bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nuclear expression of S100A4 is associated with aggressive behavior of epithelial ovarian carcinoma: An important autocrine/paracrine factor in tumor progression
Authors: Kikuchi Norihiko , Horiuchi Akiko , Osada Ryosuke , Imai Tsutomu , Wang Cuiju , Chen Xiaojun , Konishi Ikuo 
Published: August 2006

Although S100A4 expression has reportedly been associated with metastasis of various malignancies, little is known about its biological significance in ovarian carcinomas. In this study, we investigated expression and secretion of S100A4 and its extracellular function in ovarian carcinoma cells. We first used immunohistochemistry to examine the expression and localization of S100A4 in 113 epithelial ovarian neoplasms (24 benign, 20 borderline, and 69 malignant tumors) and analyzed its prognostic significance in patients with ovarian carcinoma. Then we investigated the expression, subcellular localization, and secretion of S100A4 in four ovarian carcinoma cell lines. Finally, we examined the effect of S100A4 treatment on the cell proliferation and invasiveness of ovarian carcinoma cells, along with activation of small GTPase, RhoA. Both cytoplasmic and nuclear expressions of S100A4 were significantly stronger in carcinomas than those in benign and borderline tumors. Ovarian carcinoma patients with strong nuclear S100A4 expression showed a significantly shorter survival than those without (P = 0.0045). This was not the case for cytoplasmic S100A4 expression. Ovarian carcinoma cell lines were shown to express S100A4, and secrete S100A4 into the culture media. Treatment with recombinant S100A4 resulted in the upregulation of S100A4 expression, translocation of S100A4 into the nucleus, and enhancement of invasiveness, which was associated with the upregulation of small GTPase, RhoA. These findings suggest that the nuclear expression of S100A4 is involved in the aggressive behavior of ovarian carcinoma and S100A4 is an autocrine/paracrine factor that plays an important role in the aggressiveness of ovarian carcinoma cells. (Cancer Sci 2006; 97: 1061–1069)
Do browsing elephants damage female trees more?
Authors: Hemborg Åsa M. , Bond William J. 
Published: August 2006

AbstractHerbivory in unisexual plants has mainly been assessed in studies of invertebrates, mostly insects. At a different scale of disturbance, browsing by large animals has rarely been studied. Elephants can seriously damage or kill trees by removing parts of the canopy, debark, or break the stem. We compared browsing by African elephants (Loxodonta africana) in male and female Marula trees (Sclerocarya birrea ssp. caffra). We expected females to incur more damage because of their sweet and fleshy fruits, known to attract elephants from far. Following this, we expected females to give more resistance through a denser branch wood that would break off at a larger diameter than in males. We tested this by pulling branches down to simulate elephant browsing as to compare branch resistance and design. All trees showed signs of browsing and females were generally more injured. However, there was no sexual difference in wood density and diameter at breaking point. Female branches were shorter, less ramified and carried fewer reproductive shoots than male branches. This sexual dimorphism could result from costly reproductive allocation in females and sexual selection, promoting intensive male flowering. Indirectly, elephants could reinforce this difference by engaging females more in tissue repair after browsing.
Analysis of human leukaemias and lymphomas using extensive immunophenotypes from an antibody microarray
Authors: Belov Larissa , Mulligan Stephen P. , Barber Nicole , Woolfson Adrian , Scott Mike , Stoner Kerryn , Chrisp Jeremy S. , Sewell William A. , Bradstock Kenneth F. , Bendall Linda , Pascovici Dana S. , Thomas Mervyn , Erber Wendy , Huang Pauline , Sartor Mary , Young Graham A.R. , Wiley James S. , Juneja Surender , Wierda William G. , Green Anthony R. , Keating Michael J. , Christopherson Richard I. 
Published: August 2006

SummaryA novel antibody microarray has been developed that provides an extensive immunophenotype of leukaemia cells. The assay is a solid phase cell‐capture technique in which 82 antigens are studied simultaneously. This paper presents the analysis of 733 patients with a variety of leukaemias and lymphomas from peripheral blood and bone marrow. Discriminant Function Analysis of the expression profiles from these 733 patients and 63 normal subjects were clustered and showed high levels of consistency with diagnoses obtained using conventional clinical and laboratory criteria. The overall levels of consensus for classification using the microarray compared with established criteria were 93·9% (495/527 patients) for peripheral blood and 97·6% (201/206 patients) for bone marrow aspirates, showing that the extensive phenotype alone was frequently able to classify the disease when the leukaemic clone was the dominant cell population present. Immunophenotypes for neoplastic cells were distinguishable from normal cells when the leukaemic cell count was at least 5 × 109 cells/l in peripheral blood, or 20% of cells obtained from bone marrow aspirates. This technique may be a useful adjunct to flow cytometry and other methods when an extensive phenotype of the leukaemia cell is desired for clinical trials, research and prognostic factor analysis.
Long‐term outcome results of the first tandem autotransplant trial for multiple myeloma
Authors: Barlogie Bart , Tricot Guido J. , Van Rhee Frits , Angtuaco Edguardo , Walker Ron , Epstein Joshua , Shaughnessy John D. , Jagannath Sundar , Bolejack Vanessa , Gurley Jennifer , Hoering Antje , Vesole David , Desikan Raman , Siegel David , Mehta Jayesh , Singhal Seema , Munshi Nikhil C. , Dhodapkar Madhav , Jenkins Bonnie , Attal Michel , Harousseau Jean‐Luc , Crowley John 
Published: August 2006

SummaryTotal Therapy 1, the first tandem autotransplant trial for newly diagnosed patients with multiple myeloma, was designed to increase the frequency of complete response (CR) and thereby extend survival. With a median follow‐up of 12 years, 62 of 231 initially enrolled patients are alive (17% at 15 years); 31 remain event free (7% at 15 years) including 16 of 94 (41%) that initially achieved CR. Currently alive patients less frequently had cytogenetic abnormalities (CAs) at baseline (P = 0·002), postenrolment (P < 0·001) and at relapse (P = 0·004); elevations of serum C‐reactive protein (CRP) (P = 0·003) and lactate dehydrogenase (P = 0·029), anaemia (P = 0·029) and they more often completed two transplants within 12 months (P = 0·019). Postenrolment overall survival (OS) and event‐free survival (EFS) were superior in the absence of CA of the hypodiploidy or deletion 13 variety (P < 0·001 and 0·037 respectively) and in the presence of low CRP at baseline (P = 0·001 and 0·017 respectively). Postrelapse survival was longer in the absence of CA at relapse (P < 0·001), IgA isotype (P = 0·002), International Staging System stage 3 (P = 0·014), and when patients had two protocol transplants prior to relapse (P = 0·038). Ten‐year EFS and OS could be accomplished in 15% and 33% of patients, respectively, when all agents available in 1989, especially high‐dose melphalan, were applied together upfront for the management of myeloma.
Outcomes of alemtuzumab‐based reduced intensity conditioning stem cell transplantation using unrelated donors for myelodysplastic syndromes
Authors: Lim Zi Yi , Ho Aloysius Y. L. , Ingram Wendy , Kenyon Michelle , Pearce Laurence , Czepulkowski Barbara , Devereux Stephen , Duarte Rafael F. , Pagliuca Antonio , Mufti Ghulam J. 
Published: August 2006

SummaryThis prospective study evaluated the outcomes of 75 successive patients receiving a FBC (fludarabine, busulphan, alemtuzumab) reduced‐intensity conditioning (RIC) regimen for myelodysplastic syndromes (MDS) using volunteer unrelated donors(VUD). The prognostic significance of a variety of clinical variables including the recently described haematopoietic cell transplantation co‐morbidity index (HCT‐CI) was assessed. The median age of the cohort was 52·0 years (range: 19–68 years) with a median follow‐up of 1038·5 d. Forty‐nine patients (65%) had an International Prognostic Scoring System stage of ≥Intermediate‐2, 35 (46%) had intermediate or poor risk cytogenetics, and 23 patients(31%) were human leucocyte antigen‐mismatched. The actuarial 3‐year overall survival (OS) and disease‐free survival (DFS) was 43% [95% confidence interval (CI): 37–49] and 41% (95%CI: 35–47) respectively, and the cumulative incidence of extensive chronic graft‐versus‐host disease was 22%. On multivariate analysis, presence of either one class II mismatch or a two‐antigen mismatch adversely influenced transplant‐related mortality, DFS and OS. In addition, disease status at transplantation and the haematopoietic cell transplantation‐specific comorbidity index were independent variables for overall survival. In contrast, both advanced age and pre‐transplant cytogenetic status did not significantly affect overall outcomes. RIC regimens using VUD was associated with durable long‐term survival even in older patients with MDS, and the use of a pre‐transplant comorbidity index may help to improve patient selection for transplantation.
O‐1 10 YEAR AUDIT OF GLANDULAR CYTOLOGY REPORTS WITH SPECIAL REGARD TO THE EFFECT OF CONVERSION TO LBC
Authors: Shore E. , Ash A. , Smith J. H. F. 
Published: August 2006

Recent reviews of glandular reports have confirmed a wide variation in specificity.1–3 We have reviewed our performance over the last 10 years and evaluated the effect of conversion to Liquid Based Cytology (LBC) on our reporting rates and accuracy. Audit revealed an upward trend in ability to accurately detect glandular lesions, with particular improvement in identification of Cervical Glandular Intraepithelial Neoplasia (CGIN).

Year
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005

Cases reported As? glandular neoplasia
39
26
18
27
28
16
22
12
23
29

PPV for any % significant pathology
51
58
83
78
50
63
59
92
78
93

PPV for correctly identified lesion %
21
42
67
56
36
50
41
83
78
83

Reasons for this general increase will be discussed, including changes to the laboratory staffing structure and better recognition of such lesions through improved training. In addition, the recent introduction of LBC technology may have resulted in improved sampling of the endocervical component through use of the Cervex Broom and smear taker training. In addition SurePath™ cell collection techniques with enhanced preservation of morphology may have lead to better recognition.References:  1. Mathers et alCytopathology 2002, 13, 83–912. Pisal et al Eur J Obstet Gynaecol Reprod Biol 2003, 108, 209–2123. Kirwan et alCytopathology 2004, 15, 188–194
O‐7 AUDIT OF THYROID FINE NEEDLE ASPIRATION CYTOLOGY: A PROBABILISTIC APPROACH
Authors: Venkatraman L. , Dillon K. , Anderson N. H. 
Published: August 2006

Introduction:  Recent proposals from the Papanicolaou Society of Cytopathology for reporting fine needle aspiration (FNA) specimens from thyroid nodules suggest using 6 cytodiagnostic categories. This probabilistic approach to detection of malignancy seeks to clarify clinical implications for individual categories. Our audit aims to determine the rates for neoplasia and malignancy in the five diagnostic categories currently used in our department. We have evaluated the effect of refining cytodiagnosis in the aspirates reported as equivocal.Methods:  A total of 392 thyroid FNA specimens reported between Jan 2003 and Dec 2005 were classed as inadequate, benign, equivocal, suspicious and malignant. 85 follow‐up thyroidectomies were received during this period; the histological diagnoses were correlated with the initial FNA diagnosis.Results:  The FNA diagnoses for the 85 thyroidectomies were: 7 inadequate, 37 benign, 31 equivocal, 5 suspicious for malignancy and 5 malignant. The rates for neoplasia and cancer were respectively:Inadequate: 2/7 (28.5%) & 0/7(0%)Benign: 4/37(10.8%) & 2/37(5.4%)Equivocal: 18/31(58.1%) & 11/31(35.4%)Suspicious: 4/5(80%) & 4/5(80%)Malignant: 5/5(100%) & 5/5(100%)On subdividing the category equivocal into:(1) Cellular lesion cannot exclude follicular neoplasm: the neoplasia rate was 4/12(33.3%) and the cancer rate 3/12(25%)(2) Follicular neoplasm/lesion with nuclear atypia: the neoplasia rate was 14/19 (73.7%) and the cancer rate 8/19 (42.2%)Excluding microcarcinomas, the false negative rate was 2.7%; there were no false positives.Conclusion:  The diagnostic certainty of cancer for FNA thyroid reported suspicious or malignant is high. If cytology is equivocal, thyroidectomy is appropriate for those reported follicular neoplasm ± nuclear atypia while repeat FNA is more suitable for cellular lesions where a follicular neoplasm is not the primary cytodiagnosis. neoplasm is not the primary cytodiagnosis.
P‐1 DIRECT‐TO‐VIAL USE OF THE LIQUI‐PREP™ CYTOLOGY SYSTEM
Authors: Park J. , Jung E.‐H. , Kim C. , Choi Y. H. 
Published: August 2006

Introduction:  The authors initiated the use of Liqui‐PREP™ (LGM International Inc., Fort Lauderdale, FL, USA) in August, 2005. Cytotechnologists received extensive (one month) training by cytopathologists experienced in Liquid‐based cytology. The Liqui‐PREP™ direct‐to‐vial procedure (LP) was compared to the conventional Pap smears in a routine screening population.Methods:  Data derived from 26 178 LP cervical‐vaginal (CV) specimens were compared to data derived from 218 548 conventional Pap smears (CS). Both data sets reflect patient samples collected concurrently (August–December, 2005) by 117 participating outpatient medical practices from a well‐defined geographic area. There were no significant personnel changes during the study period. The diagnostic results, classified according to Bethesda criteria were calculated.Results:

% ASC‐US
% ASC‐H
% LSIL
% HSIL+
ASCUS/ LSIL+
% Unsat.

Liqui‐PREP™
6.5
0.24
1.55
0.39
3.8
0.02

Conv. Smear
2.8
0.09
0.50
0.25
4.0
0.05

Discussion:  Liqui‐PREP™ direct‐to‐vial method for CV specimens identified 210% more LSIL and 56% more HSIL+ lesions compared to the conventional smears. The ASCUS rate was increased (perhaps due to the conservative nature of our staff and their cautious interpretation of a new preparation). The ratio of ASCUS to LSIL+ was reduced by 5% for Liqui‐Prep™. Available biopsy data showed high correlation between both LP and CS abnormal cytology diagnoses (94.1% and 89.9% respectively). These findings suggest that the Liqui‐PREP™ cytology preparation procedure identifies more pre‐malignant lesions than the conventional smear.
P‐7 P16 ANTIBODY AS AN ADJUNCT TO ROUTINE CERVICAL SCREENING IN PROBLEMATIC CASES: A COMPARISON OF TWO COMMERCIALLY AVAILABLE ANTIBODIES
Authors: Govan L. 
Published: August 2006

Objective:  The introduction of Liquid Based Technology (LBC) offers numerous advantages for cervical screening including the facility to make additional preparations after the sample has been reported. Could this additional preparation be used effectively for immunocytochemical (ICC) staining for p16? The aim of this study was to establish working techniques, a scoring system and assess the suitability of p16 for use in diagnostically difficult cases.Study design:  A working technique for two commercially available antibodies, DakoCytomation Cintec p16INK4a and Vision Biosystems Novocastra p16 was established and applied to three groups of control samples, consisting of negative, borderline and dyskaryotic cases. All dyskaryotic cases were biopsy confirmed. The results obtained were used to formulate a scoring system (0–9), based on the percentage of positive cells and intensity of stain, which could then be applied to test cases. This group of test cases consisted of diagnostically difficult samples, which had been discussed or reviewed in the laboratory.Results:  The results showed that p16 could aid in the diagnosis of difficult cases and should be assessed together with the original Papanicalaou stained slide to identify the cells in question. The scoring system with a cut off score of 4 for a positive result proved significant.Conclusion:  Use of p16 in a routine laboratory could help further reduce false positive or negative results thus improving the service offered.
Multivariate calibration of hyperspectral γ‐ray energy spectra for proximal soil sensing
Authors: Viscarra Rossel R. A. , Taylor H. J. , McBratney A. B. 
Published: August 2006

SummaryThe development of proximal soil sensors to collect fine‐scale soil information for environmental monitoring, modelling and precision agriculture is vital. Conventional soil sampling and laboratory analyses are time‐consuming and expensive. In this paper we look at the possibility of calibrating hyperspectral γ‐ray energy spectra to predict various surface and subsurface soil properties. The spectra were collected with a proximal, on‐the‐go γ‐ray spectrometer. We surveyed two geographically and physiographically different fields in New South Wales, Australia, and collected hyperspectral γ‐ray data consisting of 256 energy bands at more than 20 000 sites in each field. Bootstrap aggregation with partial least squares regression (or bagging‐PLSR) was used to calibrate the γ‐ray spectra of each field for predictions of selected soil properties. However, significant amounts of pre‐processing were necessary to expose the correlations between the γ‐ray spectra and the soil data. We first filtered the spectra spatially using local kriging, then further de‐noised, normalized and detrended them. The resulting bagging‐PLSR models of each field were tested using leave‐one‐out cross‐validation. Bagging‐PLSR provided robust predictions of clay, coarse sand and Fe contents in the 0–15 cm soil layer and pH and coarse sand contents in the 15–50 cm soil layer. Furthermore, bagging‐PLSR provided us with a measure of the uncertainty of predictions. This study is apparently the first to use a multivariate calibration technique with on‐the‐go proximal γ‐ray spectrometry. Proximally sensed γ‐ray spectrometry proved to be a useful tool for predicting soil properties in different soil landscapes.
Transforming growth factor‐beta pathway disruption and infiltration of colorectal cancers by intraepithelial lymphocytes
Authors: Baker K , Chong G , Foulkes W D , Jass J R 
Published: August 2006

Aims Colorectal cancers deficient in DNA mismatch repair (MMR) are often characterized by the presence of numerous intraepithelial lymphocytes (IELs). These CD8+ T cells selectively express CD103, which is upregulated locally by transforming growth factor (TGF)‐β, and adhere to E‐cadherin expressed by mucosal epithelia. Many of these cancers also possess inactivating mutations in the type II TGF‐β receptor and are believed to be insensitive to TGF‐β. The present study aimed to explore whether such refractoriness to TGF‐β is an independently contributing factor to IEL retention.Methods and results A panel of colorectal cancers enriched for DNA MMR deficiency was examined by immunohistochemistry to explore the expression levels and localization of various components in the TGF‐β signalling pathway. Logistic regression was then carried out in order to identify predictors of elevated lymphocytic infiltration independent of DNA MMR status. Increases in Smad4 expression, tumour cell proliferation and TGF‐β secretion each emerged as independent predictors of marked lymphocyte infiltration.Conclusions These results strongly support the hypothesis that refractoriness to normal TGF‐β signalling in colorectal cancers plays a role in the retention of lymphocytes within tumour epithelium. Since IEL infiltration is an independent predictor of favourable prognosis, the TGF‐β pathway may represent an important therapeutic target.
Hepatic progenitor cells, stem cells, and AFP expression in models of liver injury
Authors: Kuhlmann Wolf D. , Peschke Peter 
Published: August 2006

AbstractAdult hepatocytes and liver‐cell progenitors play a role in restoring liver tissue after injury. For the study of progenitor cells in liver repair, experimental models included (a) surgical removal of liver tissue by partial hepatectomy; (b) acute injury by carbontetrachloride; (c) acute injury by d‐galactosamine (GalN) and N‐nitrosomorpholine (NNM); and (d) chemical hepatocarcinogenesis by feeding NNM in low and high doses. Serological and immunohistological detection of alpha‐fetoprotein gene expression served to follow pathways of cellular differentiation. Stem cells were not required in models of surgical removal of parenchyma and in carbon tetrachloride intoxication of adult hepatocytes. In contrast, regeneration of liver occurred through biliary epithelial cells in injuries induced by GalN and NNM. These biliary epithelial cells, collectively called oval cells, are most probably derived from the canals of Hering. Proliferating bile duct cells reached a level of differentiation with reactivation of foetal genes and significant alpha‐1‐fetoprotein (AFP) synthesis signalling a certain degree of retrodifferentiation with potential stemness. Due to the same embryonic origin of bile ducts and hepatocytes, biliary epithelium and its proliferating progeny (oval cells) have a defined role in liver regeneration as a transit and amplification compartment. In their early proliferation stage, oval cells were heavily engaged in DNA synthesis ([3H]thymidine labelling). Pulse‐chase experiments during experimental hepatocarcinogenesis exhibited their development into hepatocytes with high risk for transformation and leading to foci of altered hepatocytes. Hepatocellular carcinomas may arise either from proliferating/differentiating oval cells or from adult hepatocytes; both cell types have stem‐like properties. AFP‐positive and AFP‐negative carcinomas occurred in the same liver. They may represent random clonal origin. The heterogeneity of phenotypic marker (AFP) correlated with a process of retrodifferentiation.
Light cigarette smoke‐induced emphysema and NFκB activation in mouse lung
Authors: Santos Valenca Samuel , Castro Paulo , Alves Pimenta Wagner , Lanzetti Manuella , Vargas Silva Simone , Barja‐Fidalgo Cristina , Gonçalves Koatz Vera Lúcia , Porto Luís Cristóvão 
Published: August 2006

SummaryLight cigarette (LC) exposure is supposed to be less hazardous with a decreased incidence of cancer and tobacco‐associated diseases. C57BL/6 mouse groups were subjected to smoke from 3, 6 or 12 LC for 60 days and compared with mice exposed to ambient air (EAA) in order to study lung injury by morphometrical and biochemical methods. Bronchoalveolar lavage (BAL) analysis and histology and stereology were performed. Tissue from the right lung was used for measuring thiobarbituric acid reactive substances (TBARS) and Western blot analysis. One way anova was performed followed by the Student–Newman Keuls post‐test (P < 0.05). The cellular content of BAL was 95% alveolar macrophages in all groups except in mice exposed to 3 LC, where 23% neutrophils were observed. Emphysema was not observed in three and 6 LC, but it was found in 12 LC parallel to increased volume density (Vv) of airspaces from 61.0 ± 0.6 (EAA) to 80.9 ± 1.0 (12 LC) and decreased Vv of elastic fibres from 17.8 ± 0.9 (EAA) to 11.8 ± 0.6 (12 LC). All exposed groups to LC showed low TBARS levels compared with mice EAA. Lung tissue from animals exposed to 12 LC showed decreased tissue inhibitor of metalloprotease‐2 and increased matrix metalloprotease‐12 detection, which suggests an imbalance in extracellular matrix (ECM). Increased tumour necrosis factor‐α and nuclear factor‐κB detection were observed in exposed groups to LC when compared with mice EAA. The data suggest that LC is so dangerous to lungs as full‐flavour cigarettes inducing ECM imbalance and emphysema.