PPAR-gamma has been known to induce suppression, differentiation and reversal of malignant changes in colon cancer in vitro. However, there are several reports that PPAR-gamma ligands enhance colon polyp development in APCmin mice in vivo. These contradictory results have not yet been thoroughly explained. To explain the contradictory results, we analyzed the effects of different concentrations of the PPAR-gamma agonist, 15-deoxy-D12, 14-prostaglandin (15-d Delta PGJ2) and pioglitazone, on APC gene-mutated colon cancer cell lines (HT-29). We measured cell growth and suppression by cell count and MTT assay and analyzed the expression of beta-catenin and c-Myc protein by Western blot. In addition, we inoculated HT-29 cells into APCmin mice to compare tumor size. High concentrations (10-100 microM/L 15-d Delta PGJ2 and pioglitazone) of PPAR-gamma ligand suppressed growth, while low concentrations (0.01-1 microM/L 15-d Delta PGJ2 and pioglitazone) of PPAR-gamma ligand promoted growth. In particular, the effects of 0.1 microM/L 15-d Delta PGJ2 and pioglitazone on cell growth were statistically significant (P = 0.003, P = 0.001, respectively). Tumor growth was associated with an increase in beta-catenin and c-Myc expression. The growth of xenograft tumors was greater in PPAR-gamma ligand-treated mice than in control mice (control vs day 14: P = 0.024, control vs day 28: P = 0.007). The expression of beta-catenin and c-Myc protein were also elevated in PPAR-gamma-treated mouse tissues. PPAR-gamma ligand can promote the growth of APC-mutated HT-29 colon cancer cells in vitro and in vivo. In addition, the tumor promoting effect seems to be associated with an increase in beta-catenin and c-Myc expression. We think that well-controlled clinical trials should be conducted to confirm our results and to verify clinical applications.
Belotecan was active in SCLC patients as a single agent, warranting further investigations of belotecan in combination with platinum or other active agents.
Background: Small cell lung cancer (SCLC) originates from neuroendocrine-cell precursors and is characterized by rapid growth, high response rates and development of treatment resistance in patients with metastatic disease. In the past few years its heterogeneity in form of presentation, behavior in response to therapy and time to progression has raised several questions. Method: Review of clinical files of patients with SCLC diagnosed between May 2012 and May 2017 in our hospital, according to demographic characteristics, risk factors, comorbidities, form of presentation and diagnostic approach, clinical stage, therapy performed and outcome. Result: In this period 46 patients were followed, of whom 80% were male, with an average age of 65.5 ± 9.2 years (min 45, max 88). About 96% had active or past smoking habits. Regarding to comorbidities, it was found that 61% had a history of chronic obstructive pulmonary disease, 57% of cardiovascular disease, 17% of type 2 diabetes mellitus and 9% had a history of a second tumor. One patient had a severe usual intersticial pneumonia. The most frequent forms of presentation were pneumonia (28%) followed by constitutional symptoms (15%). Histological diagnosis was achieved in most cases by bronchial biopsy (59%). At the time of diagnosis most of the patients had ECOG performance status 1 (67%) and presented stage IV disease (72%), followed by stage IIIB (13%). In 65% of patients therapy was conducted with palliative intent, 17% with curative intent and the remaining were eligible to Best Supportive Care. Only 1 patient performed surgery with curative intent. In the 30 patients submitted to first line palliative chemotherapy with platinum doublet and etoposide, 13 partial responses and 3 stable disease (according to RECIST 1.2 criteria) were observed. About outcome, there were 35 deaths (76%), 94% of whom were patients whose initial approach was palliative. Median survival was 246 days (CI 95%). Conclusion: SCLC comprehends a heterogeneous group of patients. In recent years different subtypes of SCLC have been identified and new therapeutic molecules have been tested in order to improve management of these tumors. More studies are necessary.
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