Biomedical subjects

A Bottini

Publications and source records attributed to A Bottini.

15 recordsLinked to original sources

PubMed1998

Cisplatin, epirubicin, and lonidamine combination regimen as first-line chemotherapy for metastatic breast cancer: a pilot study.

We assessed the activity and tolerability of a cisplatin, epirubicin, and lonidamine combination regimen as first-line chemotherapy in 28 advanced breast cancer patients. The schedule of treatment was as follows: 60 mg/ m2 epirubicin followed by 40 mg/m2 cisplatin given on days 1 and 2 every 21 days, with 450 mg lonidamine being given per os (three tablets) on days of chemotherapy administration and in the period intervening between one cycle and the next. Patients received a median of 5 (range 1-6) cycles. Overall, 22 patients were evaluable for response and 28, for toxicity. Four patients refused to continue the treatment after the first course, one was lost to follow-up, and one died due to toxicity (septic shock). The incidence of grade 3/4 nausea and vomiting was found to be greater than that expected with epirubicin and lonidamine alone. The addition of cisplatin resulted in an increase in platelet and hemoglobin toxicities, whereas the WBC toxicity did not differ from that expected with epirubicin and lonidamine. The hematological toxicity was found to be cumulative, leading to treatment delay in about 50% of patients at the fifth and sixth courses. The activity of this cytotoxic regimen was noteworthy, with the overall response rate being 81.8% (31.8% complete responses and 50.0% partial responses) in evaluable patients. This response rate decreased to 64.2% when all registered patients were included according to an intent-to-treat analysis. In conclusion, the association of cisplatin, epirubicin, and lonidamine given on the schedule described herein, appears to be very active but substantially toxic. We are now testing this combination in a randomized comparison, with the cisplatin dose being reduced to 30 mg/m2 given on days 1 and 2.

Administration, Oral↗

PubMed1998

Cytotoxic and antiproliferative activity of the CMF regimen administered in association with tamoxifen as primary chemotherapy in breast cancer patients.

Seventy six consecutive patients with T2-4, N0-1, M0 primary breast cancer (BC) received a median of 3 cycles of CMF (cyclophosphamide, methotrexate, 5-fluorouracil) regimen. Tamoxifen was concomitantly administered in patients with estrogen receptor positive (ER+) BC. Ki67 antigen was evaluated immunohistochemically in tumor specimens obtained before chemotherapy and at mastectomy. At post chemotherapy evaluation, tumor shrinkage greater than 50% was obtained in 60 patients (78.9%), 21 of them being complete responders (27.6%). As a whole, primary chemotherapy significantly decreased the number of Ki67 positive cells. More than 50% decrease in Ki67 expression was observed in 78.9% of patients attaining a clinical complete response (CR), in 44.7% of patients with partial remission (PR) and in 50.0% of non-responders, while an increase (>25%) in Ki67 expression was found in 5.3%, 18.4% and 18.7% of patients with CR, PR and non-response, respectively. Both CR and PR rates were superimposable in patients with ER+ and ER- primary BC, while the reduction in Ki67 expression was mainly found in ER+ cases. Patients with increased Ki67 expression from baseline, at the end of primary chemotherapy, had a shorter disease-free interval (70 months) with respect to patients with no change (88+ months) or decrease (87+ months), p<0. 05. To conclude, the activity of CMF + tamoxifen in primary BC does not seem superior to that expected administering CMF alone. The reduction in Ki67 expression, as a whole, correlated with clinical CR, but some individual discrepancies between tumor shrinkage and Ki67 pattern have been observed. The Ki67 reduction mainly confined to the ER+ primary BC suggests that tumor response in this subset may be linked to the reduction in proliferation activity, whereas other mechanisms such as apoptosis might be responsible for the tumor shrinkage in ER- tumors. Since the increase in proliferation activity after primary chemotherapy was associated with a greater recurrence rate and lower disease free interval, irrespective of tumor response, changes in proliferation activity after primary chemotherapy may represent a potentially available parameter that, in addition to the tumor response, can discriminate patients who would benefit from the cytotoxic treatment from patients who would not.

Adult↗

PubMed1997

Influence of neoadjuvant chemotherapy on serum tumor markers CA 15-3, MCA, CEA, TPS and TPA in breast cancer patients with operable disease.

Serum levels of CA 15-3, mucinous-like cancer antigen, carcinoembryonic antigen, tissue polypeptide antigen and tissue polypeptide-specific antigen (TPS) have been determined in 99 patients with T2-4 N0-1 M0 breast cancer (BC) before and after primary (neoadjuvant) chemotherapy and after surgery. As a whole, no difference in marker levels was apparent according to tumor and patient characteristics, with the only exception of TPS values, which showed an inverse relationship with the histologic grade. Serum marker levels did not substantially change with respect to baseline either after chemotherapy, despite the high response rate obtained, or after surgery. These data indicate a limited contribution of the primary tumor to the serum marker levels and are consistent for the scarce usefulness of marker evaluation in BC patients with an early stage of disease. Interestingly, pretreatment elevated CA 15-3 levels were correlated with a higher recurrence rate, further supporting the prognostic significance of this tumor marker.

Adult↗

PubMed1996

Lonidamine significantly increases the activity of epirubicin in patients with advanced breast cancer: results from a multicenter prospective randomized trial.

PURPOSE: Some evidence in vitro and in vivo shows that lonidamine (LND) can positively modulate the activity of doxorubicin and epirubicin (EPI). On this basis, a multicenter prospective randomized trial was performed in patients with advanced breast cancer (BC) to determine if the addition of LND to EPI could increase the response rate of EPI alone. PATIENTS AND METHODS: From May 1991 to May 1993, 207 patients were enrolled onto this study and randomized to receive intravenous (IV) EPI (60 mg/m2 on days 1 and 2) alone or with LND (600 mg orally daily). EPI administration was repeated every 21 days until tumor progression or for a maximum of eight cycles. LND was administered continuously until chemotherapy withdrawal. RESULTS: Response rate was significantly superior for the EPI plus LND scheme compared with the single-agent EPI either considering assessable patients (60.0% v 39.8%; P < .01) or including all registered patients according to an intention-to-treat analysis (55.3% v 37.5%; P < .02). The distribution of the response rate according to the site of disease did not show any significant difference between the treatment arms, except for the patient subgroup with liver metastases in which the combination EPI plus LND resulted in a significant improvement of responses than EPI alone. Toxicity was moderate, and except for myalgia, no adjunctive side effects were observed in the EPI plus LND arm. Overall survival and time to progression were similar in both groups. CONCLUSION: This study confirms in vivo that the administration of EPI is enhanced by the concomitant LND administration.

Adult↗

PubMed1995

Junctional sites of erythrocyte skeletal proteins are specific targets of tert-butylhydroperoxide oxidative damage.

The oxidative denaturation of the erythrocyte membrane, which is considered a major cause of the haemolytic process, was evaluated upon 'in vitro' oxidative stress with tertbutylhydroperoxide. Biochemical and ultrastructural analyses were performed to point out the effect of this substance on the skeletal network, which is mainly responsible for red cell shape and viability. Moreover, cell morphology was observed by scanning electron microscopy and membrane rigidity assessed by EPR measurements. The most relevant features of the membrane denaturation were, (i) lipid peroxidation, as assessed by malonidialdehyde production, (ii) spectrin and ankyrin degradation with simultaneous globin binding to the membrane, as evidenced by electrophoretic pattern of red cell ghosts. These phenomena were related to the drug concentration in the incubation medium, and accompanied by depletion of intracellular reduced glutathione. The denaturation of protein components hindered the release of spectrin in a hypotonic extraction medium and could be only partially reversed by dithiothreitol. The extensive membrane protein and lipid degradation, at high drug concentration, was coherent with a marked increase of membrane order (membrane 'rigidity'). No clustering of intramembrane proteins was shown by the transmission electron microscopy images. At the same time scanning electron microscopy demonstrated shrinking and disco-stomatocytic deformation of erythrocytes. Ultrastructural analysis of the membrane skeleton by fluorescence-labelling of spectrin and actin, allowed to point out that exposure to t-BHP caused the marginalization of spectrin and the rearrangement of actin molecules with formation of micro aggregates, so that a detachment of actin from the spectrin network was suggested. In addition to the generalized damage of red cell membrane, tertbutylhydroperoxide was found to induce a specific alteration of the skeletal network at the horizontal junction sites involving spectrin, actin, and protein 4.1 and thus to modify the cytoskeletal assembly. This effect on the membrane skeletal components was consistent with the hypothesis that oxidative stress plays a key role in the haemolytic process.

Ankyrins↗

PubMed1990

Melatonin and human cancer.

A number of studies performed in vitro and on experimental animals supported the view that pineal gland inhibits neoplastic growth. Data in humans are scanty and controversial. In the present study we measured serum melatonin (MT), prolactin (PRL) and growth hormone (GH) concentrations, at 08.00 and 24.00, in 132 cancer patients and in 58 healthy control subjects. The patients were stratified according to histology and stage of disease as follows: 30 stage I-II and 45 stage III-IV breast cancer (BC); 39 stage III-IV lung cancer; 18 advanced gastrointestinal (GI) cancer. We also measured MT levels, at the same time-points, in 20 women with primary BC before and after radical mastectomy. Finally, we evaluated the circadian rhythm of serum MT in 18 patients with advanced cancer. On the whole, the patients with advanced tumors showed serum MT levels significantly higher than controls, without any correlation with PRL and GH values. When looking at stage III-IV vs stage I-II BC patients, significantly higher MT levels have been found in the former group. The surgical removal of the primary BC was not associated with any changes in MT values at both time points considered. A highly significant rhythm of serum MT was recorded in advanced cancer patients and the rhythmic parameters were substantially superimposable on those of the control subjects.

Adult↗

PubMed1989

Early fresh frozen plasma prophylaxis of abnormal coagulation parameters in the severely head-injured patient is not effective.

Serious head injury may be complicated by coagulation abnormalities. Fresh frozen plasma (FFP) has been advocated as resuscitation fluid, in patients with head injury, to prevent the development of abnormal coagulation. The efficacy of this practice has never been established. We retrospectively reviewed the records of 149 head-injured patients having a Glasgow Coma Scale of 9 or less. One hundred six received FFP and were without evidence of coagulopathies, while 42 received no FFP or had coagulopathies. Group 1 received FFP within a time from injury (T1) and group 2 received FFP after time (T2) or not at all. Groups were similar in demographics, injuries, presenting Glasgow Coma Scale, and presenting hematologic parameters in serial pretreatment or posttreatment hematologic parameters (P less than .05). There were no differences between patients receiving "early" FFP, as compared with those receiving FFP later or not at all. The time of FFP administration did not appear to be critical for effective prophylaxis against coagulopathy.

Blood Coagulation Disorders↗

PubMed1987