bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE EFFECT OF DIFFERENT HEAT STERILIZATION REGIMES ON THE QUALITY OF CANNED PROCESSED CHEESE
Authors: LAZÁRKOVÁ ZUZANA , BUŇKA FRANTIŠEK , BUŇKOVÁ LEONA , HOLÁŇ FELIX , KRÁČMAR STANISLAV , HRABĚ JAN 
Published: February 2010

ABSTRACTThe impact of four different regimes of heat sterilization (110C for 100 min, 115C for 32 min, 120C for 10 min and 125C for 3.2 min) on the properties of processed cheeses was evaluated. Also, nonsterilized samples were analyzed. Samples without and with the addition of lactose (0.5–2.0% w/w) were studied because lactose might be present in raw materials at various concentrations and might significantly affect processed cheese quality. All the sterilization regimes ensured inactivation of microflora. When the sterilization temperature was reduced (with simultaneously prolonged exposure time) the samples showed worse sensory properties. Significant hydrolytic changes of proteins and larger amino acid losses were also detected. The smallest changes were noted in products treated at 125C for 3.2 min. The heat treatment at 120C for 10 min caused acceptable modification of cheese properties. Addition of lactose higher than 1.0% w/w was found unsuitable for the production of sterilized processed cheeses.PRACTICAL APPLICATIONSProcessed cheese is a natural cheese‐based foodstuff manufactured using heat treatment (especially at 80–100C). Sterilized processed cheese is a specific product with prolonged shelf life, which could be used either in everyday life or for military and rescue team boarding during operations (Buňka et al. 2004). This product is manufactured in many countries but only limited scientific information about its quality and properties is available. Powdered skim milk and whey (used mainly for cutting the costs of the ingredients), which contain high amounts of lactose, are widely used in production of processed cheese. Lactose can show a deteriorating effect on the quality of processed cheeses, especially after application of severe heat treatment. Results of this study could be useful for setting sterilization time and temperature in order to manufacture products with high nutritive and sensory value. Moreover, a comparative study exploring acceptable lactose concentration value was carried out.
Development of Trigger Levels to Assess Catchment Disturbance on Stream Suspended Sediment Loads in the Magela Creek Catchment, Northern Territory, Australia
Authors: MOLIERE DENE R. , EVANS KENNETH G. 
Published: February 2010

AbstractTrigger levels for fine suspended sediment (FSS) load in streams are required to identify rainfall‐runoff events that have significantly elevated FSS loads, compared with expected background loads, as a result of catchment disturbance. Stream FSS load data collected in the mine‐impacted Magela Creek catchment in the wet‐dry tropics were used to derive water quality management trigger levels for two approaches – a Before‐After‐Control‐Impact Paired difference design (BACIP) and a regression relationship between observed FSS load and corresponding event discharge characteristics. The results indicate that both the BACIP and regression relationship approaches behave similarly, with similar FSS load events elevated above trigger levels. Notwithstanding this, it is recommended that in order to reliably assess the location and magnitude of a catchment disturbance on FSS load, a combination of BACIP and regression relationship approaches must be adopted. In this study, an event with a FSS load above trigger levels associated with both BACIP and the regression relationship fitted for the downstream site is considered to be significantly elevated as a result of a disturbance within the mine‐impacted region. While this technique cannot conclusively determine whether the cause of the disturbance is mine‐related or natural (such as fire or bank erosion), it is an efficient statistical method of identifying events that warrant further investigation and management action, if required.
CONTINUOUS FIRST ORDER LOGIC FOR UNBOUNDED METRIC STRUCTURES
Authors: YAACOV ITAÏ BEN 
Published: February 2010

We present an adaptation of continuous first order logic to unbounded metric structures. This has the advantage of being closer in spirit to C. Ward Henson's logic for Banach space structures than the unit ball approach (which has been the common approach so far to Banach space structures in continuous logic), as well as of applying in situations where the unit ball approach does not apply (i.e. when the unit ball is not a definable set). We also introduce the process of single point emboundment (closely related to the topological single point compactification), allowing to bring unbounded structures back into the setting of bounded continuous first order logic. Together with results from [4] regarding perturbations of bounded metric structures, we prove a Ryll–Nardzewski style characterization of theories of Banach spaces which are separably categorical up to small perturbation of the norm. This last result is motivated by an unpublished result of Henson.
The Dicey Role of Dicer: Implications for RNAi Therapy
Authors: Merritt William M. , Bar-Eli Menashe , Sood Anil K. 
Published: February 2010

Abstract
The dynamic properties of RNA interference (RNAi) in cancer biology have led investigators to pursue with significant interest its role in tumorigenesis and cancer therapy. We recently reported that decreased expression of key RNAi enzymes, Dicer and Drosha, in epithelial ovarian cancers was associated with poor clinical outcome in patients. Dicer expression was also functionally relevant in that targeted silencing was limited with RNAi fragments that require Dicer function compared with those that do not. Together, this and other studies suggest that RNAi machinery expression may affect key pathways in tumorigenesis and cancer biology. Understanding alterations in the functional RNAi machinery is of fundamental importance as we strive to develop novel therapies using RNAi strategies. Cancer Res; 70(7); 2571–4
Activation of Hedgehog Signaling by the Environmental Toxicant Arsenic May Contribute to the Etiology of Arsenic-Induced Tumors
Authors: Fei Dennis Liang , Li Hua , Kozul Courtney D. , Black Kendall E. , Singh Samer , Gosse Julie A. , DiRenzo James , Martin Kathleen A. , Wang Baolin , Hamilton Joshua W. , Karagas Margaret R. , Robbins David J. 
Published: February 2010

Abstract
Exposure to the environmental toxicant arsenic, through both contaminated water and food, contributes to significant health problems worldwide. In particular, arsenic exposure is thought to function as a carcinogen for lung, skin, and bladder cancer via mechanisms that remain largely unknown. More recently, the Hedgehog signaling pathway has also been implicated in the progression and maintenance of these same cancers. Based on these similarities, we tested the hypothesis that arsenic may act in part through activating Hedgehog signaling. Here, we show that arsenic is able to activate Hedgehog signaling in several primary and established tissue culture cells as well as in vivo. Arsenic activates Hedgehog signaling by decreasing the stability of the repressor form of GLI3, one of the transcription factors that ultimately regulate Hedgehog activity. We also show, using tumor samples from a cohort of bladder cancer patients, that high levels of arsenic exposure are associated with high levels of Hedgehog activity. Given the important role Hedgehog signaling plays in the maintenance and progression of a variety of tumors, including bladder cancer, these results suggest that arsenic exposure may in part promote cancer through the activation of Hedgehog signaling. Thus, we provide an important insight into the etiology of arsenic-induced human carcinogenesis, which may be relevant to millions of people exposed to high levels of arsenic worldwide. Cancer Res; 70(5); 1981–8
The Proteasome Inhibitor Bortezomib Sensitizes Melanoma Cells toward Adoptive CTL Attack
Authors: Seeger Jens Michael , Schmidt Patrick , Brinkmann Kerstin , Hombach Andreas A. , Coutelle Oliver , Zigrino Paola , Wagner-Stippich Diana , Mauch Cornelia , Abken Hinrich , Krönke Martin , Kashkar Hamid 
Published: February 2010

AbstractAdoptive transfer of tumor-specific cytolytic T lymphocytes (CTL) results in target cell lysis by activating the intrinsic apoptotic cell death program. Not surprisingly, deregulation of the apoptotic machinery is one of the central mechanisms by which tumor cells escape immune destruction despite specific CTL recognition. Here we show that treatment with the proteasome inhibitor bortezomib sensitizes previously resistant tumor cells for cytolytic T-cell attack. Human T cells were redirected toward melanoma cells by engineered expression of an immunoreceptor with binding specificity for high molecular weight–melanoma-associated antigen. Established melanoma cell lines as well as primary melanoma cells from tumor biopsies, which are notoriously resistant toward T-cell lysis, became sensitive upon bortezomib treatment. Detailed analysis of the underlying molecular mechanism revealed that bortezomib treatment induced mitochondrial accumulation of NOXA, which potentiated the release of mitochondrial second mitochondria-derived activator of caspase (SMAC) in response to CTL effector functions, including caspase-8 and granzyme B. Our data indicate that proteasome inhibition increases the sensitivity of tumor cells toward cytolytic T-cell attack by NOXA-mediated enhancement of mitochondrial SMAC release. Cancer Res; 70(5); 1825–34
Diallyl Trisulfide Inhibits Phorbol Ester–Induced Tumor Promotion, Activation of AP-1, and Expression of COX-2 in Mouse Skin by Blocking JNK and Akt Signaling
Authors: Shrotriya Sangeeta , Kundu Joydeb Kumar , Na Hye-Kyung , Surh Young-Joon 
Published: February 2010

Abstract
An inverse relationship exists between the consumption of garlic and the risk of certain cancers. The present study was aimed at investigating the effect of garlic constituent diallyl trisulfide (DATS) on 12-O-tetradecanoylphorbol-13-acetate (TPA)–induced cyclooxygenase-2 (COX-2) expression and tumor promotion in mouse skin and to explore the underlying molecular mechanisms. Pretreatment of mouse skin with different garlic-derived allyl sulfides showed DATS to be the most potent in suppressing TPA-induced COX-2 expression. DATS significantly attenuated the DNA binding of activator protein-1 (AP-1), one of the transcription factors that regulate COX-2 expression, in TPA-stimulated mouse skin. DATS also diminished TPA-induced expression of c-Jun and c-Fos, the principal components of AP-1, and blunted the activation of c-Jun NH2-terminal kinase (JNK) and Akt. Pharmacologic inhibition of JNK or Akt by SP600125 or LY294002, respectively, resulted in diminished AP-1 DNA binding, reduced levels of c-Jun and c-Fos, and inhibition of COX-2 expression in TPA-treated mouse skin. The JNK or Akt kinase assay, taking c-Jun fusion protein as a substrate, revealed that TPA induced JNK- or Akt-mediated c-Jun phosphorylation in mouse skin, which was significantly attenuated by DATS or respective pharmacologic inhibitors. Evaluation of antitumor-promoting effect of DATS on 7,12-dimethylbenz(a)anthracene–initiated and TPA-promoted mouse skin carcinogenesis showed that pretreatment with DATS significantly reduced the incidence and multiplicity of papillomas. Taken together, the inhibitory effects of DATS on TPA-induced AP-1 activation and COX-2 expression through modulation of JNK or Akt signaling may partly account for its antitumor-promoting effect on mouse skin carcinogenesis. Cancer Res; 70(5); 1932–40
A Phase II Clinical Trial of Ixabepilone (Ixempra; BMS-247550; NSC 710428), an Epothilone B Analog, in Patients with Metastatic Renal Cell Carcinoma
Authors: Huang Hui , Menefee Michael , Edgerly Maureen , Zhuang Sen , Kotz Herb , Poruchynsky Marianne , Huff Lyn Mickley , Bates Susan , Fojo Tito 
Published: February 2010

Abstract
Purpose: Ixabepilone (Ixempra; BMS-247550) is an epothilone B analog and nontaxane microtubule-stabilizing compound with clinical activity in a range of solid tumors. This phase II study was conducted to assess the efficacy and safety of ixabepilone in patients with metastatic renal cell carcinoma.
Experimental Design: Patients with metastatic renal cell carcinoma who had measurable disease and had not received previous cytotoxic or targeted therapy were treated with 6 mg/m2 ixabepilone i.v. daily for 5 days every 3 weeks. Levels of Glu-terminated and acetylated tubulin, markers of microtubule stabilization, were assessed by Western blot. VHL gene mutation status was determined by sequencing.
Results: Eighty-seven patients received a total of 590 cycles, with a median of 5 cycles (range, 1-29). The overall response rate was 13% (Response Evaluation Criteria in Solid Tumor). One patient had a complete response, 10 patients had partial responses, and 59 patients had stable disease. The median duration of response was 5.5 months. The median overall survival of renal cell carcinoma Motzer grade 0 and 1 patients with clear cell histology was 19.25 months. Treatment-related adverse events were primarily alopecia, gastrointestinal toxicity, neuropathy, and fatigue. Biopsies were done at baseline and after five doses of ixabepilone. Microtubule target engagement was achieved in 84.6% to 92.3% of patients evaluated. No correlation was identified between the target engagement, VHL gene mutation status, and clinical response.
Conclusion: Ixabepilone can cause tumor regression in some patients with metastatic renal cell carcinoma and could be considered in combination regimens with other therapies. Clin Cancer Res; 16(5); 1634–41
Everolimus
Authors: Houghton Peter J. 
Published: February 2010

Abstract
Everolimus, an orally administered rapamycin analog, has recently been approved by the U.S. Food and Drug Administration for treatment of renal cell carcinoma (RCC) refractory to inhibitors of vascular endothelial growth factor (VEGF) receptor signaling. Everolimus significantly increased progression-free survival (median PFS for the everolimus treated group was 4.0 months versus 1.9 months for the placebo group), although tumor regressions were observed only infrequently. Although the target for everolimus, [the serine-threonine kinase mammalian target of rapamycin (mTOR)] is well established, the mechanism by which this agent retards tumor growth is not well defined. Further, biomarkers that predict tumor sensitivity are still elusive. The mechanism of action, preclinical antitumor activity, and clinical activity of everolimus against RCC are reviewed. Clin Cancer Res; 16(5); 1368–72
Lestaurtinib Enhances the Antitumor Efficacy of Chemotherapy in Murine Xenograft Models of Neuroblastoma
Authors: Iyer Radhika , Evans Audrey E. , Qi Xiaoxue , Ho Ruth , Minturn Jane E. , Zhao Huaqing , Balamuth Naomi , Maris John M. , Brodeur Garrett M. 
Published: February 2010

Abstract
Purpose: Neuroblastoma, a common pediatric tumor of the sympathetic nervous system, is characterized by clinical heterogeneity. The Trk family neurotrophin receptors play an important role in this behavior. Expression of TrkA is associated with favorable clinical features and outcome, whereas TrkB expression is associated with an unfavorable prognosis. We wanted to determine if the Trk-selective inhibitor lestaurtinib had therapeutic efficacy in a preclinical neuroblastoma model.
Experimental Design: We performed intervention trials of lestaurtinib alone or in combination with other agents in TrkB-overexpressing neuroblastoma xenograft models.
Results: Lestaurtinib alone significantly inhibited tumor growth compared to vehicle-treated animals [P = 0.0004 for tumor size and P = 0.011 for event-free survival (EFS)]. Lestaurtinib also enhanced the antitumor efficacy of the combinations of topotecan plus cyclophosphamide (P &lt; 0.0001 for size and P &lt; 0.0001 for EFS) or irinotecan plus temozolomide (P = 0.011 for size and P = 0.012 for EFS). There was no additive benefit of combining either 13-cis-retinoic acid or fenretinide with lestaurtinib compared to lestaurtinib alone. There was dramatic growth inhibition combining lestaurtinib with bevacizumab (P &lt; 0.0001), but this combination had substantial systemic toxicity.
Conclusions: We show that lestaurtinib can inhibit the growth of neuroblastoma both in vitro and in vivo and can substantially enhance the efficacy of conventional chemotherapy, presumably by inhibition of the Trk/brain-derived neurotrophic factor autocrine survival pathway. It may also enhance the efficacy of selected biological agents, but further testing is required to rule out unanticipated toxicities. Our data support the incorporation of Trk inhibitors, such as lestaurtinib, in clinical trials of neuroblastoma or other tumors relying on Trk signaling pathways for survival. Clin Cancer Res; 16(5); 1478–85
Lapatinib Restores Hormone Sensitivity with Differential Effects on Estrogen Receptor Signaling in Cell Models of Human Epidermal Growth Factor Receptor 2–Negative Breast Cancer with Acquired Endocrine Resistance
Authors: Leary Alexandra F. , Drury Suzanne , Detre Simone , Pancholi Sunil , Lykkesfeldt Anne E. , Martin Lesley-Ann , Dowsett Mitch , Johnston Stephen R.D. 
Published: February 2010

AbstractPurpose: Acquired endocrine resistance in estrogen receptor (ER)α+/human epidermal growth factor receptor 2–negative (HER2−) breast cancer has been associated with modest adaptive increases in HER2, although exactly how aberrant HER2 signaling affects the ERα pathway is poorly understood. We investigated (a) whether the epidermal growth factor receptor/HER2 inhibitor lapatinib could restore endocrine responsiveness in cell models of acquired endocrine resistance with modest increases in HER2, and (b) the nature of ERα-HER2 cross-talk in this process.Methods: Combination growth studies, ERα transcription, immunoblot, and gene expression assays were conducted in two models of acquired resistance to (a) estrogen deprivation (long-term estrogen-deprived cells) and (b) tamoxifen (long-term tamoxifen-treated cells), and in hormone sensitive controls. Changes in ERα, PgR, and HER2 were assessed in samples from patients treated with tamoxifen.Results: Both cell models of acquired endocrine resistance showed modest adaptive upregulation in HER2, and lapatinib restored endocrine sensitivity in both. The effect of lapatinib on ERα signaling varied markedly depending on the nature of the HER2/ERα cross-talk. In long-term estrogen-deprived cells characterized by enhanced ERα function, lapatinib suppressed ERα genomic activity (as measured by pERSer118, ERα transcriptional activity, and PGR gene expression). In contrast, in long-term tamoxifen-treated cells with reduced ERα activation, lapatinib reactivated ERα genomic function. Twenty percent of tamoxifen-resistant patients relapsed with modest increases in HER2 and either suppressed or enhanced ERα/PgR expression.Conclusions: Aberrant GFR signaling can augment or suppress ERα function. Regardless, interrupting the HER2/ERα cross-talk with lapatinib can restore endocrine sensitivity and should be investigated as a therapeutic strategy in combination with endocrine therapy in ERα+/HER2− patients with acquired endocrine resistance. Clin Cancer Res; 16(5); 1486–97
High-Resolution Array Comparative Genomic Hybridization in Sporadic and Celiac Disease–Related Small Bowel Adenocarcinomas
Authors: Diosdado Begoña , Buffart Tineke E. , Watkins Russell , Carvalho Beatriz , Ylstra Bauke , Tijssen Marianne , Bolijn Anne S. , Lewis Fraser , Maude Karen , Verbeke Caroline , Nagtegaal Iris D. , Grabsch Heike , Mulder Chris J.J. , Quirke Phil , Howdle Peter , Meijer Gerrit A. 
Published: February 2010

Abstract
Purpose: The molecular pathogenesis of small intestinal adenocarcinomas is not well understood. Understanding the molecular characteristics of small bowel adenocarcinoma may lead to more effective patient treatment.
Experimental Design: Forty-eight small bowel adenocarcinomas (33 non–celiac disease related and 15 celiac disease related) were characterized for chromosomal aberrations by high-resolution array comparative hybridization, microsatellite instability, and APC promoter methylation and mutation status. Findings were compared with clinicopathologic and survival data. Furthermore, molecular alterations were compared between celiac disease–related and non–celiac disease–related small bowel adenocarcinomas.
Results: DNA copy number changes were observed in 77% small bowel adenocarcinomas. The most frequent DNA copy number changes found were gains on 5p15.33-5p12, 7p22.3-7q11.21, 7q21.2-7q21.3, 7q22.1-7q34, 7q36.1, 7q36.3, 8q11.21-8q24.3, 9q34.11-9q34.3, 13q11-13q34, 16p13.3, 16p11.2, 19q13.2, and 20p13-20q13.33, and losses on 4p13-4q35.2, 5q15-5q21.1, and 21p11.2-21q22.11. Seven highly amplified regions were identified on 6p21.1, 7q21.1, 8p23.1, 11p13, 16p11.2, 17q12-q21.1, and 19q13.2. Celiac disease–related and non–celiac disease–related small bowel adenocarcinomas displayed similar chromosomal aberrations. Promoter hypermethylation of the APC gene was found in 48% non–celiac disease–related and 73% celiac disease–related small bowel adenocarcinomas. No nonsense mutations were found. Thirty-three percent of non–celiac disease–related small bowel adenocarcinomas showed microsatellite instability, whereas 67% of celiac disease–related small bowel adenocarcinomas were microsatellite unstable.
Conclusions: Our study characterized chromosomal aberrations and amplifications involved in small bowel adenocarcinoma. At the chromosomal level, celiac disease–related and non–celiac disease–related small bowel adenocarcinomas did not differ. A defect in the mismatch repair pathways seems to be more common in celiac disease–related than in non–celiac disease–related small bowel adenocarcinomas. In contrast to colon and gastric cancers, no APC nonsense mutations were found in small bowel adenocarcinoma. However, APC promoter methylation seems to be a common event in celiac disease–related small bowel adenocarcinoma. Clin Cancer Res; 16(5); 1391–401
Comparative Profiling of the Novel Epothilone, Sagopilone, in Xenografts Derived from Primary Non–Small Cell Lung Cancer
Authors: Hammer Stefanie , Sommer Anette , Fichtner Iduna , Becker Michael , Rolff Jana , Merk Johannes , Klar Ulrich , Hoffmann Jens 
Published: February 2010

Abstract
Purpose: Characterization of new anticancer drugs in a few xenograft models derived from established human cancer cell lines frequently results in the discrepancy between preclinical and clinical results. To take the heterogeneity of tumors into consideration more thoroughly, we describe here a preclinical approach that may allow a more rational clinical development of new anticancer drugs.
Experimental Design: We tested Sagopilone, an optimized fully synthetic epothilone, in 22 well-characterized patient-derived non–small cell lung cancer models and correlated results with mutational and genome-wide gene expression analysis.
Results: Response analysis according to clinical trial criteria revealed that Sagopilone induced overall responses in 64% of the xenograft models (14 of 22), with 3 models showing stable disease and 11 models showing partial response. A comparison with response rates for established drugs showed the strong efficacy of Sagopilone in non–small cell lung cancer. In gene expression analyses, Sagopilone induced tubulin isoforms in all tumor samples, but genes related to mitotic arrest only in responder models. Moreover, tumors with high expression of genes involved in cell adhesion/angiogenesis as well as of wild-type TP53 were more likely to be resistant to Sagopilone therapy. As suggested by these findings, Sagopilone was combined with Bevacizumab and Sorafenib, drugs targeting vascular endothelial growth factor signaling, in Sagopilone-resistant models and, indeed, antitumor activity could be restored.
Conclusion: Analyses provided here show how preclinical studies can provide hypotheses for the identification of patients who more likely will benefit from new drugs as well as a rationale for combination therapies to be tested in clinical trials. Clin Cancer Res; 16(5); 1452–65