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

Low-dose continuous infusion 5-fluorouracil (LDCI-FU) was administered to 28 women with advanced breast carcinoma. Daily doses ranged from 175 to 250 mg/m2. The LDCI-FU was delivered continuously until the appearance of toxicity and was reinstituted at a 20% dose reduction after toxicity completely resolved. Patients with a median age of 56 years and a median performance status of 60% (Karnofsky) had been previously treated with combination chemotherapy. Complete responses were observed in two patients with soft tissue metastases. Thirteen patients experienced partial responses with a median duration of response of 4+ months. Partial responses were predominantly observed in soft tissue disease; however, five patients with visceral metastases experienced partial tumor regression. Median survival for the study group was 4+ months. Hormonal receptor status did not predict response to LDCI-FU. Toxicities included stomatitis, ten patients; hand-foot syndrome, eight patients; mild leukopenia, two patients; moderate thrombocytopenia, two patients; diarrhea, three patients; ataxia, three patients. Catheter-related toxicities of sepsis and/or thrombosis occurred in six patients. Because of the demonstrated activity in previously treated patients (53% response rate), LDCI-FU should be investigated in combination chemotherapy regimens in untreated breast cancer patients.
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PMID:Low-dose continuous infusion 5-fluorouracil. Evaluation in advanced breast carcinoma. 291 20

Twenty-seven patients with advanced malignancies confined to the head and neck region were treated with intra-arterial (IA) cisplatin and 5-fluorodeoxyuridine (FUDR) using implantable pumps or injection ports. Tumor histologies were: 16 squamous cell, one mucoepidermoid, one adenocarcinoma, one neuroendocrine, four adenoid cystic, two acinic cell, one fibrosarcoma, and one melanoma. All primaries originated from tissues in the head and neck area. Nineteen patients had received prior treatment, including chemotherapy in 13; eight were newly diagnosed. Responses in 26 evaluable patients were two complete (CR), ten partial (PR), six minor (MR), and eight progressions. The median duration of response was 5 months, with a range of 2 to 11 months. Sites of progression were within the infused volume in 13 patients and to uninfused local-regional or distant sites in eight. The response rate in the subset of 15 patients with squamous cell head and neck cancer was 47%. Toxicity in the 26 patients included stomatitis in 88%, nausea and vomiting in 64%, myelosuppression in 15%, and grade 1 nephrotoxicity in 1%. A regional advantage for IA cisplatin and FUDR can be calculated based on total body clearance rates (CLTB) for these agents and estimates of external carotid artery (ECA) blood flow. However, frequent progression of disease outside the infused volume to regional and distant sites limits the usefulness of this approach in recurrent disease patients.
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PMID:Intra-arterial cisplatin and FUDR in advanced malignancies confined to the head and neck. 295 5

Melanoma patients were vaccinated with cell-free lysates prepared from vesicular stomatitis virus (VSV)-infected cultured autologous and allogeneic melanoma cells. Eleven patients received vaccines produced from the melanoma cell line SK-MEL-13. This cell line, derived from the melanoma of Patient AH, expresses a differentiation antigen (initially defined by autologous antibody) that is restricted to melanomas and other cells of neural crest origin (an example of a Class 2 melanoma antigen). Thirteen patients received vaccines prepared from autologous melanoma cells, the only known source of autologous unique (Class 1) melanoma antigens. VSV lysates were used for vaccination because VSV infection of tumor cells has been shown to augment the immunogenicity of tumor antigens. All patients but one vaccinated with VSV lysates of autologous melanoma cells developed antibodies against VSV, and all patients vaccinated with VSV lysates of SK-MEL-13 developed antibodies against HLA-related antigens. Antibodies against a Class 1 (unique) melanoma antigen were detected in only one case, and antibodies against Class 2 (shared) melanoma antigens were not found in any of the patients. The authors conclude that VSV lysates of melanoma cells are not effective in increasing the serologic response of melanoma patients to Class 1 or 2 melanoma antigens.
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PMID:Serological response of melanoma patients to vaccines prepared from VSV lysates of autologous and allogeneic cultured melanoma cells. 298 1

Twenty-four patients with locally advanced (19 patients) or metastatic (5 patients) tumors were treated in a Phase I study combining constant intravenous infusions of iododeoxyuridine (IUdR) and hyperfractionated radiation therapy. IUdR was given as a constant infusion for 12 hours/day for two separate 14-day infusion periods in most patients. The dose of IUdR was escalated from 250 to 1200 mg/m2/12-hour infusion in this study. The initial tumor volume was treated to 45 Gy/1.5 Gy BID/3 weeks followed by a cone-down boost to 20-25 Gy/1.25 Gy BID/2 weeks after a planned 2-week break. THe IUdR infusion preceded the initial and cone-down irradiation by 1 week. Local acute toxicity (within the radiation volume) was uncommon and few patients required an alteration of the planned treatment schedule. Two patients developed late local toxicity with one patient showing clinical signs of radiation hepatitis and another patient developing a large bowel obstruction that required surgical bypass. Dose-limiting systemic toxicity was confined to the bone marrow with moderate to severe thrombocytopenia developing on Day 10-14 of infusions at 1200 mg/m2/12 hours. Mild stomatitis and partial alopecia occurred in some patients at this dose level. No systemic skin toxicity was seen. Pharmacology studies revealed steady-state arterial plasma levels of IUdR of 1 to 8 X 10(-6) M over the dose range used. In vivo IUdR incorporation into tumors was studied in three patients with high-grade sarcomas using an anti-IUdR monoclonal antibody and immunohistochemistry and demonstrated incorporation in up to 50-70% of tumor cells. The preliminary treatment results, particularly in patients with unresectable sarcomas, are encouraging. In comparison to our previous experience with intravenous bromodeoxyuridine, this Phase I study of IUdR shows less systemic toxicity (especially to skin), higher (2-3X) steady-state arterial levels, and comparable in vivo tumor cell incorporation.
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PMID:A phase I study of intravenous iododeoxyuridine as a clinical radiosensitizer. 299 90

A series of potential prodrug 5-halouridine 3',5'-cyclic monophosphates (5-X-cUMPs, X = F, Cl, Br, I, 1-4) has been prepared and tested for antitumor activity against murine leukemia L1210/0 and human lymphoblast Raji/0 cells and their deoxythymidine kinase deficient (TK-) counterparts, as well as for antiviral activity in primary rabbit kidney cells infected with herpes simplex virus type 1 or 2, vaccinia virus, or vesicular stomatitis virus. The 5-halopyrimidine bases, nucleosides (5-X-U), and 5'-monophosphates (5-X-UMP) were tested for comparison. 5-F-cUMP (1) showed reasonably potent inhibition of tumor cell proliferation (ID50 = 0.33-1.6 micrograms/mL), while the remaining diesters displayed ID50's ranging from 210 to greater than 1000 micrograms/mL. 5-F-cUMP was 70- to 300-fold less active than 5-F-dU in the same systems. With TK- L1210 cells, 5-F-cUMP was as potent as with the normal (L1210/0) line but was about fourfold less active with TK- Raji cells compared to Raji/0 cells. The 5-X-cUMPs showed little potency as antivirals. A single-crystal X-ray analysis of the ammonium salt of 5-I-cUMP confirmed its structure and showed the conformation of the phosphate ring to be the expected chair. The ribose pucker is near 3(4)T, and the torsion angle about the beta-glycosidic N(1)-C(1') bond is in the syn range (-84.8 degrees).
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PMID:Synthesis, structure, and antitumor and antiviral activities of a series of 5-halouridine cyclic 3',5'-monophosphates. 300 59

Although BHK-21 cells persistently infected with wild-type vesicular stomatitis virus (VSV) are sensitive to natural killer (NK) cells and do not form tumors in athymic nude mice, BHK-21 cells persistently infected with a previously isolated mutant virus (VSV-P) are resistant to NK cells and form tumors in nude mice. We used this VSV-P mutant to persistently infect HeLa cells and mouse tumor cell lines. A mouse mastocytoma line (P815) persistently infected with VSV-P was similar to BHK-21 cells in that it was resistant to NK cell lysis and formed tumors in nude mice. However, neither HeLa cells nor mouse myeloma lines persistently infected with VSV-P were resistant to NK cell lysis in vitro, and neither formed tumors in nude mice. Rejection by nude mice of HeLa cells and mouse myeloma cell lines persistently infected with VSV-P could be ablated by rabbit antiserum to asialo-GM1, implicating NK cells in the in vivo rejection of these persistently infected tumors. These results suggest that NK cell recognition and killing of virus-infected cells in vivo and in vitro depend upon genetic contributions from both the virus and the host cell.
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PMID:Tumorigenicity of persistently infected tumors in nude mice is a function of both virus and host cell type. 300 96

An enzymatic activity associated with intracellular membrane fractions of Merwin plasma cell tumor II, baby hamster kidney, and chicken embryo fibroblast cells and bovine kidney has been characterized which covalently links fatty acids onto the G protein of vesicular stomatitis virus. Exogenous G protein extracted from native vesicular stomatitis virus particles can be acylated in vitro only after it has been previously deacylated. The fatty acids transferred in vitro are sensitive to treatment with hydroxylamine, indicating an ester linkage. Cell-free acyl transfer was also observed with endogenous G protein present in membrane fractions prepared from vesicular stomatitis virus-infected cells. In this case, the fatty acids become linked to a G protein species (G1) which is not terminally glycosylated and therefore has not entered the trans-Golgi compartment. The same G protein species also becomes acylated in infected cells during short pulses with radioactive palmitic acid. Acylation of the G protein in vitro with free palmitic or myristic acid is energy-dependent, and the addition of ATP is specifically required. Other nucleoside triphosphates cannot substitute for ATP in the activation of free acyl chains. Alternatively, activated fatty acids linked in a high energy thioester bond to coenzyme A, e.g. [14C] palmitoyl-CoA, are suitable lipid donors in the in vitro acylation reactions. Palmitic acid transfer onto G protein shows the typical characteristics of an enzyme-catalyzed reaction.
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PMID:Cell-free fatty acylation of microsomal integrated and detergent-solubilized glycoprotein of vesicular stomatitis virus. 303 Oct 69

The synergism of anticellular and antiviral activities of recombinant human interferon-gamma (ReIFN-gamma) and recombinant human interferon-beta (ReIFN-beta) was examined in vitro using human melanoma SK-MEL-28 cells. Some differences were detected in the kinetics of anticellular activity between both IFNs, namely the inhibitory effect of ReIFN-beta occurred earlier than that of ReIFN-gamma. Significant synergism was detected in the anticellular activity of both IFNs when growth curves and isobolograms were examined. A difference between ReIFN-gamma and ReIFN-beta was also detected in antiviral activity. The antiviral activity of ReIFN-gamma against vesicular stomatitis virus (VSV) was significantly weaker than that of ReIFN-beta, even though both IFNs exhibited almost equivalent antiviral activities against Sindbis virus. However, ReIFN-gamma and ReIFN-beta exhibited synergistic antiviral activities against both VSV and Sindbis virus. The analysis of cell cycle distribution by flow cytometry revealed that there were some differences in the distribution pattern between cells treated with ReIFN-gamma alone, ReIFN-beta alone, or ReIFN-gamma and ReIFN-beta in combination. ReIFN-beta induced a prolongation or accumulation of S phase, whereas the effect of ReIFN-gamma was cycle-nonspecific. The combination of ReIFN-gamma and ReIFN-beta induced a decrease of G1 phase and an increase of G2M phase. These results suggest that ReIFN-gamma and ReIFN-beta used in combination were more effective in inhibiting the growth of human tumor cells and the proliferation of viruses than IFN used individually.
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PMID:Synergistic anticellular and antiviral activities of human recombinant interferon-gamma and -beta. 303 Dec 63

Spleen cells from C57BL/6 (B6) mice generate a strong in vitro cytotoxic T-lymphocyte (CTL) response specific for vesicular stomatitis virus (VSV). Spleen cells from VSV-primed B6-H-2bm3 (bm3) mice, which have a mutation in H-2Kb, require approximately 10-fold more UV-inactivated VSV to generate in vitro secondary anti-VSV CTL, compared with spleen cells from primed B6 mice. Anti-VSV CTL elicited in both bm3 and B6 mice are primarily specific for the viral nucleocapsid protein (N protein), as demonstrated by using recombinant vaccinia viruses that express the VSV N protein. bm3 CTL were found to exhibit only a very low level of lytic activity when tested against autologous VSV-infected concanavalin A spleen cell blasts as well as several H-2b tumor cell lines. The weak anti-VSV response of bm3 CTL was found to be the result of a combination of inefficient recognition of VSV-infected target cells and decreased elicitation of secondary effector cells. VSV-infected bm3 target cells were not killed as well as B6 targets by either bm3 or B6 effectors. This is because of the inefficient recognition of targets, as demonstrated by the fact that VSV-infected bm3 cells were unable to competitively inhibit the lysis of VSV-infected B6 target cells by either bm3 or B6 effectors. By using cells from recombinant mice, it was shown that the CTL response restricted by H-2Kb was low in the bm3 mice, compared with that of the B6 mice. However, the H-2Db-restricted CTL activity was similarly low in both the B6 and bm3 mice. The possibility that the low response to VSV-infected bm3 cells is caused by differences between the bm3 and B6 cells in expression of either viral antigens or H-2K was investigated by radiolabeling and immunoprecipitation. VSV-infected B6 and bm3 cells were found to express equivalent levels of both viral antigens and H-2K. These results indicate that the bm3 mutation alters a functional site on the H-2Kb molecule that is involved in the recognition of VSV-infected cells. The observation that elicitation of bm3 CTL can occur at high antigen doses further suggests that the bm3 mutation results in a lower affinity of H-2K either for viral antigen or for receptor sites on the CTL.
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PMID:Possible mechanisms by which the H-2Kbm3 mutation may decrease cytotoxic T-lymphocyte recognition of vesicular stomatitis virus nucleoprotein antigen. 303 26

Cross-reactive recognition of alloantigen by "self + X"-reactive cytotoxic T lymphocytes (CTL) has been documented in a variety of systems. It has been shown previously that the H-2Kb-restricted CTL response of C57BL/6 (B6) mice to vesicular stomatitis virus (VSV) infection is partially cross-reactive on uninfected target cells expressing the H-2Kbm8 mutation. In this report, we describe the isolation and detailed characterization of such dual-reactive CTL. By employing EL4 tumor lines transfected with genes encoding various VSV proteins, we demonstrated that the majority of dual-reactive CTL recognize the internal N protein of VSV and are also reactive against uninfected bm8 targets. Although the response of normal B6 mice to bm8 stimulators shows no measurable cross-reactivity on VSV-infected targets, the response of VSV-primed B6 mice to bm8 stimulation is almost entirely cross-reactive, lysing VSV-B6 targets and uninfected bm8 targets roughly equally. Furthermore, about 70% of CTL clones isolated from such mice by bm8 stimulation are dual-reactive with respect to effector function. Analysis at the population and clonal levels with cold target competition and antibody blocking suggests that the bulk of dual-reactive CTL have a higher avidity for VSV-B6 targets than for bm8 targets. The extreme case of this is illustrated by a fraction of CTL clones, isolated and maintained on bm8 stimulators, which lyse VSV-B6 targets but do not lyse bm8 targets. One such CTL clone is shown to be specific for the bm8 antigen in proliferation assays. These results demonstrate that: the specificity of an alloreactive CTL response may be dramatically altered by previous antigenic encounters; and dual-reactive CTL display a significant difference in affinity of the CTL receptor-determinant interaction, depending on the target which is recognized.
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PMID:Characterization of dual-reactive H-2Kb-restricted anti-vesicular stomatitus virus and alloreactive cytotoxic T cells. 303 10


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