Neoadjuvant chemoradiotherapy (NCRT) followed by surgery is the gold standard for the treatment of patients with locally advanced rectal cancer (LARC). However, response is variable, and no ...predictive markers have been validated. The amplification of 13q31-34 seemed to distinguish between nonresponders and responders to NCRT. The miR-17-92a-1 cluster host gene (MIR17HG), which is involved in the development, progression, and aggressiveness of colorectal cancer, and the ABCC4 gene, an ATP-binding cassette transporter, are located at this region. Moreover, the transcription factor c-Myc is closely related to MIR17HG. The aim of this study was to examine the role of MIR17HG, ABCC4, and CMYC gene copy numbers (CNs) in determining response to NCRT. We analyzed DNA CN of pretherapy biopsies from 108 LARC patients and the expression of microRNA (miR)-17, miR-18a, miR-19a, miR-19b-1, miR-20a, and miR-92a-1 in 34 biopsies. MIR17HG, CMYC, and ABCC4 gene CNs were frequently altered in pretreatment tumors, amplification being the most frequent alteration. With regard to response to therapy, 41% of responders showed MIR17HG deletion, while MIR17HG amplification was observed in 41% of nonresponders. With regard to pathological T stage (ypT), a higher percentage of ypT3-4 than ypT0-2 tumors showed MIR17HG amplification. Finally, a higher, albeit nonsignificant, variability in the expression of MIR17HG cluster members was detected in nonresponders compared to responders. No association was observed between clinical pathological parameters and ABCC4 or CMYC CN. Our data did not highlight a significant association between MIR17HG, CMYC, and ABCC4 gene CNs and response to NCRT in LARC. However, MIR17HG gene amplification would seem to be related to a lack of response. Evaluation of the expression of MIR17HG cluster members is warranted in a larger case series, together with functional studies, to evaluate the potential of this gene as a new predictive marker.
Background: Although neoadjuvant chemoradiotherapy (NCRT) in rectal cancer represents the gold standard for clinical practice, more than one third of patients do not respond. Epigenetic aberrations, ...such as DNA methylation, have been shown to play a role in rectal cancer progression and prognosis. The present study aimed to analyze the potential of specific gene hypermethylation in predicting resistance or sensitivity to NCRT in order to optimize therapeutic strategies. Materials and Methods: Fifty candidates for NCRT were recruited, and pretreatment paraffin-embedded biopsies from all cases were analyzed by methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA). A probemix containing 26 probes was used to detect the methylation status of promoter regions of 24 different tumor suppressor genes. Methylation status was analyzed in relation to pathologic response evaluated by tumor regression grade (TRG), according to Dworak criteria. Results: Frequent high methylation was observed for six sites (ESR1, CDH13, CDKN2B, RARB, IGSF4, APC), but no correlation with TRG was found. Conversely, interesting results emerged for CHFR and BRCA2 gene methylation. In particular, low levels of CHFR and high levels of BRCA2 methylation, which characterized about 25% of the entire study population, were indicative of clinical response in 75% of cases. The inverse profile, which included another 25% of the population, was associated with clinical resistance in 91% of cases. Conclusion: The results from the present study suggest that quantitative epigenetic classification of rectal cancer by MS-MLPA could be useful in predicting radiochemosensitivity or resistance. In particular, methylation status of CHFR and BRCA2 proved indicative of sensitivity or resistance to NCRT in about 50% of the overall population. Further studies are ongoing to confirm these preliminary findings.
To evaluate the quality of life (QL) in patients with ductal carcinoma in situ of the breast treated with conservative surgery and postoperative irradiation.
A self-completed questionnaire covering ...many disease-, symptom-, and treatment-specific issues was administered to 106 conservatively treated patients affected by non-infiltrating breast cancer. The questionnaire was based on a series of 34 items assessing five main fields of post-treatment adjustment: physical well being, sexual adaptation, aesthetic outcome, emotional/psychological well being, relational behaviour. Furthermore, the patients were requested to evaluate the degree of information provided by the medical staff concerning surgical procedures and radiation therapy, and to evaluate the effects of the treatment on their social and overall life.
The questionnaire was completed by 83 patients (78%), who had a median follow-up of 54.5 months. This final sample had a median age of 50 years (range 29-88) at the time of treatment and 54 years (range 32-94) at the time of study. The patients claimed to be in good physical condition. Data relating to sexual life were provided by 93% of the sample. Some limitations in sexuality, some interference with sexual desire, and some modifications during intercourse were reported by 5, 6, and 5 patients, respectively. The subjective evaluations of the cosmetic results of the therapies were generally good. Only 13 patients (16%) reported the perception of a worsened body image. Forty-six percent of the sample (38 patients) declared that they felt tense, 48% (39 patients) nervous, 29% (38 patients) lonely, 59% (41 patients) anxious, and 41% (34 patients) depressed. Only seven patients (8%) declared that the treatment had had a bad effect on their social life, and 15 (18%) thought that their current life had been affected by the treatment. The amount of information received concerning the disease and treatment (surgery and radiotherapy) was considered sufficient by 79%, 75%, and 79% of the sample, respectively.
This study revealed a good QL in patients treated with breast conservation and postoperative irradiation, with a preserved favourable body image and a lack of negative impact on sexuality. Radiation therapy did not lead to any significant additional problems capable of affecting the QL.
From 1981 to 1991, fifty-three patients with primary gastric lymphoma were referred to our Institute and submitted to a complete pathologic staging followed by gastric resection, i.e., total or ...partial gastrectomy. According to the Working Formulation criteria, 14 patients (26.4%) were affected with high grade lymphomas, 22 (41.5%) with intermediate lymphomas and 17 (32.1%) with low grade lymphomas. MALT (mucosa associated lymphoid tissue) lymphomas were observed in > 50% of cases. At the pathologic examination of the surgical specimens, infiltration depth was assessed, according to TNM criteria, in the patients whose disease was limited to the muscular gastric wall (T1-T2) and in those whose disease spread to the serosa or beyond it (T3-T4). Twenty-five patients were classified as stage I and 28 as stage II (9 of them in stage II E1 and 19 in stage II E2 according to Musshoff's classification). The treatment protocol of these patients was as follows: stage I patients (T1-T2) with normal surgical resection margins underwent no adjuvant treatment (10 patients); stage I patients (T1-T2) with resection margins infiltrated by the disease were submitted to local irradiation; stage I (T3-T4) and stage II E1 patients underwent large-field postoperative irradiation (14 patients); stage II E2 patients (n = 19) received conventional chemotherapy (CHOP, F-CVP, N-CVP): the ones who failed to reach complete remission or presented with bulky disease at diagnosis completed the treatment with large-field irradiation (10 patients). The disease-free survival (86.5%) and the overall survival (96%) rates of stage I patients exhibited no significant difference relative to stage II patients (DFS: 87% and OS: 90%). The analysis of relapses relative to disease extent demonstrated that this parameter is more significant to prognosis than nodal involvement (T1-T2: 2/39 relapses, 5.1%; T3-T4: 4/14 relapses, 28.6%).
Even if surgical resection continues to be the mainstay of treatment in rectal cancer, preoperative chemoradiation may downstage locally advanced rectal cancer, in some cases with no residual tumors. ...Compared with surgery alone, preoperative radiotherapy and chemotherapy improves outcomes in patients with locally advanced rectal cancer. In the present review we summarize the results of preoperative chemoradiation therapy in a group of 15 patients who underwent surgical resection with total mesorectal excision (TME) for advanced mid and low rectal cancer from February 2002 to February 2004.
La grande vague de la bande dessinée horreur et gore qui submergea les kiosques italiens entre la seconde moitié des années 80 et le début des années 90 a trouvé son inspiration dans les produits ...américains. Ainsi est née en Italie une BD qui encore aujourd’hui a des milliers de lecteurs : Dylan Dog, BD de série de la maison éditrice Bonelli, créée par l’auteur Tiziano Sclavi, ouvertement composée avec des hommages cinématographiques. Peu de temps après, une BD splatter-horror métropolitaine est réalisée dans Splatter, Mostri, Blob, Profondo Rosso, Hellraiser, Gore Scanners, Horror, puis, par un certain nombre d’épigones de Dylan Dog. Alcide Pierantozzi, avec sa cruelle écriture, est fils de cette vague.
SETI-Italia is the Italian national SETI Program. It is run as a part of the Italian Bioastronomy Project, by IRA (Istituto di Radioastronomia) a subsidiary of the Istituto Nazionale di Astrofisica. ...At the moment, Italy is the only European country conducting a continuous SETI “listening” program, while occasional SETI searches may be conducted in France and the Ukraine. Outside Europe, continuous SETI programs are conducted in the USA, Australia and Argentina. The SETI-Italia activities started early in 1998 with a Serendip IV system connected in piggy-back mode to the Medicina VLBI 32-m antenna dish. In the years 2002/2003, considerable efforts were devoted to set up a fast computational system capable of computing the KLT (Karhunen–Loève transform). This is a virtually new mathematical procedure in SETI, and is much more general than the FFT. It can search for the presence of signals both narrow-band and wide-band embedded in noise both coloured and white. The mathematical features the KLT have already been described in this Conference by Claudio Maccone Innovative SETI by the KLT, Pešek Lecture 2003, paper # IAA.9.1.01 presented in Bremen, in this 2003 International Astronautical Congress
1; Telecommunications, KLT and Relativity, vol. 1, IPI Press, Colorado Springs, CO, 1994, ISBN #1-880930-04-8
2.. Our software implementation of the KLT follows these lines and also is indebted to some basic ideas put forward by Robert S. Dixon On the detection of unknown signals, in: G. Seth Shostak (Ed.), Third Decennial US–USSR Conference on SETI, Astronomical Society of the Pacific Conference Series, vol. 47, 1993, pp. 128–140 of the Ohio State Radio Observatory as early as 1993.
PDF
