bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of the fat-1 gene diminishes prostate cancer growth in vivo through enhancing apoptosis and inhibiting GSK-3β phosphorylation
Authors: Lu Yi , Nie Daibang , Witt William T. , Chen Qiuyan , Shen Miaoda , Xie Haiyang , Lai Liangxue , Dai Yifan , Zhang Jian 
Published: October 2008

Abstract
Epidemiologic studies inclusively indicate that “unhealthy” dietary fat intake is one of the potential risk factors for cancer. In dietary fat, there are two types of polyunsaturated fatty acids (PUFA), ω-3 (n-3) and ω-6 (n-6). Numerous studies support that the ratio of n-6/n-3 affects tumorigenesis. It was reported that adenoviral transfer of the fat-1 gene, which converts n-6 to n-3, into breast and lung cancer cells had an antitumor effect in vitro. However, the effects of the fat-1 gene expression on tumor growth in vivo have not been studied and the mechanisms remain unclear. Accordingly, prostate cancer DU145 and PC3 cells were transfected with either the fat-1 gene or a control vector. The cells that expressed the fat-1 gene had a lower n-6/n-3 PUFA ratio compared with the cells that expressed the control vector. The fat-1 gene expression significantly inhibited prostate cancer cell proliferation and invasion in vitro. The fat-1 and control vector-transfected prostate cancer cells were s.c. implanted into severe combined immunodeficient mice for 6 weeks. The fat-1 gene expression significantly diminished tumor growth in vivo, but the control vector had no effect. Finally, we evaluated signaling pathways that may be important for fat-1 gene function. Administration of n-3 PUFA induced caspase-3-mediated prostate cancer cell apoptosis in vitro. The fat-1 gene expression inhibited prostate cancer cell proliferation via reduction of GSK-3β phosphorylation and subsequent down-regulation of both β-catenin and cyclin D1. These results suggest that fat-1 gene transfer directly into tumor cells could be used as a novel therapeutic approach. [Mol Cancer Ther 2008;7(10):3203–11]
15-deoxy-Δ12,14-prostaglandin J2 up-regulates death receptor 5 gene expression in HCT116 cells: involvement of reactive oxygen species and C/EBP homologous transcription factor gene transcription
Authors: Su Rong-Ying , Chi Kwan-Hwa , Huang Duen-Yi , Tai Ming-Hui , Lin Wan-Wan 
Published: October 2008

Abstract
Although 15-deoxy-Δ12,14-prostaglandin J2 (15dPGJ2) was reported to up-regulate death receptor 5 (DR5) protein expression and sensitize TRAIL-induced cytotoxicity, its action mechanism remains unclear. Using HCT116 colon cancer cells, we found that sensitization of TRAIL-induced cytotoxicity by 15dPGJ2 resulted from up-regulation of DR5 via gene transcription but was not associated with PPAR-γ activation. Moreover, 15dPGJ2 induced GRP78, XBP1, and C/EBP homologous transcription factor (CHOP) expression in HCT116 cells, confirming that 15dPGJ2 is an endoplasmic reticulum stress inducer. Knockdown of the CHOP gene by siRNA attenuated DR5 up-regulation and the sensitized cytotoxicity in colon cancer HCT116 and SW480. With deletion plasmids of DR5 promoters, we found that the CHOP-binding site was involved in activating the DR5 gene by 15dPGJ2. A mechanistic study showed the contributions of reactive oxygen species (ROS) and intracellular calcium in CHOP and DR5 gene up-regulation. 15dPGJ2 was also found to induce DR5 in two prostate cancer cell lines, LNCaP and PC3. Although in LNCaP DR5 up-regulation was accompanied by CHOP expression by 15dPGJ2, no significant increase in CHOP expression or DR5 promoter activity was observed in PC3 cells. Intriguingly, 15dPGJ2 induced ROS and calcium production in PC3 cells. This inability to induce CHOP was not due to the p53-null in PC3 cells, as similar extents of increase in CHOP protein were found due to 15dPGJ2 in both wild-type and p53-null HCT116 cells. In summary, the effect of up-regulation of DR5 by 15dPGJ2 in colon cancer cells is independent of PPAR-γ and p53 but relies on CHOP induction through gene transcription involving ROS and calcium. [Mol Cancer Ther 2008;7(10):3429–40]
Antitumor activity and molecular effects of the novel heat shock protein 90 inhibitor, IPI-504, in pancreatic cancer
Authors: Song Dongweon , Chaerkady Raghothama , Tan Aik Choon , García-García Elena , Nalli Anuradha , Suárez-Gauthier Ana , López-Ríos Fernando , Zhang Xian Feng , Solomon Anna , Tong Jeffrey , Read Margaret , Fritz Christian , Jimeno Antonio , Pandey Akhilesh , Hidalgo Manuel 
Published: October 2008

Abstract
Targeting Hsp90 is an attractive strategy for anticancer therapy because the diversity and relevance of biological processes are regulated by these proteins in most cancers. However, the role and mode of action of Hsp90 inhibitors in pancreatic cancer has not been studied. This study aimed to assess the antitumor activity of the Hsp90 inhibitor, IPI-504, in pancreatic cancer and to determine the biological effects of the agent. In vitro, we show that pharmacologic inhibition of Hsp90 by IPI-504 exerts antiproliferative effects in a panel of pancreatic cancer cells in a dose- and time-dependent manner. In pancreatic cancer xenografts obtained directly from patients with pancreas cancer, the agent resulted in a marked suppression of tumor growth. Although known Hsp90 client proteins were significantly modulated in IPI-504-treated cell line, no consistent alteration of these proteins was observed in vivo other than induction of Hsp70 expression in the treated xenografted tumors. Using a proteomic profiling analysis with isotope tags for relative and absolute quantitation labeling technique, we have identified 20 down-regulated proteins and 42 up-regulated proteins on IPI-504 treatment.tumor growth Identical changes were observed in the expression of the genes coding for these proteins in a subset of proteins including HSPA1B, LGALS3, CALM1, FAM84B, FDPS, GOLPH2, HBA1, HIST1H1C, HLA-B, and MARCKS. The majority of these proteins belong to the functional class of intracellular signal transduction, immune response, cell growth and maintenance, transport, and metabolism. In summary, we show that IPI-504 has potent antitumor activity in pancreatic cancer and identify potential pharmacologic targets using a proteomics and gene expression profiling. [Mol Cancer Ther 2008;7(10):3275–84]
Curcumin suppresses constitutive activation of nuclear factor-κB and requires functional Bax to induce apoptosis in Burkitt's lymphoma cell lines
Authors: Hussain Azhar R. , Ahmed Maqbool , Al-Jomah Naif A. , Khan Asma S. , Manogaran Pulicat , Sultana Mehar , Abubaker Jehad , Platanias Leonidas C. , Al-Kuraya Khawla S. , Uddin Shahab 
Published: October 2008

AbstractWe provide evidence that curcumin, a natural compound isolated from rhizomes of plant Curcuma longa, induces apoptosis in several Burkitt's lymphoma cell lines expressing Bax protein (AS283A, KK124, and Pa682PB), whereas it has no effects in cell lines with no Bax expression (BML895 and CA46). Our data show that curcumin treatment results in down-regulation of constitutive activation of nuclear factor-κB (NF-κB) via generation of reactive oxygen species where it causes conformational changes in Bax protein leading to loss of mitochondrial membrane potential and release of cytochrome c to the cytosol. This leads to activation of caspase-9, caspase-3, and poly(ADP)-ribose polymerase cleavage leading to caspase-dependent apoptosis. In addition, curcumin treatment of Burkitt's lymphoma cell lines also causes up-regulation of DR5; however, this up-regulation does not result in apoptosis. Importantly, cotreatment with curcumin and TRAIL induces apoptosis in Bax-deficient cell lines. Taken together, our findings suggest that curcumin is able to induce apoptosis in Bax-positive cell lines, whereas combinations with TRAIL result in apoptosis in Bax-negative cell lines. These findings also raise the possibility that incorporation of curcumin in treatment regimens may provide a novel approach for the treatment of Burkitt's lymphomas and provide the molecular basis for such future translational efforts. [Mol Cancer Ther 2008;7(10):3318–29]
Polymeric nanogels containing the triphosphate form of cytotoxic nucleoside analogues show antitumor activity against breast and colorectal cancer cell lines
Authors: Galmarini Carlos M. , Warren Galya , Kohli Ekta , Zeman Arin , Mitin Anton , Vinogradov Serguei V. 
Published: October 2008

Abstract
The therapeutic efficiency of anticancer nucleoside analogues (NA) strongly depends on their intracellular accumulation and conversion into 5′-triphosphates. Because active NATP cannot be directly administrated due to instability, we present here a strategy of nanoencapsulation of these active drugs for efficient delivery to tumors. Stable lyophilized formulations of 5′-triphosphates of cytarabine (araCTP), gemcitabine (dFdCTP), and floxuridine (FdUTP) encapsulated in biodegradable PEG-cl-PEI or F127-cl-PEI nanogel networks (NGC and NGM, respectively) were prepared by a self-assembly procedure. Cellular penetration, in vitro cytotoxicity, and drug-induced cell cycle perturbations of these nanoformulations were analyzed in breast and colorectal cancer cell lines. Cellular accumulation and NATP release from nanogel was studied by confocal microscopy and direct high-performance liquid chromatography analysis of cellular lysates. Antiproliferative effect of dFdCTP nanoformulations was evaluated in human breast carcinoma MCF7 xenograft animal model. Nanoencapsulated araCTP, dFdCTP, and FdUTP showed similar to NA cytotoxicity and cell cycle perturbations. Nanogels without drugs showed very low cytotoxicity, although NGM was more toxic than NGC. Treatment by NATP nanoformulations induced fast increase of free intracellular drug concentration. In human breast carcinoma MCF7 xenograft animal model, i.v. dFdCTP-nanogel was equally effective in inhibiting tumor growth at four times lower administered drug dose compared with free gemcitabine. Active triphosphates of NA encapsulated in nanogels exhibit similar cytotoxicity and cell cycle perturbations in vitro and faster cell accumulation and equal tumor growth-inhibitory activity in vivo at much lower dose compared with parental drugs, illustrating their therapeutic potential for cancer chemotherapy. [Mol Cancer Ther 2008;7(10):3373–80]
Genistein down-regulates androgen receptor by modulating HDAC6-Hsp90 chaperone function
Authors: Basak Shashwati , Pookot Deepa , Noonan Emily J. , Dahiya Rajvir 
Published: October 2008

Abstract
Androgen receptor (AR) is a ligand-activated transcription factor belonging to the steroid hormone receptor family and is very important for the development and progression of prostate cancer. The soy isoflavone genistein has been shown previously to down-regulate AR in androgen-dependent prostate cancer cell lines such as LNCaP. However, the mechanism(s) by which AR is down-regulated by genistein is still not known fully. We show a new mechanism by which genistein inhibits AR protein levels. We show that genistein-treated LNCaP cells exhibit increased ubiquitination of AR, suggesting that AR protein is down-regulated via a proteasome-mediated pathway. AR is normally stabilized by the chaperone activity of the heat shock protein Hsp90. The increased ubiquitination of AR after genistein treatment is attributed to decreased Hsp90 chaperone activity as assessed by its increased functionally inactive acetylated form. Consistent with this result, we find that HDAC6, which is a Hsp90 deacetylase, is inhibited by the antiestrogenic activity of genistein. Hence, in this study, we elucidate a novel mechanism of AR down-regulation by genistein through inhibition of HDAC6-Hsp90 cochaperone function required to stabilize AR protein. Our results suggest that genistein could be used as a potential chemopreventive agent for prostate cancers along with known inhibitors of HDAC6 and Hsp90. [Mol Cancer Ther 2008;7(10):3195–202]
Loss of prostaglandin D2 synthase: a key molecular event in the transition of a low-grade astrocytoma to an anaplastic astrocytoma
Authors: Payne Cathy A. , Maleki Sanaz , Messina Marinella , O'Sullivan Maree G. , Stone Glenn , Hall Nathan R. , Parkinson Jonathon F. , Wheeler Helen R. , Cook Raymond J. , Biggs Michael T. , Little Nicholas S. , Teo Charles , Robinson Bruce G. , McDonald Kerrie L. 
Published: October 2008

Abstract
Reduction in the mRNA and protein expression of lipocalin-like prostaglandin D2 (PGD2) synthase (PGDS), the main arachidonic acid metabolite produced in neurons and glial cells of the central nervous system, is a significant biological event involved in the malignant progression of astrocytomas and is predictive of poor survival. In vitro, the addition of the main PGDS metabolite, PGD2, to A172 glioblastoma cells devoid of PGDS resulted in antiproliferative activity and cell death. In vitro PGD2 substitution also enhanced the efficacy of cyclo-oxygenase-2 inhibitors. This finding has exciting implications for early interventional efforts for the grade 2 and 3 astrocytomas. [Mol Cancer Ther 2008;7(10):3420–8]
A genomic approach to identify molecular pathways associated with chemotherapy resistance
Authors: Riedel Richard F. , Porrello Alessandro , Pontzer Emily , Chenette Emily J. , Hsu David S. , Balakumaran Bala , Potti Anil , Nevins Joseph , Febbo Phillip G. 
Published: October 2008

Abstract
Resistance to chemotherapy in cancer is common. As gene expression profiling has been shown to anticipate chemotherapeutic resistance, we sought to identify cellular pathways associated with resistance to facilitate effective combination therapy. Gene set enrichment analysis was used to associate pathways with resistance in two data sets: the NCI-60 cancer cell lines deemed sensitive and resistant to specific chemotherapeutic agents (Adriamycin, cyclophosphamide, docetaxel, etoposide, 5-fluorouracil, paclitaxel, and topotecan) and a series of 40 lung cancer cell lines for which sensitivity to cisplatin and docetaxel was determined. Candidate pathways were further screened in silico using the Connectivity Map. The lead candidate pathway was functionally validated in vitro. Gene set enrichment analysis associated the matrix metalloproteinase, p53, methionine metabolism, and free pathways with cytotoxic resistance in the NCI-60 cell lines across multiple agents, but no gene set was common to all drugs. Analysis of the lung cancer cell lines identified the bcl-2 pathway to be associated with cisplatin resistance and the AKT pathway enriched in cisplatin- and docetaxel-resistant cell lines. Results from Connectivity Map supported an association between phosphatidylinositol 3-kinase/AKT and docetaxel resistance but did not support the association with cisplatin. Targeted inhibition of the phosphatidylinositol 3-kinase/AKT pathway with LY294002, in combination with docetaxel, resulted in a synergistic effect in previously docetaxel-resistant cell lines but not with cisplatin. These results support the use of a genomic approach to identify drug-specific targets associated with the development of chemotherapy resistance and underscore the importance of disease context in identifying these pathways. [Mol Cancer Ther 2008;7(10):3141–9]
The heat pipe heat exchanger: a review of its status and its potential for coolness recovery in tropical buildings
Authors: Yau YH 
Published: October 2008

The heat pipe heat exchanger (HPHX) is a proven device for heat recovery in HVAC systems, and competes effectively with other available systems such as heat recovery wheels and run-around coils. This paper reviews major research work done on heat pipe heat exchangers (HPHXs) installed in HVAC systems since 1970. It reveals that research work on HPHXs for HVAC heat and coolness recovery has been done mostly in North America, Britain and Australia. Literature reviews further reveal that only limited research work on HPHXs for HVAC heat and coolness recovery has been conducted in subtropical and tropical climates and therefore, more HPHX research work for HVAC applications should be carried out in these regions in the interests of energy conservation and global green environment strategies. Practical applications: The review on recover heat or coolness in HVAC systems since 1970 described in this paper enables necessarily good understanding on recover heat or coolness technologies for the impact of energy consumption and dehumidification in buildings before actual research or retrofitting is conducted to the space's conditioning system. The results obtained from a considerable number of research work in subtropical and tropical climates could serve as a preliminary guide for mechanical and electrical (M&E) engineers and researchers who are intending to apply heat pipe heat exchangers as `coolness' recovery and dehumidification devices in HVAC systems operating in tropical countries.
Analysis of uncertainty in natural ventilation predictions of high-rise apartment buildings
Authors: Hyun SH , Park CS , Augenbroe GLM 
Published: October 2008

Quantification of natural ventilation rates is an important issue in HVAC system design. Natural ventilation in buildings depends on many parameters whose uncertainty varies significantly, and hence the results from a standard deterministic simulation approach could be unreliable and provide a false sense of security that natural ventilation will supply adequate amounts of fresh air. This study performed an uncertainty analysis to predict natural airflow rates. The paper presents relevant uncertainty in model and input parameters such as meteorological data, building properties (leakage areas of windows, doors, etc.), etc. Uncertainties of the aforementioned parameters were quantified based on data available from literature and on-site visits. The Monte-Carlo method with Latin Hypercube Sampling (LHS) was used for uncertainty propagation. The CONTAMW was chosen to simulate natural ventilation phenomena in a high-rise apartment building that is typical of residential buildings in Korea. It is shown that the uncertainty propagated through this process is not negligible and may significantly influence the prediction of the airflow rates. In the paper, the result of a sensitivity analysis is also addressed. Practical application: The paper describes a probablistic approach to predict the natural airflow rates of high-rise apartment buildings under uncertainty and could eventually replace the current conventional deterministic approach.
Air-conditioned deployable force infrastructure as a strategy to combat sleep deprivation among troops in hot countries
Authors: van Hoof J 
Published: October 2008

High-tech peacekeeping and humanitarian interventions form an increasing part of the range of duties of the military, dispatching troops to all parts of the world, with emphasis on hot climate areas. These missions call for fewer soldiers but with a more thorough, detailed and timely awareness level to reach predetermined goals. High ambient temperatures in the operational environment have a deleterious effect on performance, which is aggravated by poor sleep. Current deployable force infrastructure is often unable to support the restoration of body and brain sufficiently, while troop fitness is essential to the success of the mission. Supplying the peacekeepers with air-conditioned housing is becoming an increasingly important non-pharmacological strategy to counter the negative effects of heat. This paper investigates the influence of the military field environment, and high temperatures in particular, on sleep, comfort and performance of personnel and equipment, and looks at the benefits of installing air-conditioning systems and future trends in deployable force infrastructure. Practical application: Results of this study can be used for innovations in designing comfortable mission housing and accompanying building services that do not only offer comfort to military personnel in field settings, but also provide better conditions for sleep. Improved comfort and sleep can in turn benefit operational performance. The results can also be used for a large range of civilian purposes, for instance, the creation of comfortable bedrooms and hotel rooms.
Equivalent diameters of rectangular and oval ducts
Authors: Koch P 
Published: October 2008

To help engineers predict the pressure drop of a fluid passing along ducts of non-circular cross-section, the concept of `equivalent diameter' of a circular duct has been extensively used. This paper re-analyses two earlier sets of research data for non-circular ducts, such an analysis being easier now than at the time of the original research, 1948 and 1975. This new work reveals that equations for equivalent diameter of non-rectangular ducts lifted from the two prime sources are totally inapplicable; in short they are myths which should no longer be reiterated. In analysing the experimental results as constructively as possible to extract a more appropriate and correct relationship, the author finds that the experimental results are not sufficiently consistent to draw any reliable quantitative conclusions. Thus the experimental work needs to be repeated to verify whether hydraulic diameter may be used as an `equivalent diameter' or whether an alternative relationship can be found. Practical application: In showing that there are no reliable practical results to guide engineers in calculating pressure drop along non-circular ducts, the paper demonstrates that further practical research is necessary. In showing that the relationships used in some texts and reputedly emanating from practical research, are both invalid, the author hopes that their future use will cease. Until a proven relationship for `equivalent diameter' is forthcoming, there is no other choice than to use the hydraulic diameter.
A review of the IPCC Assessment Report Four, Part 2: Mitigation options for residential and commercial buildings
Authors: Levermore GJ 
Published: October 2008

The Intergovernmental Panel on Climate Change, (IPCC), Fourth Assessment Report, AR4, Climate Change 2007 consists of three volumes based on the work of three IPCC Working Groups (WGs). WG1 considered the scientific basis of climate change and what the climate models are showing. WG2 considered the consequences of climate change and possible adaptation to it. WG3 considered how the climate change could be mitigated. Within this WG3 volume is chapter 6 on the mitigation options for residential and commercial buildings. This paper reviews this chapter which discusses how the potential savings of greenhouse gases can be achieved through technical fixes and policies. The technical fixes are based on existing technology although it is recognised that existing building refurbishment is a major issue to be addressed and that there are a number of policies that can help achieve these reductions although some are in their infancy. Part 1 of this paper (The IPCC process and Greenhouse Gas Emission trends from Buildings worldwide) considered the history of the IPCC and the trends in emissions, particularly from buildings. Practical application: Climate change is an important topic for building services engineers, resulting in the UK in the new, performance-based Building Regulations Part L. This paper reviews the technical options that have been identified by the IPCC as potentially carbon mitigating for buildings. The context of the world situation is also considered and the policies considered by the IPCC as relevant to buildings and plant that will ultimately affect the design of building services engineers in the UK and overseas.