bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toxicity and outcome analysis of patients with recurrent head and neck cancer treated with hyperfractionated split‐course reirradiation and concurrent cisplatin and paclitaxel chemotherapy from two prospective phase I and II studies
Authors: Kramer Noel M. , Horwitz Eric M. , Cheng Jonathan , Ridge John A. , Feigenberg Steven J. , Cohen Roger B. , Nicolaou Nicos , Sherman Eric J. , Babb James S. , Damsker Jason A. , Langer Corey J. 
Published: February 2005

AbstractBackground.Patients with local recurrences or new head and neck primary tumors in previously irradiated tissues have few options for salvage treatment. One option for select patients is to undergo reirradiation with concurrent chemotherapy. The purpose of this study is to report the initial clinical results of the Fox Chase phase I and II prospective reirradiation and chemotherapy studies.Methods.Between July 1996 and January 2002, 38 patients with locally recurrent unresectable squamous cell carcinoma of the head and neck were treated with concurrent chemotherapy and reirradiation on two prospective trials. All patients had received prior radiation therapy to the head and neck region (median dose, 64.2 Gy). Patients received cisplatin and paclitaxel along with hyperfractionated external beam radiation therapy to the site of recurrence.Results.The median follow‐up was 10 months. The median survival was 12.4 months, with actuarial rates of overall survival of 50% and 35% at 1 and 2 years, respectively. During follow‐up, 63% of patients experienced local progression of disease, all in the irradiated field. Actuarial progression‐free survival at 1 year was 33%, with a median time to progression of 7.3 months. Acute grade 3 to 4 toxicity included neutropenia, nausea, emesis, and mucositis.Conclusions.Hyperfractionated split‐course reirradiation and concurrent cisplatin and paclitaxel chemotherapy demonstrates durable locoregional control in select patients, although late toxicity may occasionally be significant. Only sites of disease recurrence need to be covered in the reirradiation fields. © 2005 Wiley Periodicals, Inc. Head Neck 27: XXX–XXX, 2005
Low frequency of BRAF and CDKN2A mutations in endometrial cancer
Authors: Salvesen Helga B. , Kumar Rajiv , Stefansson Ingunn , Angelini Sabrina , MacDonald Nicola , Smeds Johanna , Jacobs Ian J. , Hemminki Kari , Das Soma , Akslen Lars A. 
Published: February 2005

AbstractSeveral pathways have been implicated in the pathogenesis of endometrial carcinoma. Based on recent reports, BRAF mutations provide an alternative route for activation of the RAS signalling pathway. The CDKN2A (p16) tumour suppressor gene is also altered in several tumour types. We therefore wanted to assess the pattern and prognostic impact of BRAF mutations and p16 alterations in endometrial carcinomas. Only 1 of 48 tumours (2%) was found to have a BRAF mutation in exon 15, whereas 8 of 45 tumours (18%) had a K‐ras mutation. Homozygous deletion, amplification, promoter region methylation or mutation of the p16 gene was seen in 6 cases (13%), and 18 cases (38%) carried polymorphisms in the p16 gene. All tumours with presence of p16 methylation, non‐sense mutation, deletion or amplification exhibited loss of p16 expression as evaluated by immunohistochemistry. Presence of a p16 hit was significantly correlated with high FIGO stage (p = 0.04), high histologic grade (p = 0.02), estrogen receptor negativity (p = 0.05), pathologic expression of p53 (p = 0.02), pathologic expression of p16 (p = 0.05) and poor survival (p = 0.02). There was also a significant correlation between loss of p16 expression and K‐ras mutations, pathologic p53 expression and serous papillary/clear cell histologic types (p = 0.05/p = 0.001/p = 0.002). In conclusion, BRAF mutation is an infrequent finding in endometrial carcinomas. Loss of p16 expression is seen in all cases with alterations of the p16 gene. The presence of a p16 hit might be important in a subset of endometrial carcinomas with aggressive clinical behaviour. However, the mechanism of p16 inactivation remains unclear for the majority of cases exhibiting loss of expression, but the interactions with K‐ras and p53 should be further studied. © 2005 Wiley‐Liss, Inc.
Dietary and other risk factors in women having fibrocystic breast conditions with and without concurrent breast cancer: A nested case‐control study in Shanghai, China
Authors: Li Wenjin , Ray Roberta M. , Lampe Johanna W. , Lin Ming‐Gang , Gao Dao Li , Wu Chunyuan , Nelson Zakia C. , Fitzgibbons E. Dawn , Horner Neilann , Hu Yong Wei , Shannon Jackilen , Satia Jessie A. , Patterson Ruth E. , Stalsberg Helge , Thomas David B. 
Published: February 2005

AbstractRisk of breast cancer is increased in women with proliferative benign breast conditions. Most of these conditions, however, do not progress to breast cancer. The purpose of our study was to identify factors possibly associated with this progression. Women with proliferative fibrocystic breast conditions alone (214), and women with proliferative fibrocystic breast conditions and concurrent breast cancer (130), were compared to each other, and each of these groups of women were also compared to 1,070 controls; and 176 women with non‐proliferative benign breast conditions alone, and 155 also with breast cancer, were similarly compared. All study subjects were selected from a cohort of women enrolled in a trial of breast self‐examination in Shanghai. Women were interviewed to ascertain information on suspected risk factors for breast cancer and dietary habits. Conditional logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). Increased risks of both proliferative fibrocystic breast conditions alone, and with breast cancer, were associated with low parity, a prior benign breast lump and breast cancer in a first‐degree relative. Decreasing trends in the risk of both conditions with increasing intake of fruits and vegetables were observed. No factors were significantly associated with risk of breast cancer relative to risk of proliferative changes. Similar, but in some instances weaker, associations were observed for non‐proliferative fibrocystic conditions with and without breast cancer. The possible risk or protective factors that were observed in our study most likely alter the risk of breast cancer at an early stage in the carcinogenic process, and probably do not alter risk of progression from proliferative fibrocystic breast conditions to breast cancer. © 2005 Wiley‐Liss, Inc.
BRCA1: A locus‐specific “liaison” in gene expression and genetic integrity
Authors: Aiyar Sarah , Sun Jian‐long , Li Rong 
Published: February 2005

AbstractMutations in BRCA1 predominantly lead to elevated risks of breast and ovarian cancers. In contrast to the tissue‐specific nature of BRCA1tumors, the normal BRCA1 gene product functions in diverse nuclear events including transcription, DNA repair, and DNA damage checkpoint. Recent findings of physical and functional associations between BRCA1 and the RNA polymerase II (RNAPII)‐dependent transcription machinery may shed some light on this longstanding paradox of BRCA1 biology. Eukaryotic gene expression is now known to be a continuous process, whereby each step is physically and functionally connected to the next. In particular, RNAPII plays a pivotal role in coordinating transcription with various pre‐mRNA processing events and stress response. Interestingly, BRCA1 preferentially interacts with the processive form of RNAPII and proteins that regulate RNAPII activity and movement during transcription elongation. In response to DNA damage, BRCA1 dissociates from RNAPII and localizes to DNA damage sites. We propose that BRCA1 may coordinate multiple steps in gene expression, including transcription initiation, elongation, and pre‐mRNA processing via its interactions with the transcription machinery at selected gene loci. The same BRCA1‐associated transcription apparatus may serve as a sensor for stress signals and facilitate the transition from a transcription state to checkpoint/DNA repair state. Such a coordinating role of BRCA1 in gene expression may ensure the appropriate quantity and quality of the mature transcripts for certain breast and ovarian cancer‐related genes, as well as the genetic integrity of the breast and ovary tissues. © 2005 Wiley‐Liss, Inc.
Histone modifications as a platform for cancer therapy
Authors: Espino Paula S. , Drobic Bojan , Dunn Katherine L. , Davie James R. 
Published: February 2005

AbstractTumorigenesis and metastasis are a progression of events resulting from alterations in the processing of the genetic information. These alterations result from stable genetic changes (mutations) involving tumor suppressor genes and oncogenes (e.g., ras, BRAF) and potentially reversible epigenetic changes, which are modifications in gene function without a change in the DNA sequence. Mutations of genes coding for proteins that directly or indirectly influence epigenetic processes will alter the cell's gene expression program. Epigenetic mechanisms often altered in cancer cells are DNA methylation and histone modifications (acetylation, methylation, phosphorylation). This article will review the potential of these reversible epigenetic processes as targets for cancer therapies. © 2005 Wiley‐Liss, Inc.
Codominant expression of genes coding for different sets of inducible salivary polypeptides associated with parotid hypertrophy in two inbred mouse strains
Authors: López‐Solís Remigio O. , Kemmerling Ulrike 
Published: February 2005

AbstractExperimental mouse parotid hypertrophy has been associated with the expression of a number of isoproterenol‐induced salivary proline‐rich polypeptides (IISPs). Mouse salivary proline‐rich proteins (PRPs) have been mapped both to chromosomes 6 and 8. Recently, mice of two inbred strains (A/Snell and A.Swiss) have been found to differ drastically in the IISPs. In this study, mice of both strains were used for cross‐breeding experiments addressed to define the pattern of inheritance of the IISP phenotype and to establish whether the IISPs are coded on a single or on several chromosomes. The IISP phenotype of individual mice was assessed by sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS–PAGE) of whole saliva collected after three daily stimulations by isoproterenol. Parental A/Snell and A.Swiss mice were homogeneous for distinctive strain‐associated IISP‐patterns. First filial generation (F1) mice obtained from the cross of A/Snell with A.Swiss mice expressed with no exception both the A/Snell and A.Swiss IISPs (coexpression). In the second filial generation (F2) both parental IISP phenotypes reappeared together with a majority of mice expressing the F1‐hybrid phenotype (1:2:1 ratio). Backcrosses of F1 × A/Snell and F1 × A.Swiss produced offsprings displaying the F1 and the corresponding parental phenotypes with a 1:1 ratio. No recombinants were observed among F2 mice or among mice resulting from backcrosses. Thus, genes coding for the IISPs that are expressed differentially in both mouse strains are located on the same chromosome, probably at the same locus (alleles) or at quite closely linked loci (nonalleles). © 2005 Wiley‐Liss, Inc.
NGX6 gene inhibits cell proliferation and plays a negative role in EGFR pathway in nasopharyngeal carcinoma cells
Authors: Wang Lili , Ma Jian , Li Jiang , Li Xiaoling , Zhang Qiuhong , Peng Shuping , Peng Cong , Zhou Ming , Xiong Wei , Yang Jianbo , Zhou Jie , Fan Songqing , Tan Chen , Yan Qun , Shen Shourong , Li Guiyuan 
Published: February 2005

AbstractNasopharyngeal carcinoma (NPC) is a common cancer in South China but is rare in other parts of the world. A novel NPC‐related gene was isolated by location candidate cloning strategy, whose expression was down‐regulated in NPC. This gene was designated human NGX6 (Genbank accession AF188239) and encoded a predicted protein of 338 amino acids that harbors an EGF‐like domain. The effects of NGX6 on cells from human NPC cell line HNE1 were investigated. The cells transfected with NGX6 had a markedly high expression of NGX6, leading to significant decrease in cell proliferation and the capability to form colonies in soft agar, delaying the G0–G1 cell cycle progression. Flow cytometry assay indicated that the expression of cyclin D1 significantly decreased in NGX6‐transfected HNE1 cells as well as cyclin A and E. There was a delay in tumor formation and a dramatic reduction in tumor size when cells transfected with NGX6 were injected into nude mice. In another way, we found NGX6 played a negative role in EGFR Ras/Mek/MAPK pathway. We propose that NGX6, as an EGF‐like domain gene, could delay cell cycle G0–G1 progression and thus inhibit cell proliferation by negatively regulating EGFR pathway in NPC cells and down‐regulating the expression of cyclin D1 and E. © 2005 Wiley‐Liss, Inc.
Discovery, regulation, and action of the major apoptotic nucleases DFF40/CAD and endonuclease G
Authors: Widlak Piotr , Garrard William T. 
Published: February 2005

AbstractToward the end of the 20th and beginning of the 21st centuries, clever in vitro biochemical complementation experiments and genetic screens from the laboratories of Xiaodong Wang, Shigekazu Nagata, and Ding Xue led to the discovery of two major apoptotic nucleases, termed DNA fragmentation factor (DFF) or caspase‐activated DNase (CAD) and endonuclease G (Endo G). Both endonucleases attack chromatin to yield 3′‐hydroxyl groups and 5′‐phosphate residues, first at the level of 50–300 kb cleavage products and next at the level of internucleosomal DNA fragmentation, but these nucleases possess completely different cellular locations in normal cells and are regulated in vastly different ways. In non‐apoptotic cells, DFF exists in the nucleus as a heterodimer, composed of a 45 kD chaperone and inhibitor subunit (DFF45) [also called inhibitor of CAD (ICAD‐L)] and a 40 kD latent nuclease subunit (DFF40/CAD). Apoptotic activation of caspase‐3 or ‐7 results in the cleavage of DFF45/ICAD and release of active DFF40/CAD nuclease. DFF40's nuclease activity is further activated by specific chromosomal proteins, such as histone H1, HMGB1/2, and topoisomerase II. DFF is regulated by multiple pre‐ and post‐activation fail‐safe steps, which include the requirements for DFF45/ICAD, Hsp70, and Hsp40 proteins to mediate appropriate folding during translation to generate a potentially activatable nuclease, and the synthesis in stoichiometric excess of the inhibitors (DFF45/35; ICAD‐S/L). By contrast, Endo G resides in the mitochondrial intermembrane space in normal cells, and is released into the nucleus upon apoptotic disruption of mitochondrial membrane permeability in association with co‐activators such as apoptosis‐inducing factor (AIF). Understanding further regulatory check‐points involved in safeguarding non‐apoptotic cells against accidental activation of these nucleases remain as future challenges, as well as designing ways to selectively activate these nucleases in tumor cells. © 2005 Wiley‐Liss, Inc.
Neurofeedback in adolescents and adults with attention deficit hyperactivity disorder
Authors: Butnik Steven M. 
Published: February 2005

AbstractNeurofeedback is being utilized more commonly today in treating individuals who have attention deficit hyperactivity disorder (ADHD). Neurofeedback, which is based on theories that recognize the organic basis of ADHD, utilizes biofeedback to guide individuals to regulate their brain activity. Neurofeedback relies on research that has demonstrated that most individuals who have ADHD, as compared to matched peers, have excess slow wave activity and reduced fast wave activity. It provides immediate feedback to the individual about his or her brain wave activity in the form of a video game, whose action is influenced by the individual's meeting predetermined thresholds of brain activity. Over several sessions of using the video and auditory feedback, individuals reduce their slow wave activity and/or increase their fast wave activity. Individuals who complete a course of training sessions often show reduced primary ADHD symptoms. Research has shown that neurofeedback outcomes compare favorably to those of stimulant medication. © 2005 Wiley Periodicals, Inc. J Clin Psychol/In Session 61: 621–625, 2005.
Differentiation of noncancerous tissue and cancer lesions by apparent diffusion coefficient values in transition and peripheral zones of the prostate
Authors: Sato Chiho , Naganawa Shinji , Nakamura Tatsuya , Kumada Hisashi , Miura Shunichi , Takizawa Osamu , Ishigaki Takeo 
Published: February 2005

AbstractPurposeTo compare the apparent diffusion coefficient (ADC) values of prostate cancer in both the peripheral zone (PZ) and the transition zone (TZ) with those of benign tissue in the same zone using echo‐planar diffusion weighted imaging with a parallel imaging technique.Materials and MethodsA total of 29 consecutive male patients (mean age 61.3 years, age range 53–88 years) with suspected prostate cancer were referred for MR imaging. All patients underwent transrectal ultrasound (TRUS)‐guided biopsy of the prostate after MR imaging at 1.5 T, including ADC. For each patient, seven to 10 specimens were obtained from the prostate, and regions of interest (ROIs) were drawn on the ADC map by referring to the urologist's illustration of TRUS‐guided biopsy sites. ADC values of cancerous tissue in both the PZ and TZ were compared to those of noncancerous tissue in the same zone.ResultsOut of 29 patients, 23 had cancer tissue. In the 23 patients with cancer, the mean ADC value of all cancer ROIs and that of all noncancer ROIs, respectively, were 1.11 ± 0.41 × 10–3 and 1.68 ± 0.40 × 10–3 mm2/second (values are mean ± SD) (P < 0.01). The mean ADC value of TZ cancer ROIs and that of TZ noncancer ROIs, respectively, were 1.13 ± 0.42 × 10–3 and 1.58 ± 0.37 × 10–3 mm2/second (P < 0.01).ConclusionsADC measurement with a parallel imaging technique showed that ADC values of prostate cancer in both the PZ and TZ were significantly lower than those of benign tissue in the PZ and TZ, respectively. J. Magn. Reson. Imaging 2005;21:258–262. © 2005 Wiley‐Liss, Inc.
Real‐time Fourier velocity encoding: An in vivo evaluation
Authors: Macgowan Christopher K. , Kellenberger Christian J. , Detsky Jay S. , Roman Kevin , Yoo Shi‐Joon 
Published: February 2005

AbstractPurposeTo compare in vivo real‐time Fourier velocity encoding (FVE), spectral‐Doppler ultrasound, and phase‐contrast (PC) magnetic‐resonance (MR) imaging.Materials and MethodsIn vivo velocity spectra were measured in the suprarenal and infrarenal aorta and the hepatic segment of the inferior vena cava of eight normal volunteers using FVE, and compared to similar measurements using Doppler ultrasound and gated PC MR imaging. In vivo waveforms were compared qualitatively according to flow pattern appearance (number, shape, and position of velocity peaks) and quantitatively according to peak velocity.ResultsGood agreement was obtained between peak velocities measured in vitro using FVE and PC MR imaging (R2 = 0.99, P = 2.10−6, slope = 0.97 ± 0.05). Qualitatively, the FVE and ultrasound measurements agreed closely in the majority of in vivo cases (excellent or good in 21/24 cases) while the PC MR method resolved fewer velocity peaks due to the inherent temporal averaging of cardiac‐gated studies (excellent or good agreement with FVE in 13/24 cases). Quantitatively, the FVE measurement of peak velocity correlated strongly with both ultrasound (R2 = 0.71, P = 2.10−7, slope = 0.81 ± 0.08) and PC MR (R2 = 0.85, P = 2.10−10, slope = 1.04 ± 0.08).ConclusionReal‐time MR assessment of blood‐flow velocity correlated well with spectral Doppler ultrasound. Such new methods may allow hemodynamic information to be acquired in vessels inaccessible to ultrasound or in patients for whom respiratory compensation is not possible. J. Magn. Reson. Imaging 2005;21:297–304. © 2005 Wiley‐Liss, Inc.
Balloon sizing and transcatheter closure of acute atrial septal defects guided by magnetic resonance fluoroscopy: Assessment and validation in a large animal model
Authors: Schalla Simon , Saeed Maythem , Higgins Charles B. , Weber Oliver , Martin Alastair , Moore Phillip 
Published: February 2005

AbstractPurposeTo quantitatively assess atrial septal defects (ASDs) with small shunts using MRI followed by transcatheter closure monitored by MR fluoroscopy.Materials and MethodsAcute ASDs were created in 14 pigs under x‐ray fluoroscopy. Six animals were studied in order to select MR‐compatible delivery systems and imaging strategies. ASDs in eight animals were examined with balloon sizing under MR fluoroscopy, flow measurements, and contrast media injections, after which transcatheter closure was performed under MR fluoroscopy. The delivery system was assembled from commercially available materials.ResultsThe ratio of pulmonary to systemic flow (Qp/Qs) was reduced from 1.23 ± 0.15 before ASD closure to 1.07 ± 0.11 after ASD closure (P < 0.001). In two out of eight animals Qp/Qs was close to 1.0 before closure despite the presence of defects >15 mm. The ASDs were measurable with MR balloon sizing in all of the animals. Balloon sizing was identical with MR (16.9 ± 2.3 mm) and x‐ray fluoroscopy (17.1 ± 1.3 mm). The in‐house‐assembled delivery system allowed successful placement of closure devices under MR guidance.ConclusionAssessment and closure of small shunts with MR fluoroscopy is feasible. A barrier to the rapid implementation of transcatheter closure in patients is uncertainty about the MR safety of guidewires and device delivery systems. J. Magn. Reson. Imaging 2005;21:204–211. © 2005 Wiley‐Liss, Inc.
A multi‐proxy study of Holocene lake development, lake settlement and vegetation history in central Ireland
Authors: Selby K. A. , O'Brien C. E. , Brown A. G. , Stuijts I. 
Published: February 2005

AbstractStratigraphical investigations, geomorphological mapping, and diatom, plant macrofossil and pollen analyses were undertaken in and around two lakes in central Ireland to establish correlations between changes in lake conditions and catchment vegetation throughout the Holocene. Similar investigations of an adjacent mire reveal early Holocene changes in lake level and area. The palaeoecological data show high correlations related to variations in lake depth and area, catchment vegetation type, organic inputs and trophic status. Catchment‐scale deforestation is gradual and occurs through the Bronze and the Iron Ages, and the construction of a crannog in the early Medieval period (seventh century AD) appears to be associated with a widespread increase in deforestation and mixed agriculture in the catchment. Both pollen and plant macrofossils suggest that one of the crannogs was used for crop storage in addition to domestic and any other activities. In the early to middle Holocene similarities in the proxy‐data appear to be climatically driven through changing lake levels and areal extent whereas the later Holocene record is clearly dominated by anthropogenic changes within the catchment and the construction of crannogs in the lakes. The advantages of combining multi‐proxy indicators of lake hydroecology with the vegetation record are illustrated. Copyright © 2005 John Wiley & Sons, Ltd.