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)

Nineteen cyclolignans of varied structures, most of them isolated from Juniperus sabina leaves, were evaluated for their antineoplastic and antiviral activities. They were subjected to screening against P-388 murine leukemia, A-549 human lung carcinoma, and HT-29 colon carcinoma, while the antiviral assays were performed on herpes simplex virus type 1 infecting fibroblasts of monkey kidney (HSV-1/CV-1) and on vesicular stomatitis virus infecting fibroblasts of hamster kidney (VSV/BHK). A number of substances were active in both types of assays at concentrations below 1 microgram/ml; deoxypodophyllotoxin and beta-peltatin A methyl ether being the most potent compounds in all cases, with IC50 values in the range 2.5-4 ng/ml for the three neoplastic systems.
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PMID:Antineoplastic and antiviral activities of some cyclolignans. 839 Nov 45

A new oral type of 5-fluorouracil (5-FU) derivative possessed of both potent antitumor activity and less gastrointestinal (GI) toxicity was investigated and developed in the form of a combination of tegafur (FT), a masked form of 5-FU, and its two peculiar biochemical modulators. One is 5-chloro-2,4-dihydroxypyridine (CDHP), a new potent inhibitor of 5-FU degradation in vivo, and another is potassium oxonate (Oxo), a characteristic inhibitor of 5-FU phosphorylation, which distributes much higher in GI tract after p.o. administration. 5-FU levels in blood of rats following administration of FT, were markedly elevated and persisted for a long-time by co-oral CDHP corresponding to over 0.4 molar ratio to FT, like the case in continuous infusion of 5-FU, which resulted in an augmentation of antitumor efficacy in Yoshida sarcoma-bearing rats, although severe GI toxicity simultaneously occurred. To reduce 5-FU-induced toxicities such as diarrhea and body weight loss and to maintain the augmented antitumor activity, 0.5 to 2 molar Oxo was orally given to rats with one molar FT plus 0.4 molar CDHP. As a result, both severe GI injury and body weight loss were markedly inhibited by coadministration of 0.5 to 1.0 molar Oxo while high antitumor efficacy (about 90% inhibition of tumor growth) was maintained. However, such almost complete antitumor effect was reduced to about 50% inhibition of tumor growth by over 2 molar Oxo combined with one molar FT plus 0.4 molar CDHP. Based on these results, a novel 5-FU derivative, named S-1, was composed of one molar FT, 0.4 molar CDHP and one molar Oxo. S-1 showed an antitumor activity over 3-fold stronger than UFT (one molar FT plus 4 molar uracil) against Yoshida sarcoma and Sato lung carcinoma in rats and human colon carcinoma (KM12C) xenografted in nude rats when its minimum toxic dose was administered. Co-oral Oxo also significantly reduced the incidence of diarrhea and stomatitis induced by administration of FT-CDHP in beagle dogs. These results suggest that high antitumor activity and less GI toxicity of S-1 was brought about by the elevation in blood and tumor tissues and by selective decrease of 5-fluoronucleotides, an active metabolite of 5-FU, in GI tract.
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PMID:[Invention of a tumor-selective 5-fluorouracil derivative named S-1 by biochemical modulation of 5-fluorouracil]. 949 31

In our phase II study an acceptable and effective agent like cisplatin was used in combination with vinorelbine and gemcitabine in patients with non-small cell lung cancer (NSCLC). These two new cytostatic drugs have demonstrated, when used as a single-agent treatment, effective response rates (vinorelbine) and minimum toxicity (gemcitabine). The following schedule was used: (i) vinorelbine 25 mg/m2 on days 1 and 8; (ii) gemcitabine 1000 mg/m2 on days 1 and 8; and (iii) cisplatin 75 mg/m2 on day 8. The schedule was repeated every 21 days, with a maximum of six cycles per patient. A total of 31 patients with a mean Karnofsky performance status of 90% were evaluated and 29 of them were finally eligible. Of the patients, five (16.1%) were at stage IIIb and the remainder (83.9%) were at stage IV. The overall response rate was 65% (20 patients); six patients (19.4%) had complete response (CR) and 14 (45.2%) had partial response (PR). Two patients (6.5%) had stable disease and seven (22.6%) had progressive disease. The most notable toxicity was hematologic. Leukoneutropenia was mainly revealed after the third or fourth cycle and granulocyte-colony stimulating factor (G-CSF) was administered in 24 patients (77.4%). Mild anemia was found in almost all patients after the third or fourth cycle (Hb 10-11 g/dl) and eight patients (25.8%) required erythropoietin (EPO). Thrombocytopenia was more often observed compared with other known chemotherapeutic regimens; six patients (19.4%) had grade I thrombocytopenia and therapy was delayed in another four patients (12.9%) due to this complication. Non-hematologic toxicity was mild and well tolerated and consisted of alopecia (54.8%), nausea and vomiting (12.9%), constipation (12.9%), peripheral neuropathy (9.6%), diarrhea (6.5%), stomatitis (3.2%) and local phlebitis (3.2%). The examined combination provides us with one of the best overall responses rates reported, however at the cost of remarkable hematologic toxicity. Therefore, it would be better applied in patients with good performance status. The high response rates give us hope of using this combination as a neoadjuvant regimen.
Lung Cancer 1999 Jan
PMID:A phase II study with vinorelbine, gemcitabine and cisplatin in the treatment of patients with stage IIIb-IV non-small cell lung cancer (NSCLC). 1010 Jan 44

Polyethylene glycol-coated (pegylated) liposomal doxorubicin (PLD) is a new formulation of doxorubicin with peculiar pharmacokinetic and pharmacodinamic properties, a favorable toxic profile and a demonstrated activity in solid tumors. We tested PLD in locally advanced or metastatic NSCLC patients, progressed after a platinum-based first-line chemotherapy. PLD was administered at the dose of 35 mg/m(2) every 21 days. After the first six patients had been accrued, due to the low toxicity shown in the first six patients, the dose was escalated to 45 mg/m(2). Seventeen patients were enrolled in the study and were considered eligible for evaluation of toxicity and response. Stomatitis, palmar-plantar erythrodysaesthesia (PPE) and asthenia were the most common toxicities and affected approximately half of the treated patients. Stomatitis occurred in 8/17 patients and was grade 3-4 in three. PPE was seen in 9/17 and was grade 3 in one. In the group treated at the dose of 45 mg/m(2) PPE was more frequent and severe and required treatment delay in some cases. Other toxicities were equally distributed among the two groups. Hematological toxicity was not common and never reached grade 3-4. However, one patient with grade 2 leucopenia had pneumonia and died. Clinically evident heart failure was never recorded. Left ventricular ejection fraction was assessed in three patients after PLD treatment (in one case after the first course, due to the occurrence of atrial fibrillation, and in two cases after six courses) and was unchanged compared to pre-treatment assessment. One confirmed partial response was observed (5.8%); five patients (29.4%) had stable disease (including one minor response) and nine (52.9%) had disease progression. Median time to progression was 9.5 weeks, median survival 18.6 weeks. PLD at the doses employed in this study can be safely administered and has shown activity in platinum pretreated NSCLC patients.
Lung Cancer 2002 Jan
PMID:Single-agent pegylated liposomal doxorubicin (Caelix) in chemotherapy pretreated non-small cell lung cancer patients: a pilot trial. 1175 Jul 14

Based on the synergistic cytotoxicity demonstrated in vitro by topoisomerase I inhibitors followed by docetaxel and the feasibility of giving both drugs on a weekly schedule avoiding overlapping toxicities, we designed a phase I trial of weekly CPT-11 (irinotecan)/docetaxel to determine the dose-limiting toxicities (DLT) and the maximum-tolerated dose (MTD) of this combination. Eighteen patients with advanced solid tumors treated with at least one prior chemotherapy regimen were included in this trial. CPT-11 was administered as a 90-min (intravenous) IV infusion followed immediately by docetaxel as a 30-min IV infusion. Both drugs were given on days 1, 8 and 15 in 4-week cycles. Four escalating dose levels of CPT-11/docetaxel (level I: 60/20 mg/m(2), level II: 60/25 mg/m(2), level III: 70/25 mg/m(2), and level IV: 70/30 mg/m(2)) were studied. Forty-seven cycles were administered (range, 1-5 courses) with a median number of 2.6 cycles per patient. Grade 4 leukopenia was the DLT reached at dose-level IV (CPT-11/docetaxel 70/30 mg/m(2)). Four patients had grade 3 anemia at dose levels III (two patients) and IV (two patients), while grade 3/4 thrombocytopenia was not seen. Grade 3/4 non-hematologic toxicities included grade 3 diarrhea in two patients (dose levels II and IV), grade 3 asthenia in one patient (dose level II) and grade 3 stomatitis in one patient (dose level I). The recommended dose of this weekly schedule is CPT-11 70 mg/m(2) and docetaxel 25 mg/m(2). DLT of this regimen is leukopenia, although toxicity is manageable at the recommended dose level. The activity of this regimen is being evaluated in a phase II study in previously treated patients with advanced non-small cell lung cancer.
Lung Cancer 2002 Aug
PMID:Phase I study of weekly CPT-11 (irinotecan)/docetaxel in patients with advanced solid tumors. 1214 Jan 45

The primary target of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is epithelial cells in the respiratory and intestinal tract. The cellular receptor for SARS-CoV, angiotensin-converting enzyme 2 (ACE2), has been shown to be localized on the apical plasma membrane of polarized respiratory epithelial cells and to mediate infection from the apical side of these cells. Here, these results were confirmed and extended by including a colon carcinoma cell line (Caco-2), a lung carcinoma cell line (Calu-3) and Vero E6 cells in our analysis. All three cell types expressed human ACE2 on the apical membrane domain and were infected via this route, as determined with vesicular stomatitis virus pseudotypes containing the S protein of SARS-CoV. In a histological analysis of the respiratory tract, ACE2 was detected in the trachea, main bronchus and alveoli, and occasionally also in the small bronchi. These data will help us to understand the pathogenesis of SARS-CoV infection.
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PMID:Analysis of ACE2 in polarized epithelial cells: surface expression and function as receptor for severe acute respiratory syndrome-associated coronavirus. 1669 Sep 35

A phase I/II trial of TS-1 combined with gemcitabine was designed to determine the maximum tolerated dose (MTD) and recommended dose (RD) and to evaluate the efficacy and toxicity in elderly patients with advanced non-small cell lung cancer (NSCLC). Patients older than 70 years of age received TS-1 orally b.i.d. on days 1-14 and gemcitabine intravenously on days 8 and 15 every 4 weeks. In phase I (n=22), each cohort received escalating doses of TS-1 (30-40 mg/m(2) b.i.d.) and gemcitabine (800-1000 mg/m(2)); MTD was 40 mg/m(2) b.i.d. TS-1 and 1000 mg/m(2) gemcitabine; RD was 30 mg/m(2) b.i.d. TS-1 and 1000 mg/m(2) gemcitabine. Dose-limiting toxicities included a grade 3 infection, skin toxicity, and stomatitis. In phase II (n=37), the overall response rate was 27% (90% confidence interval (CI): 15-42%) and the median time to progression and overall survival were 4.2 months (90% CI: 3.2-5.7) and 12.9 months (90% CI: 10.4-14.7), respectively. The most common grade 3 or higher toxicity was neutropenia (45.9%), and thrombocytopenia was observed in 13.5% of patients. Two cases each of grade 3 pneumonitis and skin toxicity were observed, but nonhematological toxicities occurred at generally low frequencies. TS-1 with gemcitabine is a promising doublet regimen in elderly patients with advanced NSCLC with acceptable toxicities.
Lung Cancer 2010 Aug
PMID:Phase I/II trial of gemcitabine plus oral TS-1 in elderly patients with advanced non-small cell lung cancer: Thoracic oncology research group study 0502. 2015 12

S-1, an oral 5-fluorouracil derivative, is effective against advanced non-small cell lung cancer (NSCLC) with mild toxicity and synergistic effects with radiation in preclinical trials. In this phase I study, we evaluated the dose-limiting toxicity and recommended dose of S-1 for a future phase II study when administered concurrently with thoracic radiation (total dose of 60 Gy at 2 Gy per daily fraction) in elderly patients (>75 years old) with localized advanced NSCLC. S-1 was administered on days 1-14 and 29-42 at the following dosages: 60, 70, and 80 mg/m(2)/day. Twenty-two previously untreated patients were enrolled in this study. Dose-limiting toxicity included febrile neutropenia, thrombocytopenia, stomatitis, and pneumonitis. One patient had grade 5 radiation pneumonitis. No other patient experienced radiation pneumonitis or esophagitis exceeding grade 2. The recommended dose for S-1 was determined to be 80 mg/m(2)/day, which produced an overall response rate of 75% (n=12). The median progression-free survival time was 11.5 months (95% confidence interval: 7.1-15.8 months) with a median follow-up time of 27.9 months. These results indicate that concurrent treatment with S-1 and thoracic radiation is a feasible option for NSCLC in the elderly. A phase II study is currently under way.
Lung Cancer 2011 Jan
PMID:A phase I study of S-1 with concurrent thoracic radiotherapy in elderly patients with localized advanced non-small cell lung cancer. 2045 Dec 85


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