bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined In vivo Effect of A12, a Type 1 Insulin-Like Growth Factor Receptor Antibody, and Docetaxel against Prostate Cancer Tumors
Authors: Wu Jennifer D. , Haugk Kathy , Coleman Ilsa , Woodke Lillie , Vessella Robert , Nelson Peter , Montgomery R. Bruce , Ludwig Dale L. , Plymate Stephen R. 
Published: October 2006

Abstract
Purpose: A human type 1 insulin-like growth factor receptor antibody (A12) has been shown to effectively inhibit human xenograft tumor growth, including androgen-dependent and androgen-independent prostate tumors. Docetaxel, either as a single agent or combined with others, has shown a survival benefit in prostate cancer patients. Based on these data, we investigated the combined in vivo effect of A12 and docetaxel on human androgen-independent and osseous prostate tumor growth.
Experimental Design: To study human androgen-independent prostate cancer model, LuCaP35V tumors were implanted s.c. into castrated severe combined immunodeficient mice. When tumors reached about 100 mm3, animals were treated with vehicle control docetaxel (10 or 20 mg/kg) and docetaxel in combination with A12 (40 μg/kg) for 4 weeks. To study human osseous prostate cancer model, LuCaP 23.1 tumors were implanted intratibiae. When serum prostate-specific antigen reached 5 to 10 ng/mL, treatments were initiated.
Results: A12 markedly augmented the inhibition of docetaxel on tumor growth. When docetaxel is combined with A12, the inhibition of tumor growth continued after treatment cessation, which was associated with continued apoptosis and decreased proliferation of tumor cells. Gene expression profiles indicated that the posttreatment suppression of tumor growth may be due to enhanced negative regulation of cell cycle progression– and/or cell survival–associated genes, some of which have been shown to induce resistance to docetaxel.
Conclusions: Our findings suggest that targeting type 1 insulin-like growth factor receptor can enhance the therapeutic effect of docetaxel on advanced prostate cancer. Our findings also suggest a potential mechanism to improve the treatment efficacy of docetaxel in prostate cancer.
Multistate Analysis of Skeletal Events in Patients with Bone Metastases
Authors: Cook Richard J. , Major Pierre 
Published: October 2006

Abstract
Cancer patients with bone metastases are at increased risk of experiencing skeletal events associated with severe morbidity. Clinical trials of palliative therapies must perform rigorous and robust evaluation of new treatments on the basis of meaningful summaries of the course of skeletal events over time, while dealing with potentially high mortality rates during observation. The purpose of this article is to present a multistate model that can be easily used to reflect possible courses of the disease process, indicate how simple methods of analysis can be used to estimate clinically relevant features of the process, and contrast this approach with some of the alternative methods. The relation between the multistate approach and previously used methods is highlighted.
Biology of Bone Cancer Pain
Authors: Goblirsch Michael J. , Zwolak Pawel P. , Clohisy Denis R. 
Published: October 2006

Abstract
Bone cancer pain is a devastating manifestation of metastatic cancer. Unfortunately, current therapies can be ineffective, and when they are effective, the duration of the patient's survival typically exceeds the duration of pain relief. New, mechanistically based therapies are desperately needed. Study of experimental animal models has provided insight into the mechanisms that drive bone cancer pain and provides an opportunity for developing targeted therapies. Mechanisms that drive bone cancer pain include tumor-directed osteoclast-mediated osteolysis, tumor cells themselves, tumor-induced nerve injury, stimulation of transient receptor potential vanilloid type 1 ion channel, endothelin A, and host cell production of nerve growth factor. Current and future therapies include external beam radiation, osteoclast-targeted inhibiting agents, anti-inflammatory drugs, transient receptor potential vanilloid type 1 antagonists, and antibody therapies that target nerve growth factor or tumor angiogenesis. It is likely that a combination of these therapies will be superior to any one therapy alone.
Treatment-Related Osteoporosis in Men with Prostate Cancer
Authors: Smith Matthew R. 
Published: October 2006

Abstract
The intended therapeutic effect of gonadotropin-releasing hormone (GnRH) agonists is hypogonadism, a major cause of acquired osteoporosis in men. Consistent with this observation, GnRH agonists increase bone turnover and decrease bone mineral density, a surrogate for fracture risk. Large claims-based analyses and other retrospective studies provide compelling evidence that GnRH agonists increase risk of clinical fractures. Estrogens play a central role in homeostasis of the normal male skeleton, and estrogen deficiency rather than testosterone deficiency seems to be primarily responsible for the adverse skeletal effects of GnRH agonists. In randomized controlled trials, bisphosphonates (pamidronate and zoledronic acid) and selective estrogen receptor modulators (raloxifene and toremifene) increased bone mineral density in GnRH agonist–treated men. Two ongoing large randomized placebo-controlled studies will prospectively define fracture outcomes in men with prostate cancer and assess the efficacy of novel pharmacologic interventions (AMG162, toremifene) during GnRH agonist treatment.
The Measurement of Pain from Metastatic Bone Disease: Capturing the Patient's Experience
Authors: Cleeland Charles S. 
Published: October 2006

Abstract
Pain is prevalent for large numbers of patients with metastatic cancer, and this pain is often due to bone metastases. Despite the availability of effective pain treatments and various pain management guidelines, multiple studies document the undertreatment of pain in patients with cancer. The most frequently identified barriers to appropriate pain management are physician underestimation of the patient's pain, inadequate pain assessment, and patient reluctance to report pain. A first step toward reducing inadequate pain control in clinical practice is adequate assessment of cancer pain using validated pain measurement instruments. Using treatment for bone pain as an example, we discuss how patient satisfaction measures and self-report measures of pain and other symptoms, symptom interference with patient function, and related adverse effects can be combined with appropriate trial design to provide the information needed to choose the best possible treatment for bone pain. Symptom assessment needs to be done via standardized questionnaires, administered at appropriate times during the trial. The Brief Pain Inventory uses 11-point numerical rating scales to measure both pain severity and the resulting functional interference caused by pain. These severity and interference ratings can be further categorized as mild, moderate, or severe, as required to implement most pain management guidelines and define outcome expectations for clinical trials. Consistent pain measurement and standardized recording of analgesic use across clinical trials would enhance comparability and increase the chances that treatment decisions for management of bone pain could be evidence based. These and other considerations in the design of clinical trials are discussed.
Gene Expression Signatures Differentiate Ovarian/Peritoneal Serous Carcinoma from Diffuse Malignant Peritoneal Mesothelioma
Authors: Davidson Ben , Zhang Zhen , Kleinberg Lilach , Li Mei , Flørenes Vivi Ann , Wang Tian-Li , Shih Ie-Ming 
Published: October 2006

Abstract
Purpose: Ovarian/primary peritoneal serous carcinoma (OC/PPC) and diffuse peritoneal malignant mesothelioma (DMPM) are highly aggressive tumors that are closely related morphologically and histogenetically. It remains unclear whether both tumors are molecularly distinct neoplasms. The current study compared global gene expression patterns in OC/PPC and DMPM.
Experimental Design: Ten OC/PPC and five DMPM effusions were analyzed for gene expression profiles using the Affymetrix U133 Plus 2 arrays and the dCHIP analysis program. Differentially expressed candidate genes were validated using quantitative real-time PCR and immunohistochemistry.
Results: Unsupervised hierarchical clustering using all 54,675 genes in the array classified the samples into two groups: DMPM specimens versus OC/PPC specimens. A total of 189 genes that were differentially expressed in these two groups were selected based on statistical significance. Genes overexpressed in DMPM (n = 68) included calretinin, vitronectin, claudin 15, α4 laminin, hyaluronan synthase 1, cadherin 11, RAB7, v-maf, and the epidermal growth factor–containing fibulin-like extracellular matrix protein 1. Genes overexpressed in OC/PPC (n = 121) included insulin-like growth factor II (IGF-II); IGF-II binding protein 3; cyclin E1; folate receptors 1 and 3; RAB25; MUC4; endothelin-1; CD24; kallikreins 6, 7, and 8; claudins 3, 4, and 6; Notch3; and MMP-7. Quantitative real-time PCR validated the differential expression of 13 genes, and immunohistochemistry confirmed the differences for four gene products.
Conclusions: Expression profiling separates OC/PPC from DMPM and identifies a number of genes that are differentially expressed in these tumors. The molecular signatures unique to OC/PPC and DMPM should provide a molecular basis to study both tumors and new potential markers for facilitating their differential diagnosis.
Hepatoma-Derived Growth Factor Is a Novel Prognostic Factor for Patients with Pancreatic Cancer
Authors: Uyama Hirokazu , Tomita Yasuhiko , Nakamura Hideji , Nakamori Shoji , Zhang Binglin , Hoshida Yoshihiko , Enomoto Hirayuki , Okuda Yorihide , Sakon Masato , Aozasa Katsuyuki , Kawase Ichiro , Hayashi Norio , Monden Morito 
Published: October 2006

Abstract
Purpose: Hepatoma-derived growth factor (HDGF) is a nucleus-targeted growth factor playing an important role in the development and progression of cancers. This study investigated the correlation of HDGF expression and prognosis in patients with pancreatic ductal carcinoma.
Patients and Methods: HDGF expression in pancreatic cancer cell lines was analyzed by Western blotting. HDGF expression was analyzed by immunohistochemistry for 50 patients with primary ductal carcinoma of the pancreas (33 male and 17 female) ranging in age from 48 to 80 years (median, 65 years) receiving surgical treatment. Cancer cells showing stronger staining than the noncancerous ducts were regarded as positive. Cases showing positive staining in &lt;90% and &gt;90% of tumor cells were regarded as HDGF labeling index (LI) levels 1 and 2, respectively. HDGF LI was determined separately for the nucleus and the cytoplasm.
Results: Western blotting showed HDGF expression in pancreatic cancer cells similar to that of hepatic cell lines. Twenty-three (46%) and 27 (54%) cases and 22 (44%) and 28 (56%) cases showed HDGF LI levels 1 and 2 for the nucleus and the cytoplasm, respectively. Patients with nuclear HDGF LI level 1 showed a significantly better 5-year survival rate (37.0%) than those with level 2 (6.8%; P = 0.023). No significant difference was observed in the cytoplasmic HDGF LI classification. Multivariate analysis revealed nuclear HDGF LI to be an independent prognosticator.
Conclusions: These findings suggest that HDGF could be a novel prognostic factor for pancreatic ductal carcinoma.
Future Treatment of Bone Metastases
Authors: Lipton Allan 
Published: October 2006

Abstract
All bone surfaces are periodically remodeled by the coupled and balanced action of osteoclasts and osteoblasts, of which the activities are regulated by a variety of cytokines and growth factors. Patients with cancer metastatic to the skeleton often develop osteolytic bone lesions, in which the actions of osteoclasts and osteoblasts remain coupled, but become imbalanced in sites adjacent to the tumor. The result is net bone loss. Many cancers secrete osteoclast-stimulating cytokines, which increase bone resorption by osteoclasts. In turn, factors released from the bone matrix during osteolysis can stimulate tumor growth. In this so-called “vicious cycle,” there are multiple sites that are targets for new bone-directed therapies. A variety of new agents for the treatment and prevention of osteolytic bone metastasis are currently being developed. These include new agents that inhibit osteoclast differentiation, bone adhesion, and osteoclast function. These new strategies have evolved from a better understanding of the interaction between tumor cells and cells in the bone marrow microenvironment. There is great promise that these new bone-targeted therapies can decrease the frequent skeletal-related events that greatly diminish quality of life of patients with bone metastases.
PIK3CA and PTEN Mutations in Uterine Endometrioid Carcinoma and Complex Atypical Hyperplasia
Authors: Hayes Monica Prasad , Wang Hong , Espinal-Witter Rosanny , Douglas Wayne , Solomon Garron J. , Baker Suzanne J. , Ellenson Lora Hedrick 
Published: October 2006

Abstract
Purpose: The tumor suppressor PTEN gene and the PIK3CA oncogene are frequently mutated in uterine endometrioid carcinoma (UEC). PTEN mutations are also common in complex atypical hyperplasia (CAH), the precursor lesion of UEC. The status of PIK3CA has not yet been explored in CAH. In this study, we evaluated both CAH and UEC for PTEN and PIK3CA mutations.
Experimental Design: Neoplastic tissue was microdissected, and DNA was extracted from 29 cases of CAH. DNA was available from 44 UEC cases previously characterized for PTEN mutations. Direct DNA sequencing of exons 9 and 20 of the PIK3CA gene was done on all 73 cases. In addition, CAH cases were analyzed for PTEN mutations. Statistical analyses were done using the Fisher's exact test.
Results: Two (7%) of 29 CAH and 17 (39%) of 44 UEC cases contained a PIK3CA mutation (P = 0.003). Fourteen (48%) of 29 CAH cases had a PTEN mutation, but none contained both a PTEN and PIK3CA mutation. Twenty-five (57%) of 44 UEC cases had a PTEN mutation, and 12 (48%) of these 25 cases also contained a PIK3CA mutation. Coexistent PIK3CA and PTEN mutations were significantly correlated with UEC compared with CAH (P = 0.002), but the association in UEC did not reach statistical significance (P = 0.21).
Conclusions: PIK3CA is the most commonly mutated oncogene in UEC; however, mutations are uncommon in CAH. Thus, mutations in PIK3CA, unlike PTEN mutations, are associated with invasion. These findings suggest that mutations in PIK3CA may serve as a marker of invasion with potential clinical use. Furthermore, PIK3CA and PTEN mutations may play distinct roles in endometrial tumorigenesis.
An investigation of extreme silver enrichment at tennantite surfaces exposed to alkaline solutions: an XPS-based study
Authors: Hobson E. L. , Wincott P. , Vaughan D. J. , Pattrick R. A. D. 
Published: October 2006

AbstractExtreme silver enrichment at the surface of the complex sulphide, tennantite (ideal formula: Cu12As4S13), occurs following exposure to alkaline solutions, and involves the development of an Ag-rich sulphide surface species. The tennantite has a low bulk Ag content of 0.3 at.%, and a percentage surface enrichment of Ag is thirty-six times that of the bulk. The techniques of X-ray photoelectron spectroscopy (XPS) and reflection extended X-ray absorption fine structure spectroscopy show the new phase to be a Ag sulphide species compositionally similar to cupriferous proustite ((Cu,Ag)3AsS3). Solution experiments and XPS depth profiling show that the surface is most depleted in Cu and Zn, and enriched in Ag compared to the bulk tennantite. Selective dissolution and reprecipitation at the tennantite surface cannot explain the enrichment of Ag relative to the bulk. Migration must have occurred and could have been driven by the leaching out of Cu which produces a metal-depleted surface, coupled to the relative incompatibility of Ag in the tennantite lattice. To account for the extreme enrichment at the surface, Ag must have diffused from depths of up to 9 nm, probably via structural weaknesses and vacancies in the tennantite lattice.
Swiss residents' speciality choices – impact of gender, personality traits, career motivation and life goals
Authors: Buddeberg-Fischer Barbara , Klaghofer Richard , Abel Thomas , Buddeberg Claus 
Published: October 2006

AbstractBackgroundThe medical specialities chosen by doctors for their careers play an important part in the development of health-care services. This study aimed to investigate the influence of gender, personality traits, career motivation and life goal aspirations on the choice of medical speciality.MethodsAs part of a prospective cohort study of Swiss medical school graduates on career development, 522 fourth-year residents were asked in what speciality they wanted to qualify. They also assessed their career motivation and life goal aspirations. Data concerning personality traits such as sense of coherence, self-esteem, and gender role orientation were collected at the first assessment, four years earlier, in their final year of medical school. Data analyses were conducted by univariate and multivariate analyses of variance and covariance.ResultsIn their fourth year of residency 439 (84.1%) participants had made their speciality choice. Of these, 45 (8.6%) subjects aspired to primary care, 126 (24.1%) to internal medicine, 68 (13.0%) to surgical specialities, 31 (5.9%) to gynaecology & obstetrics (G&O), 40 (7.7%) to anaesthesiology/intensive care, 44 (8.4%) to paediatrics, 25 (4.8%) to psychiatry and 60 (11.5%) to other specialities. Female residents tended to choose G&O, paediatrics, and anaesthesiology, males more often surgical specialities; the other specialities did not show gender-relevant differences of frequency distribution. Gender had the strongest significant influence on speciality choice, followed by career motivation, personality traits, and life goals. Multivariate analyses of covariance indicated that career motivation and life goals mediated the influence of personality on career choice. Personality traits were no longer significant after controlling for career motivation and life goals as covariates. The effect of gender remained significant after controlling for personality traits, career motivation and life goals.ConclusionGender had the greatest impact on speciality and career choice, but there were also two other relevant influencing factors, namely career motivation and life goals. Senior physicians mentoring junior physicians should pay special attention to these aspects. Motivational guidance throughout medical training should not only focus on the professional career but also consider the personal life goals of those being mentored.
Immunological consequences of using three different clinical/laboratory techniques of emulsifying peptide-based vaccines in incomplete Freund's adjuvant
Authors: Koh Yi T , Higgins Sean A , Weber Jeffrey S , Kast W Martin 
Published: October 2006

Abstract
Incomplete Freund's adjuvant (IFA) serves as a carrier for water-in-oil emulsion (W/O) vaccines. The stability of such emulsions greatly affects vaccine safety and efficacy since continued presence of antigen depots at lymphoid organs releasing low-level antigens is known to stimulate a potent immune response and high-level systemic release of antigens can lead to tolerance. W/O emulsions for the purpose of clinical and laboratory peptide-based vaccinations have been prepared using the techniques of syringe extrusion, vortex or high-speed homogenization. There is no consensus in the field over which technique would be best to use and no immunological data are available that compare the three techniques. In this study, we compared the immune responses induced by a peptide-based vaccine prepared using vortex, syringe-extrusion and homogenization. The vaccination led to tumor rejection by mice vaccinated with the peptide-based vaccine prepared using all three techniques. The immunological data from the in vivo cytotoxicity assay showed a trend for lower responses and a higher variability and greater range in the immune responses induced by a vaccine that was emulsified by the vortex or homogenizer techniques as compared to the syringe-extrusion technique. There were statistically significant lower numbers of IFNγ-secreting cells induced when the mice were vaccinated with a peptide-based vaccine emulsion prepared using the vortex compared to the syringe-extrusion technique. At a suboptimal vaccine dose, the mice vaccinated with a peptide-based vaccine emulsion prepared using the vortex technique had the largest tumors compared to the syringe-extrusion or the homogenizer technique. In the setting of a busy pharmacy that prepares peptide-based vaccine emulsions for clinical studies, the vortex technique can still be used but we urge investigators to take special care in their choice of mixing vessels for the vortex technique as that can influence the stability of the emulsion. However, in instances where the optimal dose is unknown, we caution investigators against using the vortex technique to prepare the peptide-based vaccine emulsions. Overall, we report that all three techniques can be used to prepare peptide-based vaccine emulsions under optimal dose conditions and we discuss important details regarding the proper preparation of the emulsions.
Factors masking HMGB1 in human serum and plasma
Authors: Urbonaviciute Vilma , Fürnrohr Barbara G , Weber Christian , Haslbeck Martin , Wilhelm Sabine , Herrmann Martin , Voll Reinhard E 
Published: October 2006

AbstractHigh mobility group box 1 protein (HMGB1) is a ubiquitously expressed architectural chromosomal protein. Recently, it has become obvious that HMGB1 can also act as a proinflammatory mediator when actively secreted during cell activation or passively released from necrotic cells. HMGB1 appears to play an important role in the pathogenesis of diseases, including sepsis and rheumatoid arthritis. However, easy, sensitive, and reliable detection systems are required to investigate the clinical significance of HMGB1 in clinical samples for diagnosis and prognosis of diseases. Here, we describe sensitive ELISAs for the detection of HMGB1 in cell culture medium and cell lysates. However, these assays failed to reliably quantitate HMGB1 in serum and plasma when compared with immunoblot analysis. We found that serum/plasma components bind to HMGB1 and interfere with its detection by ELISA systems. In most serum/plasma samples investigated, including those from healthy individuals, we detected IgG antibodies binding to HMGB1. The titers of these antibodies correlated with the capacity of sera to interfere with the detection of recombinant HMGB1 by ELISA. Furthermore, HMGB1 coimmunoprecipitated with several proteins including IgG1, as identified by mass spectrometry. These HMGB1 interacting proteins are currently characterized and may contribute to complex formation, masking, and possibly, modulation of cytokine activity of HMGB1.
Correlation between micro‐otoscopy, micropneumatoscopy and otoadmittance tympanometry
Authors: Buckinghamy R. A. , Farag A. Z. , Patel M. G. , Geick M. R. 
Published: October 2006

AbstractThe micro‐otoscopic, audiometric and tympanometric findings were correlated in 204 ears seen in a Veterans Administration Hospital ear clinic. Otoscopy, audiometry and tympanometry were done during the same clinical visits. In most cases pneumo‐otoscopy with the microscope also was performed. Because we were unable to standardize pressures, we found pneumo‐otoscopy of limited value.