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Biomedical subjects

F Crippa

Publications and source records attributed to F Crippa.

At least 55 records · Page 3Linked to original sources

Phase I study with 4'-deoxydoxorubicin.

4'-Deoxydoxorubicin (dxDx), a new doxorubicin analogue, was administered intravenously on a 3-week schedule to 73 patients affected by advanced malignant neoplasms. Sixty-five patients, treated with eight dose levels ranging from 10 to 45 mg/m2, were evaluable. The dose-limiting toxicity was myelosuppression, mainly leukopenia. About one third of the patients complained of vomiting which was almost always mild. Minimal hair loss was also documented in about 40% of patients. No hepatic or renal toxicity was observed. Transient and aspecific electrocardiographic changes were recorded in 6% of patients after 1 h and in 3% after 24 h from drug injection. Left ventricular ejection fraction was decreased in two patients after a cumulative dose of 90 mg/m2. One patient died with cardiorespiratory insufficiency and his initial cardiovascular disease might have been aggravated by dxDx. No changes in myocardial function parameters were documented in 18 patients who reached higher cumulative doses, i.e. greater than or equal to 100 mg/m2 and greater than or equal to 200 mg/m2. The highest total dose administered in this study was 340 mg/m2. Therapeutic activity was observed with doses ranging from 25 to 45 mg/m2. Partial response was documented in pancreatic, colon, anal and breast carcinomas as well as in non-Hodgkin's lymphoma. Minor response was observed in prostatic, thyroid, and renal carcinomas as well as in chronic lymphocytic leukemia. The maximum tolerated dose was assessed to be between 40 and 45 mg/m2. A Phase II trial is ongoing utilizing the dose of 35 mg/m2 every 3 weeks.

Adolescent↗

The effects of an energy stimulator on blood electrolyte and lactate levels in athletes under training.

The effects of a mineral-vitamin-sugar preparation has been tested on a group of volley ball players under training. Plasma electrolytes (Na, K, Cl), erythrocyte electrolyte content, plasma lactate concentration and erythrocyte water content have been determined before and after a training session in three different experimental situations: a) controls; b) acute treatment with the energy stimulator; c) chronic treatment (8 days) with a similar preparation of the energy stimulator. The results are indicative of a significantly lower lactate production and a more stable electrolyte concentration after treatment with respect to the control data.

Chlorides↗

Association of CEA test and liver scan in detection of hepatic metastases of gastrointestinal carcinoma.

The authors evaluate the combined use of liver scan and the CEA test in the diagnosis of hepatic metastases of carcinoma of the gastrointestinal tract. Association of the two tests is justified by the fact that the liver scan is very specific but not very sensitive, whereas the CEA test is more sensitive and not very specific. The sensitivity of the CEA test, on the other hand, can be increased by increasing the threshold of normality. However, the associated diagnostic use of the liver scan and the CEA test gives a loss of specificity with respect to the use of the liver scan alone. The present study, carried out on a series of 376 patients affected by gastrointestinal tumors of which 79 were of the stomach (9 with hepatic metastases), 133 of the colon and higher sigmoid (25 with hepatic metastases), and 164 of the lower sigmoid and rectum (29 with hepatic metastases), proposed to establish by use of a statistical method the optimal threshold of the CEA test that would give the best diagnostic specificity of the combined CEA test and liver scan without any relevant loss of sensitivity. A threshold of 26 ng/ml of the CEA test and gave a specificity of 92%, a sensitivity of 80%, and an accuracy of 90%. The authors think that in the detection of liver metastases of gastrointestinal tumors, the combined test can be more helpful the less the probability, for a given patient, for other metastatic localizations.

Carcinoembryonic Antigen↗

Activity and toxicity of 4'-iodo-4'-deoxydoxorubicin in patients with advanced breast cancer.

Based on our previous Phase I study indicating good tolerability of the drug, we have evaluated therapeutic activity and acute and subacute toxicities associated with repeated courses of the new anthracycline 4'-iodo-4'-deoxydoxorubicin (I-Dox) at the maximum tolerated dose (80 mg/m2) every three weeks. Thirty-three patients (31 evaluated for activity and 32 for toxicity) with relapsed (11 cases) or advanced breast cancer at presentation (22 cases) were treated with 108 cycles (median 3, range 1-7) for a median cumulative dose of 240 mg/m2. We observed no complete and 11 (35%) partial responses. Minor response was documented in 5 additional patients. The most frequent and severe toxicity was hematological. In 47% of the cycles and 34% of the patients I-Dox administration was associated with WHO grade 4 neutropenia. Severe neutropenia was more frequent after repeated cycles. Similar cumulative toxicity was observed for thrombocytopenia and anemia. In three patients (7 cycles) fever and possible infection occurred during neutropenia and required oral antibiotics. Extra-hematological side-effects were limited to mild/moderate nausea lasting for a few hours and mild fatigue lasting 1-7 days. Alopecia or oral mucositis were minimal or absent in the majority of patients. One case of potential reversible cardiac toxicity was observed after 240 mg/m2 I-Dox in a patient with preexistent cardiac risk factors. In view of the reported activity, good general tolerability, and selective hematological toxicity, I-Dox should be evaluated at higher than the conventionally defined maximum tolerated dose in combination with recombinant human hemopoietic growth factors.

Adult↗

Uptake of tritiated thymidine, deoxyglucose and methionine in three lung cancer cell lines: deoxyglucose uptake mirrors tritiated thymidine uptake.

[(18)F]-fluorodeoxyglucose and [(11)C]-methionine are tracers which are widely used in oncological positron emission tomography. This study has been designed to assess the deoxyglucose and methionine uptake behaviour in three cell lines from different lung cancer histotypes. Tracer uptake was compared with proliferative activity as determined by growth curves and tritiated thymidine uptake. Deoxyglucose paralleled thymidine in all cell lines, peaking in the lag phase, decreasing throughout the exponential phase, and reaching its minimum in the plateau phase. The correlation was statistically verified and Spearman's rho ranged from 0.79 to 0.99. The absolute methionine uptake was always highest and always peaked on day 2, followed by a quite rapid decrease. However, besides the delay in maximum uptake, methionine incorporation was also related to proliferation, although the statistical correlations were weaker. These results show for the first time a clear correlation between deoxyglucose uptake and cell proliferation in a model comparing tracer uptake in different growth phases. Although delayed, methionine uptake was also related to cell growth and its greater intensity could be of interest for clinical use.

Carcinoma, Non-Small-Cell Lung↗

Nuclear medicine advances in breast cancer imaging.

Primary breast cancer imaging can be done by various means. Mammography is the most widely used technique because of its excellent diagnostic performance, patient compliance, and cost-effectiveness ratio. Other radiological techniques (such as ultrasonography) are indicated in particular circumstances, while some (such as digital mammography and magnetic resonance imaging) seem very promising but are still under evaluation. The recent technological progress in nuclear medicine has resulted in the availability of two diagnostic procedures that have been validated by extensive international clinical experience: scintimammography with Sesta-MIBI and positron emission tomography (PET) with fluorodeoxyglucose (FDG). The general advantage of nuclear medicine imaging is that tumor-seeking radiopharmaceuticals accumulate in cancer lesions, which makes scintimammography and PET fundamentally different from the radiological techniques that image the tumor mainly on the basis of morphological alterations. Scintimammography is indicated for the study of breast lesions in patients in whom mammography is non-diagnostic or difficult to interpret; it may be useful also to assess and even predict the response to primary chemotherapy. FDG-PET is increasingly used in oncology and is particularly useful in breast cancer as it gives more accurate information than scintimammography in the evaluation of patients with ambiguous mammographies and in discriminating between viable tumor, fibrotic scar or necrosis following surgery, chemo- or radiotherapy. The FDG uptake in the tumor correlates with the histological grade and potential aggressiveness of breast cancer, which may have prognostic implications. In addition to its usefulness in the study of breast lesions, FDG-PET shows great efficacy in detecting lymph node involvement prior to surgery. Whole-body PET provides information on soft tissue and bone metastases in a single scanning session, and has an important clinical role in detecting recurrent metastatic disease. On the basis of the above-mentioned evidence, nuclear medicine techniques, integrated with radiological techniques, offer an interesting opportunity to improve the diagnostic imaging yield in breast cancer, which will eventually lead to better patient management. This paper reports on the latest developments in this field.

Breast Neoplasms↗

Indium-111-DTPA-octreotide scintigraphy modulation by treatment with unlabelled somatostatin analogue in small-cell lung cancer.

AIMS AND BACKGROUND: Small-cell lung cancer (SCLC) tissue expresses somatostatin receptors and can be visualized by means of the indium-111-labelled somatostatin analogue DTPA-D-Pheoctreotide. The aim of the study was to investigate whether treatment with a cold somatostatin analogue can affect the imaging of somatostatin receptor scintigraphy. METHODS: Three patients with SCLC were treated with 200 micrograms of cold octreotide three times a day subcutaneously for 7 days. Whole body and planar scintigraphy was performed before and after the treatment. RESULTS: 111In-DTPA-octreotide uptake was increased in cancer lesions, whereas fixation in normal tissues (liver, spleen, kidneys) decreased. CONCLUSIONS: This is the first demonstration of an enhancement of SCLC imaging following unlabelled somatostatin analogue administration. Similar results have been described by other authors in a limited number of carcinoid tumors.

Carcinoma, Small Cell↗

The influence of blood glucose levels on [18F]fluorodeoxyglucose (FDG) uptake in cancer: a PET study in liver metastases from colorectal carcinomas.

AIMS AND BACKGROUND: To study the influence of blood glucose levels on the clinical reliability of positron emission tomography (PET) with [18F]-2-fluoro-2-deoxy-D-glucose (FDG) in the detection of liver metastases from colorectal carcinomas and in the analysis of tumor uptake of FDG. METHODS: After having given their informed consent, 8 patients with 20 liver metastases (mean size, 31.5 mm; range, 10-75 mm) detected by means of CT were submitted to a first FDG-PET examination under fasting conditions and, 2 days later, to a second FDG-PET examination performed after i.v. infusion of a glucose solution (4 mg/kg/min for 2 hrs). The results of the two studies were compared in each patient, considering both the localization of the metastases and the FDG uptake in the lesions. A non-kinetic method was used, calculating the Standardized Uptake Value (SUV). RESULTS: All 20 metastases were clearly visible on FDG-PET under fasting conditions. Moreover, in 2 patients FDG-PET detected a number of unknown liver metastases. The blood glucose levels after glucose infusion were significantly higher than the levels under fasting conditions, 158 +/- 13.8 mg/100 ml (mean +/- sd) and 92.4 +/- 10.2, respectively (P < 0.001), and the quality of the FDG-PET images showed a marked deterioration. FDG-PET was unable to detect 6 of the 20 lesions and another 10 lesions were localized less clearly. Moreover, 80% of the unknown liver metastases were not detected after glucose loading. The SUVs of metastases decreased from 9.4 +/- 5.7 (mean +/- sd) under fasting conditions to 4.3 +/- 8.3 after glucose loading (P < 0.001). CONCLUSIONS: FDG-PET studies may be particularly unreliable under conditions of high levels of blood glucose. Therefore, patients entering FDG-PET studies should fast, and blood glucose concentration needs to be taken into account when evaluating FDG uptakes in follow-up studies.

Adult↗

Preliminary study on serum levels of mucinous like cancer antigen (MCA) in patients with breast disease: comparison with CEA.

MCA (mucinous-like cancer antigen) can be measured in the biological fluids of patients by means of a solid phase enzyme immunoassay. This study describes the results of MCA determination in sera of 230 patients with benign (99) and malignant (131) breast diseases. MCA levels were significantly higher in breast cancer patients than in non cancer patients and in healthy subjects (p less than 0.001). MCA concentrations tended to increase as the stage of the disease advanced. The 95th percentile of MCA value distribution in normal subjects showed a diagnostic sensitivity in breast cancer patients of 16.3% at stage I, 26.2% at stages II-III and 52% at stage IV. In a group of 118 cancer patients, MCA and CEA were tested simultaneously. The diagnostic sensitivity and specificity of MCA and CEA assays was very similar; nevertheless the association of the two tests showed 11 cases with high levels of MCA and low levels of CEA and 9 patients with high levels of CEA and low levels of MCA. Seventy-four out of 118 patients were negative for both markers and in 22 out of 118 patients markers were positive. The new marker MCA appeared to correlate with breast cancer and gave different information complementary to CEA.

Adult↗

The role of serum carcinoembryonic antigen (CEA) in the management of patients with colorectal carcinoma: the experience of the Istituto Tumori of Milan.

CEA determination has attained an important role in the clinical management of patients with tumors of the colorectal tract. In this paper the experience of the Istituto Tumori of Milan is reviewed and the results are discussed. Three hundred and thirty-six patients were followed after curative resection of colorectal carcinoma. The follow-up period was 15 years, from January 1975 to December 1990 (global follow-up 1358 years). In the course of follow-up 136 patients developed recurrent disease. The number of CEA determinations for each patient ranged from 1 to 37 (mean 8, total 3330). CEA levels of presurgical patients were related to the clinical stage. Among patients who developed recurrences 61% showed an increase in CEA serum levels. In 200 patients with a negative follow-up we observed only 15 cases of false-positive results.

Adult↗

Mucin-like carcinoma-associated antigen (MCA) in breast cancer: clinical experience at the National Cancer Institute of Milan.

Mucin-like Carcinoma-associated Antigen (MCA) is a glycoprotein belonging to the mucin family; it is defined by the monoclonal antibody b-12. Mucins represent an interesting group of tumor markers and are widely utilized in the clinical monitoring of neoplastic patients. These molecules show a certain degree of tissue specificity and MCA is preferentially associated with breast tissue. Several studies have demonstrated that patients with breast cancer usually have high MCA serum levels. In this paper the experience of the National Cancer Institute of Milan with the clinical use of MCA in breast cancer patients is reported. The observed sensitivity of the MCA test was poor in patients with early-stage disease, while it was acceptable in patients with advanced breast cancer. MCA concentrations appeared to be directly related to disease spread. A clear relationship was seen between MCA levels and lymph-nodal status. The highest MCA plasma levels were observed in patients with metastatic disease. In this group of patients the sensitivity of the test on the basis of a cut-off of 11 U/mL was 52%.

Adenofibroma↗

Radioimmunotherapy of ovarian cancer.

Radioimmunotherapy (RIT) is a new therapeutical approach where radiolabeled monoclonal antibodies (MAb) against tumor-associated antigens are administered to treat tumor lesions. Ovarian cancer is one of the most promising fields for RIT. This paper gives an overview of some biodistribution studies in animal models and in patients with radiolabeled anti-ovarian cancer MAbs, and defines the main criteria which should be considered to plan a clinical trial of RIT in ovarian cancer. As regards the clinical results, the published outcome of various trials and the experience of the National Cancer Institute of Milan are summarized. Even if the number of patients involved in these clinical studies of RIT is too small to provide conclusive indications about its role in the management of ovarian cancer, the preliminary results from qualified groups show its potential in this disease despite the current problems that limit clinical application (above all, the instability of the radiolabeled linkage, the immunogenicity of murine antibodies, the poor absolute tumor radiolabel uptake and the bone marrow toxicity).

Animals↗

The breast cancer cell line MCF7 as a model of 99mTc-SestaMIBI, 99mTc-tetrofosmin and 99mTc-Medronate incorporation.

Hexakis-2-methoxyisobutylisonitrile (SestaMIBI) and 1,2-bis[bis(2-ethoxyethyl)phosphino]ethane (tetrofosmin) are 99mtechnetium compounds widely used in oncologic imaging. We investigated the uptake and release of SestaMIBI and tetrofosmin together with 99mTc-medronate in the MCF7 breast carcinoma cell line. All the tracers showed similar uptake kinetics, with a rapid increase in the first 30 minutes and a slower trend up to 120 minutes. Cell-associated activity was the same for SestaMIBI and tetrofosmin (4% of administered activity) and considerably lower for medronate (0.8%). For all tracers, almost all the accumulated activity was released within 1 hour. Furthermore, to verify an association between cell proliferation and tracer uptake, we performed growth-curve uptake experiments. Tetrofosmin uptake was lower in the logarithmic phase and higher in the plateau phase, whilst SestaMIBI showed the opposite trend. The differences between the tracers could be due to a relationship between proliferation and SestaMIBI uptake, or even to the influence of medium pH on membrane potential.

Breast Neoplasms↗