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)

The ret transforming gene was activated by recombination between two unlinked segments of human DNA, most likely during transfection of NIH 3T3 cells. To further define this transforming gene, we isolated and sequenced ret cDNA clones. The nucleotide sequence indicates that the active ret transforming gene encodes a fusion protein with a carboxy-terminal domain which is 40 to 50% homologous to members of the tyrosine kinase gene family. This tyrosine kinase domain is preceded by a hydrophobic sequence characteristic of a transmembrane domain. Transcription of the ret tyrosine kinase sequence was detected in the SK-N-SH neuroblastoma, HL-60 promyelocytic leukemia, and THP-1 monocytic leukemia cell lines, but not in 25 other human tumor cell lines surveyed. The ret tyrosine kinase may thus represent a cell surface receptor which is expressed in a restricted range of human cells.
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PMID:ret transforming gene encodes a fusion protein homologous to tyrosine kinases. 303 15

Pirarubicin (THP-adriamycin or THP-doxorubicin) was found during a search of new anthracycline antibiotics among 4'-O-substituted compounds having less toxicities than other anthracycline anticancer drugs in 1979 by Umezawa et al. In its preclinical studies, this compound possessed almost similar antitumor efficacies to doxorubicin, but was effective against doxorubicin-resistant P388 and other murine tumor cell lines. This compound was rapidly incorporated into tumor cells, inhibiting DNA polymerase alpha and subsequently DNA synthesis. Inhibition of RNA synthesis was also noted. In the clinical studies, clinical responses were established against head and neck cancer, breast cancer, urogenital cancers, ovarian cancer, uterine cancer, acute leukemia, and malignant lymphoma, showing a wide antitumor spectrum clinically. Among the side effects, cardiac toxicity, alopecia and disturbance of the digestive organs were mild. From these results, THP-adriamycin seems to be a useful clinical drug for human solid tumors.
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PMID:[Pirarubicin (THP-adriamycin)]. 304 96

We investigated the influence of glucocorticoids on two effects of interferons (IFNs) which are thought to relate to their antitumor actions: cytotoxic activity and induction of HLA antigen expression. We treated human myeloid cell lines (U-937, HL-60, THP-1, K-562, and KG-1a), and T-(MOLT-4) and B- (Daudi) lymphoblastic cell lines with concentrations of IFN-alpha, IFN-gamma, and dexamethasone (Dex) which are commonly achieved in the circulation following therapeutic administration. The results show that for every cell line except Daudi, the greatest inhibition of cell growth occurred when IFN-gamma and Dex treatments were combined. The advantage of combined IFN-gamma and Dex treatment over treatment with either agent alone was most dramatic for the three cell lines (U-937, HL-60, and THP-1) which have monocytoid characteristics. There was also more growth inhibition by the combination of IFN-alpha and Dex than by either agent alone for all seven cell lines tested. The induction of HLA antigen expression by IFN-alpha and IFN-gamma, an effect which could increase recognition of the tumor cells by the immune system, was as great or greater in the presence of Dex as in its absence. These results demonstrate that glucocorticoids do not inhibit, and in some cases enhance, two effects of IFNs that appear to be related to their antitumor actions: inhibition of tumor cell proliferation and enhancement of HLA antigen expression.
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PMID:Individual and combined tumoricidal effects of dexamethasone and interferons on human leukocyte cell lines. 312 Nov 76

Two new recombinant TNFs (named rTNF-Scw1 and -Scw2) with higher basicity than conventional recombinant human TNF-alpha (rTNF-alpha) in the N-terminal region were constructed. Their sequences were constructed based on those of partially purified cytotoxic factors from the culture supernatant of acute monocytic leukemia cells THP-1, which unlike rTNF-alpha are cytotoxic to T24 bladder carcinoma cells in vitro. These new rTNF-Ss showed a broader cytotoxicity to tumor cells than rTNF-alpha. This increase in the basicity of the N-terminal region over that of conventional TNF significantly increased the cytotoxicity on tumor cells in vivo as well as in vitro.
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PMID:Improvement of cytotoxicity of tumor necrosis factor (TNF) by increase in basicity of its N-terminal region. 331 24

Eight-MHz radiofrequency hyperthermia (H) using Thermotron-RF8, and its combination with irradiation (RH), anticancer drugs (CH) or anticancer drugs plus irradiation (CRH), were carried out for a total of 93 urological malignancies: 19 cases of renal cancer, 3 of renal pelvic cancer, 4 of ureteral cancer 39 of bladder cancer, 8 of prostatic cancer, 14 of metastatic lesion of urological cancers and 6 of other urological cancers. All had failed in previous treatments, or had not undergone surgery because of their poor general condition. Nine cases, including 1 of renal cancer, 1 of ureteral cancer, 4 of bladder cancer, 2 of prostatic cancer and 1 of metastatic lesion of bladder cancer, were treated with (H). Fifty cases, including 4 renal cancer cases, 20 bladder cancer cases and 6 prostatic cancer cases, were treated with (RH). Eight of the 19 cases of renal cancer were treated with mitomycin C-microcapsule (MMC-mc) embolization prior to radiohyperthermia (CRH). The remaining 6 cases of renal cancer received embolization with MMC-mc followed by RE-heating (CH). Eighteen of the 48 cases of urothelial cancer or its metastasis, including 1 of renal pelvic cancer, 15 of bladder a cancer and 2 of metastatic lesion of bladder, received a combined treatment of intravenous THP-adriamycin, one of the derivatives of adriamycin and RE-heating (CH). In the remaining 2 cases, one received (CH), and the other received (CRH). Hyperthermia was given twice a week for a total of 10 sessions in 5 weeks. Intratumoral temperature was kept above 42.5 degrees C for 30 to 40 minutes during a one-hour heating. Complete tumor regression was obtained in 9 bladder cancer cases. Partial tumor regression, defined as a regression of 50% or more, was obtained in 17 cases. A pain relief was attained in 18 of 23 patients with intractable pain due to local tumor infiltration. As side effects, mild skin burns were observed in 21 cases. Ten obese cases, having subcutaneous tissue 15mm thick or more, developed fat tissue induration after treatment.
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PMID:[Eight-MHZ RF hyperthermia in urological malignancies]. 338 6

An intravesical chemotherapeutic agent must be capable of being rapidly absorbed by the tumor cells and expressing its activity while undergoing little systemic absorption. A comparative investigation was conducted on (2''R)-4'-O-tetrahydropyranyl-doxorubicin (Adriamycin) (THP) and Adriamycin (ADM) from the above viewpoint using cultured MBT-2 and T-24 cell lines. From in vitro experimental systems, it is surmized that THP is taken up by bladder tumor cells more rapidly than ADM is, and that THP is thus able to exert its effect on the bladder tumor within a shorter time than that required by ADM. This pharmacokinetic advantage of THP was proved in an in vivo experimental system; that is, bladder tumor tissue which was established by implanting MBT-2 cells into the mouse (C3H/He) bladder was found to contain THP in a concentration approximately 1.9 times higher than the concentration of ADM. The amount of systemic absorption from the bladder was small in the case of both THP and ADM. THP should be useful as a new agent for intravesical chemotherapy.
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PMID:Comparative investigation on use of (2''R)-4'-O-tetrahydropyranyl-adriamycin and adriamycin as intravesical chemotherapy for superficial bladder tumors. 340 Jan 39

In vitro studies suggest that purified IL 1 beta derived from normal human peripheral blood monocytes and human myelomonocytic cell line THP-1 cell supernatants was capable of modest augmentation of NK activity of purified LGL and of promoting monocyte cytotoxicity for the human melanoma A375 target cells. In addition, purified IL 1 beta also has direct cytostatic and cytocidal effects for A375 cells. A375 melanoma cells were cloned to obtain a homogeneous population of IL 1 receptor-bearing target cells. Recombinant human IL 1 alpha inhibited the proliferation of these cells within 48-72 h in a dose-dependent manner. Similar doses of recombinant IL 1 alpha exhibited inhibitory effects on the ornithine decarboxylase (ODC) activity of A375 cells by 6-24 h. Putrescine, a nontoxic product of the ODC pathway, could prevent the cytostatic effect of recombinant IL 1 alpha on these tumor target cells. This observation indicates that inhibition of the ODC pathway is causally related to the antiproliferative effect of IL 1 on these tumor cells.
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PMID:Mechanism of in vitro antitumor effects of interleukin 1 (IL 1). 349 32

Since the first discovery of antitumor properties of daunorubicin in 1962, several hundreds of anthracyclines have been evaluated. In 1969, the primary screening on L1210 leukemia allowed to detect doxorubicin which is more active than daunorubicin and has been found clinically active on several human solid tumors. Therefore, L1210 leukemia appeared to be a useful model for evaluating experimental antitumor activity of anthracyclines, indicating a possible correlation between this model and the clinic. Analogs which are equally or more active than doxorubicin in the primary screening are tested in the secondary screening, then eventually in models of cardiotoxicity in order to evaluate their therapeutic index. The secondary screening includes murine solid tumors (B16 melanoma, Lewis lung carcinoma, mammary adenocarcinomas, colon adenocarcinomas 26 and 38) and human tumor xenografts into nude mice or under the renal capsule of normal mice (LX1, lung - CX1, colon - MX1, breast). Various tumor localizations (i.p., i.v., s.c., i.m., i.c.), various routes of administration (mainly i.v. and p.o.), various schedules of treatment (early or delayed, repeated or intermittent) and models of polychemotherapy are used to obtain a better evaluation of the compound. P388 leukemia resistant to doxorubicin is useful to test cross resistance in vivo and also to screen compounds able to reverse this phenomenon. Until now, 17 new anthracyclines have been introduced into clinical trials. Aclacinomycin has a different mechanism of action from that of doxorubicin (induction of tumor cell differentiation, inhibition of B and T suppressor lymphocytes); it is less myelotoxic and it is not mutagenic in vitro. THP-doxorubicin is more active than doxorubicin against L1210 leukemia and some solid tumors; it seems less cardiotoxic.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Models of preclinical studies of anthracyclines]. 355 Jun 11

Cytotoxic effects of 3-deazaguanosine (3-DGUO) result from the inhibition of DNA synthesis and incorporation of the drug into DNA. Synergistic antiproliferative effects of a combination of 3-deazaguanosine and 2-beta-D-ribofuranosylthiazole-4-carboxamide, a potent inhibitor of inosine monophosphate dehydrogenase, was observed in human tumor cells. Inosine reversed the antiproliferative effects of the 3-deazaguanosine but not 2-beta-D-ribofuranosylthiazole-4-carboxamide. 3-Deazaguanosine monophosphate was shown to inhibit the activity of the de novo purine synthesis enzyme, 5'-phosphoribosyl-5-aminoimidazole-4-carboxamide transformylase. The data suggested a cytotoxic effect of 3-DGUO associated with the inhibition of de novo purine synthesis by drug nucleotides, an effect which may account for the synergistic action noted.
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PMID:Synergistic activity of purine metabolism inhibitors in cultured human tumor cells. 356 90

The response to cancer chemotherapy varies from patient to patient with the same histologic type of tumor. However, anticancer drugs are considerably toxic to the patient, and it is therefore very important to have an accurate knowledge of the sensitivity of anticancer drugs against an individual patient's tumor in establishing successful chemotherapy. We have investigated the sensitivity testing of anticancer drugs using the human tumor clonogenic assay since 1980. Specimens were obtained by aspiration of ascites, pleural effusions and bone marrow and by biopsy of primary and metastatic tumors. Drugs tested in the present study were adriamycin, aclarubicin, THP-adriamycin, mitoxantrone, 40497s (an active compound derived from ifosfamide), mitomycin C, cisplatinum and methotrexate. One hundred and fifty-two specimens were obtained from cancer patients and tested for their drug sensitivity using the assay. Of the 152 specimens, 63 (41%) formed more than 30 colonies in control plates and could be used to evaluate drug sensitivity. Of these, 45 instances were evaluable for examination in an in vitro-in vivo association, and 42 (93%) showed a correlation between in vitro sensitivity and clinical response. In summary, the results indicated that the human tumor clonogenic assay was an excellent technique for testing the in vitro sensitivity of anticancer drugs. However, technical developments yielding higher colony efficiency would be required to facilitate practical use of the assay.
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PMID:[Sensitivity testing of anticancer drugs using the human tumor clonogenic assay]. 372 43


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