Radioligand-labeled binding assay and immunochemical assay for estrogen receptor in 115 human breast cancers

The aim of this study was to evaluate the results obtained from a new enzyme immunoassay (Abbott-ER-EIA) for the determination of estrogen receptor levels in tumor cytosols in comparison with the currently used DCC method. One hundred and fifteen consecutive primary breast cancer specimens were examined; 66 of the women were postmenopausal and 49 were premenopausal. A good correlation (r = 0.88, p less than 0.001 and a slope of 1.3) was found between ER-EIA and the steroid binding assay (DCC). When these data were analyzed according to menopausal status, no differences were observed for the slopes and correlation coefficients in pre' and postmenopausal groups. The ER-EIA appears to produce results comparable to those obtained with the conventional DCC method for the determination of ER in breast tumor cytosols.     

Infliximab chimeric antitumor necrosis factor-a monoclonal antibody as potential treatment for myelodysplastic syndromes

Accumulating evidence indicates tumor necrosis factor-a (TNF-a) as a key cytokine in the pathogenesis of the myelodysplastic syndromes (MDS). The identification of TNF-a as a regulator of apoptosis and the increased susceptibility of MDS cells to this cytokine provided the basis for several clinical trials of TNF inhibitors. Infliximab is an IgG1 chimeric anti-TNF-a monoclonal antibody composed of human constant and murine variable regions that bind specifically to both soluble and membrane-bound TNF-a. To date, only 2 studies have investigated the use of infliximab in patients with low-risk MDS. In both reports the drug showed a limited but significant activity and a favorable side-effect profile. In some patients, hematopoietic response was associated with decreased apoptosis as well as a decrease in abnormal metaphases by 50%. Further studies are currently underway and should provide useful information to define the more responsive subtypes of MDS, the patient characteristics, and the proper dosing regimen.     

Palliative care in advanced cancer

Palliative care represents a new field among clinical approaches to patients with advanced or terminal cancer. The modern concept of palliative care can be considered in several ways: 1) the relationship between palliative care and primary treatments of cancer (surgery, radiotherapy or chemotherapy); 2) the treatment of symptoms and the relationship between symptom control and quality of life; 3) end-of-life care. With regard to the relationship between palliative care and primary cancer treatments, it is common opinion that a continuity of care is needed from diagnosis to the terminal phase of the disease, and oncology departments could represent the ideal dimension in which to fulfil this requirement. In a continuity-of-care setting, symptom control becomes vitally important to improve quality of life of the patient throughout all the stages of the disease. Moreover, support for the patient and his/her family during the terminal phase of the disease is one of the most important dimensions of palliative care. In addition, assistance provided during the last hours of life and support for the family after the patient's death represent the so-called global assistance, which is distinctive of palliative care.     

Combination Chemotherapy for Marrow Relapse in Children and Adolescents with Acute Lymphocytic Leukaemia

38 children with acute lymphocytic leukaemia (ALL) in haematologic relapse were retreated with vincristine, daunomycin and prednisone (VPD) together with intrathecal methotrexate and prednisone, followed by asparaginase in those patients not in complete remission after 4 weeks. The overall complete remission (CR) rate was 79%; asparaginase was needed to achieve CR in 7 of the 30 responding patients. The median duration of second remission was only 36 weeks, but 6 out of 15 children receiving the COAP-POMP-CART consolidation regimen remain in continuous second remission after 37–260 weeks; 3 of them are currently off all therapy. It is concluded that a prolonged second remission can be achieved in children with ALL in bone marrow relapse by combining intensive chemotherapy with the prevention of meningeal leukaemia.     

Adjuvant, adoptive immunotherapy with tumor infiltrating lymphocytes plus interleukin-2 after radical hepatic resection for colorectal liver metastases: 5-year analysis

BACKGROUND AND OBJECTIVES: Conventional chemotherapy has not proven effective in improving long-term results of surgery for liver metastases from colorectal cancer. We assessed the usefulness of immunotherapy with tumor infiltrating lymphocytes (TIL) plus Interleukin-2 (IL-2) as adjuvant treatment. METHODS: Between 1995 and 1998, 47 patients were enrolled onto a prospective protocol; 25 entered the treatment group (A) and 22 entered the control group (B). All patients had undergone radical liver resection. TIL obtained from surgical specimens from group A patients were cultured and activated in vitro with IL-2, then reinfused into the patients with IL-2. We investigated pre- and post-IL-2 stimulation expression of T cell receptor (TCR) zeta- and epsilon-chains, p56(lck), Fas, and Fas-L by TIL immunostaining. RESULTS: Fourteen patients from group A (56%) received immunotherapy; 14 from group B (60%) underwent conventional chemotherapy, and the remaining 19 patients did not receive any treatment. No significant differences between the two groups were found in the actuarial and disease-free survival (DSF) rates after 1, 3, and 5 years. After IL-2 exposure, TCR zeta-chain expression significantly increased (P = 0.001); An increase in TCR epsilon-chain expression (P = 0.04), and p56(lck) (P = 0.03) was detected; TCR epsilon-chain expression was significantly increased in disease-free patients compared to those who relapsed (P = 0.04). Fas-L expression was correlated with the TCR epsilon-chain and p56(lck) levels (P = 0.05). CONCLUSIONS: Our data suggest that we are still a long way from being able to propose TIL + IL-2 treatment as an effective adjuvant therapy. However, the results confirm that the biological indicators examined could play an important role in modulating immunitary response against tumor cells.     

Sustained response to recombinant human erythropoietin and intermittent all-trans retinoic acid in patients with myelodysplastic syndromes

In vitro studies suggest that all-trans retinoic acid (ATRA) synergizes with erythropoietin (EPO) for the stimulation of hematopoiesis in patients with myelodysplastic syndrome (MDS). A clinical trial was performed to evaluate whether a combination of these agents was effective in relieving the cytopenias associated with MDS. Twenty-seven patients with low- or intermediate-risk MDS were enrolled in a 12-week study. ATRA was administered orally at the dose of 80 mg/m(2) per day in 2 divided doses for 7 consecutive days every other week. Recombinant human EPO was given subcutaneously 3 times a week. The EPO dose was initiated at 150 U/kg and was increased to 300 U/kg if after 6 weeks there was no or there was suboptimal erythroid response. Patients who responded to therapy were continued on ATRA and EPO at the same doses for 6 additional months (extension phase). Further treatment was given to patients with a continued response. Clinically significant erythroid responses with increases of hemoglobin levels of at least 1 g/dL or reduction of transfusion needs were seen in 13 (48%) patients, with 4 showing improved responses after dose escalation of EPO. Ten (37%) patients displayed continued responses during 6 months of extended treatment, and 7 (26%) are still responsive after a follow-up period of 13 months. Neutrophil responses were observed in 5 of 12 patients with neutropenia, and platelet responses were observed in 6 of 9 patients with thrombocytopenia. Three patients displayed trilineage responses that were sustained during continuation therapy. Side effects were observed in all patients but were of mild entity and did not require discontinuation of therapy. It is concluded that the combination ATRA + EPO is an effective and well-tolerated treatment for patients with low- and intermediate-risk MDS. The optimal ATRA and EPO schedule and the role of maintenance treatment remain to be determined and warrant further investigation.