Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.59 (MIP)
 4,906 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This is a review of the therapeutic schedules used in our service during the past 10 years for the therapy of advanced non-small-cell lung cancer. During the first years, nonrandomized trials were conducted and several combinations were tested: MACC (methotrexate, doxorubicin, cyclophosphamide, and CCNU), cisplatin-etoposide, and cisplatin-vindesine. The results of these trials were invariably discouraging: objective responses hardly reached 30%, while the survival was around 15 months in the best case. On December 1985 a new randomized trial, based on the combination MIP (mytomicin, ifosfamide, cisplatin) was designed; 60.7% of objective responses were achieved, with 9 complete remissions (17.6%) and 22 partial remissions (43.1%). Median survival was 15 months. In order to reduce the toxicity of this combination, carboplatin was substituted for cisplatin. Unfortunately, results were very poor. No complete remission, and only 5 partial responses (20%) were achieved. At the present time, a new randomized trial is being conducted. In it, MIP combination is compared with VIP (vindesine, ifosfamide, cisplatin). Preliminary results have shown no differences between both arms in response, toxicity, or survival. New therapeutic approaches, as neoadjuvant therapy, are being explored.
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PMID:Non-small-cell lung cancer (NSCLC): chemotherapy in advanced disease. Our experience in ten years. 838 16

The FONICAP group is screening, with randomised phase II studies, the activity of new chemotherapy programmes for advanced non-small-cell lung cancer (NSCLC) looking for regimens with > 30% activity. In the present study, three regimens were tested: MIP (mitomycin 6 mg m-2, ifosfamide 3 g m-2, cisplatinum 80 mg m-2 on day 1 every 28 days); MIP-IFN (MIP and interferon alpha-2b 3 MU s.c. three times a week); and PC (cisplatinum 60 mg m-2 and carboplatin 400 mg m-2 on day 1 every 28 days). Overall 93 chemotherapy-naive patients were enrolled: 23 received MIP, 27 received MIP-IFN and 43 received PC. Eighty per cent of the patients had stage IV and 20% stage IIIb disease (positive pleural effusion or supraclavicular nodes). Response rates were as follows: MIP = 9% (95% CI 1-28%), MIP-IFN = 7% (95% CI 1-24%) and PC = 14% (95% CI 5-28%). The overall median survival was 183 days. Grade III-IV leucopenia was observed in 36% of patients treated with MIP-IFN vs 10% in the other two arms, and thrombocytopenia grade III-IV was reported in nearly 10% of patients overall. In conclusion, (1) all three regimens investigated have poor activity (< 30%); (2) when tested in multicentre randomised phase II trials, MIP displays lower activity than in phase II trials; (3) PC has similar activity to other platinum-containing regimens; (4) randomised phase II studies are a reliable and quick method of determining the anti-tumour activity of novel chemotherapeutic regimens in NSCLC.
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PMID:Mitomycin-ifosfamide-cisplatinum (MIP) vs MIP-interferon vs cisplatinum-carboplatin in metastatic non-small-cell lung cancer: a FONICAP randomised phase II study. Italian Lung Cancer Task Force. 752 22

The standard therapy for advanced non-small cell lung cancer (NSCLC) remains to be defined. The poor results from chemotherapy have favored the search for prognostic factors that help identify patients more likely to respond. Our objective was to find factors related to response, the duration of response, and overall survival in patients with advanced NSCLC. We reviewed the clinical records of 292 patients with non-operable NSCLC, all of whom had a good performance status and had received chemotherapy. Ninety percent were male and the median age was 59 years. The therapeutic regimens included MACC (methotrexate, adriamycin, cyclophosphamide and CCNU), cisplatin + vindesine or etoposide, MIP (mitomycin, ifosfamide and cisplatin) and MVP (mitomycin, vindesine and cisplatin). In the multivariate analysis, a normal albumin level and the inclusion of cisplatin were related to the achievement of a response (40% if both favorable factors were present). No factors appeared related to the duration of response. The following factors were predictive for survival: weight loss, performance status, lymphocyte count, albumin level, number of metastases and the presence of bone metastases. We conclude that the albumin level identifies a group of patients with advanced NSCLC who are more likely to respond to cisplatin-containing chemotherapy.
Lung Cancer 1995 Mar
PMID:Serum albumin and other prognostic factors related to response and survival in patients with advanced non-small cell lung cancer. 760 32

To optimize pulmonary MR angiography for the noninvasive evaluation of pulmonary vasculature, six healthy volunteers were examined using the fast radiofrequency spoiled gradient echo sequence (Fast SPGR) and standard body coil of a commercial 1.5T MR imaging system. The examinations by 2D Fast SPGR were performed under various TR, flip angles and slice thicknesses within the time of a single breath hold, and those by 3D Fast SPGR were performed under various flip angles and slab thicknesses. The most satisfactory results were obtained by 2D Fast SPGR with the parameters of TR 60 msec, TE 2.1 msec, flip angle 20 degrees slice thickness 10 mm, FOV 30-40 cm, matrix 256 x 192 and NEX1. For 3D Fast SPGR, TR 10 msec, TE 1.9 msec, flip angle 10 degrees, slab thickness 60mm (12 partitions), FOV 30-40 cm, matrix 256 x 128 and NEX1 were best. Concomitant injection of Gd-DTPA provided higher resolution of peripheral vessels. The MIP images showed pulmonary vasculature with resolution of vessels beyond 4 th order branches in 2D Fast SPGR and 5 th order branches in 3D Fast SPGR. 3D Fast SPGR with contrast enhancement was applied to patients with primary lung cancer in the hilum, malignant mediastinal tumor, pulmonary embolism, pulmonary arteriovenous fistula, pulmonary varix, and round atelectasis. Pulmonary MR angiography is considered to be a noninvasive and effective method not only for the evaluation of the tumor invasion to the central pulmonary vessels but also for the demonstration of other pulmonary vascular pathology.
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PMID:[Determination of optimal technical factors for the single breath-hold pulmonary MR angiography and its clinical applications]. 869 68

Seventy-two patients with advanced stage IIIB (42%) or stage IV (58%) non-small cell lung cancer (median age 57 years, Karnofsky PS 60-100) were treated with mitomycin C (6 mg/m2, day 1), ifosfamide (1500 mg/m2, days 1-3), and cisplatin (30 mg/m2, days 1-3) every 4 weeks. The objective response rate was 37% in the overall population; 50% in stage IIIB patients and 29% in stage IV patients. Twenty four patients achieved partial response (33%) and three patients achieved complete response. Despite this relatively high objective response rate, the overall median survival time was 32 weeks. The median survival was significantly better in stage IIIB patients (55 weeks) than in stage IV patients (25 weeks) (P = 0.003). MIP regimen was permanently suspended in 14 patients because of toxic events. Seventeen patients developed grade III or IV febrile neutropenia and two patients died from sepsis. Two patients experienced acute mitomycin peumonitis. Despite increased doses of cisplatin and ifosfamide, compared with the original description for MIC chemotherapy, with probably higher toxicity, no apparent increased response rate or median survival was observed in this study. The MIP regimen could be tested in a randomized trial in comparison with other administration plans in a comparable population.
Lung Cancer 1996 Feb
PMID:Efficacy and toxicity of mitomycin, ifosfamide, and cisplatin (MIP) in patients with inoperable non-small cell lung cancer. 869 14

The chemokines are members of a bipartite superfamily of soluble proteins that have been implicated in a wide range of acute and chronic inflammatory processes, as well as other immunoregulatory functions. Macrophage inflammatory protein-1 alpha (MIP-1alpha) belongs to the C-C subfamily of these chemokines and is primarily a potent chemoattractant and activator of monocytes. MIP-1alpha is also thought to play a role in host defence. We examined the expression of MIP-1-alpha in normal lung, inflammatory lung tissue and lung cancer cells by the immunoperoxidase method using a MIP-1alpha monoclonal antibody. MIP-1alpha protein was found to be expressed not only by alveolar macrophages, but also by bronchial ciliated cells, hyperplastic alveolar type II cells and activated fibroblasts surrounding malignant tissue. Of 33 cases of lung cancer, 23 (70%) expressed MIP-1alpha. These observations suggest that lung cancer cells, non-neoplastic alveolar type II cells and fibroblasts can participate in inflammatory cell recruitment via the production of MIP-1alpha. Tumour derived MIP-alpha may also affect the interaction between lung cancer and host inflammatory cells.
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PMID:Macrophage inflammatory protein-1 alpha expression in non-neoplastic and neoplastic lung tissue. 892 23

Despite surgery, resectable NSCLC (stage I, II, and IIIA N2) has a quite poor prognosis: about 50% of patients will die during the first 2 years by metastatic disease and only 36% are alive at 5 years after diagnosis. Postoperative radiotherapy is not effective in case of complete resection (PORT meta-analysis). The role of perioperative chemotherapy is still questionnable. Cambridge meta-analysis has shown a little benefit of cisplatin based postoperative chemotherapy. Several randomised trials are completed like Alpi Trial or ANITA or still in progress. Results would be available in 2 or 3 years. Several phase II trials of preoperative chemotherapy have demonstrated that preoperative chemotherapy is feasible, with high response rate, very few progression (mainly metastatic progression without local progression) and no increase of mortality and morbidity. Two small phase III trials have demonstrated that preoperative chemotherapy can dramatically increase survival compared with surgery alone, in case of N2 disease. The MIP trial of Depierre has studied two or four cycles of MIP regimen in perioperative setting in stage IB, II or IIIA, compared to surgery alone (TRT in case of N2 disease). After 3 years of survey there is a trend in favor of MIP in case of stage IB and II (23% increase of 3 years survival) but not in case of N2. The toxicity of MIP is a possible explanation of such poor results in N2 patients despite a high response rate (64%). Some other trials are in progress in the world. Surgery is also questionnable in case of resectable N2 disease. Several trials comparing chemo radiotherapy to chemo (+/- radiotherapy)+surgery are in progress in U.S. and Europe.
Lung Cancer 2001 Dec
PMID:The role of chemotherapy in early stage of non-small cell lung cancer. 1172 Jul 58

Activating mutations in K-ras are one of the most common genetic alterations in human lung cancer. To dissect the role of K-ras activation in bronchial epithelial cells during lung tumorigenesis, we created a model of lung adenocarcinoma by generating a conditional mutant mouse with both Clara cell secretory protein (CC10)-Cre recombinase and the Lox-Stop-Lox K-ras(G12D) alleles. The activation of K-ras mutant allele in CC10 positive cells resulted in a progressive phenotype characterized by cellular atypia, adenoma and ultimately adenocarcinoma. Surprisingly, K-ras activation in the bronchiolar epithelium is associated with a robust inflammatory response characterized by an abundant infiltration of alveolar macrophages and neutrophils. These mice displayed early mortality in the setting of this pulmonary inflammatory response with a median survival of 8 weeks. Bronchoalveolar lavage fluid from these mutant mice contained the MIP-2, KC, MCP-1 and LIX chemokines that increased significantly with age. Cell lines derived from these tumors directly produced MIP-2, LIX and KC. This model demonstrates that K-ras activation in the lung induces the elaboration of inflammatory chemokines and provides an excellent means to further study the complex interactions between inflammatory cells, chemokines and tumor progression.
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PMID:K-ras activation generates an inflammatory response in lung tumors. 1628 13

Gene transfer of Fas ligand (FasL) to tumor cells has been demonstrated to inhibit tumor growth in vivo, and neutrophils are primarily responsible for this immunoprotection. The granulocyte-macrophage colony stimulating factor (GM-CSF) secreted by tumor vaccine can recruit dendritic cells (DCs) for efficient antigen presentation to T cells that generate the tumor-specific response. To investigate whether the combination of FasL and GM-CSF can efficiently suppress tumor growth, we have established Lewis lung carcinoma (LLC-1) cells that are transduced with GM-CSF (LLC/GM-CSF), FasL (LLC/FasL) or both genes (LLC/FasL/GM-CSF) to test their tumorigenic potential in vivo. Mice inoculated with LLC/GM-CSF display high survival rates along with reduction of tumor growth. In contrast, none of the mice injected with LLC/FasL or LLC/FasL/GM-CSF develop tumors. Specific memory immune response and delayed LLC-1 tumor growth are found in mice immunized with LLC-1/FasL or LLC-1/FasL/GM-CSF. Furthermore, therapeutic effects are observed only when LLC-1/FasL/GM-CSF tumor vaccine is employed to retard growth of preexisting LLC-1 tumors. Tumor growth is also completely suppressed in mice injected with a mixture of LLC-1 and LLC-1/FasL/GM-CSF. In addition, IL-12 production, cytotoxic T-cell activity and IgG against LLC-1 are manifested in mice injected with LLC/FasL/GM-CSF. Our data show that FasL-induced pathway triggers expression of proinflammatory cytokines, including IL-1 beta, IL-6, MIP-2 and MCP-1, while GM-CSF-dependent pathway promotes functional maturation and activation of DCs. Taken together, the results indicate that dual gene-based delivery with FasL and GM-CSF may serve as a more effective tumor vaccine to suppress lung cancer cell growth in vivo.
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PMID:Combination of Fasl and GM-CSF confers synergistic antitumor immunity in an in vivo model of the murine Lewis lung carcinoma. 1838 91

Arrestins are adaptor/scaffold proteins that complex with activated and phosphorylated G protein-coupled receptor to terminate G protein activation and signal transduction. These complexes also mediate downstream signaling, independently of G protein activation. We have previously shown that beta-arrestin-2 (betaarr2) depletion promotes CXCR2-mediated cellular signaling, including angiogenesis and excisional wound closure. This study was designed to investigate the role of betaarr2 in tumorigenesis using a murine model of lung cancer. To that end, heterotopic murine Lewis lung cancer and tail vein metastasis tumor model systems in betaarr2-deficient mice (betaarr2(-/-)) and control littermates (betaarr2(+/+)) were used. betaarr2(-/-) mice exhibited a significant increase in Lewis lung cancer tumor growth and metastasis relative to betaarr2(+/+) mice. This correlated with decreased number of tumor-infiltrating lymphocytes but with elevated levels of the ELR(+) chemokines (CXCL1/keratinocyte-derived chemokine and CXCL2/MIP-2), vascular endothelial growth factor, and microvessel density. NF-kappaB activity was also enhanced in betaarr2(-/-) mice, whereas hypoxia-inducible factor-1alpha expression was decreased. Inhibition of CXCR2 or NF-kappaB reduced tumor growth in both betaarr2(-/-) and betaarr2(+/+) mice. NF-kappaB inhibition also decreased ELR(+) chemokines and vascular endothelial growth factor expression. Altogether, the data suggest that betaarr2 modulates tumorigenesis by regulating inflammation and angiogenesis through activation of CXCR2 and NF-kappaB.
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PMID:Depletion of beta-arrestin-2 promotes tumor growth and angiogenesis in a murine model of lung cancer. 1839 Jul 55


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