Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The enterochromaffin (EC) cell system is distributed throughout the entire gastrointestinal tract. Enterochromaffin cells are the major source of intestinal serotonin (5-HT), but separate subpopulations of EC cells may synthesize and store peptides as substance P (SP), motilin, and enkephalin as well. Of special interest is that 5-HT and SP, which may coexist in EC cells, have several functional similarities, i.e., inhibition of gastric acid secretion, stimulation of intestinal motility, and secretion of water and electrolytes. Carcinoid tumors are derived from the gut endocrine system. Depending on site of origin, carcinoids are divided into foregut, midgut, and hindgut derivatives with different clinical symptoms. A common biochemical feature of midgut carcinoids is the production of 5-HT and SP. Histochemically, midgut carcinoids are characterized by the argentaffin reaction--a direct reduction of silver salts owing to 5-HT. Specific antisera for the immunocytochemical demonstration of secretory products are available as well. Despite their relative infrequency, carcinoids are the most common small intestinal tumors. The common appendix tumors generally have a benign clinical course, whereas the small intestinal tumors have different growth patterns and frequently metastasize with increasing size, and may thus give rise to the carcinoid syndrome (diarrhea, facial flush, right-sided cardiac valvular disease, and asthma). Carcinoid symptoms first appear when hepatic inactivation of 5-HT is exceeded, unless the carcinoid has an extraintestinal localization, for example, ovarian lesions may elicit symptoms in the absence of hepatic disease owing to direct secretion into systemic circulation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serotonin and carcinoid tumors. 241 66

We have previously established that type I interferon (IFN), a mixture of alpha- and beta-IFN, augments the antitumor activity of alpha-difluoromethylornithine (DFMO), an inhibitor of polyamine biosynthesis, against B16 melanoma. The objective of the present investigation was to extend these earlier observations to metastatic Lewis lung carcinoma and to determine specifically which component(s) of type I IFN potentiates the antitumor activity of DFMO. Furthermore, we wanted to determine whether type II (gamma) IFN can also potentiate the antitumor activity of DFMO. Treatment of animals bearing Lewis lung carcinoma with DFMO, 2% in drinking water (3 g/kg/day), or IFN-alpha/beta (1000 units/mouse) given subcutaneously on alternate days for a total of ten doses alone resulted in 42 and 5% inhibition of tumor growth, respectively. A combination of DFMO and interferon brought about complete elimination of tumors in 12 of the 18 animals, and 94% inhibition of tumor growth in the remainder. DFMO or type I IFN administered alone caused 94 and 26% inhibition of metastasis, respectively. Combination treatment with these two agents resulted in complete elimination of visible metastases. Treatment of mice bearing B16 melanoma with DFMO resulted in 81% inhibition of tumor growth compared to controls. The administration of interferons alone resulted in tumor growth inhibition of 15, 3, 1, and 43% for type I, alpha-, beta-, and gamma-interferons, respectively. Treatment of animals with combination of DFMO and various interferons resulted in inhibition of 94, 93, 86, and 94% of B16 tumor growth for type I, alpha-, beta-, and gamma-interferons, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of murine alpha-, beta-, and gamma-interferons in combination with alpha-difluoromethylornithine, an inhibitor of polyamine biosynthesis, on the tumor growth and metastasis of B16 melanoma and Lewis lung carcinoma in mice. 249 64

Successful therapy of tumors with lymphokine-activated killer (LAK) cells is presumably dependent on their cytolytic potential and their gaining access to the target cells through the microcirculation. The latter process involves dissemination through the microvessels, adhesion to the venular walls, and extravasation through them, all of which depend on the size and deformability of these effector cells. The aim of the present study was to measure the deformability of these cells quantitatively using a micropipet aspiration technique and to analyze the deformation data using a mathematical model which yielded parameters indicative of the rigidity of the cell membrane and the cytoplasm. Adherent rat LAK cells, consisting of a highly purified population of interleukin 2-activated large granular lymphocytes, with high cytotoxicity were obtained by a recently developed method. The deformability characteristics of fresh large granular lymphocytes (mean diameter, 7.2 microns), LAK cells (11.0 microns), fresh T-cells (6.6 microns), and concanavalin A-activated T-cells (9.7 microns) were compared. LAK cells were significantly less deformable than other cell types [about one-half at an aspiration pressure of -25 mm of H2O (P less than 0.001)]. Cell deformability was independent of cell size and calcium content of the medium. Analysis of the data with the mathematical model suggested that both the cell membrane and the cytoplasmic factors contributed to the rigidity of LAK cells. This increased rigidity coupled with their large cell size may explain high retention of LAK cells in the lungs immediately after i.v. injection and a reduction in tumor targeting due to external radiation. Finally, these results suggest that LAK cell therapy might be enhanced by intraarterial injection into an organ infiltrated by tumor metastases.
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PMID:Low deformability of lymphokine-activated killer cells as a possible determinant of in vivo distribution. 250 Feb 33

Menogaril, an anthracycline analog of nogalamycin, is reported to have greater cytotoxicity against certain malignant cell lines and less cardiotoxicity in rabbits than doxorubicin. To evaluate the possible therapeutic benefit of this drug, we studied menogaril in 21 patients with metastatic sarcomas who had received no prior chemotherapy. Menogaril was administered intravenously over 1 h every 3-4 weeks at a dose of 200 mg/m2 in 500 ml of 5% dextrose in water. One patient experienced a partial regression of pulmonary metastases from malignant fibrous histiocytoma of bone (response rate of 5% with 95% confidence interval of 0.1-23.8%). Two additional patients experienced minor reductions in tumor size. The remaining 18 patients had no improvement from menogaril. The median time to disease progression was 7 weeks in all patients treated. Toxicity was acceptable, consisting primarily of leukopenia with 12 patients (57%) and 19 patients (90%) developing nadir leukocyte counts less than 2000 and 3000/microL, respectively. Cardiac toxicity was not encountered; however, only seven patients received greater than or equal to 3 cycles of menogaril. We conclude that menogaril does not appear to be useful at this dose and schedule in the treatment of metastatic sarcomas despite the use of near maximal doses in patients with no prior chemotherapy exposure.
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PMID:Evaluation of menogaril in patients with metastatic sarcomas and no prior chemotherapy exposure. 252 59

Nineteen patients with isolated colorectal liver metastases were preoperatively evaluated with five hepatic imaging studies. The results of these studies were correlated with operative findings. One study involved the use of EOE-13, an intravenously administered lipid contrast agent that enhances liver parenchyma on computed tomography (CT) scans (EOE-CT). Another study, arterial portography (AP-CT), was performed with injection of a water-soluble contrast agent into the superior mesenteric artery during CT scanning. Delayed CT scanning (DS-CT) was completed 4 hours after AP-CT. In addition, T1- and T2-weighted magnetic resonance imaging (MRI) (T1-MRI, T2-MRI) scans were done. All patients subsequently underwent laparotomy with identification of 78 lesions. A lesion-by-lesion analysis revealed that the sensitivity of EOE-CT (83%), AP-CT (78%), DS-CT (82%), and T1-MRI (84%) was comparable. T2-MRI had a significantly lower sensitivity (64%) compared with EOE-CT, DS-CT, and T1-MRI. The false-positive rate for AP-CT was 31%, which was significantly higher than that of all other studies. The T1-MRI examination had the lowest false-positive rate and proved to be the best hepatic imaging study in the detection of colorectal metastases. EOE-CT and DS-CT were comparable, whereas AP-CT and T2-MRI proved to be inferior tests.
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PMID:Prospective evaluation of hepatic imaging studies in the detection of colorectal metastases: correlation with surgical findings. 253 65

Relaxation times and relative proton densities were calculated from magnetic resonance examinations of the liver in eight patients with liver metastases from neuroendocrine tumours. Single, spin-echo sequences with eight different repetition times and a four-echo sequence were used to calculate T1 and T2 in tumour and normal liver, and the proton density tumour-liver quotient, before and during treatment with interferon. Changes over time of these parameters were compared with variations in tumour marker levels and changes in size and number of the metastases. During therapy, six out of eight cases showed a decrease in tumour T1, five responding to therapy and one with stationary disease, while the two patients with progressive disease showed unchanged tumour T1. The proton density quotient also decreased in a corresponding way, indicating a change in water content in tumours responding to interferon therapy. No significant change in liver T1, tumour T2 or liver T2 occurred in any patient. It is thus possible to perform reliable measurements of relaxation parameters over time, which may be valuable in follow-up of tumour treatment.
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PMID:Relative proton density and relaxation times in liver metastases during interferon treatment. 254 Aug 66

We reviewed available literature on the effects of inorganic arsenic on the skin to determine the potential hazards and to collate information regarding dosage and exposure to the incidence of skin cancer. Arsenic intake may result from occupational or medicinal exposure, or from drinking well water in areas with high arsenic levels in the soil. Arsenic causes a variety of benign skin lesions including hyperpigmentation and hyperkeratosis. Some hyperkeratotic lesions and squamous cell carcinomas in situ may progress to invasive carcinoma; other invasive squamous cell carcinomas will develop de novo. These cutaneous squamous cancers may metastasize; mortality is low, but has been reported. Locally invasive but non-metastasizing basal cell carcinomas may arise as well. These lesions occur in a characteristic pattern of distribution and are usually multiple. Observers reporting medicinally administered arsenic have described dose-response relationships between the amount of arsenic ingested and the frequency of various skin lesions. For arsenic found in drinking water, however, there is more controversy regarding the doses and exposure times necessary for cutaneous toxicity.
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PMID:Arsenic-induced skin toxicity. 266 2

After cystoprostatectomy for cancer of the bladder 43 men were provided with a detubularized, low pressure ileal reservoir (Kock pouch) connected to the urethra. Reflux was prevented by an intussusception valve. There was no operative mortality and few early complications. At followup the mean postoperative observation time was 13 months, with a range of 5 to 20 months. Late complications included manifestations of local tumor recurrence or distant metastases in 9 patients within 6 months postoperatively, which made adequate functional evaluation impossible. In 18 patients reflux to the upper urinary tract due to eversion or sliding of the antireflux valve occurred at various postoperative intervals. In 16 of these patients incontinence developed as a consequence of the reflux. Surgical correction of the failing antireflux valve restored reflux prevention and continence. Within 3 to 6 months the capacity of the reservoirs had reached an ultimate volume of approximately 600 ml. Pressure waves exceeding 40 cm. water seldom occurred in the mature reservoirs and then only at high filling volumes. The mean urethral resting resistance to flow was 64 cm. water. The configuration and function of the upper urinary tract improved or stabilized postoperatively. Of 34 evaluable patients 30 were continent during the day with a voiding frequency of 3 to 5 times and dry at night with a frequency of 0 to 2.
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PMID:Replacement of the bladder by the urethral Kock pouch: functional results, urodynamics and radiological features. 270 96

Neoplasms of preputial gland and skin were obtained from Fischer 344 male rats on lifetime drinking water studies of the benzidine congener 3,3'-dimethoxybenzidine, C.I. Direct Blue 15 or C.I. Acid Red 114, bisazobiphenyl dyes derived from 3,3'-dimethoxybenzidine and 3,3'-dimethylbenzidine. Portions of these well differentiated neoplasms were implanted into the left mammary fat pad of Fischer 344 male recipients. The rate of growth, presence of local invasion and distant metastases, and morphologic features were observed following 4 serial transplantations. All implants appeared early, grew rapidly, and were histomorphologically similar to the original neoplasms. Metastases from transplants were observed with both preputial gland and skin tumor lines in serial passages. The transplantation results confirm the malignant nature of these neoplasms.
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PMID:Transplantation studies of preputial gland and epithelial skin neoplasms derived from benzidine-based dye carcinogenicity assays in Fischer 344 male rats. 274 36

The administration of interleukin 2 (IL-2) to mice and humans is limited by the induction of a dose-dependent increase in vascular permeability causing a vascular leak syndrome (VLS). We have investigated the impact of the injection of recombinant interleukin 1 alpha (IL-1 alpha) on the VLS induced by IL-2 by measuring the extravasation of 125I-albumin into tissues and by assessing wet and dry lung weights. IL-1 alpha alone did not induce any significant extravasation of radiolabeled albumin. IL-2 alone, however, caused a significant increase in the extravasation compared to control lungs. IL-1 alpha injection along with IL-2 significantly reduced the IL-2-induced extravasation of radiolabeled albumin [9,886 +/- 533 (SEM) cpm were observed in IL-2 and IL-1 alpha-treated lungs compared to 14,172 +/- 2,628 cpm in lungs treated with IL-2 alone (P less than 0.02)]. IFN-alpha in combination with IL-2 produced more severe vascular leakage than caused by IL-2 alone. IL-1 alpha also significantly decreased (P less than 0.05) the vascular permeability induced by the combination of IFN-alpha and IL-2. We observed 44,811 +/- 13,131 cpm in IFN-alpha- and IL-2-treated lungs compared to 18,350 +/- 2,622 cpm in IFN-alpha-, IL-2-, and IL-1 alpha-treated lungs. The IL-2- and IFN-alpha-induced increase in lung water weight was also reduced significantly by the addition of IL-1 alpha. The decrease in vascular leakage was dependent on the dose and timing of IL-1 alpha administered. When recombinant IL-1 alpha was given as a single i.p. injection, 24 h before the injection of IL-2 (or Hanks' balanced salt solution) or IL-2 and IFN-alpha no abrogation of the VLS was observed. Although IL-1 alpha decreased VLS significantly in mice treated with IFN-alpha and IL-2 the survival of mice was not improved by the simultaneous administration of IL-1 alpha. Histologically, treatment with IFN-alpha and IL-2 produced marked perivascular and intraalveolar edema which was completely eliminated by the addition of IL-1 alpha. However, some perivascular edema in IL-1 alpha-treated mice remained which was equivalent to that caused by IL-2 alone. Treatment of MCA-106 induced pulmonary metastases was enhanced by the administration of IFN-alpha and IL-2 together.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Decrease in interleukin 2-induced vascular leakage in the lungs of mice by administration of recombinant interleukin 1 alpha in vivo. 278 61


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