Abstract:
:We previously determined that human papillomavirus (HPV) virus-like particles (VLPs) and pseudovirions (PsV) did not, respectively, bind to or infect intact epithelium of the cervicovaginal tract. However, they strongly bound heparan sulfate proteoglycans (HSPG) on the basement membrane of disrupted epithelium and infected the keratinocytes that subsequently entered the disrupted site. We here report that HPV capsids (VLP and PsV) have the same restricted tropism for a wide variety of disrupted epithelial and mesothelial tissues, whereas intact tissues remain resistant to binding. However, the HPV capsids directly bind and infect most tumor-derived cell lines in vitro and have analogous tumor-specific properties in vivo, after local or intravenous injection, using orthotopic models for human ovarian and lung cancer, respectively. The pseudovirions also specifically infected implanted primary human ovarian tumors. Heparin and ι-carrageenan blocked binding and infection of all tumor lines tested, implying that tumor cell binding is HSPG-dependent. A survey using a panel of modified heparins indicates that N-sulfation and, to a lesser degree, O-6 sulfation of the surface HSPG on the tumors are important for HPV binding. Therefore, it appears that tumor cells consistently evolve HSPG modification patterns that mimic the pattern normally found on the basement membrane but not on the apical surfaces of normal epithelial or mesothelial cells. Consequently, appropriately modified HPV VLPs and/or PsV could be useful reagents to detect and potentially treat a remarkably broad spectrum of cancers.
journal_name
Int J Cancerjournal_title
International journal of cancerauthors
Kines RC,Cerio RJ,Roberts JN,Thompson CD,de Los Pinos E,Lowy DR,Schiller JTdoi
10.1002/ijc.29823subject
Has Abstractpub_date
2016-02-15 00:00:00pages
901-11issue
4eissn
0020-7136issn
1097-0215journal_volume
138pub_type
杂志文章abstract::Nasopharyngeal carcinoma (NPC) is an aggressive tumour of multifactorial aetiology that, although rare in most parts of the world, poses a significant mortality problem in its high incidence area of Southern China. Improved therapies are an urgent requirement and, towards this end, immunotherapeutic methods are being ...
journal_title:International journal of cancer
pub_type: 杂志文章
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abstract::Although surgical resection is considered the adequate treatment in early stages of nonsmall cell lung cancer, long-term survival is not satisfactory and recurrence rate is high. We previously showed that postoperative chemotherapy at stage IB reduces recurrences and prolongs overall survival. We extended size and obs...
journal_title:International journal of cancer
pub_type: 杂志文章,随机对照试验
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abstract::Trifluorothymidine (TFT) is part of the oral drug formulation TAS-102. Both 5-fluorouracil (5-FU) and TFT can inhibit thymidylate synthase and be incorporated into DNA. TFT shows only moderate cross-resistance to 5-FU. Therefore, we examined whether mechanistic differences in cell death could underlie their different ...
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journal_title:International journal of cancer
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abstract::Gene transfer is an attractive approach to fight cancer by targeting cancer cells or their vasculature. Our study reports the inhibition of tumor growth and angiogenesis by a nonviral method using dendrimers associated with 36-mer anionic oligomers (ON36) for delivering angiostatin (Kringle 1-3) and tissue inhibitor o...
journal_title:International journal of cancer
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abstract::Ornithine decarboxylase may be a useful biomarker for risk of neoplasia in colorectal tissues. Investigators have reported enzyme activities varying by as much as 10- to 20-fold using variations of the usual 14CO2 release assay. We have examined the effect of different methodologic factors on calculated ornithine deca...
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journal_title:International journal of cancer
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abstract::Fine-needle aspiration cytology (FNAC) is currently used in evaluating the nature of breast nodules. In the present study we have examined whether monoclonal antibodies (MAbs) to breast-tumor-associated antigens (BTAA) can be employed in FNAC for the diagnosis of breast cancer. For this purpose we have used 2 murine M...
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journal_title:International journal of cancer
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journal_title:International journal of cancer
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journal_title:International journal of cancer
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journal_title:International journal of cancer
pub_type: 杂志文章
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更新日期:2000-11-01 00:00:00
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journal_title:International journal of cancer
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更新日期:1988-10-15 00:00:00
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journal_title:International journal of cancer
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abstract::Human malignant mesothelioma (HMM) is resistant to many anticancer drugs, including doxorubicin. Mevastatin and simvastatin, 2 inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase, potentiated the intracellular accumulation and the cytotoxicity of doxorubicin in HMM cells constitutively expressing P-...
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journal_title:International journal of cancer
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abstract::Gefitinib has shown meaningful antitumor activity with tolerable toxicity in chemotherapy-refractory NSCLC in previous studies. Moreover, EGFR expression failed to show a correlation with response. In an attempt to identify predictive markers of response, we have investigated the tumoral expression of key signaling mo...
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abstract::The clonotypic T-cell receptor (TCR) is a potential target antigen for specific immunotherapy of cutaneous T-cell lymphoma (CTCL). We identified T-cell epitopes from the rearranged TCR beta chain of the malignant T-cell population by the "reverse immunology" approach. Peptide-specific T-cell lines were generated again...
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