Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rats used were W/Fu strain with a reported incidence of spontaneous mammary tumors (MTs) of 17%. Most of these have been benign fibroadenomas in older females. X-ray or fast neutron irradiations were given in subthreshold doses, some as low as 10 rads. Also, low doses (150 mg) of a chemical carcinogen (N-nitroso-N-butylurea; NBU) prolactin (MtH). The prolactin was provided by grafting a syngeneic mammatropic pituitary tumor (MtT.W95 or MtT.W98). Tumors developing at the implantation site were chormophobe adenomas. The latent period of tumor induction decreased after the 4th generation of animal passage of the tumors. In some rats, ovariectomy was done 1 week before X-irradiation. No MT was found in 18 untreated controls during 1 year of observation. No MT developed in 32 rats having only the grafts for 9-12 months. Total-body-X-irradiation with 25 or 50 rads alone elicited no MT for 1 year. Among 27 rats exposed to 200 rads of X-rays 2 developed MT fibroadenomas after 5 and 7 months. The supplemental administration of prolactin greatly increased and accelerated the occurrence of MTs in irradiated rats. Most of these were adenocarcinomas. Ovariectomized rats had fewer MTs than intact females. A correlation was found between dose and MT incidence. The persistence of chemically transformed MT cells was shown by the addition of prolactin several months after NBU therapy. MTs developed in 8 of 10 rats within 3 months after the MTT graft became palpable. All but 1 of these were adenocarcinomas. Apparently there had been no repair or elimination of damaged cells in the dormant state. It is suggested that progressive growth of MTs may depend on the hormonal milieu of the host.
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PMID:Role of prolactin in rat mammary carcinogenesis: detection of carcinogenicity of low-dose carcinogens and of persisting dormant cancer cells. 32 20

Combinations of drugs are used clinically for the therapeutic advantages they may provide over single agents. We have studied the cytotoxic interaction between four either phospholipids ET-18-OCH3, BM 41.440, BN 52205 and BN 52211, and several chemotherapeutic drugs (ADM, CDDP, VLB, VP-16, MMC, BLM and MTX) on two human tumor cell lines, A427 (lung) and HT29 (colon). We have used the MTT colorimetric assay to evaluate growth inhibition and performed isobologram analysis on the IC50 data. For both cell lines a synergistic effect has been found between each of the four ether phospholipids in association with CDDP and ADM. In both cell lines only BM 41.440 and BN 52211 act synergistically with VLB while, in A427 cells, only BN 52205 behaves similarly with MMC. These results show that a positive interaction exists between ether phospholipids, spindle poisons and DNA-interactive drugs.
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PMID:Evaluation of combinations of antineoplastic ether phospholipids and chemotherapeutic drugs. 128 28

Basic fibroblast growth factor (bFGF) has been shown to be mitogenic to many different eukaryotic cell lines of mesodermal and neuroectodermal origin. Addition of exogenous bFGF to the chemically defined media of five characterized human colon tumor cell lines, cultured in the absence of epidermal growth factor (EGF), resulted in stimulation of growth from 24% to 146% in four of five cell lines, as measured by a colorimetric MTT assay. A positive dose-response relationship was observed when colon cells were treated with bFGF concentrations from 1 pM to 1 nM. bFGF showed a cumulative effect with EGF in stimulating the proliferation of colon tumor cells. The growth-inhibitory effect of exogenous transforming growth factor-beta (TGF-beta) on these cells was abolished by bFGF. When colon tumor cells were examined on immunoblots with a fibroblast growth factor (FGF) receptor-specific antibody, bands were detected at apparent molecular weights of 131 and 145 kDa. Conditioned media and cell lysates from the same human colon tumor cell lines were immunoprecipitated with a bFGF-specific antibody. An immunoreactive band was detected that comigrated with authentic human recombinant bFGF (16 kDa). Furthermore, preabsorption of anti-bFGF antibody with authentic ligand blocked immunodetection of the 16 kDa band on immunoblots. Documentation of a bFGF response, receptor, and ligand expression in human colon tumor cell lines is novel, and may represent a more widespread role for FGF that extends to epithelial cells and tumors of endodermal germ layer origin. The expression of both ligand and receptors by these cells indicates that bFGF could be involved in their growth regulation at the autocrine level.
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PMID:Identification of basic fibroblast growth factor sensitivity and receptor and ligand expression in human colon tumor cell lines. 131 Mar 24

Because most small-cell lung cancers (SCLC) are initially chemosensitive and express neuroendocrine (NE) cell markers and most non-SCLC tumors (NSCLC) are chemoresistant and do not express NE cell markers, we investigated the association between morphological type and NE cell differentiation with in vitro chemosensitivity. We tested a panel of 55 lung cancer cell lines established from previously untreated patients. These were tested against five cytotoxic drugs commonly used in the therapy of lung cancer, using the MTT assay. For comparative purposes, we also tested cell lines established from previously treated patients with SCLC and from colorectal tumors. The logarithms of the IC50 values of all of the cell lines were normally distributed, permitting the use of Student's t-test for assessment of differences. In general, the in vitro sensitivities of SCLC, NSCLC, and colorectal cell lines mirrored the clinical experience with these tumor types. Cell lines started from previously treated patients with SCLC were more resistant than those from previously untreated patients who responded to initial therapy. For all of the cell lines, the sensitivities to the five drugs tested were highly significantly correlated with each other. Thus, for comparative purposes, each group could be assigned an average standardized mean rank. About 15% of NSCLC tumors express multiple neuroendocrine (NE) cell markers and 4 of 5 lines from these NSCLC-NE tumors were relatively chemosensitive, similar to SCLC lines and significantly different from other NSCLC lines. Other NE cell lines tested included bronchial carcinoids and cell lines from small-cell carcinomas arising in extra-pulmonary locations (ExPuSC).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Association between histological type and neuroendocrine differentiation on drug sensitivity of lung cancer cell lines. 132 32

Selective toxicity against cancer cells is a most important determinant for anticancer agents. Therefore, we have preferably evaluated anticancer effects in vivo using murine tumor models for several decades. Approximately 50 anticancer agents are currently available for clinical therapy, but very few agents are effective against some types of cancer. Much progresses in cell culture techniques resulted in establishment of various human tumor cell lines. Currently, we are able to use human tumor lines as well as murine ones for the examination of drug sensitivity. A number of assay methods to evaluate anticancer activity have been developed. In the beginning, growth inhibitory activity was evaluated by counting cell numbers after drug exposure. Then, human tumor clonogenic assay (HTCA) was designed to measure only proliferative cells. Recently colorimetric MTT assay and SRB assay in 96-well microplates were developed, which were adopted in the screening system in the NCI, based on a new idea, that is, disease-oriented screening (DOS) using about 60 human tumor cell lines. In this paper outline of each method was described, adding especially several comments on disease-oriented screening.
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PMID:[Cell culture and its application--in vitro evaluation of anticancer activity using human tumor cell lines]. 132 72

Similarities between pancreatic, prostate and mammary tumors in possession of steroidal receptors and enzymes led to investigation of the responsiveness of pancreatic cancer to steroids with potential for tumor inhibition. The compounds were tested in vitro against human (HPAF and PANC-1) and hamster (HP-1) pancreatic ductal tumor cell lines using a colorimetric enzyme-based assay (MTT) to assess both cytotoxic and cytostatic effects and the 3H-thymidine uptake assay for cytostatic effects. Only certain 6-methylenic steroidal 3-ketones and the anti-estrogen tamoxifen citrate exerted appreciable anti-tumor effects. Marked cytotoxic and cytostatic activity was shown by some 6-methylenic congeners of progesterone, testosterone and its acetate, and 4-androstene-3,17-dione on both human and hamster pancreatic tumor cell lines. In contrast to prostate cancer, testosterone, but not 5 alpha-dihydrotestosterone, enhanced growth of the well differentiated HPAF cell line as well as the poorly differentiated PANC-1 cell line. It is therefore surprising that the 6-methylene derivative of testosterone acetate, which is both a potent androgen and 5 alpha-reductase inhibitor, is a very active tumor inhibitor in our assay.
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PMID:Growth modulatory effects of some 6-methylenic steroids on human and hamster pancreatic adenocarcinoma cells in vitro. 133 65

Three large cell carcinoma cell lines were established from tumors of lung cancer patients. The cell lines were named NUTLC-2, NUTLC-4 and NUTLC-5 and they were found to have the following biological characterization. 1) By chromosomal analysis, the tumor cells of two of the cell lines (NUTLC-2 and NUTLC-5) were human-origin cells. Numbers of chromosomes of these cells ranged from 52 to 59 in NUTLC-2 and from 68 to 75 in NUTLC-5, with the modal numbers of 56 and 71, respectively. 2) Primary tumor resected from the patient with lung cancer was heterotransplanted into the subcutis of a nude mouse. NUTLC-4 cell line was established in vitro from the tumor in nude mouse and the tumor cells were found to be mouse-origin cells by chromosomal analysis. Human DNA was not detected by Alu analysis. 3) The tumor cells of three cell lines could be heterotransplanted subcutaneously into nude mice. However, no natural distant metastasis in nude mouse was observed. 4) Drug sensitivity to NUTLC-2, NUTLC-4 and NUTLC-5 tumor cells differed individually according to MTT colorimetric assay, and characteristic drug sensitivity was not noted in histological types of lung cancer.
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PMID:[Human lung cancer cell lines in our laboratory: establishment of three large cell carcinoma cell lines and their biological characterization]. 133 8

We succeeded in establishing a cell line (KEN-3) for subculture from a fibrosarcoma which originated in the ovary in a girl aged 17 years. Its characteristics and sensitivity to anticancer agents are reported in this paper. 1. Characteristics of established cell line. Lined cells consist of multinucleated giant cells mixed among many spindle-shaped cells. They grow in small colonies and have none of the pavement-like arrangement characteristic of epithelial tumor cells. The number of chromosomes ranged from 45 to 128 (mode: pseudo-triploidy region, 65). The doubling time, cellular density and plating efficiency were 76.9 hours, 5.4 x 10(5)/cm2 and 30.2%, respectively. Concerning tumor markers, CEA and sialyl SSEA-1 were only produced in small quantities. Subculture was possible subcutaneously in the nude mouse with no capacity for the production of ascites. 2. Susceptibility to anticancer agents and GP170 expression. The in vitro susceptibility to about 12 types of anticancer agents was investigated with the MTT assay. IC50/PPC was shown to be less than 1 for Adriamycin only. The sensitivity to CDDP (IC50/PPC: 4.8) was low, and no sensitivity was observed at all to DTIC, which is used frequently for mesenchymal tumors. GP170 (mdr-1 products) was positive in established cells in immunohistochemical stain.
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PMID:[Establishment and characterization of human ovarian fibrosarcoma cell line and its sensitivity to anticancer agents]. 135 14

The effect of somatostatin analogue RC-160 on the growth of hepatic metastases of colon cancer was investigated in rats using magnetic resonance imaging. Experimental liver metastatic tumors were established in syngeneic BDIX rats after intrasplenic injection of DHD/K12 colon adenocarcinoma cells. Each rat with implanted liver tumors received s.c. injections of somatostatin analogue RC-160 (50 micrograms/kg) or the vehicle (control) twice a day for 4 weeks, starting 3 weeks after tumor inoculation. During the treatment with RC-160, the growth of liver tumors was studied quantitatively by measuring liver tumor volumes in vivo with magnetic resonance imaging at intervals of 7 days. Chronic administration of RC-160 inhibited the growth of hepatic metastases of colon cancer in rats. Significant inhibition of liver tumor growth in RC-160-treated rats was observed throughout the treatment. The final liver tumor volume in the treated rats was decreased by 56.1% as compared to the controls. The treatment with RC-160 reduced the percentage increase in liver tumor volume from 1575 +/- 674% (mean +/- SEM) for the control to 1034 +/- 727% in the treated group. The tumor volume doubling time in treated rats was 3.7 days longer than the controls. The liver tumor growth delay time was 15.1 days. At the end of the treatment, the incidence of ascites and the weights of tumorous livers were also decreased by RC-160 treatment. Administration of RC-160 prolonged the median survival time by 13 days in treated rats. In cell cultures, significant inhibitory effects of somatostatin-14 and RC-160 on the growth of DHD/K12 colon cancer cells were determined by MTT assay and [3H]-thymidine incorporation assay, indicating direct effects of these peptides on the growth of colon cancer cells in vitro. These data suggest that administration of RC-160 could inhibit the growth of colon cancer and their hepatic metastases in rats. Somatostatin analogue RC-160 might be considered as a potential new agent for the treatment of patients with hepatic metastases of colorectal cancers.
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PMID:Inhibitory effect of somatostatin analogue RC-160 on the growth of hepatic metastases of colon cancer in rats: a study with magnetic resonance imaging. 135 23

The high-affinity receptor for IgG, Fc gamma RI, expressed on monocytes and interferon-gamma (IFN-gamma)-stimulated neutrophils, is a trigger molecule for cell-mediated cytotoxicity. We have prepared murine monoclonal antibodies (MoAb 22 and MoAb 32) that bind to Fc gamma RI outside the ligand binding site and thus bind to and trigger cytotoxicity that is not competed by other immunoglobulins. Because of these properties, it seemed that these MoAbs would be very useful for the development of bispecific antibodies (BsAb) for targeting normal cellular immune defense mechanisms as a new form of immunotherapy for treatment of cancer. BsAbs incorporate into a single molecule the binding specifities of two different antibodies, and, thus, can be used to target myeloid cells to tumors, ensure activation of cellular cytotoxic mechanisms, and target cell lysis and/or phagocytosis. BsAbs were prepared using anti-Fc gamma RI MoAb and an anti-myeloid cell MoAb, PM81, reactive with the CD15 antigen, for studies of antibody-dependent cellular cytotoxicity. Conjugates were made by cross-linking sulfhydryl groups of Fab fragments of MoAb 32 or 22 (both IgG1) and sulfhydryl groups added to intact PM81 (an IgM) using N-succinimdyl-acetyl-S-thioacetate (SATA). The resulting product was purified by high-performance size-exclusion chromatography. The ability of the BsAbs to mediate attachment of human monocytes to tumor target cells was confirmed in a microtiter well assay of binding of MTT-labeled U937 cells (a human Fc gamma RI-bearing cell line) to SKBR-3 (PM81-reactive breast carcinoma) target cells. The ability of the BsAbs to mediate killing of HL-60 promyelocytic leukemia cells was studied using a 6-hour Chromium-51 release assay. Effector cells were monocytes obtained by cytopheresis and cultured for 18 hours with IFN-gamma. Monocytes alone caused minimal killing (5-20%), monocytes plus BsAb caused moderate killing (20-50%), and monocytes plus BsAb plus human serum resulted in maximal killing (50-80%). Experiments were performed to test the ability of the BsAb to purge bone marrow of small numbers of leukemia cells using bone marrow mononuclear phagocytes treated for 18 hours with IFN-gamma prior to adding target cells. Without the addition of human serum as a source of complement, a 90% depletion of clonogenic HL-60 cells could be demonstrated. With human complement, up to 95% depletion was seen. Thus, this BsAb possessed the ability to lyse tumor cell targets by two different mechanisms, complement and cell-mediated lysis.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Initial trial of bispecific antibody-mediated immunotherapy of CD15-bearing tumors: cytotoxicity of human tumor cells using a bispecific antibody comprised of anti-CD15 (MoAb PM81) and anti-CD64/Fc gamma RI (MoAb 32). 136 20


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