76 research outputs found
F-024TIME-TREND ANALYSIS OF THE PULMONARY FUNCTION AFTER SURGICAL TREATMENT FOR OESOPHAGEAL CANCER: POTENTIALITY AND ROLE OF PULMONARY REHABILITATION
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Farnesyltransferase inhibitors and human malignant pleural mesothelioma: a first-step comparative translational study.
It is known that the potential clinical use of farnesyltransferase
inhibitors (FTI) could be expanded to include
cancers harboring activated receptor tyrosine kinases.
Approximately 70% of malignant pleural mesotheliomas
(MPM) overexpress epidermal growth factor receptors
(EGFR) and a subset express both EGFR and transforming
growth factor A (TGF-A), suggesting an autocrine role for
EGFR in MPM. We checked on MPM cells (10 human cell
lines, 11 primary cultures obtained by human biopsies, and
7 short-term normal mesothelial cell cultures) concerning the
following: (a) the relative overexpression of EGFR (Western
blotting, flow cytometry, immunohistochemistry), (b) the
relative expression of EGFR ligands (EGF, amphiregulin,
TGF-A, ELISA), (c) the relative increase of the activated
form of Ras (Ras-bound GTP) after EGF stimulation (Ras
activation assay), (d) the efficacy of five different FTIs (HDJ2
prenylation, cell cytotoxicity, and apoptosis using ApopTag
and gel ladder). EGFR was overexpressed in MPM cells
compared with normal pleural mesothelial cells in equivalent
levels as in non\u2013small cell lung cancer cells A549.
MPM cells constitutively expressed EGFR ligands; however,
Ras activation was attenuated at high EGF concentrations
(100 ng/mL). Growth of MPM cells was substantially not
affected by treatment with different FTIs (SCH66336, BMS-
214662, R115777, RPR-115135, and Manumycin). Among
these, BMS-214662 was the only one moderately active.
BMS-214662 triggered apoptosis in a small fraction of cells
(not higher than 30%) that was paralleled by a slight
decrease in the levels of TGF-A secreted by treated MPM
cells. Our data highlighted the concept that the same
signaling pathway can be regulated in different ways and
these regulations can differ between different cells of
different origin
Mutations in K-ras Codon 12 Detected in Plasma DNA Are Not an Indicator of Disease in Patients with Non-Small Cell Lung Cancer.
post operative rehabilitation for surgically resected non small cell lung cancer patients serial pulmonary functional analysis
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ACTH-producing tumorlets and carcinoids of the lung: clinico-pathologic study of 63 cases and review of the literature.
Adrenocorticotropic hormone (ACTH)-secreting lung carcinoids represent the principal cause of ectopic Cushing syndrome, but the prevalence of ACTH expression and the association between ACTH production and Cushing syndrome in lung carcinoids have scarcely been investigated. In addition, available information on the prognostic meaning of ACTH production is controversial. The aims of this multicentric retrospective study, also including a review of the literature, were to describe the clinico-pathologic features of ACTH-producing lung carcinoids, to assess recurrence and specific survival rates, and to evaluate potential prognostic factors. To identify ACTH production in 254 unselected and radically resected lung carcinoids, we used a double approach including RT-PCR (mRNA encoding for pro-opiomelanocortin) and immunohistochemistry (antibodies against ACTH and β-endorphin). Sixty-three (24.8%) tumors produced ACTH and 11 of them (17.4%), representing 4.3% of the whole series, were associated with Cushing syndrome. The median follow-up time was 71 months. The 10-year overall and specific survival rates were 88.5% and 98.2%, respectively, with difference neither between functioning and nonfunctioning tumors nor between ACTH-positive and ACTH-negative carcinoids. At univariate analysis, histological type (typical or atypical) and Ki67 index significantly correlated with tumor recurrence. The literature review identified 172 previously reported patients with functioning ACTH-secreting lung carcinoids, and the meta-analysis of survival showed that 92% of them were alive after a mean follow-up time of 50 months. Our results demonstrate that ACTH-producing lung carcinoids are not rare, are not always associated with Cushing syndrome, and do not represent an aggressive variant of lung carcinoid
Self-Regulation Therapy to Reproduce Drug Effects: A Suggestion Technique to Change Personality and the DRD3 Gene Expression
This study proposes a strategy, based on self-regulation
therapy, to change personality and its biological substrate, the DRD3
gene expression. It has been demonstrated that acute doses of stimulating
drugs, like methylphenidate, are able to change personality
and the expression of certain genes in the short term. On the other
hand, self-regulation therapy has been proven to reproduce the effects
of drugs. Thus, it is feasible to hope that self-regulation therapy is
equally effective as methylphenidate in changing personality and the
gene expression. This is a preliminary study with a single-case experimental
design with replication in which 2 subjects participated. The
results and potential implications for research and psychotherapy are
discussed.Amigó Borrás, S.; Caselles Moncho, A.; Micó Ruiz, JC. (2013). Self-Regulation Therapy to Reproduce Drug Effects: A Suggestion Technique to Change Personality and the DRD3 Gene Expression. International Journal of Clinical and Experimental Hypnosis. 61(3):282-304. doi:10.1080/00207144.2013.784094S282304613Accili, D., Fishburn, C. S., Drago, J., Steiner, H., Lachowicz, J. E., Park, B. H., … Fuchs, S. (1996). A targeted mutation of the D3 dopamine receptor gene is associated with hyperactivity in mice. Proceedings of the National Academy of Sciences, 93(5), 1945-1949. doi:10.1073/pnas.93.5.1945Amigó, S., Caselles, A., & Micó, J. C. (2008). A dynamic extraversion model. The brain’s response to a single dose of a stimulant drug. British Journal of Mathematical and Statistical Psychology, 61(1), 211-231. doi:10.1348/000711007x185514Amigó, S., Caselles, A., & Micó, J. C. (2010). General Factor of Personality Questionnaire (GFPQ): Only one Factor to Understand Personality? 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Molecular genetic alterations in egfr CA-SSR-1 microsatellite and egfr copy number changes are associated with aggressiveness in thymoma
Background: The key role of egfr in thymoma pathogenesis has been questioned following the failure in identifying recurrent genetic alterations of egfr coding sequences and relevant egfr amplification rate. We investigated the role of the non-coding egfr CA simple sequence repeat 1 (CA-SSR-1) in a thymoma case series. Methods: We used sequencing and egfr-fluorescence in situ hybridization (FISH) to genotype 43 thymomas; (I) for polymorphisms and somatic loss of heterozygosity of the non-coding egfr CA-SSR-1 microsatellite and (II) for egfr gene copy number changes. Results: We found two prevalent CA-SSR-1 genotypes: A homozygous 16 CA repeat and a heterozygous genotype, bearing alleles with 16 and 20 CA repeats. The average combined allele length was correlated with tumor subtype: Shorter sequences were significantly associated with the more aggressive WHO thymoma subtype group including B2/B3, B3 and B3/C histotypes. Four out of 29 informative cases analysed for somatic CA-SSR-1 loss of heterozygosity showed allelic imbalance (AI), 3/4 with loss of the longer allele. By egfr-FISH analysis, 9 out of 33 cases were FISH positive. Moreover, the two integrated techniques demonstrated that 3 out of 4 CA-SSR-1-AI positive cases with short allele relative prevalence showed significantly low or high chromosome 7 "polysomy"/increased gene copy number by egfr-FISH. Conclusions: Our molecular and genetic and follow up data indicated that CA-SSR-1-allelic imbalance with short allele relative prevalence significantly correlated with EGFR 3+ immunohistochemical score, increased egfr Gene Copy Number, advanced stage and with relapsing/metastatic behaviour in thymomas
Vascular phenotype in angiogenic and non-angiogenic lung non-small cell carcinomas
We have previously described a group of non-small cell lung carcinomas without morphological evidence of neo-angiogenesis. In these tumours neoplastic cells fill up the alveoli and the only vessels present appear to belong to the trapped alveolar septa. In the present study we have characterised the phenotype of the vessels present in these non-angiogenic tumours, in normal lung and in angiogenic non-small cell lung carcinomas. The vessels, identified by the expression of CD31, were scored as mature when expressing the epitope LH39 in the basal membrane and as newly formed when expressing αVβ3 on the endothelial cells and/or lacking LH39 expression. In the nine putative non-angiogenic cases examined, the vascular phenotype of all the vessels was the same as that of alveolar vessels in normal lung: LH39 positive and αVβ3 variable or negative. Instead in 104 angiogenic tumours examined, only a minority of vessels (mean 13.1%; range 0–60%) expressed LH39, while αVβ3 (in 45 cases) was strongly expressed on many vessels (mean 55.5%; range 5–90%). We conclude that in putative non-angiogenic tumours the vascular phenotype is that of normal vessels and there is no neo-angiogenesis. This type of cancer may be resistant to some anti-angiogenic therapy and different strategies need to be developed
Aneuploidy and prognosis of non-small-cell lung cancer: a meta-analysis of published data
In lung cancer, DNA content abnormalities have been described as a heterogeneous spectrum of impaired tumour cell DNA histogram patterns. They are merged into the common term of aneuploidy and probably reflect a high genotypic instability. In non-small-cell lung cancer, the negative effect of aneuploidy has been a subject of controversy inasmuch as studies aimed at determining the survival–DNA content relationship have reported conflicting results. We made a meta-analysis of published studies aimed at determining the prognostic effect of aneuploidy in surgically resected non-small-cell lung cancer. 35 trials have been identified in the literature. A comprehensive collection of data has been constructed taking into account the following parameters: quality of specimen, DNA content assessment method, aneuploidy definition, histology and stage grouping, quality of surgical resection and demographic characteristics of the analysed population. Among the 4033 assessable patients, 2626 suffered from non-small-cell lung cancer with aneuploid DNA content (overall frequency of aneuploidy: 0.65; 95% CI: (0.64–0.67)). The DerSimonian and Laird method was used to estimate the size effects and the Peto and Yusuf method was used in order to generate the odds ratios (OR) of reduction in risk of death for patients affected by a nearly diploid (non-aneuploid) non-small-cell lung cancer. Survivals following surgical resection, from 1 to 5 years, were chosen as the end-points of our meta-analysis. Patients suffering from a nearly diploid tumour benefited from a significant reduction in risk of death at 1, 2, 3 and 4 years with respective OR: 0.51, 0.51, 0.45 and 0.67 (P< 10−4for each end-point). 5 years after resection, the reduction of death was of lesser magnitude: OR: 0.87 (P = 0.08). The test for overall statistical heterogeneity was conventionally significant (P< 0.01) for all 5 end-points, however. None of the recorded characteristics of the studies could explain this phenomenon precluding a subset analysis. Therefore, the DerSimonian and Laird method was applied inasmuch as this method allows a correction for heterogeneity. This method demonstrated an increase in survival at 1, 2, 3, 4 and 5 years for patients with diploid tumours with respective size effects of 0.11, 0.15, 0.20, 0.20 and 0.21 (value taking into account the correction for heterogeneity;P< 10−4for each end-point). Patients who benefit from a surgical resection for non-small-cell lung cancer with aneuploid DNA content prove to have a higher risk of death. This negative prognostic factor decreases the probability of survival by 11% at one year, a negative effect deteriorating up to 21% at 5 years following surgery. © 2001 Cancer Research Campaign http://www.bjcancer.co
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