Carlo Terenzio Paties

Gefitinib in Pretreated Non–Small-Cell Lung Cancer (NSCLC): Analysis of Efficacy and Correlation With HER2 and Epidermal Growth Factor Receptor Expression in Locally Advanced or Metastatic NSCLC

PURPOSE To evaluate the correlation between HER2 expression and gefitinib (ZD 1839, Iressa; AstraZeneca, London, United Kingdom) efficacy in terms of response rate, time to progression (TTP), and overall survival (OS) time. PATIENTS AND METHODS Patients with pretreated advanced non-small-cell lung cancer (NSCLC) received gefitinib at a daily dose of 250 mg until disease progression. Tumor tissue specimens obtained at the time of primary diagnosis were collected to determine HER2/epidermal growth factor receptor (EGFR) status by immunohistochemistry. RESULTS From February 2001 to June 2002, 63 consecutive patients were enrolled onto the study. The overall disease control rate was 58.7% (partial response [PR], 15.9%; stable disease [SD], 42.8%), median TTP was 3.3 months, and median OS was 4.1 months. Among the 43 patients in whom EGFR/HER2 status was determined, we observed six PRs (14%) and 18 SDs (42%). Disease control, including PR and SD, was 40% in the 15 patients overexpressing HER2 and 64.3% in the 28 patients not overexpressing HER2 (P =.126). No difference was found between the two groups in terms of TTP (3.5 v 3.7 months, respectively) and OS (5.7 v 6.8 months, respectively). In addition, we did not find any difference in TTP, OS, toxicity, and symptom outcome in the group of patients overexpressing both HER2 and EGFR compared with patients who had no overexpression of HER2 CONCLUSION According to these data, efficacy, toxicity, and symptom outcome in patients with NSCLC treated with gefitinib do not seem to be related to HER2 expression.

Molecular and functional characterization of allogantigen specific anergic T cells suitable for cell therapy

Background CD4+ regulatory T cells are a specialized subset of T cells that actively control immune responses. Several experimental protocols have been used to expand natural regulatory T cells and to generate adaptive type 1 regulatory T cells for regulatory T-cell-based therapies. Design and Methods The ability of exogenous recombinant human interleukin-10 to induce alloantigen-specific anergy in T cells was investigated and compared to that of interleukin-10 derived from tolerogenic dendritic cells, in mixed lymphocyte cultures. A detailed characterization of the effector functions of the resulting anergized T cells is reported. Results Interleukin-10, whether exogenous or derived from tolerogenic dendritic cells, induces a population of alloantigen-specific T cells (interleukin-10-anergized T cells) containing type 1 regulatory T cells, which are anergic and actively suppress alloantigen-specific effector T cells present within the mixed population. Interleukin-10-induced anergy is transforming growth factor-β independent, and is associated with a decreased frequency of alloantigen-specific cytotoxic T lymphocyte precursors, but interleukin-10-anergized T cells are still responsive to third-party, bacterial, and viral antigens. Tolerogenic dendritic cells are more powerful than exogenous interleukin-10 in generating type 1 regulatory T-cell precursors, and are also effective in the context of HLA-matched donors. Conclusions Based on these studies, we have developed an efficient and reproducible in vitro method to generate antigen-specific type 1 regulatory T-cell precursors starting from total peripheral blood cells with minimal cell manipulation and suitable for generating type 1 regulatory T cells for regulatory T-cell-based therapies.

Liver fibrosis in HIV-positive patients with hepatitis C virus: Role of persistently normal alanine aminotransferase levels

Background:Liver fibrosis requiring treatment in HIV/hepatitis C virus (HCV)-coinfected patients with persistently normal alanine aminotransferase (ALT) values (PNAL) is currently not well defined; in this study clinical and histologic features of PNAL were compared with those of subjects with elevated ALT (EAL). Methods:A total of 326 liver biopsies of HIV/HCV-coinfected patients, performed from 1997-2003, were retrospectively identified. Subjects with at least 3 consecutive normal ALT determinations during a prebiopsy follow-up of 12 months were grouped as PNAL (24 patients) and compared with EAL subjects (302 patients). Liver biopsy was classified with the modified Ishak score. Results:Age, HCV viral load, and genotype, CD4 T-cell count, and antiretroviral drugs did not show a statistical difference between the 2 groups. Statistical significance was found when comparing mean grading (1.4 ± 1.8 vs. 7.2 ± 2.6, P < 0.0001) and staging (1.4 ± 1.79 vs. 2.5 ± 1.7, P < 0.0003) between PNAL and EAL subjects. The proportion of PNAL patients fulfilling histologic criteria for anti-HCV treatment (25% with stage 2-6) was also significantly different from EAL subjects (69%; P = 0.0001). At multivariate analysis, only age, CD4 count (>500 vs. ≤500 cells/mL), and patients group (EAL vs. PNAL) were found to be independently associated with a fibrosis score of ≥2. Conclusion:Liver fibrosis requiring treatment was found in 25% of HIV/HCV-coinfected subjects with PNAL values.

Novel BRAF mutation in melanoma: A case report

In melanoma, a number of specific genetic and genomic aberrations have been identified to be important in tumorigenesis. In particular, the mutant B-Raf proto-oncogene, Serine/Threonine kinase (BRAF) gene is the target of tailored therapy with kinase inhibitor molecules. Identification of the array of mutations in patients with melanoma will be useful in determining a genetic profile of the tumor with potential implications for treatment decisions. A rare aminoacidic insertion in codon 599 of the BRAF gene (c.1797_1798insACA, T599insT) was detected by using both direct (Sanger) sequencing and pyrosequencing techniques in a metastatic melanoma of a female elderly patient. As suggested in other clinical contexts including pilocytic astrocytoma, papillary thyroid carcinomas and anaplastic thyroid carcinomas, this unusual mutation may be associated with a modified spatial structure of activated P-loop, resulting in a constitutional activation of the BRAF protein. The patient died shortly following the test, thus no biological therapy was performed. Comparable data regarding treatment of melanoma patients with rare BRAF mutations is lacking, and the response to BRAF inhibitors requires further investigation.

Poor prognosis of triple negative phenotype in endometrial cancer patients.

e17112Background: Like breast cancer, endometrial cancer can be divided into subgroups based on immunohistochemical markers such as estrogen receptors (ER), progesterone receptors (PR) and HER2. Ac...

Role of Guided - Fine Needle Biopsy of the Pancreatic Lesion

A variety of uncommon types of pancreatic carcinoma have been described, including acinar, adenosquamous, anaplastic, papillary, mucinous and microadenocarcinomas, each of which composes less than 5% of the total. All of these have similarly poor prognoses and are treated in a similar fashion. Also uncommon are mucinous cystic neoplasms (cystadenoma/cystadenocarcinoma) of the pancreas, which occur most frequently in the middle-aged women, and these are tipically located in the tail of the pancreas.