Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pleurodesis for effective control of malignant pleural effusion can be induced with various methods and agents. In 18 patients with histologically or cytologically proven malignant pleural effusion, 500 mg doxycycline hydrochloride diluted in 30 ml of saline was instilled into the emptied pleural space. Tube drainage was performed using suction or gravity. More than one doxycycline instillation was required in 13 cases. Serial chest radiography showed the response to be complete in 11 of the 18 patients and partial in four, while three did not respond. There was no difference between the results obtained with the two drainage systems. In all of the complete responders who died there was no sign of reaccumulated pleural effusion at terminal admission, despite clinical evidence of systemic tumor progression. Three patients--all with breast carcinoma--are alive after 5-27 months, two as complete responders and one as partial responder. The most common side effect was pleuritic pain, defined as significant if narcotic analgesics were required. A moderate febrile reaction appeared in four patients during the first 24 hours post-instillation. The study showed doxycycline to be an effective sclerosing agent for inducing pleurodesis, with acceptable adverse effects.
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PMID:Treatment of malignant pleural effusion with doxycycline. 316 42

Expression of CD44 isoform that contains variant exons (v1-v10) has been implicated in tumor progression and metastasis. Especially, CD44 isoform containing v6 (CD44v6) and that containing v7 (CD44v7) were shown to confer full metastatic behavior on tumor cells. We examined the expression of CD44v6 and CD44v7 in malignant pleural effusions (13 lung cancers and 4 non-lung cancers) and in benign pleural effusions (7 tuberculosis and 3 pneumonia) with Southern blot analysis of reverse transcription (RT)-polymerase chain reaction (PCR) products. CD44v6 was expressed not only in malignant pleural effusions (12 of 13 lung cancers and 4 of 4 non-lung cancers), but also in benign pleural effusions(9/10). In contrast, although expression of CD44v7 was found in most malignant pleural effusions (12 of 13 lung cancers and 4 of 4 non-lung cancers), it was found in only a few cases of benign pleural effusions. These results suggest that the expression of CD44v7 may be correlated with a tumor-specific event such as metastasis or dissemination in malignant pleural effusion, while no such correlation can be found with CD44v6.
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PMID:Differential expression of CD44 splice variants in malignant and benign pleural effusions. 894 29

The use of dendritic cells (DCs) for cancer vaccination is effective in suppressing cancer progression. This is because the DCs play a crucial role in priming tumor-specific immunity efficiently as antigen-presenting cells. In this study, we analyzed the ability of DCs to elicit tumor-specific immunity and clinical effects of DC vaccine immunotherapy targeting MUC1 tumor antigens. DCs from 14 patients with advanced or metastatic breast or lung cancer (9 positive for MUC1 and 5 negative for MUC1) were loaded with MUC1 antigens or tumor lysate and used for therapeutic vaccination. After vaccination, all the MUC1-positive patients acquired antigen-specific immunity whereas only 1 case with MUC1-negative cancer showed the specific immunity. Clinically, marked effects such as reduction in tumor sizes or tumor marker levels or disappearance of malignant pleural effusion were observed in 7 of the 9 MUC1-positive cases. However, MUC1-negative patients did not respond to DC vaccines, with the exception of 1 case with MAGE3-positive lung cancer. Survival of MUC1-positive patients was significantly prolonged in comparison with MUC1-negative patients (mean survival: 16.75 versus 3.80 months, p=0.0101). These data suggest that MUC1 is sufficiently immunogenic to elicit strong anti-tumor immunity as a tumor antigen and that DC vaccines targeting MUC1 are useful for immunotherapy of cancer.
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PMID:Dendritic cell vaccine immunotherapy of cancer targeting MUC1 mucin. 1296 25

Gefitinib is a selective inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinases, and shows favorable antitumor activity against chemorefractory non-small cell lung cancer (NSCLC). The majority of responders (patients who are sensitive to gefitinib), however, relapse within 1.5 years, indicating an acquired resistance to gefitinib. Here we report three chemotherapy refractory NSCLC patients who were retreated with gefitinib. All three cases were nonsmokers and showed an adenocarcinoma histology. While they had experienced successful control from their initial treatment with gefitinib for more than 12 months, gefitinib therapy was terminated because two cases (cases 1 and 3) relapsed during the therapy and case 2 suffered alveolar hemorrhage. After more than 7 months from the time of discontinuation of the initial gefitinib treatment, they were retreated with gefitinib, as further tumor progression was observed. Of the three cases, cases 1 and 2 were well controlled by retreatment with gefitinib monotherapy for more than 7 months, suggesting sensitivity to retreatment. Case 3 also showed a regression in size of several tumors, while some other lesions progressively enlarged and developed a malignant pleural effusion after 4 months. These observations suggest the possibility that retreatment with gefitinib might be useful when 1) initial treatment shows a favorable clinical response, and 2) there has been a period of time following the termination of the initial gefitinib treatment.
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PMID:Retreatment of lung adenocarcinoma patients with gefitinib who had experienced favorable results from their initial treatment with this selective epidermal growth factor receptor inhibitor: a report of three cases. 1611 8

We developed a novel mouse model of malignant pleural effusion (MPE) by injecting Lewis lung cancer (LLC) cells directly into the pleural space of syngeneic C57B/6 mice. The pleural effusions in this model share common cellular and biochemical features with human MPEs. Implantation and growth of pleural tumors triggers a host inflammatory response characterized by a mixed inflammatory cell influx into the pleural fluid. LLC cells exhibited high basal nuclear factor (NF)-kappaB activity in vitro and in vivo, which we used to drive expression of a NF-kappaB-dependent green fluorescent protein-firefly luciferase fusion reporter construct. NF-kappaB-dependent reporter expression allowed intravital tracing of pleural tumors. Inhibition of NF-kappaB in LLC cells did not affect cell viability in culture; however, injection of LLC cells expressing a dominant NF-kappaB inhibitor resulted in decreased tumor burden, decreased pleural effusion volume, and decreased pleural effusion TNF-alpha levels. These studies indicate that tumor NF-kappaB activity regulates pleural tumor progression. This reproducible model of MPE can be used to further study the influence of specific host and tumor factors on the pathogenesis of MPE and evaluate new therapeutic strategies.
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PMID:Nuclear factor-kappaB affects tumor progression in a mouse model of malignant pleural effusion. 1621 Jun 94

Matrix metalloproteinases (MMPs) are proteolytic enzymes that are implicated in multiple stages of cancer progression including invasion and metastasis. MMPs exert these effects by cleaving a diverse group of substrates, which include not only structural components of the extracellular matrix, but also growth factor receptors. By gelatin zymography we verified MMP activity in the pleural effusions of patients with benign and malignant disease. Of these patients, 32 had malignant pleural effusion, consisting of 20 breast cancer, 6 non-small cell lung carcinoma, 4 ovarian carcinoma, and 2 colonic adenocarcinoma, and 10 had benign pleural effusion (5 pleurisy and 5 cirrhosis). Zymography showed the constant presence of a substantial amount of MMP-2 in all samples analyzed, whereas MMP-9 was present to lesser quantities. MMP-2 activity was enhanced in pleural effusions from patients with benign diseases compared with cancer patients. MMP-9 was present in 59% of cancer patients and the lytic activity was enhanced in pleurisy and absent in cirrhosis. Furthermore, we determined the pleural effusion levels of the soluble extracellular domain of HER-2/neu. The levels of HER-2/neu ECD were above the cut-off value in breast cancer patients. No correlation between gelatinolytic activities and high HER-2/neu ECD values was found.
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PMID:Gelatinolytic activities (matrix metalloproteinase-2 and -9) and soluble extracellular domain of Her-2/neu in pleural effusions. 1761 66

Malignant pleural effusion (MPE) is associated with advanced-stage lung cancer and is a poor prognostic sign for these patients. Osteopontin (OPN) is a multifunctional cytokine that is involved in the tumor progression and angiogenesis of lung cancer cells. The purpose of this study is to investigate and provide evidence for the role of OPN in the formation of MPE associated with lung cancer. In this study, we established an OPN knockdown murine lung cancer cell line, 3LL cells, utilizing the small interfering RNA (siRNA) technique. To reveal the effect of OPN on the formation of MPE associated with lung cancer, we directly injected OPN knockdown 3LL cells, 3LL/OPN siRNA, or control cells, 3LL/control siRNA, into the pleural space of C57BL/6 mice. OPN knockdown significantly reduced the formation of MPE, but did not inhibit in vivo tumor growth of 3LL cells in mice. Vascular endothelial growth factor (VEGF) concentration in MPE was markedly decreased in the 3LL/OPN siRNA in comparison with that of the 3LL/control siRNA. In vitro, recombinant OPN protein enhanced VEGF secretion from human umbilical vein endothelial cell (HUVEC) or human mesothelial cell line, Met5A cells, in a concentration-dependent manner. These results suggest that OPN is positively involved in the formation of MPE of lung cancer presumably by promoting VEGF secretion from vascular endothelial cells or mesothelial cells. OPN could be an effective target molecule for reducing MPE in lung cancer patients.
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PMID:Osteopontin is involved in the formation of malignant pleural effusion in lung cancer. 1875 67

Secreted phosphoprotein-1 (SPP1) promotes cancer cell survival and regulates tumor-associated angiogenesis and inflammation, both central to the pathogenesis of malignant pleural effusion (MPE). Here, we examined the impact of tumor- and host-derived SPP1 in MPE formation and explored the mechanisms by which the cytokine exerts its effects. We used a syngeneic murine model of lung adenocarcinoma-induced MPE. To dissect the effects of tumor- versus host-derived SPP1, we intrapleurally injected wild-type and SPP1-knockout C57/BL/6 mice with either wild-type or SPP1-deficient syngeneic lung cancer cells. We demonstrated that both tumor- and host-derived SPP1 promoted pleural fluid accumulation and tumor dissemination in a synergistic manner (P<0.001). SPP1 of host origin elicited macrophage recruitment into the cancer-affected pleural cavity and boosted tumor angiogenesis, whereas tumor-derived SPP1 curtailed cancer cell apoptosis in vivo. Moreover, the cytokine directly promoted vascular hyper-permeability independently of vascular endothelial growth factor. In addition, SPP1 of tumor and host origin differentially affected the expression of proinflammatory and angiogenic mediators in the tumor microenvironment. These results suggest that SPP1 of tumor and host origin impact distinct aspects of MPE pathobiology to synergistically promote pleural fluid formation and pleural tumor progression. SPP1 may present an attractive target of therapeutic interventions for patients with MPE.
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PMID:Secreted phosphoprotein-1 directly provokes vascular leakage to foster malignant pleural effusion. 2237 Jun 46

Malignant pleural mesothelioma (MPM) is an aggressive malignant tumor of mesothelial origin associated with asbestos exposure. MPM exhibits a limited response to conventional chemotherapy and radiotherapy. This, early diagnosis of MPM is essential. Malignant tumor progression requires the destruction of the basement membrane, which is constructed from extracellular matrix (ECM) materials. Various types of human tumor cells are reported to produce ECM-degrading proteases that are important in tumor progression. Among this group of proteolytic enzymes, matrix metalloproteinases (MMPs) are thought to be important due to their wide degrading function. We investigated the pleural effusion MMP-3 levels of patients with MPM and compared them with those of a population with non-malignant pleuritis or lung cancer involving malignant pleural effusion. The pleural effusion MMP-3 concentrations of 52 MPM patients and 67 non-MPM patients were measured. The results showed that the MPM patients had significantly higher pleural effusion MMP-3 levels than the population with non-malignant pleuritis. The overall survival of the MPM patients with lower pleural effusion MMP-3 levels was longer than that of patients with higher pleural effusion MMP-3 levels. Our data therefore suggest a clinical role of pleural effusion MMP-3 levels in malignant pleural mesothelioma.
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PMID:Clinical role of pleural effusion MMP-3 levels in malignant pleural mesothelioma. 2274 Sep 56

Epithelial-to-mesenchymal transition (EMT) is a process in which cells undergo a developmental switch from epithelial to mesenchymal phenotype. This process has been related to embryologic morphogenesis but also to cancer progression and metastasis. The aim of the current study was to investigate the expression of EMT-related markers in adherent and spheroid cell cultures derived from malignant pleural effusions (MPEs) of patients affected by lung adenocarcinoma. On the basis of efficient in vitro propagation, six cases of MPEs were selected and analyzed by immunocytochemistry staining for EMT markers and by RT-PCR for transcription factors known to orchestrate EMT. EMT markers immunostaining showed in spheroids a statistically significant correlation between the loss of E-cadherin immunoreactivity and overexpression of N-cadherin (P < 0.001). Likewise loss of EpCAM epithelial marker was coincident with Vimentin overexpression (P < 0.001). RT-PCR analysis of transcription factors Snail, Slug, and Twist showed a highly variable expression, although a general trend to increase was observed. Importantly, in some selected cases it was possible to establish a precise relationship between spheroid formation, EMT switch and increased upregulation of the marker related to cancer stemness such as ALDH positivity. Therefore, MPE-derived cell cultures, while recapitulating the heterogeneity of lung cancer, are a suitable system to study the mechanisms at the basis of EMT and to understand its relationship with the generation of cancer stem cells.
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PMID:EMT markers in lung adenocarcinoma pleural effusion spheroid cells. 2325 65


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