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 reduce the incidence of in vivo metastases. Here, we show that oral NaHCO(3) selectively increased the pH of tumors and reduced the formation of spontaneous metastases in mouse models of metastatic breast cancer. This treatment regimen was shown to significantly increase the extracellular pH, but not the intracellular pH, of tumors by (31)P magnetic resonance spectroscopy and the export of acid from growing tumors by fluorescence microscopy of tumors grown in window chambers. NaHCO(3) therapy also reduced the rate of lymph node involvement, yet did not affect the levels of circulating tumor cells, suggesting that reduced organ metastases were not due to increased intravasation. In contrast, NaHCO(3) therapy significantly reduced the formation of hepatic metastases following intrasplenic injection, suggesting that it did inhibit extravasation and colonization. In tail vein injections of alternative cancer models, bicarbonate had mixed results, inhibiting the formation of metastases from PC3M prostate cancer cells, but not those of B16 melanoma. Although the mechanism of this therapy is not known with certainty, low pH was shown to increase the release of active cathepsin B, an important matrix remodeling protease.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Robey IF,Baggett BK,Kirkpatrick ND,Roe DJ,Dosescu J,Sloane BF,Hashim AI,Morse DL,Raghunand N,Gatenby RA,Gillies RJdoi
10.1158/0008-5472.CAN-07-5575subject
Has Abstractpub_date
2009-03-15 00:00:00pages
2260-8issue
6eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-07-5575journal_volume
69pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract：:We have recently reported that apoptosis of T cells induced by squamous cell carcinoma of the head and neck (SCCHN) is partly Fas dependent. This tumor-induced T-cell death is mediated by the activities of caspase-8 and caspase-3 and is partially inhibited by antibodies to either Fas or Fas ligand. We report here that...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2000-12-15 00:00:00
abstract：:An unusual isozyme of lactate dehydrogenase, lactate dehydrogenase associated with Kirsten murine sarcoma virus (LDHk) was found in the sera of many patients with malignant tumors, while the sera of healthy persons had little or no such activity. This isozyme was detectable only when assayed in a nitrogen atmosphere, ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1984-05-01 00:00:00
abstract：:Proliferating mammalian stem and cancer cells express telomerase [telomerase reverse transcriptase (TERT)] in an effort to extend chromosomal G-overhangs and maintain telomere ends. Telomerase-expressing cells also have higher levels of the single-stranded DNA-binding protein SSB1, which has a critical role in DNA dou...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-14-2289
更新日期：2015-03-01 00:00:00
abstract：:Infection of tumor cells by herpes simplex virus 1 (HSV-1) results in cell destruction and production of progeny virion in a process referred to as viral oncolysis. In this study, an HSV-1 mutant (HSV1yCD) was engineered such that the viral ribonucleotide reductase gene is disrupted by sequences encoding yeast cytosin...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2001-07-15 00:00:00
abstract：:Emerging evidence suggests that cancer preventative agents might be combined with chemotherapy or radiotherapy for the more effective treatment of cancer. Recent studies suggest that genistein and other dietary compounds that prevent cancer may enhance the efficacy of cancer therapeutics by modifying the activity of k...
journal_title：Cancer research
pub_type： 杂志文章,评审
doi：10.1158/0008-5472.CAN-05-4526
更新日期：2006-04-01 00:00:00
abstract：:The anticarcinogenic activities of retinoic acid (RA) are believed to be mediated by the nuclear RA receptor (RAR) and by the RA-binding protein cellular RA-binding protein-II (CRABP-II). In MCF-7 mammary carcinoma cells, growth inhibition by RA entails an early cell cycle arrest followed by induction of apoptosis. He...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-06-0989
更新日期：2007-01-15 00:00:00
abstract：:The ubiquitin proteasome system is responsible for the proteolysis of important cell cycle and apoptosis-regulatory proteins. In this paper we report that the dipeptidyl proteasome inhibitor, phthalimide-(CH2)8CH-(cyclopentyl) CO-Arg(NO2)-Leu-H (CEP1612), induces apoptosis and inhibits tumor growth of the human lung c...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2001-02-15 00:00:00
abstract：:The cytotoxicity of a diphtheria toxin-human epidermal growth factor fusion protein (DAB(389)EGF) was tested against 14 human glioma cell lines. After cells were cultured for 48 h with various concentrations of DAB(389)EGF, the percentage reduction in thymidine incorporation was determined. For 13 of 14 cell lines, po...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2003-04-15 00:00:00
abstract：:The cell cycle stimulation of individual species of the uracil DNA glycosylase was examined in WI-38 normal diploid fibroblasts. The nuclear uracil DNA glycosylase was induced as WI-38 cells traversed the cell cycle. In contrast, the specific activity of the mitochondrial glycosylase remained constant during cell prol...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1981-08-01 00:00:00
abstract：:The complement system is important in immunosurveillance against tumors. However, malignant cells are usually resistant to complement-mediated lysis. In this study, we examine the expression of factor H, an inhibitor of complement activation, and factor H-like protein 1 (FHL-1), its alternatively spliced form, in lung...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-03-2328
更新日期：2004-09-01 00:00:00
abstract：:The prodrug of 9-beta-D-arabinosylguanine (ara-G), nelarabine, demonstrated efficacy against T-cell acute lymphoblastic leukemia, and its effectiveness correlated with the accumulation of the triphosphate form (ara-GTP). Although in vitro investigations using purified deoxycytidine kinase (dCK) or deoxyguanosine kinas...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2002-06-01 00:00:00
abstract：:Autotaxin (ATX) is an exoenzyme that potently induces tumor cell motility, and enhances experimental metastasis and angiogenesis. ATX was shown recently to be identical to serum lysophospholipase D activity, producing lysophosphatidic acid (LPA) from lyso-glycerophospholipids. LPA, itself a strong chemoattractant for ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2003-09-01 00:00:00
abstract：:A novel, substituted 4-quinolinecarboxylic acid (NSC 339768) demonstrated antitumor activity against L1210 leukemia and B16 melanoma in the National Cancer Institute's Developmental Therapeutics Program. An extensive analogue synthesis program was initiated; over 200 derivatives were synthesized and tested for antican...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1985-11-01 00:00:00
abstract：:An interstitial deletion of the short arm of a chromosome 11 was found in Wilms' tumor cells of a patient without aniridia. The chromosomes in her peripheral blood lymphocytes were normal. The karyotype of the tumor cells is similar to that reported for the somatic cells of patients with aniridia-Wilms' tumor associat...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1981-11-01 00:00:00
abstract：:Clonal proliferation of human T-lymphotropic virus type I (HTLV-I)-infected cells has been detected by Southern blot analysis and inverse PCR in patients with adult T-cell leukemia, patients with HTLV-I-associated diseases, and even in asymptomatic carriers. Combining inverse PCR with long PCR, we amplified the genomi...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1997-11-01 00:00:00
abstract：:The lipid hydrolase enzyme acid sphingomyelinase (ASM) is required for the conversion of the lipid cell membrane component sphingomyelin into ceramide. In cancer cells, ASM-mediated ceramide production is important for apoptosis, cell proliferation, and immune modulation, highlighting ASM as a potential multimodal the...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-16-3313
更新日期：2017-11-01 00:00:00
abstract：:One of the body's natural defense mechanisms against tumor cells is lysis of the invading cell by cytotoxic T-cells and natural killer (NK) cells. Five human hepatocellular carcinoma cell lines were found to have different sensitivities to killing by peripheral blood monocytes in a 51Cr release assay. This killing was...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1989-09-01 00:00:00
abstract：:Murine fibrosarcoma UV-2237MM cells were implanted into different organs of syngeneic C3H/HeN mice. The resultant tumors were treated by i.v. administration of Adriamycin (ADR). Despite the high sensitivity of the fibrosarcoma cells to ADR in vitro, the established tumors growing in vivo exhibited marked differences i...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1990-12-15 00:00:00
abstract：:Previously, we identified an amplified gene in a stomach cancer cell line, KATO-III, and designated it K-sam. This gene was later found to be identical with a gene for a receptor tyrosine kinase, bek/FGFR2. One of the characteristics of the K-sam gene is structural diversity of its transcripts; K-sam complementary DNA...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1994-01-15 00:00:00
abstract：:Mc3 is a murine mAb that is highly effective in treating breast tumors in experimental radioimmunotherapy. Mc3 binds to BA46, a 46-kDa glycoprotein of the human milk fat globule membrane that is also expressed in breast carcinoma cells. We cloned and sequenced cDNAs encoding the variable regions of Mc3 and constructed...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1995-04-15 00:00:00
abstract：:Chinese hamster ovary cells exposed to the sulfhydryl compound cysteamine combined with heat treatment at 44 degrees C developed thermotolerance within 8 h. After initial treatment either with 15 min cysteamine (0.4 mM) at 37 degrees C immediately followed by 15 min heat at 44 degrees C or with 15 min cysteamine (0.4 ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1987-05-01 00:00:00
abstract：:Prostate cancer has become epidemic, and environmental factors such as cadmium may be partly responsible. This study reports malignant transformation of the nontumorigenic human prostatic epithelial cell line RWPE-1 by in vitro cadmium exposure. The cadmium-transformed cells exhibited a loss of contact inhibition in v...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2001-01-15 00:00:00
abstract：:Osteosarcoma is the most frequent primary bone tumor that develops mainly in the young, the median age of diagnosis being 18 years. Despite improvement in osteosarcoma treatment, survival rate is only 30% at 5 years for patients with pulmonary metastases at diagnosis. This warrants exploration of new therapeutic optio...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-06-4130
更新日期：2007-08-01 00:00:00
abstract：:Radiation resistance poses a major clinical challenge in cancer treatment, but little is known about how microRNA (miR) may regulate this phenomenon. In this study, we used next-generation sequencing to perform an unbiased comparison of miR expression in PC3 prostate cancer cells rendered resistant to fractionated rad...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-13-1657
更新日期：2013-12-01 00:00:00
abstract：:Specific progesterone binding by cultured human breast carcinoma T47D, MCF-7, and ZR75-1 cells was decreased 25-40% by epidermal growth factor (EGF), with a 50% effective dose of 0.1 nM EGF. Studies with the soluble and particulate fractions prepared after homogenization of T47D cells grown in glass roller bottles rev...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1988-09-15 00:00:00
abstract：:Tumor-infiltrating lymphocytes (TIL) are potent mediators of an antitumor response. However, their function is attenuated in solid tumors. CD8+ T-cell effector functions, such as cytokine and granzyme production, depend on cytoplasmic Ca2+, which is controlled by ion channels. In particular, Kv1.3 channels regulate th...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-16-2372
更新日期：2017-01-01 00:00:00
abstract：:The early detection of prostate cancer is a life-saving event in patients harboring potentially aggressive disease. With the development of malignancy, there is a dramatic reduction in the zinc content of prostate tissue associated with the inability of cancer cells to accumulate the ion. In the current study, we used...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-10-1008
更新日期：2010-08-01 00:00:00
abstract：:The PDLIM2 protein regulates stability of transcription factors including NF-κB and STATs in epithelial and hemopoietic cells. PDLIM2 is strongly expressed in certain cancer cell lines that exhibit an epithelial-to-mesenchymal phenotype, and its suppression is sufficient to reverse this phenotype. PDLIM2 supports the ...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-18-2787
更新日期：2019-05-15 00:00:00
abstract：:Although the concept that cancers originate from stem cells (SC) is becoming scientifically accepted, mechanisms by which SC contribute to tumor initiation and progression are largely unknown. For colorectal cancer (CRC), investigation of this problem has been hindered by a paucity of specific markers for identificati...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-08-4418
更新日期：2009-04-15 00:00:00
abstract：:Mucin-depleted foci (MDF) are microscopic dysplastic lesions induced in the colon of rodents by specific colon carcinogens. Most MDF show Wnt pathway activation, whereas only a subset shows mutations in the Ctnnb1 gene, coding for beta-catenin. Because Apc is a member of the Wnt pathway and the most frequent mutated g...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-06-3861
更新日期：2007-01-15 00:00:00
