Neoplasia (New York, N.Y.)最新文献

{"title":"Inhibition of tumor growth and angiogenesis by soluble EphB4.","authors":"Georg Martiny-Baron,&nbsp;Thomas Korff,&nbsp;Florence Schaffner,&nbsp;Norbert Esser,&nbsp;Stefan Eggstein,&nbsp;Dieter Marmé,&nbsp;Hellmut G Augustin","doi":"10.1593/neo.3457","DOIUrl":"https://doi.org/10.1593/neo.3457","url":null,"abstract":"<p><p>EphB receptors and their ephrinB ligands play a key role in the formation of a regular vascular system. Recent studies have also shown the involvement of Eph/ephrin interactions in malignant tumor progression and angiogenesis. We have generated soluble monomeric EphB4 (sEphB4)-expressing A375 melanoma cells to study the effect of dominant negatively acting sEphB4 on tumor growth and angiogenesis. Soluble EphB4-expressing A375 tumors grown subcutaneously in nude mice show dramatically reduced tumor growth compared to control tumors. The proliferative capacity of sEphB4-expressing cells in monolayer culture is not altered. Yet, sEphB4-expressing A375 cells cannot establish proper cell-cell contacts in three-dimensional spheroids. However, sEphB4 transfectants have reduced proliferation and apoptosis rates when grown in three-dimensional culture in vitro or in subcutaneous tumors in vivo. Analysis of the vascular phenotype of the tumors revealed a reduction of intratumoral microvessel density in sEphB4-expressing tumors. Corresponding to these mouse experiments, a matched pair analysis of EphB4 and ephrinB2 expression in human colon carcinomas revealed significantly upregulated levels of EphB4 expression compared to adjacent normal tissue. Taken together, the data identify dual effects of sEphB4 on the tumor and the vascular compartment that collectively inhibit tumor growth.</p>","PeriodicalId":18888,"journal":{"name":"Neoplasia (New York, N.Y.)","volume":"6 3","pages":"248-57"},"PeriodicalIF":0.0,"publicationDate":"2004-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1502094/pdf/neo0603_0248.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24528186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Photodynamic therapy of established prostatic adenocarcinoma with TOOKAD: a biphasic apparent diffusion coefficient change as potential early MRI response marker.","authors":"Vicki Plaks,&nbsp;Natalia Koudinova,&nbsp;Uri Nevo,&nbsp;Jehonathan H Pinthus,&nbsp;Hannah Kanety,&nbsp;Zelig Eshhar,&nbsp;Jacob Ramon,&nbsp;Avigdor Scherz,&nbsp;Michal Neeman,&nbsp;Yoram Salomon","doi":"10.1593/neo.3352","DOIUrl":"https://doi.org/10.1593/neo.3352","url":null,"abstract":"<p><p>The goal of this study was to examine the use of diffusion-weighted magnetic resonance imaging (DW-MRI) for the assessment of early progression of photodamage induced by Pd-bacteriopheophorbide (TOOKAD)-based photodynamic therapy (PDT). TOOKAD is a novel second-generation photosensitizer for PDT of solid tumors developed in our laboratory and presently under clinical trials for prostate cancer (PC) therapy. Using the subcutaneous human prostate adenocarcinoma WISH-PC14 xenografts in nude mice as a model, a unique biphasic change in the apparent diffusion coefficient (ADC) was observed within the first 24 hours post-PDT, with initial decrease followed by an increase in ADC. Using DW-MRI, this phenomenon enables the detection of successful tumor response to PDT within 7 hours posttreatment. This process was validated by direct, histological, and immunohistochemical examinations and also by evaluation of serum prostate-specific antigen (PSA) levels that decreased significantly already 7 hours posttreatment. In vitro studies of multicellular cell spheroids confirmed a PDT-induced decrease in ADC, suggesting that lipid peroxidation (LPO) significantly contributes to ADC decline observed after PDT. These results demonstrate that TOOKAD-based PDT successfully eradicates prostate adenocarcinoma xenografts and suggests DW-MRI to be useful for the detection of early tumor response and treatment outcome in the clinical setting.</p>","PeriodicalId":18888,"journal":{"name":"Neoplasia (New York, N.Y.)","volume":"6 3","pages":"224-33"},"PeriodicalIF":0.0,"publicationDate":"2004-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1502095/pdf/neo0603_0224.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24527645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tax-independent constitutive IkappaB kinase activation in adult T-cell leukemia cells.","authors":"Noriko Hironaka,&nbsp;Kanako Mochida,&nbsp;Naoki Mori,&nbsp;Michiyuki Maeda,&nbsp;Naoki Yamamoto,&nbsp;Shoji Yamaoka","doi":"10.1593/neo.3388","DOIUrl":"https://doi.org/10.1593/neo.3388","url":null,"abstract":"<p><p>Adult T-cell leukemia (ATL) is a fatal T-cell malignancy that arises long after infection with human T-cell leukemia virus type I (HTLV-I). We reported previously that nuclear factor-kappaB (NF-kappaB) was constitutively activated in ATL cells, although expression of the viral proteins was barely detectable, including Tax, which was known to persistently activate NF-kappaB. Here we demonstrate that ATL cells that do not express detectable Tax protein exhibit constitutive IkappaB kinase (IKK) activity. Transfection studies revealed that a dominant-negative form of IKK1, and not of IKK2 or NF-kappaB essential modulator (NEMO), suppressed constitutive NF-kappaB activity in ATL cells. This IKK activity was accompanied by elevated expression of p52, suggesting that the recently described noncanonical pathway of NF-kappaB activation operates in ATL cells. We finally show that specific inhibition of NF-kappaB by a super-repressor form of IkappaBalpha (SR-IkappaBalpha) in HTLV-I-infected T cells results in cell death regardless of Tax expression, providing definitive evidence of an essential role for NF-kappaB in the survival of ATL cells. In conclusion, the IKK complex is constitutively activated in ATL cells through a cellular mechanism distinct from that of Tax-mediated IKK activation. Further elucidation of this cellular mechanism should contribute to establishing a rationale for treatment of ATL.</p>","PeriodicalId":18888,"journal":{"name":"Neoplasia (New York, N.Y.)","volume":"6 3","pages":"266-78"},"PeriodicalIF":0.0,"publicationDate":"2004-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1502096/pdf/neo0603_0266.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24527519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glioma tropic neural stem cells consist of astrocytic precursors and their migratory capacity is mediated by CXCR4.","authors":"Moneeb Ehtesham,&nbsp;Xiangpeng Yuan,&nbsp;Peter Kabos,&nbsp;Nancy H C Chung,&nbsp;Gentao Liu,&nbsp;Yasuharu Akasaki,&nbsp;Keith L Black,&nbsp;John S Yu","doi":"10.1593/neo.3427","DOIUrl":"https://doi.org/10.1593/neo.3427","url":null,"abstract":"<p><p>Malignant gliomas spawn disseminated microsatellites, which are largely refractory to currently employed therapies, resulting in eventual tumor recurrence and death. The use of tumor-tropic neural stem cells (NSCs) as delivery vehicles for therapeutic gene products represents an attractive strategy specifically focused at treating these residual neoplastic foci. We wished to elucidate the biological cues governing NSC tropism for glioma. In this context, we describe that tumor-tropic NSCs comprise largely of astrocytic progenitors expressing chemokine receptor 4 (CXCR4). Blocking of CXCR4 significantly inhibits NSC migration toward the tumor. These findings define specific characteristics associated with the cell populations within transplanted NSCs that demonstrate glioma-tracking behavior.</p>","PeriodicalId":18888,"journal":{"name":"Neoplasia (New York, N.Y.)","volume":"6 3","pages":"287-93"},"PeriodicalIF":0.0,"publicationDate":"2004-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1502097/pdf/neo0603_0287.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24528193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic contrast-enhanced magnetic resonance imaging rapidly indicates vessel regression in human squamous cell carcinomas grown in nude mice caused by VEGF receptor 2 blockade with DC101.","authors":"Fabian Kiessling,&nbsp;Nabeel Farhan,&nbsp;Matthias P Lichy,&nbsp;Silvia Vosseler,&nbsp;Melanie Heilmann,&nbsp;Martin Krix,&nbsp;Peter Bohlen,&nbsp;Dan W Miller,&nbsp;Margareta M Mueller,&nbsp;Wolfhard Semmler,&nbsp;Norbert E Fusenig,&nbsp;Stefan Delorme","doi":"10.1593/neo.3394","DOIUrl":"https://doi.org/10.1593/neo.3394","url":null,"abstract":"The purpose of our study was the investigation of early changes in tumor vascularization during antiangiogenic therapy with the vascular endothelial growth factor (VEGF) receptor 2 antibody (DC101) using dynamic contrast-enhanced magnetic resonance imaging (DCE MRI). Subcutaneous heterotransplants of human skin squamous cell carcinomas in nude mice were treated with DC101. Animals were examined before and repeatedly during 2 weeks of antiangiogenic treatment using Gd-DTPA-enhanced dynamic T1-weighted MRI. With a two-compartment model, dynamic data were parameterized in \"amplitude\" (increase of signal intensity relative to precontrast value) and k(ep) (exchange rate constant). Data obtained by MRI were validated by parallel examinations of histological sections immunostained for blood vessels (CD31). Already 2 days after the first DC101 application, a decrease of tumor vascularization was observed, which preceded a reduction of tumor volume. The difference between treated tumors and controls became prominent after 4 days, when amplitudes of treated tumors were decreased by 61% (P =.02). In line with change of microvessel density, the decrease in amplitudes was most pronounced in tumor centers. On day 7, the mean tumor volumes of treated (153 +/- 843 mm(3)) and control animals (596 +/- 384 mm(3)) were significantly different (P =.03). After 14 days, treated tumors showed further growth reduction (83 +/- 93 mm(3)), whereas untreated tumors (1208 +/- 822 mm(3)) continued to increase (P =.02). Our data underline the efficacy of DC101 as antiangiogenic treatment in human squamous cell carcinoma xenografts in nude mice and indicate DCE MRI as a valuable tool for early detection of treatment effects before changes in tumor volume become apparent.","PeriodicalId":18888,"journal":{"name":"Neoplasia (New York, N.Y.)","volume":"6 3","pages":"213-23"},"PeriodicalIF":0.0,"publicationDate":"2004-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1502099/pdf/neo0603_0213.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24527644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-resolution analysis of gene copy number alterations in human prostate cancer using CGH on cDNA microarrays: impact of copy number on gene expression.","authors":"Maija Wolf,&nbsp;Spyro Mousses,&nbsp;Sampsa Hautaniemi,&nbsp;Ritva Karhu,&nbsp;Pia Huusko,&nbsp;Minna Allinen,&nbsp;Abdel Elkahloun,&nbsp;Outi Monni,&nbsp;Yidong Chen,&nbsp;Anne Kallioniemi,&nbsp;Olli-P Kallioniemi","doi":"10.1593/neo.3439","DOIUrl":"https://doi.org/10.1593/neo.3439","url":null,"abstract":"<p><p>Identification of target genes for genetic rearrangements in prostate cancer and the impact of copy number changes on gene expression are currently not well understood. Here, we applied high-resolution comparative genomic hybridization (CGH) on cDNA microarrays for analysis of prostate cancer cell lines. CGH microarrays identified most of the alterations detected by classic chromosomal CGH, as well as a number of previously unreported alterations. Specific recurrent regions of gain (28) and loss (18) were found, and their boundaries defined with sub-megabasepair accuracy. The most common changes included copy number decreases at 13q, and gains at 1q and 5p. Refined mapping identified several sites, such as at 13q (33-44, 49-51, and 74-76 Mbp from the p-telomere), which matched with minimal regions of loss seen in extensive loss of heterozygosity mapping studies of large numbers of tumors. Previously unreported recurrent changes were found at 2p, 2q, 3p, and 17q (losses), and at 3q, 5p, and 6p (gains). Integration of genomic and transcriptomic data revealed the role of individual candidate target genes for genomic alterations as well as a highly significant (P <.0001) overall association between copy number levels and the percentage of differentially expressed genes. Across the genome, the overall impact of copy number on gene expression levels was, to a large extent, attributable to low-level gains and losses of copy number, corresponding to common deletions and gains of often large chromosomal regions.</p>","PeriodicalId":18888,"journal":{"name":"Neoplasia (New York, N.Y.)","volume":"6 3","pages":"240-7"},"PeriodicalIF":0.0,"publicationDate":"2004-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1502104/pdf/neo0603_0240.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24528185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zoning of mucosal phenotype, dysplasia, and telomerase activity measured by telomerase repeat assay protocol in Barrett's esophagus.","authors":"James J Going,&nbsp;Aileen J Fletcher-Monaghan,&nbsp;Lisa Neilson,&nbsp;Bea A Wisman,&nbsp;Ate van der Zee,&nbsp;Robert C Stuart,&nbsp;W Nicol Keith","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Glandular dysplasia in Barrett's esophagus may regress spontaneously but can also progress to cancer. The human telomerase RNA template and the human telomerase reverse transcriptase enzyme which do not, of themselves, correlate strongly with telomerase activity, are too often overexpressed in Barrett's dysplasia to predict individual cancer risk. This study relates telomerase activity, mucosal phenotype, and dysplasia in Barrett's esophagus. Biopsies (n = 256) from squamous esophagus, columnar-lined esophagus every 2 cm, esophago-gastric junction, gastric body, and antrum from 32 patients with long-segment Barrett's esophagus were evaluated by telomerase repeat assay protocol (TRAP). Three biopsies for histology (n = 794) were simultaneously taken at each anatomical level. These and all prior and subsequent biopsies (n = 1917) were reviewed for mucosal phenotypes and dysplasia severity. Intestinal-type Barrett's mucosa was present at all levels in Barrett's esophagus. At least one Barrett's biopsy was TRAP(+) in 22 of 32 patients. TRAP positivity of intestinal-type Barrett's mucosa increased distally, possibly as a consequence of mucosal exposure to acid or bile reflux. Native gastric mucosa was rarely TRAP(+) (1/31 corpus, 2/32 antrum), whereas native squamous mucosa usually was TRAP(+) (31/32). Dysplasia almost always involved intestinal-type Barrett's mucosa (85/87; P <.00001), without evidence of proximal-distal zoning. TRAP could be positive without dysplasia and negative in extensive, even high-grade, dysplasia. TRAP activity merits evaluation as a candidate biomarker for increased risk of persistent dysplasia and cancer progression in Barrett's esophagus.</p>","PeriodicalId":18888,"journal":{"name":"Neoplasia (New York, N.Y.)","volume":"6 1","pages":"85-92"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1508632/pdf/neo0601_0085.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24455142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The hypercoagulable state of malignancy: pathogenesis and current debate.","authors":"Graham J Caine, Paul S Stonelake, Gregory Y H Lip, Sean T Kehoe","doi":"10.1038/sj.neo.7900263","DOIUrl":"10.1038/sj.neo.7900263","url":null,"abstract":"<p><p>A hypercoagulable or prothrombotic state of malignancy occurs due to the ability of tumor cells to activate the coagulation system. It has been estimated that hypercoagulation accounts for a significant percentage of mortality and morbidity in cancer patients. Prothrombotic factors in cancer include the ability of tumor cells to produce and secrete procoagulant/fibrinolytic substances and inflammatory cytokines, and the physical interaction between tumor cell and blood (monocytes, platelets, neutrophils) or vascular cells. Other mechanisms of thrombus promotion in malignancy include nonspecific factors such as the generation of acute phase reactants and necrosis (i.e., inflammation), abnormal protein metabolism (i.e., paraproteinemia), and hemodynamic compromise (i.e., stasis). In addition, anticancer therapy (i.e., surgery/chemotherapy/hormone therapy) may significantly increase the risk of thromboembolic events by similar mechanisms, e.g., procoagulant release, endothelial damage, or stimulation of tissue factor production by host cells. However, not all of the mechanisms for the production of a hypercoagulable state of cancer are entirely understood. In this review, we attempt to describe what is currently accepted about the pathophysiology of the hypercoagulable state of cancer. We also discuss whether or not to screen patients with idiopathic deep venous thrombosis for an underlying malignancy, and whether this would be beneficial to patients. It is hoped that a better understanding of these mechanisms will ultimately lead to the development of more targeted treatment to prevent thromboembolic complications in cancer patients. It is also hoped that antithrombotic strategies may also have a positive effect on the process of tumor growth and dissemination.</p>","PeriodicalId":18888,"journal":{"name":"Neoplasia (New York, N.Y.)","volume":"4 6","pages":"465-73"},"PeriodicalIF":0.0,"publicationDate":"2002-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1550339/pdf/neo0406_0465.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22088921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Implications of mapping the human telomerase gene (hTERT) as the most distal gene on chromosome 5p.","authors":"J W Shay,&nbsp;W E Wright","doi":"10.1038/sj.neo.7900093","DOIUrl":"https://doi.org/10.1038/sj.neo.7900093","url":null,"abstract":"","PeriodicalId":18888,"journal":{"name":"Neoplasia (New York, N.Y.)","volume":"2 3","pages":"195-6"},"PeriodicalIF":0.0,"publicationDate":"2000-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1507567/pdf/neo0203_0195.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21773393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lymphoma Research Foundation of America: shedding light and saving lives.","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":18888,"journal":{"name":"Neoplasia (New York, N.Y.)","volume":"2 3","pages":"287-8"},"PeriodicalIF":0.0,"publicationDate":"2000-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1507565/pdf/neo0203_0287.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21774544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}