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Biomedical subjects

F Guadagni

Publications and source records attributed to F Guadagni.

At least 73 records · Page 4Linked to original sources
PubMedDate not supplied

Effects of isolated limb perfusion with tumor necrosis factor-alpha on circulating levels of proinflammatory cytokines.

Hyperthermic isolated limb perfusion (ILP) with tumor necrosis factor-a (TNFalpha) and cytotoxic drugs is currently used for treatment of melanoma and sarcoma of the limbs. Tumor necrosis factor-alpha is involved in the systemic inflammatory response syndrome as a result of activation of inflammatory cells and production of bioactive substances. The goal of this study was to determine the circulating levels of proinflammatory cytokines and soluble adhesion molecules in 19 patients with limb melanoma or sarcoma undergoing ILP with (n = 9) or without TNFalpha (n = 10). The results obtained demonstrated that ILP with TNFalpha was responsible for a leakage of TNFalpha in the systemic circulation, followed by a rise in interleukin (IL)-6 and IL-8 levels within I h. Elevated soluble (s)P-selectin levels were found 1-3 h after ILP. Plasma sE-selectin peaked 6-9 h after ILP, and soluble vascular cell adhesion molecule (sVCAM) levels reached a maximum after 24 h. Significant correlations were observed among these variables, confirming the interdependence of all changes observed. On the other hand, ILP with cytotoxic drugs alone induced only a modest release of TNFalpha, which was not followed by an immediate rise in IL-6 and IL-8. Four of the 9 patients undergoing ILP with TNF had severe systemic toxicity. No association was found between systemic TNF levels and the clinical outcome, whereas elevated TNF perfusion levels as well as systemic IL-6 and IL-8 levels were constantly elevated in patients with severe toxicity. These results are suggestive of an important role of TNFalpha levels in the perfusion system (more than leakage of perfusate) in causing postoperative toxicity, although other ILP-related factors should not be excluded.

Adult↗
PubMedDate not supplied

Minimal sentinel node procedure for staging early breast cancer.

AIMS AND BACKGROUND: Sentinel lymph node dissection (SLND) has recently been evaluated as a new staging technique for early breast cancer. To minimize the extent of surgery, the feasibility of eradicating primary breast lesions and the relative sentinel lymph nodes (SLN) under regional anesthesia was evaluated in this study. METHODS AND STUDY DESIGN: A selected population of 76 patients with suspected operable breast cancer and no clinically palpable lymph nodes was enrolled in the study. Intra- and perilesional administration of a radiotracer was performed. Lymphoscintigraphy was carried out to confirm the drainage pathway and locate the SLN. The following day, after inducing a nervous block induction of the ipsilateral intercostal nerves, we performed the surgical procedure with the help of a hand-held gamma-detecting probe. In case the primary lesion was diagnosed as invasive carcinoma by frozen section, the SLN and the remaining axillary lymph nodes (non-SLNs) were removed. The status of SLN and non-SLNs was compared. RESULTS: The primary breast lesion was located and excised in all cases (identification rate: 100%). Lymphoscintigraphy positively identified SLNs in 40/45 (89%) patients; in five patients no lymphatic drainage was detected. In 38 cases an average of 1.5 SLNs and 14 non-SLNs per patient were removed and pathologically analyzed; the remaining two patients showed SLNs in the internal mammary chain, which were not excised. Twenty-nine percent of the patients showed metastatic disease in the lymph nodes examined. Of all patients with affected nodes, 55% had cancer cells only in the SLN. No false negatives (skip metastases) were found. No immediate or long-term anesthesia-related complications (e.g., pleural lesions, intravascular injection) were observed. CONCLUSIONS: Our data confirm the feasibility of single radiotracer administration for both occult lesion and SLN localization as well as the usefulness of SLND in staging early breast cancer. Regional anesthesia resulted in easy management and good patient compliance. This time-saving procedure allowed the completion of the whole surgical plan, reducing the recovery time without modifying the effectiveness of surgery.

Adult↗
PubMedDate not supplied

Sentinel lymphadenectomy in cutaneous melanoma.

AIMS AND BACKGROUND: In the last ten years validation of the sentinel lymph node (SLN) concept has led to modification of the surgical approach for patients with intermediate-risk cutaneous melanoma. METHODS AND STUDY DESIGN: Forty-eight patients affected by cutaneous melanoma with a Breslow thickness between 0.65 and 4 mm were enrolled in the study. Approximately 2 mCi of radiotracer and 1 mL of vital blue dye were injected in each patient around the site of the primary lesion. Lymphoscintigraphy was performed until the lymphatic basin and the respective SLN were localized. The whole surgical procedure consisted of enlargement of the surgical margins followed by localization and excision of the SLN(s) by using both radiotracer and vital dye. Whenever the SLN proved to be histologically positive for metastasis, complete regional lymphadenectomy was performed. RESULTS: Within 15 minutes of radiotracer administration the lymphatic basin was localized in all 4 patients by lymphoscintigraphy. Vital dye and radiotracer successfully allowed SLN localization and excision in 46 of 48 patients (97%); in one case the SLN was detected by radiotracer alone. The SLN proved to be metastatic in six (13%) of 46 evaluable patients; interestingly, in three of them the presence of metastatic cells was revealed only by immunohistochemistry. All patients with tumor-positive SLNs had primary lesions with a Breslow thickness = 2 mm. CONCLUSIONS: Sentinel lymphadenectomy is able to identify lymph node involvement in patients with cutaneous melanoma with a Breslow thickness > 1 mm, thus avoiding the risks associated with radical regional lymphadenectomy. Lymphoscintigraphy proved to be an important tool to obtain correct preoperative localization of the drainage basin, especially for melanomas located on the face and trunk.

Adolescent↗
PubMedDate not supplied

Prognostic value of serum and tumor tissue CA 72-4 content in gastric cancer.

To date no general agreement has been reached regarding the prognostic significance of CEA, CA 19-9 and CA 72-4 as serum markers in gastric cancer, and only scattered information is available on the predictive value of marker expression in tumor tissue. Therefore, a longitudinal study was designed to analyze the presurgical serum and tumor tissue content of CA 72-4, CEA and CA 19-9 in 166 patients at different stages of gastric cancer, and to evaluate the possible correlation with clinicopathological features in respect to prognostic information on relapse-free survival. The results obtained showed that 48.4% of patients with tumor recurrence had positive presurgical CA 72-4 levels compared to approximately 24% of patients who remained free of disease. Furthermore, the median presurgical serum CA 72-4 levels were significantly elevated in relapsing patients. Serosa and lymph node involvement as well as positive presurgical serum CA 72-4 levels had independent prognostic value in predicting recurrence. A significant association between disease-free survival and lymph node involvement, depth of invasion and tumor tissue content of CA 72-4 was also demonstrated. We may therefore conclude that CA 72-4 antigen can be considered the marker of choice in the follow-up of gastric cancer patients and may be used as a prognostic indicator of relapse.

Adult↗
PubMedDate not supplied

Soluble selectin levels in patients with lung cancer.

Increased expression of selectins has been found on endothelial cells of venules and capillaries in the tumor stroma of non-small cell lung cancer, suggesting their functional role in the process of chemotaxis for tumor cells. The present study was aimed at analyzing the role of both soluble (s)P-selectin and sE-selectin levels in association with clinico-pathological variables in 116 patients with lung cancer, 38 patients with benign diseases and 59 healthy donors. The results obtained showed that sP-selectin and sE-selectin levels were higher in patients with lung cancer compared to normal donors (p<0.02 and p<0.005, respectively). No differences were observed among patients with various benign diseases for both selectins. Increased levels of sP-selectin and sE-selectin were significantly associated with squamous lung cancer at late stages (p<0.05), but not adenocarcinoma. Both sP- and sE-selectin were independently related to the stage of squamous lung cancer by stepwise regression analysis (p<0.02 and p<0.03, respectively), while only sE-selectin was independently related to the presence of distant metastasis in the same histotype (p<0.02). These results suggest that measurement of plasma soluble selectins might represent a useful laboratory parameter in the management of patients with squamous lung cancer.

Adenocarcinoma↗
PubMedDate not supplied

Evaluation of the CA 242 tumor antigen as a potential serum marker for colorectal cancer.

OBJECTIVE: The present study was designed to define the performance of serum CA 242 as a marker in colorectal cancer patients. PATIENTS AND METHODS: Serum samples from 1,013 subjects (440 healthy volunteers, 384 patients with primary or recurrent colorectal carcinoma and 189 with benign colorectal diseases) were evaluated. RESULTS: The measurement of serum CA 242 levels in the population of healthy subjects demonstrated the presence of positive levels in approximately 5% of the cases. Interestingly, similar results (5.8%) were obtained in patients with benign colorectal disease, demonstrating the high specificity of CA 242. When serum samples from colorectal cancer patients were analyzed, a sensitivity of 34.9% was observed. Moreover, 18.6% Stage A and B patients had positive CA 242 levels, compared to 33.3% and 58.8% of Stage C and D patients, respectively, indicating a correlation with the stage of disease. A comparison between preoperative and immediate postoperative CA 242 levels showed a consistent relationship between the efficacy of surgery and the reduction in serum CA 242 levels; further, elevated CA 242 levels were present in the immediate postsurgical follow-up of patients undergoing palliative surgery. A longitudinal evaluation of serum CA 242 levels demonstrated that this marker was indicative of the status of disease. CONCLUSIONS: The results obtained suggest the possible utility of CA 242 in monitoring the disease status, providing a rationale for future studies focusing on the longitudinal monitoring of colorectal cancer patients.

Adenocarcinoma↗
PubMedDate not supplied

CA 19-9 monosialoganglioside content of human colorectal tumor cells correlates with tumor cell-induced platelet aggregation.

BACKGROUND: Gangliosides are involved in tumor cell-induced platelet aggregation (TCIPA). CA 19-9 is a monosialoganglioside detected in colon carcinoma cells. Therefore, this study was designed to evaluate whether there was any correlation between the CA 19-9 monosialoganglioside content and TCIPA. MATERIALS AND METHODS: The CA 19-9 content was determined on gangliosidic extracts of human colorectal tumor cells (GEO, WiDr, DLD-1, MIP) in comparison with the degree of TCIPA. RESULTS: CA 19-9 was detected in all cell lines, except MIP. The mean CA 19-9 content was 10.2, 30.2 and 82.6 U/microgram of sialic acid for GEO, DLD-1 and WiDr, respectively. CA 19-9 content directly correlated with TCIPA (p < 0.0001). Furthermore, incorporation of exogenous gangliosides in GEO cells resulted in an increase of CA 19-9 content, paralleled by a concomitant increase of TCIPA. CONCLUSIONS: The CA 19-9 monosialoganglioside may be involved in platelet/tumor cell interactions, thus playing an important role in the haematogenous metastases of colorectal cancer.

CA-19-9 Antigen↗
PubMedDate not supplied

Effect of 5-fluorouracil on carcinoembryonic antigen expression and shedding at clonal level in colon cancer cells.

BACKGROUND: The carcinoembryonic antigen (CEA) is a tumor marker largely utilized for the detection of minimal disease or as a target of immunotherapeutic approaches. In preclinical models CEA has been found to be up-regulated after exposure of cancer cells to 5-fluorouracil (5-FU). In the present study, the clonal distribution of CEA and its regulation by 5-FU at clonal level was investigated using human HT-29 colon cancer cells. MATERIALS AND METHODS: The extent of CEA expression was measured in terms of: (a) antigen levels on plasma membrane, by flow cytometry; (b) cytoplasm and membrane protein, by Western blot analysis: (c) transcript, by Northern blot analysis; (d) CEA shedding by radioimmunossay. RESULTS: CEA protein and gene transcript were variably expressed among different clones. In all cases 5-FU was able to increase the percentage of CEA-positive cells, the amount of antigen, either in the membrane or cytosolic fractions, and the corresponding transcript. Moreover, a marked increase of CEA shedding was found in drug-treated cells with respect to that of controls. The increase of CEA induced by the antimetabolite was not the result of a selection mechanism based on preferential killing of CEA negative cells. The antimetabolite was capable of enhancing antigen expression also in other CEA-positive tumor cell lines with different basal levels of the marker. CONCLUSIONS: The present findings could be of potential value to increase the sensitivity of diagnostic procedures based on detection of CEA positive tumor cells. Moreover, the antimetabolite might be included in immunotherapeutic protocols to facilitate recognition of CEA-positive cancer cells by immune responses.

Antimetabolites, Antineoplastic↗
PubMedDate not supplied

Comparative analysis of CA 242 and CA 19-9 serum tumor markers in colorectal cancer patients. A longitudinal evaluation.

OBJECTIVE: Following the encouraging results obtained on CA 242 as an adjunctive marker for colorectal cancer this study was designed to compare the clinical behavior of CA 242 to that of its related marker CA 19-9. PATIENTS AND METHODS: Sera from 630 patients with benign (n = 201) or malignant (n = 429) colorectal diseases were evaluated. Moreover, 50 patients with colorectal cancer were longitudinally monitored during. post-surgical follow-up for either a minimum of 5 years or until time of recurrence. Serum CEA, CA 19-9 and CA 242 levels were determined before treatment and at each scheduled follow-up. RESULTS: The distribution of CA 242 levels in colorectal cancer patients demonstrated a similar positivity rate (32.9%) compared to that of CA 19-9 (29.8%), although both sensitivities were lower than that of CEA (43.8%). Moreover, elevated CA 242 serum levels were found in metastatic disease (58.2%). A longitudinal evaluation demonstrated that serum CEA, CA 19-9 and CA 242 levels were elevated in 63.9%, 63.9% and 66.7% of recurrences. Combined evaluation of CEA, CA 19-9 and CA 242 serum levels in the overall population demonstrated a complementarity of CEA with the latter two markers. Conversely, a highly significant correlation was observed, suggesting that the two assays might recognize the same macromolecular complex. CONCLUSION: CA 242 determination does not seem to offer a particular advantage over CA 19-9, while CEA remains the marker of choice in monitoring colorectal cancer patients.

Adult↗
PubMedDate not supplied

Radioguided-surgery of early breast lesions.

BACKGROUND: Radioguided-surgery has been recently proposed in patients with clinically occult breast lesions. This study aimed to evaluate the feasibility of correctly locating and eradicating, by a single intralesional injection of a radiotracer, any breast lesion and, in the case of malignancy, to perform simultaneous sentinel lymph node (SLN) biopsy procedure. PATIENTS AND METHODS: Sixty-three women with early breast lesions were enrolled: 42 were invasive carcinomas, 16 in situ ductal carcinomas (DCIS) and 5 fibroadenomas. RESULTS: Scintigraphic images clearly identified the lesions in all patients while SLN/s were evident in 88% of them. At surgery all the breast lesions were easily radiolocalized and eradicated with minimum surgical trauma and, for those patients with invasive carcinomas, the SLN technique was performed in 86% of them. No skip metastases were found. CONCLUSION: A single intralesional administration of radiotracer is an easy and reliable procedure to simultaneously locate and remove both the non-palpable breast lesion and the SLN when primary malignancy was intraoperatively confirmed.

Adult↗
PubMedDate not supplied

Biological effects of a software-controlled voltage pulse generator (PhyBack PBK-2C) on the release of vascular endothelial growth factor (VEGF).

BACKGROUND: Electrical stimulation (ES) may induce vascular permeability and physiological angiogenesis. ES of rat muscles significantly increases the microvessel density and vascular endothelial growth factor (VEGF) protein levels. Thus, a pilot study was designed to analyze the effects of low-voltage electric impulses on VEGF levels in patients with dystrophic ulcers. MATERIALS AND METHODS: Circulating VEGF levels were analyzed in 9 patients undergoing an ES session with low voltage software-controlled impulses applied through topical transducers (1-9 micros width, 1-420-Hz frequency and 30-120 V strength-100 microA max). RESULTS: The session was accompanied by a peak of circulating VEGF (3-10 min from start) in all 9 patients, which was preceded by a rise of TNF-alpha (2-min) and was independently associated with soluble E-selectin levels. Nitric oxide generation was significantly improved on the day after treatment. No hemostatic activation or sustained inflammatory reaction were observed. CONCLUSION: ES may represent a safe method for augmenting VEGF-mediated vascular protection, either directly or by induction of NO.

Aged↗
PubMedDate not supplied

Clinical evaluation of the new tumor marker TAG-72.

Tumor-associated glycoprotein-72 (TAG-72) is a high molecular weight glycoprotein found in the sera of patients diagnosed with gastrointestinal and other malignancies. TAG-72 was detected in the serum of a significant percentage of patients whose CEA levels were negative which underscores the possibility of exploiting the complementarity of the two tumor markers in the diagnosis of gastrointestinal (G.I.) carcinoma. Moreover, the measurement of TAG-72 may also be clinically useful in discriminating malignant from benign effusions. Serum TAG-72 and CEA levels were evaluated longitudinally in a series of patients following resection of primary G.I. carcinomas. A consistent relationship between efficacy of the surgery and serum TAG-72 clearance was observed, and TAG-72 alone or in combination with CEA accurately predicted recurrence of malignant disease in greater than 90% of the patients. The results indicate that TAG-72 is a new human serum tumor marker which, measured alone or in combination with other well established markers, may improve the diagnosis and/or clinical management of malignant disease.

Adenocarcinoma↗
PubMedDate not supplied

Maintenance of expression of tumor antigens in three-dimensional in vitro human tumor gel-supported histoculture.

Tumor-specific antigens are important in the study of tumor biology, tumor diagnosis and prognosis and possibly in tumor therapy. We demonstrate in this report that surgical specimens of colon, breast and ovarian tumors in native-state in vitro gel-supported three-dimensional in vitro histoculture maintain in vivo-like expression of the important tumor antigens TAG-72 and CEA. These results are in contrast to previously-reported studies indicating lack of expression of TAG-72 in monolayer cultures. Our knowledge and utilization of tumor-specific antigens, including the potential for therapy and predicting individual sensitivities could be enhanced in studies using in vitro three-dimensional gel-matrix histoculture for human tumors.

Antibodies, Monoclonal↗
PubMedDate not supplied

Correlation between positive CA 72-4 serum levels and lymph node involvement in patients with gastric carcinoma.

CA 72-4 serum marker has been shown to be one of the most specific and sensitive markers for monitoring gastric cancer. In the present study we evaluated the correlation between CA 72-4, CA 19-9 and CEA serum levels, and tumor size and lymph node involvement in gastric carcinoma patients. One-hundred sixty-one patients with primary or recurrent gastric carcinoma were studied. Elevated CA 72-4, CA 19-9, and CEA serum levels were found in 42.2%, 32.3% and 24.2%, respectively. As previously shown, the combination of CA 72-4 and CA 19-9 increased positive samples to 56.5%, while the addition of CEA did not further improve this percentage. Unlike what has been previously published, none of the markers showed a significant correlation with serosal involvement. In fact, elevated serum levels were observed for the three markers in a very low percentage of cases either in T1-T2N0 or T3-T4N0 patients. In contrast, CA 72-4 showed a highly significant correlation with lymph node involvement: T1-T4N0 patients had positive CA 72-4 levels in 5 out of 37 (13.5%), while T1-T4N1 in 12 out of 32 (37.5%), and T1-T4N2 in 20 out of 40 (50%) (p < 0.003). CA 19-9 and CEA serum levels were not significantly correlated. Since the presence of lymph node metastases is considered a negative prognostic factor, these results suggest that the measurement of CA 72-4 serum levels may be an important parameter in the diagnosis and clinical follow-up of patients with gastric carcinoma.

Adult↗
PubMedDate not supplied

Biological response modifiers as adjuvants in monoclonal antibody-based treatment (review).

Compelling experimental evidence suggest that the use of differentiation-inducing agents which enhance tumor antigen expression may play a pivatal role in MAb-based approaches to tumor diagnosis and/or therapy. In particular, interferons can up-regulate CEA and TAG-72 expression on the surface of human carcinoma cells which leads to an enhanced MAb tumor localization. The ability to target additional MAb to the tumor site has subsequently been shown to augment radioimmunodetection and therapy in experimental models. Initial clinical studies reported that interferon administration to patients diagnosed with malignant melanoma improved the tumor distribution of antimelanoma MAb without an accompanying increase of antibody in normal tissues. The findings from our phase 1A trial clearly showed that intracavitary IFN-gamma administration augmented TAG-72 and CEA expression on carcinoma cells isolated from malignant ascites from patients diagnosed with ovarian or gastrointestinal cancer. Future efforts need to further investigate the molecular mechanisms involved in the regulation of these and other human tumor antigens by the interferons as well as other differentiation-inducing agents. Additional clinical studies should evaluate the overall effectiveness of combining an antigen up-regulation protocol with a conjugated MAb in the hope of improving tumor diagnosis and therapy.

Adjuvants, Immunologic↗
PubMedDate not supplied

Clinical value of radiolabeled monoclonal antibodies in the management of carcinoma patients.

A significant number of monoclonal antibodies, suitable for in vivo management of carcinoma patients, have been recently developed and evaluated in clinical trials. They can be used successfully either for imaging or for radioimmunotherapy, although their clinical application shows advantages and limitations. With the advent of genetic engineering, it has become feasible to design molecules (i.e. chimeric and humanized antibodies, single-chain) to circumvent drawbacks or enhance a certain property. Several radionuclides can actually be used to be linked to monoclonal antibodies, including radiometallic isotopes which need bifunctional chelators. Coupling these radiometals to proteins will greatly increase diagnostic and therapeutic possibilities. The ability of radiolabeled monoclonal antibodies to localize tumors, markedly contributed to the development of a new intraoperative approach termed "Radioimmunoguided Surgery". This system, being used to better define tumor margin resection as well as occult tumor sites, is of importance in postoperative decision-making. Optimization of this technique is actually under evaluation at our Institution, especially in combination with Biological Response Modifiers.

Adult↗