126 research outputs found
Surgical treatment in patient with non-small-cell lung cancer with fissure involvement: Anatomical versus nonanatomical resection
OBJECTIVE: Despite the intense debate concerning the prognostic impact of fissure involvement (FI) in patients with non-small-cell lung cancer, no specific surgical strategies have been yet recommended when this condition occurs. In this setting, we report our monocentric 10-years experience to investigate this issue. METHODS: From January 2000 to January 2010, the clinical data of 40 non-small-cell lung cancer patients with FI undergoing curative resection were retrospectively reviewed. The sample was stratified according to the type of resection: group A (28 patients): anatomical resection (bilobectomy [21 patients], pneumonectomy [7 patients]); group B (12 patients): nonanatomical resection (lobectomy plus wedge resection [LWR]). The end-points were (1) impact of different surgical approach on the pulmonary function (measured before surgery and 1 month after discharge); (2) disease-specific survival; and (3) tumor recurrence.The t test, χ, and log-rank tests, Kaplan-Meier method, and Cox and logistic regression analyses were used for the statistical analysis. RESULTS: No differences between the two groups were found when comparing the clinical characteristics, histology, pN or pT status, p-stage, residual (R1) disease, tumor grading, or tumor size. Similarly, the baseline preoperative function (tested as forced expiratory volume in 1 second-%-predicted, FEV1%) was likewise comparable (92.5% ± 21.0% in group A versus 85.2% ± 20.0% in group B; p = not significant). The decline of FEV1% after surgery was slightly higher in group A (-24.9% ± 13.5%) when compared with that in group B (-19.5% ± 13.3%), but this difference was not statistically significant (p = ns). Nevertheless, the 5-year disease-specific survival was 56% for group A and 47% for group B (p = ns). The recurrence rate did not differ between the patients undergoing a LWR (3 of 12 patients) and those undergoing a bilobectomy or pneumonectomy (9 of 28 patients) (p = ns). The presence of FI extended for more than 3 cm was found to be the most significant prognostic factor when analyzing survival (p = 0.002) and recurrence rate (p< 0.001). CONCLUSIONS: Our results suggest that nonanatomical resection (LWR) could be considered as a feasible surgical option (especially in "frail" patients with an extent of FI less than 3 cm) in the light of the similar oncological and functional outcome compared with anatomical resection. Further studies based on larger series are needed to confirm these preliminary data and also to investigate the impact on the postoperative quality of life
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
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? The Spanish journal of psychology, 13(1), 5-17. doi:10.1017/s1138741600003644Barbanti, P., Bronzetti, E., Ricci, A., Cerbo, R., Fabbrini, G., Buzzi, M. G., … Lenzi, G. L. (1996). Increased density of dopamine D5 receptor in peripheral blood lymphocytes of migraineurs: a marker for migraine? Neuroscience Letters, 207(2), 73-76. doi:10.1016/0304-3940(96)12491-5Barbanti, P., Fabbrini, G., Ricci, A., Bruno, G., Cerbo, R., Bronzetti, E., … Luigi Lenzi, G. (2000). Reduced density of dopamine D2-like receptors on peripheral blood lymphocytes in Alzheimer’s disease. Mechanisms of Ageing and Development, 120(1-3), 65-75. doi:10.1016/s0047-6374(00)00183-4Barbanti, P., Fabbrini, G., Ricci, A., Pascali, M. P., Bronzetti, E., Amenta, F., … Cerbo, R. (2000). Migraine Patients Show an Increased Density of Dopamine D3 and D4 Receptors on Lymphocytes. Cephalalgia, 20(1), 15-19. doi:10.1046/j.1468-2982.2000.00001.xBarr, G. A., Sharpless, N. S., Cooper, S., Schiff, S. R., Paredes, W., & Bridger, W. H. (1983). Classical conditioning, decay and extinction of cocaine-induced hyperactivity and stereotypy. Life Sciences, 33(14), 1341-1351. doi:10.1016/0024-3205(83)90817-2Baumann, F. (1970). Hypnosis and the Adolescent Drug Abuser. American Journal of Clinical Hypnosis, 13(1), 17-21. doi:10.1080/00029157.1970.10402074Bayot, A., Capafons, A., & Cardeña, E. (1997). Emotional Self-Regulation Therapy: A New and Efficacious Treatment for Smoking. American Journal of Clinical Hypnosis, 40(2), 146-156. doi:10.1080/00029157.1997.10403418Berke, J. D., Paletzki, R. F., Aronson, G. J., Hyman, S. E., & Gerfen, C. R. (1998). A Complex Program of Striatal Gene Expression Induced by Dopaminergic Stimulation. The Journal of Neuroscience, 18(14), 5301-5310. doi:10.1523/jneurosci.18-14-05301.1998Blachly, P. H. (1971). An «Electric Needle» for Aversive Conditioning of the Needle Ritual. International Journal of the Addictions, 6(2), 327-328. doi:10.3109/10826087109057791Brown, E., Robertson, G., & Fibiger, H. (1992). Evidence for conditional neuronal activation following exposure to a cocaine-paired environment: role of forebrain limbic structures. The Journal of Neuroscience, 12(10), 4112-4121. doi:10.1523/jneurosci.12-10-04112.1992Caine, S., & Koob, G. (1993). Modulation of cocaine self-administration in the rat through D-3 dopamine receptors. Science, 260(5115), 1814-1816. doi:10.1126/science.8099761Capafons, A., & Amigoó, S. (1995). Emotional Self-Regulation Therapy for Smoking Reduction: Description and Initial Empirical Data. International Journal of Clinical and Experimental Hypnosis, 43(1), 7-19. doi:10.1080/00207149508409372Caselles, A., Micó, J. C., & Amigó, S. (2010). Cocaine addiction and personality: A mathematical model. British Journal of Mathematical and Statistical Psychology, 63(2), 449-480. doi:10.1348/000711009x470768Caselles, A., Micó, J. C., & Amigó, S. (2011). Dynamics of the General Factor of Personality in Response to a Single Dose of Caffeine. The Spanish journal of psychology, 14(2), 675-692. doi:10.5209/rev_sjop.2011.v14.n2.16Comings, D., Gade-Andavolu, R., Gonzalez, N., Wu, S., Muhleman, D., Blake, H., … MacMurray, J. (2001). A multivariate analysis of 59 candidate genes in personality traits: the temperament and character inventory. Clinical Genetics, 58(5), 375-385. doi:10.1034/j.1399-0004.2000.580508.xCzermak, C., Lehofer, M., Renger, H., Wagner, E. M., Lemonis, L., Rohrhofer, A., … Liebmann, P. M. (2004). Dopamine receptor D3 mRNA expression in human lymphocytes is negatively correlated with the personality trait of persistence. Journal of Neuroimmunology, 150(1-2), 145-149. doi:10.1016/j.jneuroim.2004.01.009Daly, S. A., & Waddington, J. L. (1993). Behavioural effects of the putative D-3 dopamine receptor agonist 7-OH-DPAT in relation to other «D-2-like» agonists. Neuropharmacology, 32(5), 509-510. doi:10.1016/0028-3908(93)90177-5Gilbert, D. G., & Hagen, R. L. (1985). Electrodermal responses to movie stressors: Nicotine × extraversion interactions. Personality and Individual Differences, 6(5), 573-578. doi:10.1016/0191-8869(85)90006-6Gilbert, D. B., Millar, J., & Cooper, S. J. (1995). The putative dopamine D3 agonist, 7-OH-DPAT, reduces dopamine release in the nucleus accumbens and electrical self-stimulation to the ventral tegmentum. Brain Research, 681(1-2), 1-7. doi:10.1016/0006-8993(95)00247-nHastings, A. (2006). An Extended Nondrug MDMA-Like Experience Evoked Through Posthypnotic Suggestion. Journal of Psychoactive Drugs, 38(3), 273-283. doi:10.1080/02791072.2006.10399853Ilani, T., Ben-Shachar, D., Strous, R. D., Mazor, M., Sheinkman, A., Kotler, M., & Fuchs, S. (2001). A peripheral marker for schizophrenia: Increased levels of D3 dopamine receptor mRNA in blood lymphocytes. Proceedings of the National Academy of Sciences, 98(2), 625-628. doi:10.1073/pnas.98.2.625Kollins, S. H., MacDonald, E. K., & Rush, C. R. (2001). Assessing the abuse potential of methylphenidate in nonhuman and human subjects: a review. Pharmacology Biochemistry and Behavior, 68(3), 611-627. doi:10.1016/s0091-3057(01)00464-6Lejeune, F., & Millan, M. J. (1995). Activation of dopamine D3 autoreceptors inhibits firing of ventral tegmental dopaminergic neurones in vivo. European Journal of Pharmacology, 275(3), R7-R9. doi:10.1016/0014-2999(95)00106-uLevant, B. (1998). Differential distribution of D3 dopamine receptors in the brains of several mammalian species. Brain Research, 800(2), 269-274. doi:10.1016/s0006-8993(98)00529-0LEVINE, D. G. (1974). «Needle Freaks»: Compulsive Self-Injection Drug Users. American Journal of Psychiatry, 131(3), 297-300. doi:10.1176/ajp.131.3.297LYNCH, J. J., STEIN, E. A., & FERTZIGER, A. P. (1976). AN ANALYSIS OF 70 YEARS OF MORPHINE CLASSICAL CONDITIONING. The Journal of Nervous and Mental Disease, 163(1), 47-58. doi:10.1097/00005053-197607000-00007Merchant, K. M., Figur, L. M., & Evans, D. L. (1996). Induction of c-fos mRNA in Rat Medial Prefrontal Cortex by Antipsychotic Drugs: Role of Dopamine D2 and D3 Receptors. Cerebral Cortex, 6(4), 561-570. doi:10.1093/cercor/6.4.561Muntaner, C., Cascella, N. G., Kumor, K. M., Nagoshi, C., Herning, R., & Jaffe, J. (1989). Placebo responses to cocaine administration in humans: effects of prior administrations and verbal instructions. Psychopharmacology, 99(2), 282-286. doi:10.1007/bf00442823Musek, J. (2007). A general factor of personality: Evidence for the Big One in the five-factor model. Journal of Research in Personality, 41(6), 1213-1233. doi:10.1016/j.jrp.2007.02.003Nagai, Y., Ueno, S., Saeki, Y., Soga, F., Hirano, M., & Yanagihara, T. (1996). Decrease of the D3 dopamine receptor mRNA expression in lymphocytes from patients with Parkinson’s disease. Neurology, 46(3), 791-795. doi:10.1212/wnl.46.3.791Neisewander, J. L., Baker, D. A., Fuchs, R. A., Tran-Nguyen, L. T. L., Palmer, A., & Marshall, J. F. (2000). Fos Protein Expression and Cocaine-Seeking Behavior in Rats after Exposure to a Cocaine Self-Administration Environment. The Journal of Neuroscience, 20(2), 798-805. doi:10.1523/jneurosci.20-02-00798.2000IMissbrandt, H., Ekman, A., Eriksson, E., & Heilig, M. (1995). Dopamine D3 receptor antisense influences dopamine synthesis in rat brain. NeuroReport, 6(3), 573-576. doi:10.1097/00001756-199502000-00041O’BRIEN, C. P., CHILDRESS, A. R., McLELLAN, A. T., & EHRMAN, R. (1992). Classical Conditioning in Drug-Dependent Humans. Annals of the New York Academy of Sciences, 654(1 The Neurobiol), 400-415. doi:10.1111/j.1749-6632.1992.tb25984.xO’Brien, C. P., Nace, E. P., Mintz, J., Meyers, A. L., & Ream, N. (1980). Follow-up of Vietnam veterans. I. relapse to drug use after Vietnam service. Drug and Alcohol Dependence, 5(5), 333-340. doi:10.1016/0376-8716(80)90159-3Pilla, M., Perachon, S., Sautel, F., Garrido, F., Mann, A., Wermuth, C. G., … Sokoloff, P. (1999). Selective inhibition of cocaine-seeking behaviour by a partial dopamine D3 receptor agonist. Nature, 400(6742), 371-375. doi:10.1038/22560Post, R. M., Lockfeld, A., Squillace, K. M., & Contel, N. R. (1981). Drug-environment interaction: Context dependency of cocaine-induced behavioral sensitization. Life Sciences, 28(7), 755-760. doi:10.1016/0024-3205(81)90157-0Ricci, A., Bronzetti, E., Mignini, F., Tayebati, S. K., Zaccheo, D., & Amenta, F. (1999). Dopamine D1-like receptor subtypes in human peripheral blood lymphocytes. Journal of Neuroimmunology, 96(2), 234-240. doi:10.1016/s0165-5728(99)00042-9Schiltz, C. A., Kelley, A. E., & Landry, C. F. (2005). Contextual cues associated with nicotine administration increasearcmRNA expression in corticolimbic areas of the rat brain. European Journal of Neuroscience, 21(6), 1703-1711. doi:10.1111/j.1460-9568.2005.04001.xSchutte, N. S., Malouff, J. M., Segrera, E., Wolf, A., & Rodgers, L. (2003). States reflecting the Big Five dimensions. Personality and Individual Differences, 34(4), 591-603. doi:10.1016/s0191-8869(02)00031-4Smith, B. D., Rockwell-Tischer, S., & Davidson, R. (1986). Extraversion and arousal: Effects of attentional conditions on electrodermal activity. Personality and Individual Differences, 7(3), 293-303. doi:10.1016/0191-8869(86)90004-8Stewart, J., de Wit, H., & Eikelboom, R. (1984). Role of unconditioned and conditioned drug effects in the self-administration of opiates and stimulants. Psychological Review, 91(2), 251-268. doi:10.1037/0033-295x.91.2.251Strange, P. G. (1993). New insights into dopamine receptors in the central nervous system. Neurochemistry International, 22(3), 223-236. doi:10.1016/0197-0186(93)90050-fSuzuki, M., Hurd, Y. L., Sokoloff, P., Schwartz, J.-C., & Sedvall, G. (1998). D3 dopamine receptor mRNA is widely expressed in the human brain. Brain Research, 779(1-2), 58-74. doi:10.1016/s0006-8993(97)01078-0Takahashi, N., Nagai, Y., Ueno, S., Saeki, Y., & Yanagihara, T. (1992). Human peripheral blood lymphocytes express D5 dopamine receptor gene and transcribe the two pseudogenes. FEBS Letters, 314(1), 23-25. doi:10.1016/0014-5793(92)81452-rTorres, G., & Rivier, C. (1994). Induction of c-fos in rat brain by acute cocaine and fenfluramine exposure: a comparison study. Brain Research, 647(1), 1-9. doi:10.1016/0006-8993(94)91391-9Volkow, N. D., Wang, G.-J., Fowler, J. S., Gatley, S. J., Logan, J., Ding, Y.-S., … Pappas, N. (1998). Dopamine Transporter Occupancies in the Human Brain Induced by Therapeutic Doses of Oral Methylphenidate. American Journal of Psychiatry, 155(10), 1325-1331. doi:10.1176/ajp.155.10.1325Volkow, N. D., Wang, G.-J., Fowler, J. S., Telang, F., Maynard, L., Logan, J., … Swanson, J. M. (2004). Evidence That Methylphenidate Enhances the Saliency of a Mathematical Task by Increasing Dopamine in the Human Brain. American Journal of Psychiatry, 161(7), 1173-1180. doi:10.1176/appi.ajp.161.7.1173Vorel, S. R., Ashby, C. R., Paul, M., Liu, X., Hayes, R., Hagan, J. J., … Gardner, E. L. (2002). Dopamine D3Receptor Antagonism Inhibits Cocaine-Seeking and Cocaine-Enhanced Brain Reward in Rats. The Journal of Neuroscience, 22(21), 9595-9603. doi:10.1523/jneurosci.22-21-09595.2002Yano, M., & Steiner, H. (2004). Topography of Methylphenidate (Ritalin)-Induced Gene Regulation in the Striatum: Differential Effects on c-Fos, Substance P and Opioid Peptides. Neuropsychopharmacology, 30(5), 901-915. doi:10.1038/sj.npp.130061
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
Randomised study of adjuvant chemotherapy for completely resected p-stage I–IIIA non-small cell lung cancer
We evaluated the therapeutic usefulness of adjuvant chemotherapy in patients with completely resected non-small cell lung cancer (NSCLC). We also examined the relation between DNA ploidy pattern and the response to chemotherapy. A total of 267 patients with NSCLC (pathologically documented stage I, II, or IIIA) underwent complete resection, and DNA ploidy pattern was analysed. Patients with stage I disease (n=172) were randomly assigned to receive surgery alone (group A) or surgery followed by adjuvant chemotherapy (UFT (oral anti-cancer drug, a combination of Uracil and Tegaful) 400 mg day−1 for 1 year after surgery; group B). Stage II or IIIA disease patients (n=95) were randomly assigned to surgery alone (group C) or surgery followed by chemotherapy (two 28-day courses of cisplatin 80 mg m−2 on day 1 plus vindesine 3 mg m−2 on days 1 and 8, followed by UFT 400 mg day−1 for at least 1 year; group D). Eight-year overall survival rate in patients with stage I disease was 74.2% (95% confidence interval (CI): 64.4–84.0%) in group B and 57.6% (95% CI: 46.4–68.8%) in group A (P=0.045 by log-rank test). In patients with stage II and IIIA disease, no difference was found between groups C and D. Analysis according to DNA ploidy pattern revealed no difference between the groups. Postoperative chemotherapy with UFT was suggested to be useful in patients with completely resected stage I NSCLC. No difference was seen in relation to DNA pattern in any treatment group
- …