A phase II study on metastatic breast cancer patients treated with weekly vinorelbine with or without trastuzumab according to HER2 expression: changing the natural history of HER2-positive disease.

PURPOSE: To observe whether in pretreated metastatic breast cancer patients with HER2-positive disease vinorelbine plus trastuzumab can produce different overall response rate (ORR), time to progression (TTP), and overall survival (OS) from women with HER2-negative tumors treated with vinorelbine alone. METHODS: Between June 2000 and January 2004, 68 consecutive women were enrolled: 33 patients received vinorelbine (V) alone, while 35 patients were given trastuzumab plus vinorelbine (T+V) according to HER2 expression determined by immunohistochemistry. In tumors scored +2, HER2 gene amplification was determined by fluorescence in situ hybridization. RESULTS: In patients treated with V (HER2-negative tumors) the ORR was 27.3%, while in those given T+V (HER2 positive tumors) the ORR was 51.4%. The median duration of response was 8 months for women treated with V and 10 months for those who received T+V. Patients given T+V had a longer TTP (9 months) and OS (27 months) than those receiving V alone (6 months and 22 months respectively). Toxicity was mild in both groups. Concerning cardiotoxicity in T+V group, 7 patients (20%) had left ventricular systolic disfunction. CONCLUSION: Our data suggest that trastuzumab can change the natural history of HER2-positive metastatic breast cancer. In fact, when treated with trastuzumab, women with HER2-positive disease had better prognosis than patients with HER2-negative tumors. Conducting a formal phase III trial comparing vinorelbine alone vs vinorelbine plus trastuzumab in HER2-positive metastatic breast cancer women could be debatable.

Choroid plexus carcinoma in the adult: is there a role for chemotherapy?

Choroid plexus carcinoma is a rare primary brain neoplasm arising from epithelial differentiated tissue, originating from the choroids plexus of the ventricles and, in 90% of the cases, in the lateral and fourth ventricles. This neoplasm is seen mainly in children and reported infrequently in adults. The treatment of choroid plexus carcinoma is based on scarce evidence in literature. We report a rare case of an adult woman affected by a choroid plexus tumour and a discussion on the therapeutic management of this uncommon adult malignancy.

[New and old procedures in the diagnosis of dubious breast lesions]. / Procedure diagnostiche tradizionali e di recente introduzione nelle lesioni mammarie di dubbia interpretazione.

In the last years the detection of early breast cancers (lesions less than one centimetre in diameter, with good prognosis) has consistently increased for the wide application of mammary screening programs. At the same time, an increasing number of radiographically detected unexpected lesions (nonpalpable breast lesions) has been evidenced. In those cases, often both mammography and ultrasound evaluation are dubious and a multidisciplinary diagnostic approach is mandatory. Fine-needle aspiration (FNA) and core biopsy (CB) are well established diagnostic methods but, in recent years, new microinvasive bioptic procedures (as the Mammotome and the ABBI systems) have been introduced. In this review the limits and the possibilities of the classical and new cytohistological techniques are evaluated. A possible multistep diagnostic approach is described on a cost-benefit basis and in consideration of the various procedures.

[Tumor markers in epithelial ovarian cancer]. / Marcatori tumorali nel carcinoma epiteliale dell'ovaio.

Many circulating markers are already in clinical practice and in experimental use for the diagnosis, therapeutic monitoring, and in the follow-up of ovarian cancer. The cancer antigen-125 (CA-125) has shown to be useful in epithelial ovarian cancer, but its specificity is too low for the test to be used as a primary screening technique in early stage and particularly in premenopausal women. In the last few years, several studies have focused on using the serial measurement of complementary serum markers to improve the positive predictive value and diagnostic accuracy. The main problem is that the different cellular lines express these markers in a very variable way.

[A new drug in the therapy of chronic myeloid leukemia: ST1571]. / La nuova realtà terapeutica della leucemia mieloide cronica: ST1571.

The therapy of chronic myeloid leukemia, characterized by the presence of the Philadelphia chromosome in the clonal hematopoietic stem cells, has changed dramatically in the last years with the development of a specific inhibitor of the BCR-ABL tyrosine kinase: tyrosine kinase inhibitor imatinib mesylate (formerly STI571, [Glivec]). Glivec selectively blocks cellular proliferation and induces apoptosis in Philadelphia chromosome-positive (Ph+) cells harbouring the Bcr-Abl tyrosine kinase. Clinical development of imatinib mesylate began with 3 large, multicenter, phase II trials. The majority (88%) of interferon-alpha-resistant or intolerant patients in chronic-phase CML, achieved a complete hematologic response to imatinib mesylate. More importantly, approximately half of the patients achieved a major cytogenetic response, a result historically associated with improved survival. Furthermore, 21% of patients in accelerated-phase CML and 13.5% of patients in blastic-phase CML (patient populations with typically poor prognosis before the advent of imatinib mesylate) achieved major cytogenetic responses.

[Testis cancer markers. Clinical use]. / I marcatori sierici delle neoplasie del testicolo. Uso clinico.

Testis tumour is relatively rare and more frequent between 15-35 years of age. The 90% of this tumour derivates from germinal cells, the remaining cases originate from stromal cells or are secondary lesions from other neoplasms. The present clinical use of serum markers, especially alfa-fetoprotein (AFP), human chorionic gonadotrophin protein (HCG) and serum lactate dehydrogenase (LDH) is examined.

In vitro assessment of cytotoxicity and carcinogenic potential of chemicals: evaluation of the cytotoxicity induced by 58 metal compounds in the Balb/3T3 cell line.

A new, mechanistically based, in vitro strategy involving Balb/c 3T3 clone A 31-1-1 mouse embryo fibroblasts has been proposed for the determination of the carcinogenic potential of inorganic chemicals, in order to establish priority of metal compounds to be tested and, whenever possible, to compare the in vitro results with the corresponding in vivo data. As a first step in this research, this study reports on the cytotoxic effects of 58 metal compounds in the Balb/3T3 cell line. After harmonisation and standardisation of the Balb/3T3 protocol, cells were exposed for 72 hours to a fixed dose (100 microM) of 58 individual compounds. The cytotoxicity induced by some metal compounds was found to be related to their chemical form (for example, Cr(NO(3))(3) and Na(2)CrO(4)), suggesting that the Balb/3T3 cell line is a valuable cellular model in relation to this aspect of metal speciation. The results of the systematic study on the metal-induced cytotoxic effects in the Balb/3T3 cell line could be arbitrarily classified into three groups according to the degree of cytotoxicity. Group I includes 26 species that induced no observable effect or only a slight cytotoxic effect; Group II includes 13 metal compounds that exhibited an obvious degree of cytotoxicity; and Group III includes 19 metal species that displayed a strong cytotoxic response. Metal compounds of Groups II and III are considered to be of the highest priority for setting of dose-effect relationships for a subsequent in vitro study on metal-induced concurrent cytotoxicity and morphological transformation in the Balb/3T3 cell line.

Implication of laminin and collagen type IV expression in the progression of breast carcinoma.

BACKGROUND: The prognostic variability in breast cancer patients prompted the authors to investigate specific biological markers for the identification of high-risk breast cancer groups. In the present study, attention was focused on the interaction between tumor cells and the extracellular matrix, an important requisite in the metastatic process. MATERIALS AND METHODS: Fifty-six primary breast carcinoma specimens obtained by mastectomy or quadrantectomy plus axillary dissection were examined with immunohistochemistry, for the determination of laminin, collagen type IV and hormone receptor expression and with static cytometry, for the determination of the DNA content. RESULTS: Laminin and collagen type IV expression was observed on the membrane and in the cytoplasm of neoplastic cells. Laminin and collagen type IV were present, respectively, in 85.4% and 73.8% of the cases which showed recurrence. CONCLUSION: The results of this study have shown that high expression of laminin and collagen type IV may have a value in the prognosis of disease free survival and may be linked to other classical clinical, histological and biological parameters in the evaluation of breast cancer patients.

The use of pre-implantation mouse embryos cultured in vitro in toxicological studies.

The preimplantation mouse embryo has been found to be a good model for various toxicological investigations. This communication deals with two examples of research activities carried out in our laboratory to detect the embryotoxic properties of tritium and of 1,2:3,4-diepoxybutene (DEB). Exposures of blastocysts for 24 hr to concentrations as high as 0.296 kBq/ml tritiated amino acids or nucleoside induced a statistically significant reduction in the percentage of embryos that reached the stage of two-layer inner cell mass (ICM). The same quantity of tritiated arginine, but not of thymidine or tryptophan, also induced a lower percentage of differentiating ICM than the control when added to culture medium during the second cleavage division. These findings support the idea that tritium released by nuclear power plants as HT or as tritiated water (HTO) could become a radiotoxicological problem since it can be converted easily into organic compounds by living organisms. DEB was found to be highly embryotoxic in preimplantation mouse embryos in vitro at micromolar concentrations. This compound is formed in mammalian cells by the oxidative metabolism of 1,3-butadiene, a chemical used in rubber industries and present in tobacco smoke. Again, the most sensitive stages of preimplantation development were found to be the two- and the four-cell embryos. These results were confirmed by in vivo measurements.