hjälpa de elever som har svårigheter i eller ligger i riskzonen för att ha svårigheter i dessa kunskapsområden i Biologi.Metod och genomförande: Undersökningen har dels genomförts med en diagnostisk test, dels genom intervjuer av tre lärare på gymnasieskolan. Eleverna har även fått två analysfrågor som berörde deras uppfattningar om användandet av denna test inom ämnet Biologi.Resultat: Resultatet visar att eleverna har bristande förkunskaper inom områdena fotosyntes och betydelse av växthusgaser. Både elever och intervjuade lärare är positivt inställda till diagnostisk test i Biologi. Eleverna anser att diagnostisk test med fördel kan införas så länge dessa används för kartläggning av elevernas förkunskaper, samt som ett verktyg för att ge dem individuellt stöd till vidare kunskapsutveckling. Trots att lärarna verkar ha skilda uppfattningar om inflytandet av den eventuella diagnostiska testen på undervisningens upplägg och arbetsformer, tycker samtliga att nivågrupperingar inte är någon givande arbetsform, en mer blandad kunskapsnivå i grupper är ett mer effektivt sätt att hjälpa de elever som har bristande förkunskaper. Dessutom räknas språk och läsförståelse som viktiga faktorer för lärandets framgång

Embryonic ecdysone-induced gene expression and progression of organ morphogenesis

The formation of an epithelial organ requires a set of organ-specific gene programs that instruct parallel and successive developmental events. Still, it is unclear what are the core regulatory programs and how such programs are timely coordinated within the organ. We use mainly the Drosophila trachea (respiratory system) as a model to understand epithelial organ development. The trachea is a network of epithelial tubes, and its morphology is sensitive to mutations in genes whose products participate in consecutive steps of branching morphogenesis and tube size maturation. In paper I, we identified two gene functions required for tracheal tube elongation. We show that tracheal cells, at a specific time in development, acquire an ability to elongate that is mediated by a protein involved in actin organization. A luminal matrix holds back this elongation, and temporal expression of an anion channel appears required to modify the luminal matrix and thereby permit a controlled extent of elongation. In paper II, we show that a mucin-like protein is temporally expressed in the trachea and is required for tube elongation. The protein also drives diameter expansion of the hindgut, where it fills the growing lumen and appears to physically dilate the tube. The work demonstrates that regulated expression of a single protein can model epithelial tube diameter. In papers III and IV, we focused on the temporal regulation of tracheal gene expression, and uncovered an important function for the mid-embryonic ecdysone hormone pulse in progression of organ development. In paper III, we analysed the mechanism of embryonic ecdysone signalling and found that the hormone causes pan-embryonic activation of Ecdysone Receptor (EcR). EcR acts tissue-autonomously together with Ultraspiracle to promote concurrent progression of organ development. In paper IV, we show that ecdysone, via EcR and a downstream cascade of gene regulators is needed to advance parallel tracheal-specific gene programs. Together, the results reveal novel gene functions during epithelial tube formation, and show that correct temporal unfolding of the tracheal gene network relies on gene-regulatory input from an external cue in form of a hormone pulse

Diagnostiska test i Biologi för kartläggning av elevers förkunskaper in i gymnasieskolan

Syfte: Syftet med detta examensarbete är att kartlägga förkunskaperna i områdena fotosyntes, biologisk mångfald, växthusgaser, energi och hållbar utveckling, samt evolution och naturligt urval hos gymnasieelever som läser ämnet Biologi 1 på det naturvetenskapliga programmet på en gymnasieskola i västra Götaland. Syftet är också att utvärdera betydelsen av diagnostiska test för dessa elever och deras lärare. Avsikten är även att presentera möjliga förslag till att utnyttja resultaten av dessa test för att på bästa sätt kunna hjälpa de elever som har svårigheter i eller ligger i riskzonen för att ha svårigheter i dessa kunskapsområden i Biologi. Metod och genomförande: Undersökningen har dels genomförts med en diagnostisk test, dels genom intervjuer av tre lärare på gymnasieskolan. Eleverna har även fått två analysfrågor som berörde deras uppfattningar om användandet av denna test inom ämnet Biologi. Resultat: Resultatet visar att eleverna har bristande förkunskaper inom områdena fotosyntes och betydelse av växthusgaser. Både elever och intervjuade lärare är positivt inställda till diagnostisk test i Biologi. Eleverna anser att diagnostisk test med fördel kan införas så länge dessa används för kartläggning av elevernas förkunskaper, samt som ett verktyg för att ge dem individuellt stöd till vidare kunskapsutveckling. Trots att lärarna verkar ha skilda uppfattningar om inflytandet av den eventuella diagnostiska testen på undervisningens upplägg och arbetsformer, tycker samtliga att nivågrupperingar inte är någon givande arbetsform, en mer blandad kunskapsnivå i grupper är ett mer effektivt sätt att hjälpa de elever som har bristande förkunskaper. Dessutom räknas språk och läsförståelse som viktiga faktorer för lärandets framgång

Liver-derived IGF-I is permissive for ovariectomy-induced trabecular bone loss

INTRODUCTION: Estrogen deficiency results in trabecular bone loss, associated with T-cell proliferation in the bone marrow. Insulin-like growth factor I (IGF-I) is involved in the regulation of both bone metabolism and lymphopoiesis. A major part of serum IGF-I is derived from the liver. The aim of the present study was to investigate the role of liver-derived IGF-I for ovariectomy (ovx)-induced trabecular bone loss. MATERIALS AND METHODS: Mice with adult liver-specific IGF-I inactivation (LI-IGF-I-/-) and wild type mice (WT) were either ovx or sham operated. After 5 weeks, the skeletal phenotype was analyzed by pQCT and microCT. The bone marrow cellularity was analyzed using FACS technique, and mRNA levels were quantified using real-time PCR. RESULTS: Ovx resulted in a pronounced reduction in trabecular bone mineral density (-52%,

A luminal glycoprotein drives dose-dependent diameter expansion of the Drosophila melanogaster hindgut tube.

International audienceAn important step in epithelial organ development is size maturation of the organ lumen to attain correct dimensions. Here we show that the regulated expression of Tenectin (Tnc) is critical to shape the Drosophila melanogaster hindgut tube. Tnc is a secreted protein that fills the embryonic hindgut lumen during tube diameter expansion. Inside the lumen, Tnc contributes to detectable O-Glycans and forms a dense striated matrix. Loss of tnc causes a narrow hindgut tube, while Tnc over-expression drives tube dilation in a dose-dependent manner. Cellular analyses show that luminal accumulation of Tnc causes an increase in inner and outer tube diameter, and cell flattening within the tube wall, similar to the effects of a hydrostatic pressure in other systems. When Tnc expression is induced only in cells at one side of the tube wall, Tnc fills the lumen and equally affects all cells at the lumen perimeter, arguing that Tnc acts non-cell-autonomously. Moreover, when Tnc expression is directed to a segment of a tube, its luminal accumulation is restricted to this segment and affects the surrounding cells to promote a corresponding local diameter expansion. These findings suggest that deposition of Tnc into the lumen might contribute to expansion of the lumen volume, and thereby to stretching of the tube wall. Consistent with such an idea, ectopic expression of Tnc in different developing epithelial tubes is sufficient to cause dilation, while epidermal Tnc expression has no effect on morphology. Together, the results show that epithelial tube diameter can be modelled by regulating the levels and pattern of expression of a single luminal glycoprotein

Loss of <i>tnc</i> causes reduced apical cell circumferences, altered cell arrangement, and a smaller outer tube diameter.

<p>(A–H) Embryos were labelled with anti-DECad, and serial z-stacked images spanning the upper half of the hindgut tube were merged to reveal apical cell circumferences. Arrows point to the Si/Li border. The hindgut of a wild type and <i>tnc</i> mutant embryo at dorsal view (A and B) is shown together with high magnifications of respective Si (in C and D) and posterior Li (in E and F). Identically sized squares (in C and D) span ∼10 cells of the wild type Si and ∼18 cells of the mutant Si. Brackets of identical size (in E and F) illustrate that cells are more elongated along the lumen perimeter in the wild type compared to the mutant. In the dorsal Li (G and H, ventral view), identically sized brackets span 9 or 11 cells along the border cells in the wild type and mutant hindgut, respectively. The mutant hindgut also has fewer cells at the dorsal lumen perimeter. (I and J) The outer hindgut diameter, visualized by labelling for Dg (green) and merging serial z-stacked images that span the entire hindgut, is reduced in the mutants. Stippled and full lines represent wild type Si and Li diameter, respectively. (K and L) Labelling with anti-Fas3 (green) reveal comparable level and distribution of Fas3 (bracket) in the hindgut epithelium of wild type (K) and <i>tnc</i> mutant (L) embryos. Co-staining for Tnc (magenta) shows the absence of Tnc in the mutant hindgut. All images are of stage 16 embryos. Scale bars: 10 µm in A (A and B), 10 µm in C (C–H), 10 µm in I (I and J), 10 µm in K (K and L).</p

Tnc acts non-cell-autonomously.

<p>(A) <i>enGAL4</i> drives expression of <i>UAS-GFP</i> in the dorsal Li (bracket), as seen by labelling with anti-GFP (green) and anti-Crb (magenta). (B and C) Stage 16 embryos stained for DECad and Crb show that <i>enGAL4</i>-driven expression of <i>tnc</i> in dorsal Li (bracket) caused enlarged apical cell circumferences in both dorsal and ventral Li (C), when compared to embryos that only express <i>enGAL4</i> (B). (D–G) <i>enGAL4</i> drives expression of <i>UAS-GFP</i> (green) in a cluster of cells in the anterior salivary gland (D, stage 13). <i>enGAL4</i>-driven expression of Tnc in salivary glands resulted in local tube dilation (E). By merging serial z-stacked images, the apical cell circumferences were visualized (F). Note that <i>enGAL4</i> drives expression in one side of the tube, but all cells at the perimeter show enlarged apical cell circumference. Co-staining for Tnc (green) and Crb (magenta) shows that luminal Tnc localizes to the dilated part of the salivary gland lumen (G). (H) A possible model for the function of Tnc during lumen dilation. Expression of <i>tnc</i> in the tubular epithelium causes tube dilation according to the level of expression (“low" and “high") and causes differential dilation along the tube. Once inside the lumen, Tnc acts on surrounding cells, possibly by generating a mechanical pressure, to expand the tube wall.</p