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Biomedical subjects

A Cardillo

Publications and source records attributed to A Cardillo.

At least 19 recordsLinked to original sources

Role of endocrine responsiveness and adjuvant therapy in very young women (below 35 years) with operable breast cancer and node negative disease.

BACKGROUND: There is limited knowledge about prognosis, and treatment effects in young women with node-negative disease. PATIENTS AND METHODS: We evaluated biological features, treatment recommendations and prognosis for 841 premenopausal patients with pT1-3, pN0 and M0, operated from 1997 to 2001. RESULTS: Patients below 35 years (101, 12%) were more likely to have tumors > 2 cm (35.6% versus 24.2%, P = 0.002), grade 3 (48.5% versus 31.9%, P = 0.009) and with elevated Ki-67 expression (62.4% versus 50.7%, P = 0.002). At the multivariate analysis a statistically significant difference in disease-free survival (DFS, HR 4.44; 95% CI 2.53 to 7.78, P < 0.0001), risk of distant metastases (DDFS) (HR 3.23; 95% CI 1.32 to 7.94, P = 0.011) and overall survival (OS) (HR 2.89; 95% CI 1.06 to 7.87, P = 0.038) was observed for younger versus older patients and in the subgroup with endocrine responsive tumors (DFS, HR 5.17, 95% CI 2.72-9.83, P = < 0.0001; DDFS, 3.76, 95% CI 1.33-10.6, P = 0.013; OS, 4.71, 95% CI 1.09-20.4, P = 0.039 ). CONCLUSIONS: Compared with less young, very young patients with endocrine responsive and node-negative breast cancer have a worse prognosis. Tailored treatments should be explored in this cohort of patients.

Adult↗

Transplant surgeon formation: vocation, incentives, between old and new surgeon generations.

The training of the transplant surgeon is one of the most difficult paths in medicine. The transplant surgeon must be trained as a general and a vascular surgeon; he has to be skilled and upgraded in transplant surgical technique; he has to decide the suitability of the donor and of the organs as well as the immunosuppressive therapy for each recipient; he must know the intensive care unit, hepatology, and nephrology. The transplant surgeon has to deal with surgical, infectious, and metabolic complications after organ transplantation. Thus, clinical formation of the transplant surgeon is multifactorial and always upgraded. However, transplants never happen in the morning; retrivals are more likely to be in the night (especially the holidays ones). "Weekend" is a word not frequently used by transplant surgeons. Moreover, when the transplant procedure happens, the normal activity of the ward and of the outpatient clinic were have to be done. The transplant surgeon must have a sort of "vocation" for such a job. Organ harvesting setting is a good proof of adaptability, always during nighttime, often in small hospitals with operating room nurses unfamiliar with the procedure, sometimes waiting for some colleagues or delaying the surgery. This vocation is enhanced by enthusiasm, but incentives are necessary to feed this love. Incentives should be professional and economic; transplant surgeons should be allowed to make clinical decisions, to choose the surgical technique of transplantation, to control the decision process. Lastly, due to the "total on call," the surgeon should profit from a right salary avoiding extramural activities.

Adult↗

Breast cancer vaccines: a clinical reality or fairy tale?

The characterization of tumor antigens recognized by immune effector cells has opened the perspective of developing therapeutic vaccines in the field of breast cancer. The potential advantages of the vaccines are: (i) the induction of a robust immune response against tumors that are spontaneously weekly immunogenic; (ii) the tumor specificity for some antigens; (iii) the good tolerance and safety profile and (iv) the long-term immune memory, critical to prevent efficiently tumor recurrence. Most trials evaluating breast cancer vaccines have been carried out in patients with extended metastatic breast cancer, characterized by aggressive tumors, resistant to standard cytotoxic treatments, so that clinical efficacy was difficult to achieve. However, some significant immune responses against tumor antigens induced upon vaccinations were recorded. The aim of this review is to analyze the activity of vaccination strategies in current clinical trials. Data of clinical activity have been observed by using vaccines targeting HER2/neu protein, human telomerase reverse transcriptase, carcinoembryonic antigen and carbohydrate antigen given after stem cell rescue. The review discusses possible future directions for vaccine development and applications in the adjuvant setting.

Antigens, Neoplasm↗

A novel method for monitoring response to chemotherapy based on the detection of circulating cancer cells: a case report.

We describe a novel method for detecting micrometastasis in the blood stream of cancer patients based on RT-PCR amplification of tumor-associated carcinoembryonic antigen (CEA) mRNA. To increase sensitivity and specificity of RT-PCR, CEA transcript was selectively up-regulated in cancer cells by exposure of peripheral blood to non-toxic concentrations of staurosporine (ST). Thereafter, polyA(+) RNA was extracted from tumor cells captured by means of magnetic beads coated with a monoclonal antibody against a common human epithelial antigen. Finally, RNA was subjected to RT-PCR analysis of CEA transcript. Using this approach, we demonstrated an ST-mediated increase in CEA transcript in blood specimens collected from a patient with metastatic colon cancer before receiving treatment with 5-fluorouracil/leucovorin. After a few cycles of chemotherapy, CEA-positive tumor cells were no longer detected. Clinical follow-up of this patient indicated that treatment with chemotherapy induced a dramatic reduction in liver metastasis. Therefore, it can be hypothesized that lack of CEA transcript detection might be consistent with disappearance or at least marked reduction of circulating tumor cells.

Adenocarcinoma↗

Drug-induced modulation of carcinoembryonic antigen (CEA) expression in neoplastic cells from a patient with rectal cancer.

Treatment with 5-fluorouracil (5-FU) or recombinant interferon-gamma (IFN), alone or in combination, was found to increase carcinoembryonic antigen (CEA) expression in several carcinoma cell lines. In this study we examined the in vitro effect of these agents on CEA expression of tumor cells, obtained from a patient operated for rectal cancer. The results showed that exposure of cancer cells to 5-FU or to IFN resulted in increased CEA levels in terms of percentage of CEA-positive cells and mean fluorescence values, as indicated by FACS analysis. However, drug combination did not induce CEA expression higher than that provided by single agents alone. Treatment with 5-FU or with IFN produced a reduction of the total number of viable cells. Moreover, Western blot analysis revealed that exposure of cancer cells to each drug was followed by a substantial increase of the total cellular CEA content. On the contrary, 5-FU in combination with IFN did not increase the expression of the antigen more than that obtained by single agents. Noteworthy, exposure of CEA-negative cells from adjacent normal rectal tissue to both agents alone or in combination, did not result in CEA induction. In conclusion, the present results suggest new approaches aimed at (a) increasing the sensitivity of diagnostic procedures based on detection of CEA-positive tumor cells; (b) facilitating the recognition of CEA-positive cancer cells by immune responses induced by anti-CEA peptide vaccines.

Adult↗

Sequential molecular monitoring of chimerism in chronic myeloid leukemia patients receiving donor lymphocyte transfusion for relapse after bone marrow transplantation.

Recent observations of chimerism in patients relapsed following an allotransplant suggest the persistence of immunotolerance, thus offering a biologic rationale for the use of donor lymphocyte transfusion (DLT). In this study, we have analyzed by PCR amplification of several VNTR regions, sequential bone marrow and peripheral blood DNA samples in four patients who received DLT for CML relapse after bone marrow transplantation. Prior to DLT, all patients showed mixed chimerism in peripheral blood cells while two had mixed chimerism and two no chimerism in the BM. None of these four patients showed evidence of chimerism at the cytogenetic level (all had 100% +ve metaphases). After DLT, a complete hematologic and molecular remission (ie disappearance of the BCR/ABL fusion transcript) was obtained in the two patients who had bone marrow mixed chimerism prior to DLT. The two patients without evidence of marrow chimerism prior to DLT converted to a pattern of mixed chimerism after DLT, but both developed a severe bone marrow aplasia occurring at day 56 and 36, respectively. With regard to the sequential analysis of bone marrow chimerism after DLT we observed that: (1) the disappearance of BCR/ABL +ve cells paralleled the conversion to a pattern of full donor chimerism; and (2) the time interval to achieve CR was inversely correlated with the percentage of donor DNA in bone marrow. In conclusion, we have shown here that the assessment of bone marrow pre-DLT chimerism by PCR analysis might predict the response in patients with favorable characteristics, and also might identify patients at high risk of developing severe myelosuppression.

Adult↗

Radiotracer binding to brain microsomes determined by thin-layer chromatography.

A thin-layer chromatography (TLC) assay was developed to monitor the interaction of radiotracers with brain microsomes. Murine brain microsomes were coated onto a zone of a TLC strip, the unreacted sites blocked with gelatin, and the radiotracers chromatographed over the microsomes. Radiotracers bound to the microsomes and were separated from the unreacted materials which migrated at or near the solvent front. Up to 80% of the applied radioactivity bound to the brain microsomes when using 99mTc-(d,l) hexamethyl-propyleneamine oxime (HMPAO) and 123I-(S)-2-hydroxy-3-iodo-6-methoxy-N-[(1-ethyl-2-pyrrolidinyl) methyl]-benzamide (123I-IBZM) as tracers. On the other hand, the presumptive negative control materials p-I-15-phenyl-pentadecanoic acid-123I (123I-IPPA) and 99mTc-mercapto-acetyl triglycine (MAG3) bound poorly (7% and 4%, respectively). 99mTc-ethyl cysteinate dimer (ECD) interacted poorly (9.9%), a result thought to be consistent with its known inability to be metabolized by nonprimate brain tissue. Radiolabeled octreotide analogues (radiolabeled with 111In, I-131 or 99mTc) also bound, and the binding could be reduced by excess unlabeled octreotide. Also, chemical modification by acylation of Lys5 in 111In-labeled octreotide led to decreased binding (approximately 70%) compared to the original radiotracer. Chromatography of the various radiotracers over TLC strips coated only with gelatin was used to monitor nonspecific binding and was low and frequently below 5%. This technique does not require wash steps or centrifugation, and assays are rapidly completed. The assay could be useful in monitoring the interaction of radiotracers with brain microsomes and in evaluating and developing new radiotracers.

Animals↗

The role of tissue colonization and bacterial resistance in recurrent tonsillitis.

Unsuccessful medical therapy for treatment of acute tonsillitis frequently results in onset of recurrent or chronic forms rendering surgical treatment necessary. We have studied some of the factors involved in the evolution of these chronic or recurrent forms and, in particular, the distribution of different bacterial strains in tonsillar tissue, their response to treatment with antibiotics and mechanisms of bacterial resistance. The distribution of bacterial flora (saprophytic and pathogenic) present on the surface of the tonsils, in the crypts and in the tonsillar tissue was studied in a control population of 30 children (20 boys and 10 girls) aged between 2-13 years, all affected with chronic tonsillitis and submitted to tonsillectomy. The same study was performed in a group of 80 sex and aged matched children, also presenting with chronic or recurrent tonsillitis and treated with amoxicillin or amoxicillin-clavulanic acid or cefaclor or clarithromycin 72 h before surgery. The 80 subjects were randomly divided into four groups so that each antibiotic was tested on 20 subjects. The distribution of the bacterial population on the surface of tonsillar tissue, in the crypts and in the deeper tonsillar tissue is of particular interest concerning the affinity of bacteria to the different tissue areas. In particular the interaction between crypt and tonsillar core, which could be a factor involved in the process of worsening of bacterial infection in the tonsils, is evidenced. The four antibodies tested showed different abilities to eradicate infection: Haemophilus influenzae was found to be the most resistant germ to antibiotic therapy and was thus the most frequent cause of recurrent infections. The characteristics and the mechanisms of adherence and resistance to beta lactam antibiotics were also analysed.

Adolescent↗

[Spontaneous grade I bundle of His block. Clinical, electrocardiographic and electrophysiological studies in 37 patients].

The clinical, ECG and electrophysiological data of 37 patients (28 males and 9 females) with spontaneous intra-hisian block are reported. Of these patients, 11 had hypertensive heart disease and 5 had ischemic heart disease with previous myocardial infarction; in 21 patients, clinical signs of heart disease were not evident. In 18 patients, a single or recurrent episode of syncope had occurred. One patient had junctional rhythm and 36 sinus rhythm; among these, 12 patients presented PR greater than 200 msec (7 with a narrow and 5 with a wide QRS); 12 patients had a single or bilateral bundle branch block; 12 had a normal ECG. The electrophysiological study showed a split H-H1 in 22 patients, a wide His deflection (H greater than 25 msec) in 4 and HV greater than 65 msec with narrow QRS in 11. In 17 patients a more or less marked sinoatrial node and/or atrioventricular node dysfunction was present. Atrial pacing, performed in all, induced 2nd degree Mobitz 2 intra-hisian block in 9 patients. Ajmaline was used in 16 patients but induced a complete intra-hisian block in only one. In 28 patients a preventive pacemaker was implanted after electrophysiological study. During the follow-up (mean 25 months/pt.), 38% of the patients developed complete atrioventricular block. No recurrence of syncope occurred in the paced patients. Comparison of patients who developed atrioventricular block and those who maintained normal atrioventricular conduction did not show differences as far as heart disease, previous syncope, ECG pattern and results were concerned.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Membrane proteins in human skin tumors.

The microsomal, mitochondrial, and nuclear fractions of cutaneous tumors have been investigated. Cutaneous tumors were homogenized and microsomal, mitochondrial, and nuclear fractions were purified. The membrane proteins were solubilized with sodium duodecyl sulfate (SDS). The membrane lipids were removed and membrane proteins were solubilized again in a small volume of SDS solution and chromatographed in SDS-acrylamide slab-gel. The plates were stained with Coomassie Brilliant Blue to show protein bands. The preliminary results show that the electrophoretic profiles of microsomal proteins are characteristic of some tumors.

Carcinoma↗