Efficacy and safety of zoledronic acid in patients with breast cancer metastatic to bone: a multicenter clinical trial.

Purpose: This study evaluated the efficacy and safety of zoledronic acid in breast cancer patients with newly diagnosed bone metastases.

Materials And Methods: Patients diagnosed with bone metastases < or = 6 weeks prior to first visit were enrolled. Zoledronic acid (4 mg) was administered via a 15-minute infusion every 3 or 4 weeks for 12 infusions.

Occupational exposure to solvents and the risk of lymphomas.

Background: A number of studies have shown possible associations between occupational exposures, particularly solvents, and lymphomas. The present investigation aimed to evaluate the association between exposure to solvents and lymphomas (Hodgkin and non-Hodgkin) in a large population-based, multicenter, case-control study in Italy.

Methods: All newly diagnosed cases of malignant lymphoma in men and women age 20 to 74 years in 1991-1993 were identified in 8 areas in Italy.

Randomized Phase II Trial of weekly paclitaxel alone versus trastuzumab plus weekly paclitaxel as first-line therapy of patients with Her-2 positive advanced breast cancer.

Background: A randomized Phase II study evaluated the activity of weekly paclitaxel versus its combination with trastuzumab for treatment of patients with advanced breast cancer overexpressing HER-2.

Patients And Methods: Among 124 patients randomized, 123 are assessable for toxicity and 118 for response. Patients received weekly paclitaxel single agent (80 mg/m2) or combined with trastuzumab (4 mg/kg loading dose, then weekly 2 mg/kg).

Molecular characterization of cytotoxic and resistance mechanisms induced by NCX 4040, a novel NO-NSAID, in pancreatic cancer cell lines.

Although non steroidal antiinflammatory drugs (NSAIDs) have been shown to be effective as chemopreventive agents, important side-effects limit their clinical use. A promising novel class of drugs, nitric oxide-donating NSAIDs (NO-NSAIDs), has been found to be more active than classical NSAIDs. This study explored the effect of the NO-donating aspirin derivative, NCX 4040, on three human pancreatic adenocarcinoma cell lines (Capan-2, MIA PaCa-2 and T3M4).

Efficacy of a nitric oxide-releasing nonsteroidal anti-inflammatory drug and cytotoxic drugs in human colon cancer cell lines in vitro and xenografts.

We previously showed that NCX 4040 inhibits in vitro and in vivo tumor growth and induces apoptosis in human colon cancer cell lines. On the basis of these results, NCX 4040 antitumor activity in combination with 5-fluorouracil (5-FU) or oxaliplatin was evaluated in vitro and in vivo in human colon cancer models. The cytotoxicity of different NCX 4040 and 5-FU or oxaliplatin combination schemes was evaluated on a panel of colon cancer lines (LoVo, LoVo Dx, WiDr, and LRWZ) by the sulforhodamine B assay, and apoptosis was assessed by flow cytometry.

Phase II study of gemcitabine, doxorubicin and paclitaxel (GAT) as first-line chemotherapy for metastatic breast cancer: a translational research experience.

Background: Patients with metastatic breast cancer are frequently treated with anthracyclines and taxanes, which are among the most active agents in this disease. Gemcitabine is an interesting candidate for a three-drug combination because of its different mechanism of action and non-overlapping toxicity with respect to the other two drugs. We aimed to evaluate the activity and toxicity of the GAT (gemcitabine, doxorubicin and paclitaxel) regimen, derived from experimental preclinical studies, as first-line chemotherapy in patients with stage IIIB-IV breast cancer.

Paclitaxel, cisplatin and 5-fluorouracil in recurrent squamous cell carcinoma of the head and neck: a phase II trial from an Italian cooperative group.

The aim of this multicenter trial was to test the feasibility and the activity of a three-drug combination where paclitaxel is added to cisplatin and 5-fluorouracil. Patients with metastatic or relapsed SCC-HN unsuitable for further loco-regional radical treatment, not previously treated with chemotherapy, were eligible to receive paclitaxel 160 mg/m2 (3-hr infusion) day 1, CDDP 25 mg/m2/day and 5-FU 250 mg/m2/day bolus on days 1, 2, 3 every three weeks up to a maximum of five courses. Fourty-seven patients were enrolled by five Institutions in Italy.

The global breast cancer burden: variations in epidemiology and survival.

Breast cancer is the most common type of cancer and the most common cause of cancer-related mortality among women worldwide. However, the burden is not evenly distributed, and, according to the best available data, there are large variations in the incidence, mortality, and survival between different countries and regions and within specific regions. Many complex factors underlie these variations, including population structure (eg, age, race, and ethnicity), lifestyle, environment, socioeconomic status, risk factor prevalence, mammography use, disease stage at diagnosis, and access to high-quality care.

Usefulness of immunological detection of the human telomerase reverse transcriptase.

Objective: Recent years have seen a considerable wealth of studies conducted on the potential usefulness of telomerase determination in diagnosis, prognosis and targeted cancer therapy. The frequently used Telomeric Repeat Amplification Protocol assay suffers from some drawbacks, the most important being the rate of false positives. In situ analysis using well characterised antibodies directed against the human telomerase reverse transcriptase (hTERT) would therefore appear to be important to morphologically identify the nature of telomerase positive cells.

Secondary lung tumors in hematological patients.

Advances made in the field of chemotherapy and radiotherapy have considerably increased the survival of patients with Hodgkin's disease (HD), non-Hodgkin's lymphoma (NHL), and chronic lymphocytic leukemia (CLL). Unfortunately, these antiblastic therapies have also increased the risk of late complications such as second tumors, especially second lung cancers. Although the role of ionizing radiations in carcinogenesis is now clear, less is known about the damage caused by chemotherapy, immunodeficiency induced by drugs or hematological pathologies, and cigarette smoking.

Impact of palliative care unit admission on symptom control evaluated by the edmonton symptom assessment system.

The aim of the present study was to evaluate the impact of palliative care on patients' symptoms, using the Edmonton Symptom Assessment System (ESAS) to measure symptom intensity at the time of admission and variations registered during the first 7 days' hospitalization. Three hundred fourteen patients were admitted to the unit during its first year of activity. Of these, 162 patients (51.

Relevance of urine telomerase in the diagnosis of bladder cancer.

Context: The identification of new molecular markers is one of the most challenging goals for the early detection of bladder cancer because available noninvasive methods have neither sufficient sensitivity nor specificity to be acceptable for routine use.

Objective: To develop a relatively simple, inexpensive, and accurate test that measures telomerase activity in voided urine to apply to large-scale screening programs for bladder cancer detection.

Design, Setting, And Participants: Case-control study conducted in 218 men (84 healthy individuals and 134 patients at first diagnosis of histologically confirmed bladder cancer), frequency matched by age and recruited between March 2003 and November 2004 in Italy.

WWOX gene restoration prevents lung cancer growth in vitro and in vivo.

The WWOX (WW domain containing oxidoreductase) gene at the common fragile site, FRA16D, is altered in many types of cancer, including lung cancer. We have examined the tumor suppressor function of WWOX in preclinical lung cancer models. The WWOX gene was expressed in lung cancer cell lines through recombinant adenovirus (Ad) infection (Ad-WWOX), and through a drug [ponasterone A, (ponA)]-inducible system.

p16INK4A and CDH13 hypermethylation in tumor and serum of non-small cell lung cancer patients.

Aberrant promoter hypermethylation of several known or putative tumor suppressor genes occurs frequently during the etiopathogenesis of lung cancer and is a promising tool for cancer detection. In the present study, promoter hypermethylation of p16INK4A and CDH13 genes was investigated in tumor tissue and in matched serum from 61 patients with histologically confirmed non-small cell lung cancer. Using a fluorescence-based method of methylation-specific PCR (F-MSP), methylation of p16INK4A and CDH13 was detected in 79% and 66% of tumors, respectively, and was not significantly related to conventional clinicopathological characteristics of patients or tumors.

Addition of 5-fluorouracil to doxorubicin-paclitaxel sequence increases caspase-dependent apoptosis in breast cancer cell lines.

Introduction: The aim of the study was to evaluate the activity of a combination of doxorubicin (Dox), paclitaxel (Pacl) and 5-fluorouracil (5-FU), to define the most effective schedule, and to investigate the mechanisms of action in human breast cancer cells.

Methods: The study was performed on MCF-7 and BRC-230 cell lines. The cytotoxic activity was evaluated by sulphorhodamine B assay and the type of drug interaction was assessed by the median effect principle.

Development and characterization of a monoclonal antibody directed against human telomerase reverse transcriptase (hTERT).

Telomerase activity plays an important role in the two complementary processes of cellular immortalization and senescence. This enzyme is active in almost all tumors, but also in inflammatory and many normal proliferating cells. Therefore, the main limits of molecular determinations, such as telomeric repeat amplification protocol assay is that they are not able to discriminate between the enzymatic activity of tumor and normal cells.

Loss of heterozygosity at 17p13.3-ter, distal to TP53, correlates with negative hormonal phenotype in sporadic breast cancer.

Genetic alterations on chromosome 17p are frequent in a variety of human malignancies such as sporadic breast carcinomas. The clinico-pathological significance of it remains to be elucidated. The purpose of this study was to explore whether the allelic loss (LOH) in 17p13.

Switching to anastrozole versus continued tamoxifen treatment of early breast cancer: preliminary results of the Italian Tamoxifen Anastrozole Trial.

Purpose: Tamoxifen, which is actually the gold standard adjuvant treatment in estrogen receptor-positive early breast cancer, is associated with an increased risk of endometrial cancer and other life-threatening events. Moreover, many women relapse during or after tamoxifen therapy because of the development of resistance. Therefore new approaches are required.

Improved analysis of 5-Fluorouracil and 5,6-dihydro-5-Fluorouracil by HPLC with diode array detection for determination of cellular dihydropyrimidine dehydrogenase activity and pharmacokinetic profiling.

Administration of 5-fluorouracil (5-FU) may be associated with severe toxicities in patients who are deficient of dihydropyrimidine dehydrogenase (DPD) activity. For this reason, a sensitive HPLC method for the analysis of 5-FU and 5-fluoro-5,6-dihydrouracil (5-FDHU) was developed in the present study for the determination of DPD activity in nucleated cells of peripheral blood and pharmacokinetic analysis of 5-FU and 5-FDHU in humans. 5-FU and 5-FDHU were extracted from biologic matrices by adding sodium acetate, sodium sulfate, and diethyl ether/propanol.

A validation study of the WHO analgesic ladder: a two-step vs three-step strategy.

Goals Of Work: The aims of the present study were to verify whether an innovative therapeutic strategy for the treatment of mild-moderate chronic cancer pain, passing directly from step I to step III of the WHO analgesic ladder, is more effective than the traditional three-step strategy and to evaluate the tolerability and therapeutic index in both strategies.

Methods: Patients aged 18 years or older with multiple viscera or bone metastases or with locally advanced disease were randomized. Pain intensity was assessed using a 0-10 numerical rating scale based on four questions selected from the validated Italian version of the Brief Pain Inventory.

Mutation analysis of p53, K-ras, and BRAF genes in colorectal cancer progression.

Gene mutations in APC, K-ras, and p53 are thought to be essential events for colorectal cancer development. Recent data seem to indicate that K-ras and p53 mutations rarely co-exist in the same tumor, indicating that these alterations do not represent a synergistic evolutionary pathway. Moreover, an inverse relation between K-ras gene activation and BRAF mutations has been demonstrated, suggesting alternative pathways for colorectal cancer transformation.

In vitro and in vivo evaluation of NCX 4040 cytotoxic activity in human colon cancer cell lines.

BACKGROUND: Nitric oxide-releasing nonsteroidal antiinflammatory drugs (NO-NSAIDs) are reported to be safer than NSAIDs because of their lower gastric toxicity. We compared the effect of a novel NO-releasing derivate, NCX 4040, with that of aspirin and its denitrated analog, NCX 4042, in in vitro and in vivo human colon cancer models and investigated the mechanisms of action underlying its antitumor activity. METHODS: In vitro cytotoxicity was evaluated on a panel of colon cancer lines (LoVo, LoVo Dx, WiDr and LRWZ) by sulforhodamine B assay.

Immunosuppression in renal cancer: differential expression of signal transduction molecules in tumor-infiltrating, near-tumor tissue, and peripheral blood lymphocytes.

Alterations in the expression of signal activation molecules, such as the T-cell receptor (TCR) zeta and epsilon chains and p56lck tyrosine kinase, are described in tumor-infiltrating lymphocytes (TIL). The aim of this study was to ascertain if such molecules were present in near-tumor-tissue lymphocytes (NTTL) and peripheral blood lymphocytes (PBL), as well as TIL, of renal cell carcinoma patients, to verify whether this tumor induces immunosuppression only locally or affects distant lymphocytes as well. Tissue from the tumor and from healthy nearby sites, as well as blood samples, were obtained from 27 consecutive patients who had undergone radical nephrectomy for renal cell carcinoma.

Innovative sequence of docetaxel-gemcitabine based on preclinical data in the treatment of advanced non small cell lung cancer: a phase I study.

Based on our previous preclinical data, a phase I study was designed to investigate the tolerability of a novel sequence, docetaxel (DOC)-gemcitabine (GEM), in the treatment of non small cell lung cancer (NSCLC). Preclinical study: We evaluated the cytotoxicity of DOC and GEM on NSCLC cell lines and assessed the type of interaction between drug activities following different treatment schemes. Clinical study: Fifteen patients with stage IIIB-IV NSCLC received DOC (day 1) and GEM (days 3 and 8) every 21 days.

[Production and diffusion of scientific results in oncology].

The production of data from oncological research must follow specific steps linked to the type of research carried out. Research can be subdivided into the following areas: translational research, clinical research (Phases I, II and III), pharmacoutilization research, meta-analysis, and guidelines. A topic for discussion is represented by levels of evidence (LOE) of research, considered necessary for the transferral of therapeutic approaches to clinical practice.