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Biomedical subjects

S Carlini

Publications and source records attributed to S Carlini.

At least 19 recordsLinked to original sources

Correlation between tumor necrosis factor-alpha and D-dimer levels in non-small cell lung cancer patients.

The present study was designed to investigate whether a correlation exists between IL-6, TNF-alpha and coagulation (Thrombin-antithrombin, TATc) or fibrinolysis (D-dimer) activation in non-small cell lung cancer (NSCLC) patients. One hundred thirty patients with NSCLC (n=65, 53 males, mean age 65 +/- 8, adenocarcinoma n=32, squamous cancer n=33) or chronic obstructive pulmonary disease (COPD) (n=65, 51 males, mean age 67 +/- 9) were studied. As control group 65 healthy donors (51 males, mean age 61 +/- 14) were also evaluated. The results obtained showed that median D-dimer levels were higher in NSCLC patients (3.0 microg/ml) compared either to COPD patients (1.1 microg/ml, P<0.05) or controls (0.3 microg/ml, P<0.0001). Positive TNF-alpha levels (>10 pg/ml) were found in 26% of NSCLC compared to 3% of COPD (P<0.002) and 5% of controls (P<0.0005). On the other hand, positive (>8.5 pg/ml) IL-6 levels were found in 53% of NSCLC and 21% of COPD patients, compared to 5% of control subjects (P<0.001). Median TATc levels were elevated in either NSCLC (6.9 microg/l) or COPD (5.7 microg/l) patients compared to controls (1.8 microg/l, P<0.0001). Elevated D-dimer levels were significantly associated to positive TNF-alpha levels in patients without distant metastasis (F=4.3, P<0.05). Moreover, TNF-alpha levels (P<0.01) were independently related to the presence of positive D-dimer levels in patients with non-metastatic NSCLC. These results suggest that increased levels of TNF-alpha might be responsible for an activation of fibrinolysis in patients with NSCLC.

Aged↗

Detection of blood-borne cells in colorectal cancer patients by nested reverse transcription-polymerase chain reaction for carcinoembryonic antigen messenger RNA: longitudinal analyses and demonstration of its potential importance as an adjunct to multiple serum markers.

The use of reverse transcription-PCR (RT-PCR) to analyze cells in the blood of cancer patients for the detection of mRNA expressed in tumor cells has implications for both the prognosis and the monitoring of cancer patients for the efficacy of established or experimental therapies. Carcinoembryonic antigen (CEA) is expressed on approximately 95% of colorectal, gastric, and pancreatic tumors, and on the majority of breast, non-small cell lung, and head and neck carcinomas. CEA shed in serum is useful as a marker in only approximately 50% of colorectal cancer patients and rarely is shed by some other carcinoma types. RT-PCR has been used previously to detect CEA mRNA in cells in the blood and lymph nodes of cancer patients. Under the assay conditions validated in the studies reported here, 34 of 51 (67%) patients with different stages of colorectal cancer had blood cells that were positive by RT-PCR for CEA mRNA, whereas none of 18 patients with colonic polyps were positive; 2 of 60 apparently healthy individuals (who were age and sex matched with the carcinoma patients and were part of a colon cancer screening program as controls) were marginally positive. The results of CEA PCR in the blood of the carcinoma patients and the other groups showed strong statistical correlation with the disease (P2 < 0.0001). Analyses were carried out to detect both serum CEA protein levels and CEA mRNA in blood cells of colorectal carcinoma patients by RT-PCR. For all stages of disease, 18 of 51 patients (35%) were positive for serum CEA, whereas 35 of 51 (69%) were positive by RT-PCR. More importantly, only 5 of 23 (20%) of stage B and C colorectal cancer patients were positive for serum CEA, whereas 16 of 23 (70%) were positive by RT-PCR. The use of two other serum markers (CA19.9 and CA72-4) for colorectal cancer in combination with serum CEA scored two additional patients as positive; both were positive by RT-PCR for CEA mRNA. Pilot long-term longitudinal studies conducted before and after surgery identified some patients with CEA mRNA in blood cells that were negative for all serum markers, who eventually developed clinical metastatic disease. The studies reported here are the first to correlate RT-PCR results for CEA mRNA in blood cells with one or more serum markers for patients with different stages of colorectal cancer, and are the first long-term longitudinal studies to use RT-PCR to detect CEA mRNA in blood cells of cancer patients. Larger cohorts will be required in future studies to define the impact, if any, of this technology on prognosis and/or disease monitoring.

Adenocarcinoma↗

Serum tissue polypeptide specific antigen (TPS): a complementary tumor marker to CA 15-3 in the management of breast cancer.

The efficacy of CEA and CA15-3 tumor markers in monitoring breast cancer was evaluated in 1365 patients with either benign (n = 534) or malignant (n = 831) breast diseases. Thirty-nine breast cancer patients were monitored before and after neoadjuvant chemotherapy. Three hundred forty-nine patients were monitored during post-surgical follow-up for either a minimum of 5 years or until time of recurrence. Twenty-one patients with metastases were also monitored during chemotherapy. Elevated CA 15-3 and TPS levels were found in 28.6% and 30.0% of patients. CA 15-3 and TPS sensitivities rose to 71.9% and 66.3% in metastatic patients, respectively. The addition of TPS to CA 15-3 increased the sensitivity up to 44.4% in the overall population, and to 87.6% in patients with metastases. During post-surgical follow-up CA 15-3 was elevated in 65.7% and TPS in 61.3% of patients with recurrence. The combination of TPS and CA 15-3 increased the overall sensitivity by 12.7%. Longitudinal monitoring of metastatic patients undergoing chemotherapy demonstrated that, when positive, both CA 15-3 and TPS paralleled response to treatment. TPS monitoring may provide additional value when used in combination with CA15-3 during post-surgical follow-up of breast cancer patients.

Adolescent↗

A re-evaluation of carcinoembryonic antigen (CEA) as a serum marker for breast cancer: a prospective longitudinal study.

PURPOSE: Carcinoembryonic antigen (CEA) is still a widely used test for monitoring breast cancer, although recent reports discourage its routine use because of low sensitivity. This is a prospective study evaluating the efficacy of CEA and CA 15.3 in monitoring breast cancer. EXPERIMENTAL DESIGN: Serum CEA and CA 15.3 were measured in 2191 patients with either benign (n = 738) or malignant (n = 1453) breast diseases. Five hundred and forty-nine patients were monitored during postsurgical follow-up for either a minimum of 5 years or until time of recurrence. Fifty-three patients with metastases were also monitored during chemotherapy. RESULTS: Elevated CEA and CA 15.3 levels were found in 16.7% and 33.0% of patients, respectively. CEA sensitivity rose to 41.3% and CA 15.3 sensitivity rose to 80.8% in metastatic patients. The adjunct of CEA increased the CA 15.3 sensitivity by 6% in the overall population and by only 2.1% for patients with metastases. During postsurgical follow-up, CEA was elevated in 38.0% and CA 15.3 in 70.2% of patients with recurrence. The combination of CEA and CA 15.3 increased the overall sensitivity by only 1.4%. Longitudinal monitoring of 53 metastatic patients undergoing chemotherapy demonstrated that, when positive, both CEA and CA 15.3 paralleled response to treatment, although CA 15.3 was a significantly more powerful marker for determining response to treatment. The cost effectiveness ratio of CEA was clearly less favorable than that of CA 15.3. CONCLUSIONS: CEA monitoring should be considered an expensive and inefficient method of follow-up evaluation for breast cancer patients, and it provides no additional value when used in combination with CA 15.3.

Adenocarcinoma↗

BRCA1 and BRCA2 mutations in central and southern Italian patients.

Protein truncation test (PTT) and single-strand conformation polymorphism (SSCP) assay were used to scan the BRCA1 and BRCA2 genes in 136 unrelated Italian breast/ovarian cancer patients. In the sample tested, BRCA1 and BRCA2 equally contributed to site-specific breast cancer patients who reported one to two breast cancer-affected first-/ second-degree relative(s) or who were diagnosed before age 40 years in the absence of a family history of breast/ovarian cancer. BRCA1 and BRCA2 mutations were mostly found in patients with disease diagnosis before and after age 50 years, respectively. Moreover, in cases with familial clustering of site-specific breast cancer, BRCA1 mostly accounted for tumours diagnosed before age 40 years and BRCA2 for tumours diagnosed after age 50 years. The BRCA1 and BRCA2 mutation spectrum was consistent with a lack of significant founder effects in the sample of patients studied.

Adult↗

Interrelation between angiographic severity of coronary artery disease and plasma levels of insulin, C-peptide and plasminogen activator inhibitor-1.

Plasma insulin, C-peptide and plasminogen activator inhibitor-1 (PAI-1) levels were measured in 64 men with coronary artery disease (CAD) documented by angiography. Coronary arteriograms were analyzed, and the severity and diffusion of coronary lesions were quantified by score systems. C-peptide and PAI-1 levels in patients with CAD were significantly higher than in 30 control subjects. Insulin, C-peptide and PAI-1 showed a highly significant correlation with the severity scores for coronary lesions (C-peptide more than insulin), but only a weak correlation with diffusion scores. Highly significant correlations were found between insulin and PAI-1, and even greater ones between C-peptide and PAI-1. It has been proposed that hyperinsulinemia may be involved in the etiology of atherosclerotic cardiovascular disease by dysregulating lipoprotein metabolism and blood pressure. These findings support that hypothesis and suggest that insulin secretion may be an index of the severity of CAD. Because a direct effect of insulin on the cells that synthesize PAI-1 has been shown, the present data further indicate that the effect of insulin on fibrinolysis may be another way by which hyperinsulinemia accelerates atherogenesis.

Body Mass Index↗

Serum levels of soluble interleukin-2 receptor in Hodgkin disease. Relationship with clinical stage, tumor burden, and treatment outcome.

BACKGROUND: Previous studies suggested a possible role for the detection of soluble interleukin-2 receptor (sIL-2R) in Hodgkin disease (HD). In this study, the authors investigated, in a large series of patients, sIL-2R serum levels in relation to disease features at presentation and prognosis. Their usefulness as markers in the management of individual cases was evaluated. METHODS: The sIL-2R serum levels were measured in 195 patients at diagnosis. In 72 of these patients, sIL-2R serum levels were also monitored after diagnosis. An additional 87 cases were tested only in complete remission (CR), and 25 were tested only at relapse. RESULTS: The sIL-2R levels at diagnosis were increased (mean +/- 1222 +/- 1012 versus 331 +/- 145 U/ml in controls, P < 0.0001) and correlated with the stage and tumor burden (Stages I and II = 1058 +/- 1007, Stages III and IV = 1502 +/- 942 U/ml, P = 0.003; Stage A = 954 +/- 705, Stage B = 1880 +/- 1238 U/ml, P < 0.0001; bulky presentation = 1958 +/- 1430, nonbulky presentation = 1043 +/- 791 U/ml, P < 0.0001). Response to treatment was associated with progressive reduction of sIL-2R levels, which were normal in virtually all cases 1 year after CR. Significantly greater levels at diagnosis were found in 11 patients who experienced a poor response or progression after treatment (P = 0.004). Overall, abnormal data in CR were found in 59 of 159 patients and 9 of them subsequently experienced a relapse. CONCLUSIONS: The sIL-2R serum levels in HD correlate with features at presentation and subsequent clinical courses. Higher levels at diagnosis entail a significantly higher risk of treatment failure.

Adolescent↗

Levels of plasma factor VII and factor VII activated forms as a function of plasma triglyceride levels.

It has been shown that triglyceride levels are one of the determinants of factor VII levels. In this study we have simultaneously evaluated, in a group of 102 healthy individuals, the different forms of factor VII, namely factor VII mass, factor VII coagulant activity, activated factor VII double-chain form and factor VII-phospholipid complex, in relation to triglyceridaemia. The data showed a highly significant correlation of factor VII mass, factor VII coagulant activity and factor VII-phospholipid complex with triglycerides. No correlation was observed between the activated factor VII double-chain form and triglycerides. These data, together with analysis of the linear and orthogonal regression slopes, suggest that increase of plasma factor VII coagulant activity as a function of plasma triglyceride levels is attributable to an increase in both mass and activity of factor VII and that the increase in activity is dependent on an increase of factor VII-phospholipid complex rather than activated factor VII double-chain form. The ratio between the slopes of the regression straight line of factor VII mass and factor VII-phospholipid complex in relation to triglycerides was 2.23 (95% confidence limits 1.74-2.50), thus indicating that the contribution of factor VII mass is prevalent over that of the factor VII-phospholipid complex.

Adult↗

Hyperthermic antiblastic perfusion for the treatment of soft tissue limb sarcoma.

Eighty patients with locally advanced, high grade soft tissue sarcoma of the extremities were studied prospectively in order to determine the efficacy of hyperthermic antiblastic perfusion (H.A.P.) as the first step of a combined multimodality therapy. All of the patients have been evaluated in terms of functional results, loco-regional control and survival according to the different treatment schedules adopted. The first clinical trial employed H.A.P., followed by surgery alone. Because the results obtained were unsatisfactory, the protocol was modified to include a continuous intra-arterial (i.a.) infusion of doxorubicin (dx) or radiotherapy before surgery. The best results have been obtained with the radiotherapy-including protocol showing a conservative surgery rate of 100% and a 94% rate of loco-regional control. The disease-free, distant disease-free and overall survival rates were 68%, 75% and 70%, respectively. The importance of the treatment protocol has been confirmed in a multivariate analysis which demonstrated that the treatment protocol adopted is one of the prognostic factors with an independent value (p = 0.06).

Chemotherapy, Cancer, Regional Perfusion↗

Prognostic variables in recurrent limb melanoma treated with hyperthermic antiblastic perfusion.

Between October 1969 and December 1986, 136 patients with recurrent limb melanoma were treated with hyperthermic antiblastic perfusion (HAP). This retrospective analysis is aimed at identifying tumor-related and treatment-related variables likely to influence tumor response, locoregional control, disease-free survival, and overall survival. Independent factors predicting a complete response (CR) were the number of lesions (P less than 0.0001) and the minimum tumor temperature (minT) (P = 0.03). Only a positive trend was observed for the drug dose (P = 0.08). However, the proportion of CR was significantly higher (57.7%; P = 0.02) in patients who had a minT of 41.5 degrees C or greater and who were given a dose equal to or greater than the standard dose than in patients treated with lower temperatures and/or lower drug doses. The occurrence of a CR significantly increased the rates of locoregional control (77%; P = 0.007), disease-free survival (55.6%; P = 0.006), and overall survival (68.6%; P = 0.03). Treatment optimization may provide further therapeutic improvements by increasing the incidence of CR. However, the overall survival rates also were influenced by the number of lesions (P = 0.0014), sex (P = 0.04), and the number of previous relapses (P = 0.01). Therefore, tumor aggressiveness also is crucial in determining the outcome of the disease, and only early treatment with HAP can reduce the risk of distant metastases.

Adult↗

Role of hyperthermic perfusion in the treatment of limb osteogenic sarcoma.

The role of hyperthermic perfusion (HP) for the treatment of limb osteogenic sarcoma was evaluated in 76 patients. Twelve patients were treated with HP alone, and a 5- and 10-year survival rate of 25.5% was obtained. When amputation was systematically associated to HP (12 patients), a 5- and 10-year survival rate of 50.9% was achieved. Twenty-seven patients were treated with hyperthermic antiblastic perfusion (HAP) followed by amputation 4 weeks later. With this treatment, the 5- and 10-year actuarial rates rose to 71.4 and 65%, respectively, with a 5-year disease-free survival rate of 67.4%. Fifteen patients were treated with HAP followed by an 'en bloc' resection and bone reconstruction. The 5- and 10-year actuarial survival rate obtained was 63.5% with a 5-year disease-free survival rate of 53.6%. These results seem to indicate that HAP permits carrying out conservative rather than ablative surgery for the treatment of limb osteogenic sarcoma.

Actuarial Analysis↗

Lonidamine and hyperthermia: clinical experience in melanoma. Preliminary results.

Lonidamine alone or in combination with hyperthermic perfusion, with or without melphalan, was investigated in 12 patients with stage II, III, and IV malignant melanoma. The authors evaluated the most effective methods and sequence of Lonidamine administration. Preliminary results suggest that the highest effectiveness is obtained with the simultaneous administration of Lonidamine and hyperthermia.

Administration, Oral↗