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Biomedical subjects

Orietta Gandini

Publications and source records attributed to Orietta Gandini.

6 recordsLinked to original sources
PubMed2007

Gemcitabine-induced apoptosis in 5637 cell line: an in-vitro model for high-risk superficial bladder cancer.

Recent data suggest that new treatment options for superficial bladder cancer are necessary, owing to the high recurrence rate after conventional treatment, especially in T1G3 and Bacillus Calmette-Guerin-refractory patients. Phase I and II studies have demonstrated that gemcitabine may represent a candidate for intravesical therapy in superficial bladder cancer. Despite clinical trials, the in-vitro cytotoxic and proapoptotic effects of gemcitabine have been poorly investigated. In the present study, we investigated how gemcitabine affects apoptosis in bladder cancer cell line 5637, which has the same molecular features of high-risk superficial bladder cancer. Apoptosis was evaluated by DNA fragmentation, flow cytometry and caspase activation. bcl-2, bcl-X, bax, survivin and fas gene expression were also evaluated by reverse-transcriptase polymerase chain reaction. Nuclear factor-kappa B activation was assessed by immunofluorescence. Gemcitabine induced apoptosis in 5637 cells in a time-dependent manner, with activation of caspase-3, -8 and -9. Expression of bcl-2, bax, survivin and bcl-X was not affected by treatment, whereas fas strongly increased after 24 h of treatment. After treatment, we failed to find any nuclear localization of nuclear factor-kappa B. As gemcitabine-induced apoptosis involves fas upregulation, these results may encourage the investigation of intravesical gemcitabine in fas-negative bladder tumors. Furthermore, as nuclear factor-kappa B activation by cisplatin, doxorubicin and adriamycin may result in enhanced proliferation, migration, immortality and inhibition of apoptosis, the observation that gemcitabine does not activate nuclear factor-kappa B may have implications in intravesical therapy of high-risk superficial bladder cancer.

Antimetabolites, Antineoplastic↗
PubMed2005

Tenascin C and epidermal growth factor receptor as markers of circulating tumoral cells in bladder and colon cancer.

Tenascin C has been recently suggested as a tumor marker, however, its levels in serum has been evaluated only in patients with head and neck cancer and melanoma. In this study, we investigated Tenascin C expression in blood samples from colorectal and bladder cancer patients, compared to that of epidermal growth factor receptor (EGFR), a known circulating tumor marker in these cancer types. RT-PCR specific for Tenascin C and EGFR was performed on RNAs extracted from blood samples of 60 patients affected by colon or bladder cancer. We then investigated the statistical association between Tenascin C, EGFR expression and disease-free survival using the Kaplan-Meier method. Furthermore, in order to select which variable between EGFR and Tenascin C was the most predictive for recurrence, a Cox model for proportional risk was applied. Among all patients analysed, a significantly higher disease-free time was found in the group negative for both EGFR and Tenascin C expression; EGFR expression was significantly correlated to disease progression in stages III and IV, whereas in all patients with stage I and II disease Tenascin C correlated better with prognosis. Negative expression of both EGFR and Tenascin C identifies a group of patients with poor tendency to disease recurrence and longer relapse-free time. While Tenascin C expression seems to influence prognosis in patients with low-stage disease, EGFR appears a marker of worse prognosis in patients with high-staged tumors.

Biomarkers, Tumor↗
PubMed2003

Persistence of epidermal growth factor receptor and interleukin 10 in blood of colorectal cancer patients after surgery identifies patients with high risk to relapse.

PURPOSE: Despite the great number of studies performed to detect circulating markers of disease progression in colorectal cancer, few have shown a clinical use; among those, epidermal growth factor receptor (EGFR) and, more recently, interleukin (IL)-10. In this article, we sought to investigate how primary surgery could affect expression levels of EGFR, IL-6, and IL-10 in blood from colorectal cancer patients. EXPERIMENTAL DESIGN: We investigated by reverse transcriptase-PCR assay the expression at mRNA level of EGFR, IL-6, and IL-10 in blood samples taken from 56 colorectal cancer patients. Each gene expression was evaluated 1 day before and 20 days after primary surgery. Persistence of each gene in blood after surgery was then correlated to the relapse free time in a follow-up of 3 years. RESULTS: In blood samples taken before surgery, EGFR, IL-6, and IL-10 were found expressed in 62, 100, and 100% of patients, respectively. EGFR expression, but not IL-6 and IL-10, correlates with stage of disease. In the group of 41 patients who underwent follow-up studies, EGFR was found persistently high in 67%; 94% of them had relapse. Persistence of IL-10 after surgery also identifies relapses in 89% of cases. IL-6 persistence was not found to significantly correlate to progression of disease. CONCLUSIONS: Persistence of both EGFR and IL-10 in blood of colorectal cancer patients after surgery identifies patients with high propensity to relapse. These findings may suggest a clinical use of preoperative EGFR/IL-10 reverse transcriptase-PCR assay in the prediction of tumor recurrence.

Actins↗
PubMedDate not supplied

Detection of CK19, CK20 and EGFR mRNAs in peripheral blood of carcinoma patients: correlation with clinical stage of disease.

Expression of genes such as cytokeratin 19 (CK19), cytokeratin 20 (CK20) and epidermal growth factor receptor (EGFR) has been investigated at mRNA level in peripheral blood of carcinoma patients to detect the presence of circulating tumor cells (CTC). We performed this study because recent literature emphasizes that the importance of CK19, 20 and EGFR mRNAs in CTC as prognostic factors remains unclear especially for breast, head and neck and colon cancer patients. Reverse transcriptase polymerase chain reaction (RT-PCR) followed by Southern blot hybridization was performed in blood samples from 47 subjects (12 colorectal, 15 head and neck and 20 breast carcinoma patients), as well as in 35 healthy donors. The CK19 expression was found in 36/47 patients (9 colorectal, 9 head and neck and 18 breast cancer), two patients (one affected by colorectal and one by head and neck cancer) were positive for CK20 whereas EGFR was found expressed in 9 patients (3 colorectal, 5 head and neck and one breast cancer). Seven of 35 and 4/35 healthy donors displayed positivity for the expression of CK19 and CK20 genes respectively, whereas no EGFR mRNA was found in this group. The correlation of the detection of CTC in peripheral blood with progression of the disease in a follow-up period of 40 months did not show any prognostic value to the presence of mRNAs of these biomarkers in blood. We believe that research should be addressed, at least for breast cancer, to the identification of occult metastases in sentinel lymph nodes, such as recently performed in melanoma patients.

Adolescent↗
PubMedDate not supplied

Is DD3 a new prostate-specific gene?

The search for new and more specific molecular markers of prostatic cancers has led, in recent years, to the identification of the DD3 gene. Using reverse transcription (RT)-PCR, we investigated DD3 gene expression in human cell lines, in blood samples from healthy men and women donors and in various neoplastic and non-neoplastic tissues from the prostate and other organs. Whereas RT-PCR analysis using primers that amplified the region spanning exons 1 and 3 yielded DD3 gene expression in all samples examined, a primer downstream to exon 4 detected the expected size DD3 band only in benign and malignant prostatic tissues. These findings indicate that the only prostate specific region of DD3 is exon 4.

Antigens, Neoplasm↗