bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumour cell and stromal features in metastatic and non‐metastatic non‐small cell lung carcinomas
Authors: Minamoto H , Antonângelo L , Da Silva A G P , Gallo C P , De Andrade e Silva F B , Fenezelian S , Rodrigues O R , Jatene F , Saldiva P , Capelozzi V L 
Published: December 2004

Aims:  Tumour cell behaviour depends on the interactions between nuclear genetic changes in the malignant cells and a stroma favourable for growth, invasion and metastasis. To evaluate such interactions, we studied the relationship between tumour cell and stromal features for proliferative factors, p53, microvessel density and metalloproteinases, controlled for the extent of the primary lesion (T1 to T4), in early (non‐metastatic) and late (metastatic) non‐small cell lung carcinomas (NSCLC).Methods and results:  Variables were examined for differences and correlations in the frequency of p53, AgNOR, CD34 and MMP‐9 expression in primary lesions and metastases of NSCLC using a general linear model. The patients included 58 males and 22 females (mean age 62 ± 9 years) with 19 T1 (23.8%), 40 T2 (50.0%), 14 T3 (17.5%) and seven T4 (8.8%). In late disease, AgNOR and p53 were statistically related to the extent of the primary lesion, whereas in early disease AgNOR tended to be increased in tumours without metastasis, while p53 expression tended to decrease progressively in tumours with metastasis. Microvessel density in late disease was of no statistical significance, whereas in early disease strong CD34 expression was seen in tumours with metastasis, being at its maximum in T3 primary lesions. The best marker for the extent of the lesion and its progression was MMP‐9, with greater expression by tumours with metastasis than those without.Conclusions:  Different tumour cell and stromal interactions control metastasis and therefore the biological risk of NSCLC. A panel of molecular markers, such as p53, MMP‐9 and CD34 could help to identify subgroups of patients that could benefit from adjuvant therapy.
Hepatic ‘stem cell’ malignancies in adults: four cases
Authors: Theise N D , Yao J L , Harada K , Hytiroglou P , Portmann B , Thung S N , Tsui W , Ohta H , Nakanuma Y 
Published: December 2004

Aims:  Combined hepatocellular/cholangiocarcinomas have been explained by some investigators as bidirectional differentiation of neoplastic progenitor cell populations. The presence of hepatic progenitor cells has now been confirmed in humans, though whether they can give rise to malignant tumours has not been confirmed. We report four cases of small tumours identified in livers with features of chronic hepatitis which may suggest a role for malignant transformation of hepatic stem cells in hepatic malignancies.Methods:  Tumour samples were studied from four patients by histochemistry and immunohistochemistry.Results:  Two patients had chronic hepatitis B, one had chronic hepatitis C and chronic alcoholic liver injury, and one had non‐B non‐C chronic hepatitis. Stages of disease ranged from portal fibrosis to cirrhosis. All tumours contained undifferentiated cells with morphological and immunohistochemical features that would be expected of hepatic progenitor cells. These cells merged with both hepatocellular carcinoma and cholangiocarcinoma components as well as with mature appearing hepatocytes within the tumours.Conclusion:  We suggest that these tumours are of hepatic progenitor cell origin, supporting the concepts that human hepatocarcinogenesis can be based on transformation of progenitor cells and that such a process may underlie development of some mixed hepatocellular/cholangiocarcinomas and dysplastic nodules.
Phenotypic alteration in malignant transformation of colonic villous tumours: with special reference to a comparison with tubular tumours
Authors: Takata M , Yao T , Nishiyama K‐I , Nawata H , Tsuneyoshi M 
Published: December 2004

Aims:  To clarify the cellular differentiation of colorectal villous tumours in malignant transformation, compared with that of tubular tumours (tubular adenoma and adenocarcinoma arising in tubular adenoma).Methods and results:  Forty‐nine cases of colorectal villous tumours [six cases of low‐grade villous adenoma, 21 of high‐grade villous adenoma (VA), nine of invasive carcinoma in villous adenoma (CIVA), and 13 of pure villous carcinoma (PVC)] and 46 cases of tubular tumours [14 cases of low‐grade and 17 of high‐grade tubular adenoma (TA), and 15 cases of carcinoma in tubular adenoma (CITA)] were selected for this study based on their expression patterns of CD10 (small intestinal brush border), MUC2 (intestinal goblet cell), and HGM (gastric foveolar epithelium). HGM was more frequently expressed in the adenomatous components of villous tumours (63%) than in those of tubular tumours (14%) (P < 0.05). CD10 expression of high‐grade TAs (47%) and carcinomas arising in TA (60%) was significantly higher than that of villous tumours (0%) (P < 0.05).Conclusions:  There were significant differences in the phenotypic expression of adenoma and adenocarcinoma between villous and tubular tumours, respectively. Villous tumours have a pathway of malignant transformation different from that of tubular tumours. Because of biological differences, colorectal villous tumours should be distinguished from tubular neoplasia. The analysis of the phenotype of colorectal neoplasms is useful for the evaluation of tumour progression.
Altered expression of DNA double‐strand break detection and repair proteins in breast carcinomas
Authors: Angèle S , Treilleux I , Brémond A , Tanière P , Hall J 
Published: December 2004

Aims:  To determine whether the expression of DNA damage detection and repair proteins is frequently altered in breast carcinomas.Methods and results:  The expression profiles of five such proteins: ATM, p53, NBS1, MRE11 and Rad50 were analysed in 99 in‐situ and invasive ductal breast carcinomas of different grades using an immunohistochemical approach, and compared with those seen in eight independent non‐cancer (normal) breast samples and in the surrounding normal tissues of the breast carcinomas examined. ATM protein expression was reduced in 75% of the tumours compared with the levels found in normal tissues. Fewer tumours had reduced protein levels of the members of the MRE11, NBS1 and Rad50 (MNR) complex (31%, 46% and 28%, respectively) with p53 being over‐expressed in 30%. In the majority of tumours (92%) we observed a good correlation between the expression of the three proteins of the MNR complex with low NBS1, MRE11 or Rad50 expression rarely found alone, suggesting that this event occurs subsequently to the deregulation in expression of other DNA repair proteins.Conclusion:  The pattern of protein changes observed supports our hypothesis that alterations in DNA double‐strand break repair capacity are involved in mammary carcinogenesis.
Refining the diagnosis of hydatidiform mole: image ploidy analysis and p57KIP2 immunohistochemistry
Authors: Crisp H , Burton J L , Stewart R , Wells M 
Published: December 2004

Aim:  To determine whether image analysis of ploidy status and immunohistochemical analysis of p57KIP2 (a paternally imprinted, maternally expressed gene) can be used to refine the diagnosis of molar pregnancy.Methods and results:  The original histological diagnosis in 40 randomly selected cases of hydatidiform mole was reviewed and confirmed in 38 cases (22 complete moles, 16 partial moles). These cases were anonymized and submitted for further analysis. Tissue from each case was submitted for flow cytometric assessment of DNA ploidy using a FACSort flow cytometer and for automated image cytometric assessment using a novel digital imaging system. Tissue sections from each case were immunostained with a monoclonal mouse antibody to p57KIP2. Correlations between the histopathological diagnosis, image cytometry, flow cytometry and p57KIP2 immunohistochemistry were determined using κ statistics. The concordance between histological diagnosis and p57KIP2 was very good (κ = 0.89). Twenty of the 22 (90.9%) complete moles showed no immunoreactivity for p57KIP2. The remaining two cases showed nuclear immunoreactivity in villous cytotrophoblast. In one of these, the pattern of staining resembled that of a partial mole. In the other, the staining pattern supported the diagnosis of a twin molar/non‐molar pregnancy. All 16 partial moles were p57KIP2 immunoreactive. On flow cytometry, all 22 complete moles were diploid and 12/16 partial moles were triploid (the remaining four cases originally diagnosed as partial moles were found to be diploid). On image cytometry, one case originally diagnosed as complete mole was found to contain a triploid population. Thus, by using a combination of image cytometry and p57KIP2 status we were able to refine the diagnosis of molar pregnancy in five (13%) of the cases studied.Conclusions:  Automated image cytometry is a readily performed investigation which is comparable to, but more sensitive than, flow cytometry. Complementary use of ploidy analysis and p57KIP2 status can now help to distinguish a diploid hydropic miscarriage (p57KIP2‐positive), diploid complete mole (p57KIP2‐negative) and triploid partial mole (p57KIP2‐positive).
Decrease of Deleted in Malignant Brain Tumour‐1 (DMBT‐1) expression is a crucial late event in intrahepatic cholangiocarcinoma
Authors: Sasaki M , Huang S‐F , Chen M‐F , Jan Y‐Y , Yeh T‐S , Ishikawa A , Mollenhauer J , Poustka A , Tsuneyama K , Nimura Y , Oda K , Nakanuma Y 
Published: December 2004

Aims:  To investigate the participation of DMBT‐1, a candidate tumour suppressor gene, in the development of intrahepatic cholangiocarcinoma via intraductal papillary neoplasm of the liver (IPN‐L) arising in hepatolithiasis. DMBT‐1 plays a role in mucosal immune defence.Methods and results:  The expression of DMBT‐1 was examined immunohistochemically in biliary epithelial cells in hepatolithiasis (n = 25), invasive and non‐invasive cholangiocarcinoma associated with hepatolithiasis (n = 52), IPN‐L with hepatolithiasis (n = 49), cholangiocarcinoma without hepatolithiasis (n = 32), and 10 normal control livers. DMBT‐1 was expressed more frequently in the biliary epithelia of hepatolithiasis when compared with normal livers (P < 0.05). DMBT‐1 expression was also frequent in IPN‐L (57%) and non‐invasive cholangiocarcinoma (79%). By contrast, DMBT‐1 was decreased in invasive cholangiocarcinoma with and without hepatolithiasis (50% and 30%, respectively) (P < 0.05). The homozygous deletion of the DMBT‐1 gene was recognized in four (20%) of 20 cholangiocarcinoma tissues and two (50%) of four cholangiocarcinoma cell lines, corresponding to the reduction of DMBT‐1 expression. No deletion was detected in hepatolithiasis tissues.Conclusion:  DMBT‐1 expression is increased in IPN‐L and non‐invasive cholangiocarcinoma as well as in biliary epithelia in hepatolithiasis. Decreased expression of DMBT‐1 and homozygous deletion of the DMBT‐1 gene in invasive cholangiocarcinoma suggest that they occur in the late stage of cholangiocarcinogenesis.
Analysis of the prognostic implications of different tumour margin types in renal cell carcinoma
Authors: Thomas D H , Verghese A , Kynaston H G , Griffiths D F R 
Published: December 2004

Aims: Invasion of perinephric tissues is part of the Union Internationale Contre le Cancer (UICC) (1997) T staging criteria for renal cell carcinoma (RCC) and appears to confer a worse prognosis. However, there are no established histological criteria to determine if this has occurred and histopathologists differ in their interpretation of the tumour margin. The purpose of this study was to determine histological criteria for invasion of perinephric tissues that may be used in staging.Methods and results: We assessed the prognostic implications of different margin types in 176 cases of RCC with good follow‐up data. The tumour margin type in each cases was classified as follows: fibrous tumour capsule; rim of kidney; fibrous capsule with ‘collar stud’ invasion; pushing margin, no capsule; and tumour cell invasion of fat. The margin types were used in univariate and multivariate survival analysis to determine which had most impact on disease‐free survival. In Cox regression analysis with all other influential covariates cellular invasion of fat was the only margin type that had any prognostic impact, conferring a 2.9 relative hazard compared with tumours with a fibrous capsule (P = 0.007).Conclusions: For staging purposes the designation of a tumour as invading perinephric tissues should be limited to those cases that have tumour cells invading the perinephric fat.
ALK‐negative anaplastic large‐cell lymphoma demonstrates similar poor prognosis to peripheral T‐cell lymphoma, unspecified
Authors: Ten Berge R L , De Bruin P C , Oudejans J J , Ossenkoppele G J , Van Der Valk P , Meijer C J L M 
Published: December 2004

Aims:  Anaplastic large cell lymphoma (ALCL) is classically considered a clinicopathological entity separate from other nodal mature T‐cell lymphomas (TCL). Recently, the anaplastic lymphoma kinase (ALK) protein was shown to identify a subgroup of nodal ALCL with an excellent prognosis, whereas ALK‐negative ALCLs are more heterogeneous. The aim of this study was to investigate the clinicopathological parameters in relation to clinical behaviour of ALK‐negative ALCL compared with other nodal mature TCL, i.e. peripheral TCL, unspecified (PTCL‐NOS) and angioimmunoblastic lymphoma (AILT).Methods and results:  Clinicopathological data of ALK‐positive (n = 28) and ALK‐negative (n = 46) ALCL; PTCL‐NOS (n = 47); and AILT (n = 12) were analysed for their prognostic significance. While ALK‐positive ALCL shows favourable clinical features and a good prognosis, ALK‐negative ALCL, PTCL‐NOS and AILT are all associated with high age groups, advanced disease stage, and poor prognosis (<45% 5‐year survival). In multivariate analysis of overall survival time, performed in the combined group of ALK‐negative nodal mature T‐cell lymphomas, only age and the International Prognostic Index (IPI) remained independent prognostic parameters, while lymphoma subtype (ALCL versus PTCL‐NOS versus AILT) gave no additional information.Conclusions:  The distinction between ALK‐negative ALCL and PTCL‐NOS or AILT is of limited clinical relevance as they show comparable poor prognosis. In these lymphoma subtypes, only age and the IPI are of significant prognostic value.
MOC‐31/Ep‐CAM immunoreactivity in Merkel cells and Merkel cell carcinomas
Authors: García‐Caballero T , Pintos E , Gallego R , Parrado C , Blanco M , Bjornhagen V , Forteza J , Beiras A 
Published: December 2004

Aims:  To evaluate the monoclonal antibody MOC‐31 in Merkel cell carcinomas and normal Merkel cells. Merkel cell carcinoma is a rare and aggressive tumour that occurs mainly in elderly individuals. The histological diagnosis of Merkel cell carcinoma can be difficult because it looks similar to other small blue cell tumours, particularly skin metastases of small‐cell lung carcinomas. This antibody recognizes the epithelial cell adhesion molecule (Ep‐CAM), that has been assigned to the small cell lung cancer cluster 2 of antibodies. To the best of our knowledge, immunostaining for MOC‐31/Ep‐CAM has not been previously described in Merkel cells or Merkel cell carcinomas.Methods and results:  Thirty‐one cases of Merkel cell carcinoma and three samples of normal human fingertip were selected to analyse the expression of MOC‐31/Ep‐CAM by immunohistochemistry. A high number of Merkel cell carcinomas (21/31, 67.7%) showed intense and readily interpretable positivity. Immunostaining was diffuse or focal and always localized to the plasma membrane. Normal Merkel cells of human fingertip also showed plasma membrane immunoreactivity for MOC‐31/Ep‐CAM.Conclusion:  The demonstration of positivity for MOC‐31/Ep‐CAM in Merkel cell carcinomas precludes the use of this immunohistochemical marker to distinguish between tumours and skin metastases of small‐cell lung carcinoma.
A preliminary in vitro study of the incidence and position of the root canal isthmus in maxillary and mandibular first molars
Authors: Teixeira F. B. , Sano C. L. , Gomes B. P. F. A. , Zaia A. A. , Ferraz C. C. R. , Souza‐Filho F. J. 
Published: December 2004

AbstractAim  To investigate in vitro the incidence and position of the root canal isthmus in extracted mesiobuccal roots of maxillary and mesial roots of mandibular first molars.Methodology  Fifty maxillary and 50 mandibular molars were included in the study. The mesiobuccal roots of maxillary molars and the mesial roots of mandibular molars were sectioned from their crowns in the furcation region and embedded in clear resin. Transverse serial 1‐mm‐thick sections from the apical 6 mm were prepared. The apical side of each section was stained with India ink and observed through a light microscope. The sample images were saved to disk using a digital camera and the root canals in terms of the number present and the incidence and classification of isthmuses.Results  In the mesiobuccal root of the maxillary first molars, 70% had one canal, whereas 29.5% had two canals. In the mesial root of mandibular molars, 41% had one canal, whereas 59% had two canals. In some sections, more than two canals were found close to the apical foramen. The isthmus incidence was greatest 3–5 mm from the apex. In teeth having two canals, a complete or partial isthmus was frequently observed in the sections between 3 and 4 mm from the apex. Of the isthmuses present, 22% were complete and 37% partial in mandibular molars and 17.3% were complete and 11.7% partial in maxillary molars.Conclusions  The incidence of isthmus in the mesiobuccal root of the maxillary first molars and in the mesial root of the mandibular first molars was high, particularly in sections 3–5 mm from the apex. Cleaning the isthmus is a major challenge during root canal treatment.
Evaluation of damage to the testicular cells of golden hamsters caused by experimental cryptorchidism using flow cytometry and confocal microscopy
Authors: Vigodner M. , Lewin L. M. , Shochat L. , Oschry I. , Lotan G. , Kleen B. , Golan R. 
Published: December 2004

SummaryArtificial unilateral cryptorchidism was performed in golden hamsters which were then held for different periods of time. The non‐operated side was used as a control. At various times from 4 to 15 days, hamsters were killed, testes were removed and weighed, single cell suspensions were prepared for flow cytometry analysis and seminiferous tubules were fixed for confocal microscopy. Using DNA staining by propidium iodide or acridine orange followed by flow cytometry analysis, a marked decrease in the haploid condensed cell fraction was detected at the beginning stages of experimental cryptorchidism. In correlation with flow cytometry results, spermiogenic arrest at stages IX and X of seminiferous epithelium was detected in these animals by confocal microscopy and there were no mature forms of haploid cells in the cryptorchid testis. In the testis with more severe damage, there were almost no haploid cells in the seminiferous tubules of cryptorchid animals. In addition, a significant decrease in tetraploid cell fraction and an increase in S‐phase fraction was obtained in severe cases. This may be explained by cell arrest before entrance into meiosis. Destruction of tubule structure and cell arrangement were also observed by confocal microscopy in such cases.In conclusion, flow cytometry, combined with confocal analysis, added useful information about spermatogenesis disturbances in cryptorchid testis and it may be used as diagnostic tools in other cases of spermatogenic disorders.
The Y chromosome and male fertility and infertility1
Authors: Krausz Csilla , Forti G. , McElreavey Ken 
Published: December 2004

SummarySince 1995, thanks to a large number of studies, Y chromosome microdeletion screening has become part of the routine diagnostic work‐up of severe male factor infertility. Many initial contradictory issues such as variability in deletion frequency, markers to be tested, presence of deletions in ‘fertile’ men, and genotype–phenotype correlation has been resolved. Past and present unresolved issues are discussed in this review.
Participation of superoxide anion in the capacitation of cryopreserved bovine sperm
Authors: O'Flaherty C. , Beorlegui N. , Beconi M. T. 
Published: December 2004

SummaryMammalian spermatozoa must undergo a preparation period known as capacitation to become capable of fertilizing oocytes. Controlled amounts of reactive oxygen species (ROS), such as superoxide anion (O2·–) and hydrogen peroxide (H2O2) have been shown essential for capacitation and acrosome reaction. The presence of an oxidase in the sperm plasma membrane has been suggested. The objective of the present study was to provide evidence for the production of O2·–by capacitating cryopreserved bovine spermatozoa. Percentages of capacitation and acrosome reaction were determined by the chlortetracycline assay. The effect of several nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitors on capacitation was also studied. H2O2production was determined by the fluorometric assay using thep‐hydroxyphenylacetic acid‐horseradish peroxidase system. Superoxide dismutase (SOD) activity was determined spectrophotometrically at 480 nm. Heparin‐dependent capacitation was inhibited by all NADPH oxidase inhibitors tested (p < 0.05). Significant levels of H2O2were produced during capacitation with heparin; such production was inhibited by diphenyleneiodonium, one of the NADPH oxidase inhibitors. The addition of catalase to the incubation medium failed to modify the capacitation rate; inhibition was only observed when SOD was present (p < 0.05). Endogenous SOD activity was diminished during heparin‐dependent capacitation (p < 0.05). Similar levels of acrosome reaction induced by lysophosphatidylcholine were obtained in both heparin and O2·–‐dependent capacitation. Overall results suggest the participation of a sperm oxidase in bovine sperm capacitation. H2O2, generated by O2·–dismutation, failed to participate in capacitation, although this ROS may have been able to decrease endogenous SOD activity. Exogenous O2·–promotes physiological capacitation in cryopreserved bovine sperm, thus allowing the acquisition of fertilizing capacity.
The role of the c‐kit receptor in the regenerative differentiation of rat Leydig cells
Authors: Tsuchida Junji , Dohmae Kayoko , Kitamura Yukihiko , Nishimune Yoshitake 
Published: December 2004

SummaryTo determine the physiological role of the c‐kit receptor, which is highly expressed in Leydig cells, the regenerative differentiation of Leydig cells was studied following transient degeneration induced by ethane dimethyl sulphonate (EDS) in c‐kit‐deficient mutant rats (Ws/Ws). EDS caused the destruction of Leydig cells; their functional recovery was evaluated by the weight change of the target organs of androgens, which occurred at the same rate in Ws/Ws and wild‐type rats. These results indicate that the tyrosine kinase activity of the c‐kit receptor does not play an essential role in the regenerative differentiation of Leydig cells.