bluuebunny/crossref_metadata_2025_split huggingface dataset:
Breast Cancer Resistance Protein Impacts Clinical Outcome in Platinum-Based Chemotherapy for Advanced Non-Small Cell Lung Cancer
Authors: Yoh Kiyotaka , Ishii Genichiro , Yokose Tomoyuki , Minegishi Yuji , Tsuta Kohji , Goto Koichi , Nishiwaki Yutaka , Kodama Tetsuro , Suga Moritaka , Ochiai Atsushi 
Published: September 2005

Abstract
Purpose: The purpose of this study was to investigate the relationship between the level of expression of ATP-binding cassette (ABC) transporter proteins, and response to chemotherapy and prognosis in advanced non-small cell lung cancer (NSCLC).
Experimental Design: Expression of ABC transporter proteins, including P-glycoprotein, multidrug resistance protein (MRP) 1, MRP2, MRP3, and breast cancer resistance protein (BCRP), was examined immunohistochemically in 72 formalin-fixed tumor samples from untreated stage IIIB or IV NSCLC patients. All of the patients received platinum-based chemotherapy. Response to chemotherapy, progression-free survival (PFS), and overall survival were compared in relation to expression of each of the ABC transporter proteins and clinicopathological factors.
Results: Expression of P-glycoprotein, MRP1, and MRP3 was not significantly associated with response to chemotherapy or survival. MRP2 expression was associated with overall survival (P = 0.002) but not with response to chemotherapy and PFS. By contrast, the response rate to chemotherapy of patients with BCRP-negative tumors was 44%, as opposed to 24% in patients with BCRP-positive tumors. Response rate was lower in BCRP-positive tumors, although this difference was not statistically significant (P = 0.08). BCRP-positive patients had also shorter PFS (P = 0.0003) and overall survival (P = 0.004) than BCRP-negative patients. Multivariate analysis confirmed BCRP status as an independent variable related to PFS (P = 0.001).
Conclusions: Positive immunostaining for BCRP appears to be a predictor of survival in patients with advanced NSCLC. These findings indicate that BCRP may serve as a molecular target for reducing drug resistance to chemotherapy in advanced NSCLC patients.
CCL19 and CXCL12 Triggerin VitroChemotaxis of Human Mantle Cell Lymphoma B Cells
Authors: Corcione Anna , Arduino Nicoletta , Ferretti Elisa , Raffaghello Lizzia , Roncella Silvio , Rossi Davide , Fedeli Franco , Ottonello Luciano , Trentin Livio , Dallegri Franco , Semenzato Gianpietro , Pistoia Vito 
Published: September 2005

AbstractPurpose: Few data are available in the literature on chemokine receptor expression and migratory capability of mantle cell lymphoma (MCL) B cells. Information on these issues may allow us to identify novel mechanisms of chemokine-driven tumor cell migration.Experimental Design: The research was designed to investigate: (a) expression of CCR1 to CCR7 and CXCR1 to CXCR5 chemokine receptors; and (b) chemotaxis to the respective ligands in MCL B cells and in their normal counterparts, i.e., CD5+ B cells.Results: Malignant B cells from MCL patients and normal counterparts displayed similar chemokine receptor profiles. MCL B cells were induced to migrate by CXCL12 and CCL19, whereas normal CD5+ B cells migrated to the former, but not the latter chemokine. Overnight culture of MCL B cells and their normal counterparts with CXCL12 cross-sensitized other chemokine receptors to their ligands in some tumor samples but not in CD5+ B cells.Conclusions: CCR7 and CXCR4 ligands may play a key role in tumor cell migration and spreading in vivo. CXCL12 may additionally contribute by sensitizing MCL B cells to respond to the ligands of other chemokine receptors.
Expression of Valosin-Containing Protein in Colorectal Carcinomas as a Predictor for Disease Recurrence and Prognosis
Authors: Yamamoto Shinji , Tomita Yasuhiko , Hoshida Yoshihiko , Sakon Masato , Kameyama Masao , Imaoka Shingi , Sekimoto Mitsugu , Nakamori Shoji , Monden Morito , Aozasa Katsuyuki 
Published: September 2005

Abstract
Purpose: Valosin-containing protein (VCP or p97) is associated with antiapoptotic function and metastasis via activation of the nuclear factor-κB signaling pathway. The present study was designed to investigate the prognostic significance of VCP expression in colorectal adenocarcinoma.
Experimental Design: We analyzed VCP expression immunohistochemically in 129 patients with colorectal carcinoma ages 35–84 years. The staining intensity of tumor cells was categorized as either weaker-to-equal (low VCP expression) or stronger (high expression) than that in noncancerous colonic mucosa. We also analyzed 8 colorectal adenomas and 10 metastatic foci.
Results: Low VCP expression was noted in 41 (31.8%) cases and high expression in 88 (68.2%) cases. A low level of VCP expression was noted in all adenomas, whereas a high level was seen in all metastatic tumors. A significant difference was observed in depth of invasion (T1–2 versus T3–4, P &lt; 0.05), presence or absence of venous invasion (P &lt; 0.05), and tumor stage (I and II versus III and IV; P &lt; 0.05) between adenocarcinomas with low and high VCP expression. Patients with high VCP-expressing tumors had a higher recurrence rate (P &lt; 0.001) and poorer disease-free and overall survival (P &lt; 0.01 and P &lt; 0.05, respectively) compared with the low expression group. Multivariate analysis revealed VCP expression level to be an independent prognosticator for both disease-free and overall survival. VCP level was an indicator of disease-free survival in both stage II and III (pathological Tumor-Node-Metastasis classification, P &lt; 0.05 and &lt;0.01, respectively).
Conclusions: A high expression level of VCP in tumors is a poor prognostic marker in patients with colorectal carcinomas.
E1A Specifically Enhances Sensitivity to Topoisomerase IIα Targeting Anticancer Drug by Up-Regulating the Promoter Activity
Authors: Zhou Zhichao , Guan Hui , Kleinerman Eugenie S. 
Published: September 2005

Abstract
DNA topoisomerases I and II (topo I and II) are nuclear enzymes involved in cellular replication and are targets for several anticancer drugs. We showed previously that E1A gene transfer enhanced the sensitivity of Ewing's sarcoma cells to the topo IIα targeting agents etoposide and Adriamycin in vitro and in vivo. To determine whether this effect was specific for topo IIα, we investigated the effect of E1A gene transfer on cell sensitivity to agents that target topo I and IIβ. Transfecting TC71 human Ewing's sarcoma cells with an adenoviral vector containing the E1A gene enhanced their sensitivity to the topo IIα targeting agents etoposide (16-fold) and Adriamycin (8-fold). By contrast, E1A gene transfer did not affect cellular sensitivity to either amsacrine or camptothecin. Western blot analysis indicated that topo IIα protein levels increased 3.1-fold after E1A gene transfer, but topo I and IIβ protein levels did not change. A plasmid containing topo IIα gene promoter with luciferase reporter gene was constructed to determine the effects of E1A gene transfer on the activity of the topo IIα promoter. E1A increased the activity of the topo IIα gene promoter by 3.5-fold relative to that of cells transfected with Ad-β-gal. These results suggest that elevated topo IIα protein levels and enhanced sensitivity to topo IIα targeting agents were secondary to a direct effect of E1A on the topo IIα promoter. Combining E1A gene therapy with topo IIα targeting anticancer drugs may therefore have therapeutic benefit by increasing tumor cell sensitivity.
Sphingosine-1-Phosphate Lyase Regulates Sensitivity of Human Cells to Select Chemotherapy Drugs in a p38-Dependent Manner
Authors: Min Junxia , Van Veldhoven Paul P. , Zhang Lei , Hanigan Marie H. , Alexander Hannah , Alexander Stephen 
Published: September 2005

Abstract
Resistance to cisplatin is a common problem that limits its usefulness in cancer therapy. Molecular genetic studies in the model organism Dictyostelium discoideum have established that modulation of sphingosine kinase or sphingosine-1-phosphate (S-1-P) lyase, by disruption or overexpression, results in altered cellular sensitivity to this widely used drug. Parallel changes in sensitivity were observed for the related compound carboplatin but not for other chemotherapy drugs tested. Sensitivity to cisplatin could also be potentiated pharmacologically with dimethylsphingosine, a sphingosine kinase inhibitor. We now have validated these studies in cultured human cell lines. HEK293 or A549 lung cancer cells expressing human S-1-P lyase (hSPL) show an increase in sensitivity to cisplatin and carboplatin as predicted from the earlier model studies. The hSPL-overexpressing cells were also more sensitive to doxorubicin but not to vincristine or chlorambucil. Studies using inhibitors to specific mitogen-activated protein kinases (MAPK) show that the increased cisplatin sensitivity in the hSPL-overexpressing cells is mediated by p38 and to a lesser extent by c-Jun NH2-terminal kinase MAPKs. p38 is not involved in vincristine or chlorambucil cytotoxicity. Measurements of MAPK phosphorylation and enzyme activity as well as small interfering RNA inhibition studies show that the response to the drug is accompanied by up-regulation of p38 and c-Jun NH2-terminal kinase and the lack of extracellular signal-regulated kinase up-regulation. These studies confirm an earlier model proposing a mechanism for the drug specificity observed in the studies with D. discoideum and support the idea that the sphingosine kinases and S-1-P lyase are potential targets for improving the efficacy of cisplatin therapy for human tumors.
Expression profiling of laser-microdissected intrapulmonary arteries in hypoxia-induced pulmonary hypertension
Authors: Kwapiszewska Grazyna , Wilhelm Jochen , Wolff Stephanie , Laumanns Isabel , Koenig Inke R , Ziegler Andreas , Seeger Werner , Bohle Rainer M , Weissmann Norbert , Fink Ludger 
Published: September 2005

Abstract

Background
Chronic hypoxia influences gene expression in the lung resulting in pulmonary hypertension and vascular remodelling. For specific investigation of the vascular compartment, laser-microdissection of intrapulmonary arteries was combined with array profiling.

Methods and Results
Analysis was performed on mice subjected to 1, 7 and 21 days of hypoxia (FiO2 = 0.1) using nylon filters (1176 spots). Changes in the expression of 29, 38, and 42 genes were observed at day 1, 7, and 21, respectively. Genes were grouped into 5 different classes based on their time course of response. Gene regulation obtained by array analysis was confirmed by real-time PCR. Additionally, the expression of the growth mediators PDGF-B, TGF-β, TSP-1, SRF, FGF-2, TIE-2 receptor, and VEGF-R1 were determined by real-time PCR. At day 1, transcription modulators and ion-related proteins were predominantly regulated. However, at day 7 and 21 differential expression of matrix producing and degrading genes was observed, indicating ongoing structural alterations. Among the 21 genes upregulated at day 1, 15 genes were identified carrying potential hypoxia response elements (HREs) for hypoxia-induced transcription factors. Three differentially expressed genes (S100A4, CD36 and FKBP1a) were examined by immunohistochemistry confirming the regulation on protein level. While FKBP1a was restricted to the vessel adventitia, S100A4 and CD36 were localised in the vascular tunica media.

Conclusion
Laser-microdissection and array profiling has revealed several new genes involved in lung vascular remodelling in response to hypoxia. Immunohistochemistry confirmed regulation of three proteins and specified their localisation in vascular smooth muscle cells and fibroblasts indicating involvement of different cells types in the remodelling process. The approach allows deeper insight into hypoxic regulatory pathways specifically in the vascular compartment of this complex organ.
Modeling the emergence of multi-protein dynamic structures by principles of self-organization through the use of 3DSpi, a multi-agent-based software
Authors: Soula Hédi , Robardet Céline , Perrin François , Gripon Sébastien , Beslon Guillaume , Gandrillon Olivier 
Published: September 2005

Abstract
Background
There is an increasing need for computer-generated models that can be used for explaining the emergence and predicting the behavior of multi-protein dynamic structures in cells. Multi-agent systems (MAS) have been proposed as good candidates to achieve this goal.

Results
We have created 3DSpi, a multi-agent based software that we used to explore the generation of multi-protein dynamic structures. Being based on a very restricted set of parameters, it is perfectly suited for exploring the minimal set of rules needed to generate large multi-protein structures. It can therefore be used to test the hypothesis that such structures are formed and maintained by principles of self-organization. We observed that multi-protein structures emerge and that the system behavior is very robust, in terms of the number and size of the structures generated. Furthermore, the generated structures very closely mimic spatial organization of real life multi-protein structures.

Conclusion
The behavior of 3DSpi confirms the considerable potential of MAS for modeling subcellular structures. It demonstrates that robust multi-protein structures can emerge using a restricted set of parameters and allows the exploration of the dynamics of such structures. A number of easy-to-implement modifications should make 3DSpi the virtual simulator of choice for scientists wishing to explore how topology interacts with time, to regulate the function of interacting proteins in living cells.
MAOA haplotypes associated with thrombocyte-MAO activity
Authors: Jansson Mårten , McCarthy Shane , Sullivan Patrick F , Dickman Paul , Andersson Björn , Oreland Lars , Schalling Martin , Pedersen Nancy L 
Published: September 2005

Abstract

Background
The aim was to ascertain whether thrombocyte MAO (trbc-MAO) activity and depressed state are genetically associated with the MAO locus on chromosome X (Xp11.3 – 11.4). We performed novel sequencing of the MAO locus and validated genetic variants found in public databases prior to constructing haplotypes of the MAO locus in a Swedish sample (N = 573 individuals).

Results
Our results reveal a profound SNP desert in the MAOB gene. Both the MAOA and MAOB genes segregate as two distinct LD blocks. We found a significant association between two MAOA gene haplotypes and reduced trbc-MAO activity, but no association with depressed state.

Conclusion
The MAO locus seems to have an effect on trbc-MAO activity in the study population. The findings suggest incomplete X-chromosome inactivation at this locus. It is plausible that a gene-dosage effect can provide some insight into the greater prevalence of depressed state in females than males.
Adaptive designs based on the truncated product method
Authors: Neuhäuser Markus , Bretz Frank 
Published: September 2005

Abstract
Background
Adaptive designs are becoming increasingly important in clinical research. One approach subdivides the study into several (two or more) stages and combines the p-values of the different stages using Fisher's combination test.

Methods
Alternatively to Fisher's test, the recently proposed truncated product method (TPM) can be applied to combine the p-values. The TPM uses the product of only those p-values that do not exceed some fixed cut-off value. Here, these two competing analyses are compared.

Results
When an early termination due to insufficient effects is not appropriate, such as in dose-response analyses, the probability to stop the trial early with the rejection of the null hypothesis is increased when the TPM is applied. Therefore, the expected total sample size is decreased. This decrease in the sample size is not connected with a loss in power. The TPM turns out to be less advantageous, when an early termination of the study due to insufficient effects is possible. This is due to a decrease of the probability to stop the trial early.

Conclusion
It is recommended to apply the TPM rather than Fisher's combination test whenever an early termination due to insufficient effects is not suitable within the adaptive design.
Pre-exenterative chemotherapy, a novel therapeutic approach for patients with persistent or recurrent cervical cancer
Authors: Lopez-Graniel Carlos , Dolores Rigoberto , Cetina Lucely , Gonzalez Aaron , Cantu David , Chanona Jose , Uribe Jesus , Candelaria Myrna , Brom Rocio , de la Garza Jaime , Duenas-Gonzalez Alfonso 
Published: September 2005

Abstract

Background
Most cervical cancer patients with pelvic recurrent or persistent disease are not candidates for exenteration, therefore, they only receive palliative chemotherapy. Here we report the results of a novel treatment modality for these patients pre-exenterative chemotherapy- under the rational that the shrinking of the pelvic tumor would allow its resection.

Methods
Patients with recurrent or persistent disease and no evidence of systemic disease, considered not be candidates for pelvic exenteration because of the extent of pelvic tumor, received 3-courses of platinum-based chemotherapy. Response was evaluated by CT scan and bimanual pelvic examination; however the decision to perform exenteration relied on the physical findings. Toxicity to chemotherapy was evaluated with standard criteria. Survival was analyzed with the Kaplan-Meier method.

Results
Seventeen patients were studied. The median number of chemotherapy courses was 4. There were 9 patients who responded to chemotherapy, evaluated by bimanual examination and underwent pelvic exenteration. Four of them had pathological complete response. Eight patients did not respond and were not subjected to surgery. One patient died due to exenteration complications. At a median follow-up of 11 months, the median survival for the whole group was 11 months, 3 months in the non-operated and 32 months in those subjected to exenteration.

Conclusion
Pre-exenterative chemotherapy is an alternative for cervical cancer patients that are no candidates for exenteration because of the extent of the pelvic disease. Its place in the management of recurrent disease needs to be investigated in randomized studies, however, its value for offering long-term survival in some of these patients with no other option than palliative care must be stressed.
Usefulness of PKH fluorescent labelling to study leukemic cell proliferation with various cytostatic drugs or acetyl tetrapeptide – AcSDKP
Authors: Boutonnat Jean , Faussat Anne-Marie , Marie Jean-Pierre , Bignon Jérôme , Wdzieczak-Bakala Johanna , Barbier Magali , Thierry Josiane , Ronot Xavier , Colle Pierre-Emmanuel 
Published: September 2005

Abstract

Background
PKH67 labelling was compared for classical proliferation assessment (using S phase evaluation) to analyse the cell proliferation of 29 AML patients treated or not with various drugs. Among these drugs, the effect of tetrapeptide AcSDKP or AcSDKP-NH2 on AML cells, stimulated or not by cytokines, was also evaluated in order to determine (i) if AcSDKP was able to inhibit blast cell proliferation as it inhibits haematopoietic progenitors (ii) if AcSDKP-NH2 was more stable than AcSDKP with FBS.

Methods
For PKH labeling, cells were suspended in Diluent C, and rapidly admixed with PKH67 solution at 20 μM PKH67. Staining was stopped by addition of FBS.

Results
A good correlation between PKH67 labelling and bromodeoxyuridine incorporation was obtained first with 6/9 patients for control cells, then for 11/17 AML patients treated with classical antileukemic drugs (among whom 4 were also treated with AcSDKP). The effect of AcSDKP was also studied on 7 patients. The discrepancy between both methods was essentially due to an accumulation of cells into different cycle phases measured by BrdUrd incorporation secondary to drug action and PKH67 labelling which measured the dynamic proliferation. This last method allows identifying resistant cells which still proliferate. AcSDKP or AcSDKP-NH2 induced a decrease of leukemic cell proliferation in 5/7 patients when cytokines were added (in order to stimulate proliferation) one day after tetrapeptide AcSDKP or AcSDKP-NH2. No effect on proliferation was noted when cytokines were added to AcSDKP-NH2.

Conclusion
PKH67 labelling method is a powerful tool for cell proliferation assessment in patients with AML, even in cells treated by various drugs.
Public beliefs about causes and risk factors for mental disorders: a comparison of Japan and Australia
Authors: Nakane Yoshibumi , Jorm Anthony F , Yoshioka Kumiko , Christensen Helen , Nakane Hideyuki , Griffiths Kathleen M 
Published: September 2005

AbstractBackgroundSurveys of the public in a range of Western countries have shown a predominant belief in social stressors as causes of mental disorders. However, there has been little direct cross-cultural comparison. Here we report a comparison of public beliefs about the causes of mental disorders in Japan and Australia.MethodsSurveys of the public were carried out in each country using as similar a methodology as feasible. In both countries, household interviews were carried out concerning beliefs about causes and risk factors in relation to one of four case vignettes, describing either depression, depression with suicidal thoughts, early schizophrenia or chronic schizophrenia. In Japan, the survey involved 2000 adults aged between 20 and 69 from 25 regional sites spread across the country. In Australia, the survey involved a national sample of 3998 adults aged 18 years or over.ResultsIn both countries, both social and personal vulnerability causes were commonly endorsed across all vignettes. The major differences in causal beliefs were that Australians were more likely to believe in infection, allergy and genetics, while Japanese were more likely to endorse "nervous person" and "weakness of character". For risk factors, Australians tended to believe that women, the young and the poor were more at risk of depression, but these were not seen as higher risk groups by Japanese.ConclusionIn both Japan and Australia, the public has a predominant belief in social causes and risk factors, with personal vulnerability factors also seen as important. However, there are also some major differences between the countries. The belief in weakness of character as a cause, which was stronger in Japan, is of particular concern because it may reduce the likelihood of seeking professional help and support from others.
Acute unilateral hearing loss as an unusual presentation of cholesteatoma
Authors: Thio Daniel , Ahmed Shahzada K , Bickerton Richard C 
Published: September 2005

Abstract

Background
Cholesteatomas are epithelial cysts that contain desquamated keratin. Patients commonly present with progressive hearing loss and a chronically discharging ear. We report an unusual presentation of the disease with an acute hearing loss suffered immediately after prolonged use of a pneumatic drill.

Case presentation
A 41 year old man with no previous history of ear problems presented with a sudden loss of hearing in his right ear immediately following the prolonged use of a pneumatic drill on concrete.
The cause was found to be a fractured long process of incus which had been eroded by the presence of an attic cholesteatoma.
A tympanomastoidectomy and ossiculoplasty was performed with good result.

Conclusion
Cholesteatomas may be asymptomatic and insidious in their onset. This case illustrates the point that an indolent disease such as this may present in unusual ways and the clinician must always have a high index of suspicion combined with thorough assessment and examination of every patient.