Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dipyridamole, an inhibitor of nucleoside transport, increases the activity of 5-fluorouracil in a dose-dependent manner. The purpose of the present study was to determine whether dipyridamole with 5-fluorouracil and leucovorin gave an improved therapeutic outcome. Sixty patients entered in the present pilot study had previously received 5-fluorouracil (450 mg/m2) and leucovorin (100 mg/m2), every week, and relapsed during this treatment, which ended at least 6 weeks prior to study entry. Dipyridamole was administered at three different dosing schedules (DS) and methods of administration in three groups of patients. DS I: dipyridamole, 30 mg/m2 in normal saline solution, in 90 min iv infusion, followed by leucovorin, 100 mg/m2 iv push, followed by 5-fluorouracil, 450 mg/m2 in normal saline solution, in 60 min iv infusion, dipyridamole tablets (75 mg) every 12 hrs, continuously during the time of chemotherapy. DS II: dipyridamole, 50 mg/m2 in normal saline solution, in 90 min iv infusion, and the rest was the same as DS I. DS III: without oral dipyridamole, patients received dipyridamole (50 mg/m2) iv in the same manner as in DS I and II. Treatment was continued until tumor progression or unacceptable toxicity. All patients (n = 60) entered in the present study were assessable for response and toxicity. No complete response was observed. No patient at DS I responded, whereas 2 patients at DS II and 3 at DS III had a partial response (P <0.1). Stable disease was found with DS I (n = 1), DS II (n = 8) and DS III (n = 9) (P <0.01). More patients progressed at DS I (n = 19) than at DS II (n = 10) and DS III (n = 8) (P <0.0007). The median duration of response was 11 weeks (range, 8-16). Time to progression was 17 weeks for DS I, 15 weeks (range, 10-19) for DS II, and 14 weeks (range, 11-21) for DS III (P = 0.43). Median survival did not differ significantly between DS I (29 weeks; range, 14-48), DS II(31.5 weeks; range, 17-63) and DS III (36 weeks; range, 16-58) (P = 0.2). Neutropenia was most severe with DS I (grade 2, P<0.01) and DS II (grade 1, P<0.05) and nausea/vomiting with DS I (grade 0, P < 0.0005, grade 1, P <0.0002, grade 2, P <0.02) and DS III (grade 3, P<0.0009). Diarrhea was most severe in DS II (grade 3, P <0.005). Mucositis was increased in DS II (grade 0, P <0.008), anorexia in DS II (grade 0, P <0.032) and fatigue in DS I (grade 0, P <0.003). More patients in DS I than with the other two DS experienced headache (P <0.044). According to the response achieved at DS III (15% partial response and 45% stable disease) and the toxicity which was well tolerated mainly in this DS (except for nausea and vomiting grade 3, P <0.009), it can be stated that DS III is the appropriate dose and the simplest schedule of administration (administration of dipyridamole during therapy only). In conclusion, it appears that dipyridamole might still have a role in enhancing the clinical activity of drugs involved in the inhibition of the thymidylate synthetase biochemical pathway and its activity in combination with these agents (5-fluorouracil + leucovorin) as frontline treatment should therefore be explored in future phase II studies.
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PMID:Leucovorin + 5-fluorouracil plus dipyridamole in leucovorin + 5-fluorouracil-pretreated patients with advanced colorectal cancer: a pilot study of three different dipyridamole regimens. 1176 78

The aim of the present study was to investigate the expression of thymidylate synthase (TYMS) in the primary foci and metastatic lymph nodes of low-grade glioma, and to analyze the function of TYMS in the lymph node metastases from low-grade glioma. The study included 93 cases of surgically resected and pathologically confirmed low-grade glioma, form patients treated at Huaihe Hospital of Henan University (Kaifeng, China). The following clinical data was obtained from each patient: Gender, age, subjective symptoms (dizziness, headache, a feeling of pressure in the head, etc.), site of disease, tumor type, pathological stage, degree of differentiation and lymph node involvement. The surgically resected gliomas and dissected cervical lymph nodes were immunohistochemically stained, and DNA was extracted from the tumor and lymph node tissues samples for polymerase chain reaction sequencing and amplification. The expression of TYMS in the primary foci and metastatic lymph nodes of low-grade glioma was examined. Additionally, the association between pathological features and the postoperative survival rate of the patients was analyzed. The primary lesions of all 93 cases exhibited positive TYMS expression and 43/157 (27.39%) lymph nodes exhibited positive TYMS expression. Factors that significantly influenced the postoperative survival rate of the patients, included the metastasis of the cervical lymph nodes (P<0.01), the number of dissected cervical lymph nodes (P<0.01) and the degree of differentiation (P<0.05). The metastasis of the cervical lymph nodes was the only independent risk factor affecting postoperative disease-free survival. The risk of recurrence in patients with metastasis of the cervical lymph nodes was 6.3-fold higher than in those without metastasis (P<0.01). Thus, the results of the present study provide a theoretical basis for accurately predicting the prognosis of patients with low-grade malignant brain glioma, reducing the conjecture involved in selecting postoperative treatment strategies and improving therapeutic efficacy.
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PMID:Expression of TYMS in lymph node metastasis from low-grade glioma. 2662 11