Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recombinant human interferon-gamma (rHuIFN-gamma) was associated with liposomes in an attempt to improve its therapeutic efficiency. It was associated with liposomes composed of phosphatidylserine (PS) and phosphatidylcholine (PC) at a ratio of 3:7, and of PS:PC and cholesterol (CHOL) at a ratio of 1:4:5 with efficiencies of 13% and 21%, respectively. The lipid composition influenced the antiviral activity of the liposome-complexed IFN-gamma tested against vesicular stomatitis virus. IFN associated with PS:PC liposomes was fully bioavailable and degraded by trypsin treatment. In contrast, PS:PC:CHOL-IFN was resistant to trypsin, and appeared latent as its full biological activity was seen only after disruption of the liposomes with detergent. Four human tumor cell lines were exposed to free and liposome-associated IFN-gamma. The growth of three solid tumor lines (colon, bladder, and lung) was inhibited by similar concentrations of free IFN and PS:PC-IFN. In contrast, less PS:PC-IFN than free IFN was needed to inhibit histiocytic lymphoma cells. Higher concentrations of PS:PC:CHOL-IFN than of free IFN were needed to inhibit growth of all four cell lines. The specificity of these effects of liposome-associated IFN-gamma were shown by their partial or complete neutralization by antibody to IFN-gamma. When liposome-IFN complexes of either type were stored at 4 degrees C, 30% of the IFN activity remained after 7 days; thereafter, decay was minimal over the next 3 weeks. These data show the formation of stable HuIFN-gamma-liposomes and indicate that the lipid components of these complexes influence their antiviral and antiproliferative activity for several different cell types.
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PMID:Antiviral and antiproliferative properties of liposome-associated human interferon-gamma. 211 53

KW2083 7-N-(p-hydroxyphenyl) mitomycin C is a mitomycin C derivative, but not its masked compound. KW2083 differs from mitomycin C in various points. A phase I study of KW2083 by single intravenous injection was performed in 21 patients with advanced solid tumor. The dose limiting factor of this drug is marrow depression, and 70mg/m2 causing marked thrombocytopenia was determined as maximum tolerated dose. The thrombocyte count and the WBC count reached to nadir the minimum 2 to 3 weeks after and 1 to 2 weeks after the administration and recovered in 1 to 2 weeks and in 2 to 3 weeks respectively. As gastrointestinal symptoms, nausea or vomiting (38.1%), and anorexia (28.6%) occurred soon after the administration, and stomatitis and diarrhea were also observed in one case each. In addition, petechia, hemorrhagic tendency and fever were found in one case each. Patients receiving 70mg/m2 showed slight alopecia and transient slight in GOT and GPT elevation.
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PMID:[Phase I study of KW2083 7-N-(p-hydroxyphenyl) mitomycin C]. 718 79

Fazarabine (Arabinofuranosyl-5-azacytosine) is a synthetic pyrimidine nucleoside which combines the arabinose sugar of cytosine arabinoside with the triazine base of 5-azacytidine. It has demonstrated activity against a variety of human solid tumor xenografts including colon, lung and breast cancers. Eighteen patients with refractory metastatic colon cancer were enrolled in a phase II trial of fazarabine. The drug was administered as a 72 hr continuous infusion every 3-4 weeks; the starting dose was 2 mg/m2/hr as established in a previous phase I study. The major toxicity was neutropenia, as predicted from the phase I study. The median time to nadir for cycle 1 was 20 days, with a median granulocyte count of 437/microliters (range 36-1600/microliters); recovery was within 2-4 days, with only one incidence of fever and neutropenia in 42 cycles. Especially noted for their absence were thrombocytopenia, nausea, vomiting and stomatitis. No objective clinical responses were seen; one patient had stabilization of rapidly growing liver metastases for a period of 7 months. In view of fazarabine's narrow range of toxicities, future dose intensification trials utilizing fazarabine in combination with hematopoietic growth factors are worthy of consideration.
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PMID:Phase II study of fazarabine (NSC 281272) in patients with metastatic colon cancer. 768 14

9-Amino-20(S)-camptothecin (9-AC) is an analog of camptothecin with limited water solubility which has shown significant preclinical activity in a variety of human solid tumor xenografts. A Phase I trial using a soluble formulation of 9-AC, given as a 72-hour continuous infusion, has been completed. Thirty-one patients with resistant cancers received 5-60 micrograms/M2/h at three week intervals. The Maximum Tolerated Dose (MTD) was 45 micrograms/M2/hour. Neutropenia was the dose limiting toxicity, with few significant non-myelosuppressive toxicities. Minor responses were seen in 3/31 patients. Pharmacokinetic studies of 9-AC lactone (closed ring) showed substantial interpatient variability with a predicted half-life of 36 hours. A phase I/II trial of the same formulation of 9-AC is ongoing in refractory leukemia. Stomatitis and diarrhea are the non-myelosuppressive dose limiting toxicities. Evidence of antineoplastic activity has been seen in 3/15 patients. A Phase II trial in previously untreated metastatic breast cancer is also underway. A Phase I trial of a colloidal dispersion formulation, not yet completed, is better tolerated with a MTD > 45 micrograms/M2/h as a 72-hour continuous infusion. Evidence of antineoplastic activity has also been demonstrated.
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PMID:Trials of 9-amino-20(S)-camptothecin in Boston. 899 18

We examined the transduction efficiency of a VSV-G (vesicular stomatitis virus G protein)-pseudotyped vector encoding beta-galactosidase (lacZ) into human solid tumor cell lines and murine fibroblasts, compared with that of an amphotropic vector carrying the same RNA sequence. The ratio of cells transduced with the VSV-G-pseudotyped vector corresponded closely to 1 - e(-m.o.i.), as predicted from a Poisson distribution of transduction to the entire cellular population, while this was not the case for the amphotropic vector. Here m.o.i. (multiplicity of infection) is defined as the ratio of input infectious units (titrated on the corresponding cell line) to the number of cells used for the transduction. At high m.o.i.s (values greater than 3), the VSV-G-pseudotyped vector transduced approximately 95% of the culture population of all cell lines examined. The transduction efficiency of the amphotropic vector, however, was not dose-dependent and reached a plateau or even decreased, especially at high m.o.i.; this may be attributable at least in part to the presence of envelope protein and noninfectious particles that compete for the receptor of infectious amphotropic virus. The copy number of integrated vector proviral DNA and the expression level of lacZ increased almost linearly with the dose of the VSV-G-pseudotyed vector, which could readily achieve multiple transduction of more than 10 copies per cell and afforded about 100-fold more transgene product than could be achieved with the amphotropic vector. These features of both the VSV-G-pseudotyped vector and the amphotropic vector were essentially unaffected by purification using centrifugation. These properties of the vector should be highly advantageous for gene transfer into entire populations of human tumor cell lines at a designed dosage.
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PMID:Dose-dependent transduction of vesicular stomatitis virus G protein-pseudotyped retrovirus vector into human solid tumor cell lines and murine fibroblasts. 1040 62

The biological therapy of tumors using live viruses was first proposed a century ago but was abandoned due to potential virulence of wild-type strains. Thanks to advances in recombinant technology, replication-restricted strains have been genetically engineered, which replicate selectively within tumor cells. Examples include replication-competent mutants of herpes simplex virus (HSV), adenovirus, vesicular stomatitis virus, reovirus and measles virus. Replication-restricted oncolytic viruses are able to propagate selectively within solid tumor nodules exerting direct antitumor activity by killing infected tumor cells at the completion of a replicative cycle. In the process, they generate an intratumoral inflammatory response, which under the appropriate circumstances, may trigger the activation of an adaptive antitumor immune response, a process that has been named in situ tumor vaccination. Recombinant HSV may offer distinct advantages in oncolytic therapy of epithelial tumors. HSV is highly infectious to tumors of epithelial origin, resulting in high efficacy, there is considerable redundancy in HSV receptors, which makes the loss of HSV receptors by tumors due to mutations less likely and potent anti-herpetic drugs are commercially available, which may be used clinically to control undesired side effects. Herewith we describe the use of oncolytic viral therapy against intraperitoneal malignancies with special emphasis on oncolytic herpes simplex virus. We review the preclinical evidence on the efficacy and safety of intraperitoneal applications of HSV and discuss the rationale for its use for oncolytic therapy and in situ tumor vaccination of intraperitoneal tumors.
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PMID:Intraperitoneal oncolytic and tumor vaccination therapy with replication-competent recombinant virus: the herpes paradigm. 1265 5

Malignant gliomas are the most frequent primary brain tumors and have a dismal prognosis due to their infiltrative growth. Gene therapy using viral vectors represents an attractive alternative to conventional cancer therapies. In a previous study, we established lentiviral vectors pseudotyped with lymphocytic choriomeningitis virus (LCMV) glycoproteins (GPs) and demonstrated transduction of human malignant glioma cells in culture. In the current approach, we compared the transduction efficacy of LCMV-GP- and vesicular stomatitis virus glycoprotein (VSV-G)-pseudotyped lentiviral vectors for malignant glioma cells and normal brain cells in vitro and in vivo. LCMV-GP pseudotypes transduced almost exclusively astrocytes, whereas VSV-G pseudotypes infected neurons as well as astrocytes. LCMV-GP pseudotypes showed an efficient transduction of solid glioma parts and specific transduction of infiltrating tumor cells. In contrast, VSV-G-pseudotyped lentiviral vectors transduced only a few tumor cells in solid tumor parts and infected mostly normal brain cells in infiltrating tumor areas. In conclusion, lentiviral vectors pseudotyped with LCMV glycoproteins represent an attractive option for gene therapy of malignant glioma.
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PMID:Selective transduction of malignant glioma by lentiviral vectors pseudotyped with lymphocytic choriomeningitis virus glycoproteins. 1561 Jun 9

A 61-year-old female with surgically treated rectal cancer that had metastasized to lung and lymph nodes was treated with bevacizumab (BV) plus 5-fluorouracil (5-FU) and leucovorin (LV) as third-line chemotherapy after treatment failures with infusional 5-FU, LV and oxaliplatin (FOLFOX regimen); and infusional 5-FU, LV and irinotecan (FOLFIRI regimen). After four cycles of treatment, a computed tomography scan revealed reduced sizes of the lung and lymph node metastases. Tumor response has still been maintained after six cycles of treatment, and the chemotherapeutic response was evaluated as partial response according to the Response Evaluation Criteria In Solid Tumor guidelines. Manageable toxicity included grade 2 hypertension, grade 1 epistaxis and grade 1 stomatitis. Although there are no clinical trial results supporting the use of BV-containing therapy as third-line chemotherapy for advanced colorectal cancer, BV plus 5-FU and LV was effective and feasible in our patient with colon cancer that had progressed after treatment with 5-FU, irinotecan and oxaliplatin.
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PMID:Metastatic rectal cancer responding to third-line therapy employing bevacizumab after failure of oxaliplatin and irinotecan: case report. 1856 98