bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunoglobulin G in cystic lesions of rat enamel organ following fluoride intoxication
Authors: NORDLUND ANITA LANGE , LINDSKOG SVEN 
Published: October 2007

Abstract –Fluoride given as a high single dose to young rats with developing molars has earlier been shown to cause subameloblastic cysts with disorganized ameloblasts in the cystic wall and an irregular mineralization pattern of the underlying enamel. In the present study irnmunohist‐ochemistry has been employed to determine if an increased permeability of the enamel organ occurred at the areas of cell disturbances. For this purpose 5‐day‐old rats were injected with 60 mg sodium fluoride per kg body weight. They were decapitated after 24 h, the maxilla prepared histologically and paraffin sections incubated for the demonstration of IgG according to the avidin‐biotin‐peroxidase complex method. Staining for IgG was present in the cystic lumina and in areas of disorganized ameloblasts. No reaction was observed in areas of unaffected ameloblasts. It was suggested that the fluoride‐induced cell injury increased the permeability of the ameloblastic cell layer. Diffusion of IgG and most likely other substances as well, through the ameloblastic layer may have contributed to cyst formation and to the irregular mineral deposits that have been found in the ameloblastic layer and at the enamel surface.
Clinical and radiographic appearance of proximal carious lesions at the time of operative treatment in young permanent teeth
Authors: MEJÀRE INGEGERD , MALMGREN BARBRO 
Published: October 2007

Abstract –Clinical tissue changes were recorded during restorative treatment of proximal carious lesions of young premolars and molars. 60 proximal surfaces with radiolucencies in the inner half of the enamel or the outer half of the dentin were treated. The extent and character of the tissue changes were documented with photographs taken during drilling and evaluated after magnification. The maximum extent for each lesion was correlated to the extent of the radiographically observed lesion. The results showed that 70% of the restored surfaces were associated with a breakdown of the enamel surface. When the radiolucency did not extend deeper than into the inner half of the enamel, cavities were found in 61%; for lesions with a radiolucency extending into the outer half of the dentin the percentage was 78%. In the majority of cases the cavity was limited to the enamel. In all cases discoloration was observed in the enamel. The dentin was soft and discolored in 83%. Severe damage of tooth substance was found in 12% of the teeth.
An in vivo method for microhardness measurements on human teeth
Authors: FOSSE GISLE , ROSENGREN BENGT , SKAALE SIREN , LEKNES KNUT , WULFF LENA 
Published: October 2007

Abstract –A non‐destructive, in vivo method of measuring the enamel hardness directly on patients is described. Normal values on 39 students arc given and compared with those of five patients, one of whom suffered from abnormal oral acid concentration, and the others from the effects of various degrees of hyposialosis caused by radiologic treatment of tumors in head and neck. The difference between the two groups was significant below the 0.1% level. It was suggested that the method may be used to test the degree of salivary gland inactivation after radiologic treatment and the efficiency of different saliva substitutes used to alleviate the effects of hyposialosis.
Staining patterns of rodent squamous epithelia by monoclonal anti‐keratin antibodies
Authors: REIBEL JESPER , DABELSTEEN ERIK 
Published: October 2007

Abstract –Anti‐keratin staining patterns were examined by immunofluorescence in the epidermis, oral mucosa and forestomach of rats and mice by monoclonal antibodies AE1 and AE2. In contrast to human tissues enzymatic pretreatment of sections was necessary even when freshfrozen tissue was used, suggesting masking of the antigens in vivo. AE1 stained the cytoplasm of spinous cells in most epithelia, whereas basal cell staining varied. AE2 showed suprabasal cytoplasmic staining in epidermis, forestomach and palate, whereas the other epithelia were stained only in keratohyalin granules and membranes of cornified cells. In some epithelia a small number of irregularly distributed basal cells stained positive with AE2, indicating heterogeneity in the basal cell compartment. Thus, the anti‐keratin staining pallern varies both regionally and, as earlier shown in human epithelium, with the stage of maturation of cells within a given epithelium. The present study provides a basis for further studies of epithelial differentiation during normal and pathologic development.
In vitro activation of amphibian dermal melanocytes by nicotine
Authors: HEDIN C. ANDERS , LARSSON ÅKE 
Published: October 2007

Abstract –Epidemiologic investigations have shown that nicotine could be a factor causing oral melanin pigmentation in man. Nicotine was therefore tested on amphibian skin melanocytes. Cell reactions were registered by spectrophotometry, in vitro light microscopy, photomicrography and light and electron microscopy. It was found that dermal melanocytes in the toad Bufo bufo and the frog Rana arvalis were activated by nicotine and that this activation was not mediated via β‐adrenergic receptors in melanocytes.
Dentin bonding: effect of tubule orientation on hybrid‐layer formation
Authors: Schüpbach Peter , Krejci Ivo , Lutz Felix 
Published: October 2007

Schüpbach P. Krejci I, Felix L: Dentin bonding: effect of tubule orientation on hybrid‐layer formation.In an attempt to compare the morphology of the resin‐dentin interface in areas where the dentinal tubules run perpendicularly or at an angle to the cavity surface with that of areas where they run parallel to it, we studied a dentin adhesive system using transmission electron microscopy and fluorescence confocal laser scanning microscopy. The design of the study included the simulation of the normal hydrostatic pressure within the pulp and the dentinal tubules. Following acid etching of the dentinal surface with maleic acid/HEMA, the smear layer was removed, and a superficial zone was demineralized in such a way that the exposed collagenous dentin matrix retained its integrity. Confocal laser scanning microscopal investigations using primer labeled with rhodamine B showed that the penetration of the primer occurred not only vertically via surface porosities, but mainly laterally, via the dentinal tubules. The adhesive resin labeled with fluorescein completely infiltrated the demineralized layer, thereby forming a hybrid layer. The orientation of the dentinal tubules had a profound effect on the formation of the hybrid layer. In areas with perpendicular tubule orientation, the layer was 3.2 ± 0.8 μm thick, showing solid 27.2 ± 0.8 μm long resin tags in the dentinal tubules, and a network of tiny tags in their side‐branches. In areas with parallel tubule orientation, the layer was significantly thinner (1.3 ± 0.6 μm) and resin tags were absent.
A Novel Variant of Ileal Bile Acid Binding Protein Is Up-regulated through Nuclear Factor-κB Activation in Colorectal Adenocarcinoma
Authors: Fang Changming , Dean Jarrod , Smith Jeffrey W. 
Published: October 2007

Abstract
Ileal bile acid binding protein (IBABP) is the only cytosolic protein known to bind and transport bile acids. Because IBABP is reportedly up-regulated in colorectal cancer, it has been suggested as a link between bile acids and the risk of colorectal cancer. However, in this study, we show that IBABP is not up-regulated. Rather, a novel transcript of the IBABP gene, which encodes an additional 49 NH2-terminal amino acid residues, is up-regulated in colorectal cancer (P &lt; 0.001). The novel transcript, called IBABP-L, is also distinct from IBABP because its transcription is controlled by nuclear factor-κB (NF-κB) rather than by the farnesoid X receptor. Most significantly, IBABP-L is necessary for the survival of HCT116 colon cancer cells in the presence of physiologic levels of the secondary bile acid deoxycholate. Collectively, the studies point toward a unique bile acid response pathway involving NF-κB and IBABP-L that could be useful for diagnosis and could potentially be targeted for therapeutic benefit. [Cancer Res 2007;67(19):9039–46]
The Activity of Zoledronic Acid on Neuroblastoma Bone Metastasis Involves Inhibition of Osteoclasts and Tumor Cell Survival and Proliferation
Authors: Peng Hongjun , Sohara Yasuyoshi , Moats Rex A. , Nelson Marvin D. , Groshen Susan G. , Ye Wei , Reynolds C. Patrick , DeClerck Yves A. 
Published: October 2007

Abstract
Metastasis to the bone is seen in 56% of patients with neuroblastoma and contributes to morbidity and mortality. Using a murine model of bone invasion, we have reported previously that neuroblastoma cells invade the bone by activating osteoclasts. Here, we investigated the antitumoral and antiosteolytic activities of zoledronic acid, a bisphosphonate inhibitor of osteoclasts, in combination with cytotoxic chemotherapy in our model. We first show that zoledronic acid given at the same time (early prevention) or 2 weeks after tumor cell injection (late prevention) significantly prevented the formation of severe osteolytic lesions. It also prevented formation of these lesions when given 4 weeks after tumor cell injection (intervention) when combined with chemotherapy including cyclophosphamide and topotecan. The combination of zoledronic acid + cyclophosphamide/topotecan also significantly improved survival (P &lt; 0.001). In mice treated with zoledronic acid, we observed a marked inhibition of osteoclasts inside the bone associated with a decrease in tumor cell proliferation and increase in tumor cell apoptosis. In vitro, zoledronic acid inhibited neuroblastoma cell proliferation and induced apoptosis, and these effects were significantly enhanced by the addition of 4-hydroxyperoxycyclophosphamide (4-HC). The proapoptotic effect of zoledronic acid and zoledronic acid in combination with 4-HC on tumor cells was associated with an increase in caspase-3 activity and a decrease in phosphorylated Bcl-2, Bcl-2, and Bcl-XL expression. Zoledronic acid inhibited the association of Ras with the plasma membrane and activation of c-Raf, Akt, and extracellular signal-regulated kinase 1/2. The data indicate that zoledronic acid, in addition to inhibiting osteoclasts, is active against tumor cells and suggest that zoledronic acid in combination with cytotoxic chemotherapy may be effective in children with neuroblastoma that has metastasized to the bone. [Cancer Res 2007;67(19):9346–55]
High Cancer-Specific Expression of Mesothelin (MSLN) Is Attributable to an Upstream Enhancer Containing a Transcription Enhancer Factor–Dependent MCAT Motif
Authors: Hucl Tomas , Brody Jonathan R. , Gallmeier Eike , Iacobuzio-Donahue Christine A. , Farrance Iain K. , Kern Scott E. 
Published: October 2007

Abstract
Identification of genes with cancer-specific overexpression offers the potential to efficiently discover cancer-specific activities in an unbiased manner. We apply this paradigm to study mesothelin (MSLN) overexpression, a nearly ubiquitous, diagnostically and therapeutically useful characteristic of pancreatic cancer. We identified an 18-bp upstream enhancer, termed CanScript, strongly activating transcription from an otherwise weak tissue-nonspecific promoter and operating selectively in cells having aberrantly elevated cancer-specific MSLN transcription. Introducing mutations into CanScript showed two functionally distinct sites: an Sp1-like site and an MCAT element. Gel retardation and chromatin immunoprecipitation assays showed the MCAT element to be bound by transcription enhancer factor (TEF)-1 (TEAD1) in vitro and in vivo. The presence of TEF-1 was required for MSLN protein overexpression as determined by TEF-1 knockdown experiments. The cancer specificity seemed to be provided by a putative limiting cofactor of TEF-1 that could be outcompeted by exogenous TEF-1 only in a MSLN-overexpressing cell line. A CanScript concatemer offered enhanced activity. These results identify a TEF family member as a major regulator of MSLN overexpression, a fundamental characteristic of pancreatic and other cancers, perhaps due to an upstream and highly frequent aberrant cellular activity. The CanScript sequence represents a modular element for cancer-specific targeting, potentially suitable for nearly a third of human malignancies. [Cancer Res 2007;67(19):9055–65]
Tenascin-W Is a Novel Marker for Activated Tumor Stroma in Low-grade Human Breast Cancer and Influences Cell Behavior
Authors: Degen Martin , Brellier Florence , Kain Renate , Ruiz Christian , Terracciano Luigi , Orend Gertraud , Chiquet-Ehrismann Ruth 
Published: October 2007

Abstract
This is the first report about human tenascin-W, the fourth and final member of the extracellular matrix protein family of tenascins. Sixty-three human breast tumor extracts were analyzed by Western blotting for the presence of tenascin-W and compared with tenascin-C, an established marker of tumor stroma. Interestingly, we found tenascin-W expression in the majority of the tumor tissues, but no detectable expression in the normal mammary parenchyma. Eighty-one percent of the breast tumor samples were tenascin-W positive and 86% showed expression of tenascin-C. However, tenascin-W and tenascin-C amounts varied greatly between tumors and some contained either tenascin-W or tenascin-C exclusively, indicating independent mechanisms regulating their expression. Although there was no difference between high- or low-grade tumors with respect to the presence of tenascin-C, tenascin-W was more prominent in low-grade tumors. For 42 of the breast cancer tissues, a frozen tumor microarray was available to confirm the Western blot data by immunohistochemistry. Similar to tenascin-C, tenascin-W was detected in the tumor stroma. Fibroblasts adhered to tenascin-W in a β1 integrin–dependent manner and spread with a distinctive morphology under conditions where they remained round on tenascin-C. CHOB2 cells expressing αvβ1 or α4β1 integrins were able to spread on tenascin-W. Furthermore, addition of tenascin-W to the culture medium increased migration of breast cancer cells toward a fibronectin substratum in vitro. These data imply that tenascin-W expression in the activated tumor stroma facilitates tumorigenesis by supporting the migratory behavior of breast cancer cells. [Cancer Res 2007;67(19):9169–79]
Systemic Therapy of Spontaneous Prostate Cancer in Transgenic Mice with Oncolytic Herpes Simplex Viruses
Authors: Varghese Susan , Rabkin Samuel D. , Nielsen G. Petur , MacGarvey Usha , Liu Renbin , Martuza Robert L. 
Published: October 2007

Abstract
Oncolytic viruses are an innovative therapeutic strategy for cancer, wherein viral replication and cytotoxicity are selective for tumor cells. Here we show the efficacy of systemically administered oncolytic viruses for the treatment of spontaneously arising tumors, specifically the use of oncolytic herpes simplex viruses (HSV) administered i.v. to treat spontaneously developing primary and metastatic prostate cancer in the transgenic TRAMP mouse, which recapitulates human prostate cancer progression. Four administrations of systemically delivered NV1023 virus, an HSV-1/HSV-2 oncolytic recombinant, to TRAMP mice at 12 or 18 weeks of age (presence of prostate adenocarcinoma or metastatic disease, respectively) inhibited primary tumor growth and metastases to lymph nodes. Expression of interleukin 12 (IL-12) from NV1042 virus, a derivative of NV1023, was additionally effective, significantly reducing the frequency of development of prostate cancer and lung metastases, even when the mice were treated after the onset of metastasis at 18 weeks of age. NV1042-infected cells, as detected by 5-bromo-4-chloro-3-indolyl-β-d-galactopyranoside staining for Lac Z expressed by the virus, were present in prostate tumors 1 week after the final virus injection and viral DNA was detected at 2 weeks after final virus injection by real-time PCR in primary and metastatic tumors but not in liver or blood. No toxicity was observed in any of the treated mice. The efficacy of the IL-12–expressing NV1042 virus in this aggressive prostate cancer model using a clinically relevant treatment paradigm merits its consideration for clinical studies. [Cancer Res 2007;67(19):9371–9]
Roles for the Stem Cell–Associated Intermediate Filament Nestin in Prostate Cancer Migration and Metastasis
Authors: Kleeberger Wolfram , Bova G. Steven , Nielsen Matthew E. , Herawi Mehsati , Chuang Ai-Ying , Epstein Jonathan I. , Berman David M. 
Published: October 2007

Abstract
The intermediate filament protein Nestin identifies stem/progenitor cells in adult tissues, but the function of Nestin is poorly understood. We investigated Nestin expression and function in common lethal cancers. Nestin mRNA was detected in cell lines from small cell lung, and breast cancers, and particularly elevated in cell lines derived from prostate cancer metastases. Whereas the androgen-independent lines PC3, 22RV1, and DU145 all expressed Nestin transcripts under standard culture conditions, the androgen-dependent line LnCaP expressed Nestin only on androgen withdrawal. We confirmed associations of Nestin expression, androgen withdrawal, and metastatic potential by immunohistochemical analysis of samples from 254 prostate cancer patients. Cytoplasmic Nestin protein was readily identifiable in prostate cancer cells from 75% of patients with lethal androgen-independent disease, even in cancer sampled from the prostate itself. However, Nestin expression was undetectable in localized androgen-deprived tumors and in metastases without prior androgen deprivation. To address its function, we reduced Nestin levels with short hairpin RNAs, markedly inhibiting in vitro migration and invasion in prostate cancer cells but leaving cell growth intact. Nestin knockdown also diminished metastases 5-fold compared with controls despite uncompromised tumorigenicity at the site of inoculation. These results specify a function for Nestin in cell motility and identify a novel pathway for prostate cancer metastasis. Activity of this pathway may be selected by the extraprostatic environment or, as supported by our data, may originate within the prostate after androgen deprivation. Further dissection of this novel Nestin migration pathway may lead to strategies to prevent and neutralize metastatic spread. [Cancer Res 2007;67(19):9199–206]
Epigenetic Inactivation of a Cluster of Genes Flanking MLH1 in Microsatellite-Unstable Colorectal Cancer
Authors: Hitchins Megan P. , Lin Vita Ap , Buckle Andrew , Cheong Kayfong , Halani Nimita , Ku Su , Kwok Chau-To , Packham Deborah , Suter Catherine M. , Meagher Alan , Stirzaker Clare , Clark Susan , Hawkins Nicholas J. , Ward Robyn L. 
Published: October 2007

Abstract
Biallelic promoter methylation and transcriptional silencing of the MLH1 gene occurs in the majority of sporadic colorectal cancers exhibiting microsatellite instability due to defective DNA mismatch repair. Long-range epigenetic silencing of contiguous genes has been found on chromosome 2q14 in colorectal cancer. We hypothesized that epigenetic silencing of MLH1 could occur on a regional scale affecting additional genes within 3p22, rather than as a focal event. We studied the levels of CpG island methylation and expression of multiple contiguous genes across a 4 Mb segment of 3p22 including MLH1 in microsatellite-unstable and -stable cancers, and their paired normal colonic mucosa. We found concordant CpG island hypermethylation, H3-K9 dimethylation and transcriptional silencing of MLH1 and multiple flanking genes spanning up to 2.4 Mb in microsatellite-unstable colorectal cancers. This region was interspersed with unmethylated genes, which were also transcriptionally repressed. Expression of both methylated and unmethylated genes was reactivated by methyltransferase and histone deacetylase inhibitors in a microsatellite-unstable colorectal carcinoma cell line. Two genes at the telomeric end of the region were also hypermethylated in microsatellite-stable cancers, adenomas, and at low levels in normal colonic mucosa from older individuals. Thus, the cluster of genes flanking MLH1 that was specifically methylated in the microsatellite-unstable group of cancers extended across 1.1 Mb. Our results show that coordinate epigenetic silencing extends across a large chromosomal region encompassing MLH1 in microsatellite-unstable colorectal cancers. Simultaneous epigenetic silencing of this cluster of 3p22 genes may contribute to the development or progression of this type of cancer. [Cancer Res 2007;67(19):9107–16]
ABCG2/BCRP Expression Modulates d-Luciferin–Based Bioluminescence Imaging
Authors: Zhang Yimao , Bressler Joseph P. , Neal Jeff , Lal Bachchu , Bhang Hyo-Eun C. , Laterra John , Pomper Martin G. 
Published: October 2007

Abstract
Bioluminescence imaging (BLI) is becoming indispensable to the study of transgene expression during development and, in many in vivo models of disease such as cancer, for high throughput drug screening in vitro. Because reaction of d-luciferin with firefly luciferase (fLuc) produces photons of sufficiently long wavelength to permit imaging in intact animals, use of this substrate and enzyme pair has become the method of choice for performing BLI in vivo. We now show that expression of the ATP-binding cassette (ABC) family transporter ABCG2/BCRP affects BLI signal output from the substrate d-luciferin. In vitro studies show that d-luciferin is a substrate for ABCG2/BCRP but not for the MDR1 P-glycoprotein (ABCB1/Pgp), multidrug resistance protein 1 (MRP1/ABCC1), or multidrug resistance protein 2 (MRP2/ABCC2). d-Luciferin uptake within cells is shown to be modulated by ABC transporter inhibitors, including the potent and selective ABCG2/BCRP inhibitor fumitremorgin C. Images of xenografts engineered to express transgenic ABCG2/BCRP, as well as xenografts derived from the human prostate cancer cell line 22Rv1 that naturally express ABCG2/BCRP, show that ABCG2/BCRP expression and function within regions of interest substantially influence d-luciferin–dependent bioluminescent output in vivo. These findings highlight the need to consider ABCG2/BCRP effects during d-luciferin–based BLI and suggest novel high throughput methods for identifying new ABCG2/BCRP inhibitors. [Cancer Res 2007;67(19):9389–97]