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)

Guanidinothiazolecarboxamides (GTCs) are a novel class of antitumor agents found to be systemically active against experimental pulmonary metastases of 3LL Lewis lung carcinoma. A series of substituted benzothiazole GTCs were found to produce enhancement of survival in this model by using 8 days of intraperitoneal dosing initiated 2 days after intravenous tumor challenge. Quantitative structure-activity relationships have been discovered in the GTC series with survival enhancement correlated to substituent parameters. Optimal correlations were found between the probit transform of the drug-induced increased lifespan (ILS) and field and pi parameters. Among the most effective analogues in this series was N-(5-fluorobenzothiazol-2-yl)-2-guanidinothiazole-4-carboxam ide.
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PMID:Quantitative structure-activity relationships of antitumor guanidinothiazolecarboxamides with survival enhancement for therapy in the 3LL Lewis lung carcinoma model. 206 70

We studied fundamentally subrenal capsule assay, using human tumor specimens (breast, gastric and colon cancers) serially transplanted in nude mice. When cancer anticancer agents such as mitomycin C (MMC) and 5-fluorouracil (5-FU) were injected into immunocompetent mice treated with various dosages of cyclosporin A (CsA) after tumor implantation, optimal schedule of each drug was examined on the points of effects and toxicity against host mice. The following results were obtained. Control groups were set up as immunocompetent mice which treated daily with 60 mg/kg CsA from day 1 after tumor implantation. Optimal treatment schedule was judged as MMC 3 mg/kg i.v. injection on day 1 following by daily 60 mg/kg CsA treatment, and 5-FU was injected 25 mg/kg subcutaneous injection every day from day 1 without CsA treatment, each schedule showed an appropriate anti-tumor activity profiles against implanted tumor xenografts, and had less toxicity to the hosts.
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PMID:[Experimental studies on subrenal capsule assay using cyclosporin A treated mice--the optimal treatment schedules of CsA and anticancer agents (mitomycin C and 5-fluorouracil)]. 210 99

A variety of biologic and synthetic agents protect BALB/c mice against experimental M109 micrometastases. We have presented evidence that eradication of these metastases is mediated by the activation of host macrophages to the tumoricidal state. We now present evidence that injection of H22, a neutralizing hamster IgG monoclonal antibody to murine interferon-gamma (IFN-gamma; macrophage activating factor), 2 days prior to i.v. tumor inoculation markedly increases the metastatic capacity of M109 lung carcinoma cells. Therefore, we tested several cytokines that induce or mediate macrophage-mediated cytotoxicity, including IFN-gamma, tumor necrosis factor-alpha, and interleukin-1 beta (IL-1 beta), for their ability to inhibit the development of experimental M109 lung metastases. Intraperitoneal treatment with recombinant murine (rMu) IFN-gamma (greater than or equal to 10,000 units/mouse) or recombinant murine TNF-alpha (greater than or equal to 10,000 units/mouse) produced greater than 60% inhibition of metastasis formation. Optimal therapy was observed when cytokines were administered 2 days prior to i.v. tumor cell inoculation. Neither IFN-gamma nor TNF-alpha inhibited colony formation of M109 cells in vitro, suggesting a host-mediated mechanism for antitumor activity. Peritoneal macrophages were primed for tumor cytotoxicity by treatment with either IFN-gamma or TNF-alpha. Intraperitoneal treatment with recombinant human IL-1 beta (1 X 10(5) units) lacked antimetastatic activity. The results further support the role of activated macrophages in the destruction of M109 micrometastases.
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PMID:Protective activity of recombinant murine tumor necrosis factor-alpha and interferon-gamma against experimental murine lung carcinoma metastases. 211 56

Optimal techniques for the preoperative assessment and intraoperative management of the petrous carotid artery remain undefined. While purposeful "avoidance" of this structure may result in partial tumor removal, limited exposure of the petrous carotid artery may lead to inadvertent injury with life-threatening neurovascular sequelae. Twenty-five cases are reported in which surgical manipulation of the petrous carotid artery was necessary to accomplish total tumor removal or gain operative exposure to the skull base. A standard diagnostic radiographic assessment consisted of high-resolution computed tomography, magnetic resonance imaging, and a 4-vessel angiography. Preoperative balloon occlusion of the involved internal carotid artery was performed in four patients. Surgical approaches used in this series were broadly classified as: infratemporal-anterolateral (14), pterional-infratemporal (6), or pterional-anterolateral (5). Intraoperative management of the carotid artery consisted of total decompression in 19 cases, decompression with mobilization in four patients, and resection in two instances. Major neurovascular complications included one stroke and death caused by arterial occlusion, one stroke and death caused by arterial spasm, one stroke caused by brain edema, and one death related to a postoperative carotid hemorrhage. Other nonvascular complications included brain swelling, cranial nerve palsies, dysphagia, ataxia, cerebrospinal fluid fistulae, flap necrosis with wound infection, and pneumocephalus. Invasive and noninvasive methods are outlined for the preoperative assessment of the petrous carotid in cases of advanced skull base disease and intraoperative management options are detailed.
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PMID:The perioperative management of the petrous carotid artery in contemporary surgery of the skull base. 211 30

LAK cell activity of peripheral blood from normal donors was induced by interleukin 2 (IL-2). Optimal induction of LAK cells was obtained by 3-4 day incubation of PBMC in the presence of 30-40 units/ml of IL-2. Several cell lines Raji, CEM, HeLa, 109 (esophageal carcinoma) and OC (ovarian carcinoma) which were NK cell resistant tumor cells could be lysed by LAK cells. PHA was unable to markedly induce the LAK cell activity. Although both LAK and NK cell activity was decreased by mitomycin C treatment, their degree of susceptibility to such treatment was quite different. NK cells were more sensitive to mitomycin C than LAK cells. In contrast to the significant inhibition of the NK cell-mediated lysis by the addition of anti-CD 2 monoclonal antibody during cytotoxicity assay LAK cell-mediated lysis was not affected. These results indicate that LAK cells are capable of lysing a variety of tumor cells that are resistant to NK cells and their biological characteristics are also different.
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PMID:[Human LAK cell induction and its biological characteristics]. 212 54

Endogenous opioids and opioid receptors (i.e. endogenous opioid systems) are involved in carcinogenesis. Using homogenates of S20Y neuroblastoma (NB) cells grown in culture, the binding of a growth-selective ligand, [Met5]enkephalin, was examined to ascertain the zeta (zeta) opioid receptor. Specific and saturable binding of [3H]-[Met5]enkephalin was detected in NB cells; the data were consistent with a single binding site. Scatchard analysis yielded a Kd of 1.6 nM and a binding capacity (Bmax) of 48.1 fmol/mg protein; 14,000 receptors per cell were estimated. Binding was dependent on protein concentration, time, temperature, and pH, and was sensitive to 100 nM, but not 5 nM, Na+, Ca2+, and Mg2+; GppNHp at concentrations of 100-500 mM had little effect on binding. Optimal binding required protease inhibitors, and pretreatment of the tumor cell homogenates with trypsin markedly reduced [3H]-[Met5]enkephalin binding, suggesting that the binding site was proteinaceous in character. Displacement experiments indicated that [Met5]enkephalin was the most potent displacer of [3H]-[Met5]enkephalin. Cell density (log, confluence, postconfluence) did not alter the Kd or Bmax. This study serves as the first demonstration and characterization of the zeta (zeta) opioid receptor in tissue culture cells. The homogeneous nature of NB cell cultures, along with the enrichment in receptor number, provides an excellent model system to isolate and purify the zeta receptor.
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PMID:Demonstration and characterization of zeta (zeta), a growth-related opioid receptor, in a neuroblastoma cell line. 215 55

We evaluated the entrapment of 21 different water-insoluble aglycones or anthracycline antibiotics in multilamellar liposomes composed of dimyristoyl phosphatidyl choline and dimyristoyl phosphatidyl glycerol at a 7:3 molar ratio. The drug:lipid weight ratio was 1:15 to 1:50. The different analogues tested were modified at position 4 in the aglycone portion (4-demethoxy) and/or positions 2' (halo), 3' (hydroxy, acetoxy), or 4' (epi, acetoxy) in the sugar portion. The entrapment efficiency was assessed by measuring the amount of free drug remaining in the supernatant after centrifugation of the liposomes and by direct examination of the pellets by fluorescent microscopy. Optimal entrapment (greater than 98%) was observed with only four compounds: 4-demethoxyadriamycinone; 2'-iododaunorubicin; 4-demethoxydaunorubicin; and 2'-iodo-3'-hydroxy-4'-epi-4-demethoxydoxorubicin (Compound 22). All other compounds showed significant drug precipitation outside the multilamellar vesicles when observed by fluorescent microscopy. Compound 22, entrapped in liposomes, was evaluated in vivo against i.p. L-1210 leukemia by the i.p. route, and liver metastases of M5076 reticulosarcoma by the i.v. route. In both models, liposome-entrapped Compound 22 was more active than doxorubicin at the optimal dose [median survival (given in percentage) of treated to control animals was for L-1210, greater than 600 versus 212; for M5076, 200 versus 133]. 4-Demethoxy and 2'-iodo are structural modifications that markedly enhance the affinity of anthracycline antibiotics for lipid bilayers without compromising biological activity. These findings will serve as a guideline to obtain liposome-anthracycline preparations, with optimal formulation characteristics, enhanced tumor-targeting properties, and non-cross-resistance with doxorubicin.
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PMID:Anthracycline antibiotics with high liposome entrapment: structural features and biological activity. 219 51

Pathologic examination of urinary specimens is increasingly recognized as an essential component of detection and monitoring for patients with bladder neoplasms. Among the available techniques, urinary cytology is the most useful. The current status of urinary cytology can be summarized as follows: 1. The demand for urinary cytology is steadily increasing as clinicians have realized the limitations of cystoscopy and even biopsy for monitoring bladder cancer patients, especially those having carcinoma in situ or receiving topical therapy. 2. Urinary cytology is currently an essential procedure for monitoring all patients with urothelial neoplasms and, if consistently used, can actually decrease the frequency with which patients need to be subjected to cystoscopy. 3. Even in moderately experienced hands, urinary cytology can detect almost all high-grade urothelial neoplasms. 4. The cytologic interpretation of low-grade transitional cell neoplasia requires expertise. These cells lack many of the features of malignancy, a source of confusion for the diagnostician but a positive factor for the patient since neoplasms composed of these cells are almost never aggressive. 5. The most useful type of urinary specimen for routine diagnostic interpretation is freshly voided, randomly collected urine. Catheterized specimens and bladder washings may yield more and better preserved cells, but no patient should be catheterized solely to obtain diagnostic material. 6. Preservation of urinary specimens in alcohols is not necessary unless prolonged storage is contemplated. Refrigeration to prevent bacterial growth and inhibit further cellular degeneration is required, however. 7. Cytologic details are best displayed with membrane filtration but other types of processing are adequate. The computer-programmed cytocentrifuge is currently most popular. 8. Optimal recognition of cytologic details requires some form of Papanicolaou staining; Romanovsky dyes are less desirable. 9. Urothelial cells with nuclear:cytoplasmic ratios of 1:2 or less should not be interpreted as malignant regardless of the degree of anaplasia of their nuclei. 10. Papillary aggregation is not a reliable feature of low-grade neoplasia in urinary samples. 11. Using appropriate criteria, the differential diagnosis of urothelial neoplasia versus the reactive/regenerative/reparative changes secondary to urinary stones can almost always be accomplished. 12. Alkylating agents such as Cytoxan, thio-TEPA, and mitomycin C produce characteristic but nonspecific changes in urothelial cells. These changes rarely mimic those of carcinoma. The diagnosis of urothelial neoplasia need not be confounded by previous treatment. 13. Flow cytometry and digitized image analysis are currently used for diagnostic interpretations of urinary specimens in selected centers. Their routine use must await further refinements in instrumentation and the formulation of more searching questions.
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PMID:Current status of urinary cytology in the evaluation of bladder neoplasms. 220 72

1. B-85-0040 is a new cisplatin analogue with dose limiting myelosuppression. 2. The maximum tolerated dose ranges between 300 and 525 mg/kg for single i.p. bolus injection in mice. 3. Its toxicity is circadian-stage dependent with optimal tolerance between 16 and 17 hours after lights on. 4. B-85-0040 is active in L1210 leukemia. Anti-tumor activity seems to be unrelated to the circadian stage of treatment. Optimal drug timing can therefore increase its therapeutic index.
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PMID:Improved therapeutic index of cisplatin analogue: B-85-0040 by circadian timing. 221 24

Survival of ovarian carcinoma patients undergoing second-look laparotomy after primary surgery and adjunctive chemotherapy was evaluated by retrospective chart review. From August 1976 to August 1987, 102 patients with stage I-IV disease underwent second-look laparotomy. Optimal tumor debulking and early (stage I or II) disease were positively correlated with a negative second-look laparotomy. Of the 49 patients with a "negative" second look, 15 demonstrated recurrent tumor from 12.5 to 52.5 months after laparotomy. Of the 15 recurrences, 6 were documented more than 3 years following second look. Half of the 28 patients with stage III disease and a "negative" second look have demonstrated recurrent tumor. Fifty-three patients (52%) were found to have residual disease at second-look laparotomy. Initial chemotherapy (melphalan or multiple agent) and the adequacy of primary debulking surgery (optimal vs suboptimal) were not significant factors contributing to patient survival after a positive second look. However, the size of residual disease at second-look laparotomy was a significant factor in subsequent patient survival (P less than or equal to 0.01). Fifteen patients were free of gross disease at laparotomy, but had residual tumor on microscopic examination of the specimens submitted. These patients had a 2-year actuarial survival of 78%. Forty-seven percent have survived 5 or more years after second look. Nineteen patients with tumor implants 2 cm or smaller had 2- and 5-year actuarial survivals of 61 and 31%, respectively. Nineteen patients with tumor nodules larger than 2 cm in diameter had a 2-year actuarial survival of 6%. Only 1 of 19 patients with nodules greater than 2 cm could be effectively redebulked.
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PMID:Survival of patients with ovarian epithelial carcinomas after second-look laparotomy. 229 51


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