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Gaetano Apice

Publications and source records attributed to Gaetano Apice.

10 recordsLinked to original sources
PubMed2006

Expression of transcription factor Yin Yang 1 in human osteosarcomas.

The transcription factor Yin Yang 1 (YY1) is known to be present in some human cancer cell lines and its expression correlates with immune-mediated apoptosis. By using Western blot analysis, we have shown that the YY1 protein is strongly expressed in human osteosarcoma cells and localised mainly in the nucleus. Moreover, by using immunohistochemistry and RT-PCR techniques, we have analysed the expression of YY1 protein in biopsies from human osteosarcomas. The YY1 protein was not detectable by immunohistochemistry in osteoid tissue. However, its expression was restricted to osteosarcoma tissues. These data were confirmed by densitometric analysis of RT-PCR for YY1 expression. Thus, YY1 gene activation appears to be an early event in the process of osteoblastic transformation and its detection may represent, together with the analysis of other established markers, a useful diagnostic tool in human osteosarcomas.

Adolescent↗
PubMed2006

New emerging drugs in soft tissue sarcoma.

Doxorubicin and ifosfamide are the two most active drugs in the treatment of patients with advanced, soft tissue sarcoma (STS) of most histologic subtypes, aside from gastrointestinal stromal tumor (GIST). However, after failure of these drugs, alone or in combination, patients with advanced STS have few therapeutic options and the search for new active drugs is well worth pursuing. ET-743, a DNA minor groove binder, which blocks cell cycle progression in G2/M phase through a p53-independent apoptotic process, represents the most promising among novel compounds in STS, since recently completed phase II trials have consistently shown high survival, in spite of the relatively low incidence of major objective responses. The potential for combination with other active compounds further increases the appeal of ET-743. Imatinib mesylate is being tested also in STS other than GIST, which can overexpress one or more of the tyrosine kinases inhibited by imatinib; however, negative data have recently been presented. Clinical studies with a number of other compounds are ongoing or planned. However, investigators involved in the management of patients with advanced STS are to be increasingly aware of the emergence of new molecular targets and genetic profiles in different histologic subtypes, according to which treatment strategies should be adapted.

Antineoplastic Agents↗
PubMed2006

Primary gastrointestinal stromal tumor of the liver with lung metastases successfully treated with STI-571 (imatinib mesylate).

We report a case of a primary malignant GIST of the liver metastatic to the lung in a 37 years-old man. The liver tumor showed histological feature of a GIST and expressed vimentin, and diffusely exhibited CD117. One year after the resection of the liver mass, the patient developed multiple small lung metastases which completely disappeared with STI-571 (imatinib mesylate--Gleevec) therapy. C.T. or PET did not show any mass in the abdomen. These findings suggest that the liver mass was a primary rather than a metastatic tumour. They also support the hypothesis that GIST could originate from undifferentiated mesenchymal cells capable to differentiate toward a pacemaker cell phenotype, which are present in sites other than the G.I. tract.

Adult↗
PubMed2004

Prognostic value of CD40 in adult soft tissue sarcomas.

PURPOSE: The purpose is to evaluate the expression of CD40, a membrane protein predominantly expressed on B cells, dendritic cells, and macrophages, in a series of adult soft tissue sarcomas and to test its possible prognostic value. EXPERIMENTAL DESIGN: CD40 expression was studied by immunohistochemistry. Correlations with other baseline characteristics of patients and tumors were analyzed with chi(2) test. The prognostic value was studied with univariable and multivariable analysis adjusted by age, sex, tumor size, grade, location, and distant metastases. RESULTS: Eighty-two patients, between January 1994 and May 2001, were analyzed. Membrane or cytoplasmic staining for CD40 protein was absent in 30% of the tumors but present in <10% of cells in 22 (27%), in 10% to 50% in 23 (28%), and in >50% of cells in 12 (15%) tumors. There was no correlation between CD40 expression and age, sex, size, grade, and location of the primary tumor and distant metastases. With 61 patients (74.4%) progressed and 31 (37.8%) dead, CD40 expression was a significant prognostic factor for disease-free and overall survival at univariable and multivariable analysis. Patients with tumors expressing CD40 in >50% of cells had a dramatically unfavorable prognosis with median disease-free and overall survival of 7 and 17 months, respectively, and hazard ratios of relapse and death as compared with patients with CD40-negative tumors of 2.89 (95% confidence interval: 1.26-6.60) and 6.92 (95% confidence interval: 2.18-22.0), respectively. CONCLUSIONS: These data suggest that expression of CD40 protein in >50% of cells might indicate an unfavorable prognosis in adult soft tissue sarcomas.

Age Factors↗
PubMedDate not supplied

CD40 activation as potential tool in malignant neoplasms.

BACKGROUND: CD40, a cell surface molecule, is expressed on B-cell malignancies and many different solid tumors. It is capable of mediating diverse biological phenomena such as the induction of apoptosis in tumors and stimulation of the immune response. It has thus been studied as a possible target for antitumor therapy. The general aim of this review is to focus the attention of clinical oncologists on the involvement of CD40 in tumors and the rationale of CD40-activation-based therapies in new, biologically oriented antitumor protocols. METHODS: A Medline review of published papers about the role of CD40 activation in cancer therapy. RESULTS: Many authors have shown that CD40 activation promotes apoptotic death of tumor cells and that the presence of the molecule on the surface of carcinoma lines is an important factor in the generation of tumor-specific T-cell responses that contribute to tumor cell elimination. The CD40 ligand (CD40L) is the natural ligand for CD40; it is expressed primarily on the surface of activated T lymphocytes. Preclinical studies suggest that CD40-CD40L interaction could be useful for cytotoxicity against CD40-expressing tumors and for immune stimulation. Tumor inhibition was observed when tumor cells were treated with agonistic anti-CD40 monoclonal antibodies or with the soluble form of CD40L. The results of the first phase I clinical trial to treat cancer patients with subcutaneous injection of recombinant human CD40L have been recently reported. Immunohistochemical studies have revealed that detection of CD40 in primary cutaneous malignant melanoma and lung cancer may have a negative prognostic value. Interestingly, up-regulation of CD40 was observed in the tumor vessels of renal carcinomas and Kaposi's sarcoma, suggesting possible involvement of CD40 in tumor angiogenesis. Recently, it has also been shown that CD40 engagement on endothelial cells induces in vitro tubule formation and expression of matrix metalloproteinases, two processes involved in the neovascularization and progression of tumors. CONCLUSIONS: CD40 activation represents an exciting target for hematological malignancies and solid tumors expressing the molecule, but its functional role in cancer development still remains unclear and controversial.

Animals↗
PubMedDate not supplied

Adjuvant treatment of high-risk adult soft tissue sarcomas: a survey by the Italian Sarcoma Group.

AIMS AND BACKGROUND: After the first adjuvant study on adult soft tissue sarcomas was concluded, the participating institutions continued to select and treat patients according to that protocol. The aim of this study was to test the protocol reproducibility when applied as a standard practice. METHODS: A call for retrospective data was launched in June 1999 (self-referral of consecutive unregistered patients); thereafter, a prospective follow-up was performed. The treatment regimen consisted of epirubicin (60 mg/m2 days 1 and 2), ifosfamide (3 g/m2/die for 3 days) and equimolar doses of 6-mercapto-ethansulfonate (MESNA), with 300 microg G-CSF administered subcutaneously from day +8 until recovery, every 3 weeks for a total of 5 cycles. RESULTS: From November 1996 to June 1999, 55 high-risk, adult patients were treated. The average median dose intensity was 89% of the planned program. Grade 3-4 toxicities were leukopenia (49%), thrombocytopenia (14%), transfusion requiring anemia in 7 patients (16%), and alopecia in all patients (100%). After a median follow-up of 70 months, 23 patients (41.8%) relapsed and 19 died. Median disease-free, local disease-free and overall survival rates have not yet been reached. The disease-free survival rates at 2 and 4 years were 73% and 57%, respectively; the corresponding overall survival rates were 91% and 70%, respectively. CONCLUSIONS: The feasibility and reproducibility of the original protocol were confirmed, since disease-specific overall survival and disease-free survival rates at the same period of observation and with the same prolonged follow-up did not differ.

Adolescent↗
PubMedDate not supplied

In vitro and in vivo expression of somatostatin receptors in intermediate and malignant soft tissue tumors.

BACKGROUND: Previous studies showed that the subtype 2 of somatostatin receptors (sstr2) is generally expressed by soft tissue sarcomas. MATERIALS AND METHODS: Using reverse transcription-polymerase chain reaction (RT-PCR), the present study evaluated the expression of sstr mRNA in 31 human intermediate and malignant soft tissue tumors. In 8 patients somatostatin receptor scintigraphy was performed to detect soft tissue tumor sites and visualize in vivo sstr expression. RESULTS: Somatostatin receptors were identified in 84% of the tumors analyzed by RT-PCR analysis. sstr1 and sstr2 were the receptors most frequently detected. Somatostatin receptor scintigraphy was able to identify primary and/or metastatic sites in 7 out of 8 patients, with an overall sensitivity per site of 87%. Concordant results were found between in vitro and in vivo techniques. CONCLUSION: The wide expression of sstrs in soft tissue tumors suggest a relevant role for these receptors in diagnosis and may have therapeutic applications.

Adult↗
PubMedDate not supplied

Biological prognostic factors in adult soft tissue sarcomas.

Adult soft tissue sarcomas (STSs) are a rare group of highly heterogeneous neoplasms arising in different tissues. They are locally aggressive and can produce recurrence and distant metastasis. The most common metastatic sites are lung, lymph nodes, liver, bone and soft tissues. Staging for STSs has been based on some prognostic information: grade (low vs. intermediate/high grade), size (small vs. large tumors), depth of infiltration (superficial vs. deep neoplasms) and presence or not of distant metastasis. In the last 10 years, a plethora of new markers (proliferation markers and DNA alteration, P-gp, p53, TLS-CHOP, cyclins, survivin, TERT, PAX3-PAX7/FKHR, SYT-SSX1/2, VEGF, E-cadherin and beta-catenin, nm23, SKP-2, p27, CD40) has been studied with regard to their role in promoting progression (in a laboratory setting) and then determining prognosis and therapy (in a clinical setting). In the present survey, we focused on the role of new biological prognostic factors in STSs and also reported the quality of such studies with an ad hoc designed questionnaire.

Adult↗