Abstract:
:Resistance may be classified as active (or competitive) (due to excess amount of a factor) vs passive (or non-competitive) (due to a deficiency of a factor). Passive resistance may be important in human solid tumors. In passive resistance, the dose-response curve may be shallow, or may flatten at a relatively low dose. We hypothesized that, if passive resistance were important, it might be advantageous to use low doses of multiple concurrent chemotherapy agents with differing mechanisms of action, rather than using high doses of 2 or 3 drugs. We combined single day cisplatin 60 mg/m2, cyclophosphamide 250 mg/m2, epirubicin 40 mg/m2, paclitaxel 60 mg/m2, and vinblastine 2.5 mg/m2, with 5 days of 5-fluorouracil 200 mg/m2, folinic acid 20 mg/m2 and dexamethasone 4 mg orally q.i.d. every 3 weeks. In later cohorts, doses were escalated, and tamoxifen and verapamil were added. Twenty-three patients were entered. ECOG performance status was 1 in 15 patients and 2 in 8. Number of prior chemotherapy regimens was 0 in 4 patients, 1 in 4, 2 in 8, 3 in 4, 4 in 2, and 7 in 1. Sixteen patients had prior radiotherapy, and 3 had no prior therapy. Myelosuppression and febrile neutropenia were frequent, and 4 heavily pretreated patients died of pneumonia contracted while neutropenic. Diarrhea, nausea and vomiting, and fatigue were also prominent. Among 9 patients with non-small cell lung cancer, one had a partial remission, 4 had stable disease (including 3 with minor objective responses). Two additional non-small cell lung cancer patients also had objective tumor regression, but were coded as failures, since one had tumor progression in <6 weeks and the other died of respiratory failure (thought to be due to severe mucous plugging) one week after his first course of treatment. Among 14 patients with other tumor types, there was one partial response (esophageal carcinoma), 6 patients with stable disease for >6 weeks (including minor responses in one patient each with adenocarcinomas of kidney and breast), and 7 failures (including one patient with adenocarcinoma unknown primary who had minor tumor regression lasting 4 weeks). Despite the unacceptably high toxic death rate, median survival time was 24 weeks (range, 1 week to >104 weeks). This regimen is toxic, but survival duration is longer than would be expected in this heavily pre-treated population. Doses recommended for further study are those used in the first treatment cohort (as described above). Since myelosuppression is the major toxic effect, hemopoietic growth factors might prove helpful with this regimen.
journal_name
Int J Oncoljournal_title
International journal of oncologyauthors
Stewart DJ,Goel R,Gertler SZ,Huan S,Tomiak EM,Yau J,Cripps C,Evans WKdoi
10.3892/ijo.15.4.693keywords:
subject
Has Abstractpub_date
1999-10-01 00:00:00pages
693-9issue
4eissn
1019-6439issn
1791-2423journal_volume
15pub_type
临床试验,杂志文章abstract::VEGF, Hedgehog, FGF, Notch, and WNT signaling pathways network together for vascular remodeling during embryogenesis, tissue regeneration, and carcinogenesis. VEGFA (VEGF), VEGFB, VEGFC, VEGFD (FIGF) and PGF (PlGF) are VEGF family ligands for receptor tyrosine kinases, including VEGFR1 (FLT1), VEGFR2 (KDR) and VEGFR3 ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2006-06-01 00:00:00
abstract::The purpose of this present study was to investigate the role of inhibitor of apoptosis proteins (IAPs), their inhibitor, Smac, and the focal adhesion kinase (FAK) in the laminin enhancement of cisplatin-induced apoptosis in a testicular tumor germ cell line, NCCIT. We demonstrated that specifically in laminin-adheren...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2006-02-01 00:00:00
abstract::The purpose of the study was to assess response rate, clinical outcome, organ/function preservation and toxicity in head and neck cancer patients treated with induction chemotherapy followed by concomitant chemoradiotherapy and, when necessary, limited surgery. The study design was a phase II non-randomized trial in h...
journal_title:International journal of oncology
pub_type: 临床试验,杂志文章
doi:10.3892/ijo.16.6.1227
更新日期:2000-06-01 00:00:00
abstract::Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft tissue tumors arising sporadically although more frequently in patients with Neurofibromatosis type 1. Prognosis remains dismal as chemo- and radiotherapy have not been shown to be successful. The heparin-binding growth factor, Midkine (MK), is impl...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2005-11-01 00:00:00
abstract::The monocyte chemotactic protein 3 (MCP-3) belongs to the MCP subgroup of the CC chemokines and promotes chemotaxis of immune cells. MCP-1 is believed to play an important role in monocyte infiltration into tumor tissues; however, the relationship between tumor-infiltrating macrophage/microglia (TIM/M) and the express...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo_00000292
更新日期:2009-06-01 00:00:00
abstract::The aim of this study was to assess pivotal factors determining the oxygenation status of malignant tumors, and, for comparison, of normal tissues. For this purpose, microvascular patterns, blood flow data, O2 consumption rates and O2 extractions were correlated to the median pO2 values of isografted rodent and xenogr...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2003-04-01 00:00:00
abstract::Growth factors may play a role in autocrine or paracrine growth control of tumour cells. We have now examined the expression pattern in vivo by in situ hybridization (ISH) on a series of 13 ductal adenocarcinomas of the pancreas using the non-radioactive digoxigenin system to generate specific antisense orientated rib...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.4.6.1219
更新日期:1994-06-01 00:00:00
abstract::A series of different human MDR (multidrug-resistant) cell lines including a HeLa-MDR1 transfectant which exhibit high overexpression of the MDR1/P-glycoprotein gene, but no enhanced expression of the MRP (multidrug resistance associated protein) gene, showed different ratios of relative resistances to the taxanes tax...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.8.5.951
更新日期:1996-05-01 00:00:00
abstract::Glioma is the most prevalent and fatal primary tumor of the central nervous system in adults, while the development of effective therapeutic strategies in clinical practice remain a challenge. Nucleotide-binding domain leucine-rich family pyrin-containing 3 (NLRP3) has been reported to be associated with tumorigenesis...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2018.4480
更新日期:2018-09-01 00:00:00
abstract::Antisense oligonucleotides have been investigated as anticancer agents administered alone or in combination with conventional chemotherapeutics. In the present study, we demonstrated synergistic effects between anti-MDM2 antisense oligonucleotides and the clinically used anticancer agent irinotecan, using nude mouse m...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2002-04-01 00:00:00
abstract::We have established a new human alphafetoprotein (AFP)-producing gallbladder carcinoma (GBC) cell line, termed KMG-C, from a 67-year-old Japanese male. KMG-C and its reconstituted tumors in nude mice showed the morphological features of an adenocarcinoma. Functionally, KMG-C secreted AFP, carcinoembryonic antigen, and...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.8.6.1179
更新日期:1996-06-01 00:00:00
abstract::Choriocarcinoma is a highly malignant trophoblastic tumor related to pregnancy that often occurs with a complete hydatidiform mole. It grows quickly and can also widely metastasize to other organs or tissues through both the venous and lymphatic systems. The transforming growth factor-β1 (TGF-β1) belongs to a growth f...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2013.2026
更新日期:2013-10-01 00:00:00
abstract::In the multistep progressive pathogenesis of human breast cancer, comedo ductal carcinoma in situ (DCIS) represents a preinvasive precursor lesion for therapy resistant invasive cancer. Human tissue derived cell culture models exhibiting molecular similarities to clinical DCIS facilitate an important preclinical mecha...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2002-10-01 00:00:00
abstract::Simultaneous resistance of cancer cells to multiple cytotoxic drugs, multidrug resistance (MDR), is the major limitation to the successful chemotherapeutic treatment of disseminated neoplasms. The 'classical' MDR phenotype is conferred by MDR1/P-glycoprotein (MDR1/P-gp) that is expressed in almost 50% of human cancers...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2007-08-01 00:00:00
abstract::A group of 133 primary oral squamous cell carcinomas were studied concerning a relationship between exposure factors and tumour biological parameters with a focus on the TP53 gene and p53 protein status. Tumours were evaluated using immunohistochemistry (IHC) for expression of p53, PCNA, Ki-67 and bcl-2 proteins. The ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.22.4.861
更新日期:2003-04-01 00:00:00
abstract::Overexpression of p185erbB2/neu has been demonstrated in approximately 30% of prostatic carcinomas and has been shown to induce tumorigenesis and metastasis in a prostatic epithelial cell line, NbE. To metastasize successfully, cells must be able to proliferate, degrade and be motile on a variety of substrates; thus a...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:1998-12-01 00:00:00
abstract::We report here that lysocellin, a polyether antibiotic from a streptomycete, induces G1 phase arrest in human osteosarcoma MG63 cells. Lysocellin up-regulates p21WAF1/Cip1 and down-regulates cyclin D1 at the mRNA level. In addition, cyclin D1 is down-regulated by the proteasome-dependent signal pathway in MG63 cells. ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2006-04-01 00:00:00
abstract::Idarubicin (IDA) is a 4-demethoxy-anthracycline analogue of daunorubicin (DNR). IDA has been recognized as a potent anti-leukemic agent. However, the molecular mechanism of IDA-induced cell death remains unclear. In the present study, we investigated the activity of IDA to induce apoptosis in human leukemia HL-60 and ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2003-05-01 00:00:00
abstract::Telomeres, repeated DNA sequences (T2AG3)n that guard the ends of chromosomes, serve as a checkpoint for cell-cycle progression and regulate cell senescence and apoptosis. Loss of the telomeric repeats promotes genomic instability, which is the hallmark of most cancer cells. Whether this loss differs among tumor cells...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.15.3.423
更新日期:1999-09-01 00:00:00
abstract::We have previously isolated a drug-resistant, [PC3(R)], variant of human prostate PC3 cell line, which showed significant resistance (>10-fold) to adriamycin. No known mechanisms of drug resistance were found; however, resistant cells expressed more bcl2, c-myc, and ms oncogenes compared to the sensitive cells. In thi...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.11.4.819
更新日期:1997-10-01 00:00:00
abstract::Early gastric cancers (EGC) may be subdivided into 2 groups by means of the use of mitotic index, apoptotic index and cell density: EGCs with high cell turnover and low cell density, which show high cell dissociation and, more frequently, lymph node invasion; EGCs with low cell turnover and high cell density. The same...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.12.4.883
更新日期:1998-04-01 00:00:00
abstract::The isolation of circulating tumor cells (CTCs) from the blood of patients afflicted with solid malignant tumors becomes increasingly important as it may serve as a 'liquid biopsy' with the potential of monitoring the course of the cancer disease and its response to cancer therapy, with subsequent molecular characteri...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2012.1557
更新日期:2012-10-01 00:00:00
abstract::Pyrogallol (PG) inhibits the growth of various cells via stimulating O2•--mediated death. This study investigated the effects of PG on cell death in human pulmonary fibroblast (HPF) cells in relation to reactive oxygen species (ROS) and glutathione (GSH) levels. PG inhibited the growth of HPF cells with an IC50 of ~50...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2016.3543
更新日期:2016-08-01 00:00:00
abstract::CDH13 (H-cadherin) is a member of the cadherin superfamily, which plays an important role in cell recognition and adhesion. We examined the expression and methylation status of the CDH13 gene in diffuse large B cell lymphomas (B-DLCLs). We found decreased expression of the CDH13 gene in all of 6 hematopoietic cell lin...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2004-09-01 00:00:00
abstract::Cancer represents a severe challenge to healthcare systems and individuals worldwide. The development of multiple drug resistance is a major issue regarding cancer therapy, which can result in the progression of disease. Cholesterol is a major constituent of cell membranes and participates in the regulation of several...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2020.5124
更新日期:2020-09-22 00:00:00
abstract::Chlorophyllin (CHL) is the sodium-copper salts of chlorophyll derivatives. In this study, the CHL was derived from a traditional Chinese medicine, the Bombyx mori excreta. The CHL, at concentrations 25-400 microg/ml, reduced the proliferation of HL-60, K-562, S-180, and MCF-7 cells by 8.2-95.7% after 72 h of incubatio...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2003-09-01 00:00:00
abstract::On the basis of the gene expression profiles of 120 lung cancer cases using a cDNA microarray containing 27,648 genes or expressed sequence tags (ESTs), we identified LRRC42 (Leucine-rich repeat containing 42) to be significantly upregulated in the majority of lung cancers. Northern blot analysis demonstrated that LRR...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2014.2418
更新日期:2014-07-01 00:00:00
abstract::Lumican is a member of a small leucine-rich proteoglycan family and is highly expressed in several types of cancer cells and/or stromal tissue. Lumican expression in the cytoplasm in advanced colorectal cancer correlates with poor patient prognosis. The expression of lumican in stromal tissues is associated with a hig...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2008-12-01 00:00:00
abstract::Raf-1 protein kinase plays an important role in cell growth, proliferation and cell survival. We have previously described the use of liposome-entrapped antisense raf oligonucleotide (LErafAON) to inhibit Raf-1 expression resulting in tumor growth inhibition and radiosensitization. The present study was undertaken to ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2004-05-01 00:00:00
abstract::Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related mortality worldwide. We have previously reported that LASP-1 is a downstream protein of the urokinase type plasminogen activator (uPA). Here we investigated the role of LASP-1 in HCC by a molecular and biological characterization of LASP-1...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2015.2923
更新日期:2015-05-01 00:00:00