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)

Alveolar macrophage (AM) phagocytic activity and glucose metabolism were evaluated during lung tumour growth in adult rats challenged i.v. with 10(5) viable Walker 256 tumour cells. Phagocytosis was estimated by the in vitro uptake of (14)C-labelled Pseudomonas aeruginosa and glucose oxidation was evaluated by (14)CO(2) production from 1-(14)C-glucose. AM were harvested by lung lavage from rats prior to and at 7 and 21 days following i.v. tumour-cell challenge. Macroscopic lung tumour nodules were not observed by 7 days after tumour challenge. However, 3 weeks after tumour challenge, tumour nodules were clearly identifiable on the surfaces of the lungs. One week after the i.v. tumour challenge a marked increase in the number of AM was evident. The in vitro phagocytosis of (14)C-labelled Pseudomonas aeruginosa was unaltered at that time, but became progressively depressed thereafter. Three weeks after tumour challenge, this decrease in phagocytic activity was evident when cells were incubated in normal serum, and was furtheri ntensified by serum obtained from tumour-bearing animals. Glucose oxidation by AM in either the resting condition or during bacterial phagocytosis was clearly decreased at both 1 and 3 weeks following i.v. tumour challenge. These findings indicate that the growth of pulmonary metastases is associated with a depression of alveolar macrophage bacterial phagocytic capacity, perturbations in serum opsonic activity and distinct alterations in macrophage energy metabolism. The metabolic dysfunction may impair pulmonary macrophage host defences against lung tumour growth.
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PMID:Inhibition of phagocytosis and glucose metabolism of alveolar macrophages during pulmonary tumour growth. 59 70

It is well established that transfusions given prior to transplantation diminish rejection, and recent reports suggest that transfused patients having surgery for cancer developed more metastases than those who did not receive transfusions. To our knowledge, however, there are no studies evaluating whether transfusions result in increased rates of infections. To investigate this, 295 Lewis rats were subjected to a 25% total body surface area burn and were given either 3 mL of Lewis blood, 3 mL of A'Solagoft Cancer Institute rat blood, or 9 mL of lactated Ringers' solution intravenously on day 1 before burn or on the day of burn. One additional group received 1-mL transfusions on days 9, 7, and 5 before burn. The burns were painted with 1 X 10(8) Pseudomonas aeruginosa lot No. 1244 on postburn days 0, 1, or 2. All rats were followed up for 28 days and survival and mean survival times were recorded. Transfusion of A'Solagoft Cancer Institute blood increased mortality unless given within 24 hours prior to Pseudomonas challenge, when it diminished mortality. Transfusion with syngenic Lewis blood had no effect. We conclude that transfusions may adversely affect survival when given before bacterial challenge, possibly due to immunosuppression from exposure to non-self-histocompatibility antigens.
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PMID:Effect of transfusion on immune function in a traumatized animal model. II. Effect on mortality rate following septic challenge. 349 65

Antitumour, antileukosis and antimetastatic effects of lipopolysaccharide (LPS) isolated from Pseudomonas solanacearum have been studied. It is established that LPS does not possess the antitumour effect on experimental animals with Lewis lung carcinoma, melanoma B-16 and sarcoma S-37 and vice versa, intensifies the tumour growth. The life time of animals with experimental leukoses lymphocytic leukemia P-388 and lymphoid leukemia L 1210 inconsiderably increases. At the same time LPS possesses the expressed antimetastatic effect that has manifested in the decrease of the volume (40 and 5 times) and of the amount (4-4.2 times) of metastases in mice with Lewis lung carcinoma and melanoma B-16, respectively. Study of the contribution of certain structural components of LPS molecule to the total biological activity has shown that O-specific polysaccharide and oligosaccharide of core take the expressed antimetastatic effect. Lipid A in the used dose weakly modified the development of Lewis lung carcinoma metastases.
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PMID:[The biological activity of Pseudomonas solanacearum polysaccharide]. 766 47

Metastasis to the central nervous system in patients with small cell lung cancer is not uncommon, and a fraction of the cases have leptomeningeal disease for which no effective therapy is available. To establish an experimental model for evaluation of new therapeutic approaches for such tumor lesions, 1 x 10(6) human H-146 cells were injected directly into the cerebrospinal fluid in the cisterna magna of nude rats. Small, superficial leptomeningeal tumors developed, consistently resulting in symptoms of central nervous system involvement after a mean latency of 20 days. The model was used to study the efficacy of intrathecal targeted therapy with immunotoxins. The monoclonal anti-carcinoma antibodies MOC-31 and NrLu10 and the growth factor transferrin were conjugated to Pseudomonas exotoxin A (PE), and 1 day after tumor cell inoculation instilled in the cisterna magna as a single bolus dose of 1.5 micrograms. The antibody conjugates, which were highly cytotoxic to target cells in a protein synthesis inhibition assay in vitro, increased the symptom-free latency by 35-46%. PE had no effect, reflecting a lower in vitro cytotoxicity and possibly also a down-regulation of transferrin-receptor expression in the meningeal H-146 tumors. Delayed or repeated treatment with MOC-31-PE was less effective than day 1 administration, whereas the addition of 10% glycerol to the injection solution increased the symptom-free period to 72%. The efficacy of MOC-31-PE is superior to reported effects obtained in similar models with other therapies, and the results support the development of this immunotoxin towards clinical evaluation in small cell lung cancer patients with leptomeningeal carcinomatosis.
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PMID:Targeted therapy with immunotoxins in a nude rat model for leptomeningeal growth of human small cell lung cancer. 817 21

Pseudomonas aeruginosa is a very rare cause of septicaemia in adults without significant underlying disease. A case of pseudomonas septicaemia occurring as a complication of a ruptured hydatid cyst in an apparently healthy young soldier is presented. This patient also had unusual pulmonary sequelae resembling pulmonary metastases together with massive haemoptysis.
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PMID:Ruptured hepatic hydatid cyst and an unusual case of pseudomonas septicaemia. 860 56

Tumor cells have been found in autologous hematopoietic cell transplants used after high-dose chemotherapy. To specifically eliminate contaminating mammary tumor cells during ex vivo expansion of CD34+ hematopoietic progenitor cells, we used recombinant immunotoxins (ITs) directed against cell-surface antigens expressed on mammary carcinoma cells. ITs were expressed from fusion cDNAs combining a single-chain antibody fragment (scFv) directed against the Erb-B2 or epidermal growth factor (EGF) receptors with a truncated Pseudomonas exotoxin A fragment devoid of its cell-binding domain. CD34+ hematopoietic progenitor cells did not express Erb-B2 and EGF receptors as detected by Western blotting. Ex vivo expansion of total hematopoietic cells or of colony-forming cells from CD34+ progenitors in the presence of stem-cell factor (SCF), interleukin-1 (IL-1), IL-3, IL-6, and erythropoietin (Epo) was not affected when ITs were added to the cultures. In contrast, MDA-MB 453 and MCF-7 mammary carcinoma cells were depleted in a dose- and time-dependent manner by more than 3 log in coculture with CD34+ cells over a period of 7 days in the presence of 100 to 1,000 ng/mL of anti-Erb-B2 IT. This included elimination of the subpopulations with regrowth potential. Similarly, addition of either anti-Erb-B2 or anti-EGF receptor ITs to primary breast cancer cells isolated from patients with metastatic disease resulted in elimination of cytokeratin-positive cells in seven of seven samples. ITs are highly efficient and convenient to use for the depletion of mammary tumor cells during ex vivo expansion of hematopoietic progenitor-cell autografts.
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PMID:Purging of mammary carcinoma cells during ex vivo culture of CD34+ hematopoietic progenitor cells with recombinant immunotoxins. 947 51

High-grade sarcomas have a high rate of local recurrence as well as distant metastases. This has led to the development of intra-arterial chemotherapy (IAC) as part of a multimodal approach to control local disease and/or reduce the extent of surgical resection. Intra-arterial catheters are positioned by an interventional radiologist into the feeding vessels of the tumor. Adriamycin and 5-fluorodeoxyuridine are infused intra-arterially. Cisplatinum, with or without granulocyte colony stimulating factor, is given systemically. Patients usually experience acute self-limited soft-tissue inflammation in the treated area. In our experience of 118 patients, 3 patients experienced soft-tissue necrosis that required excision and reconstruction. The first was treated for synovial sarcoma of a metatarsal. After IAC with Adriamycin, she sloughed the skin, subcutaneous tissue, and some of the posterior compartment musculature of her calf. This tissue was debrided. A gastrocnemius flap and skin graft were used for coverage. She is free of disease and ambulatory. The second patient was treated with IAC Adriamycin for a radial head chondrosarcoma. She developed soft-tissue slough, which became infected with Pseudomonas. She required extensive debridement of the skin, subcutaneous tissue, and muscle, and was subsequently reconstructed with a latissimus flap and a split-thickness skin graft (STSG). She later developed a local recurrence requiring amputation. The latissimus was elevated and used to cover the distal stump. She also is free of disease. The third patient was treated with IAC Adriamycin for Ewing's sarcoma of the right femur. This was complicated by fat necrosis and persistent pain. Subsequent radiotherapy only worsened her symptoms. She underwent wide excision and muscle flap/STSG repair, which relieved her pain. She is currently ambulatory and free of disease. In conclusion, as the use of IAC continues, its complications may become more common. Our experience with this previously unknown entity is illustrated and therapeutic options are discussed.
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PMID:Soft-tissue complications of intra-arterial chemotherapy for extremity sarcomas. 955 93

Receptor-mediated targeted tumor therapy is an important applied consequence of the studies on the genetic causes of cancer. These therapy concepts have to be evaluated in novel animal models that reflect the molecular aberrations found in human tumors. Here we introduce an animal model that allows the evaluation of drugs directed against a surface receptor that is frequently altered in primary human adenocarcinomas. Tumor toxins are polypeptides in which a tumor cell-specific recognition domain and a toxic effector domain have been joined by DNA recombination in vitro. Tumor cell recognition is contributed by a single-chain antibody domain specific for the extracellular domain of the erbB-2 receptor [scFv(FRP5)] and cytotoxicity by the enzymatically active domain of a bacterial exotoxin (exotoxin A from Pseudomonas aeruginosa). The erbB-2 receptor is overexpressed in many primary human cancer cells and is a favorable target for directed tumor therapy. The fusion protein scFv(FRP5)-exotoxin A has previously been shown to be able to efficiently and specifically kill erbB-2 receptor-expressing tumor cells. We have investigated the potential of this tumor toxin to detect and eliminate metastasizing tumor cells upon systemic administration. Murine renal carcinoma cells genetically modified with human erbB-2 receptor and bacterial beta-galactosidase genes form large pulmonary metastases when injected into the tail vein of BALB/c mice. Administration of the tumor toxin over a 10-day time period starting 1 day after tumor cell transplantation totally suppressed the formation of metastases. The treatment of animals 11 days after tumor cell transplantation, allowing the establishment of many pulmonary metastases, led to a drastic reduction in their number and size.
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PMID:Systemic treatment with a recombinant erbB-2 receptor-specific tumor toxin efficiently reduces pulmonary metastases in mice injected with genetically modified carcinoma cells. 963 94

Cytotoxic strategies which are directed to tumor-associated antigens might be most beneficial for cancer patients with minimal tumor load such as in an adjuvant setting after initial therapy. We have recently described a highly potent single chain antibody-toxin, scFv(14E1)-ETA, which consists of the variable domains of the antibody 14E1 genetically fused to a truncated form of Pseudomonas exotoxin A. ScFv(14E1)-ETA specifically recognizes the human epidermal growth factor receptor (EGFR) and the oncogenically activated receptor variant EGFRvIII, which have been implicated in the development of various human malignancies. Here we have investigated the antimetastatic activity of bacterially expressed scFv(14E1)-ETA and its disulfide-stabilized derivative ds-scFv(14E1)-ETA in a novel model for disseminated disease which is based on murine renal carcinoma cells subsequently transfected with the E. coli beta-galactosidase gene, and human full-length or variant EGFR cDNAs. Intravenous injection of these Renca-lacZ/EGFR and Renca-lacZ/EGFRvIII cells in syngenic Balb/c mice led to the formation of pulmonary metastases which were readily detectable upon excision of the lungs and X-gal staining. Systemic treatment of mice with scFv(14E1)-ETA resulted in the complete suppression of Renca-lacZ/EGFRvIII metastasis formation and drastically reduced the number of pulmonary Renca-lacZ/EGFR tumor nodules. The ds-scFv(14E1)-ETA derivative where the antibody variable regions are connected by an artificial disulfide bond displayed improved thermal stability at physiological temperature but due to reduced cytotoxic activity was less potent than the original scFv(14E1)-ETA in metastasis suppression.
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PMID:Suppression of metastasis formation by a recombinant single chain antibody-toxin targeted to full-length and oncogenic variant EGF receptors. 1020 32

Urologic emergencies are common in the cancer patient and relate mainly to complications of bladder hemorrhage, upper or lower urinary tract obstruction, urinary tract infection, and priapism. Hemorrhagic cystitis is commonly due to bladder injury from radiation therapy, viral infection, or metabolites of chemotherapeutic agents. Treatments aimed at ameliorating the effects of theses metabolites, such as mesna and intravenous (IV) hydration, coupled with cystoscopy, evacuation of clots, and formalin instillation, have given clinicians an effective means of avoiding exsanguinating hemorrhage from the bladder. Malignant ureteral obstruction is an ominous sign in the cancer patient and may be due to tumor compression, retroperitoneal adenopathy, or direct tumor invasion. The endourologic procedures of ureteral stenting and percutaneous nephrostomy are effective means of palliation; however, complications of infection, stent obstruction, and stent migration can result in hospital admission and a decline in quality of life. Median survival for patients with malignant ureteral obstruction is less than 7 months, regardless of the tumor of origin. Bladder outlet obstruction leading to urinary retention can be due to mechanical factors involving the bladder neck or prostate, or to a breakdown in the neurophysiologic function of the bladder. Every attempt is made to avoid surgical intervention or the placement of chronic in-dwelling catheter in these often debilitated patients. Patients are often effectively treated with a variety of pharmacologic agents, such as alpha-adrenergic receptor blockers or by the initiation of chronic intermittent catheterization. Urinary tract infections are particularly dangerous in neutropenic and bone marrow transplant patients, with bladder catheters the most common portal entry. The colonization and later infection by resistant nosocomial organisms, such as Pseudomonas aeruginosa and Candida albicans, can rapidly lead to life-threatening sepsis. On rare occasions, emergency surgical intervention with adequate open drainage or nephrectomy is required to control such infections. Priapism can be caused by hematologic malignancy with hypercoagulation, metastatic disease involving the corpora cavernosa with thrombosis of the venous outflow from the penis, or rarely from intracavernous injections used for the treatment of impotence. If effective treatment exists for the primary tumor, improvement or resolution of the state of priapism may occur. Radiation therapy may be required to decrease the pain associated with malignant priapism, but surgical shunting procedures are rarely effective.
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PMID:Urologic emergencies in the cancer patient. 1086 17


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