bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optical coherence tomography of chorioretinal and choroidal folds
Authors: Giuffrè Giuseppe , Distefano Mauro G. 
Published: October 2006

Abstract.Purpose:  To report the optical coherence tomography (OCT) findings in cases of chorioretinal and choroidal folds.Methods:  Eight subjects with folds of the fundus of the eye were examined with fundus photography, fluorescein angiography, B‐scan ultrasonography and Stratus OCT.Results:  Two types patterns were found on OCT. Five cases showed undulating retinal as well as retinal pigment epithelial lines of normal thickness; these were defined as chorioretinal folds. The posterior vitreous surface often adhered to the crests of the folds only. Three cases exhibited a wavy appearance of the retinal pigment epithelium and a flat retinal surface; these were classified as choroidal folds.Conclusions:  Scanning by OCT can differentiate chorioretinal folds from choroidal folds and reveal the relationships between the folds and the posterior vitreous surface.
Movement patterns of the invasive signal crayfish determined by PIT telemetry
Authors: Bubb Damian H. , Thom Timothy J. , Lucas Martyn C. 
Published: October 2006

In one of the first field studies to utilize passive integrated transponder (PIT) telemetry to study space use of invertebrates, movement of the introduced signal crayfish ( Pacifastacus leniusculus (Dana, 1852)) was examined intensively in a high-density population in an upland river in northern England from 18 August to 6 September 2004. Crayfish (carapace length 21.0–67.3 mm) were tracked with externally attached PIT tags, enabling remote detection of tagged crayfish by the use of a portable detector. Of the 406 crayfish tagged, 356 (87.7%) were subsequently relocated at least once. The majority of crayfish remained close to the release location (median distance between release and final locations 36.3 m; 25th percentile 10.4 m, 75th percentile 91.6 m). However, movements of up to 345 m were recorded. There was no relationship between sex or size and distance moved. A small waterfall, upstream of the release location, appeared to form a barrier preventing movements of tagged crayfish upstream past it during the study period. PIT telemetry can provide an effective method for detailed recording of space use compared with standard mark–recapture or radiotelemetry methods.
Pharmacokinetics and Toxicity of Weekly Docetaxel in Older Patients
Authors: Hurria Arti , Fleming Mark T. , Baker Sharyn D. , Kelly Wm. Kevin , Cutchall Katie , Panageas Katherine , Caravelli James , Yeung Henry , Kris Mark G. , Gomez Jorge , Miller Vincent A. , D'Andrea Gabriella , Scher Howard I. , Norton Larry , Hudis Clifford 
Published: October 2006

Abstract
Purpose: To evaluate the pharmacokinetics of weekly docetaxel in a cohort of older patients with metastatic cancer and to explore the relationship of pharmacokinetic variables, Erythromycin Breath Test results, age, geriatric assessment variables, and toxicity to therapy.
Experimental Design: Twenty patients ages ≥65 years with metastatic breast, prostate, or lung cancer entered an Institutional Review Board–approved protocol to evaluate the pharmacokinetics of weekly docetaxel administered at 35 mg/m2 i.v. for 3 weeks followed by a 1-week break. The Erythromycin Breath Test and geriatric assessment were done before the first dose. Blood samples were collected for pharmacokinetic analysis with the first dose of docetaxel.
Results: Of the 20 patients who entered the study, 19 were evaluable. There were no age-related differences in the pharmacokinetics of weekly docetaxel. Fifty-eight percent (11 of 19) experienced grade ≥3 toxicity: 16% (3 of 19) grade ≥3 hematologic toxicity, and 53% (10 of 19) grade ≥3 nonhematologic toxicity. There was an association between the Erythromycin Breath Test results and docetaxel pharmacokinetic variables; however, there was no association between Erythromycin Breath Test results or docetaxel pharmacokinetics with frequency of grade ≥3 toxicity.
Conclusions: Despite no statistically significant age-related differences in weekly docetaxel pharmacokinetics, over half of these older patients experienced a grade ≥3 toxicity at the 35 mg/m2 starting dose. We advocate a starting dose of 26 mg/m2 on this weekly schedule and dose escalating if no toxicity.
Prognostic Value of Prostate Secretory Protein of 94 Amino Acids and its Binding Protein after Radical Prostatectomy
Authors: Reeves Jonathan R. , Dulude Hélène , Panchal Chandra , Daigneault Luc , Ramnani Dharam M. 
Published: October 2006

Abstract
Purpose: To establish the prognostic value of total and free prostate secretory protein of 94 amino acids (PSP94) and the PSP94-binding protein (PSPBP) following radical prostatectomy.
Experimental Design: One hundred and eighty-five serum samples were obtained from patients with localized prostate cancer prior to treatment with radical prostatectomy at Virginia Urology (Richmond, VA). Patients were followed up for a median of 48 months (range, 1-66 months) and biochemical relapse was indicated as total prostate-specific antigen (tPSA) levels increasing to &gt;0.1 ng/mL. The available clinical variables included initial tPSA, Gleason score, surgical margin status, and clinical stage. Total PSP94, free PSP94, and the PSPBP were quantified in the pretreatment serum using new ELISA tests (Medicorp, Inc. and Ambrilia Biopharma, Inc., Montreal, Quebec, Canada). Univariate and multivariate Cox proportional hazards models were used to assess the ability of PSP94 and PSPBP to predict time to recurrence.
Results: Thirty-one patients had biochemical recurrence. Gleason score, margin status, clinical stage, and initial tPSA significantly predicted recurrence risk (all P &lt; 0.001). In addition, PSPBP was negatively associated with recurrence risk (P = 0.005), and, consistent with previous studies, the bound/free PSP94 ratio was positively associated with recurrence risk (P = 0.008). Multivariate analysis showed that PSPBP, as well as the bound/free PSP94 ratio, were independent predictors of biochemical relapse risk adjusting for tPSA, Gleason score, and margin status.
Conclusions: Bound/free PSP94 and PSPBP are novel and independent prognostic markers following radical prostatectomy for prostate cancer.
A Homeobox Protein, Prox1, Is Involved in the Differentiation, Proliferation, and Prognosis in Hepatocellular Carcinoma
Authors: Shimoda Masayuki , Takahashi Meiko , Yoshimoto Takanobu , Kono Tomoya , Ikai Iwao , Kubo Hajime 
Published: October 2006

Abstract
Purpose: It has been shown that a lymphatic differentiation master gene, prox1, also plays an essential role in fetal hepatocyte migration. Its expression is detected in embryonic hepatoblasts and in adult hepatocytes. Hepatoma cells are similar to embryonic hepatoblasts to a certain extent because they both proliferate and invade the surrounding tissue. To address the possibility that Prox1 may be involved in the tumorigenesis of hepatocellular carcinoma (HCC), human clinical samples were analyzed.
Experimental Design: To screen prox1 as a potential tumor suppressor gene, its expression was analyzed in HCC cell lines and in human HCC tissues. Its growth-conferring abilities were assessed by transiently overexpressing Prox1 in HCC cell lines and by knocking down its expression by RNA interference.
Results: We found that there was a significant correlation between Prox1 expression and the differentiation scores of the tumors. Subsequently, we also showed that low expression of Prox1 in tumors was closely associated with a poor prognosis. The specific knockdown of Prox1 by RNA interference strongly accelerated in vitro cell growth, whereas the overexpression of Prox1 greatly suppressed the growth.
Conclusions: Our results suggest that Prox1 is involved in the differentiation and progression of HCC, and thus it may be a candidate for the development of novel diagnostic and therapeutic strategies for HCC.
GROα Is Highly Expressed in Adenocarcinoma of the Colon and Down-Regulates Fibulin-1
Authors: Wen Yu , Giardina Sarah F. , Hamming David , Greenman Jennifer , Zachariah Emmanuel , Bacolod Manny D. , Liu Hao , Shia Jinru , Amenta Peter S. , Barany Francis , Paty Phillip , Gerald William , Notterman Daniel 
Published: October 2006

AbstractPurpose: The growth-related oncogene α (GROα) is a secreted interleukin-like molecule that interacts with the CXCR2 G-protein–coupled receptor. We found that the mRNA and protein products of GROα are more highly expressed in neoplastic than normal colon epithelium, and we studied potential mechanisms by which GROα may contribute to tumor initiation or growth.Experimental Design: Cell lines that constitutively overexpress GROα were tested for growth rate, focus formation, and tumor formation in a xenograft model. GROα expression was determined by Affymetrix GeneChip (241 microdissected colon samples), real-time PCR (n = 32), and immunohistochemistry. Primary colon cancer samples were also employed to determine copy number changes and loss of heterozygosity related to the GROα and fibulin-1 genes.Results: In cell cultures, GROα transfection transformed NIH 3T3 cells, whereas inhibition of GROα by inhibitory RNA was associated with apoptosis, decreased growth rate, and marked up-regulation of the matrix protein fibulin-1. Forced expression of GROα was associated with decreased expression of fibulin-1. Expression of GROα mRNA was higher in primary adenocarcinomas (n = 132), adenomas (n = 32), and metastases (n = 52) than in normal colon epithelium (P &lt; 0.001). These results were confirmed by real-time PCR and by immunohistochemistry. Samples of primary and metastatic colon cancer showed underexpression of fibulin-1 when compared with normal samples. There were no consistent changes in gene copy number of GROα or fibulin-1, implying a transcriptional basis for these findings.Conclusion: Elevated expression of GROα is frequent in adenocarcinoma of the colon and is associated with down-regulation of the matrix protein fibulin-1 in experimental models and in clinical samples. GROα overexpression abrogates contact inhibition in cell culture models, whereas inhibition of GROα expression is associated with apoptosis. Importantly, coexpression of fibulin-1 with GROα abrogates key aspects of the transformed phenotype, including tumor formation in a murine xenograft model. Targeting GRO proteins may provide new opportunities for treatment of colon cancer.
Gene Therapy Using Adenovirus-Mediated Full-length Anti-HER-2 Antibody for HER-2 Overexpression Cancers
Authors: Jiang Minghong , Shi Wenfang , Zhang Qi , Wang Xinhua , Guo Minggao , Cui Zhenfu , Su Changqin , Yang Qing , Li Yuemin , Sham Jonathan , Liu Xinyuan , Wu Mengchao , Qian Qijun 
Published: October 2006

Abstract
Purpose: Therapeutic monoclonal antibody is increasingly applied in many clinical applications, although complicated technologies and high cost still limit their wide applications. To obtain the sustained serum antibody concentration with one single injection and lower the cost of antibody protein therapy, an adenovirus-mediated full-length antibody gene therapy was developed.
Experimental Design: Full-length antibody light-chain and heavy-chain sequences were linked with internal ribosome entry site and constructed into adenoviral vector under the control of cytomegalovirus promoter. Antibody expression in vitro and in vivo were tested with ELISA, and its antitumor efficacy was evaluated in SKOV-3-inoculated nude mice.
Results: Ad5-TAb–generated anti-HER-2 antibody presented the similar binding specificity with commercial trastuzumab. A single i.v. injection of 2 × 109 plaque-forming units of Ad5-TAb per mouse resulted in not only a sustained over 40 μg/mL serum antibody level for at least 4 weeks but also significant tumor elimination in the ovarian cancer SKOV-3-inoculated nude mice.
Conclusions: An in vivo full-length antibody gene delivery system allows continuous production of a full-length antibody at high concentration after a single administration. Bioactive antibody macromolecules can be generated via gene transfer in vivo. All the data suggest that this novel adenovirus-mediated antibody gene delivery can be used for the exploitation of antibodies, without being hampered by the sophisticated antibody manufacture techniques and high cost, and, furthermore, can shorten the duration and reduce the expense of antibody developments.
Breast Cancer: Bisphosphonate Therapy for Metastatic Bone Disease
Authors: Body Jean-Jacques 
Published: October 2006

Abstract
The indications of bisphosphonate therapy in breast cancer patients go from the correction of hypercalcemia to the prevention of cancer treatment-induced bone loss. Bisphosphonates are part of our therapeutic armamentarium against metastatic bone pain, and at least 50% of the patients benefit from a clinically relevant analgesic effect. Placebo-controlled trials with oral or i.v. bisphosphonates have shown that prolonged administration can reduce the frequency of skeletal-related events by 30% to 40%. The superiority of zoledronic acid compared with pamidronate has been shown by a multiple-event analysis in a large randomized trial. The short infusion time of zoledronic acid also constitutes a convenient therapy. Where available, oral ibandronate offers an interesting alternative, especially for patients receiving hormone therapy. There are some toxicity concerns with the prolonged use of bisphosphonates. The occasional renal toxicity of zoledronic acid has led to the recommendation to monitor renal function before each infusion and to adjust the dose according to creatinine clearance. Osteonecrosis of the jaw could occur in up to 2.5% of breast cancer patients during long-term bisphosphonate therapy. It is often a significant complication that seems to be linked with the duration of therapy.
A Phase I Dose Escalation Study with Anti-CD44v6 Bivatuzumab Mertansine in Patients with Incurable Squamous Cell Carcinoma of the Head and Neck or Esophagus
Authors: Tijink Bernard M. , Buter Jan , de Bree Remco , Giaccone Giuseppe , Lang Margreet S. , Staab Alexander , Leemans C. René , van Dongen Guus A.M.S. 
Published: October 2006

Abstract
Purpose: To assess safety, pharmacokinetics, maximum tolerated dose, and preliminary efficacy of bivatuzumab mertansine. Bivatuzumab is a humanized monoclonal antibody directed against CD44v6, which previously seemed to be safe in phase I radioimmunotherapy trials, whereas the conjugated mertansine is a potent maytansine derivative.
Experimental Design: Patients with incurable squamous cell carcinoma of the head and neck or esophagus were eligible. Bivatuzumab was given weekly for 3 consecutive weeks by i.v. infusion. One patient was planned to be treated at each dose tier as long as toxicity did not reach grade 2; otherwise, three patients had to be treated until dose-limiting toxicity occurred. Starting dose was 20 mg/m2 and dose was subsequently escalated in steps of 20 mg/m2. Patients without disease progression and not experiencing dose-limiting toxicity were eligible for repeated courses. Blood serum samples were taken throughout the treatment period to determine the pharmacokinetic properties of bivatuzumab mertansine and to assess the human anti–bivatuzumab mertansine antibody response.
Results: Seven patients received a total of 23 weekly doses of bivatuzumab mertansine. One patient at the 100 mg/m2 and one at the 120 mg/m2 level experienced stable disease during treatment phase but also developed grade 1 skin toxicity (desquamation). One of them received a second treatment course. At the highest dose level achieved in this study (140 mg/m2), one patient developed toxic epidermal necrolysis after two infusions and died. Massive apoptosis of skin keratinocytes had occurred, whereas only symptomatic therapy for skin toxicity was available. The risk-benefit assessment of all patients treated in the total phase I program (4 clinical trials, 70 patients) turned out to be negative after consideration of this case of a toxic epidermal necrolysis and the skin-related adverse events observed in the other trials. Therefore, development of the conjugate was discontinued. Interindividual variability in pharmacokinetic variables was low and exposure to BIWI 1 increased proportionally with dose. No anti–bivatuzumab mertansine reactions were observed.
Conclusion: The main toxicity of bivatuzumab mertansine was directed against the skin, most probably due to CD44v6 expression in this tissue. The majority of skin reactions was reversible; however, one fatal drug-related adverse event had occurred. Clinical development was discontinued before reaching maximum tolerated dose.
Targeting Bone Metastasis in Prostate Cancer with Endothelin Receptor Antagonists
Authors: Carducci Michael A. , Jimeno Antonio 
Published: October 2006

Abstract
Recent advances in the understanding of prostate cancer biology and its progression to bone metastasis have led to the development of drugs directed against precise molecular alterations in the prostate tumor cell and host cells in the normal bone environment such as osteoclasts and osteoblasts. Endothelins (ETs) and their receptors have emerged as a potential target in prostate cancer bone metastasis. By activating the ETA receptor, ET-1 is pathogenically involved in facilitating several aspects of prostate cancer progression, including proliferation, escape from apoptosis, invasion, and new bone formation, processes that are general to many malignancies. Notwithstanding, there are a number of features specifically driven by the ET axis in prostate cancer, such as creating and perpetuating a unique interaction between the metastatic prostate cancer cell and the bone microenvironment (osteoblast, osteoclast, and stroma) or altering the equilibrium in pain modulation. These features have led to the preferential clinical evaluation of atrasentan (ABT-627) as a biological therapy in prostate carcinoma, first in hormone-refractory prostate cancer. Biological activity of atrasentan in patients with prostate cancer has been shown by the suppression of biochemical markers of prostate cancer progression in bone, and clinical activity is evidenced by a consistent trend demonstrating a delay in time to disease progression when compared with placebo, especially in patients with bone metastases. Further studies of atrasentan and other selective ET-1 antagonists (ZD4054) are ongoing.
Clinical Features of Metastatic Bone Disease and Risk of Skeletal Morbidity
Authors: Coleman Robert E. 
Published: October 2006

Abstract
The skeleton is the most common organ to be affected by metastatic cancer and the site of disease that produces the greatest morbidity. Skeletal morbidity includes pain that requires radiotherapy, hypercalcemia, pathologic fracture, and spinal cord or nerve root compression. From randomized trials in advanced cancer, it can be seen that one of these major skeletal events occurs on average every 3 to 6 months. Additionally, metastatic disease may remain confined to the skeleton with the decline in quality of life and eventual death almost entirely due to skeletal complications and their treatment. The prognosis of metastatic bone disease is dependent on the primary site, with breast and prostate cancers associated with a survival measured in years compared with lung cancer, where the average survival is only a matter of months. Additionally, the presence of extraosseous disease and the extent and tempo of the bone disease are powerful predictors of outcome. The latter is best estimated by measurement of bone-specific markers, and recent studies have shown a strong correlation between the rate of bone resorption and clinical outcome, both in terms of skeletal morbidity and progression of the underlying disease or death. Our improved understanding of prognostic and predictive factors may enable delivery of a more personalized treatment for the individual patient and a more cost-effective use of health care resources.
Oral Bisphosphonates as Adjuvant Therapy for Operable Breast Cancer
Authors: Powles Trevor , McCroskey Eugene , Paterson Alexander 
Published: October 2006

Abstract
Bone is the most common site of metastatic spread from primary operable breast cancer, causing pain, fractures, and hypercalcemia. This spread depends on the release of osteolytic substances by the cancer cells, which activate osteoclasts to cause bone resorption. The osteoclasts also release growth factors that can act back on the cancer cells to activate growth. This vicious circle thereby facilitates the growth of metastases in bone, thus making this a preferential site for relapse. Agents, such as the bisphosphonates, which block osteoclast function, have been shown to reduce the progression of established bone metastases. The oral bisphosphonate clodronate (1,600 mg/d) is effective for treatment of patients with bone metastases. When used as adjuvant therapy, given to patients with operable breast cancer for 2 years, clodronate has been reported to significantly reduce the risk of bone metastases during the 2-year study period [19 clodronate patients versus 35 placebo patients; hazard ratio (HR), 0.546; P = 0.03] and 5-year study period (51 clodronate patients versus 73 placebo patients; HR, 0.692; P = 0.04) with a significant reduction in mortality (HR, 0.768; P = 0.048). This benefit, together with the low toxicity and safety of clodronate, supports its use as additional adjuvant therapy for patients with primary breast cancer. Further, similarly designed trials are under way to establish the optimal duration of therapy, the efficacy in stage I disease, and the relative potential of other bisphosphonates, particularly the more powerful aminobisphosphonates, such as ibandronate and zoledronate.
Advances in Treating Metastatic Bone Cancer: Summary Statement for the First Cambridge Conference
Authors: Lipton Allan , Berenson James R. , Body Jean-Jacques , Boyce Brendan F. , Bruland Oyvind S. , Carducci Michael A. , Cleeland Charles S. , Clohisy Denis R. , Coleman Robert E. , Cook Richard J. , Guise Theresa A. , Pearse Roger N. , Powles Trevor J. , Rogers Michael J. , Roodman G. David , Smith Matthew R. , Suva Larry J. , Vessella Robert L. , Weilbaecher Katherine N. , King Laura 
Published: October 2006

Abstract
The First Cambridge Conference on Advances in Treating Metastatic Bone Cancer, a symposium held in Cambridge, Massachusetts, October 28 to 29, 2005, was convened to discuss recent advances and research related to the natural history of bone metastases and skeletal complications, bone cancer biology, treatment of myeloma and other solid tumors, and treatment-induced bone loss. The conference format combined brief presentations with extended periods of discussion. The conclusions reached during the 2-day meeting are summarized in this article and presented in more detail in the individual articles and accompanying discussion sessions that comprise the conference proceedings.