Abstract：
:Dissemination of tumor to the leptomeninges and cerebrospinal fluid represents a common pattern of metastasis for many cancers; however, few chemotherapeutic agents are available for intrathecal (i.t.) use and treatment results are often poor. We studied the neurotoxicity and pharmacokinetics of i.t. 4-hydroperoxycyclophosphamide (4-HC) in the rabbit and the activity of i.t. 4-HC in a VX2 rabbit model of leptomeningeal carcinomatosis to evaluate the potential use of 4-HC in the treatment of leptomeningeal tumors. Toxicity studies examined 4-HC doses ranging from 0.5 to 6.0 mumol administered by intraventricular injection weekly for 4 to 8 weeks. Clinical or histological neurotoxicity was not observed in rabbits treated with < 1.0 mumol 4-HC for 4 weeks. Clinical toxicity, characterized by lethargy, weight loss, seizures, or death, was apparent at doses > 2.0 mumol. Vasculitis of superficial arteries was observed in rabbits treated with > 1.0 mumol 4-HC. In cerebrospinal fluid pharmacokinetic studies, the mean drug half-life after intraventricular or intralumbar administration was 24.3 and 18.2 min. Regional inequities in drug exposure were apparent as area under the clearance curve values for cerebrospinal fluid distant from the injection site were lower than those of proximate sites (P < 0.001). Weekly intraventricular treatment of VX2 leptomeningeal tumor-bearing rabbits with 0.5 or 1.0 mumol of 4-HC resulted in an increased life span of 22.5 and 35%, respectively. These results indicate that i.t. 4-HC, at doses lower than those producing neurotoxicity in the rabbit, is effective treatment for VX2 leptomeningeal carcinomatosis.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Phillips PC,Than TT,Cork LC,Hilton J,Carson BS,Colvin OM,Grochow LBsubject
Has Abstractpub_date
1992-11-15 00:00:00pages
6168-74issue
22eissn
0008-5472issn
1538-7445journal_volume
52pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract：:The presence of common genomic deletions in the 19q13 chromosomal region in neuroblastomas and gliomas strongly suggests the presence of a putative tumor suppressor gene for these neoplasms in this region that, despite much effort, has not yet been identified. In an attempt to address this issue, we compared the expre...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-04-4283
更新日期：2005-04-01 00:00:00
abstract：:Triple-negative breast cancer (TNBC) is a highly aggressive, heterogeneous disease with poor prognosis and no effective targeted therapies. EGFR is highly expressed in basal-like TNBC and is considered as a potential therapeutic target. However, EGFR targeting exerts only marginal clinical benefits, possibly due to ac...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-16-1797
更新日期：2017-01-01 00:00:00
abstract：:Tumor-initiating properties of complete carcinogens such as 7,12-dimethylbenz(a)anthracene (DMBA) are well known but not the mechanism of DMBA-mediated tumor promotion. Our hypothesis is that interleukin (IL)-1alpha, an early proinflammatory cytokine that initiates a cascade of other cytokines and growth factors, is u...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2002-01-15 00:00:00
abstract：:The anticancer agent saintopin induces DNA cleavage mediated by both topoisomerase (topo) I and topo II in vitro through stabilization of the reversible enzyme-DNA cleavable complex. We established saintopin-resistant cell lines (KB/STP-1 and KB/STP-2) from human epidermoid cancer KB cells by stepwise exposure to incr...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1996-05-15 00:00:00
abstract：:The gastrin gene is expressed widely in pancreatic adenocarcinomas and the study aimed to assess its role in both the resistance of cancer cells to apoptosis and the sensitivity of cells to chemotherapeutic agents. Two human pancreatic cell lines, PAN1 and BXPC3, expressed gastrin at both the RNA and protein levels an...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-04-0106
更新日期：2004-08-15 00:00:00
abstract：:The external pH of solid tumors is acidic as a consequence of increased metabolism of glucose and poor perfusion. Acid pH has been shown to stimulate tumor cell invasion and metastasis in vitro and in cells before tail vein injection in vivo. The present study investigates whether inhibition of this tumor acidity will...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-07-5575
更新日期：2009-03-15 00:00:00
abstract：:Despite studies that show the antitumor activity of Hsp90 inhibitors, such as geldanamycin (GA) and its derivative 17-allylamino-demethoxygeldanamycin (17-AAG), recent reports indicate that these inhibitors lack significant single-agent clinical activity. Resistance to Hsp90 inhibitors has been previously linked to ex...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-07-5175
更新日期：2008-09-15 00:00:00
abstract：:Angiogenesis, the sprouting of new blood vessels from existing vessels, occurs in many physiological and pathological processes, including embryonic development, wound healing, and tumor growth. It is required for tumor growth because new blood vessel formation is necessary for tumors to expand beyond a minimum volume...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1996-04-01 00:00:00
abstract：:We have screened 57 cases of primary, nonfunctional, pituitary adenomas for loss of heterozygosity of markers on chromosome 9p. Using a panel of 11 microsatellite markers, we found hemizygous deletion with at least one of the markers in 18 tumors (31.5%). The frequency of loss was similar in both noninvasive (8 of 26;...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1997-07-01 00:00:00
abstract：:The role of dietary fat in cancer etiology is briefly discussed in terms of several major types of epidemiological evidence: geographic correlations, migrant studies, low-risk populations, and dietary modification trials. It appears that there is no conclusive evidence that lowering dietary fat intake will result in l...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1981-09-01 00:00:00
abstract：:The human urinary bladder carcinogen, 4-aminobiphenyl (ABP), is known to undergo hepatic metabolism to an N-hydroxy arylamine and its corresponding N-glucuronide. It has been proposed that these metabolites are both transported through the blood via renal filtration to the urinary bladder lumen where acidic pH can fac...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1991-08-15 00:00:00
abstract：:Bik was initially identified as a BH3-domain-only protein that interacts with E1B 19K. Although systemically administered wild-type Bik significantly inhibited tumor growth and metastasis in an orthotopic nude mouse model, the proapoptotic potency of Bik can be modulated by posttranslational phosphorylation. Here, we ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2003-11-15 00:00:00
abstract：:Monoclonal antibodies (Mabs) against human ovarian mucinous and serous carcinoma were obtained by the Mab technique. Their reactivities against human tumors were tested by indirect immunofluorescence. One of the Mabs, named 4C7, derived from the spleen cells of mice immunized with mucinous carcinoma line OVA-1, reacte...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1985-05-01 00:00:00
abstract：:Immunologic targeting of the oncoprotein HER2/neu with monoclonal antibodies is an important component of current therapeutic strategies for patients with locally and systemically advanced breast cancer. Engineered antibodies targeting HER2 may have agonist or antagonist effects on HER2, but little is known about whet...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2005-01-15 00:00:00
abstract：:We postulated that increased expression of the cell cycle regulators cyclin D1 and cyclin-dependent kinase (Cdk) 4 may be involved in the development of intestinal adenomas associated with familial adenomatous polyposis (FAP). In the present study of multiple intestinal neoplasia (Min) mice and human FAP patients, the...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1997-01-01 00:00:00
abstract：:Suppression of gluconeogenesis elevates glycolysis and is commonly observed in tumors derived from gluconeogenic tissues including liver and kidney, yet the definitive regulatory mechanism remains elusive. Here, we screened an array of transcription regulators and identified the enhancer of zeste homolog 2 (EZH2) as a...
journal_title：Cancer research
pub_type： 评论,杂志文章
doi：10.1158/0008-5472.CAN-19-2060
更新日期：2020-02-15 00:00:00
abstract：:The effects of retinyl acetate and all-trans-retinoic acid on the growth rate, saturation density, and cytoplasmic underlapping of normal and carcinogen-initiated C3H/1OT1/2 cells were examined. Retinyl acetate (a) decreased the saturation density by as much as 45%, (b) had no effect on the growth rate, (c) reduced cy...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1983-02-01 00:00:00
abstract：:A series of 152 human bladder tumors, 14 bladder tumor cell lines, and 1 immortal urothelial cell line were examined by single-strand conformation polymorphism (SSCP) and designed restriction fragment.length polymorphism analyses for mutations in exons 1 and 2 of the H-ras gene. Nine tumors (6%) contained mutations. T...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1993-01-01 00:00:00
abstract：:Groups of 120 male and 120 female rats were exposed by inhalation to 0, 2, 6, or 15 ppm formaldehyde vapor 6 hr/day, 5 days/week, for 18 months of a 24-month study. The present communication describes interim findings based on data available after 18 months of exposure. Squamous cell carcinomas occurred in the nasal c...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1980-09-01 00:00:00
abstract：:SIRT6 is a SIR2 family member that regulates multiple molecular pathways involved in metabolism, genomic stability, and aging. It has been proposed previously that SIRT6 is a tumor suppressor in cancer. Here, we challenge this concept by presenting evidence that skin-specific deletion of SIRT6 in the mouse inhibits sk...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-14-1308
更新日期：2014-10-15 00:00:00
abstract：:Antigenic stimulation of athymic mice on the BALB/c background by infection with the pinworms Aspiculuris tetraptera and Syphacia obvelata or by xenografts of human tumors induced a proliferation of T- and B-lymphocytes in spleen and lymph nodes and occasional germinal center formation. The proliferating T-lymphocytes...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1981-06-01 00:00:00
abstract：:HER-2/neu (neu-N) transgenic mice, which express the nontransforming rat proto-oncogene, develop spontaneous focal mammary adenocarcinomas beginning at 5-6 months of age. The development and histology of these tumors bears a striking resemblance to what is seen in patients with breast cancer. We have characterized the...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2000-07-01 00:00:00
abstract：:Human cancer cell lines are commonly used in basic cancer research to understand the behavior of primary tumors. Aberrations in the DNA methylation patterns are nowadays recognized as a hallmark of the cancer cell. However, no comprehensive study defines the DNA methylation environment present in the established cance...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2003-03-01 00:00:00
abstract：:The uptake of m-[125I]iodobenzylguanidine (mIBG), a compound structurally analogous to the antihypertensive drug guanethidine, was examined in various human cell lines. Of three neuroblastoma lines, SK-N-LO, IMR-32, and SK-N-SH, only the last showed specific uptake of the compound. In contrast, only a nonspecific upta...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1985-12-01 00:00:00
abstract：:Methotrexate (MTX) is one of the most commonly used agents in the treatment of solid malignancies; however, the toxicities of MTX to bone marrow and gastrointestinal tract complicate this therapy. We, therefore, propose a gene-dependent enzyme prodrug therapy to limit these toxicities by localizing the production of M...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2000-02-01 00:00:00
abstract：:Increasing evidence points to an active stromal involvement in cancer initiation and progression. Cytokines derived from tumor cells are believed to modulate stromal cells to produce growth and angiogenic factors, which in turn provide the tumor with the necessary microenvironment for expansion and invasion. Transform...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-07-0444
更新日期：2007-06-15 00:00:00
abstract：:Transduction of mitogenic signals in cells can be mediated by molecules derived from the synthesis and breakdown of the major membrane phospholipid, phosphotidylcholine. Studies were performed on human mammary epithelial cells in culture to understand the impact of malignant transformation and progression on membrane ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1999-01-01 00:00:00
abstract：:Cancer in a host induces responses that increase the ability of the microenvironment to sustain the growing mass, for example, angiogenesis, but cancer cells can have varying sensitivities to these sustainability signals. Here, we show that these sensitivities are significant determinants of ultimate tumor fate, espec...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-12-4590
更新日期：2013-06-15 00:00:00
abstract：:Flow cytometry was used to determine the daunomycin content of rat bone marrow cells after incubation in vitro. The spontaneous fluorescence of daunomycin was measured upon excitation with laser light at 488 nm. Forward and perpendicular light scatters of the cells were simultaneously measured to allow identification ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1983-11-01 00:00:00
abstract：:Two mutations of the ATM gene were recently suggested to confer breast cancer risks similar to mutations of BRCA1 or BRCA2. Here, we set out to confirm these findings in 961 families with non-BRCA1/BRCA2 breast cancer from diverse geographical regions. We did not detect the ATM 7271T-->G mutation in any family. The AT...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.can-03-2678
更新日期：2004-02-01 00:00:00
