bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi‐centre assessment of mycotic rhinosinusitis in dogs: a retrospective study of initial treatment success (1998 to 2008)
Authors: Sharman M. , Paul A. , Davies D. , MacKay B. , Swinney G. , Barrs V. , Arteaga A. , Robertson I. D. , Mansfield C. 
Published: June 2010

Objectives: To retrospectively review the first treatment response of dogs with mycotic rhinosinusitis to commonly utilised treatment techniques.Methods: Medical records of dogs treated for mycotic rhinosinusitis were obtained retrospectively via a manual review of the clinical databases of six veterinary referral centres for the period of January 1998 to June 2008, and first treatment outcome was evaluated. Historical and clinicopathological findings were also reviewed to evaluate their impact on treatment success or failure.Results: There was no significant difference in first treatment outcome between treatment groups (P=0·21). When all topical treatments were considered together (n=85), 39 dogs (45·8%) had a successful first treatment. Initial treatment success was associated with a younger age (56·3versus75·8 months; P=0·02) and was 2·7 times more likely in dogs with unilateral disease, although this was not significant (P=0·07). Adjunctive therapy with systemic antifungal agents was associated with treatment failure (PÄ0·01). Fifty‐nine dogs (69·4%) responded successfully following multiple treatments.ClinicalSignificance: Treatment of mycotic rhinosinusitis remains challenging, and multiple treatments are frequently required for adequate treatment. Reasons for first treatment failure are likely multifactorial in origin, making it difficult to predict those dogs that are likely to have a superior prognosis, regardless of the treatment type used.
ORIGINAL ARTICLE: Squamous cell carcinoma of the oral tongue in patients younger than 30 years: clinicopathologic features and outcome
Authors: Soudry E. , Preis M. , Hod R. , Hamzany Y. , Hadar T. , Bahar G. , Strenov Y. , Shpitzer T. 
Published: June 2010

Clin. Otolaryngol. 2010, 35, 307–312Objective:  To assess the possible effect of young age on clinical behaviour and survival outcome of squamous cell carcinoma of the oral tongue.Design:  Retrospective, case control study.Setting:  A major tertiary referral centre.Participants:  Eighty‐five patients with oral tongue squamous cell carcinoma with at least 2 years of follow‐up.Main outcome measurements:  Clinical and histopathological staging, disease‐free survival, disease‐specific survival and overall survival.Results:  Eleven patients (13%) were younger than 30 years. Compared to the older patients, they had a significantly worse N stage (P = 0.041), more perineural invasion (P = 0.012), and higher rates, though not significant, of treatment failure (46%, including 60% with distant metastases, versus 35%, nearly all locoregional) and mortality (100% of treatment failures versus 73%). There were no significant between‐group differences in 5‐year disease‐free, disease‐specific, and overall survival.Conclusion:  In this study, patients younger than 30 years of age presented with advanced tumour stages and with a different failure pattern compared to the older age group. This may be attributable to age‐related biologic behaviour or delayed cancer diagnosis. Differences in disease free survival and overall survival could not be established.
Ultrasound of the posterior circumflex humeral artery
Authors: Robinson DJ , Marks P , Schneider‐Kolsky ME 
Published: June 2010

SummaryQuadrilateral space syndrome (QSS) is described as compression neuropathy of the axillary neurovascular bundle in the quadrilateral space of the shoulder. This neurovascular bundle includes the posterior circumflex humeral artery (PCHA). Historically, angiography and more recently magnetic resonance angiography have been used to assess occlusion and stenosis of the PCHA in cases of suspected QSS. These traditional imaging techniques have a number of disadvantages in terms of cost, availability, invasiveness and patient comfort. We undertook to examine the ability of ultrasound to reliably visualise the PCHA. Asymptomatic adult volunteers were recruited from staff, and patients attending the radiology department who presented for pathologies unrelated to the shoulder. We used a new technique to assess blood flow in the PCHA, performing the scan from a posterolateral approach on the upper arm just above the level of the surgical neck of the humerus. This technique enabled the scan to be undertaken with the patient seated comfortably. Fifty volunteers were recruited into the study. The mean (±SD) age was 35 (±14 years). The PCHA was visualised in all patients. Our method was able to maximise Doppler sensitivity and visualisation of the artery without discomfort to the patient in less than 10 min. Ultrasound can be used to reliably visualise the PCHA. Ultrasound has potential to be used in the assessment of the PCHA in cases of QSS.
Clinical care and technical recommendations for 90yttrium microsphere treatment of liver cancer
Authors: Wang S‐C , Bester L , Burnes JP , Clouston JE , Hugh TJ , Little AF , Padbury RTA , Price D 
Published: June 2010

SummarySelective internal radiation therapy (SIRT) with 90yttrium microspheres is a relatively new clinical modality for treating non‐resectable malignant liver tumours. This interventional radiology technique employs percutaneous microcatheterisation of the hepatic arterial vasculature to selectively deliver radioembolic microspheres into neoplastic tissue. SIRT results in measurable tumour responses or delayed disease progression in the majority of eligible patients with hepatocellular carcinoma or hepatic metastases arising from colorectal cancer. It has also been successfully used as palliative therapy for non‐colorectal malignancies metastatic to the liver. Although most adverse events are mild and transient, SIRT also carries some risks for serious and – rarely – fatal outcomes. In particular, entry of microspheres into non‐target vessels may result in radiation‐induced tissue damage, such as severe gastric ulceration or radiation cholecystitis. Radiation‐induced liver disease poses another significant risk. By careful case selection, considered dose calculation and meticulous angiographic technique, it is possible to minimise the incidence of such complications to less than 10% of all treatments. As the number of physicians employing SIRT expands, there is an increasing need to consolidate clinical experience and expertise to optimise patient outcomes. Authored by a panel of clinicians experienced in treating liver tumours via SIRT, this paper collates experience in vessel mapping, embolisation, dosimetry, microsphere delivery and minimisation of non‐target delivery. In addition to these clinical recommendations, the authors propose institutional criteria for introducing SIRT at new centres and for incorporating the technique into multidisciplinary care plans for patients with hepatic neoplasms.
Randomised, placebo‐controlled, crossover trial of sildenafil citrate in the treatment of erectile dysfunction following external beam radiation treatment of prostate cancer
Authors: Harrington C , Campbell G , Wynne C , Atkinson C 
Published: June 2010

SummaryErectile dysfunction (ED) commonly affects the quality of life of men after treatment of prostate cancer. We conducted a placebo‐controlled, crossover randomised trial to assess the efficacy and tolerability of sildenafil citrate in the treatment of ED developing after external beam radiation treatment (EBRT) of localized prostate cancer. Sixty‐six patients who had developed ED following radiation treatment agreed to participate and were allocated to sildenafil or placebo to be taken prior to four sexual attempts. In the crossover period, subjects received the alternative tablet for a further four attempts. Allocation was centrally randomized, and researchers and patients were both blinded to the trial arm. Efficacy was assessed using the International Index of Erectile Function (IIEF) questionnaire and with a separate global efficacy question. Forty‐three subjects completed the study. There was a significant increase in mean scores from baseline for all domains of the IIEF with sildenafil compared with placebo (P < 0.001). Affirmative response to the global efficacy question was more common after taking sildenafil compared with placebo. In approximately half of the patients, the improvement in the erectile function domain score corresponded to a moderate improvement in ED (e.g. success ‘sometimes’ to ‘most times’). Sildenafil was associated with mild flushing, nasal stuffiness or indigestion in 8–10% patients and moderate flushing in 10%. The current study adds to the evidence that phosphodiesterase inhibitors are an effective and well‐tolerated treatment for ED after EBRT for prostate cancer.
Improving bladder cancer treatment with radiotherapy using separate intensity modulated radiotherapy plans for boost and elective fields
Authors: Van Rooijen DC , Van De Kamer JB , Hulshof MCCM , Koning CCE , Bel A 
Published: June 2010

SummaryThe aim of this study is to investigate to what extent IMRT can decrease the dose to the organs at risk in bladder cancer treatment compared with conformal treatment while making separate treatment plans for the elective field and the boost. Special attention is paid to sparing small intestines. Twenty patients who were treated with the field‐in‐field technique (FiF) were re‐planned with intensity modulated radiotherapy (IMRT) using five and seven beams, respectively. Separate treatment plans were made for the elective field (including the pelvic lymph nodes) and the boost, which enables position correction for bone and tumour separately. The prescribed dose was 40 Gy to the elective field and 55 or 60 Gy to the planning target volume (PTV). For bladder and rectum, V45Gy and V55Gy were compared, and for small intestines, V25Gy and V40Gy. The dose distribution with IMRT conformed better to the shape of the target. There was no significant difference between the techniques in dose to the healthy bladder. The median V40Gy of the small intestines decreased from 114 to 66 cc (P = 0.001) with five beam IMRT, and to 55 cc (P = 0.001) with seven beam IMRT compared with FiF. V45Gy for rectum decreased from 34.2% to 17.5% (P = 0.004) for both five and seven beam plans, while V55Gy for rectum remained the same. With IMRT, a statistically significant dose decrease to the small intestines can be achieved while covering both tumour and elective PTV adequately.
Effect of lateral target motion on image registration accuracy in CT‐guided helical tomotherapy: A phantom study
Authors: Medwig J , Gaede S , Battista JJ , Yartsev S 
Published: June 2010

SummaryOptimisation of imaging modes for kilovoltage CT (kVCT) used for treatment planning and megavoltage CT (MVCT) image guidance used in ungated helical tomotherapy was investigated for laterally moving targets. Computed tomography images of the QUASAR™ Respiratory Motion Phantom were acquired without target motion and for lateral motion of the target, with 2‐cm peak‐to‐peak amplitude and a period of 4 s. Reference kVCT images were obtained using a 16‐slice CT scanner in standard fast helical CT mode, untagged average CT mode and various post‐processed 4D‐CT modes (0% phase, average and maximum intensity projection). Three sets of MVCT images with different inter‐slice spacings of were obtained on a Hi‐Art tomotherapy system with the phantom displaced by a known offset position. Eight radiation therapists performed co‐registration of MVCT obtained with 2‐, 4‐ and 6‐mm slice spacing and kVCT studies independently for all 15 CT imaging combinations. In the investigated case, the untagged average kVCT and 4‐mm slice spacing for the MVCT yielded more accurate registration in the transverse plane. The average residual uncertainty of this combination of imaging procedures was 0.61 ± 0.16 mm in the longitudinal direction, 0.45 ± 0.14 mm in the anterior–posterior direction and insignificant in the lateral direction. Manual registration of MVCT–kVCT study pairs is necessary to account for a target in significant lateral motion with respect to bony structures.
Scaling Laws for Plasma Concentrations and Tolerable Doses of Anticancer Drugs
Authors: Dawson Thomas H. 
Published: June 2010

AbstractGeneral scaling laws are developed for projecting measurements of the plasma concentrations of anticancer drugs from laboratory animals to humans and among humans of different sizes. Associated scaling laws for critical drug doses are established from these laws. Broad categories of single and periodic i.v. bolus dosings are considered. Validity of the relations is shown using measurement from the literature for several well-known cytotoxic agents. The scaling theory is also shown to apply to novel anticancer drugs now available or presently under development, as represented by the p.o. administered prodrug capecitabine, the gene silencing inhibitor zebularine, and the blood vessel inhibitor bevacizumab. Scaling considerations for the modern practice of combination chemotherapy are also discussed. Cancer Res; 70(12); 4801–8. ©2010 AACR.
E6-Associated Protein Is Required for Human Papillomavirus Type 16 E6 to Cause Cervical Cancer in Mice
Authors: Shai Anny , Pitot Henry C. , Lambert Paul F. 
Published: June 2010

Abstract
High-risk human papillomaviruses (HPV) cause certain anogenital and head and neck cancers. E6, one of three potent HPV oncogenes that contribute to the development of these malignancies, is a multifunctional protein with many biochemical activities. Among these activities are its ability to bind and inactivate the cellular tumor suppressor p53, induce expression of telomerase, and bind to various other proteins, including Bak, E6BP1, and E6TP1, and proteins that contain PDZ domains, such as hScrib and hDlg. Many of these activities are thought to contribute to the role of E6 in carcinogenesis. The interaction of E6 with many of these cellular proteins, including p53, leads to their destabilization. This property is mediated at least in part through the ability of E6 to recruit the ubiquitin ligase E6-associated protein (E6AP) into complexes with these cellular proteins, resulting in their ubiquitin-mediated degradation by the proteasome. In this study, we address the requirement for E6AP in mediating acute and oncogenic phenotypes of E6, including induction of epithelial hyperplasia, abrogation of DNA damage response, and induction of cervical cancer. Loss of E6AP had no discernible effect on the ability of E6 to induce hyperplasia or abrogate DNA damage responses, akin to what we had earlier observed in the mouse epidermis. Nevertheless, in cervical carcinogenesis studies, there was a complete loss of the oncogenic potential of E6 in mice nulligenic for E6AP. Thus, E6AP is absolutely required for E6 to cause cervical cancer. Cancer Res; 70(12); 5064–73. ©2010 AACR.
Cyclin E Deregulation Impairs Mitotic Progression through Premature Activation of Cdc25C
Authors: Bagheri-Yarmand Rozita , Nanos-Webb Angela , Biernacka Anna , Bui Tuyen , Keyomarsi Khandan 
Published: June 2010

Abstract
The cyclin E–cyclin-dependent kinase 2 (CDK2) complex accelerates entry into the S phase of the cell cycle and promotes polyploidy, which may contribute to genomic instability in cancer cells. The effect of low molecular weight isoforms of cyclin E (LMW-E) overexpression on mitotic progression and its link to genomic instability were the focus of this study. Here, we show that full-length cyclin E (EL) and LMW-E overexpression impairs the G2-M transition differently by targeting dual-specificity phosphatase Cdc25C activity. We identify Cdc25C as an interaction partner and substrate for cyclin E/CDK2 kinase. Specifically, the cyclin E/CDK2 complex phosphorylates Cdc25C on Ser214, leading to its premature activation, which coincides with higher cyclin B/CDK1 and Polo-like kinase 1 (PLK1) activities in an S-phase–enriched population that result in faster mitotic entry. Whereas EL overexpression leads to hyperactivation of Cdc25C, cyclin B/CDK1, and PLK1 in a G2-M–enriched population, LMW-E overexpression causes premature inactivation of Cdc25C and PLK1, leading to faster mitotic exit. In addition, LMW-E–overexpressing cells showed a reduction in the mitotic index in the presence of a spindle poison and faster degradation of cyclin B, suggesting an increased rate of mitotic slippage and adaptation to the spindle checkpoint. Lastly, downregulation of Cdc25C inhibits LMW-E–mediated chromosome missegregation, anaphase bridges, and centrosome amplification. These results suggest that the high levels of LMW-E isoforms found in breast cancer may contribute to cellular transformation and genomic instability by impairing mitotic progression involving Cdc25C. Cancer Res; 70(12); 5085–95. ©2010 AACR.
High-Mobility Group A1 Proteins Regulate p53-Mediated Transcription of Bcl-2 Gene
Authors: Esposito Francesco , Tornincasa Mara , Chieffi Paolo , De Martino Ivana , Pierantoni Giovanna Maria , Fusco Alfredo 
Published: June 2010

Abstract
We have previously described a mechanism through which the high-mobility group A1 (HMGA1) proteins inhibit p53-mediated apoptosis by delocalizing the p53 proapoptotic activator homeodomain-interacting protein kinase 2 from the nucleus to the cytoplasm. By this mechanism, HMGA1 modulates the transcription of p53 target genes such as Mdm2, p21waf1, and Bax, inhibiting apoptosis. Here, we report that HMGA1 antagonizes the p53-mediated transcriptional repression of another apoptosis-related gene, Bcl-2, suggesting a novel mechanism by which HMGA1 counteracts apoptosis. Moreover, HMGA1 overexpression promotes the reduction of Brn-3a binding to the Bcl-2 promoter, thereby blocking the Brn-3a corepressor function on Bcl-2 expression following p53 activation. Consistently, a significant direct correlation between HMGA1 and Bcl-2 overexpression has been observed in human breast carcinomas harboring wild-type p53. Therefore, this study suggests a novel mechanism, based on Bcl-2 induction, by which HMGA1 overexpression contributes to the escape from apoptosis leading to neoplastic transformation. Cancer Res; 70(13); 5379–88. ©2010 AACR.
The Polycomb Group Protein Bmi-1 Is Essential for the Growth of Multiple Myeloma Cells
Authors: Jagani Zainab , Wiederschain Dmitri , Loo Alice , He Dan , Mosher Rebecca , Fordjour Paul , Monahan John , Morrissey Michael , Yao Yung-Mae , Lengauer Christoph , Warmuth Markus , Sellers William R. , Dorsch Marion 
Published: June 2010

Abstract
Bmi-1 is a member of the Polycomb group family of proteins that function in the epigenetic silencing of genes governing self-renewal, differentiation, and proliferation. Bmi-1 was first identified through its ability to accelerate c-Myc–induced lymphomagenesis. Subsequent studies have further supported an oncogenic role for Bmi-1 in several cancers including those of the breast, lung, prostate, and brain. Using a stable and inducible shRNA system to silence Bmi-1 gene expression, we show a novel role for Bmi-1 in regulating the growth and clonogenic capacity of multiple myeloma cells both in vitro and in vivo. Moreover, to elucidate novel gene targets controlled by Bmi-1, global transcriptional profiling studies were performed in the setting of induced loss of Bmi-1 function. We found that the expression of the proapoptotic gene Bim is negatively regulated by Bmi-1 and that Bim knockdown functionally rescues the apoptotic phenotype induced upon loss of Bmi-1. Therefore, these studies not only highlight Bmi-1 as a cancer-dependent factor in multiple myeloma, but also elucidate a novel antiapoptotic mechanism for Bmi-1 function involving the suppression of Bim. Cancer Res; 70(13); 5528–38. ©2010 AACR.
Downregulation of Gadd45β Expression by Hepatitis C Virus Leads to Defective Cell Cycle Arrest
Authors: Higgs Martin R. , Lerat Hervé , Pawlotsky Jean-Michel 
Published: June 2010

AbstractMembers of the Gadd45 family play central roles in the cellular response to genotoxic stress and have been implicated in several human cancers, including hepatocellular carcinomas. Chronic infection by hepatitis C virus (HCV) is a major risk factor for the onset and development of primary hepatocellular tumors, although the underlying mechanisms are unclear. Here, we show a novel link between diminished Gadd45β expression and HCV infection. Inhibited Gadd45β expression was observed in both nontumoral and tumoral tissues from infected individuals, and in cell lines harboring a HCV replicon and the infectious HCV strain JFH1. Decreased Gadd45β expression was confirmed in vivo in a transgenic murine model expressing the entire HCV open reading frame. Mechanistically, hypermethylation of the Gadd45β promoter in the presence of HCV is responsible for this defect. Diminished Gadd45β expression leads to aberrant cell cycle arrest and diminished DNA excision repair. Together, these results provide a novel insight into the mechanisms involved in HCV-associated hepatocellular carcinomas, showing that reduced Gadd45β expression may play a contributory role to this process, and providing evidence that HCV may interfere with epigenetic gene expression by altering promoter methylation. Cancer Res; 70(12); 4901–11. ©2010 AACR.
FoxM1 Mediates Resistance to Herceptin and Paclitaxel
Authors: Carr Janai R. , Park Hyun Jung , Wang Zebin , Kiefer Megan M. , Raychaudhuri Pradip 
Published: June 2010

Abstract
Inherent and acquired therapeutic resistance in breast cancer remains a major clinical challenge. In human breast cancer samples, overexpression of the oncogenic transcription factor FoxM1 has been suggested to be a marker of poor prognosis. In this study, we report that FoxM1 overexpression confers resistance to the human epidermal growth factor receptor 2 monoclonal antibody Herceptin and microtubule-stabilizing drug paclitaxel, both as single agents and in combination. FoxM1 altered microtubule dynamics to protect tumor cells from paclitaxel-induced apoptosis. Mechanistic investigations revealed that the tubulin-destabilizing protein Stathmin, whose expression also confers resistance to paclitaxel, is a direct transcriptional target of FoxM1. Significantly, attenuating FoxM1 expression by small interfering RNA or an alternate reading frame (ARF)–derived peptide inhibitor increased therapeutic sensitivity. Our findings indicate that targeting FoxM1 could relieve therapeutic resistance in breast cancer. Cancer Res; 70(12); 5054–63. ©2010 AACR.