Value of reading aloud to children

Guiding children into the world of quality literature is one of the greatest gifts parents and teachers can give to their children. Enjoyment of a piece is the first purpose of literature. Literature develops imagination, offers vicarious experiences, and develops insight into human behavior. Through quality literature, one can respond to the universality of human conflict. Literature can constitute a curricular base as it provides models of language and exposure to the meanings provided by the various genres and offers natural connections between the comprehension/composition processes (Huck, Hepler, & Hickman, 1987)

Keratin 13 Is Enriched in Prostate Tubule-Initiating Cells and May Identify Primary Prostate Tumors that Metastasize to the Bone.

BackgroundBenign human prostate tubule-initiating cells (TIC) and aggressive prostate cancer display common traits, including tolerance of low androgen levels, resistance to apoptosis, and microenvironment interactions that drive epithelial budding and outgrowth. TIC can be distinguished from epithelial and stromal cells that comprise prostate tissue via cell sorting based upon Epcam, CD44, and CD49f antigenic profiles. Fetal prostate epithelial cells (FC) possess a similar antigenic profile to adult TIC and are capable of inducing tubule formation. To identify the TIC niche in human prostate tissue, differential keratin (KRT) expression was evaluated.ResultsGene expression data generated from Affymetrix Gene Chip human U133 Plus 2.0 array of sorted adult and fetal epithelial cells revealed KRT13 to be significantly enriched in FC and TIC compared to basal cells (BC) and luminal cells (LC) (p<0.001). Enriched KRT13 expression was confirmed by RT-PCR and cytospin immunostaining. Immunohistochemical analysis of KRT13 expression revealed rare KRT13+ epithelia throughout prostatic ducts/acini in adult tissue specimens and differentiated tubules in 24-week recombinant grafts, In contrast, abundant KRT13 expression was observed in developing ducts/acini in fetal prostate and cord-like structures composing 8-week recombinant grafts. Immunostaining of a prostate tissue microarray revealed KRT13+ tumor foci in approximately 9% of cases, and this subset displayed significantly shorter time to recurrence (p = 0.031), metastases (p = 0.032), and decreased overall survival (p = 0.004). Diagnostic prostate needle biopsies (PNBX) from untreated patients with concurrent bone metastases (clinical stage M1) displayed KRT13+ tumor foci, as did bone metastatic foci.ConclusionsThe expression profile of KRT13 in benign fetal and adult prostate tissue and in recombinant grafts, as well as the frequency of KRT13 expression in primary and metastatic prostate cancer indicates that it may be a marker of a stem/progenitor-like cell state that is co-opted in aggressive tumor cells. KRT13 is enriched in benign stem-like cells that display androgen-resistance, apoptosis-resistance, and branching morphogenesis properties. Collectively our data demonstrate that KRT13 expression is associated with poor prognosis at multiple stages of disease progression and may represent an important biomarker of adverse outcome in patients with prostate cancer

Keratin 13 Is Enriched in Prostate Tubule-Initiating Cells and May Identify Primary Prostate Tumors that Metastasize to the Bone

<div><p>Background</p><p>Benign human prostate tubule-initiating cells (TIC) and aggressive prostate cancer display common traits, including tolerance of low androgen levels, resistance to apoptosis, and microenvironment interactions that drive epithelial budding and outgrowth. TIC can be distinguished from epithelial and stromal cells that comprise prostate tissue via cell sorting based upon Epcam, CD44, and CD49f antigenic profiles. Fetal prostate epithelial cells (FC) possess a similar antigenic profile to adult TIC and are capable of inducing tubule formation. To identify the TIC niche in human prostate tissue, differential keratin (KRT) expression was evaluated.</p><p>Results</p><p>Gene expression data generated from Affymetrix Gene Chip human U133 Plus 2.0 array of sorted adult and fetal epithelial cells revealed KRT13 to be significantly enriched in FC and TIC compared to basal cells (BC) and luminal cells (LC) (p<0.001). Enriched KRT13 expression was confirmed by RT-PCR and cytospin immunostaining. Immunohistochemical analysis of KRT13 expression revealed rare KRT13⁺ epithelia throughout prostatic ducts/acini in adult tissue specimens and differentiated tubules in 24-week recombinant grafts, In contrast, abundant KRT13 expression was observed in developing ducts/acini in fetal prostate and cord-like structures composing 8-week recombinant grafts. Immunostaining of a prostate tissue microarray revealed KRT13⁺ tumor foci in approximately 9% of cases, and this subset displayed significantly shorter time to recurrence (p = 0.031), metastases (p = 0.032), and decreased overall survival (p = 0.004). Diagnostic prostate needle biopsies (PNBX) from untreated patients with concurrent bone metastases (clinical stage M1) displayed KRT13⁺ tumor foci, as did bone metastatic foci.</p><p>Conclusions</p><p>The expression profile of KRT13 in benign fetal and adult prostate tissue and in recombinant grafts, as well as the frequency of KRT13 expression in primary and metastatic prostate cancer indicates that it may be a marker of a stem/progenitor-like cell state that is co-opted in aggressive tumor cells. KRT13 is enriched in benign stem-like cells that display androgen-resistance, apoptosis-resistance, and branching morphogenesis properties. Collectively our data demonstrate that KRT13 expression is associated with poor prognosis at multiple stages of disease progression and may represent an important biomarker of adverse outcome in patients with prostate cancer.</p></div

IHC analysis of KRT13 expression in fetal and adult prostate tissue and recombinant grafts.

<p>(A) Immunohistochemical (IHC) analysis of fetal prostate tissue, benign adult prostate tissue, and HGPIN lesion. Representative images of fetal tissue 14–18 weeks gestation are shown. KRT13+ Benign and HGPIN lesions were routinely observed in radical prostatectomy specimens. (B) Schematic of <i>in vivo</i> prostate recombination assay. All grafts were generated from freshly dissociated prostate cells combined with hFPS and injected subcutaneously with Matrigel^™ <i>in vivo</i>. (C) IHC analysis of recombinant grafts stained for KRT13. 8-week graft demonstrates predominantly cord-like structures, and 24-week grafts demonstrate differentiated tubules with lumens. Grafts generated from 3 individual prostate specimens were collected at each time period (<12 weeks and >24 weeks). Representative images of KRT13 expression are shown.</p

Differential KRT expression in fractionated prostate epithelial cells.

<p>(A). Differential expression of the basal KRT5, luminal KRT 8 and KRT 13 among the four cell populations analyzed (FC-red dot, LC-blue dots, BC-green dots, and TIC-purple dots) from the Affymetrix Gene Chip Human U133 PLUS 2.0 Array analysis. Each dot represents an individual sample, with the exception of the FC, where 6 samples were pooled to generate sufficient RNA for analysis. (B) RNA was isolated from sorted cell fractions generated from 3 unique prostate tissue specimens and evaluated via Quantitative RT-PCR. Unfractionated total prostate cell control is represented by the black column, Epcam⁺CD44⁺CD49f^Hi basal cells (BC) represented by green column, Epcam⁺CD44^-CD49f^hi tubule initiating cells (TIC) represented by purple column, and Epcam⁺CD44^-CD49f^Lo luminal cells (LC) represented by blue column. TIC had significantly higher expression than BC (p<0.05). (C) KRT13 immunostaining of cytospin slides of sorted cell fractions (BC, TIC, and LC) demonstrates relative abundance of KRT13⁺ cells, designated by brown staining, within the TIC fraction relative to BC and LC. The bar graph demonstrates the average cell count of KRT13⁺ cells per/cytospin slide (average of 3–5 slides, P<0.05).</p

KRT13 expression in prostate cancer.

<p>(A) KRT13 expression is detected (from right to left) in a cancer core from the WLA TMA, a diagnostic PNBX core from a patient with diffuse bone metastases, a biopsy of a bone metastatic site, and residual prostate glands in a prostate specimen from a patient treated with radiation and ADT. (B) Bar graph representing the relative abundance of KRT13⁺ tumor foci identified in localized (stage M0) and metastatic (stage M1) cases. KRT13⁺ foci are identified in approximately 9% of prostate cancer cores from M0 cases in the WLA TMA. In contrast, all diagnostic PNBX from patients with diffuse bone metastases display KRT13⁺ tumor foci.</p

KRT13 expression in localized cancer is significantly associated with shorter time to recurrence.

<p>Kaplan Meier curves generated from outcomes of cases compiled in the WLA TMA and stratified based on the presence of KRT13⁺ tumor foci. A. Time to recurrence (P = 0.031). B. Time to CRPC (P = 0.331). C. Time to metastases (p = 0.032). D. Overall survival (p = 0.004).</p

Kaplan-Meier Estimated Probabilities for Survival.

<p>Kaplan-Meier Estimated Probabilities for Survival.</p