Experimental search for the violation of Pauli exclusion principle: VIP-2 Collaboration.

The VIolation of Pauli exclusion principle -2 experiment, or VIP-2 experiment, at the Laboratori Nazionali del Gran Sasso searches for X-rays from copper atomic transitions that are prohibited by the Pauli exclusion principle. Candidate direct violation events come from the transition of a 2p electron to the ground state that is already occupied by two electrons. From the first data taking campaign in 2016 of VIP-2 experiment, we determined a best upper limit of [Formula: see text] for the probability that such a violation exists. Significant improvement in the control of the experimental systematics was also achieved, although not explicitly reflected in the improved upper limit. By introducing a simultaneous spectral fit of the signal and background data in the analysis, we succeeded in taking into account systematic errors that could not be evaluated previously in this type of measurements.

Evaluation of creatine kinase isoenzyme BB as a marker of neoplastic growth in Yoshida ascites hepatoma of the rat.

A considerable interest has recently been shown for the measurement of isoenzyme BB of creatine kinase as a diagnostic and prognostic indicator of tumor growth. This isoenzyme belongs to the group of oncofetal antigens and in human cancer elevated levels occur frequently in patients with metastatic disease. In this study we have attempted to quantify CK-BB serum levels during the growth of an experimental tumor (Yoshida Hepatoma AH 130) in male albino rats to determine if a significant correlation exists between isoenzyme serum levels and the rate of tumor growth. Creatine kinase-BB was measured spectrophotometrically by immunoinhibition of creatine kinase-M subunits. CK-BB normal values were 4.19 +/- 0.4 U/L and between days 5 and 9, where there is an increase in the rate of proliferation of neoplastic cells, CK-BB serum levels reaches its maximum 69.01 +/- 2.2 U/L. These data are in agreement with the hypothesis that the highest isoenzyme levels are a measure of the aggressiveness of the neoplastic clone. Moreover, this hypothesis is consistent with the proposed mathematical model, and we plan to expand this line of study to evaluate the predictive potential of this tumor marker in man.

Protective effect of L-carnitine on cardiac metabolic damage induced by doxorubicin in vitro.

Carnitine, a naturally occurring compound which is an important cofactor in the transport of fatty acids within inner mitochondria, aids myocardial cells in efficiently meeting energy requirements. L-Carnitine has been texted in this study as a possible protective agent against doxorubicin-induced cardiac toxicity. Rat heart slices were incubated with doxorubicin (14 micrograms/ml), L-carnitine (600 micrograms/ml), and L-carnitine plus doxorubicin for 60 min at 38 degrees C. Cellular oxygen uptake, ATP, intracellular Ca2+, and 14C-Leucine incorporation were measured. L-carnitine pre-incubation significantly reduced (p less than 0.001) the metabolic cardiac impairment due to doxorubicin. The inhibition of oxygen uptake declined from 38% to 7%; of ATP cellular concentration from 78% to 27%; and that of protein synthesis from 11% to 6%. L-carnitine moreover acts to eliminate completely the Ca2+ increase induced by doxorubicin. Thus, it appears L-carnitine may be useful in the prevention of doxorubicin-induced cardiac toxicity.

Complete androgen blockade as treatment for advanced prostate cancer: clinical response and side-effects.

Treatment of advanced prostatic cancer is currently based on hormonal manipulation. In 1982 Labrié supported a new concept of hormonal treatment based on complete androgen blockade. The objective of this study was to evaluate the effects of total androgen suppression, achieved by the combination of a LHRH agonist (buserelin) plus a pure anti-androgen (flutamide) in the long-term treatment of advanced prostate cancer. Forty-seven untreated consenting patients with advanced prostatic cancer entered in the study, and 41 of these proved evaluable for response and toxicity. Buserelin and Flutamide were administered three times daily, intranasally and orally respectively, at a dose of 1.2 mg and 750 mg for twelve months. Circulating testosterone levels, regularly measured during the study, were reduced by the treatment to castrated levels. Clinical results are encouraging for the high rate of objective and clinical responses PR + SD = 37 (90%), for its duration (12 months), for the significant improvement of urological symptoms and for the decrease of cancer-related pain, even in cases with detectable bone metastases. Compliance was excellent in all the subjects and no patient was forced to interrupt treatment because of cardiovascular toxicity or severe side-effects, which were limited to occasional loss of libido and potency, hot-flashes, mild diarrhea and nausea.

Creatine kinase isoenzyme BB: a lung cancer associated marker.

We investigated the diagnostic role of creatine kinase isoenzyme BB (CK-BB) in lung cancer. CK-BB was assayed using a radioimmunological system by saturation with Mallinchrodt double antibody 125I labelled (RIA Quant-CPK-BB). Sensitivity was 97% and specificity 90% in 44 cancers (T2-T3), in 36 non-cancers (chronic bronchitis) and in 48 healthy controls. Mean serum CK-BB values for patients with chronic bronchitis (2.64 +/- 1.1 ng/ml) were virtually the same as in normal subjects. Patients with lung cancer had markedly higher serum CK-BB values (9.17 +/- 2.6 ng/ml) than either the control group (healthy subjects) or the chronic bronchitis patients (p less than 0.01). These results lead us to suggest that CK-BB serum determination might prove useful in screening pulmonary disorders. However, further studies are essential to establish: 1) the relationship between serum levels of the isoenzyme and the histology and stage of the neoplastic disease; 2) the relation between CK-BB and the aggressive potential of the neoplastic clone.

Echocardiographic assessment of anthracycline cardiotoxicity during different therapeutic regimens.

The use of doxorubicin (Dx) in treating malignancies is limited by a potentially fatal cardiomyopathy. Prevention of this related cardiotoxicity has been attempted either by using doxorubicin analogues such as 4'-epidoxorubicin (4'-EpiDx) or by simultaneous administration of other pharmacological substances. Fifteen patients with breast and lung cancer divided into three groups, treated respectively with Dx alone, Dx and L-carnitine and 4'-EpiDx, were studied to assess the effects of these therapeutic regimens on left ventricular performance. For this purpose the maximum velocities of fibre shortening and lengthening (VcF), obtained by computerized M-Mode echocardiography were used as indices of systolic and diastolic function respectively. Data from patients and from 25 healthy subjects were evaluated by analysis of variance and Tukey test. No significant difference was found in baseline systolic and diastolic VcF values. Significantly lower systolic VcF (p less than 0.05) was shown by patients treated with Dx alone, while diastolic VcF was significantly lower in those treated with 4'-EpiDx after four cycles. Systolic VcF of patients treated with Dx and L-carnitine and with 4'-EpiDx did not significantly differ from controls even after six therapeutic cycles. These data demonstrate that systolic VcF is not affected by 4'-EpiDx or by Dx when administrated with L-carnitine. The reduction of diastolic VcF by 4'-EpiDx and not by Dx could be due to different effects of these drugs on the calcium transport since early isovolumic relaxation depends on an energy-dependent process of calcium removal.

Study of cosmic rays and light flashes on board Space Station MIR: the SilEye experiment.

The SilEye experiment aims to study the cause and processes related to the anomalous Light Flashes (LF) perceived by astronauts in orbit and their relation with Cosmic Rays. These observations will be also useful in the study of the long duration manned space flight environment. Two PC-driven silicon detector telescopes have been built and placed aboard Space Station MIR. SilEye-1 was launched in 1995 and provided particles track and LF information; the data gathered indicate a linear dependence of FLF(Hz) ( 4 2) 10(3) 5.3 1.7 10(4) Fpart(Hz) if South Atlantic Anomaly fluxes are not included. Even though higher statistic is required, this is an indication that heavy ion interactions with the eye are the main LF cause. To improve quality and quantity of measurements, a second apparatus, SilEye-2, was placed on MIR in 1997, and started work from August 1998. This instrument provides energetic information, which allows nuclear identification in selected energy ranges; we present preliminary measurements of the radiation field inside MIR performed with SilEye-2 detector in June 1998.

Clinical utility of the combined use of plurime tumor markers in human breast cancer.

Many biological substances are commonly used as markers for malignant neoplasms, but no single marker with high specificity and sensitivity has been found for cancer to date. In this study we evaluated simultaneously the serum levels of five biomarkers of malignancy: phosphohexose-isomerase (PHI), creatine kinase isoenzyme BB (CK-BB), alpha 1-acid glycoprotein (AAG), beta 2-microglobulin (BMG), and ferritin. In 89 female patients with breast lesions, we identified 30 benign lesions, 32 primary breast cancers, and 27 metastatic breast cancers (pulmonary and/or bone metastases). Each marker was assayed individually and in a combination and was compared with other markers. The results revealed that in benign lesions only 7% had PHI values higher than our cut-off limit value, while 3% had elevated values of AAG, BMG, and ferritin. In primary breast cancer we discovered pathological values of CK-BB and AAG in 71%, of PHI in 69%, of BMG in 50%, and of ferritin in 47%. Metastatic disease was associated with elevated values in 88% of CK-BB, in 70% of PHI and AAG, and in only 55% of BMG and ferritin. Combined pathological values for primary and metastatic breast cancer were 79% for CK-BB, 71% for AAG, 70% for PHI, and only 55% for BMG and ferritin. These data were assessed by the Student t test, which revealed for each marker a significant capacity (P less than 0.01) to discriminate between benign lesions and neoplastic diseases. The same capacity to distinguish between primary and metastatic cancer was obtained by the simultaneous use of three markers (CK-BB, PHI, and AAG).(ABSTRACT TRUNCATED AT 250 WORDS)

Doxorubicin and epirubicin cardiotoxicity: experimental and clinical aspects.

Epirubicin (EpiDx) belongs to the class of anthracycline antibiotics. It is an analog of doxorubicin (Dx) modified in the sugar moiety and in which the stereochemistry at the hydroxyl group bearing C-4' has been inverted. The purpose of this study was to evaluate in an experimental model and in a clinical trial the cardiotoxic effects of EpiDx vs Dx. Cellular oxygen uptake was measured in vitro for equal concentration of Dx and EpiDx with a Warburg manometric apparatus and ATP intracellular concentration by high-pressure liquid chromatography. Dx inhibits cellular endogenous respiration of rat heart slices by 34% vs control, while EpiDx reduces oxygen uptake by 18%. ATP intracellular concentration was significantly reduced by both anthracycline derivates. The same results were obtained after Dx administration in vivo which enabled us to correlate the biochemical parameter (QO2) with the histological cardiac damages shown by light microscopy. For the clinical trial, we studied a total of 22 patients undergoing chemotherapy for solid tumors in an advanced stage. Nine of these were treated with Dx for a total of 66 therapeutic cycles and reached a maximal cumulative dose of 540 mg/m2. Thirteen were treated with EpiDx for a total of 121 cycles (maximal dose reached 720 mg/m2). The dosage of both agents were equal, 60 mg/m2 every 3 weeks. Acute cardiotoxicity was evaluated, measuring creatine-kinase isoenzyme MB(CK-MB) serum level before and 15 h after anthracyclines administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Osteocalcin as a biological marker in the therapeutic management of breast cancer bone metastases.

Circulating osteocalcin (BGP), the major noncollagenous bone protein, is elevated in patients with certain metabolic bone disease while its behavior in cancer patients, particularly those with bone metastases, is unclear. We measured circulating BGP in 37 healthy females, in 13 female patients with benign breast disease, and in a group of 51 cancer patients (breast, lung, prostate, and bladder) with and without bone metastases, before and after 4'-epidoxorubicin (4'-Epidx) therapy (4'-Epidx 120 mg/m2 every 3 weeks). Under basal conditions, mean BGP levels of all of these subjects fell within the normal range of 2.0-5.0 ng/ml (mean +/- SD, 4.8 +/- 1.0 ng/ml). In cancer patients without bone metastases BGP levels measured before and after 4'-Epidx therapy were not significantly different (4.4 versus 4.6 ng/ml). Only in breast cancer patients with multiple bone metastases was circulating BGP higher after the onset of antiblastic treatment and through the entire course of therapy, accompanied by bone pain remission and regression of bone lesions (BGP = 6.7 +/- 1.3 ng/ml). Thus an increase in BGP concentration can be considered as a biological marker of recovered osteoblast activity during therapeutically induced stabilization or regression of skeletal metastatic lesions.

Epirubicin high-dose therapy in advanced breast cancer: preliminary clinical data. Epirubicin as a single agent in breast cancer.

Of the new anthracycline derivatives, epirubicin is the antibiotic whose antitumor activity is comparable to that of doxorubicin while its cardiotoxicity is reduced by half. We therefore incorporated into our continuing study on anthracycline antitumor effects and toxicity a group of 22 evaluable patients, mean age 52 years, with advanced breast cancer, all of whom had previously undergone chemotherapy, radiotherapy and/or hormonal therapy. Epirubicin was administered at a dose of 120 mg/M2 every 3 weeks, for a maximum of 10 such cycles. The left ventricular ejection fraction (LVEF), determined by radionuclide ventriculography, was measured periodically in all patients. We observed 2 complete responses and 13 partial responses (CP + PR = 69%) of 61 weeks' mean duration; in 3 cases lesions remained stationary while the disease progressed in 4 patients. No patients died of acute toxicity. The main side effects were severe alopecia in 82% of the subjects and moderate degrees of nausea without vomiting in 41%. After 6 treatment cycles, 4 patients showed mild cardiotoxicity and at an epirubicin cumulative dose of 1,200 mg/M2 2 patients developed congestive heart failure (CHF). Hematological toxicity was in no case so severe as to require a reduction in the dose but only a postponement of treatment by 3 to 5 days in 9% of cycles. Without increasing hematological or cardiac toxicity, epirubicin, at a dose of 120 mg/M2, has shown itself to be a highly effective agent against advanced breast cancer.

Circulating immune complexes (CIC) as tumor marker in the follow-up of breast cancer.

We report on the possible diagnostic and prognostic role of circulating immune complexes (CIC) determination in breast cancer. A sensitivity of 87% and a specificity of 90% were observed in a case-control study of 15 cancers and 25 noncancer healthy controls. A direct correlation of CIC level to the presence and probably to the entity of the tumor mass was assessed by comparing preoperative to postoperative CIC determinations in cancer cases: CIC levels were significantly lower after tumor removal. These preliminary results suggest further studies on the use of CIC determination in the follow-up of breast cancer for the early diagnosis of recurrent disease.

Ventricular late potentials in the assessment of mitoxantrone cardiotoxicity.

Sixteen female patients underwent signal-averaged electrocardiography and radionuclide angiography for the assessment of the resting left ventricular ejection fraction in the course of chemotherapy with mitoxantrone (MTX) for advanced breast cancer. Nine patients had received prior cardiotoxic treatments. Our findings indicate that patients treated with MTX may develop late potentials.

First Mass-resolved Measurement of High-Energy Cosmic-Ray Antiprotons.

We report new results for the cosmic-ray antiproton-to-proton ratio from 3 to 50 GeV at the top of the atmosphere. These results represent the first measurements, on an event-by-event basis, of mass-resolved antiprotons above 18 GeV. The results were obtained with the NMSU-WIZARD/CAPRICE98 balloon-borne magnet spectrometer equipped with a gas-RICH (Ring-Imaging Cerenkov) counter and a silicon-tungsten imaging calorimeter. The RICH detector was the first ever flown that is capable of identifying charge-one particles at energies above 5 GeV. The spectrometer was flown on 1998 May 28-29 from Fort Sumner, New Mexico. The measured p&d1;/p ratio is in agreement with a pure secondary interstellar production.