bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Phase I Combination Study of Olaparib with Cisplatin and Gemcitabine in Adults with Solid Tumors
Authors: Rajan Arun , Carter Corey A. , Kelly Ronan J. , Gutierrez Martin , Kummar Shivaani , Szabo Eva , Yancey Mary Ann , Ji Jiuping , Mannargudi Baskar , Woo Sukyung , Spencer Shawn , Figg William Douglas , Giaccone Giuseppe 
Published: February 2012

AbstractPurpose: To determine the safety and tolerability of olaparib with cisplatin and gemcitabine, establish the maximum tolerated dose (MTD), and evaluate the pharmacodynamic and pharmacokinetic profile of the combination.Experimental Design: We conducted a phase I study of olaparib with cisplatin and gemcitabine in patients with advanced solid tumors. Treatment at dose level 1 (DL1) consisted of olaparib 100 mg orally every 12 hours on days 1 to 4, gemcitabine 500 mg/m2 on days 3 and 10, and cisplatin 60 mg/m2 on day 3. PAR levels were measured in peripheral blood mononuclear cells (PBMC).Results: Dose-limiting toxicities (DLT) in two of three patients at DL1 included thrombocytopenia and febrile neutropenia. The protocol was amended to enroll patients treated with ≤2 prior severely myelosuppressive chemotherapy regimens and treated with olaparib 100 mg once daily on days 1 to 4 (DL−1). No DLTs were seen in six patients at DL−1. Because of persistent thrombocytopenia and neutropenia following a return to DL1, patients received 100 mg olaparib every 12 hours on day 1 only. No hematologic DLTs were observed; nonhematologic DLTs included gastrointestinal bleed, syncope, and hypoxia. Of 21 patients evaluable for response, two had partial response. Olaparib inhibited PARP in PBMCs and tumor tissue, although PAR levels were less effectively inhibited when olaparib was used for a short duration.Conclusions: Olaparib in combination with cisplatin and gemcitabine is associated with myelosuppression even at relatively low doses. Modified schedules of olaparib in chemotherapy naive patients will have to be explored with standard doses of chemotherapy. Clin Cancer Res; 18(8); 2344–51. ©2012 AACR.
A Phase II Study of Lapatinib in Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck
Authors: de Souza Jonas A. , Davis Darren W. , Zhang Yujian , Khattri Arun , Seiwert Tanguy Y. , Aktolga Serdal , Wong Stuart J. , Kozloff Mark F. , Nattam Sreenivasa , Lingen Mark W. , Kunnavakkam Rangesh , Stenson Kerstin M. , Blair Elizabeth A. , Bozeman Jeffrey , Dancey Janet E. , Vokes Everett E. , Cohen Ezra E.W. 
Published: February 2012

AbstractPurpose: This study sought to determine the efficacy and safety profile of lapatinib in patients with recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN).Experimental Design: This phase II multiinstitutional study enrolled patients with recurrent/metastatic SCCHN into two cohorts: those without (arm A) and those with (arm B) before exposure to an epidermal growth factor receptor (EGFR) inhibitor. All subjects were treated with lapatinib 1,500 mg daily. Primary endpoints were response rate (arm A) and progression-free survival (PFS; arm B). The biologic effects of lapatinib on tumor growth and survival pathways were assessed in paired tumor biopsies obtained before and after therapy.Results: Forty-five patients were enrolled, 27 in arm A and 18 in arm B. Diarrhea was the most frequent toxicity occurring in 49% of patients. Seven patients experienced related grade 3 toxicity (3 fatigue, 2 hyponatremia, 1 vomiting, and 1 diarrhea). In an intent-to-treat analysis, no complete or partial responses were observed, and stable disease was the best response observed in 41% of arm A (median duration, 50 days, range, 34–159) and 17% of arm B subjects (median, 163 days, range, 135–195). Median PFS was 52 days in both arms. Median OS was 288 (95% CI, 62–374) and 155 (95% CI, 75–242) days for arms A and B, respectively. Correlative analyses revealed an absence of EGFR inhibition in tumor tissue.Conclusion: Lapatinib as a single agent in recurrent/metastatic SCCHN, although well tolerated, appears to be inactive in either EGFR inhibitor naive or refractory subjects. Clin Cancer Res; 18(8); 2336–43. ©2012 AACR.
Celastrol Suppresses Growth and Induces Apoptosis of Human Hepatocellular Carcinoma through the Modulation of STAT3/JAK2 Signaling Cascade In Vitro and In Vivo
Authors: Rajendran Peramaiyan , Li Feng , Shanmugam Muthu K. , Kannaiyan Radhamani , Goh Jen Nee , Wong Kwong Fai , Wang Wei , Khin Ester , Tergaonkar Vinay , Kumar Alan Prem , Luk John M. , Sethi Gautam 
Published: February 2012

Abstract
Cumulative evidences(s) have established that the constitutive activation of STAT3 plays a pivotal role in the proliferation, survival, metastasis, and angiogenesis and thus can contribute directly to the pathogenesis of hepatocellular carcinoma (HCC). Thus, novel agents that can inhibit STAT3 activation have potential for both prevention and treatment of HCCs. The effect of celastrol on STAT3 activation, associated protein kinases, STAT3-regulated gene products, cellular proliferation, and apoptosis was investigated. The in vivo effect of celastrol on the growth of human HCC xenograft tumors in athymic nu/nu mice was also examined. We observed that celastrol inhibited both constitutive and inducible STAT3 activation, and the suppression was mediated through the inhibition of activation of upstream kinases c-Src, as well as Janus-activated kinase-1 and -2. Vanadate treatment reversed the celastrol-induced modulation of STAT3, suggesting the involvement of a tyrosine phosphatase. The inhibition of STAT3 activation by celastrol led to the suppression of various gene products involved in proliferation, survival, and angiogenesis. Celastrol also inhibited the proliferation and induced apoptosis in HCC cells. Finally, when administered intraperitoneally, celastrol inhibited STAT3 activation in tumor tissues and the growth of human HCC xenograft tumors in athymic nu/nu mice without any side effects. Overall, our results suggest for the first time that celastrol exerts its antiproliferative and proapoptotic effects through suppression of STAT3 signaling in HCC both in vitro and in vivo. Cancer Prev Res; 5(4); 631–43. ©2012 AACR.
Reduction of thrombus size in murine models of thrombosis following administration of recombinant α1-proteinase inhibitor mutant proteins
Authors: Eltringham-Smith Louise J. , Bhakta Varsha , Gataiance Sharon , Sheffield William P. 
Published: February 2012

SummaryThe variant serpin α1-PI M358R inhibits thrombin and other proteases such as activated protein C (APC) and factor XIa. We previously described recombinant proteins HAPI M358R (α1-PI M358R containing an N-terminal extension corresponding to residues 1–75 of heparin cofactor II) and HAPI RCL5 (HAPI M358R with F352-I356 and I360 substituted for the corresponding residues of antithrombin), with enhanced selectivity for thrombin over APC inhibition. We tested the hypotheses that these recombinant proteins would limit thrombosis in three mouse models, and that the HAPI chimeric proteins would be more effective than α1-PI M358R. Recombinant serpins were purified from Escherichia coli by nickel chelate and ion exchange affinity chromatography, and administered to mice intravenously. HAPI RCL5 reduced incorporation of radiolabelled fibrin(ogen) into thrombi in the ferric chloride-injured vena cava in a dose-dependent manner; HAPI M358R was less effective and α1-PI M358R was without effect. In a model of murine endotoxaemia, HAPI RCL5 was more effective than α1-PI M358R in reducing radiolabelled fibrin(ogen) deposition in heart and kidneys; immunohis-tochemistry of tissue sections showed lesser staining with anti-fibrin(ogen) antibodies with both treatments. In the ferric chloride-injured murine carotid artery, administration of both recombinant serpins was equally effective in lengthening the vessel’s time to occlusion. Our results show that the antithrombotic efficacy of the recombinant serpins correlates with their potency as thrombin inhibitors, since HAPI RCL5 inhibits thrombin, but not factors Xa, XIa, XIIa, or neutrophil elastase, more rapidly than α1-PI M358R.
Micro-array profiling exhibits remarkable intra-individual stability of human platelet micro-RNA
Authors: Stratz Christian , Nührenberg Thomas G. , Binder Harald , Valina Christian M. , Trenk Dietmar , Hochholzer Willibald , Neumann Franz , Fiebich Bernd L. 
Published: February 2012

SummaryPlatelets play an important role in haemostasis and thrombus formation. Latest research identified platelets harbouring so called microRNAs (miRNA). MiRNAs are short single-stranded RNAs modulating gene expression by targeting mRNAs. Limited data exist on inter-individual variability of platelet miRNA profile while no data are available on intra-individual variability. We assessed platelet miRNA profile in five volunteers at five time points over a time course of 10 days; 24 hours prior to the last blood sampling, subjects took 500 mg acetylsali-cylic acid (ASA). Platelet miRNA was isolated from leucocyte-depleted platelet-rich plasma, and miRNA array-analysis was performed. Temporal patterns and ASA effect were explored by a linear mixed effects model for each miRNA. For the 20 most abundantly expressed platelet miRNAs, target gene search was performed and an annotation network was created. MiRNA expression profiling of 1,281 human miRNAs revealed relevant expression of 221 miRNAs consistently expressed in all samples at all time points. Correlation of platelet miRNA ranks was highly significant to other studies. Global distribution of miRNA expression was relatively similar in all subjects. No miRNA exhibited a significant effect of time at level 0.05. After 24 hours, no significant effect of ASA was found. Concerning functional implications of the 20 most abundantly expressed miRNAs, we found six functional themes. In conclusion, platelet miRNA profile is remarkably stable over the time period studied. Single-point analysis of platelet miRNA profile is reasonable when inter-individual differences are studied. The functional annotation network points toward extra-platelet effects of platelet miRNAs.
The role of microRNAs in arterial remodelling
Authors: Nazari-Jahantigh Maliheh , Wei Yuanyuan , Schober Andreas 
Published: February 2012

SummaryAdaptive alterations of the vessel wall architecture, called vascular remodelling, can be found in arterial hypertension, during the formation of aneurysms, in restenosis after vascular interventions, and in atherosclerosis. MicroRNAs (miR) critically affect the main cellular players in arterial remodelling and may either promote or inhibit the structural changes in the vessel wall. They regulate the phenotype of smooth muscle cells (SMCs) and control the inflammatory response in endothelial cells and macrophages. In SMCs, different sets of miRs induce either a synthetic or contractile phenotype, respectively. The conversion into a synthetic SMC phenotype is a crucial event in arterial remodelling. Therefore, reprogramming of the SMC phenotype by miR targeting can modulate the remodelling process. Furthermore, the effects of stimuli that induce remodelling, such as shear stress, angiotensin II, oxidised low-density lipoprotein, or apoptosis, on endothelial cells are mediated by miRs. The endothelial cell-specific miR-126, for example, is transferred in microvesicles from apoptotic endothelial cells and plays a protective role in atherogenesis. The inflammatory response of the innate immune system, especially through macrophages, promotes arterial remodelling. miR-155 induces the expression of inflammatory cytokines, whereas miR-146a and miR-147 are involved in the resolution phase of inflammation. However, in vivo data on the role of miRs in vascular remodelling are still scarce, which are required to test the therapeutic potential of the available, highly effective miR inhibitors.
Extended Osteocartilaginous Spreader Graft for Reconstruction of Deviated Nose
Authors: Sadooghi Mahmood , Ghazizadeh Matin 
Published: February 2012

ObjectiveCorrection of a deviated nose is a challenging problem for which different approaches may be considered. This study was designed to introduce a new technique for correction of a deviated nose with a high success rate.Study DesignThe study was a prospective follow‐up of 59 patients with deviated nose who had undergone corrective surgery.SettingAn extended osteocartilaginous spreader graft was harvested from the quadrangular septum and the perpendicular plate of the ethmoid. After a medial osteotomy that was performed on the concave side, the nasal bone was lateralized and an extended osteocartilaginous spreader graft was inserted between the nasal bone and the septum to prevent further retraction of the concave side due to fibrotic scar tissue. On the contralateral side, a low lateral osteotomy was done as routine.Subjects and MethodsThe operation was done on the 59 cases with deviated nose. The subjects were followed up during a period of 8 months to 4 years. According to physical examination, postoperative photography, and patients’ satisfaction, the final results were categorized as excellent, fair, or poor.ResultsForty‐eight patients (81.3%) were categorized as having excellent results. Eight patients (13.6%) showed fair improvement, while the results of surgery in only 3 patients (5.1%) were classified as poor.ConclusionAn extended osteocartilaginous spreader graft, with medial osteotomy and lateralization of the nasal bone on the concave side, is a new technique with a high success rate for correction of deviated nose.
Mastoidectomy Cavity Obliteration with Bioactive Glass
Authors: Silvola Juha Tapio 
Published: February 2012

ObjectiveTo show that mastoid cavities with continuous infections and cleaning problems can be obliterated with bioactive glass (BG) and to present results of a pilot study for 16 operations on adults.Study DesignCase series with planned data collection.SettingPäijät‐Häme Central Hospital, Finland—a single ear, nose, and throat (ENT) hospital department serving a population of 216,000.Subjects and MethodsFourteen patients had a large open radical cavity with recurrent infections. Two ears had discharge and pain after simple mastoidectomy. A re‐mastoidectomy included support of the cavity skin and obliteration with BG. The mean follow‐up time was 2.2 years.ResultsAll ears became dry. One reoperation was needed as the fascia support to the ear canal (EC) skin was too weak, and part of the BG leaked into the EC. The ear stayed dry, and the missing BG was replaced in a reoperation. A slightly short musculoperiosteal flap supported the EC skin in 1 ear. A minor amount of BG leaked into the EC. The ear stayed dry. The aim was an ample ear canal. One ear was overfilled and required meatoplasty. Simple mastoid cavities were isolated from the middle ear and become asymptomatic.ConclusionsIn this pilot study, BG works safely and with success as an obliteration material in problematic open radical cavities. Bioactive glass seems to tolerate chronic infection in the mastoid and prevent postoperative infections.
Malpractice in Head and Neck Surgery
Authors: Simonsen Andrew R. , Duncavage James A. , Becker Samuel S. 
Published: February 2012

ObjectiveTo examine the sources of litigation related to the practice of head and neck surgery.Study DesignAnalysis of malpractice claims directly related to the diagnosis and treatment of head and neck disease provided by 16 medical liability insurance companies.SettingNot applicable.Subjects and MethodsData were obtained from 16 members of the Physician Insurers Association of America. All claims were either filed or closed between 1978 and 2007. Claims were evaluated for patient age, the cause for the claim, any surgical complications, and indemnity paid.ResultsThree hundred fifteen claims were identified between 1978 and 2007. The mean patient age was 48 years (median, 47 years). The greatest number of claims came from the 36‐ to 45‐years age group (n = 68, 24.6%). Perioperative complications represented the largest cause of claims (n = 169, 53.7%), followed by delay of or missed diagnosis (n = 109, 34.6%) and persistence or recurrence of disease (n = 21, 6.7%). Among perioperative complications, nerve injuries were the largest group (n = 64, 20.3%), followed by airway‐related claims (n = 27, 8.6%), esophageal injuries (n = 14, 4.4%), poor cosmetic results (n = 14, 4.4%), vessel injuries (n = 11, 3.5%), and postoperative infections (n = 2, 0.6%). Overall, mortalities resulted in 62 (19.7%) claims.ConclusionsFour important risks for malpractice litigation in head and neck surgery were identified: young patient age, perioperative complications, delay of or missed diagnosis, and persistence or recurrence of disease.
Qualitative and Quantitative Differences between 2 Robotic Thyroidectomy Techniques
Authors: Terris David J. , Singer Michael C. 
Published: February 2012

ObjectivesTwo distinct remote access robotic thyroidectomy techniques were implemented in a high‐volume endocrine surgery practice. Important technical and clinical differences were observed and are described.Study DesignCross‐sectional study with planned data collection.SettingThyroid center.Subjects and MethodsA panel of demographic and clinical parameters was captured in a series of patients undergoing 1 of 2 robotic thyroidectomy techniques (robotic axillary thyroidectomy [RAT] or robotic facelift thyroidectomy [RFT]). Particular attention was paid to time of surgery, ease of dissection, complications, use of drains, and length of stay.ResultsFifteen robotic hemithyroidectomies were accomplished by either RAT (n = 5) or RFT (n = 10). The duration of surgery for RAT averaged 196 ± 38.1 minutes, with no clear downward trend observed. The mean time of surgery for RFT was 156.9 ± 16.3 minutes, with a steady trend toward shorter surgical times. All 5 RAT patients were managed with drains and as inpatients (length of stay = 1.0 days); 9 of 10 RFT patients were managed without drains and on an outpatient basis (the first patient had a drain and was observed for 1 night in the hospital; P <. 001). Ease of surgery, familiarity with anatomic dissection planes, and surgeon comfort level all favored RFT.ConclusionsIn an early experience of a small series of patients, a more rapid learning curve reflected by shorter operative times was observed with robotic facelift thyroidectomy compared with robotic axillary thyroidectomy. Furthermore, the vast majority of patients could be managed as outpatients, which represents one of several apparent advantages.
Customer Focus in the Liberalized Era of Marketing
Authors: Agrawal Mohan Lal 
Published: February 2012

The decade just ended will be most remembered in India for forcing a sea change in the mindset of Indian marketers. Traditionally engaged in rationing, distributing or selling their wares, they now have to market products and face fierce competition. They need to redefine themselves and dig out the concept of customer focus afresh. Their very survival depends on how swiftly and effectively they incorporate the customer in business plans. While conceptualizing customer focus for such marketers, the paper tracks the evolving instruments of customer focus from a pre-historic period of marketing to the present era of post-modern marketing. With a case illustration from Bajaj Auto, the paper suggests multiple ways in which marketers can discover customer focus and come out leaders in the postmodern era of marketing.
Child Labour in a Rural Non-Farm Sector – A Study of the Silk Reeling Industry
Authors: Reddy Y. Gangi 
Published: February 2012

Child labour must not be tolerated in any form and must be prevented and eliminated. It is imperative to abolish the most exploitative and intolerable forms of child labour as a first priority. - The UN System in India Silk reeling is one of those small scale hazardous industries in which child labour is dominant in India. A detailed study made in Ramanagaram, a reeling centre in Karnataka, shows that about 50 per cent of the workers are children below 14, working for a pittance, a major human tragedy. The responsibility for this tragedy lies both with the parents and the owners of the reeling units. Most of the children are eager to go to school and with the help of the state government and some NGOs, a bridge course has been started to help them fulfil their desires. Some live case studies document the facts uncovered.
Green Consumer: An Initial Study
Authors: Verma Harsh V. 
Published: February 2012

Marketing philosophy was crystallized in 1950s. But the real business practices remained tar from what marketing proposed. The result was the growth of customer dissatisfaction. This led to the rise of the first ‘ism’ viz., consumerism. During the 1970s the West saw the emergence of another ‘ism’. This time it was the concern and care for the environment. It was environmentalism. Environmentalism is a major force in the developed markets of the world. It has impacted the business through enaction of various laws and the rejection of companies and their products which behaved in ecologically inconsistent fashion. This paper reports the findings of an initial study done to explore some aspects related to the greenness of consumers. The data were collected on the constructs like perception of environmental problems, perceived consumer effectiveness in solving problems, and environmentally-conscious consumer behaviour. The consumers do perceive various listed problems as serious. But their concern level is not much with these problems. The study of the behaviour reveals the consumers do not behave in environmentally conscious manner. At present, only early signs of greening are visible. It would take some more time for the consumers to become green. Once that happens taking cognizance of this development would become a necessity for any business.
Occupational Diseases and Their Determinants
Authors: Sarkar Debasish , Husain Zakir , Bhattacharya Rabindra N , Kanjilal Barun 
Published: February 2012

In recent years theoretical and empirical are focussing on occupational health hazards in industries that deal with gemstone, lime, etc. In this paper the focus is on one such industry – coal. We seek to examine the nature and magnitude of occupational diseases in coal-mining. The socio-economic and technological factors determining the incidence of occupational diseases on workers is also identified using a Tobit model. Finally, the implications of the findings of this paper for designing an optimal health care strategy have been stated. The work is based on a survey of three coal mines in the state of West Bengal, India.
A Study of Corporate Social Responsiveness
Authors: Chacharkar D. Y. , Shukla A. V. 
Published: February 2012

Geographic distribution of industries in India has been an unbalanced one leading to lop sided regional growth. Thus, far the efforts of the GOI and the State Governments to remedy the situation have not met with much success. This is mainly due to the lack of desire on the part of business houses to enter into economically non-viable areas just to take care of balanced regional development. This paper attempts to present the picture in a slightly changed setting. It is reasoned that corporates should become increasingly socially committed not on the call of philanthropy but on sound business sense. A socially committed business house, to begin with, gains only on a few visible benefits but in the long run this business unit stands to gain in a number of ways. This is due to the Iceberg effect of social responsibility, it is felt. The paper presents a model of social responsibility, which enable business houses to sharpen their marketing tools. Besides guidelines to develop corporate – government partnership aimed at rapid growth and development leading to mutual benefits for all are also presented.