Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0000737 (abdominal pain)
 31,184 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ten patients with ovarian cancer refractory to conventional therapy were treated with intraperitoneal (i.p.) recombinant interleukin-2 (rIL-2) and lymphokine-activated killer cells (LAK). The 28-day protocol consisted of 6 priming i.p. rIL-2 infusions on days 0, 4, 6, 8, 10, and 12. Leukapheresis was performed for mononuclear cell collection on days 15, 16, 17, and 18 and lymphokine-activated killer cells were given i.p. with the rIL-2 on days 19 and 21. Three additional i.p. rIL-2 infusions were given on days 23, 25, and 27. Three dose levels of rIL-2 were tested: 5 X 10(5), 2 X 10(6), and 8 X 10(6) units/m2 body surface area. The dose-limiting toxicity was abdominal pain secondary to ascites accumulation with significant weight gain. Other toxic effects included decreased performance status, fever, nausea and vomiting, diarrhea, and anemia. Peripheral lymphocytosis and eosinophilia were seen at all dose levels. The maximum tolerated dose is 8 X 10(6) units/m2/dose. Peripheral and peritoneal IL-2 levels were measured with a bioassay using an IL-2-dependent cell line. At the highest dose level, serum IL-2 was greater than 10 units/ml for 18 h. After the first infusion, a 2-log dilution of the i.p. IL-2 was measured in the serum. In the postleukapheresis i.p. IL-2-dosing period less IL-2 was detected in the serum than in the earlier i.p. IL-2-priming period. The induction and persistence of LAK activity were studied. Peritoneal LAK activity was detected as early as 4 days after the first i.p. infusion, by day 11 in all evaluable patients, and persisted for the 6-day interval between priming IL-2 and LAK/IL-2 infusion. Peritoneal lytic activity persisted until day 28 in 5 tested patients. These peritoneal cells retained lytic activity 48 h in culture medium without rIL-2 present. Peritoneal LAK activity correlated with the percentage of mononuclear cells and the percentage of CD56-positive mononuclear cells in the peritoneum. The yield of peripheral lymphocytes after the six i.p. priming doses of rIL-2 correlated with the dose level of rIL-2 infused. Peripheral blood LAK activity showed a minimal, however progressive, increase during the treatment protocol. LAK activity could be enhanced if rIL-2 was present during the 4-h assay. These studies indicate that i.p. rIL-2 infusion induced durable regional LAK activity and primes peripheral blood cells for LAK activity if exposed briefly to additional IL-2.
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PMID:Phase I trial of intraperitoneal recombinant interleukin-2/lymphokine-activated killer cells in patients with ovarian cancer. 220 79

Autologous lymphokine-activated killer (LAK) cells and recombinant human interleukin-2 (rIL-2) were administered intraperitoneally (IP) to 24 patients with malignancies limited to the peritoneal space. Ten patients had ovarian cancer, 12 had colorectal cancer, and one patient each had endometrial carcinoma and primary small-bowel adenocarcinoma. All ovarian cancer patients, three of twelve colorectal cancer patients, and one patient with endometrial carcinoma had received prior therapy. Patients received IL-2 100,000 U/kg every 8 hours intravenously (IV) for 3 days, and 2 days later underwent daily leukapheresis for 5 days. LAK cells were generated in vitro by incubating the peripheral blood mononuclear cells in IL-2 for 7 days and were then administered IP daily for 5 days through a Tenckhoff catheter (Davol, Inc, Cranston, RI) together with IL-2 25,000 U/kg IP every 8 hours. All but one patient completed at least one cycle of therapy. Toxic side effects included minor to moderate hypotension, fever, chills, rash, nausea, vomiting, abdominal pain and distension, diarrhea, oliguria, fluid retention, thrombocytopenia, and minor elevations of liver function tests; all of these rapidly improved after discontinuation of IL-2. One patient had a grand mal seizure, and one suffered a colonic perforation; these were felt to be treatment-related. IP fibrosis developed in 14 patients and limited repeated cyclic administration of this therapy in five patients. Two of 10 (20%) ovarian cancer patients and five of 12 (42%) colorectal cancer patients had laparoscopy- or laparotomy-documented partial responses. We conclude that LAK cells and rIL-2 can be administered IP to cancer patients, resulting in moderate to severe short-term toxicity and modest therapeutic efficacy. Further investigation of this form of adoptive immunotherapy modified to address the problem of IP fibrosis and with lower IP IL-2 doses is justified by these initial results.
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PMID:Intraperitoneal lymphokine-activated killer-cell and interleukin-2 therapy for malignancies limited to the peritoneal cavity. 221 99

To develop a T-cell-based therapy for carcinomas, the superantigen staphylococcal enterotoxin A (SEA) was supplied with tumor specificity by means of a recombinant fusion of the Fab fragment of the monoclonal antibody C242 recognizing human colorectal (CRC) and pancreatic carcinomas (PC). Using this Fab-SEA fusion protein (PNU-214565), potent cytotoxicity by activation of T cells can be obtained in the targeted area. Twenty-one patients with CRC and 3 with PC were treated with single, escalating doses of PNU-214565 to establish the maximum tolerated dose (MTD) and to define toxicities. The doses ranged from 0.01 ng/kg to 4.0 ng/kg with three patients at each dose level, except for the dose of 1.5 ng/kg with which six patients were treated because of dose-limiting toxicity. Adverse events (AE) were transient: 13 patients experienced mild to moderate fever. In one patient, a grade 3 fever was followed by a grade 2 hypotension. Other mild or moderate AEs were fatigue, nausea, vomiting, diarrhea, and abdominal pain. No significant hematological toxicity occurred. Immune activation was highly variable with strong activity in peripheral blood seen only in two patients at the dosage level 1.5 ng/kg. They showed pronounced elevations of interleukin-2 (IL-2), IL-6, tumor necrosis factor-alpha, and interferon-gamma, 3-5 hours after the start of infusion. In one patient, IL-2 and IL-6 increased substantially (2,925 U/mL and 32,000 U/mL) concomitantly with grade 3 fever and transient grade 2 neutropenia, grade 2 lymphopenia, and grade 2 monocytopenia. In conclusion, a single 3-hour infusion of PNU-214565 could be safely administered up to 4 ng/kg. MTD was not determined. Instead, a repeat-dose trial was initiated starting at 0.5 ng/kg, considered safe in this trial, with the objective of defining the MTD.
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PMID:Phase I study of single, escalating doses of a superantigen-antibody fusion protein (PNU-214565) in patients with advanced colorectal or pancreatic carcinoma. 1068 47

High-dose interleukin-2 (IL-2) results in objective clinical regression in up to 17% of patients with metastatic melanoma and renal cell carcinoma, with about half of these patients experiencing a complete regression of all lesions. Gastrointestinal (GI) perforation is a rare but potentially serious complication of IL-2 administration. A retrospective review of all patients treated with IL-2 in the Surgery Branch of the National Cancer Institute (NCI) between Nov. 1, 1984, and May 1, 2002, was performed. In addition, a review of the published English literature on GI perforation in conjunction with IL-2 therapy was performed. Among the 1,797 patients treated at the NCI, there were eight (0.44%) cases of GI perforation. Seven of the eight patients were treated with high-dose (720,000 IU/kg every 8 hours) intravenous IL-2 (7/1,680, 0.42%) and one was treated with subcutaneous IL-2 (1/117, 0.85%). These patients developed various signs and symptoms of GI perforation. Six patients developed abdominal pain, yet only two of the eight patients had a fever. All six patients who underwent radiographic evaluation prior to diagnosis had free intraperitoneal air seen on the study. The location of the perforation included the stomach, small bowel, appendix, and colon. All underwent surgical treatment successfully, and four patients received further IL-2 therapy after recovering from the perforation. With the patients presented in this article, there have now been 20 cases reported in the English literature. Two of the patients at the NCI had a ruptured appendix, which has not been previously reported in the literature. The key to early diagnosis of GI perforation during IL-2 therapy is radiographic evaluation. Patients with GI perforation can be safely retreated with IL-2 if they are given adequate time to recover from their surgical intervention and if careful assessment is performed to rule out residual infection.
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PMID:Gastrointestinal perforations associated with interleukin-2 administration. 1507 43

Enteric-coated mycophenolate sodium (EC-MPS) is therapeutically equivalent to mycophenolate mofetil, but delays release of mycophenolic acid until it reaches the small intestine. De novo renal transplant patients taking part in a 12-month, multicenter, randomized study received cyclosporine microemulsion (CsA-ME, early or delayed to day 6), EC-MPS, steroids, and interleukin-2 antagonist induction. Tolerability data relating to EC-MPS are reported. Ninety-seven patients were randomized to early CsA-ME and 100 patients to delayed CsA-ME. Median daily dose of EC-MPS was 1440 mg at all time points throughout the 12-month period. The most frequently reported adverse events were constipation, anemia, urinary tract infection, abdominal pain, leukopenia, and cytomegalovirus infection; there were four malignancies. Fifty patients (24.6%) discontinued EC-MPS prematurely by 12 months, including 42 patients (84%) who discontinued owing to adverse events. No patient discontinued treatment because of gastrointestinal adverse events. Two-thirds of patients (137 [67.5%]) maintained full EC-MPS dose throughout the 12-month study and did not require any dose reduction or dose interruption. EC-MPS is well tolerated in de novo renal transplant recipients when administered in combination with CsA-ME and steroids, with low rates of dose reductions or interruptions. Gastrointestinal adverse events were responsible for dose reduction or interruption in only 5% of patients.
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PMID:Tolerability of enteric-coated mycophenolate sodium to 1 year in combination with cyclosporine and corticosteroids in renal transplant recipients. 1711 49

Angiosarcoma is rare and highly malignant vascular neoplasm, and primary retroperitoneal angiosarcoma is extremely rare. Preoperative diagnosis is very difficult because there are no specific imaging features, and definitively effective treatment has not yet been established. We recently treated a patient with primary retroperitoneal angiosarcoma in which a prompt and exact diagnosis was difficult to obtain. One month after surgery, local recurrence appeared, but salvage immunotherapy using recombinant interleukin-2 (rIL-2) showed good efficacy, and the patient obtained complete response. Here we report this rare case of angiosarcoma. A 60-year-old woman with abdominal pain was diagnosed with a left retroperitoneal mass on CT scan. The tumor was about 9 cm in diameter and positioned above the left kidney. Further study using MRI, 131I-MIBG scintigraphy, and enhanced CT suggested chronic expanding hematoma and the patient underwent surgical resection. Histopathological diagnosis was primary retroperitoneal angiosarcoma based on positive staining for VIII factor, CD31, CD34, and p53. One month after surgery, FDG-PET revealed local recurrence adjacent to the psoas major. We initiated salvage immunotherapy using rIL-2. The patient was treated effectively and achieved complete response. She is alive and well 19 months after surgery and rIL-2 treatment.
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PMID:[A case of retroperitoneal angiosarcoma effectively treated with recombinant interleukin-2]. 2426 Nov 93

The aim of the study was to investigate the effects of recombinant human growth hormone on protein malnutrition and insulin-like growth factor-1 (IGF-1) and interleukin-2 (IL-2) gene expressions in chronic nephrotic syndrome. Eighty patients with chronic nephrotic syndrome were admitted to our hospital. The patients were included in the study period from January 2015 to December 2016 and were divided into two groups (40 cases in each group) according to the random number method. All the patients enrolled received symptomatic and supportive treatment. The observation group was injected subcutaneously with recombinant human growth hormone, while the control group was treated with Shenyankangfu tablets. The recovery time of the clinical symptoms, change in serum protein, caloric intake and protein metabolism after intervention were compared between the two groups. Changes in serum cystatin C, IGF-1 and IL-2 before intervention, and at 1 week, 1 month and 3 months after intervention were detected, and the adverse reactions in the two groups were observed during the treatment. After intervention, the improvement time of proteinuria, hypoproteinemia, edema and hyperlipidemia in the observation group was significantly shorter than that in the control group (P<0.05). The expression of transferrin, pre-albumin, albumin and total protein in the observation group was significantly superior increased compared to those in the observation group prior to intervention and the control group after intervention (P<0.05). In addition the caloric intake, protein intake and urea nitrogen survival rate in the observation group were significantly superior to those in the observation group prior to intervention and the control group after intervention (P<0.05). At 1 week, 1 month and 3 months after intervention, the levels of serum cystatin C, IGF-1 and IL-2 in the observation group were markedly obviously lower than those in the control group during the same period (P<0.05). The total proportion of allergy, systemic pruritus, nausea and vomiting, abdominal distension and abdominal pain in the observation group was obviously lower than that in the control group (P<0.05). Compared with the traditional Chinese medicine Shenyankangfu tablets applied in the control group, the recombinant human growth hormone used for patients with chronic nephrotic syndrome can improve the clinical symptoms more quickly, regulate the protein metabolism and reduce the inflammatory response in the body, which also has fewer adverse reactions and higher safety.
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PMID:Effects of recombinant human growth hormone on protein malnutrition and IGF-1 and IL-2 gene expression levels in chronic nephrotic syndrome. 2972 65