Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q96S42 (nodal)
 22,877 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Between June 1982 and July 1990, 55 patients (41 with bladder cancers and 14 with renal pelvic or ureteral cancers) who had undergone radical extirpative surgery and/or node dissection for pathological stage pT2-4 and/or nodal disease received adjuvant chemotherapy consisting of cisplatin alone or in combination with other agents. In all, 26 of the bladder-cancer patients also received preoperative chemotherapy consisting of arterial infusion of cisplatin, mitomycin C, and Adriamycin. Adjuvant chemotherapy was performed according to the following protocol. Between June 1982 and July 1987, 30-50 mg/m2 cisplatin either alone or in combination with Adriamycin and 5-fluorouracil (CAF) was given to 35 patients in an induction and maintenance setting for 1 year. After July 1987, short-course cisplatin (70 mg/m2) or cisplatin, etoposide, and Adriamycin combination chemotherapy (CVA) was given to 20 patients. Of the 55 patients, 38 are alive and show no evidence of disease, three are alive with disease, 13 have died of their disease, and 1 has died of an unrelated cause. The 5-year survival of all patients was 65.1%. The survival of the 20 patients who were treated after July 1987 was better than that of the 35 patients who were treated before June 1987. Local recurrence and/or distant dissemination occurred in 16 patients, 13 of whom died of cancer progression. Nausea and vomiting and anorexia occurred in most patients during the administration of cisplatin. Mild to moderate myelosuppression developed in patients who received CAF or CVA combination chemotherapy. Although adjuvant chemotherapy combined with radical surgery seemed to be effective in cases with a pathological stage of pT3a or less, more intensive pre- or postoperative chemotherapy is needed to improve the poor prognosis of patients with deeply invasive uroepithelial cancer.
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PMID:Results of adjuvant chemotherapy for invasive uroepithelial cancer. 139 19

Mexiletine is a Class IB antiarrhythmic which has basic and clinical electrophysiologic properties similar to lidocaine. Like other Class I antiarrhythmic agents, mexiletine blocks the rapid inward sodium current responsible for phase 0 of the action potential. It has been noted in the clinical electrophysiology laboratory to have minimal effect on sinus node function and AV nodal and His-Purkinje system conduction. Pharmacokinetic studies have shown that oral absorption is rapid with bioavailability of 80-90%. Mexiletine is predominantly metabolized by the liver with elimination half-life of 9 to 12 hours. The antiarrhythmic effects of the primary drug's metabolites remain to be defined. Hemodynamic studies have shown mexiletine to have a lesser negative inotropic effect than procainamide or disopyramide. Although mexiletine as a single agent successfully suppresses 60 to 80% of spontaneous ventricular arrhythmias, it has lower efficacy in suppression of induced ventricular arrhythmias. Multiple studies have shown that as monotherapy mexiletine is effective in preventing the induction of ventricular tachycardia in approximately 20% of patients. When used in combination with a Class IA antiarrhythmic drug for suppression of induced ventricular arrhythmias, multiple investigators have reported greater efficacy. Neurological side effects (tremor, dizziness, memory loss) occur in approximately 10% of patients while gastrointestinal side effects (nausea, anorexia, gastric irritation) occur in up to 40% of patients. Proarrhythmia or other serious toxicity from the drug is uncommon.
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PMID:Mexiletine: pharmacology and therapeutic use. 218 14

Seventeen patients with advanced uroepithelial cancer were treated with M-VAC regimen. Out of 17 patients, 10 were evaluable but 7 were not. Evaluable 10 patients comprised 7 males and 3 females ranging in age from 50 to 83 (median 69.5). The number of performed cycle ranged from 1 to 3 and the performance status was from 0 to 2. Complete response (CR) was observed in 2, partial response (PR) in 4 and no change (NC) in 4 out of 10 patients. The efficacy rate was 60%. Every site of the tumor responded well and CR was observed, in particular, in nodal and pulmonary metastasis. One of 2 CR patients relapsed and died. One of 4 PR patients died of cancer, 2 are alive with regrowing tumors and the other is alive without disease after surgical removal of all residual tumors. The same regimen was carried out again to 2 patients with regrowing tumors, but no response was observed. As to drug toxicity in total 31 cycles (17 patients), gastrointestinal disturbances, anorexia and alopecia were reversible but hematological toxicity was serious and 3 of 17 (17.6%) died of severe bone marrow suppression. M-VAC is an effective regimen for advanced uroepithelial cancer, but bone marrow suppression was serious. Therefore, special attention should be paid to myelosuppression.
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PMID:[Combination chemotherapy of M-VAC (methotrexate, vinblastine, adriamycin and cisplatin) for advanced uroepithelial cancer]. 235 21

Based upon the in vitro synergistic activity of interferon-beta (IFN-beta) and interferon-gamma (IFN-gamma) observed in melanoma cells, we initiated a Phase II trial using the combination to determine the clinical antitumor efficacy in patients with advanced disease. Fifteen patients with metastatic malignant melanoma were given 2,000 micrograms of recombinant IFN-gamma (rIFN-gamma) (Biogen) intravenously (i.v.) over 10 min, followed by a 10 min i.v. injection of 30 million units of recombinant IFN-beta (rIFN-beta ser) (Triton) 3 x/week. Six patients had skin, soft tissue, nodal, or subcutaneous metastases, 6 had visceral disease only, and 3 had both. Seven patients had received prior treatment, including chemotherapy (6), radiotherapy (3), and/or immunotherapy (3). Side effects included typical IFN constitutional symptoms such as anorexia, fatigue, nausea, and myalgias, but were not dose limiting. The mean drop in the white blood cell count (WBC) following 1 month of therapy, compared to baseline, was 3.3 x 10(3)/mm2 (p = 0.002); the mean increase in SGOT was 24.1 U/l (p less than 0.001). One patient had a dose reduction for Grade III anorexia and fatigue which did not resolve with repeated treatment. One patient with liver metastases had radiographical and clinical stabilization of his disease for 1 year. No responses were seen. The median time to progression was 6 weeks. Two patients' tumors were evaluable in the human tumor colony forming assay (HTCFA) and were markedly sensitive to the antiproliferative effects of IFN combinations. Both patients, however, failed to respond clinically.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phase II trial of a combination of interferon-beta ser and interferon-gamma in patients with advanced malignant melanoma. 314 69

Increasing recognition of the importance of calcium in the pathogenesis of cardiovascular disease has stimulated research into the use of calcium channel blocking agents for treatment of a variety of cardiovascular diseases. The favorable efficacy and tolerability profiles of these agents make them attractive therapeutic modalities. Clinical applications of calcium channel blockers parallel their tissue selectivity. In contrast to verapamil and diltiazem, which are roughly equipotent in their actions on the heart and vascular smooth muscle, the dihydropyridine calcium channel blockers are a group of potent peripheral vasodilator agents that exert minimal electrophysiologic effects on cardiac nodal or conduction tissue. As the first dihydropyridine available for use in the United States, nifedipine controls angina and hypertension with minimal depression of cardiac function. Additional members of this group of calcium channel blockers have been studied for a variety of indications for which they may offer advantages over current therapy. Once or twice daily dosage possible with nitrendipine and nisoldipine offers a convenient administration schedule, which encourages patient compliance in long-term therapy of hypertension. The coronary vasodilating properties of nisoldipine have led to the investigation of this agent for use in angina. Selectivity for the cerebrovascular bed makes nimodipine potentially useful in the treatment of subarachnoid hemorrhage, migraine headache, dementia, and stroke. In general, the dihydropyridine calcium channel blockers are usually well tolerated, with headache, facial flushing, palpitations, edema, nausea, anorexia, and dizziness being the more common adverse effects.
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PMID:Differential effects of 1,4-dihydropyridine calcium channel blockers: therapeutic implications. 332 59

Peripheral lymph node enlargement was found in 14 of a series of 132 feline lymph node biopsy specimens. Six of nine cats tested had antibodies for feline leukemia virus (FeLV). Half of the cats were clinically normal while the remainder had fever, lethargy, anorexia, and hepatosplenomegaly. There was severe distortion of lymph nodal architecture with variable loss of discernible follicles and sinuses. Histiocytes, lymphocytes, immunoblasts, and plasma cells were present in expanded paracortical regions which encroached on, and occasionally effaced, lymphoid follicles. Postcapillary venules were numerous and prominent throughout the paracortex. The lymphadenopathy was most commonly transient (86% of cases) with subsequent development of lymphoma in one cat. Lymph nodes from seven kittens with experimental FeLV infection were compared with spontaneously enlarged lymph nodes; four of seven had B and T lymphocyte hyperplasia with normal nodal architecture. Three had partial loss of nodal architecture as a result of expanded paracortical regions populated largely by histiocytes and lymphocytes. Proliferation of postcapillary venules was not prominent in nodes from FeLV-infected cats. The cause of spontaneous lymph node hyperplasia of young cats was not determined. However, the similarity of lesions to those of kittens with experimental FeLV infection and the association with FeLV by serologic tests in six of nine cats suggest that this retrovirus may be involved in the pathogenesis of the lesion.
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PMID:Distinctive peripheral lymph node hyperplasia of young cats. 375 Jul 32

Twenty-one evaluable patients with metastatic breast cancer received three pulses of intravenous cyclophosphamide, escalating from 1.5 g/m2 to 2.5 g/m2 in the second and third courses. There were eight partial remissions (34.7%), but most were of short duration. All responding patients had soft tissue or nodal disease, but additional sites of response were bone (three cases), liver and lung (one case each). Marked leucopaenia (median WBC 0.7 X 10(9)/L) occurred 10-12 days after the higher doses (2.5 g/m2) and was associated with nine episodes of severe infection in five patients. Marked vomiting and anorexia led to significant weight loss (mean 4.5 kg) in half the patients, and alopecia was universal. In metastatic breast cancer cyclophosphamide seems to have a shallow dose response curve and high intermittent dosage seems to have no advantage over chronic daily administration.
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PMID:Intermediate dose single agent cyclophosphamide chemotherapy of advanced breast cancer. 661

An analysis was performed of 229 cases of carcinoma of the stomach presenting between 1970 and 1975 and followed up until 1980. The average age of the patients was 67 years with a range of 24 to 96 years. The predominant symptoms were weight loss, epigastric pain, anorexia, vomiting and an abdominal mass of two of 18 months duration. All cancers were adenocarcinomata, most commonly in the distal third of the stomach; most were bulky (T3) on diagnosis and of poor histological differentiation. Some tumours had not spread to nodes but most had nodal involvement of the first and second order. Over half showed evidence of wide-spread dissemination at presentation. The operative mortality of all procedures including curative resection, palliative resection and by-pass was high, reflecting the high exploration rate (81.6%), high resection rate (56%) and the extent and hazards of major operation. Total gastrectomy was associated with twice the operative mortality of subtotal gastrectomy. Five year survival was in each case 17.3% and 16.3% respectively but it should be noted that the larger, more bulky and infiltrative tumours could not have been dealt with by anything less than total gastric resection. Average survival time in the "curative" surgery group was 27.9 months and of all 229 patients presenting, only 11 (4.8%) were alive after five years. Factors which may lead to improvement in this dismal outlook are discussed. Earlier diagnosis and multimodal chemotherapy as an adjunct to traditional surgery appear to offer the greatest prospects of improvement.
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PMID:Carcinoma of the stomach: the need for a new approach. 695 9

The purpose of this pilot study was to evaluate the acute gastrointestinal morbidity of adjuvant radiotherapy (RT) for Stage I seminoma of the testis. Ten Stage I patients receiving para-aortic and ipsilateral pelvic nodal (dog-leg) RT provided a toxicity baseline (group A). Twenty Stage I patients, randomized to dog-leg RT or para-aortic RT (10 per group) were further randomized to received prophylactic ondansetron or expectant therapy with metoclopramide (group B). Daily patient-completed questionnaires evaluated acute toxicity. In group A (n = 10), nausea, vomiting, diarrhoea and abdominal discomfort were experienced in 90%, 80%, 70% and 90% respectively. Antiemetic and antidiarrhoeal agents were required in 70% and 10% respectively, with good response. For group B (n = 20), the overall incidences of nausea, vomiting diarrhoea and abdominal discomfort were 80%, 45%, 60% and 80% respectively. The ondansetron group experienced less nausea (P = 0.02) and less vomiting (P = 0.06). Both reduced field size and ondansetron groups appeared to have less diarrhoea (P = 0.06). The use of antiemetics in the expectant therapy groups resulted in at least a two-level reduction of toxicity grade in 86% of patients. A high incidence of lethargy, anorexia and headaches was noted for all groups. The incidence of headaches was not increased with ondansetron. Dog-leg RT for Stage I seminomas is associated with readily demonstrable gastrointestinal tract (GIT) toxicity. The number of patients in this study is too small to produce definitive results, but there appears to be reduced GIT toxicity with prophylactic antiemetics. The effect of reduced RT fields has been assessed further in the MRC randomized trial of field sizes (TE10).
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PMID:The effect of antiemetics and reduced radiation fields on acute gastrointestinal morbidity of adjuvant radiotherapy in stage I seminoma of the testis: a randomized pilot study. 931 92

A 77-year-old woman complaining of anorexia and nausea was referred to the hospital with a diagnosis of advanced gastric cancer. The patient also had congestive heart failure with atrial fibrillation and severe hypoproteinemia. Proteinuria, hypoproteinemia and other laboratory data suggested that she had nephrotic syndrome. Total protein level was 4.6 g/dl and albumin level was 1.6 g/dl. In order to avoid postoperative complications such as wound dehiscence, anastomotic leakage and so on, careful pre- and post-operative management of nephrotic syndrome is necessary. Administration of albumin and fresh frozen plasma regimen was continued after the operation. Urinary protein level started to decrease after subtotal gastrectomy. Histological examination revealed moderately differentiated tubular adenocarcinoma with nodal metastases. Her post-operative course was uneventful. Although the signs and symptoms of nephrotic syndrome did not improve immediately, twelve months after operation she has become well and has no symptoms of ascites and hypoproteinemia.
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PMID:A case of gastric cancer with nephrotic syndrome. 978


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