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 presence of a local tumour and pulmonary metastases is studied after the administration of the Lewis Lung Carcinoma at different sites of transplantation. The intravenous administration routes, in the tail vein and in the portal vein, injections in the liver and in the muscle of the left hindleg are used. The injection in the tail vein induces pulmonary "metastases". The injection in the portal vein is followed by multiple tumours in the whole liver and pulmonary metastases. An unilobar hepatic tumour and early pulmonary metastases appear after transplantation in the liver. Intra-muscular injection gives a local tumour which can be weighed after amputation of the leg and pulmonary metastases. A test of treatment by Sulphadiazine Triazene points out a weak action on the primary tumour and a larger one on the metastases.
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PMID:[Local and metastatic growth of Lewis lung carcinoma as a function of its transplantation site. Application to the study of the pharmacology of sulphadiazine triazene]. 12 32

Studies were carried out on the combination of Cimetidine (CMTD) with Cytoxan (CTX) in three murine tumors. While the combination significantly potentiated the anticancer effect of CTX in L1210 leukemia, the results with P388 leukemia were not significantly different. The results with Lewis Lung Carcinoma showed a consistent reduction in the number of metastases. However, there was no consistent concomitant prolongation in survival. The host strain, biology of the tumour and the drug used in combination with CMTD might be some of the factors responsible for the varied response.
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PMID:Effects of cimetidine combination with cyclophosphamide in transplanted murine tumors. 259 43

Role of spleen in CY-induced enhancement of experimental lung metastases of Lewis Lung Carcinoma LL2 cells was studied. Reconstitution with spleen cells abolished the enhancing effect of CY. Conversely, removal of spleen in CY treated mice caused about two-fold increase in the number of metastases. In addition in splenectomized mice, the effect of CY was augmented.
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PMID:Potentiation of cyclophosphamide-induced enhancement of experimental metastasis by splenectomy. 263 36

The effects of two new concentrated perfluorochemical emulsions based on F-66E and PFOB, which carry significantly more oxygen than Fluosol-DA 20%, were tested on normal tissues (toxicity and radiation response) and on the development of metastases from Lewis Lung Carcinoma (3LL) in female C57 BL/6 mice. Twenty one days after injection of F-66E or PFOB emulsions (15 ml/kg body weight), the spleen and liver weights were significantly increased but had returned to normal after 2-3 months. Splenomegaly already observed in 3LL bearing mice was significantly increased by F-66E emulsion injection. The radiosensitivity of GM-CFC was not altered when unanesthetized GM-CFC was not altered when unanesthetized mice were pretreated with F-66E emulsions and/or carbogen 1 hr prior to and during irradiation. The rate of tumor take and the period before detection of tumors were not modified when an emulsion of F-66E was injected simultaneously or 10 days after 3LL cells. Mean survival of mice, and the number of metastases on lung surfaces were similar in F-66E injected mice and control mice.
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PMID:New high O2 carrying perfluorochemical emulsions: toxicity, radiosensitivity of GM-CFC and development of metastases in mice. 271 62

Studies were performed to determine whether localized treatment of subcutaneously growing Lewis Lung Carcinoma (LLC) in C57BL/6 mice with porphyrin photodynamic therapy (PDT) affects the formation of distant metastases. Treatments consisted of a 10 mg kg-1 dose of dihematoporphyrin-ether (Photofrin II) followed 24 h later by local tumour irradiation with 630 nm red light. Total doses of light ranged from 0-500 J cm-2 and the irradiance of delivered light was 150 mW cm-2. Primary LLC tumours were treated at a volume of 25-30 mm3, and lung metastases were determined 21 days following transplantation. Mice exposed to PDT treatment which produced either partial or complete local tumoricidal responses had significantly decreased numbers of metastatic lung colonies compared to controls. In addition, PDT treated mice had equal or less metastatic lung colonies than comparable mice treated with local surgical excision of the primary LLC lesion. These results indicate that local PDT does not enhance metastatic spread of LLC following either curative or noncurative treatments.
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PMID:The effect of localized porphyrin photodynamic therapy on the induction of tumour metastasis. 295 84

The anti-tumor effect of immunization with heat-killed Mycobacterium tuberculosis (Tbc) and Tuberculin (PPD)-coupled syngeneic tumor cells was examined in vivo. Three tumor cell lines were employed. Immunization of Tbc-primed BALB/c mice with PPD-coupled syngeneic Meth-A tumor cells displayed a potent anti-tumor effect on viable Meth-A cells inoculated subcutaneously. Neither PPD-coupled LLC (Lewis Lung Carcinoma) cells nor sonicated PPD-coupled Meth-A cells were capable of immunizing these mice. PPD-coupled syngeneic whole tumor cells were indispensable for induction of this tumor-specific resistance. Immunization of Tbc-primed C3H/He mice with PPD-coupled syngeneic MH134 tumor cells did not elicit anti-tumor activity against MH134, but additional pretreatment of mice with cyclophosphamide brought on an anti-tumor effect. Antimetastatic reactivity was investigated in C57BL/6 mice bearing LLC, with a reduction in metastases noted. This antimetastatic effect was observed even when the mice were immunized with PPD-coupled LLC cells three days after removal of the initial tumor. Immunization with Tbc and PPD-coupled Meth-A cells together with intraperitoneal administration of murine or rat interleukin 2 (IL 2) further augmented anti-Meth-A resistance. Murine IL 2 further inhibited tumor growth during the early stage, while rat IL 2 showed an anti-tumor effect throughout the course of tumor growth.
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PMID:Augmentation of anti-tumor activity by immunization with Mycobacterium tuberculosis (Tbc) and tuberculin-coupled tumor cells. 392 81

The most common cause of death of cancer sufferers is through the occurrence of metastases. The metastatic behaviour of tumour cells is regulated by extracellular growth factors such as hepatocyte growth factor (HGF), a ligand for the c-Met receptor tyrosine kinase, and aberrant expression/activation of the c-Met receptor is closely associated with metastatic progression. Nk4 (also known as Interleukin (IL)32b) is a competitive antagonist of the HGF c-Met system and inhibits c-Met signalling and tumour metastasis. Nk4 has an additional anti-angiogenic activity independent of its HGF-antagonist function. Angiogenesis-inhibitory as well as cancer-specific apoptosis inducing effects make the Nk4 sequence an attractive candidate for gene therapy of cancer. This study investigates the inhibition of tumour metastasis by gene therapy mediated production of Nk4 by the primary tumour. Optimal delivery of anti-cancer genes is vital in order to achieve the highest therapeutic responses. Non-viral plasmid delivery methods have the advantage of safety and ease of production, providing immediate transgene expression, albeit short-lived in most tumours. Sustained presence of anti-angiogenic molecules is preferable with anti-angiogenic therapies, and the long-term expression mediated by Adeno-associated Virus (AAV) might represent a more appropriate delivery in this respect. However, the incubation time required by AAV vectors to reach appropriate gene expression levels hampers efficacy in many fast-growing murine tumour models. Here, we describe murine trials assessing the effects of Nk4 on the spontaneously metastatic Lewis Lung Carcinoma (LLC) model when delivered to primary tumour via plasmid lipofection or AAV2 vector. Intratumoural AAV-Nk4 administration produced the highest therapeutic response with significant reduction in both primary tumour growth and incidence of lung metastases. Plasmid-mediated therapy also significantly reduced metastatic growth, but with moderate reduction in primary subcutaneous tumour growth. Overall, this study demonstrates the potential for Nk4 gene therapy of metastatic tumours, when delivered by AAV or non-viral methods.
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PMID:Anti-metastatic effects of viral and non-viral mediated Nk4 delivery to tumours. 1927 40

British developed Bisdioxopiperazine compound (Biz compounds) {ICRF-159 or ICRF-187 (razoxane, Raz)} which was the first agent ever to be observed inhibiting and controlling the spontaneous pulmonary metastases of murine Lewis Lung Carcinoma (LLC) tumor model worldwide. Since 1980, two new Biz compounds {probimane (Pro, AT-2153, MST-2) and MST-16} have been synthesized at the Shanghai Institute of Materia Medica, Chinese Academy of Sciences, PR China, based on structural modifications from British developed Biz compounds. Despite some similarities and differences of structural and pharmacological activities observed between Raz, Pro and MST-16, the systematic comparisons of their pharmacological activities and mechanisms, especially on neoplasm metastases, are still much needed. This work demonstrates that Biz compounds may inhibit tumor cell migration in vitro through a Matrigel-Coated Transwell plate assay and a wound-healing assay by using three human mammary tumor cell lines (MDA-MB-231, MDA-MB-435 and MDA-MB-468). Pro, ICRF-187 and MST-16 affect the network of actin assembly. We conclude that Biz compounds might inhibit neoplasm metastases via affecting a cascade of GTPases, cell skeleton polarizations and cell movements.
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PMID:Cell biological manifestations of bisdioxopiperazines treatment of human tumor cell lines in culture. 2123 36

Pro-oxidative stressors including cigarette smoke (CS) generate novel lipids with platelet-activated factor-receptor (PAF-R) agonistic activity mediate systemic immunosuppression, one of the most recognized events in promoting carcinogenesis. Our previous studies have established that these oxidized-PAF-R-agonists augment murine B16F10 melanoma tumor growth in a PAF-R-dependent manner because of its effects on host immunity. As CS generates PAF-R agonists, the current studies sought to determine the impact of PAF-R agonists on lung cancer growth and metastasis. Using the murine Lewis Lung Carcinoma (LLC1) model, we demonstrate that treatment of C57BL/6 mice with a PAF-R agonist augments tumor growth and lung metastasis in a PAF-R-dependent manner as these findings were not seen in PAF-R-deficient mice. Importantly, this effect was because of host rather than tumor cells PAF-R dependent as LLC1 cells do not express functional PAF-R. These findings indicate that experimental lung cancer progression can be modulated by the PAF system.
Cancer Growth Metastasis 2014
PMID:Systemic Platelet-activating Factor Receptor Activation Augments Experimental Lung Tumor Growth and Metastasis. 2500 16

Systemic inhibition of Dll4 has been shown to thoroughly reduce cancer metastasis. The exact cause of this effect and whether it is endothelial mediated remains to be clarified. Therefore, we proposed to analyze the impact of endothelial Dll4 loss-of-function on metastasis induction on three early steps of the metastatic process, regulation of epithelial-to-mesenchymal transition (EMT), cancer stem cell (CSC) frequency and circulating tumor cell (CTC) number. For this, Lewis Lung Carcinoma (LLC) cells were used to model mouse tumor metastasis in vivo, by subcutaneous transplantation into endothelial-specific Dll4 loss-of-function mice. We observed that endothelial-specific Dll4 loss-of-function is responsible for the tumor vascular regression that leads to the reduction of tumor burden. It induces an increase in tumoral blood vessel density, but the neovessels are poorly perfused, with increased leakage and reduced perivascular maturation. Unexpectedly, although hypoxia was increased in the tumor, the number and burden of macro-metastasis was significantly reduced. This is likely to be a consequence of the observed reduction in both EMT and CSC numbers caused by the endothelial-specific Dll4 loss-of-function. This multifactorial context may explain the concomitantly observed reduction of the circulating tumor cell count. Furthermore, our results suggest that endothelial Dll4/Notch-function mediates tumor hypoxia-driven increase of EMT. Therefore, it appears that endothelial Dll4 may constitute a promising target to prevent metastasis.
Clin Exp Metastasis 2019 08
PMID:Metastasis is impaired by endothelial-specific Dll4 loss-of-function through inhibition of epithelial-to-mesenchymal transition and reduction of cancer stem cells and circulating tumor cells. 3111 45


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