Abstract:
:Some new phenothiazines have been synthesized on the basis of previous studies. The anticancer activity of "half-mustard type" phenothiazines was investigated on sixty different cancer cell lines in vitro. The percentage of growth (PG), 50% inhibition of growth (GI50), the tumor growth inhibition (TGI) and the concentration required for 50% lethality of cells (IC50) were examined and calculated in the presence of various (from 10(-4) to 10(-8) M) concentrations of phenothiazine alkylurea derivatives. The following cell lines were involved in the study: 6 leukemia, 9 non-small-cell lung cancer, 7 colon cancer, 6 central nervous system cancer, 8 melanoma, 6 ovarian cancer, 8 renal cancer, 2 prostate and 8 breast cancer cell lines. The antileukemic activity of four chloroethyl-substituted phenothiazine-alkylureas was shown by considerable growth inhibition, in the 10(-5) M range, of the six different leukemia cell lines. The 50% inhibition of growth was nearly the same for the four compounds on all cell lines. Tumor growth inhibition (TGI) and IC50 value to cells varied from -4.0 to -4.66. The two derivatives with the butylene bridge were more effective than propylene linked compounds against the CCRP-CEM, HL60 (TB), K-562 and MOLT-4 cell lines. However, the anti-leukemic activity of the derivatives was nearly the same for RPMT 8226 and SR cell lines. The substituent at the 2- position of phenothiazine ring and the length of the linker between the side chain nitrogen and the phenothiazine ring system are apparently important for antileukemic activity. Four of the 9 non-small-cell lung cancer cell lines were sensitive, while the other 5 cell lines were not. The compounds had a slight growth inhibitory effect on colon cell carcinoma and melanoma cells in which case the butylene linker seemed to be more effective than the propylene linker. At the same time, all of the compounds were weak or mostly inactive on cancer cells from the central nervous system. One ovarian cancer line of the 6, the IGROVI was sensitive to butylurea phenothiazines, however, the other five were not sensitive at all. The difference in the sensitivity of various renal cell carcinomas was significant: 5 lines were not sensitive, three of them (786-0, RXF-393 and TK-10) were sensitive to only butylene-substituted phenothiazine-ureas, propylene substitution resulted in ineffective compounds. The compounds were not able to inhibit the 2 prostate and 4 breast cancer cell lines, even at 10(-4) M. It was interesting that propylene-linked ureas were more effective than butylene-linked derivatives on MCF-7, but butylene-linked derivatives were more effective than propylene-linked compounds on MDA MB-231 and MDA-N. In addition, MDA MB 435 was more sensitive to the trifluoromethyl derivatives than the compounds without this substituent. Since the phthalimido-alkyl phenothiazines were not active at the first level of prescreen, these compounds were omitted from this study. The drug sensitivity of some cancer cell lines was not uniform for the different groups, therefore we postulate that the resistance can be related to some kind of (existing) drug-efflux mechanism. Apparently, the tumor specificity of phenothiazine alkylureas is more related to the leukemia specificity of alkylureas than to any CNS or lung specificity of phenothiazines.
journal_name
Anticancer Resjournal_title
Anticancer researchauthors
Wuonola MA,Palfreyman MG,Motohashi N,Kawase M,Gabay S,Gupta RR,Molnár Jsubject
Has Abstractpub_date
1998-01-01 00:00:00pages
337-48issue
1Aeissn
0250-7005issn
1791-7530journal_volume
18pub_type
杂志文章abstract:BACKGROUND:Epithelial protein lost in neoplasm-α (EPLIN-α) is a cytoskeletal protein whose expression is often lost or is aberrant in cancerous cells and tissues and whose loss is believed to be involved in aggressive phenotype. Our current study examined this molecule in human oesophageal tissues and investigated the ...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2012-04-01 00:00:00
abstract::We investigated the anti-metastatic effect of PKC412, a selective inhibitor of protein kinase C (PKC), on a spontaneous metastatic mouse model, which was prepared by inoculation with B16-BL6 mouse melanoma cells into the footpad of the right hind leg. At two weeks after inoculation, the primary tumor was amputated com...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2003-03-01 00:00:00
abstract::A female patient with stage IV-M1c (distant lymph node and breast metastases), chemotherapy-refractory melanoma was treated with the cytotoxic T-lymphocyte antigen 4 (CTLA-4)-inhibitory monoclonal antibody ipilimumab. At first evaluation following induction treatment, there was marked increase in the volume of the lym...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2012-04-01 00:00:00
abstract::The development and maintenance of testicular interstitial cell (IC) tumors under the conditions of low LH levels were examined in aged Fischer 344 rats, and the enzyme activities for androgen synthesis in the tumors were estimated. Sixty-week old rats received injections of an LH-RH agonist (LH-RHa) for 28 weeks or w...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:1990-03-01 00:00:00
abstract:BACKGROUND:Antibodies against human epidermal growth factor receptor 2 (HER2) affect metastatic breast cancer cells and cardiac myocytes. Guidelines recommend evaluation of cardiac ejection fraction (EF) every 3 months despite little supporting evidence for this need. We assessed the impact of EF screening on clinical ...
journal_title:Anticancer research
pub_type: 杂志文章
doi:10.21873/anticanres.11749
更新日期:2017-07-01 00:00:00
abstract::Chronic lymphocytic leukaemia remains the most common adult leukaemia in Western countries. In this review we tried to give an overview of the important prognostic markers and the developments in this field. We also reflected about the accumulative character of the disease and the influence of the micro-environment on...
journal_title:Anticancer research
pub_type: 杂志文章,评审
doi:
更新日期:2009-02-01 00:00:00
abstract::We report on a case of low-grade periductal stromal tumor of the breast with synchronous bilateral breast carcinoma. A 45-year-old woman came to our Hospital because of a palpable mass of the right breast. An approximately 5-cm mass was palpated in the upper right breast. The mammographic and sonographic findings of t...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2014-07-01 00:00:00
abstract::12-O-retinoylphorbol-13-acetate (RPA), an incomplete tumor promoter of the phorbol ester type and protein kinase C (PKC) activator, consists of two characteristic structural elements: the phorbol body and the retinoyl ester chain. Therefore, possible binding of the incomplete tumor promoter RPA to the human transport ...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2005-09-01 00:00:00
abstract::Para-aminobenzoic acid (PABA) has been previously reported as being an inhibitor of DDP toxicity, and its use did not result in any observable loss in antitumor activity of DDP. The following studies investigated the effect of PABA on the pharmacokinetics and urinary excretion of cis-diamminedichloroplatinum(II) (DDP)...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:1995-11-01 00:00:00
abstract:BACKGROUND/AIM:Fluorescence-guided surgery (FGS) of cancer is an emerging technology. We have previously shown the importance of resecting both the tumor and the tumor microenvironment (TME) for curative FGS. We also previously developed a syngeneic model using the mouse lymphoma cell line EL-4, expressing red fluoresc...
journal_title:Anticancer research
pub_type: 杂志文章
doi:10.21873/anticanres.10988
更新日期:2016-09-01 00:00:00
abstract:BACKGROUND:As cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are being increasingly adopted as the standard treatment for peritoneal surface malignancies, familiarity with this procedure's adverse events is also growing. Herein, we describe an unreported adverse event of exocrine panc...
journal_title:Anticancer research
pub_type: 杂志文章
doi:10.21873/anticanres.12482
更新日期:2018-04-01 00:00:00
abstract:BACKGROUND/AIM:The impact of testosterone or obesity on the pathological grade of prostate cancer remains controversial. Therefore, in this study, we investigated the relationship of serum testosterone and body mass index (BMI) to Gleason score at biopsy. PATIENTS AND METHODS:This study included 128 Japanese patients ...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2015-11-01 00:00:00
abstract::In the presence study we demonstrated that hycanthone and chlorophenoxamine can modulate the resistance of multidrug resistant (MDR) murine L1210 leukemia tumor lines in vitro and in vivo. The circumvention of MDR by hycanthone and chlorophenoxamine in vitro was demonstrated by a short-term test using tritiated nuclei...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:1991-05-01 00:00:00
abstract::TNF alpha is known to exert multi-regulatory effects on normal and malignant cell functions by binding to the corresponding cell surface receptor. However, the existence of cross interaction between TNF alpha and EGF receptor has been proposed. In this study, we investigated the modulatory effect of TNF alpha on EGF r...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:1996-09-01 00:00:00
abstract::In order to improve the knowledge of prolactin receptors (PRL-R) in human breast tumors, we studied PRL-R modulation by lactogenic and steroid hormones in the PRL-R rich human breast cancer cell-line, T-47 D. The PRL-R were assayed on a preparation of cell total membranes. We demonstrated an abnormal homologous in vit...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:1989-05-01 00:00:00
abstract::Human epidemiological studies suggest an association between N-acetyltransferase (NAT) activity and the incidence of bladder and colorectal cancers. In this study, paclitaxel was selected to examine the inhibition of arylamine NAT activity, gene expression and 2-aminofluorene-DNA adduct formation in a human osteogenic...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2004-01-01 00:00:00
abstract:BACKGROUND:Previous studies have shown that tumor necrosis factor-alpha (TNF-alpha) encapsulated in sterically-stabilized PEGylated STEALTH liposomes (SL) can better and more safely augment the efficacy of other treatment modalities than free TNF-alpha. The aim of this study was to examine the effects of SL-TNF-alpha i...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2002-03-01 00:00:00
abstract:BACKGROUND:Amrubicin is an active agent for the treatment of small-cell lung cancer (SCLC). However, there have been no reports of long-term amrubicin use. PATIENTS AND METHODS:Twelve patients with SCLC who were treated with eight or more cycles of amrubicin chemotherapy were retrospectively reviewed. RESULTS:The med...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2012-04-01 00:00:00
abstract:AIM:To evaluate the usefulness of Ki-67 index and survivin as predictive prognostic factors for rectal cancer treated with preoperative chemoradiotherapy. PATIENTS AND METHODS:The Ki-67 index and survivin expression were examined in patients with stage II/III rectal cancer (n=46) by immunohistochemistry. Patients were...
journal_title:Anticancer research
pub_type: 杂志文章
doi:10.21873/anticanres.12409
更新日期:2018-03-01 00:00:00
abstract:AIM:The purpose of the present study was to determine whether genes involved in the organization of the hematopoietic niche were dysregulated in patients with primary myelofibrosis (MF) treated with lenalidomide. MATERIALS AND METHODS:We used reverse-transcription quantitative polymerase chain reaction to study the ex...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2015-10-01 00:00:00
abstract:AIM:The aim of the present study was to determine if febuxostat could prevent tumor lysis syndrome (TLS) in children who received induction chemotherapy for hematologic malignancies. PATIENTS AND METHODS:A retrospective analysis was performed in 45 pediatric patients with hematological malignancies who received febuxo...
journal_title:Anticancer research
pub_type: 杂志文章
doi:10.21873/anticanres.12028
更新日期:2017-10-01 00:00:00
abstract::The immunomodulatory and antimetastatic/antitumor activity of thymic humoral factor-gamma 2 (THF-gamma 2) was evaluated in BALB/c-mice. Daily subcutaneous applications (7 consecutive days, 20, 200 ng of THF-gamma 2 per injection/mouse) upregulated counts of thymocytes and peripheral blood cells in tumor bearing mice. ...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2000-11-01 00:00:00
abstract::The M14 human melanoma cell line was characterized either for some biological features in vitro and in vivo or for responsiveness to a panel of anti-tumor agents of clinical interest. The results of our study show that the M14 cells in culture resemble the in vivo melanomas both biologically and functionally, thus sug...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:1987-07-01 00:00:00
abstract::Primary cultures from 30 human gliomas (26 high grade, 3 low grade, and one oligoastrocytoma) were studied to examine the mixture of cells that make up the outgrowth, and their interactions. GFAP + ve Fibronectin - ve cells had a predominantly process forming (PF) morphology and formed complex networks around explants...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:1986-07-01 00:00:00
abstract:BACKGROUND:Human carcinomas not only consist of neoplastic epithelial cells but also of tumor stroma, which may play an important role in tumor-progression. Whereas the tumor surrounding stroma is generally believed to represent a reactive component induced by tumor cell derived factors, a contribution of neoplastic ce...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2001-07-01 00:00:00
abstract:BACKGROUND:The prognostic significance of angiogenesis, proliferation and apoptosis after interferon (IFN) was investigated in 96 patients with renal cell carcinoma (RCC). MATERIALS AND METHODS:Microvessel density in the tumor(MVD), proliferative index(PI) and apoptotic index(AI) were quantified using immunohistochemi...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2000-01-01 00:00:00
abstract::Urinary gonadotropin peptide (UGP) has been measured in gynecological and urological cancers, but its usefulness in the diagnosis of cancers of digestive organs has not been investigated. In this report, UGP was measured by sandwich enzyme immunoassay in 311 patients, including 166 patients with cancers of digestive o...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:1996-07-01 00:00:00
abstract::Calcium signalling was studied in porcine aortic endothelial cells stably transfected with wild type or mutants of the human platelet-derived growth factor (PDGF) beta-receptor and fibroblast growth factor (FGF) receptor-1 (FGFR1). Phospholipase C-gamma (PLC-gamma) has a consensus binding site at phosphorylated Tyr102...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:1998-05-01 00:00:00
abstract::The melastatin-like transient receptor potential M2 (TRPM2) channel is a Ca2+ permeable channel that is activated by reactive oxygen species (ROS), and its activation induces necrotic cell death. The effect of insertion of TRPM2 into A172 human glioblastoma cells (A172 cells) was investigated. The insertion of TRPM2 c...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2007-11-01 00:00:00
abstract:BACKGROUND:We have identified a novel cancer/testis antigen, TRAG-3, (Taxol Resistance Associated Gene-3) that was initially discovered in search for new genes involved in drug resistance by differential display. Early study of TRAG-3 revealed minimal to absent expression in various normal tissues and over-expression i...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2000-11-01 00:00:00