bluuebunny/crossref_metadata_2025_split huggingface dataset:
A healthy understanding of intraflagellar transport
Authors: Sloboda Roger D. 
Published: August 2002

AbstractA microtubule‐dependent motility process called intraflagellar transport (IFT) occurs beneath the plasma membrane of cilia and flagella. IFT was first observed in Chlamydomonas, and orthologs of some of the polypeptides involved in IFT have recently been identified in other organisms, including C. elegans and the mouse. In addition to a role in the assembly and maintenance of cilia and flagella, evidence is reviewed here that indicates defects in the process of IFT may be related to problems with human health. Moreover, recent data suggest the possibility of two new roles for IFT in cell function. The first is in transcriptional control of the genes encoding ciliary and flagellar proteins. IFT could provide a mechanism whereby the cell senses the presence or absence of its cilia or flagella and responds by turning on gene transcription resulting in replacement of the missing organelle. The second role is in signal transduction, whereby cilia act as sensors of the external cellular environment and transduce information about the surroundings into intracellular signals that are sent via IFT to the cell body, thus inducing an appropriate cellular response to the environment. Cell Motil. Cytoskeleton 52:1–8, 2002. © 2002 Wiley‐Liss, Inc.
Coexpression of ephrin‐Bs and their receptors in colon carcinoma
Authors: Liu Wenbiao , Ahmad Syed A. , Jung Young D. , Reinmuth Niels , Fan B.S. Fan , Bucana Corazon D. , Ellis Lee M. 
Published: August 2002

AbstractBACKGROUNDThe erythropoietin‐producing hepatoma amplified sequence (Eph) family is the largest subfamily of receptor tyrosine kinases (RTKs). The Ephs (receptors) bind to specific cell‐bound ligands, called ephrins. The binding of this ligand‐receptor system is dependent on cell‐cell interactions. The ephrin‐Eph system is important in embryologic development and differentiation of the nervous and vascular systems. In the current study, the authors hypothesized that ephrins may play a role in the growth and development of colon carcinoma and may be expressed differentially in normal and malignant colonic tissues.METHODSReverse transcriptase‐polymerase chain reaction (RT‐PCR), Northern Blot analyses, and immunohistochemistry were used to examine 11 colon carcinoma cell lines and 20 human colon carcinoma specimens with adjacent uninvolved mucosa for the expression of EphB and ephrin‐B family members.RESULTSEphB2, EphB3, and EphB4 mRNA expression and ephrin‐B2 mRNA expression was detected in all the cell lines and colon carcinoma specimens examined. Immunohistochemical analysis showed that ephrin‐B2 had higher expression in the colon carcinoma specimens studied than in adjacent normal mucosa. Ephrin‐B2 and EphB4 most frequently were expressed on the luminal surface of colon carcinoma epithelium.CONCLUSIONSThe results of the current suggest that the ephrin‐Bs are expressed differentially in colon carcinoma and normal mucosa specimens and thus may play a role in the progression of colon carcinoma. Further studies are necessary to determine the functional role of ephrin‐Bs in colon carcinoma angiogenesis and growth. Cancer 2002;94:934–9. © 2002 American Cancer Society.DOI 10.1002/cncr.10122
Lack of significant differences in the corrected activity of lysophospholipase D, producer of phospholipid mediator lysophosphatidic acid, in incubated serum from women with and without ovarian tumors
Authors: Tokumura Akira , Tominaga Kyoko , Yasuda Katsuhiko , Kanzaki Hideharu , Kogure Kentaro , Fukuzawa Kenji 
Published: August 2002

AbstractBACKGROUNDSeveral studies have shown that lysophosphatidic acid (LPA), a phospholipidic chemical mediator, is relevant to the pathogenesis of ovarian carcinoma. Higher plasma levels of LPA have been reported in patients with ovarian carcinoma than in healthy patients, and LPA is known to activate ovarian carcinoma cells. To determine the reason for the increased plasma LPA levels in ovarian carcinoma patients, we compared the activities of serum lysophospholipase D, a novel LPA‐producing metallo‐enzyme, in healthy volunteers, patients with benign ovarian tumor, and patients with ovarian carcinoma.METHODSLysophospholipase D activity was assessed by measuring the percentage conversion of [14C]palmitoyl‐lysophosphatidylcholine (LPC) added to human serum. The apparent enzyme activities were corrected based on the serum levels of palmitoyl‐LPC determined by gas‐liquid chromatography after its purification and conversion to fatty acid methyl esters.RESULTSThe apparent activity of lysophospholipase D in serum preparations from four patients with ovarian carcinoma at Stage IV was significantly higher than those from five healthy subjects, five patients with benign ovarian tumors, and fourteen patients with ovarian carcinoma at Stages I (n = 5), II (n = 4), and III (n = 5). The serum levels of LPC, an endogenous substrate of lysophospholipase D, in ovarian carcinoma patients were less than those in patients with benign ovarian tumors. There were no significant differences in the corrected lysophospholipase D activity for the LPC levels in healthy women, patients with benign ovarian tumors, and patients with ovarian carcinoma at various stages.CONCLUSIONSThe current results suggest that lysophospholipase D is not associated with the elevated plasma levels of LPA in ovarian carcinoma patients previously reported, although only a limited number of patients were analyzed. Cancer 2002;94:141–51. © 2002 American Cancer Society.
Influences of the lysosomal associated membrane proteins (Lamp‐1, Lamp‐2) and Mac‐2 binding protein (Mac‐2‐BP) on the prognosis of pancreatic carcinoma
Authors: Künzli Beat M. , Berberat Pascal O. , Zhu Zhaowhen W. , Martignoni Marcus , Kleeff Jörg , Tempia‐Caliera Adrien A. , Fukuda Minoru , Zimmermann Arthur , Friess Helmut , Büchler Markus W. 
Published: August 2002

AbstractBACKGROUNDLamps and Mac‐2‐BP are ligands of galectin‐3, and they were suggested to influence tumor proliferation and metastasis formation. The authors studied the expression of Lamp‐1, Lamp‐2, and Mac‐2‐BP in pancreatic carcinoma and evaluated their influence on patient prognosis.METHODSNorthern blot analysis, in situ hybridization, and immunohistochemistry were performed in 12 normal and 28 pancreatic carcinoma tissue samples and in pancreatic carcinoma cell lines. The molecular findings in the tumor samples were correlated with the prognosis and histopathologic tumor characteristics. In addition, in Lamp‐1 transfected CAPAN‐1 pancreatic carcinoma cells, cell proliferation was analyzed.RESULTSLamp‐1, Lamp‐2, and Mac‐2‐BP were overexpressed in 61% (1.6‐fold increase, not significant), 71% (3.0‐fold increase, P < 0.01), and 93% (5.6‐fold increase, P < 0.01) of the pancreatic carcinoma samples. Lamp‐1 and Lamp‐2 immunoreactivity was present at the luminal side of the ductal carcinoma cells whereas Mac‐2‐BP immunoreactivity was diffusely spread over the whole cytoplasm and the nucleolus of ductal carcinoma cells. Correlation of the molecular data with clinical patient parameters revealed that patients whose tumors exhibited high Lamp‐1 mRNA expression lived significantly longer (median, 17 months) after tumor resection than patients whose tumors exhibited low to moderate Lamp‐1 mRNA levels (median, 8 months; P < 0.02). No relation between Lamp‐2 and Mac‐2‐BP mRNA expression and any of the histopathologic parameters was found. Lamp‐1 transfected CAPAN‐1 cells showed decreased cell growth compared with the nontransfected cells.CONCLUSIONSLamp‐1 might influence local tumor progression rather than the formation of tumor metastasis in pancreatic carcinoma, whereas Mac‐2‐BP and Lamp‐2 seem to have little influence on these parameters in pancreatic carcinoma. Cancer 2002;94:228–39. © 2002 American Cancer Society.
Very early detection of RET proto‐oncogene mutation is crucial for preventive thyroidectomy in multiple endocrine neoplasia type 2 children
Authors: Sanso Gabriela E. , Domene Horacio M. , Garcia Rudaz Maria C. , Pusiol Eduardo , de Mondino Ana K. , Roque Maria , Ring Alejandro , Perinetti Hector , Elsner Boris , Iorcansky Sonia , Barontini Marta 
Published: August 2002

AbstractBACKGROUNDMultiple endocrine neoplasia type 2 (MEN 2) is an inherited disease caused by germline mutations in the RET proto‐oncogene, and is responsible for the development of endocrine neoplasia. Its prognosis is dependent on the appearance and spread of medullary thyroid carcinoma (MTC). Relatives at risk can be identified before clinical or biochemical signs of the disease become evident.METHODSTwenty‐one families with MEN 2 (16 families with MEN 2A and 5 families with MEN 2B) were studied. Peripheral blood DNA was amplified by polymerase chain reaction. DNA sequence or restriction enzyme analysis was performed to detect mutations of RET proto‐oncogene exons 10, 11, and 16. Molecular analysis was carried out in all index patients as well as in 98 relatives of MEN 2A patients (60 juveniles, ages 6 months to 21 years, and 38 adults, ages 22 to 81 years) and in 13 relatives (6 juveniles ages 10 to 21 years, and 7 adults ages 41 to 66 years) from MEN 2B families.RESULTSMolecular studies showed a mutation at codon 634, exon 11 in all MEN 2A patients. All MEN 2B patients showed an ATG to ACG (Met918Thr) mutation. In MEN 2A families, 42 out of 98 relatives were affected. Total thyroidectomy was performed in 18 juvenile carriers ages 17 months to 21 years. Histopathologic studies of the glands revealed parafollicular cell (C‐cell) hyperplasia in all of these carriers, medullary thyroid carcinoma in 15 carriers, and only one carrier with lymph node metastases.CONCLUSIONSThe consistent finding of C‐cell disease in all the juvenile carriers who underwent preventive thyroidectomy emphasizes the relevance of early screening in children at risk of developing MTC. The presence of MTC in the specimen of prophylactic thyroidectomy from a 17 month old girl highlights the importance of thyroidectomy as soon as the molecular diagnosis is confirmed. Cancer 2002;94:323–30. © 2002 American Cancer Society.
Central nervous system relapse in adults with acute lymphoblastic leukemia
Authors: Surapaneni Usha R. , Cortes Jorge E. , Thomas Deborah , O'Brien Susan , Giles Francis J. , Koller Charles , Faderl Stefan , Kantarjian Hagop 
Published: August 2002

AbstractBACKGROUNDRecurrence of acute lymphoblastic leukemia (ALL) in the central nervous system (CNS) in adults is considered a poor prognostic feature. Few reports have analyzed this issue. The objective of this study was to analyze the experience with CNS recurrence in adult patients with ALL.METHODSBetween December 1982 and April 2000, the records of 527 consecutive, newly diagnosed patients with ALL who were treated at the M. D. Anderson Cancer Center were reviewed. Patients were treated with one of two published regimens: vincristine, doxorubicin, and dexamethasone (VAD; n = 237 patients) or hyperfractionated cyclophosphamide plus VAD (hyper‐CVAD) (n = 290 patients). Among 439 patients (83%) who achieved complete remission (CR), 32 patients (7%) had a CNS recurrence. All patients had received CNS prophylaxis tailored to the risk of CNS recurrence with systemic chemotherapy with or without intrathecal (IT) chemotherapy; none received cranial radiotherapy for prophylaxis. The records of these patients were reviewed.RESULTSThe median age at the time of diagnosis was 33 years. The median CR duration prior to CNS recurrence was 36 weeks (range, 2–185 weeks). Three groups were identified: 1) patients with an isolated CNS recurrence (n = 17 patients), 2) patients with CNS recurrences after bone marrow (BM) recurrence (n = 8 patients), and 3) patients with simultaneous CNS and BM recurrences (n = 7 patients). IT chemotherapy was effective in achieving a CNS CR in 30 patients (94%), but 10 patients (31%) had a second CNS recurrence. The median survival from CNS recurrence was 6 months; 28% of patients were alive at 1 year, and 6% of patients were alive at 4 years.CONCLUSIONSAdults with ALL and CNS recurrences have a poor prognosis despite effective IT chemotherapy. Future studies should investigate better approaches in the treatment of these patients to improve their long‐term survival. Effective CNS prophylaxis remains the single best approach for treating patients with CNS leukemia. Cancer 2002;94:773–9. © 2002 American Cancer Society.DOI 10.1002/cncr.10265
Presence of active gelatinases in endometrial carcinoma and correlation of matrix metalloproteinase expression with increasing tumor grade and invasion
Authors: Di Nezza Lisa A. , Misajon Aileen , Zhang Jin , Jobling Tom , Quinn Michael A. , Östör Andrew G. , Nie Guiying , Lopata Alex , Salamonsen Lois A. 
Published: August 2002

AbstractBACKGROUNDThe actions of the extracellular‐matrix degrading enzymes, matrix metalloproteinases (MMPs), are implicated in tumorigenesis. The cellular localization of MMP‐2, MMP‐9, membrane type 1 (MT1)‐MMP, tissue inhibitors of metalloproteinases (TIMPs) 1‐3, and the presence of active gelatinases were investigated in endometrial carcinoma.METHODSEndometrial carcinomas were grouped according to histologic grade (Grades 1‐3), depth of myometrial invasion (0, < 50%, > 50%) and the presence of vascular/lymphatic invasion. Twenty‐nine endometrial carcinoma biopsies were investigated immunohistochemically to determine the tissue localization of MMP‐2 (gelatinase A), MMP‐9 (gelatinase B), MT1‐MMP, and TIMPs 1‐3. In situ hybridization was performed to localize MMP‐2 and MMP‐9 mRNA. The presence of active gelatinases was assessed using in situ zymography.RESULTSEpithelial tumor cells were the main site of MMP‐2, MMP‐9, and MT1‐MMP protein. Variable stromal cell localization was also observed, particularly in areas adjacent to tumor nests. Semiquantitative analysis revealed increases in MMP‐9 and MMP‐2 but not MT1‐MMP staining scores in tumor epithelial cells in the transition from histologic Grade 1 to Grades 2 and 3. Matrix metalloproteinase‐9 and MT1‐MMP staining scores in tumor cells were significantly associated with the presence of myometrial invasion and vascular/lymphatic invasion, while MMP‐2 did not correlate with these factors. In addition, MT1‐MMP was co‐localized with MMP‐2, supporting its role in the activation of proMMP‐2. Tumor cells from all histologic grades stained intensely for TIMP‐2 and TIMP‐3 proteins, while variable stromal staining was observed. In Grade 1 carcinomas TIMP‐1 was predominantly immunolocalized to the stromal compartment with variable tumor cell localization being observed in Grades 2 and 3 carcinomas. Matrix metalloproteinase‐9 and MMP‐2 mRNAs were predominantly observed in tumor epithelial cells as well as in the stroma to varying degrees. In situ zymography revealed active forms of gelatinases at the cellular surface and in association with tumor epithelial cells within endometrial carcinoma tissues.CONCLUSIONSThese data suggest that increasing expression of MMPs and endometrial carcinoma progression are closely related. Active gelatinases are present in endometrial carcinoma, resulting in alterations to the microenvironment that promote tumor invasion and metastasis. Cancer 2002;94:1466–75. © 2002 American Cancer Society.DOI 10.1002/cncr.10355
Trimodality treatment in Stage III nonsmall cell lung carcinoma
Authors: Broermann Petra , Junker Klaus , Brandt Burkhard H. , Heinecke Achim , Freitag Lutz , Klinke Folker , Berdel Wolfgang E. , Thomas Michael 
Published: August 2002

AbstractBACKGROUNDIn a trimodality treatment approach for Stage III nonsmall cell lung carcinoma (NSCLC), the prognostic impact of the ras mutation status in resection specimens was evaluated.METHODSForty patients with Stage III NSCLC underwent tumor resection after neoadjuvant treatment with two cycles of chemotherapy (ifosfamide, carboplatin, and etoposide) and subsequent twice‐daily radiotherapy (45 grays [Gy]; 2 × 1.5 Gy/day) with concurrent carboplatin and vindesine. Assessment of K‐ras codon 12 mutation status was performed in the paraffin embedded resection specimens by a two‐step polymerase chain reaction followed by restriction fragment length polymorphism analysis.RESULTSK‐ras mutation status could be assessed in 28 cases. A K‐ras codon 12 point mutation was found in 13 of 28 resection specimens (46%). The mutation was found independently of gender, age, tumor stage, and clinical response status and occurred more frequently in adenocarcinomas. Even after complete resection, the presence of a K‐ras mutation was a significant predictor for a poor progression free survival (P = 0.005).CONCLUSIONSThese data suggest that further evaluation of the K‐ras codon 12 mutation status in trials on neoadjuvant and adjuvant therapy is warranted. This may contribute to the identification of stratification variables for future treatment approaches. Cancer 2002;94:2055–62. © 2002 American Cancer Society.DOI 10.1002/cncr.10387
Cell types and response properties of neurons in the ventral division of the medial geniculate body of the rabbit
Authors: Cetas Justin S. , Price Robin O. , Velenovsky David S. , Crowe Jennifer J. , Sinex Donal G. , McMullen Nathaniel T. 
Published: August 2002

AbstractAlthough there is evidence for multiple classes of thalamic relay neurons in the auditory thalamus, correlative anatomical and physiological studies are lacking. We have used the juxtacellular labeling technique, in conjunction with Nissl, Golgi, and immunocytochemical methods, to study the morphology and response properties of cells in the ventral division of the medial geniculate body of the rabbit. Single units in the ventral division of the medial geniculate body (MGV) were characterized extracellularly with monaural and binaural tone and noise bursts (100‐ to 250‐msec duration). Characterized units were filled with biocytin and visualized with an antibody enhanced diaminobenzidine reaction. A total of 31 neurons were physiologically characterized and labeled with the juxtacellular technique. Labeled neurons were fully reconstructed from serial sections by using a computer microscope system. Three subregions of the rabbit MGV were identified, each characterized by differences in Nissl architecture, calcium‐binding protein expression, and by the dendritic orientation of tufted relay neurons. In general, the dendritic fields of relay neurons were closely aligned with the cellular laminae. Qualitative and quantitative analyses revealed two types of presumptive relay neurons within the MGV. Type I cells had thick dendrites with a greater total volume and morphologically diverse appendages compared with the Type II cells whose dendrites were thin with a moderate number of small spines. Both classes were acoustically responsive and exhibited a variety of response patterns, including onset, offset, and sustained responses. In terms of binaural characteristics, most (ca. 53%) labeled neurons were of the EE type, with the remaining cells classified as EO (27%) or EI (20%) response types. Two types of presumptive interneurons were also seen: bipolar neurons with large dendritic fields and a small neurogliaform variety. Cell types and dendritic orientation within the MGV are discussed in terms of the physiological organization of the rabbit auditory thalamus. J. Comp. Neurol. 445:78–96, 2002. © 2002 Wiley‐Liss, Inc.
Electrophysiological profile of avian hippocampal unit activity: A basis for regional subdivisions
Authors: Siegel Jennifer J. , Nitz Douglas , Bingman Verner P. 
Published: August 2002

AbstractElectrophysiological activity was recorded from single neurons (units) in the hippocampal formation (HF) of freely moving homing pigeons in order to provide a taxonomy of unit types found in the avian HF; a taxonomy that could be used to define regional subdivisions and be compared with unit types found in the mammalian hippocampus. Two distinct types of unit were observed in the avian HF. One type was uniformly characterized by relatively rapid firing rates and shorter spike widths, and was found throughout the HF. The other type was more variable in activity profile but, compared with the fast‐firing units, was characterized by slower firing rates and longer spike widths. However, despite the variable nature of the slow‐firing units, most slow‐firing units recorded within a given anatomical region displayed similar firing rates, spike widths, and interspike intervals. In general, ventral HF units displayed activity patterns similar to projection cells found in the mammalian Ammon's horn. Most dorsocaudal units displayed activity patterns similar to presumed granular cells in the mammalian dentate gyrus. By contrast, most dorsorostral units displayed activity patterns similar to a type of unit found in the mammalian subiculum. Although different in some details, the overall activity profile of units found in the avian HF, and their regional distribution, is strikingly similar to unit types found in the mammalian hippocampus, suggesting that unit activity profile is one hippocampal dimension conserved through evolution. J. Comp. Neurol. 445:256–268, 2002. © 2002 Wiley‐Liss, Inc.
Cortical and thalamic axon pathfinding defects in Tbr1, Gbx2, and Pax6 mutant mice: Evidence that cortical and thalamic axons interact and guide each other
Authors: Hevner Robert F. , Miyashita‐Lin Emily , Rubenstein John L.R. 
Published: August 2002

AbstractDuring development, cortical areas establish precise reciprocal projections with corresponding thalamic nuclei. Pioneer axons from the cortex and thalamus first meet in the intermediate zone of the subcortical telencephalon (subpallium). Their close interactions in the subpallium suggest that they may use each other for guidance. To test this hypothesis, the development of corticothalamic and thalamocortical connections was studied in mice with mutations of transcription factor genes expressed specifically in the cortex (Tbr1), the dorsal thalamus (Gbx2), or both (Pax6). In Tbr1 mutants, cortical pioneer axons entered the subpallium at the appropriate time, but most stopped growing without entering the diencephalon. Surprisingly, thalamic axons (which do not express Tbr1) deviated into the external capsule and amygdala regions, without entering the cortex. Conversely, in most Gbx2 mutants, thalamic axons were reduced in number and grew no farther than the subpallium. Cortical axons (which do not express Gbx2) grew into the subpallium but did not enter the diencephalon. In one Gbx2– /– case, sparse thalamocortical and corticothalamic projections both developed, but in no case did one projection reach its target and not the other. In Pax6 mutants, neither corticothalamic nor thalamocortical axons reached their targets. These results suggest that thalamocortical and corticothalamic projections may not form independently. After reaching the subpallium, each projection may require a molecularly intact reciprocal projection for further guidance. This type of mechanism ensures that thalamocortical and corticothalamic axons project reciprocally. However, the exact nature of the interaction between cortical and thalamic pioneer axons remains to be elucidated. J. Comp. Neurol. 447:8–17, 2002. © 2002 Wiley‐Liss, Inc.