bluuebunny/crossref_metadata_2025_split huggingface dataset:
Matrix metalloproteinases (MMP) and cathepsin K contribute differently to osteoclastic activities
Authors: Delaissé Jean‐Marie , Andersen Thomas L. , Engsig Michael T. , Henriksen Kim , Troen Tine , Blavier Laurence 
Published: July 2003

AbstractThe best established proteolytic event of osteoclasts is bone matrix solubilization by the cysteine proteinase cathepsin K. Here, however, we draw the attention on osteoclastic activities depending on matrix metalloproteinases (MMPs). We discuss the observations supporting that MMPs contribute significantly to bone matrix solubilization in specific areas of the skeleton and in some developmental and pathological situations. Our discussion takes into account (1) the characteristics of the bone remodeling persisting in the absence of cathepsin K, (2) the ultrastructure of the resorption zone in response to inactivation of MMPs and of cathepsin K in different bone types, (3) bone resorption levels in MMP knockout mice compared to wild‐type mice, (4) the identification of MMPs in osteoclasts and surrounding cells, and (5) the effect of different bone pathologies on the serum concentrations of specific collagen fragments believed to discriminate between cathepsin K and MMP cleavage. Next, we provide evidence that MMPs are very critical for osteoclast migration, thereby controlling also the cell‐matrix interactions required for cell attachment/detachment. The evidence supporting this role is based on a model of osteoclast recruitment in primitive long bones, an assay of osteoclast invasion through collagen gel, and the effect of proteinase inhibitors/knockouts in these models. Furthermore, we mention observations indicating a role of MMPs in initiation of bone resorption. Finally, we emphasize the many distinct ways MMPs may alter focally the extracellular environment thereby regulating the osteoclast behavior. Although the understanding of MMPs in osteoclast biology is rapidly expanding, it is suspected that important roles remain to be discovered. Microsc. Res. Tech. 61:504–513, 2003. © 2003 Wiley‐Liss, Inc.
Osteoclast diseases
Authors: Helfrich Miep H. 
Published: July 2003

AbstractOsteoclasts are the only cells capable of resorbing mineralised bone, dentine and cartilage. Osteoclasts act in close concert with bone forming osteoblasts to model the skeleton during embryogenesis and to remodel it during later life. A number of inherited human conditions are known that are primarily caused by a defect in osteoclasts. Most of these are rare monogenic disorders, but others, such as the more common Paget's disease, are complex diseases, where genetic and environmental factors combine to result in the abnormal osteoclast phenotype. Where the genetic defect gives rise to ineffective osteoclasts, such as in osteopetrosis and pycnodysostosis, the result is the presence of too much bone. However, the phenotype in many osteoclast diseases is a combination of osteosclerosis with osteolytic lesions. In such conditions, the primary defect is hyperactivity of osteoclasts, compensated by a secondary increase in osteoblast activity. Rapid progress has been made in recent years in the identification of the causative genes and in the understanding of the biological role of the proteins encoded. This review discusses the known osteoclast diseases with particular emphasis on the genetic causes and the resulting osteoclast phenotype. These human diseases highlight the critical importance of specific proteins or signalling pathways in osteoclasts. Microsc. Res. Tech. 61:514–532, 2003. © 2003 Wiley‐Liss, Inc.
Osteoclastic bone resorption around intraosseous screws in rat and pig mandibles
Authors: Schulten Alcuin J.M. , Zimmermann Corinna E. , Glowacki Julie 
Published: July 2003

AbstractThis report describes osteoclastic bone resorption around intraosseous fixation screws in rat and pig mandibles. These screws supported distraction devices and provided for neutral fixation following the distraction period. Progressive clinical instability of bicortical screws and radiographic and histologic evidence of osseous resorption were frequent findings. In rats, clinical evaluation revealed screw loss and/or loosening in 50% of the rats between 11 and 30 days of neutral fixation. Radiographic signs of resorption were apparent around 60% of the screws that were in place at the end of the observation period. The total rate of resorption or loss was 64 of 80 screws (80%). Histologic examination showed partial or extensive osteolysis around the screw holes in 87% of screws that were clinically fixed in the bone at sacrifice. In histologic sections of porcine specimens, osseous resorption around identifiable screw holes was present in 75% of the cases, and showed progressive increase in resorption with time. Osteoclastic resorption was common around bicortical screws that were evaluated after they had served for osseous stability. Microsc. Res. Tech. 61:533–539, 2003. © 2003 Wiley‐Liss, Inc.
Transcription and immunolocalization of Runx2/Cbfa1/Pebp2αA in developing rodent and human craniofacial tissues: Further evidence suggesting osteoclasts phagocytose osteocytes
Authors: Bronckers Antonius L.J.J. , Sasaguri Kenichi , Engelse Marten A. 
Published: July 2003

AbstractRunx2/Cbfa1 is a transcription factor, essential for the osteogenic/chondrogenic and odontogenic lineage. Three isoforms of Cbfa1 have been identified, type I (Pebp2αA isoform), type II (til‐1 isoform), and type III (Osf2 isoform). Here we examined the expression of the Runx2/Cbfa1 during intramembranous and enchondral bone formation in the craniofacial tissues of neonatal rodents (hamster, rat, mouse) and the human fetus. We used a monoclonal antibody raised against the Pebp2αA portion and thus potentially recognizing all three isoforms of Runx2/Cbaf1. We report Cbfa1 at the mRNA and protein level in periosteum, preosteoblasts, osteoblasts, young osteocytes, perichondrium, resting and hypertrophic chondrocytes. During active bone remodeling, almost one third of tartrate resistant acid phosphatase (TRAP) positive multinuclear cells identified as osteoclasts were also stained with anti‐Pebp2αA antibodies. Osteoclasts, however, did not express mRNA transcripts of the Pebp2αA gene. Some of the immunopositive structures within these osteoclasts resembled (ingested) cells. TRAP‐positive mononuclear cells not attached to bone surfaces did not stain with anti‐Pebp2αA antibodies. We concluded that the tissue distribution of Runx2/Cbaf1/Pebp2αA in ossifying bones of the human fetus is similar to that in neonatal rodent tissues. Osteoclasts do not transcribe the Runx2/Cbfa1 gene but become immunostained by phagocytosing and digesting osteocytes/hypertrophic chondrocytes. The substantial number of osteoclasts involved in phagocytosis of Runx2/Cbfa1 immunopositive cells suggests that phagocytosis is a major way of removing osteocytes/hypertrophic chondrocytes during resorption of bone and cartilage. Finally, the data indicate that positive immunostaining of osteoclasts for typical osteogenic/chondrogenic markers has to be interpreted with caution due to the phagocytosing capacity of these cells. Microsc. Res. Tech. 61:540–548, 2003. © 2003 Wiley‐Liss, Inc.
Sri Lanka's plantation sector: a before‐and‐after privatization comparison
Authors: Loh Ai Tee , Kam Booi Hon , Jackson John T. 
Published: July 2003

AbstractSri Lanka's plantation sector was privatized in 1992. By comparing the performance of the State Corporations prior to 1992 and that of the transformed privatized entities post‐1992, this paper examines whether the operational efficiency of the sector has improved since privatization using six major efficiency indicators. While the results tend to favor the interpretation of an improvement in operational efficiency, data deficiency has made it difficult to identify possible causes for such an improvement. Copyright © 2003 John Wiley & Sons, Ltd.
BRCA1 expression in leukoplakia and carcinoma of the tongue
Authors: Vora Hemangini H. , Shah Neelam G. , Patel Devendra D. , Trivedi Trupti I. , Choksi Tejal J. 
Published: July 2003

AbstractBackground and ObjectivesExpression of BRCA1 was examined in patients with leukoplakia and carcinoma of the tongue. Its prognostic value was evaluated in patients with tongue cancer.MethodsExpression of BRCA1 was studied by immunohistochemical localization. Cytoplasmic staining of BRCA1 was observed in both leukoplakia and carcinoma of the tongue.ResultsIn leukoplakia, 61% and 39% of the patients expressed BRCA1 expression with a staining intensity of 1+ and 2+, respectively. In patients with hyperplasia (67%), BRCA1 expression with a staining intensity of 1+ was 67%; BRCA1 expression with a staining intensity of 2+ was 33%. In patients with dysplasia (33%; mild and moderate), BRCA1 expression with a staining intensity of 1+ and 2+ was 50% each. In carcinoma of the tongue, only 34% of the patients showed BRCA1 expression. In this group, 33% of the tumors exhibited 1+ staining, and only 1% of the tumors expressed 2+ staining. Moreover, BRCA1 expression with a staining intensity of 2+ was significantly higher in patients with dysplasia (50%) than in those with hyperplasia (33%), followed by patients with squamous cell carcinoma of the tongue (1%). The percentage positivity of BRCA1 expression in tongue cancer patients was significantly lower (34%), as compared with patients with leukoplakia (100%; P = 0.000001). A significant positive correlation was noted between BRCA1 and c‐myc (P = 0.012). Univariate survival analysis by log‐rank test and multivariate survival analysis by Cox regression showed that BRCA1 expression was the most significant prognostic factor predicting relapse‐free survival of early‐stage patients.ConclusionsSubcellular localization of the BRCA1 gene product provided evidence of its involvement in the pathogenesis of tongue tumors. J. Surg. Oncol. 2003;83:232–240. © 2003 Wiley‐Liss, Inc.
Role of MUC1 and MUC5AC expressions as prognostic indicators in gastric carcinomas
Authors: Wang Jaw‐Yuan , Chang Chiao‐Tang , Hsieh Jan‐Sing , Lee Li‐Wei , Huang Tsung‐Jen , Chai Chee‐Yin , Lin Shiu‐Ru 
Published: July 2003

AbstractBackground and ObjectivesThe aim of this study is to clarify the relationship between the expression of MUC1 and MUC5AC mucins and the clinicopathological features in human gastric carcinomas using the mouse monoclonal antibodies VU‐4H5 and Clone 45M1, respectively. Furthermore, the possibility of using phenotypes (MUC1+/MUC5AC+, MUC1+/MUC5AC−, MUC1−/MUC5AC−, MUC1−/MUC5AC+) to predict prognosis of the patients is evaluated.MethodsFormalin‐fixed, paraffin wax‐embedded tissues from 76 cases of gastric cancer were examined for the expression of MUC1 and MUC5AC mucin antigens immunohistochemically using the avidin–biotin‐peroxidase method.ResultsOf the 76 cases, MUC1 and MUC5AC immunoreactivities were observed in 49 (64.5%) and in 32 (42.1%) of gastric carcinoma tissues, respectively. MUC1 expression was significantly correlated to the depth of invasion, lymph node metastasis, peritoneal dissemination, and tumor stage. On the other hand, MUC5AC was inversely associated with depth of invasion, lymph node metastasis, liver metastasis, and tumor stage. Multivariate analyses indicated that tumor stage and MUC1 mucin expression were independently correlated with overall survival. The patients with MUC1+/MUC5AC− antigen staining in carcinoma tissues showed the lowest survival rate among four phenotypes. In contrast, the patients with MUC1−/MUC5AC+ antigen staining in carcinoma tissues showed the highest survival rate.ConclusionsAltogether these data suggest that combined evaluation of MUC1 and MUC5AC mucin staining may be clinically helpful to predict outcome in patients with gastric cancer. J. Surg. Oncol. 2003;83:253–260. © 2003 Wiley‐Liss, Inc.
Gallbladder cancer invading the perimuscular connective tissue: Results of reresection after prior non‐curative operation
Authors: Muratore Andrea , Amisano Marco , Viganò Luca , Massucco Paolo , Capussotti Lorenzo 
Published: July 2003

AbstractBackground and ObjectivesMost T2 gallbladder cancers are diagnosed at final pathology after cholecystectomy. Reoperations including liver resection and regional lymph node dissection are needed to achieve better long‐term results. The aim of this study is to evaluate long‐term results of reresections after prior non‐curative surgery for T2 carcinomas.MethodsRetrospective study from January 1985 to July 2001. Twelve out of 14 pT2 cancers were found postoperatively. All but one underwent reresection: these 11 patients are the basis of our series.ResultsThe in‐hospital mortality rate was 0%. Overall 5‐year survival was 63.5% with a median survival of 25 months. Median and 5‐year survival of the eight cases without preoperative signs of disease (Group A) were 46.7 months and 100%. These results were significantly better than those obtained in the subset (Group B: three cases) with preoperative signs of disease (P = 0.01): all these patients died of recurrence within 25 months from the reoperation. Mean time between cholecystectomy and reresection was 2.2 and 11.3 months in the Group A and B (P = 0.01), respectively.ConclusionsT2 cancers discovered incidentally after simple cholecystectomy should be reoperated on as soon as possible, as the appearance, before reoperation, of a recurrence is significantly related to a dismal prognosis. J. Surg. Oncol. 2003;83:212–215. © 2003 Wiley‐Liss, Inc.
Prognostic implication of cyclin E expression and its relationship with cyclin D1 and p27Kip1 expression on tissue microarrays of node negative breast cancer
Authors: Han Sehwan , Park Kyeongmee , Bae Byung‐Noe , Kim Ki Hwan , Kim Hong‐Joo , Kim Young‐Duck , Kim Hong‐Yong 
Published: July 2003

AbstractBackground and ObjectivesAltered expression of cell‐cycle regulators is prevalent in clinical breast cancer. This study was performed to analyze the impact of cyclin E expression to the outcome of breast cancer together with cyclin D1 and p27Kip1.MethodsThe correlation between cyclin D1/E and p27Kip1 expression was analyzed in tissue arrays of 175 node‐negative breast cancers treated by the same chemotherapy composed of fluorouracil, cyclophosphamide, and methotrexate. Data from the immunohistochemical assays of three molecules were correlated and were analyzed with clinical outcome of the patients.ResultsCyclin E expression was observed in 48 (27.4%) of 175 breast carcinomas. Cyclin E expression was significantly increased in young age patients and poorly differentiate tumors. Expression of cyclin E was significantly increased in cyclin D1 expressing tumors (P = 0.034). p27Kip1 expression was preserved above the 50% level in 87 tumors (49.7%) and was inversely correlated with cyclin E expression (P = 0.042). Ki67 labeling index was significantly increased in cyclin E–expressing tumors (P = 0.033) and was inversely related with p27Kip1 expression. In multivariate survival analysis, cyclin E expression was significant for the prediction of poor survival of the patients.ConclusionsCyclin E expression was associated with poor prognosis and intimately correlated with the expression of cyclin D1 and p27Kip1. Integration of TMA technology allowed a high‐throughput analysis for correlating molecular in situ findings with clinico‐pathologic information. J. Surg. Oncol. 2003;83:241–247. © 2003 Wiley‐Liss, Inc.
Serum interleukin‐6 levels reflect the disease status of colorectal cancer
Authors: Chung Yuan‐Chang , Chang Ya‐Fen 
Published: July 2003

AbstractBackground and ObjectivesInterleukin‐6 (IL‐6) has been shown to be associated with cancer development. However, its role in the progression of colorectal cancer has never been elucidated. Our intention was to investigate this role and identify its prognostic significance.MethodsOne hundred and sixty‐four consecutive colorectal cancer patients, whose local lesions were resected, were selected. The preoperative serum IL‐6 levels were measured and the relationships between the elevation of IL‐6 and both the clinicopathological factors and prognosis of patients were investigated.ResultsMedian IL‐6 level was significantly higher in patients with colorectal cancer than in normal controls. High levels of serum IL‐6 (>12 pg/ml) were correlated with larger tumor size, elevated serum CRP levels, and liver metastases (P < 0.05). IL‐6 levels also increased in a stage‐related manner (P < 0.01). Although serum IL‐6 correlated with survival, it is not an independent prognostic indicator.ConclusionsSerum IL‐6 levels correlated with disease status of colorectal cancer but could not be regarded as an independent predictor for prognosis. J. Surg. Oncol. 2003;83:222–226. © 2003 Wiley‐Liss, Inc.
Total abdominal colectomy, pelvic peritonectomy, and end‐ileostomy for the surgical palliation of mucinous peritoneal carcinomatosis from non‐gynecologic cancer
Authors: Stamou Konstantinos M. , Karakozis Stavros , Sugarbaker Paul H. 
Published: July 2003

AbstractBackground and ObjectivesThe optimal management of symptomatic advanced peritoneal carcinomatosis of non‐gynecologic origin is not defined. Historic controls of surgical efforts report high postoperative mortality and morbidity rates with equivocal palliation. Novel surgical procedures need to be tested in terms of the impact on survival and quality of life.Study DesignWe studied 46 consecutive patients who underwent total abdominal colectomy, pelvic peritonectomy with construction of an end‐ileostomy for palliation of peritoneal carcinomatosis.ResultsTotal abdominal colectomy, pelvic peritonectomy, and end‐ileostomy was successfully performed in 46 patients of median age of 54.4 years. Overall median survival was 10.7 months, with a mean follow‐up period of 12 months. Patients with appendiceal malignancy had a median survival of 19.7 months. Prognosis was poorer for patients with colon cancer, who had a median survival of 7.0 months, while patients with primary peritoneal carcinomatosis had a median of 7.8 months. Postoperative morbidity and mortality rates were 19.5 and 8.6%, respectively.ConclusionsTotal abdominal colectomy, pelvic peritonectomy, and end‐ileostomy is a technically feasible procedure and is advocated for the palliation of patients with peritoneal carcinomatosis of appendiceal origin. It is not clear if the procedure should be advocated for more invasive gastrointestinal malignancies. J. Surg. Oncol. 2003;83:197–203. © 2003 Wiley‐Liss, Inc.
Recovery of upper limb function after axillary dissection
Authors: Gosselink Rik , Rouffaer Lieven , Vanhelden Peter , Piot Wim , Troosters Thierry , Christiaens Marie‐Rose 
Published: July 2003

AbstractBackground and ObjectivesAfter surgery for breast cancer, data on the long‐term impairment of upper limb activities of daily living (ADL) are scarce. The purpose of this study was to investigate the short‐ and long‐term recovery of upper limb ADL function after surgery for breast cancer.MethodsSeventy‐six patients, who underwent either a breast‐conserving procedure with axillary dissection (BCP, n = 45) or a modified radical mastectomy (MRM, n = 31), were included. The patients were assessed on the fourth postoperative day, after 3 weeks, and after 3 months. Shoulder mobility, arm circumference, and upper limb ADL (score from 1 to 7) were evaluated.ResultsIn the early postoperative phase, a considerable decrease in shoulder mobility and the ability to perform upper limb ADL were observed. After 3 months, MRM patients had more limitations in shoulder mobility than BCP patients (shoulder flexion: 150° vs. 126°, respectively, P = 0.0001). In addition, upper limb ADL was still significantly impaired: MRM patients suffered from greater functional disabilities than BCP patients, ADL score 2.7 and 1.8, respectively (P = 0.037). Patients with axillary radiation experienced greater disability of shoulder mobility and ADL.ConclusionsThree months after surgery for breast cancer, impaired shoulder mobility, and ADL persisted in a substantial number of patients. Type of surgery and axillary irradiation contributed significantly to upper limb recovery. This observation warrants considering continuation of physiotherapy aiming to improve restoration of upper limb function. J. Surg. Oncol. 2003;83:204–211. © 2003 Wiley‐Liss, Inc.
Color multiplex polymerase chain reaction for quantitative analysis of epidermal growth factor receptor genes in colorectal adenocarcinoma
Authors: Layfield Lester J. , Bernard Philip S. , Goldstein Neil S. 
Published: July 2003

AbstractBackground and ObjectivesEpidermal growth factor receptor (EGFR) is a 170‐kDa transmembrane cell surface receptor, which belongs to the c‐erbB family of tyrosine kinases. Chimeric anti‐EGFR monoclonal antibody is an investigational therapy for advanced adenocarcinoma of the colon. Anti‐EGFR is believed to be most effective against those neoplasms with elevated EGFR levels. Possible mechanisms for over expression of EGFR include gene amplification, transcriptional upregulation, or decreased degredation of the EGFR protein.MethodsWe analyzed a series of 36 specimens of colonic adenocarcinoma with known levels of EGFR protein expression for amplification of the gene sequence of EGFR. Carcinomas were considered positive for EGFR expression when greater than 10% of the neoplastic cells stained at a level of 2+ or 3+. Foci of adenocarcinoma were microdissected from paraffin sections and quantitative real‐time PCR (polymerase chain reaction) performed using a thermal cycler with real time fluorescence capability (Light cyclerTM, Roche Diagnostics, Indianapolis, IN). A relative quantitation assay comparing the EGFR gene to the control albumin gene was performed by 2‐color multiplexing.ResultsUsable data on gene amplification status were obtained in 31 of the 36 samples. The average EGFR/albumin gene copy number ratio for the 31 samples of colon adenocarcinoma in which PCR results were obtained was 1.13 ± 0.55 with a range of 0.26–2.29. The average EGFR/albumin gene copy number ratio obtained for 16 normal DNA leukocyte samples used to establish the efficiency curves was 1.03 ± 0.31 with a range of 0.49–1.51.ConclusionsEGFR protein is overexpressed in a significant percentage of colonic adenocarcinomas. As with Her‐2/neu overexpression, overexpression of EGFR serves as a basis for specific antibody therapy in a subset of carcinomas. Unlike Her‐2/neu, where most overexpression is secondary to gene amplification, overexpression of EGFR appears to be unrelated to gene amplification. J. Surg. Oncol. 2003;83:227–231. © 2003 Wiley‐Liss, Inc.