Abstract：
:The orally administered tubulin-binding agent 1069C85 was developed with the hope of overcoming the multidrug resistance associated with existing anti-tubulin agents, such as the vinca alkaloids. A phase I study was performed using a single oral dose every 3 weeks, administered as a suspension reconstituted in 0.1% Tween 80 and 0.9% saline. The starting dose was 2.8 mg m-2, and dose doubling was permitted until the area under curve (AUC) was > or = 40% of that at the mouse LD10; thereafter, a modified Fibonacci scheme was used. The formulation proved to be unsatisfactory, resulting in inconsistent absorption. The terminal elimination half-life was prolonged (range 18-73.5 h). Sporadic central neurotoxicity was observed, which was grade 3 in one patient treated at 200 mg m-2. A revised formulation with micronized drug was more easily suspended and appeared to increase the bioavailability by a factor of 2-4. Severe central neurotoxicity, up to grade 4, was then observed at doses of 50-100 mg m-2. Unfortunately, toxicity was not predictable and one patient, with a previous history of partial intestinal obstruction, treated at 50 mg m-2, cleared the drug very slowly, possibly because of prolonged, delayed absorption. This patient died from pancytopenia and severe gastrointestinal damage. It was concluded that such unpredictable behaviour would be incompatible with safe evaluation in phase II studies; the trial was closed and further clinical development abandoned.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Judson I,Briasoulis E,Raynaud F,Hanwell J,Berry C,Lacey Hdoi
10.1038/bjc.1997.107subject
Has Abstractpub_date
1997-01-01 00:00:00pages
608-13issue
4eissn
0007-0920issn
1532-1827journal_volume
75pub_type
临床试验,杂志文章abstract：:The establishment and characterisation (morphology, ultrastructure, tumourigenicity) of six cell lines from primary human colorectal adenocarcinomas is described. These lines were established from surgical specimens, from 49 unselected patients, without the use of 'feeder' cells, 'conditioned' medium or passage of cel...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1986.132
更新日期：1986-06-01 00:00:00
abstract：:The nonsteroidal anti-inflammatory drug aspirin and the spice curcumin retard adenoma formation when administered long-term to Apc(Min/+) mice, a model of human familial adenomatous polyposis coli. Both agents interfere with cyclooxygenase activity. When aspirin is administered to Apc(Min/+) mice only postweaning, but...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6600900
更新日期：2003-05-06 00:00:00
abstract：:The biguanide drug metformin profoundly affects cell metabolism, causing an impairment of the cell energy balance and triggering a plethora of pleiotropic effects that vary depending on the cellular or environmental context. Interestingly, a decade ago, it was observed that metformin-treated diabetic patients have a s...
journal_title：British journal of cancer
pub_type： 杂志文章,评审
doi：10.1038/bjc.2016.385
更新日期：2016-12-06 00:00:00
abstract：:A total of 165 adult patients with Hodgkin's disease (HD) were questioned following treatment to examine their perceptions of actual and desired involvement and provision of information in the treatment decision-making process. Irrespective of the degree to which patients felt they had been involved in the decision-ma...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1996.39
更新日期：1996-01-01 00:00:00
abstract：BACKGROUND:Four-and-a-half LIM domains protein 2 (FHL2) is a component of the focal adhesion structures and has been suggested to have a role in cancer progression. It has been shown to be overexpressed in the colorectal cancer (CRC). METHODS:Here, we examined a possible prognostic value of FHL2 in CRC. Immunohistoche...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2013.290
更新日期：2013-07-09 00:00:00
abstract：:Thirty-eight patients with previously treated Hodgkin's disease were given high dose combination chemotherapy using melphalan and BCNU and autologous bone marrow transplantation. In 25 patients etoposide was added in conventional dosage. During the course of the study the dose of melphalan was increased from 80 to 140...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1989.128
更新日期：1989-04-01 00:00:00
abstract：:Previous studies have characterized the enzymatic properties and inhibition of a trypsin-like neutral protease on the surface of Ehrlich ascites cells by means of kinetic analysis. The present study links these kinetic studies with the recently reported role of a tumour-cell membrane-bound serine protease in tumour-in...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1982.304
更新日期：1982-12-01 00:00:00
abstract：BACKGROUND:The intestinal uptake of the taxanes paclitaxel and docetaxel is seriously hampered by drug efflux through P-glycoprotein (P-gp) and drug metabolism via cytochrome P450 (CYP) 3A. The resulting low oral bioavailability can be boosted by co-administration of P-gp or CYP3A4 inhibitors. METHODS:Paclitaxel or do...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2014.222
更新日期：2014-05-27 00:00:00
abstract：:The survival of 64 consecutive patients with disseminated midgut carcinoid tumours was compared in a retrospective study with that of 25 consecutive patients with sporadic malignant endocrine pancreatic tumours treated according to similar surgical principles. The presence of hepatic metastases implied a worse prognos...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6690494
更新日期：1999-06-01 00:00:00
abstract：:The tumour suppressor gene CDKN2A, located on chromosome 9p21, encodes the cell cycle regulatory protein p16. Inactivation of the CDKN2A gene could lead to uncontrolled cell growth. In order to determine the role of CDKN2A in the development of sporadic ovarian cancer, loss of heterozygosity at 9p21-22, homozygous del...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6690621
更新日期：1999-08-01 00:00:00
abstract：:In addition to hypoxia, acidic extracellular pH (pH(e)) is recognised as one of the microenvironmental characteristics of solid tumours. A number of studies have examined ways to increase tumour acidity in order to improve tumour-specific targeting of certain drugs and the effectiveness of hyperthermia. However, previ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6601766
更新日期：2004-05-04 00:00:00
abstract：:Two transplantable, highly immunogenic syngeneic C57BL fibrosarcomas, FS1 and FS6, were shown to have tumour-specific rejection antigens, as shown by excision of the primary tumours and i.p. or i.m. injection of graded doses of the specific and unrelated tumour cells. I.p. challenge with tumour cells induced a large a...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1978.253
更新日期：1978-11-01 00:00:00
abstract：:Patient participation in medical consultations has been demonstrated to benefit their subsequent psychological well being. Question asking is one way in which patients can be active. We investigated 2 means of promoting cancer patient question asking. One was the provision of a question prompt sheet to patients prior ...
journal_title：British journal of cancer
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1054/bjoc.2001.2073
更新日期：2001-11-02 00:00:00
abstract：BACKGROUND:Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) contains crucial information about tumour heterogeneity and the transport limitations that reduce drug efficacy. Mathematical modelling of drug delivery and cellular responsiveness based on underutilised DCE-MRI data has the unique potential to p...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6605773
更新日期：2010-08-10 00:00:00
abstract：:High expression of thymidylate synthase (TS) and inactivation of p53 are allegedly associated with chemoresistance. The authors evaluated TS and p53 expression in gastric cancer treated with neoadjuvant S-1/cisplatin chemotherapy. Paraffin sections of pretreatment biopsy and surgical specimens from 41 gastric cancers ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6603546
更新日期：2007-01-29 00:00:00
abstract：:A multicentric, prospective phase III study was carried out with the aim of testing the so-called 'worst drug rule' hypothesis, which suggests the use of an effective but 'less active' regimen that first eradicates tumoral cells resistant to a second effective and 'more active' regimen. With respect to this hypothesis...
journal_title：British journal of cancer
pub_type： 临床试验,杂志文章,多中心研究,随机对照试验
doi：10.1038/bjc.1997.586
更新日期：1997-01-01 00:00:00
abstract：:The purpose of this study was to evaluate the occurrence of lymphatic drainage to non-axillary sentinel nodes and to determine the implications of this phenomenon. A total of 549 breast cancer patients underwent lymphoscintigraphy after intratumoural injection of (99m)Tc-nanocolloid. The sentinel node was intraoperati...
journal_title：British journal of cancer
pub_type： 临床试验,杂志文章
doi：10.1038/sj.bjc.6600359
更新日期：2002-09-23 00:00:00
abstract：:In a case-control study using a large UK primary care database, we found that non-steroidal anti-inflammatory drugs had no protective effect against biliary carcinomas (cholangiocarcinoma and gall bladder cancer). Increased risks were observed for cigarette smoking, diabetes, gallstone disease and obesity. ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6604765
更新日期：2009-01-13 00:00:00
abstract：:The expression of urokinase-type plasminogen activator (uPA) was investigated in squamous cell carcinoma of the human larynx. For this purpose, tissue extracts from 25 matched samples of normal mucosa and neoplastic larynx were compared for the levels of uPA activity as evaluated by a chromogenic PA assay and sodium d...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1996.512
更新日期：1996-10-01 00:00:00
abstract：BACKGROUND:Diet modulates inflammation and inflammatory markers have been associated with cancer outcomes. In the Women's Health Initiative, we investigated associations between a dietary inflammatory index (DII) and invasive breast cancer incidence and death. METHODS:The DII was calculated from a baseline food freque...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2016.98
更新日期：2016-05-24 00:00:00
abstract：:Two hundred and thirteen lung tumours of primary site and 42 metastases were heterotransplanted into nude mice with an overall success rate of 44%. There were differences in success between the histological types. Squamous cell and adenocarcinoma had the highest success rate (51% and 43%, respectively) whereas large c...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1985.29
更新日期：1985-02-01 00:00:00
abstract：:Geographical correlations between standardized, mortality ratios (SMRs) of cancers and consumption of different types of alcoholic beverages (saké synthetic saké, shochu, beer, wine, and whisky), of cigarettes, and urbanization were examined for all 46 prefectures in Japan. Suggestive correlations were observed betwee...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1979.200
更新日期：1979-09-01 00:00:00
abstract：:Major advances in cancer immunotherapy have dramatically expanded the potential to manipulate immune cells in cancer patients with metastatic disease to counteract cancer spread and extend patient lifespan. One of the most successful types of immunotherapy is the immune checkpoint inhibitors, such as anti-CTLA-4 and a...
journal_title：British journal of cancer
pub_type： 杂志文章,评审
doi：10.1038/s41416-020-01160-5
更新日期：2021-01-01 00:00:00
abstract：:Oestrogen receptor alpha (ER-alpha) gene has two specific promoters, distal (P0) and proximal (P1), which induce almost identical transcripts in size due to different splicing. We examined the methylation at both promoter regions of the ER-alpha gene using HpaII, a methylation-sensitive restriction enzyme, prior to po...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6690631
更新日期：1999-08-01 00:00:00
abstract：:The neuropsychological performance of 85 women with early stage breast cancer scheduled for chemotherapy, 43 women scheduled for endocrine therapy and/or radiotherapy and 49 healthy control subjects was assessed at baseline (T1), postchemotherapy (or 6 months) (T2) and at 18 months (T3). Repeated measures analysis fou...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6603029
更新日期：2006-03-27 00:00:00
abstract：:Experimental studies indicated that long-chain polyunsaturated fatty acids may increase sensitivity of mammary tumours to several cytotoxic drugs. To evaluate this hypothesis in breast cancer, we have prospectively studied the association between levels of fatty acids stored in breast adipose tissue and the response o...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6690281
更新日期：1999-04-01 00:00:00
abstract：:Pancreatic cancers occurring in carriers of a pathogenic germline alteration in BRCA1/2 (gBRCA1/2) are assumed to demonstrate homologous recombination repair deficiency (HRD), associated with sensitivity to platinum-based chemotherapy and synthetic lethality with PARP inhibitors (PARPi). However, primary and secondary...
journal_title：British journal of cancer
pub_type： 评论,社论
doi：10.1038/s41416-019-0645-9
更新日期：2020-02-01 00:00:00
abstract：:A phase I study of the bispecific antibody MDX-H210 in combination with granulocyte colony-stimulating factor (G-CSF) was performed in stage IV breast carcinoma patients, overexpressing HER-2/neu. MDX-H210, constructed by crosslinking antigen binding fragments (F(ab') fragments) of monoclonal antibody (mAb) H22 to Fc ...
journal_title：British journal of cancer
pub_type： 临床试验,杂志文章
doi：10.1038/sj.bjc.6601367
更新日期：2003-12-15 00:00:00
abstract：:A crude membrane fraction isolated from mouse tumour cells was treated with various chemicals. The effects on the immunogenicity of the membrane sample were tested in syngeneic mice for tumour protection, using a challenge dose of 10(5) viable tumour cells. Best protection was obtained after immunization of mice with ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1978.236
更新日期：1978-10-01 00:00:00
abstract：:A multicentre phase 2 trial (single-stage design) was undertaken to test the efficacy and toxicity of carboplatin (AUC 6 according to Calvert) plus paclitaxel (175 mg/m(2)3-h infusion) every 4 weeks in the first line treatment of patients affected by extensive small cell lung cancer. The primary end-point of the trial...
journal_title：British journal of cancer
pub_type： 临床试验,杂志文章,多中心研究
doi：10.1054/bjoc.2000.1541
更新日期：2001-01-05 00:00:00
