Phase II study of temozolomide plus pegylated liposomal doxorubicin in the treatment of brain metastases from solid tumours.

Objective: A combination regimen of temozolomide (TMZ) and pegylated liposomal doxorubicin has been evaluated in the treatment of brain metastases from solid tumours.

Study Design: Nineteen consecutive patients (pts) have been enrolled in a prospective phase II trial and treated with TMZ 200 mg/m2 (days 1-5) and pegylated liposomal doxorubicin 35 mg/m2 (day 1) every 28 days. The study was prospectively projected according to the Simon's two-stage optimal design.

Dendritic cell-mediated cross-presentation of antigens derived from colon carcinoma cells exposed to a highly cytotoxic multidrug regimen with gemcitabine, oxaliplatin, 5-fluorouracil, and leucovorin, elicits a powerful human antigen-specific CTL response with antitumor activity in vitro.

Gemcitabine, oxaliplatin, leucovorin, and 5-fluorouracil (GOLF) is a novel multidrug regimen inducing high levels of necrosis and apoptosis in colon carcinoma cells. This regimen is also able to promote a process of Ag remodeling including up-regulation of immunotherapy targets like carcinoembryonic Ag (CEA), thymidylate synthase (TS). We have conducted a preclinical study aimed to investigate whether these drug-induced modifications would also enhance colon cancer cell immunogenicity.

Combined effects of protein kinase inhibitors and 5-fluorouracil on CEA expression in human colon cancer cells.

Previous studies showed that 5-fluorouracil (5-FU) and Staurosporine (ST), a protein kinase inhibitor (PKI), were able to increase the expression of carcinoembryonic antigen (CEA) in human colon cancer cells. In the present study, we examined the in vitro effects of five PKIs, i.e.

Phase II study of sequential hormonal therapy with anastrozole/exemestane in advanced and metastatic breast cancer.

Hormonal therapy is the preferred systemic treatment for recurrent or metastatic, post-menopausal hormone-receptor-positive breast cancer. Previous studies have shown that there is no cross-resistance between exemestane and reversible aromatase inhibitors. Exposure to hormonal therapy does not hamper later response to chemotherapy.

Adjuvant therapy of melanoma patients (stage II, III): a pilot immuno-toxicological study.

A pilot study was conducted to assess the tolerability and the effect on host immunity of a post-surgery adjuvant treatment of melanoma patients with an anti-angiogenic agent, Tamoxifen (TAM, 20 mg/die p.o., daily), combined with immunomodulating cytokines, i.

Preclinical studies on detection of circulating melanoma cells in patients: telomerase as a recognition marker of malignancy.

Preclinical studies based on a "simulation design", were performed with cultured melanoma cells prelabeled with 51Cr, added to normal blood and subjected to separation and recognition steps. Mononuclear cells (MNC) were isolated on ficollhypaque gradient, and melanoma cells were separated from lymphocytes using anti-CD45 immunomagnetic beads. Malignant cells were then recognized by measuring telomerase activity (TRAP and TRAP-ELISA assays).

Translational and post-translational modifications of proteins as a new mechanism of action of alpha-interferon: review article.

Interferon-alpha (IFNalpha) is a recombinant protein widely used in the therapy of several neoplasms such as myeloma, renal cell carcinoma, epidermoid cervical and head and neck tumours and melanoma. IFNalpha, the first cytokine to be produced by recombinant DNA technology, has emerged as an important regulator of cancer cell growth and differentiation, affecting cellular communication and signal transduction pathways. However, the way by which tumour cell growth is directly suppressed by IFNalpha is not well known.

The farnesyl transferase inhibitor R115777 (Zarnestra) synergistically enhances growth inhibition and apoptosis induced on epidermoid cancer cells by Zoledronic acid (Zometa) and Pamidronate.

Pamidronate (PAM) and zoledronic acid (ZOL) are aminobisphosphonates (BPs) able to affect the isoprenylation of intracellular small G proteins. We have investigated the antitumor activity of BPs and R115777 farnesyl transferase inhibitor (FTI) against epidermoid cancer cells. In human epidermoid head and neck KB and lung H1355 cancer cells, 48 h exposure to PAM and ZOL induced growth inhibition (IC(50) 25 and 10 microM, respectively) and apoptosis and abolished the proliferative and antiapoptotic stimuli induced by epidermal growth factor (EGF).

Molecular technology and the recombinant TSH have changed diagnostics of thyroid carcinoma with positive I-131 whole body scan but low serum thyroglobulin.

The early detection of recurrent differentiated thyroid carcinoma (DTC) cells in the post surgery DTC patients relies on the sensitivity of measuring both the level of thyroglobulin (Tg) and 131-Iodine distribution by Whole Body Scan (WBS). Undetectable level of Tg associated with negative WBS or elevated levels of Tg associated with positive WBS ("concordant") is ordinarily indicative of either absence or presence of disease. At times, elevated level of Tg with negative WBS or low levels of Tg with positive WBS ("discordant") could also occur.

Oxaliplatin/rituximab combination in the treatment of intermediate-low grade non-Hodgkin's lymphoma of elderly patients.

High and intermediate grade non-Hodgkin's lymphomas (NHL) require treatments with aggressive chemotherapy schedules. However, low grade NHLs display a low chemoresponsiveness and patients aged >65 years often do not tolerate anthracycline and corticosteroid-containing chemotherapy regimens. Therapeutic options in this subset of patients are watchful waiting, oral alkylating agents, purine nucleoside analogues, combination chemotherapy, interferon and monoclonal antibodies.

A novel biweekly multidrug regimen of gemcitabine, oxaliplatin, 5-fluorouracil (5-FU), and folinic acid (FA) in pretreated patients with advanced colorectal carcinoma.

Previous results suggest that GEM affects 5-fluorouracil (5-FU) metabolism and pharmacokinetics in cancer patients, while combined with oxaliplatin, levo-folinic acid, and 5-FU (GOLF regimen), at doses achievable in cancer patients, determines high cytotoxic and proapoptotic antitumour activity in colon cancer cells in vitro. On these bases we designed a phase I-II clinical trial testing the GOLF regimen in patients with metastatic colorectal carcinoma, who had received at least a prior line of chemotherapy. In total, 29 patients (20 males and nine females) enrolled in the study received every 2 weeks, gemcitabine (patients #1-3 received 600 mg m(-2); patients # 4-6 received 850 mg m(-2); while patients # 7-29 received 1000 mg m(-2)) on the day 1, levo-folinic acid (100 mg m(-2)) on the days 1 and 2; 5-fluorouracil (400 mg m(-2)) in bolus injection, followed by a 22-h continuous infusion (800 mg m(-2)) on the days 1 and 2, and oxaliplatin (85 mg m(-2)), 6 h after the 5-FU bolus on day 2.

Atrial fibrillation following chemotherapy for stage IIIE diffuse large B-cell gastric lymphoma in a patient with myotonic dystrophy (Steinert's disease).

The authors describe the unusual association between diffuse B-cell gastric lymphoma and myotonic dystrophy, the most common form of adult muscular dystrophy, and sudden atrial fibrillation following one cycle of doxorubicin-based chemotherapy in the same patient. Atrial fibrillation or other cardiac arrhythmias are unusual complications in patients treated with chemotherapy. The cardiac toxicity intrinsically associated with the aggressive chemotherapy employed could function as a triggering factor for the arrhythmia in the predisposed myocardium of this patient.

Drug-induced increase of carcinoembryonic antigen expression in cancer cells.

Most of gastrointestinal, breast and lung cancer cells express carcinoembryonic antigen (CEA). Therefore, this protein represents a suitable target for innovative diagnostic and immunotherapeutic strategies of various tumours. Presently CEA can be involved in three main approaches concerning cancer detection and therapy, i.

DNA repair enzymes and cytotoxic effects of temozolomide: comparative studies between tumor cells and normal cells of the immune system.

O6-alkylguanine-DNA alkyltransferase (OGAT) and the mismatch repair system (MRS) play a crucial role in the susceptibility of tumor cells to the cytotoxic effects of agents that generate O6-methylguanine in DNA, including the triazene compound temozolomide (TMZ). Studies performed with peripheral blood mononuclear cells (MNC) showed that TMZ was scarcely active on lymphocyte functions not dependent on cell proliferation (e.g.

Combined fludarabine and rituximab for low grade lymphoma and chronic lymphocytic leukemia.

As both fludarabine and rituximab are active against indolent lymphoproliferative disorders, we have studied the combination of fludarabine and rituximab in patients with low-grade lymphoma and chronic lymphocytic leukemia (CLL) in phase I/II fashion. Of 33 patients enrolled, 21(63.6%) had low-grade lymphoma and 12 (36.

Treatment of colon and breast carcinoma cells with 5-fluorouracil enhances expression of carcinoembryonic antigen and susceptibility to HLA-A(*)02.01 restricted, CEA-peptide-specific cytotoxic T cells in vitro.

Cancer vaccines directed against tumor associate antigen (TAA) have produced encouraging results in preclinical models but not in cancer patients. A major limitation of this strategy is the relative degree of tolerance to these antigens and the low and heterogeneous tumor cell expression of TAA and major histocompatibility complex (MHC). Previous studies have shown that 5-fluorouracil (5-FU) can upregulate the expression of membrane-associated carcino-embryonic antigen (CEA), and MHC molecules in colon and breast carcinoma cell lines.

Percutaneous ethanol injection efficacy in the treatment of large symptomatic thyroid cystic nodules: ten-year follow-up of a large series.

We present a prospective study on the long-term efficacy of percutaneous ethanol injection (PEI) treatment of a large series of symptomatic thyroid cystic nodules (STCN). Ninety-eight patients (72 females and 26 males) were treated. The mean basal volume of the STCN was 35.

A novel method for monitoring response to chemotherapy based on the detection of circulating cancer cells: a case report.

We describe a novel method for detecting micrometastasis in the blood stream of cancer patients based on RT-PCR amplification of tumor-associated carcinoembryonic antigen (CEA) mRNA. To increase sensitivity and specificity of RT-PCR, CEA transcript was selectively up-regulated in cancer cells by exposure of peripheral blood to non-toxic concentrations of staurosporine (ST). Thereafter, polyA(+) RNA was extracted from tumor cells captured by means of magnetic beads coated with a monoclonal antibody against a common human epithelial antigen.

Comparison of two provocative tests for calcitonin in medullary thyroid carcinoma: omeprazole vs pentagastrin.

Background: Provocative tests for calcitonin (CT) are fundamental in the diagnosis and follow-up of C-cell disease and in the detection of hereditary medullary thyroid carcinoma (MTC) carriers with unknown RET mutations. A recent report has proposed omeprazole, which can increase endogenous gastrin (GT), as a new provocative test for MTC.

Methods: We compared the omeprazole test (20 mg twice a day for 4 days) to the pentagastrin test (0.

Oxaliplatin plus raltitrexed and leucovorin-modulated 5-fluorouracil i.v. bolus: a salvage regimen for colorectal cancer patients.

The aim of the present study was to define the activity and tolerability of a triplet regimen including oxaliplatin 130 mg x m(-2) (2 h i.v. infusion) and raltitrexed 3.

Low-dose recombinant IL-2 induces psychological changes: monitoring by Minnesota Multiphasic Personality Inventory (MMPI).

Background: Chronic subcutaneous rIL-2 at low doses produces long-lasting immunomodulatory effects and is considered an effective treatment for renal cell carcinoma with marginal activity in malignant melanoma and colorectal cancer.

Patients And Methods: In this study we evaluated, by Minnesota Multiphasic Personality Inventory (MMPI), the psychological changes induced by rIL-2 in 10 patients with advanced tumors.

Results: After 3 months of rIL-2 treatment, 80% of the patients had a significantly increased score on the clinical scale of depression (D) and psychasthenia (Pt) (p<0.

Pharmacological modulation of carcinoembryonic antigen in human cancer cells: studies with staurosporine.

Preliminary studies, performed in our laboratory, showed that staurosporine (ST), a protein-kinase (PK) inhibitor, increases the expression of the carcinoembryonic antigen (CEA) in a human colon cancer cell line. The present study explores the cellular and molecular effects of ST on the CEA expression in breast cancer MCF-7 line and in a number of colon cancer cell lines characterized by the different basal levels of the antigen, including two cloned sublines (i.e.

In vitro generation of cytotoxic T lymphocytes against HLA-A2.1-restricted peptides derived from human thymidylate synthase.

5-Fluorouracil (5-FU) is a pyrimidine antimetabolite active against colorectal carcinoma and other malignancies of the digestive tract. Over-expression or mutation of thymidylate synthase (TS), the target enzyme of the 5-FU metabolite, 5-fluorodeoxyuridine monophosphate, is strictly correlated with cancer cell resistance to 5-FU. On this basis we investigated whether TS is a potential target for active specific immunotherapy of human colon carcinoma, which acquires resistance to 5-FU.