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)

Carbonic anhydrase-related protein VIII (CA-RP VIII) is expressed in most non-small cell lung cancer, and especially strongly at the front of tumor progression. Screening analysis of CA-RP VIII expression in a panel of cultured lung cancer cell lines showed that a well differentiated adenocarcinoma cell line, PC-9, appeared to lack CA-RP VIII. Subsequently, CA8 cDNA was transfected with an expression vector into PC-9. Ectopic overexpression of CA-RP VIII reduced the growth of PC-9 cells on uncoated culture dishes, especially when the cultures were started at low cell density, but increased cell growth on laminin-coated dishes. Interestingly, ectopic CA-RP VIII expression markedly reduced caspase-3 activity induced by serum starvation and anti-cancer agents in PC-9 cells. The present findings suggest that CA-RP VIII expression promotes progression of lung cancer by multifarious mechanisms.
 ...
PMID:Effect of carbonic anhydrase-related protein VIII expression on lung adenocarcinoma cell growth. 1514 May 39

Mice bearing LP07 lung adenocarcinoma show some characteristics that are similar to those present in patients with NSCLC. LP07 tumor-bearing mice develop the paraneoplastic syndromes of cachexia, leukocytosis and hypercalcemia. These symptoms may be partly due to a systemic inflammatory response. Our aim was to determine if treatment with NSAIDs would lower tumor and metastasis growth and their accompanying syndromes. The nonselective COX inhibitor indomethacin and the selective COX-2 inhibitor celecoxib reduced tumor growth and metastasis outcome in s.c. LP07 tumor-bearing mice. Both drugs also inhibited the development of leukocytosis and the weight loss associated with LP07 progression. Serum levels of the inflammatory cytokines IL-1beta and IL-6, mediators of cachexia, were modulated by NSAIDs. Inhibition of in vitro migration and invasion and reduction in angiogenesis were attained when cells were treated with either indomethacin or celecoxib. MMP-9 activity was also reduced in conditioned media from LP07 cells treated with celecoxib. These data suggest that several processes implicated in tumor progression can be modulated with NSAID treatment. Improvement in performance status through modulation of cachexia may offer a possibility for combining anti-inflammatory treatments with more aggressive therapies.
 ...
PMID:Reduction of tumor progression and paraneoplastic syndrome development in murine lung adenocarcinoma by nonsteroidal antiinflammatory drugs. 1517 Jun 63

Preclinical studies suggest that cyclooxygenase (COX)-2 may be involved in the molecular pathogenesis of some types of lung cancer. Most of the available studies point to its involvement in non-small cell lung cancer. Survival of patients with non-small cell lung cancer expressing high levels of COX-2 is markedly reduced. Treatment of humans with the selective COX-2 inhibitor celecoxib augments the antitumor effects of chemotherapy in patients with non-small cell lung cancer. COX-2 has been shown to regulate some aspects of tumor-associated angiogenesis. Most of the results we have published point to effects on the regulation of vascular endothelial growth factor. However, prostaglandins derived from COX-2 affect other signaling pathways as well, such as the epidermal growth factor and its receptor. Others have recently shown that non-small cell lung cancer exhibits a COX-2 downstream enzyme expression pattern that is altered in lung tumor cells and tumor-supplying vessels. Therefore, COX-2 and prostaglandins may have a major impact on lung tumor progression and tumor-associated inflammation. Clinical trials currently underway are exploring the potential of targeting COX-2 in lung cancer.
 ...
PMID:Cyclooxygenase as a target in lung cancer. 1521 72

Cyclooxygenase-2 (Cox2) may play a crucial role in lung carcinogenesis. In fact, overexpression of Cox2 is common in non-small cell lung cancer (NSCLC) and seems to be associated with tumor progression, invasion and metastasis. In experimental animal models Cox2 has been shown to be involved in tumor angiogenesis, suggesting that Cox2 is a potential target for NSCLC therapy. Several in vivo studies have already shown that Cox2 specific inhibitors (celecoxib, rofecoxib) have anti-tumor activity and clinical trials using Cox2 inhibitors are currently ongoing in patients with NSCLC.
 ...
PMID:[Cyclooxygenase 2 inhibitors and lung carcinoma]. 1523 38

Cyclooxygenase-2 (Cox2) may play a crucial role in lung carcinogenesis. In fact, overexpression of Cox2 is common in non-small cell lung cancer (NSCLC) and seems to be associated with tumor progression, invasion and metastasis. In experimental animal models Cox2 has been shown to be involved in tumor angiogenesis, suggesting that Cox2 is a potential target for NSCLC therapy. Several in vivo studies have already shown that Cox2 specific inhibitors (celecoxib, rofecoxib) have anti-tumor activity and clinical trials using Cox2 inhibitors are currently ongoing in patients with NSCLC.
 ...
PMID:[Cyclooxygenase 2 inhibitors and lung carcinoma]. 1589 34

On August 19, 2004, pemetrexed for injection (Alimta); Eli Lilly and Company, Indianapolis, IN, http://www.lilly.com) received accelerated approval as monotherapy for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who had received prior chemotherapy. Approval was primarily based on a single, controlled, unblinded trial. Five hundred seventy-one protocol-eligible patients were randomized to receive either pemetrexed or docetaxel (Taxotere); Aventis Pharmaceuticals Inc., Bridgewater, NJ, http://www.aventispharmaus.com). The primary efficacy end point was overall survival. The median survival times were 8.3 months in the pemetrexed arm and 7.9 months in the docetaxel arm. Neither superiority nor noninferiority for overall survival could be demonstrated, the latter because a reliable and consistent survival effect of docetaxel could not be estimated and because of significant crossover of pemetrexed-treated patients to docetaxel after tumor progression. Comparable response rates, 9.1% for pemetrexed and 8.8% for docetaxel, times to progressive disease, and progression-free survival times supported the conclusion that an effect of pemetrexed on survival was reasonably likely, however. In addition, pemetrexed was felt to have a more favorable safety profile than docetaxel. Of greatest importance, pemetrexed caused significantly less neutropenia, febrile neutropenia, neutropenic infections, and need for granulocyte/macrophage colony-stimulating factors.
 ...
PMID:FDA drug approval summary: pemetrexed for injection (Alimta) for the treatment of non-small cell lung cancer. 1596 29

It has been documented that estrogen receptor (ER) transcription silencing due to hypermethylation is linked to the tumor progression of breast, uterine and prostate cancers. Additionally, ER hypermethylation in lung tumors has been associated with the exposure of specific carcinogens in animal study. The role of hypermethylation-induced ER transcription silencing in lung tumor progression and its prognostic value for non-small cell lung cancer (NSCLC) patients remained unclear. In our study, ER hypermethylation of 123 lung tumors and adjacent normal parts were examined by methylation-specific PCR (MSP). Estrogen receptor mRNA expression in lung tumors was determined by RT-PCR. Our data indicated that ER hypermethylation was only detected in lung tumors, but not in adjacent normal lung tissues. This suggests that ER hypermethylation may be associated with lung tumorigenesis. Among the clinical parameters studied, only gender factor was correlated with ER hypermethylation with a higher frequency of ER hypermethylation being in male patients than in female patients (58 vs. 34%, p = 0.01). After being stratified by gender and cigarette smoking status, a similarly high prevalence of ER hypermethylation was found in male smoking and nonsmoking patients (60 vs. 61%) as compared to that of female nonsmoking patients (34%). To investigate if 17-beta estradiol (E2) was responsible for such gender difference in ER hypermethylation, a lung cancer A549 cell with ER hypermethylation and without ER mRNA expression was treated with E2 of various concentrations for defined time intervals to show that an E2 treatment could restore the expression of ER mRNA and eliminate ER hypermethylation. Western blot data also showed that acetylated histone 3 and histone 4 of chromatin were increased significantly by E2 treatment. Thus, E2 can make ER mRNA re-expression by eliminating ER hypermethylation. To elucidate the prognostic value of ER hypermethylation, Kaplan-Meier analysis was carried out to show that patients with ER hypermethylation had a poorer prognosis than those without ER hypermethylation. Such prognostic prediction, however, applied only to male (p = 0.0044) patients. Cox regression analysis further showed the feasibility of ER hypermethylation as an independent prognostic factor of NSCLC (p = 0.007). It is possible that antiestrogens may have different therapeutic values for male and female lung cancer patients.
 ...
PMID:Gender difference in estrogen receptor alpha promoter hypermethylation and its prognostic value in non-small cell lung cancer. 1598 39

Pancreatic cancer (PanC) is an extremely lifethreatening neoplasm due to its late discovery, rapid progression and resistance to chemo- and radiotherapy. In the past years a significant research attention turned to this cancer. Extensive genomic analysis of PanC revealed numerous alterations, however, none of them emerged yet as a key regulator of tumor progression. Our increasing knowledge on the molecular targets in various cancer types started to change their management. Examples of success of the molecular therapies (in CML, GIST, NSCLC) may initiate more activity in pancreatic cancer as well.
 ...
PMID:Genomics of pancreatic cancer: does it make any improvement in diagnosis, prognosis and therapy? 1599 49

The role of matrix metalloproteinase (MMP)9 in lung cancer progression is controversial. MMP9 promotes local tumor progression and distant metastasis in mouse models by enhancing extracellular matrix degradation, releasing VEGF from extracellular matrix and promoting vascular pericyte recruitment. Furthermore, increased plasma MMP9 expression levels in human subjects with metastatic non-small cell lung cancer (NSCLC) inversely correlates with survival. In contrast, MMP9 can benefit the host by generating inhibitors of endothelial cell proliferation such as angiostatin and NC1 domains of collagen IV. To better understand the role of host MMP9 on the primary growth and metastatic potential of NSCLC, we performed an orthotopic model of NSLC in integrin alpha1-null mice (a genetic model for increased MMP9). In these mice we observed decreased number, size and vascularization of primary NSCLC tumors when compared to wild type controls. In addition, decreased number and size of NSCLC-derived metastases were evident in the alpha1-null mice. Furthermore, pharmacological inhibition of MMPs in the alpha1-null mice at the time of tumor cell injection resulted in an increase in the number of both primary and metastatic lung cancer as compared to untreated mice, suggesting that primary growth and metastases of NSCLC are worsened by the early inhibition of MMPs. In conclusion, although MMP9 may potentially promote tumor growth and metastasis, production of MMP-dependent anti-angiogenic factors seems to override these effects and protects the host from NSCL growth and progression.
 ...
PMID:An orthotopic model of lung cancer to analyze primary and metastatic NSCLC growth in integrin alpha1-null mice. 1608 39

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.
 ...
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


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>