bluuebunny/crossref_metadata_2025_split huggingface dataset:
Whole-Body Optical Imaging in Animal Models to Assess Cancer Development and Progression
Authors: Kaijzel Eric L. , van der Pluijm Gabri , Löwik Clemens W.G.M. 
Published: June 2007

Abstract
Different optical-based imaging models were used to investigate tumor progression and metastasis with particular emphasis on metastasis to bone and bone marrow. We describe how optical imaging can be used to follow important processes in tumor development and treatment response, including angiogenesis, apoptosis, and proteolysis. Finally, we discuss the translation of one optical imaging modality, near-IR fluorescence, from animal validation studies to applications in the clinic related to cancer management.
Sorafenib inhibits the angiogenesis and growth of orthotopic anaplastic thyroid carcinoma xenografts in nude mice
Authors: Kim Seungwon , Yazici Yasemin D. , Calzada Gabriel , Wang Zhuo-Ying , Younes Maher N. , Jasser Samar A. , El-Naggar Adel K. , Myers Jeffrey N. 
Published: June 2007

Abstract
Anaplastic thyroid carcinoma (ATC) remains one of the most lethal human cancers. We hypothesized that sorafenib, a multikinase inhibitor of the BRaf, vascular endothelial growth factor receptor-2, and platelet-derived growth factor receptor-β kinase, would decrease tumor growth and angiogenesis in an orthotopic model of ATC. The in vitro antiproliferative and proapoptotic effects of sorafenib on ATC cell lines were examined. To study the in vivo effects of sorafenib on orthotopic ATC tumors in nude mice, sorafenib was given p.o. at 40 or 80 mg/kg daily. Intratumoral effects were studied using immunohistochemical analysis. The effect of sorafenib on survival of the mice was also studied. Sorafenib inhibited the in vitro proliferation of ATC cell lines. Sorafenib also significantly inhibited tumor angiogenesis via the induction of endothelial apoptosis in an orthotopic model of thyroid cancer. As result, the growth of orthotopic ATC xenografts was reduced and the survival of the test animals was improved. Sorafenib exerts significant antitumor activity in an orthotopic xenograft model of ATC via a potent antiangiogenic effect. The antiangiogenic effects of sorafenib suggest that its use in clinical setting may not depend on the BRAF mutational status of thyroid tumors. Given the lack of curative options for patients with ATC, sorafenib warrants further study as a therapeutic agent against ATC. [Mol Cancer Ther 2007;6(6):1785–92]
Inhibition of ABCG2-mediated transport by protein kinase inhibitors with a bisindolylmaleimide or indolocarbazole structure
Authors: Robey Robert W. , Shukla Suneet , Steadman Kenneth , Obrzut Tomasz , Finley Elizabeth M. , Ambudkar Suresh V. , Bates Susan E. 
Published: June 2007

Abstract
ABCG2 is a transporter with potential importance in cancer drug resistance, drug oral absorption, and stem cell biology. In an effort to identify novel inhibitors of ABCG2, we examined the ability of commercially available bisindolylmaleimides (BIM) and indolocarbazole protein kinase inhibitors (PKI) to inhibit ABCG2, given the previous demonstration that the indolocarbazole PKI UCN-01 interacted with the transporter. At a concentration of 10 μmol/L, all of the compounds tested increased intracellular fluorescence of the ABCG2-specific substrate pheophorbide a in ABCG2-transfected HEK-293 cells by 1.3- to 6-fold as measured by flow cytometry; the ABCG2-specific inhibitor fumitremorgin C increased intracellular fluorescence by 6.6-fold. In 4-day cytotoxicity assays, wild-type ABCG2-transfected cells were not more than 2-fold resistant to any of the compounds, suggesting that the PKIs are not significantly transported by ABCG2. BIMs I, II, III, IV, and V, K252c, and arcyriaflavin A were also able to inhibit [125I]iodoarylazidoprazosin labeling of ABCG2 by 65% to 80% at 20 μmol/L, compared with a 50% to 70% reduction by 20 μmol/L fumitremorgin C. K252c and arcyriaflavin A were the most potent compounds, with IC50 values for inhibition of [125I]iodoarylazidoprazosin labeling of 0.37 and 0.23 μmol/L, respectively. K252c and arcyriaflavin A did not have any effect on the ATPase activity of ABCG2. Four minimally toxic compounds—BIM IV, BIM V, arcyriaflavin A, and K252c—reduced the relative resistance of ABCG2-transfected cells to SN-38 in cytotoxicity assays. We find that indolocarbazole and BIM PKIs directly interact with the ABCG2 protein and may thus increase oral bioavailability of ABCG2 substrates. [Mol Cancer Ther 2007;6(6):1877–85]
5-Azacytidine, a DNA methyltransferase inhibitor, induces ATR-mediated DNA double-strand break responses, apoptosis, and synergistic cytotoxicity with doxorubicin and bortezomib against multiple myeloma cells
Authors: Kiziltepe Tanyel , Hideshima Teru , Catley Laurence , Raje Noopur , Yasui Hiroshi , Shiraishi Norihiko , Okawa Yutaka , Ikeda Hiroshi , Vallet Sonia , Pozzi Samantha , Ishitsuka Kenji , Ocio Enrique M. , Chauhan Dharminder , Anderson Kenneth C. 
Published: June 2007

AbstractIn this study, we investigated the cytotoxicity of 5-azacytidine, a DNA methyltransferase inhibitor, against multiple myeloma (MM) cells, and characterized DNA damage–related mechanisms of cell death. 5-Azacytidine showed significant cytotoxicity against both conventional therapy-sensitive and therapy-resistant MM cell lines, as well as multidrug-resistant patient-derived MM cells, with IC50 of ∼0.8–3 μmol/L. Conversely, 5-azacytidine was not cytotoxic to peripheral blood mononuclear cells or patient-derived bone marrow stromal cells (BMSC) at these doses. Importantly, 5-azacytidine overcame the survival and growth advantages conferred by exogenous interleukin-6 (IL-6), insulin-like growth factor-I (IGF-I), or by adherence of MM cells to BMSCs. 5-Azacytidine treatment induced DNA double-strand break (DSB) responses, as evidenced by H2AX, Chk2, and p53 phosphorylations, and apoptosis of MM cells. 5-Azacytidine–induced apoptosis was both caspase dependent and independent, with caspase 8 and caspase 9 cleavage; Mcl-1 cleavage; Bax, Puma, and Noxa up-regulation; as well as release of AIF and EndoG from the mitochondria. Finally, we show that 5-azacytidine–induced DNA DSB responses were mediated predominantly by ATR, and that doxorubicin, as well as bortezomib, synergistically enhanced 5-azacytidine–induced MM cell death. Taken together, these data provide the preclinical rationale for the clinical evaluation of 5-azacytidine, alone and in combination with doxorubicin and bortezomib, to improve patient outcome in MM. [Mol Cancer Ther 2007;6(6):1718–27]
Therapeutic effect of CS-706, a specific cyclooxygenase-2 inhibitor, on gallbladder carcinoma in BK5.ErbB-2 mice
Authors: Kiguchi Kaoru , Ruffino Lynnsie , Kawamoto Toru , Franco Eugenia , Kurakata Shin-ichi , Fujiwara Kosaku , Hanai Masaharu , Rumi Mohammad , DiGiovanni John 
Published: June 2007

Abstract
Biliary tract cancer is still challenging to treat and manage due to its poor sensitivity to conventional therapies and the inability to prevent or detect the early tumor formation. The most well known risk factor for gallbladder cancer is the presence of chronic inflammation, usually related to gallstones. It has been suggested that cyclooxygenase-2 (COX-2) plays a variety of roles in the gastrointestinal tract, including pathogenic processes such as neoplasia. Recently, we have generated transgenic mice that overexpress rat ErbB-2 under the control of bovine keratin 5 promoter (BK5.ErbB-2 mice). Homozygous BK5.ErbB-2 mice develop adenocarcinoma of gallbladder with an ∼90% incidence. In addition to the activation of ErbB-2 and epidermal growth factor receptor, mRNA and protein levels of COX-2 were up-regulated in the gallbladder carcinomas that developed in these transgenic mice. The aim of this study was to examine the effects of a COX-2 inhibitor, CS-706, on the development of gallbladder carcinomas using the BK5.ErbB-2 mouse model. Ultrasound image analysis as well as histologic evaluation revealed a significant therapeutic effect of CS-706 on the gallbladder tumors, either as reversion to a milder phenotype or inhibition of tumor progression. The antitumor effect was associated with inhibition of prostaglandin E2 synthesis. CS-706 treatment also down-regulated the activation of ErbB-2 and epidermal growth factor receptor, resulting in decreased levels of phosphorylated Akt and COX-2 in gallbladder cancers of BK5.ErbB-2 mice. Based on our results, targeting COX-2 could provide a potentially new and effective therapy alone or in combination with other therapeutic agents for patients with biliary tract cancer. [Mol Cancer Ther 2007;6(6):1709–17]
Breast cancer cells with acquired antiestrogen resistance are sensitized to cisplatin-induced cell death
Authors: Yde Christina Westmose , Gyrd-Hansen Mads , Lykkesfeldt Anne E. , Issinger Olaf-Georg , Stenvang Jan 
Published: June 2007

Abstract
Antiestrogens are currently used for treating breast cancer patients who have estrogen receptor–positive tumors. However, patients with advanced disease will eventually develop resistance to the drugs. Therefore, compounds effective on antiestrogen-resistant tumors will be of great importance for future breast cancer treatment. In this study, we have investigated the effect of the chemotherapeutic compound cisplatin using a panel of antiestrogen-resistant breast cancer cell lines established from the human breast cancer cell line MCF-7. We show that the antiestrogen-resistant cells are significantly more sensitive to cisplatin-induced cell death than antiestrogen-sensitive MCF-7 cells and we show that cisplatin induces cell death by activating both the caspase and lysosomal death pathways. The antiestrogen-resistant cell lines express lower levels of antiapoptotic Bcl-2 protein compared with parental MCF-7 cells. Our data show that Bcl-2 can protect antiestrogen-resistant breast cancer cells from cisplatin-induced cell death, indicating that the reduced expression of Bcl-2 in the antiestrogen-resistant cells plays a role in sensitizing the cells to cisplatin treatment. [Mol Cancer Ther 2007;6(6): 1869–76]
The role of integrin-linked kinase in melanoma cell migration, invasion, and tumor growth
Authors: Wong Ronald P.C. , Ng Philip , Dedhar Shoukat , Li Gang 
Published: June 2007

Abstract
Melanoma is a life-threatening disease with a high mortality rate due to rapid metastasis. Currently, there is no effective treatment for metastatic melanoma. Integrin-linked kinase (ILK) is a serine/threonine kinase and has its role implicated in connecting cell-extracellular matrix interaction and growth factor signaling to cell survival, cell migration, invasion, anchorage-independent growth, angiogenesis, and epithelial-mesenchymal transition. However, the functional role of ILK in melanoma progression is not completely understood. We have previously shown that strong ILK expression was significantly associated with melanoma thickness. In this study, we further elucidate the role of ILK in melanoma cell migration, invasion, anchorage-independent growth, and tumor growth in vivo by specific ILK knockdown using small interfering RNA and short hairpin RNA. We found that ILK knockdown impeded melanoma cell migration, which was associated with reduced stress fiber formation, cell spreading, and cell adhesion. Furthermore, ILK knockdown decreased the invasion ability of melanoma cells and the formation of anchorage-independent colonies in soft agar. Moreover, ILK knockdown significantly impaired the growth of melanoma xenografts in severe combined immunodeficient mice. This study highlights the importance of ILK in melanoma progression and provides an attractive target for the treatment of melanoma. [Mol Cancer Ther 2007;6(6):1692–1700]
A New Technique for Reconstruction of the Ulnar Collateral Ligament of the Thumb
Authors: Baskies Michael A. , Tuckman David , Paksima Nader , Posner Martin A. 
Published: June 2007

Background Several previous studies have described reconstructive methods for the treatment of an injury to the ulnar collateral ligament of the thumb. However, there are few biomechanical studies to date to analyze the strength of the surgical reconstruction. Purpose To evaluate 2 reconstruction techniques with use of a cadaveric model (1) reconstruction with the use of a free tendon graft placed in a figure-of-8 fashion through drill holes in the metacarpal and proximal phalanx of the thumb, and (2) reconstruction with the use of the Bio-Tenodesis Screw System. Study Design Controlled laboratory study. Methods Eight matched pairs of cadaveric specimens underwent removal of the proper and accessory ulnar collateral ligaments. One of the 2 reconstruction methods was performed, and specimens were mounted on a materials-testing machine. The specimens were subjected to valgus stress to failure at 30° of flexion. Failure was defined as valgus laxity of 30° at the metacarpophalangeal joint. Results The peak load to failure was 23.5 ± 11.4 N for the figure-of-8 reconstruction and 24.3 ± 12.3 N for the reconstruction using the Bio-Tenodesis Screw System. Comparing the 2 groups, there was no statistically significant difference in peak loads to failure (P = .88). Conclusion There was no statistically significant difference between the peak loads to failure of the 2 reconstructions. Clinical Relevance The Bio-Tenodesis Screw System may provide another viable option for surgical reconstruction of the ulnar collateral ligament of the thumb.
Selecting dissimilar genes for multi-class classification, an application in cancer subtyping
Authors: Cai Zhipeng , Goebel Randy , Salavatipour Mohammad R , Lin Guohui 
Published: June 2007

Abstract

Background
Gene expression microarray is a powerful technology for genetic profiling diseases and their associated treatments. Such a process involves a key step of biomarker identification, which are expected to be closely related to the disease. A most important task of these identified genes is that they can be used to construct a classifier which can effectively diagnose disease and even recognize the disease subtypes. Binary classification, for example, diseased or healthy, in microarray data analysis has been successful, while multi-class classification, such as cancer subtyping, remains challenging.

Results
We target on the challenging multi-class classification in microarray data analysis, especially on the cancer subtyping using gene expression microarray. We present a novel class discrimination strength vector to represent individual genes and introduce a new measurement to quantify the class discrimination strength difference between two genes. Such a new distance measure is employed in gene clustering, and subsequently the gene cluster information is exploited to select a set of genes which can be used to construct a sample classifier.
We tested our method on four real cancer microarray datasets each contains multiple subtypes of cancer patients. The experimental results show that the constructed classifiers all achieved a higher classification accuracy than the previously best classification results obtained on these four datasets. Additional tests show that the selected genes by our method are less correlated and they all contribute statistically significantly to the more accurate cancer subtyping.

Conclusion
The proposed novel class discrimination strength vector is a better representation than the gene expression vector, in the sense that it can be used to effectively eliminate highly correlated but redundant genes for classifier construction. Such a method can build a classifier to achieve a higher classification accuracy, which is demonstrated via cancer subtyping.
Utilization of the PICO framework to improve searching PubMed for clinical questions
Authors: Schardt Connie , Adams Martha B , Owens Thomas , Keitz Sheri , Fontelo Paul 
Published: June 2007

Abstract

Background
Supporting 21st century health care and the practice of evidence-based medicine (EBM) requires ubiquitous access to clinical information and to knowledge-based resources to answer clinical questions. Many questions go unanswered, however, due to lack of skills in formulating questions, crafting effective search strategies, and accessing databases to identify best levels of evidence.

Methods
This randomized trial was designed as a pilot study to measure the relevancy of search results using three different interfaces for the PubMed search system. Two of the search interfaces utilized a specific framework called PICO, which was designed to focus clinical questions and to prompt for publication type or type of question asked. The third interface was the standard PubMed interface readily available on the Web. Study subjects were recruited from interns and residents on an inpatient general medicine rotation at an academic medical center in the US. Thirty-one subjects were randomized to one of the three interfaces, given 3 clinical questions, and asked to search PubMed for a set of relevant articles that would provide an answer for each question. The success of the search results was determined by a precision score, which compared the number of relevant or gold standard articles retrieved in a result set to the total number of articles retrieved in that set.

Results
Participants using the PICO templates (Protocol A or Protocol B) had higher precision scores for each question than the participants who used Protocol C, the standard PubMed Web interface. (Question 1: A = 35%, B = 28%, C = 20%; Question 2: A = 5%, B = 6%, C = 4%; Question 3: A = 1%, B = 0%, C = 0%) 95% confidence intervals were calculated for the precision for each question using a lower boundary of zero. However, the 95% confidence limits were overlapping, suggesting no statistical difference between the groups.

Conclusion
Due to the small number of searches for each arm, this pilot study could not demonstrate a statistically significant difference between the search protocols. However there was a trend towards higher precision that needs to be investigated in a larger study to determine if PICO can improve the relevancy of search results.
Replacing the projected retiring baby boomer nursing cohort 2001 – 2026
Authors: Schofield Deborah J 
Published: June 2007

Abstract
Background
The nursing population in Australia is ageing. However, there is little information on the rate and timing of nursing retirement.

Methods
Specifically designed health workforce extracts from the Australian Bureau of Statistics (ABS) censuses from 1986 to 2001 are used to estimate the rate of nursing retirement. The 2001 nursing data are then "aged" and retirement of the nursing workforce projected through to 2026. ABS population projections are used to examine the future age structure of the population and the growth and age distribution of the pool of labour from which future nurses will be drawn.

Results
Attrition rates for nurses aged 45 and over are projected to be significantly higher between the base year of 2006 and 2026, than they were between 1986 and 2001 (p < 0.001).
Between 2006 and 2026 the growth in the labour force aged 20 to 64 is projected to slow from 7.5 per cent every five years to about 2 per cent, and over half of that growth will be in the 50 to 64 year age group. Over this period Australia is projected to lose almost 60 per cent of the current nursing workforce to retirement, an average of 14 per cent of the nursing workforce every five years and a total of about 90,000 nurses.

Conclusion
The next 20 years will see a large number of nursing vacancies due to retirement, with ageing already impacting on the structure of the nursing workforce. Retirement income policies are likely to be a key driver in the retirement rate of nurses, with some recent changes in Australia having some potential to slow retirement of nurses before the age of 60 years. However, if current trends continue, Australia can expect to have substantially fewer nurses than it needs in 2026.
Role of CD151, A tetraspanin, in porcine reproductive and respiratory syndrome virus infection
Authors: Shanmukhappa Kumar , Kim Jeong-Ki , Kapil Sanjay 
Published: June 2007

AbstractBackgroundPorcine reproductive and respiratory syndrome virus (PRRSV) is a RNA virus causing respiratory and reproductive diseases in swine. The susceptibility for PRRSV varies between the different breeds of swine. In cell culture, PRRSV virus can be propagated in primary porcine alveolar macrophages and some African green monkey kidney cell lines, such as MARC-145 cells. Previous studies have shown that 3' untranslated region (UTR) RNAs of the arteriviruses play an important role in the replication of the virus through interactions with cellular proteins. To better understand the differences in the replication capability of PRRSV in different cell lines, we sought to identify the host cellular proteins interacting with PRRSV 3' UTR RNA. We constructed a cDNA library of MARC-145 cell line in lambda ZAP Express vector and screened the library with the positive sense 3' UTR RNA of PRRSV.ResultsWe found that CD151, a host cellular protein, interacting with PRRSV 3' UTR RNA. The specificity of the interaction between CD151 and PRRSV 3' UTR RNA was examined by gel shift assay as well as North-Western hybridization. The transfection of CD151 expression clone into BHK-21 rendered these cells susceptible to PRRSV infection, and the transfection of siRNA against CD151 into MARC-145 significantly reduced the level of PRRSV infection. Also, anti-CD151 antibody treatment to MARC-145 completely blocked PRRSV infection.ConclusionBased on our results, we suggest that CD151 should cooperate in PRRSV infectionin vitroin MARC-145 and BHK-21 cells.
An oestrogen-dependent model of breast cancer created by transformation of normal human mammary epithelial cells
Authors: Duss Stephan , André Sylvie , Nicoulaz Anne-Laure , Fiche Maryse , Bonnefoi Hervé , Brisken Cathrin , Iggo Richard D 
Published: June 2007

Abstract
Introduction
About 70% of breast cancers express oestrogen receptor α (ESR1/ERα) and are oestrogen-dependent for growth. In contrast with the highly proliferative nature of ERα-positive tumour cells, ERα-positive cells in normal breast tissue rarely proliferate. Because ERα expression is rapidly lost when normal human mammary epithelial cells (HMECs) are grown in vitro, breast cancer models derived from HMECs are ERα-negative. Currently only tumour cell lines are available to model ERα-positive disease. To create an ERα-positive breast cancer model, we have forced normal HMECs derived from reduction mammoplasty tissue to express ERα in combination with other relevant breast cancer genes.

Methods
Candidate genes were selected based on breast cancer microarray data and cloned into lentiviral vectors. Primary HMECs prepared from reduction mammoplasty tissue were infected with lentiviral particles. Infected HMECs were characterised by Western blotting, immunofluorescence microscopy, microarray analysis, growth curves, karyotyping and SNP chip analysis. The tumorigenicity of the modified HMECs was tested after orthotopic injection into the inguinal mammary glands of NOD/SCID mice. Cells were marked with a fluorescent protein to allow visualisation in the fat pad. The growth of the graft was analysed by fluorescence microscopy of the mammary glands and pathological analysis of stained tissue sections. Oestrogen dependence of tumour growth was assessed by treatment with the oestrogen antagonist fulvestrant.

Results
Microarray analysis of ERα-positive tumours reveals that they commonly overexpress the Polycomb-group gene BMI1. Lentiviral transduction with ERα, BMI1, TERT and MYC allows primary HMECs to be expanded in vitro in an oestrogen-dependent manner. Orthotopic xenografting of these cells into the mammary glands of NOD/SCID mice results in the formation of ERα-positive tumours that metastasise to multiple organs. The cells remain wild type for TP53, diploid and genetically stable. In vivo tumour growth and in vitro proliferation of cells explanted from tumours are dependent on oestrogen.

Conclusion
We have created a genetically defined model of ERα-positive human breast cancer based on normal HMECs that has the potential to model human oestrogen-dependent breast cancer in a mouse and enables the study of mechanisms involved in tumorigenesis and metastasis.