0000000000009199
AUTHOR
C. Intrivici
4843delC of the BRCA1 gene is a possible founder mutation in Southern Italy (Sicily).
Various studies have been published in Italy regarding the different BRCA1 mutations, but only the BRCA1-5083del19 mutation is recurrent and specific to individuals of Italian descent with a founder effect on the Calabrian population. In our previous study, BRCA1-5083del19 mutation carriers were found in four index cases of 106 Sicilian patients selected for familial and/or hereditary breast/ovarian cancers. The high frequency rate of this mutation identified in the Sicilian population led us to perform haplotype analysis in all family carriers. Five highly polymorphic microsatellite markers were used (D17S1320, D17S932, D17S1323, D17S1326, D17S1325) to establish whether or not all these fa…
Autoimmunity predicts prolonged survival in colon cancer patients undergoing GOLFIG biochemotherapy
14542 Background: A multi-center phase II trial has been designed to evaluate toxicity, anti-tumour and immune-biological activity of the bio-chemotherapy GOLFIG regimen in advanced colorectal cancer (A-CRC). Methods: The trial involved 46 patients (34/46 2nd line or more). The biweekly GOLFIG regimen consisted of gemcitabine (1,000 mg/m2, day 1), oxaliplatin (85 mg/m2, day 2), levofolinic acid (100 mg /m2, day 1,2) and 5-FU (400 mg/m2 as a bolus, and 800 mg/m2 as 24 hour infusion, days 1,2) followed by sc GM-CSF (100 μg, days 3 to 8) and sc IL-2 (0.5 X 106 IUs twice a day, days 9 to 14). Results: GOLFIG regimen was well tolerated and resulted very active (ORR = 56.5%; disease control = 91…
Aurora-A overexpression as an early marker of reflux-related columnar mucosa and Barrett's oesophagus.
Abstract BACKGROUND: The development of oesophageal adenocarcinoma is generally closely associated with the presence of a specialised intestinal-type epithelium such as that found in Barrett's oesophagus (BO). A particular histological condition is when the distal oesophagus showing cardiac and/or fundic mucosa without intestinal metaplasia cannot be defined as 'Barrett's mucosa' [condition that we call 'columnar-lined oesophagus' (CLO)] and up till now, there has been no agreement in literature about the management of this condition. Aurora-A overexpression leads to centrosome amplification, chromosomal instability and aneuploidy in mammalian cells. PATIENTS AND METHODS: A prospective stud…
Gemcitabine (GEM) plus oxaliplatin, folinic acid, and 5-fluorouracil (FOLFOX-4) in patients with advanced gastric cancer
Abstract BACKGROUND AND AIMS: oxaliplatin in combination with folinic acid (FA) and infusional 5-fluorouracil (5-FU) has shown significant anti-tumor activity in gastric cancer patients (FOLFOX). Previous studies have shown that gemcitabine (GEM), a new fluorinated anti-metabolite, enhances the individual anti-tumor activity of either 5-FU or oxaliplatin. We have therefore designed a multi-center phase II trial in order to test a novel GEM+FOLFOX-4 regimen in patients with metastatic gastric cancer. METHODS: we enrolled 36 patients, 28 males and 8 females, with an average age of 64.4 years (range 37-78), who received bi-weekly treatment with GEM (1,000 mg/m2 on day 1), levo-FA (100 mg/m2 on…
Weekly paclitaxel and Pegylated liposomal doxorubicin as first line treatment in metastatic breast cancer patients
Background: Paclitaxel-Doxorubicin combination chemotherapy is highly active in metastatic breast cancer patients (pts) but may be cardiotoxic in a small percentage of cases. PLD is a new formulation of Doxorubicin with significant reduced cardiac toxicity and for this reason PLD can be given safe in elderly patients with cardiac risk factors or in younger patients with prior exposure to anthracycline-containing regimens. The main side effect of PLD is Hand-Foot syndrome but when given in intervals not below 4 weeks and with a dose intensity not exceeding 10 mg/sqm per week, this side effects is clearly reduced. Methods: : We carried out a phase 2 study to verify the activity of P 70 mg/sm …
Gastrointestinal stromal tumors (GISTs): Focus on histopathological diagnosis and biomolecular features
Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors of the gastrointestinal tract that are believed to originate from a neoplastic transformation of the intestinal pacemaker cells (interstitial cells of Cajal) normally found in the bowel wall or their precursors. Although the microscopic features have been known for a long time, the defining characteristic of GIST is the presence of the cell-surface antigen CD117 (KIT), which is demonstrated by immunohistochemistry. KIT, which is a growth factor transmembrane receptor, is the product of the proto-oncogene c-kit (chromosome 4). Surgical removal remains the only curative treatment for patients with GISTs. Tumor size, mitotic index,…
Molecular detection of TP53, Ki-Ras and p16INK4A promoter methylation in plasma of patients with colorectal cancer and its association with prognosis. Results of a 3-year GOIM (Gruppo Oncologico dell'Italia Meridionale) prospective study
BACKGROUND:Despite the improvement in detection and surgical therapy in the last years, the outcome of patients affected by colorectal carcinoma (CRC) remains limited by metastatic relapse. The aim of this study was to investigate the presence of free tumor DNA in the plasma of CRC patients in order to understand its possible prognostic role. PATIENTS AND METHODS: Ki-Ras, TP53 mutations and p16(INK4A) methylation status were prospectively evaluated in tumor tissues and plasma of 66 CRC patients. RESULTS: In 50 of the 66 primitive tumor cases (76%) at least one significant alteration was identified in Ki-Ras and/or TP53 and/or p16(INK4A) genes. Eighteen of the 50 patients presented the same …
The use of zoledronic acid in patients with bone metastases from prostate carcinoma: Effect on analgesic response and bone metabolism biomarkers
Zoledronic acid is a bisphosphonate that is effective in the treatment of complications of metastatic bone disease. We have carried out a perspective study on 24 consecutive patients with prostate cancer metastatic to bone to verify the effect of zoledronic acid on analgesic response and a possible relationship with the levels of bone metabolism biomarkers. Eligibility for this study required prostate cancer patients with metastatic bone disease and pain not controlled by analgesics. Patients were excluded from the study if they were receiving cytotoxic chemotherapy or radiation therapy within three months. Eighteen patients (75%) were considered responder to acid zoledronic, only 6 patient…
A case of guillain-barre syndrome in a patient with non small cell lung cancer treated with chemotherapy
Guillain-Barré Syndrome (GBS) is a demyelinating polyneuropathy of probable autoimmune pathogenesis characterized by rapidly progressive symmetric paralysis. In the literature some cases of GBS associated with anticancer chemotherapy are reported. We present a case of a 55-year old woman who complained of progressive motor deficit in four limbs, areflexia in lower limbs and facial nerve paralysis one week after beginning cisplatin-gemcitabine chemotherapy for metastatic lung cancer. The cerebrospinal fluid analysis showed a strong positive Pandy reaction with 435 mg/dl total protein. The electromyography and the electroneuronography established the diagnosis of inflammatory demyelinating po…
Aberrant methylation within RUNX3 CpG island associated with the nuclear and mitochondrial microsatellite instability in sporadic gastric cancers. Results of a GOIM (Gruppo Oncologico dell'Italia Meridionale) prospective study.
Background: Gastric cancer (GC) development is a multistep process, during which numerous alterations accumulate in nuclear and mitochondrial DNA. A deficiency of repair machinery brings about an accumulation of errors introduced within simple repetitive microsatellite sequences during replication of DNA. Aberrant methylation is related to microsatellite instability (MSI) by the silencing of the hMLH1 gene. The aim of this study is to investigate a possible relationship between the RUNX3 promoter methylation, nuclear microsatellite instability (nMSI) and mitochondrial microsatellite instability (mtMSI), in order to clarify its biological role in GC. Patients and methods: nMSI and mtMSI were…
Gemcitabine plus metronomic 5-fluorouracil or capecitabine as a second-/third-line chemotherapy in advanced adrenocortical carcinoma: a multicenter phase II study.
Adrenocortical carcinoma (ACC) is a rare neoplasm characterized by poor prognosis. First-line systemic treatments in advanced disease include mitotane, either alone or in combination with chemotherapy. Studies evaluating second-line therapy options have obtained disappointing results. This trial assessed the activity and toxicity of gemcitabine plus metronomic fluoropyrimidines in heavily pretreated advanced ACC patients. From 1998 to 2008, 28 patients with advanced ACC progressing after mitotane plus one or two systemic chemotherapy lines were enrolled. They received a combination of i.v. gemcitabine (800 mg/m2, on days 1 and 8, every 21 days) and i.v. 5-fluorouracil protracted infusion (2…
BRCA1 genetic testing in 106 breast and ovarian cancer families from Southern Italy (Sicily): a mutation analyses.
PURPOSE: To evaluate the contribution of germline BRCA1 mutations in the incidence of hereditary and familial Breast Cancer (BC) and/or Ovarian Cancer (OC) in patients from Southern Italy (in the region of Sicily) and to identify a possible association between the higher frequency of BRCA1 mutations and a specific familial profile. EXPERIMENTAL DESIGN: A consecutive series of 650 patients with BC and/or OC diagnosed between 1999 and 2005 were recruited from the Southern Italian region of Sicily, after interview at the "Regional Reference Centre for the Characterization and Genetic Screening of Hereditary Tumors" at the University of Palermo. Genetic counselling allowed us to recruit a total…