bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of steroid receptor coactivators and corepressors in human endometrial hyperplasia and carcinoma with relevance to steroid receptors and Ki‐67 expression
Authors: Uchikawa Junko , Shiozawa Tanri , Shih Hsien‐Chang , Miyamoto Tsutomu , Feng Yu‐Zhen , Kashima Hiroyasu , Oka Kenji , Konishi Ikuo 
Published: October 2003

AbstractBACKGROUNDTo examine the steroid hormone dependent growth mechanism of human endometrial hyperplasia and carcinoma, expression levels of steroid receptor cofactors, such as coactivators (steroid receptor coactivator 1 [SRC‐1] and p300/cyclic AMP‐response element‐binding protein (p300/CBP]) and corepressors (nuclear receptor corepressor [NCoR] and silencing mediator for retinoid and thyroid‐hormone receptors [SMRT]), were investigated.METHODSThe expression levels of cofactors were examined immunohistochemically using 20 samples of normal endometria, 36 samples of hyperplastic endometria, and 58 of malignant endometria and were compared with the expression levels of estrogen receptor (ER), progesterone receptor (PR), and a proliferation marker, Ki‐67.RESULTSIn samples of normal endometria, the expression of coactivators was observed diffusely in glandular cells in the proliferative phase, with a mean positivity index (PI) of 81.8 for SRC‐1 and 91.3 for p300/CBP, whereas expression levels decreased in endometrial hyperplasia (PI: SRC‐1, 58.9; p300/CBP, 83.8) and endometrial carcinoma (PI: SRC‐1, 45.0; p300/CBP, 55.4). In endometrial hyperplasia, there was a significant correlation between the expression of ER and SRC‐1 or p300/CBP. In contrast, there were no significant statistical or topologic correlations between the expression of coactivators and the expression of ER/PR in endometrial carcinoma. The expression of corepressors generally was limited, except for elevated expression of NCoR in endometrial hyperplasia (PI, 23.8).CONCLUSIONSThe current study showed that expression levels of the steroid receptor coactivators SRC‐1 and p300/CBP were reduced in endometrial carcinoma compared with normal and hyperplastic endometrium. In addition, topologic coexpression of both coactivators and ER/PR was lost in endometrial carcinoma. Accordingly, limited response to sex steroids in patients with endometrial carcinoma may be ascribed to the dissociation of cofactors and ER/PR. Cancer 2003. © 2003 American Cancer Society.
Occult “micrometastases” in ductal carcinoma in situ
Authors: Weaver Donald L. 
Published: October 2003

Sentinel lymph node biopsy is frequently associated with identification of micrometastatic tumor deposits. The clinical relevance of identifying micrometastases in breast cancer must be evaluated in the statistical context of the lymph node evaluation strategy and the likelihood of missing a metastasis of similar size.See also pages 2105–13.
Vascular endothelial growth factor is associated with the efficacy of endocrine therapy in patients with advanced breast carcinoma
Authors: Manders Peggy , Beex Louk V. A. M. , Tjan‐Heijnen Vivianne C. G. , Span Paul N. , Sweep C. (Fred) G. J. 
Published: October 2003

AbstractBACKGROUNDVascular endothelial growth factor (VEGF) is a mediator of angiogenesis and is associated with a poor prognosis in patients with primary breast carcinoma. In the current study, the authors investigated whether there was an association between VEGF levels in tumor tissues and response rates to first‐line, systemic therapy in patients with advanced breast carcinoma.METHODSIn 172 tumors from patients with primary breast carcinoma who developed distant metastases during follow‐up, cytosolic levels of VEGF were measured using a quantitative enzyme‐linked immunosorbent assay. Patients received either endocrine therapy (n = 96) or chemotherapy (n = 76) as first‐line treatment after they were diagnosed with advanced disease.RESULTSIn univariate logistic regression analysis for response to endocrine therapy in 96 patients, an increasing level of VEGF, as a log‐transformed, continuous variable, was correlated with a poor rate of response (P = 0.043). In multivariate analysis, a significantly lower rate of response to first‐line endocrine therapy was found for patients who had high VEGF levels compared with patients who had low VEGF levels (P = 0.025). Similar results were found for the subgroup of 82 patients who received tamoxifen (P = 0.011). An association of VEGF with response to first‐line endocrine therapy was found in addition to a predictive impact for estrogen receptor/progesterone receptor status (P = 0.027). VEGF levels did not predict the rate of response to first‐line chemotherapy.CONCLUSIONSThe results demonstrated that the level of VEGF affects response to endocrine therapy independent of steroid hormone receptor status and may help to refine further the indication for this treatment in individual patients. Further studies are warranted to explain this underlying resistance to endocrine therapy. Cancer 2003. © 2003 American Cancer Society.
Intraarterial cisplatin with intravenous paclitaxel and ifosfamide as an organ‐preservation approach in patients with paranasal sinus carcinoma
Authors: Papadimitrakopoulou Vassiliki A. , Ginsberg Lawrence E. , Garden Adam S. , Kies Merrill S. , Glisson Bonnie S. , Diaz Eduardo M. , Clayman Gary , Morrison William H. , Liu Diane D. , Blumenschein George , Lippman Scott M. , Schommer Donald , Gillenwater Ann , Goepfert Helmuth , Hong Waun K. 
Published: October 2003

AbstractBACKGROUNDThe objectives of this study were to determine the efficacy, organ‐preservation rate, and safety of intraarterial (IA) cisplatin in combination with intravenous paclitaxel and ifosfamide in patients with locally advanced carcinoma of the paranasal sinuses who required orbital exenteration or major craniofacial resection for complete tumor resection.METHODSPatients were treated with intravenous paclitaxel (135 mg/m2) on Day 1, ifosfamide (1000 mg/m2) on Days 1–3, sodium mercaptoethanesulfonate (600 mg/m2) on Days 1–3, and IA cisplatin (100 mg/m2) on Day 1 every 21 days.RESULTSOf 24 study participants, 20 patients received at least 1 course of IA cisplatin, 1 patient had an early death, and 19 patients were evaluable for response. Five of those 19 patients (26%) achieved a complete response (CR), 6 patients (32%) achieved a partial response, and 8 patients (42%) had stable disease or developed progressive disease. Eye‐sparing surgery followed by radiotherapy (RT) was feasible in 7 of 24 patients, RT was offered to only 7 patients, whereas 3 patients received chemotherapy and RT, 2 patients refused further therapy, 3 patients underwent craniofacial resection with orbitectomy, and 1 patient was treated systemically for metastatic disease. At the completion of treatment, 14 of 23 patients (61%) with locally advanced disease were disease free, and the orbit was preserved in 21 of 24 patients (88%). The overall survival, progression‐free survival, and disease‐free survival rates at 2 years were 60%, 50%, and 84%, respectively. Toxicity was substantial, with two patients experiencing cerebrovascular ischemia (one transient and one cerebrovascular accident) and three patients experiencing cranial neuropathy, which was reversible in two patients.CONCLUSIONSDespite the encouraging organ‐preservation rate, the approach studied resulted in substantial toxicity, and more effective adjunctive therapy is needed. Alternative approaches, including the integration of targeted therapy agents in induction chemotherapy regimens followed by concomitant chemotherapy and RT or eye‐sparing surgery, need further exploration. Cancer 2003. © 2003 American Cancer Society.
Definitive radiotherapy alone or combined with a planned neck dissection for squamous cell carcinoma of the pharyngeal wall
Authors: Hull Matthew C. , Morris Christopher G. , Tannehill Scott P. , Werning John W. , Amdur Robert J. , Hinerman Russell W. , Villaret Douglas B. , Mendenhall William M. 
Published: October 2003

AbstractBACKGROUNDIn the current study,the authors analyzed the results of definitive radiotherapy for squamous cell carcinoma of the pharyngeal wall.METHODSBetween 1964 and 2000, 148 patients were treated with definitive radiotherapy. All patients had a 2‐year minimum follow‐up.RESULTSThe following 5‐year rates of local and ultimate local control were obtained: T1 disease, 93% and 93%; T2 disease, 82% and 87%; T3 disease, 59% and 61%; and T4 disease, 50% and 50%, respectively. Multivariate analysis revealed that twice‐daily fractionation (P= 0.0009), American Joint Committee on Cancer Stage I–II disease (P= 0.0051), and oropharyngeal primary site (P= 0.0193) were associated with improved locoregional control. The following 5‐year absolute and cause‐specific survival rates were obtained: Stage I, 56% and 89%; Stage II, 52% and 88%; Stage III, 24% and 44%; Stage IV, 22% and 34%; and overall, 30% and 49%, respectively. Eight patients (5%) died of complications.CONCLUSIONSLocoregional control and survival were found to be related to site, extent of disease, and fractionation schedule. Although outcomes have improved in recent years, the morbidity of treatment was significant in the current study and a substantial proportion of patients died secondary to the malignancy. Cancer 2003. © 2003 American Cancer Society.
Antiangiogenetic therapy with pioglitazone, rofecoxib, and metronomic trofosfamide in patients with advanced malignant vascular tumors
Authors: Vogt Thomas , Hafner Christian , Bross Klaus , Bataille Frauke , Jauch Karl‐Walter , Berand Anna , Landthaler Michael , Andreesen Reinhard , Reichle Albrecht 
Published: October 2003

AbstractBACKGROUNDSystemic therapy options for patients with advanced angiosarcomas are limited, and their prognosis is poor. The idea of angiostatic therapy following the paradigm of metronomic dosed chemotherapeutics combined with proapoptotic biomodulators had not been considered previously in these patients. Therefore, in a pilot study, the efficacy of metronomically scheduled, low‐dose trofosfamide in combination with the peroxisome proliferator‐activated receptor γ agonist, pioglitazone, and the selective cyclooxygenase‐2 inhibitor, rofecoxib, was evaluated in patients with advanced vascular malignancies.METHODSSix patients with advanced and pretreated but progressive, malignant vascular tumors (5 angiosarcomas and 1 hemangioendothelioma) received a combination of pioglitazone (45 mg per day orally) plus rofecoxib (25 mg per day orally) and, after 14 days, trofosfamide (3 × 50 mg per day orally). The therapy was administered continuously until progression was observed. If necessary, doses were modified according to side effects.RESULTSTwo patients responded with complete remission of disease, one patient responded with partial remission, and three patients achieved stabilization of disease (no change). The median progression‐free survival was 7.7 months (range, 2–15 months). Side effects generally were mild (World Health Organization Grade 1–2). Hospitalization was not necessary.CONCLUSIONSThis new triple combination of low‐dose metronomic trofosfamide, pioglitazone, and rofecoxib may represent a feasible new alternative in the palliative treatment of patients with advanced malignant vascular tumors. Cancer 2003. © 2003 American Cancer Society.
Weekly paclitaxel, estramustine phosphate, and oral etoposide in the treatment of hormone‐refractory prostate carcinoma
Authors: Meluch Anthony A. , Greco F. Anthony , Morrissey Lisa H. , Raefsky Eric L. , Steis Ronald G. , Butts James A. , Hainsworth John D. 
Published: October 2003

AbstractBACKGROUNDThe objective of the current study was to evaluate the efficacy and toxicity of weekly paclitaxel, oral etoposide, and estramustine phosphate in the treatment of patients with advanced, hormone‐refractory prostate carcinoma.METHODSPatients with hormone‐refractory prostate carcinoma who had received no more than one previous chemotherapy regimen were eligible for this trial. Forty‐two patients were treated between February 1998 and March 2000. Toxicity was excessive in the first 3 patients treated (Grade 3–4 leukopenia, 3 patients; death due to sepsis, 1 patient); the remaining 39 patients received lower doses of etoposide and estramustine phosphate (paclitaxel 50 mg/m2 as a 1‐hour, intravenous infusion on Days 1, 8, 15; etoposide 50 mg orally twice daily on Days 1–10; and estramustine phosphate 280 mg orally 3 times daily on Days 1–10). Courses were repeated every 28 days. Patients were evaluated for objective and/or serologic response after two courses of treatment; responding patients continued treatment for six courses.RESULTSFourteen of 40 evaluable patients (35%) had either an objective response or a serologic response to treatment. The median survival for the entire group was 9.5 months, with 1‐year, 2‐year, and 3‐year survival rates of 38%, 12%, and 10%, respectively. Neutropenia was the most common Grade 3–4 toxicity and occurred in 38% of patients (11% of courses). Thirteen patients (33%) had severe fatigue, and 2 patients had treatment‐related deaths due to sepsis.CONCLUSIONSAlthough the three‐drug combination had activity in patients with hormone‐refractory prostate carcinoma, the results did not appear any better than the results achieved with less toxic taxane/estramustine phosphate combinations. Further development of this three‐drug regimen is not recommended. Cancer 2003. © 2003 American Cancer Society.
Gemtuzumab ozogamicin in the treatment of acute myeloid leukemia
Authors: Giles Francis , Estey Elihu , O'Brien Susan 
Published: October 2003

AbstractGemtuzumab ozogamicin (GO) is a chemotherapeutic agent that consists of a humanized anti‐CD33 antibody (hP67.6) linked to N‐acetyl‐γ calicheamicin 1,2‐dimethyl hydrazine dichloride, a potent enediyne antitumor antibiotic. GO was approved conditionally by the Federal Drug Administration in May 2000 as single‐agent therapy for first recurrence of acute myeloid leukemia (AML) in a subset of older patients. Data on studies in AML with GO‐based regimens have been reported rapidly in addition to new observations on the target antigen, CD33. These data indicate promising new areas of investigation with GO, including its application as maintenance therapy in patients with AML and as an induction and/or maintenance agent in patients with acute promyelocytic leukemia;, and they also have highlighted challenges in the development of GO, particularly its association with hepatic venoocclusive disease. In vitro data on the mechanism of action of GO may be particularly helpful in the design of future clinical studies. Cancer 2003. © 2003 American Cancer Society.
Characterization of the dual‐specificity phosphatase PYST2 and its transcripts
Authors: Levy‐Nissenbaum Orlev , Sagi‐Assif Orit , Witz Isaac P. 
Published: October 2003

AbstractPYST2 is a member of a structurally homologous subfamily of MAP kinase phosphatases. A computer‐based analysis of the PYST2 locus revealed that it harbors two alternative open reading frames promoted by two conserved promoter regions. Using Northern blot analysis and reverse transcription–polymerase chain reaction followed by sequencing and alignment of the products, we confirmed the existence of two mRNAs that were transcribed from this genomic region. Western blot analysis indicated that these transcripts were translated. Functional bioinformatic analysis of both transcripts revealed that exon 2 exists in only one of the PYST2 transcripts, designated PYST2‐L, and has the consensus elements of the phosphatase catalytic domain (PCD). We found that the translation from the PYST2‐L transcript starts 46 codons upstream from the (already‐known) PYST2 5′ sequence. Furthermore, the existence of three PYST2‐L transcripts was indicated. These transcripts differ only in their 5′ untranslated regions (5′UTRs). Unlike PYST2‐L, the other mRNA (PYST2‐S) is devoid of any known PCD. Analysis of the predicted Pyst2‐S protein revealed the presence of the vertebrate metallothionein signature I, the mammalian defensin, and the zinc‐containing alcohol dehydrogenase motifs. These motifs might confer on this protein the ability to sense changes in the cellular environment. From these and previous results, we speculate that Pyst2‐S may function as a negative regulator of Pyst2‐L. © 2003 Wiley‐Liss, Inc.
Analysis of chromosomal imbalances in de novo CD5‐positive diffuse large‐B‐cell lymphoma detected by comparative genomic hybridization
Authors: Karnan Sivasundaram , Tagawa Hiroyuki , Suzuki Ritsuro , Suguro Miyuki , Yamaguchi Motoko , Okamoto Masataka , Morishima Yasuo , Nakamura Shigeo , Seto Masao 
Published: October 2003

AbstractWe recently demonstrated that the prognosis for de novo CD5‐positive (CD5+) diffuse large‐B‐cell lymphoma (DLBCL) is markedly worse than that for CD5‐negative (CD5−) DLBCL. Our findings also suggested that on the basis of its clinical features CD5+ DLBCL may constitute a unique disease category. However, the genetic basis for these two categories has not been established. Therefore, we performed comparative genomic hybridization analysis (CGH) of 26 cases of CD5+ DLBCL and 44 cases of CD5− DLBCL. Several identical changes in CD5+ and CD5− DLBCLs were found, such as gains of 3q, 9p, 12q, 13q, and 18q and losses of 1p, 6q, 17p, and 19p. However, distinct differences between the two categories were also detected. These included gains of 11q21‐q24 (P = 0.032) and 16p (P = 0.005) in CD5+ DLBCL, and loss of 16p (P = 0.028) in CD5− DLBCL. A comparison with results reported for mantle cell lymphoma, chronic lymphocytic leukemia, and Richter's syndrome demonstrated that the CGH pattern of CD5+ DLBCL was markedly different. This indicates that CD5+ DLBCL constitutes a disease category distinct from that of CD5− DLBCL and other CD5+ malignancies. © 2003 Wiley‐Liss, Inc.
t(14;19)(q32;q13): A recurrent translocation in B‐cell precursor acute lymphoblastic leukemia
Authors: Robinson Hazel M. , Taylor Kerry E. , Jalali G. Reza , Cheung Kan Luk , Harrison Christine J. , Moorman Anthony V. 
Published: October 2003

AbstractThe recurrent t(14;19)(q32;q13) translocation associated with chronic B‐cell lymphoproliferative disorders, such as atypical chronic lymphocytic leukemia, results in the juxtaposition of the IGH@ and BCL3 genes and subsequent overexpression of BCL3. We report six patients with B‐cell precursor acute lymphoblastic leukemia who have a cytogenetically identical translocation with different breakpoints at the molecular level. Fluorescence in situ hybridization with locus‐specific probes confirmed the involvement of the IGH@ gene but showed that the breakpoint on 19q13 lay outside the region documented in t(14;19)(q32;q13)‐positive chronic lymphocytic leukemia. This newly described translocation constitutes a distinct cytogenetic subgroup that is confined to older children and younger adults with B‐cell precursor acute lymphoblastic leukemia. © 2003 Wiley‐Liss, Inc.
Transient human cortical responses during the observation of simple finger movements: A high‐resolution EEG study
Authors: Babiloni Claudio , Del Percio Claudio , Babiloni Fabio , Carducci Filippo , Cincotti Febo , Moretti Davide V. , Rossini Paolo M. 
Published: October 2003

AbstractHigh‐resolution event‐related potentials (ERPs) were used to model the hemispherical representation of the transient cortical responses relating to the observation of movement during execution (right or left aimless finger extension). Subjects were seated in front of the observed person and looked at both their own and the observer's hand to receive similar visual feedback during the two conditions. In a visual control condition, a diode light moved at the observed person's hand. A first potential accompanying the movement execution peaked at about +110 msec over the contralateral somatomotor areas. It was followed by a potential (P300) peaking at about +350 msec over the central midline. In contrast, the potentials accompanying the movement observation peaked later over parietal‐occipital other than somatomotor areas (N200 peak, +200 msec; P300 peak, +400 msec). Notably, the N200 was maximum in left parietal area whereas the P300 was maximum in right parietal area regardless the side of the movement. They markedly differed by the potentials following the displacement of the diode light. These results suggest a rapid time evolution (∼200–400 msec) of the cortical responses characterizing the observation of aimless movements (as opposite to grasping or handling). The execution of these movements would mainly involve somatomotor cortical responses and would be scarcely founded on the visual feedback. In contrast, the observation of the same movements carried out by others would require dynamical responses of somatomotor and parietal‐occipital areas (especially of the right hemisphere), possibly for a stringent visuospatial analysis of the motor event. Hum. Brain Mapping 20:148–157, 2003. © 2003 Wiley‐Liss, Inc.
Detection and quantification of a wide range of fMRI temporal responses using a physiologically‐motivated basis set
Authors: Harms Michael P. , Melcher Jennifer R. 
Published: October 2003

AbstractThe temporal dynamics of fMRI responses can span a broad range, indicating a rich underlying physiology, but also posing a significant challenge for detection. For instance, in human auditory cortex, prolonged sound stimuli (∼30 sec) can evoke responses ranging from sustained to highly phasic (i.e., characterized by prominent peaks just after sound onset and offset). In the present study, we developed a method capable of detecting a wide variety of responses, while simultaneously extracting information about individual response components, which may have different neurophysiological underpinnings. Specifically, we implemented the general linear model using a novel set of basis functions chosen to reflect temporal features of cortical fMRI responses. This physiologically‐motivated basis set (the “OSORU” basis set) was tested against (1) the commonly employed “sustained‐only” basis “set” (i.e., a single smoothed “boxcar” function), and (2) a sinusoidal basis set, which is capable of detecting a broad range of responses, but lacks a direct relationship to individual response components. On data that included many different temporal responses, the OSORU basis set performed far better overall than the sustained‐only set, and as well or better than the sinusoidal basis set. The OSORU basis set also proved effective in exploring brain physiology. As an example, we demonstrate that the OSORU basis functions can be used to spatially map the relative amount of transient vs. sustained activity within auditory cortex. The OSORU basis set provides a powerful means for response detection and quantification that should be broadly applicable to any brain system and to both human and non‐human species. Hum. Brain Mapp. 20:168–183, 2003. © 2003 Wiley‐Liss, Inc.
How much confidence should we place in efficiency estimates?
Authors: Street Andrew 
Published: October 2003

AbstractOrdinary least squares (OLS) and stochastic frontier (SF) analyses are commonly used to estimate industry‐level and firm‐specific efficiency. Using cross‐sectional data for English public hospitals, a total cost function based on a specification developed by the English Department of Health is estimated. Confidence intervals are calculated around the OLS residuals and around the inefficiency component of the SF residuals. Sensitivity analysis is conducted to assess whether conclusions about relative performance are robust to choices of error distribution, functional form and model specification. It is concluded that estimates of relative hospital efficiency are sensitive to estimation decisions and that little confidence can be placed in the point estimates for individual hospitals. The use of these techniques to set annual performance targets should be avoided. Copyright © 2002 John Wiley & Sons, Ltd.