Granulocytosis-inducing factor from the mouse submaxillary gland.
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Animals↗
Biomedical subjects
L Frati
Publications and source records attributed to L Frati.
Human decay accelerating factor transgenic pigs for xenotransplantation obtained by sperm-mediated gene transfer.
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Animals↗
Disruption of the immunopeptidergic network in dietary migraine.
This investigation is devoted to the study of the time-course of a cytokines panel (IL-4, IL-6, IFN-gamma, GM-CSF) in plasma samples from migraine patients. The data obtained during challenged migraine crises was compared to the baseline values. Time-data series analysis showed a fall after a challenge test for IL-4 and IL-6 plasma levels and an opposite trend for gamma-IFN and GM-CSF levels. The implication of this phenomenon in dietary migraine is not readily evident. There may possibly be an activation of this cytokine network together with the well-known impairment in the neuropeptidergic system, considering the close links between interleukins and other cytokines and the neuro-mediators of pain, such as histamine and 5-HT.
Adult↗
Concurrent chemoimmunotherapy in metastatic clear cell sarcoma: a case report.
Clear cell sarcoma is a rare tumor with a poor prognosis. The therapeutic approach in the metastatic disease stage is controversial: to the authors' knowledge the use of concurrent chemoimmunotherapy has not been previously reported. We present a case of a 57-year-old male with metastatic clear cell sarcoma treated simultaneously with subcutaneous interferon-a 2b and six courses of chemotherapy according to the CyVEDIC regimen. Disease stabilization lasting 17 months was achieved.
Antineoplastic Combined Chemotherapy Protocols↗
Cell kinetics and tumor-associated antigen expression in human mammary carcinomas.
Twenty-six primary breast carcinomas were studied to evaluate cell proliferation as assessed by thymidine labeling index (TLI), and antigenic phenotype, as defined by immunohistochemistry using eight monoclonal antibodies (MAbs) to tumor-associated antigens (TAAs). The majority of tumors had low TLI values. Reactivity to MAbs B72.3, CC49, CC83 (anti TAG 72), COL-12 (anti CEA) and MOv2 (against a tumor-associated mucoprotein) was restricted to less than 50% of the tumors studied, while MAbs B1.1 (anti CEA), MBrl and MBr8 (to tumor-associated carbohydrates) reacted with greater than 50% of the cases. Correlations between expression of TAAs and proliferative activity showed that the tumors could be divided into three groups, two characterized by either high proliferative activity and absence of antigenic expression or low proliferative activity and strong antigenic expression, and the third showing no relation between these two biological features. We defined two antigenic phenotypes associated with specific cellular kinetics: one characterized by negative immunoreaction with MAbs, CC49, CC83 and COL-12 and high proliferative activity; the other characterized by intense immunoreactivity with these antibodies and low proliferative activity. The data suggest that cell proliferation and antigenic phenotype may define biologic subsets of breast carcinomas.
Antibodies, Monoclonal↗
Comparative evaluation of serum markers in prostate disease and in patients with age-related risk.
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Acid Phosphatase↗
Skeletal alkaline phosphatase as a serum marker of bone metastases in the follow-up of patients with breast cancer.
Immunoradiometric determination of the bone isoenzyme of alkaline phosphatase with a method provided by Hybritech Inc., San Diego CA (USA) was carried out in 145 female patients, 97 of whom with radically operated breast cancer and 48 with benign mammary cysts, in order to evaluate the correlation of serum levels with the metabolic process of bone rearrangement in patients with bone metastases. This study shows that skeletal ALP, having high specificity (86.48%) and sensitivity (78.6%) for early progression (the average anticipation time compared to scintigraphic detection was 101 days) could represent a valid marker for bone metastases in association with mucinous markers in the follow-up of patients operated for breast cancer. In addition, dynamic serum determination of skeletal ALP could be a valid help in monitoring the efficacy of therapy in patients with bone progression.
Alkaline Phosphatase↗
Influence of vindesine on the lytic phase of mouse natural cytotoxicity against human leukemic cells.
Vindesine (VDS), a structural analogue of Vinca Alkaloids, was found to increase the NK-mediated cytolytic effects of mouse lymphocytes against human K562 target cells in a 18-hr assay. Pretreatment of effector or target cells with the drug did not affect substantially the NK reaction. The phenomenon has been detected using splenocytes of either congenitally athymic or conventional euthymic mice of different strains. Effector lymphocytes deprived of cells adherent to plastic surface or to nylon-wool column were still competent for drug-mediated increase of NK function. It is suggested that modification of the membrane make-up of effector or target cells reversibly induced by VDS, would promote higher NK-mediated cytolytic effects.
Animals↗
Variable levels of bcl-2, bcl-x and bax mRNA in bladder cancer progression.
We investigated the expression of the anti-apoptotic genes bcl-2 and bcl-X and the pro-apoptotic gene bax in bladder tumors and normal samples from urinary bladder, using RT-PCR analysis. Bcl-2 mRNA was not detected in any of the normal samples, while it was found expressed in 66% of the low stage tumors and in 100% of the high stage tumors. Bax expression had an inverse progress, being present in 62% of the normal tissues examined, in 16% of the low stage tumors and in 14% of the high stage. Bcl-X gene expression was quite variable among all samples (37% in normal tissues, 50% in the low stage tumors and 14% in the high stage). bcl-X mRNA was only found in the isoform bcl-XL, with anti-apoptotic functions, whereas no sample expressed the isoform bcl-XS, which is known to suppress bcl-2 functions. Most samples expressing bcl-2 did not express bcl-X, and vice versa. These results, besides confirming the potential role of these genes in the pathogenesis of low stage bladder cancer strengthen the hypothesis concerning their possible interaction in the progression of disease.
Apoptosis↗
The patentability of living organisms between science, law and ethics.
The approval on May 1998 of the European Union (EU) directive on the legal protection of biotechnological inventions has aligned Europe to the international trend about the patenting of biotechnologies. Many questions are still unresolved, i.e. the differences between the article 53b of the European Patent Convention (EPC), which prohibits patenting of plants and animal varieties, whereas the directive states that Oinvention whose object are plants or animals may be patented if the practicability of the invention is not technically confined to a particular plant or animal varietyO (article 12). Again, the interpretation of plants or animal species specificity and that on the threatening public order and morality (which inhibits patenting) may have doubtful interpretations, according to the different EU States morality and law (e.g. Denmark does not admit patentability of transgenic animals). Despite difficulties, biotechnology Research and Development for applications to medicine, veterinary sciences, agriculture and foods is continuously growing. Bioethical independent evaluations of the applications of biotechnologies and of their side-effects (risk for biodiversity of plants and animals, safety of procedures to save mankind, respect of human dignity and of fundamental human rights, etc.) are mandatory to link the interests of science and industrial productions together with those of mankind. This is the original meaning given by van Potter to the word bioethics, as a bridge to the future.
Animal Population Groups↗
Xenotransplantation: state of the art.
Organ transplantation is unfortunately limited by the number of cadaveric human donor organs that become available. Xenotransplantation - the transplantation of organs and tissues between animal species - would supply an unlimited number of organs and offer many other advantages. The leading candidate as a source of organs for xenotransplantation is the pig, as it is anatomically and physiologically similar to man. However, organ transplantation between distantly related species results in hyperacute rejection (HAR) of the transplant, which consists of a violent immune response involving the complement system, unleashed when organs are transplanted between distant relatives, such as pigs and humans. HAR destroys the blood vessels in the transplanted organs and kills them within minutes. Complement attack is due to the antibody-mediated activation of the complement cascade (human anti-pig antibodies have been identified as being directed against Gal-a1-3galactose epitopes on pig vascular endothelium), and this phenomenon is physiologically subjected to negative regulation by a set of species-specific proteins, known as regulators of complement activation (RCA), such as decay accelerating factor (DAF), membrane cofactor protein (MCP) and CD59. If human RCA are expressed by mammalian cells in vitro, the cells are protected against the lysis by human complement. Therefore the incorporation of human RCA into a xenogeneic organ by transgenesis should protect the transplanted organ or tissue from in vivo lysis by human complement. Major efforts are being made to overcome this hyperacute rejection. Methods being investigated include: i. depletion or inhibition of recipient antibodies or complement; ii. development of immunological tolerance to pig organs in the recipient; and iii. development of transgenic pigs that do not express the a-Gal epitope and/or express a human complement inhibiting protein (i.e., DAF). A small number of research teams, including our group, have embarked on programs to produce transgenic pigs for one of the human RCA, in the attempt to produce animals whose organs may be suitable for transplantation into humans.
Animals↗
Effects of triptorelin, a gonadotropin-releasing hormone agonist, on the human prostatic cell lines PC3 and LNCaP.
Some analogues of gonadotropin-releasing hormone (GnRH) influence the in vitro proliferation of cultured human cells by complex interactions that are only partially understood. This study explored the effect of Triptorelin, a GnRH agonist, on the LNCaP and PC3 prostatic cell lines, which are, respectively, responsive and unresponsive to androgen stimulation. The toxicity and cell cycle modifications induced by the drug were investigated by FACScan analysis; the effect on cell proliferation in different culture conditions was determined by counting in a Burker chamber; and the expression of binding sites for 125I-Triptorelin was revealed by displacement experiments. PC3 cell growth was completely unaffected by Triptorelin. The drug caused a double stimulatory-inhibitory action on the growth of actively proliferating LNCaP cells, depending upon the dose and environment. A significant inhibitory effect on proliferation, ranging from 25% to 65% compared with controls, was observed at a high dose (10(-4) M) according to the culture conditions; and a proliferative effect (42% compared with controls) was observed at a lower dose (10(-7) M) only in fetal bovine serum-supplemented medium. Displacement experiments revealed the expression of moderately high affinity and low affinity binding sites in LNCaP cells (Kd = 2.6 x 10(-8) and 7.7 x 10(-6) M) but only low affinity binding sites in PC3 cells (Kd = 2.7 x 10(-6) M), which suggests that the expression of binding sites with different affinity could be associated with a biological response to the drug. Proliferation studies in the presence of Cetrorelix, a GnRH antagonist, confirmed the different sensitivity of the 2 cell lines to GnRH analogues and showed that the proliferative effect of Triptorelin on LNCaP cells can be inhibited by the antagonist. Data confirm the cell specificity of Triptorelin's action and the peculiarity of its effects on prostatic cell proliferation in our experimental conditions.
Cell Cycle↗
A phase II study of gemcitabine and tamoxifen in advanced pancreatic cancer.
BACKGROUND: Advanced pancreatic cancer (APC) constitutes a poor-prognosis disease with few and disappointing therapeutic options. In recent years chemotherapy has demonstrated a positive effect on disease-related symptoms with the introduction of a novel pyrimidine analogue, gemcitabine. Moreover there is experimental and clinical evidence that endocrine therapy may play a small but unexplored role in the management of APC. Therefore we performed a phase II study to assess whether the combination of gemcitabine and tamoxifen could be an active and safe schedule for the treatment of APC in terms of response rate and clinical benefits. MATERIALS AND METHODS: Twenty-seven evaluable consecutive patients with locally advanced, unresectable or metastatic adenocarcinoma of the pancreas were treated with gemcitabine (1000 mg/mq given as a short infusion once weekly for 3 consecutive weeks out of every 4 weeks) and tamoxifen (20 mg daily starting the second day after gemcitabine). The treatment was continued until progression or unacceptable toxicity. Evaluation of efficacy included response rate, time to progression, survival and clinical benefit, an integrated measurement of pain parameters, weight and performance status. RESULTS: A partial response was achieved in 11% of patients while 48% experienced stable disease, lasting at least 8 weeks; disease progression was documented in 41% of patients. The median time of progression was 4.5 months; the median survival-time was 8 months and one-year survival was 31%. Clinical benefit was documented in 59% of patients with a median duration of 13 weeks. No gastrointestinal or haematological grade 4 toxicity was observed. In general the treatment showed a satisfactory safety profile and tamoxifen-related toxicity was not documented. CONCLUSION: The combination of gemcitabine and tamoxifen appears to be an innovative therapeutic approach in the management of APC with interesting clinical activity and a good profile of toxicity. This novel schedule of treatment deserves further investigation in large randomized trials to assess if the addition of tamoxifen could improve the therapeutic results of gemcitabine in APC, mostly in term of quality of lfe.
Aged↗
[Levels of university training of professional nurses in oncologic surgery].
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Education, Nursing↗
Characterization of monoclonal antibody 436 recognizing the Arg-Pro-Ala-Pro sequence of the polymorphic epithelial mucin (PEM) protein core in breast carcinoma cells.
Epithelial mucins have obtained increasing clinical relevance since they were found in the serum of cancer patients and were shown to be elevated in metastatic disease. We report here the characterization of the monoclonal antibody (MAb) 436 which recognises the protein core of the polymorphic epithelial mucin (PEM) of the human breast. MAb 436 was generated by immunizing Balb/c mice with membrane-enriched fractions prepared from metastatic lesions in the axillary lymph nodes. The antigenic determinant recognized by the MAb 436 is expressed on the surface of breast cancer cells and was measured by ELISA on all of 50 cytosol preparations of primary breast tumors. Immunohistochemistry showed 98% of primary and 100% of metastatic breast cancer lesions to be positive with the 436 antigenic determinant expressed both in the cytoplasm and at the plasma membrane level of the tumor cells. Moreover, the antigen was expressed in a homogeneous fashion (80-100% of the total number of tumor cells) in more than 60% of the tumors. Reactivity with normal tissues was rare and scattered and restricted to glandular structures particularly at the luminal border level except for the distal and collecting tubules of adult and fetal kidney, where a cytoplasmic 436 antigen distribution was observed. Other cancers proved positive but the reactivity was always variable and heterogeneous. The antigen recognized by MAb 436 appears in Western Blotting as a M(r) of more than 200,000 daltons protein resolved in two bands. Epitope mapping experiments using overlapping octapeptides in the repeat unit of the PEM identified in the RPAP (Arg-Pro-Ala-Pro) sequence the binding site of the 436 antigen.(ABSTRACT TRUNCATED AT 250 WORDS)
Amino Acid Sequence↗
Post-transfusional human retrovirus infection in 41 Italian beta-thalassemic patients.
BACKGROUND: Previous studies have demonstrated that HTLV-I is present in Italy both in endemic form in Southern Apulia and in epidemic form among the population of intravenous drug addicts. In the present paper we intend to evaluate the risk for transfusional HTLV-I transmission in our country, as well as the already known risk for HIV1. METHODS: A population of 41 polytransfused Italian beta-thalassemic patients was examined by serological methods and PCR (polymerase chain reaction) for human retrovirus infection. Genomic DNA from PBMCs was analyzed by PCR with primer pairs specific for the HTLV-I gag, pol and env regions, and the HTLV-II env region. RESULTS: Two patients were found to be weakly seroreactive to p19 and p24 HTLV-I/HTLV-II proteins by Western blot. The analysis of genomic DNA from PBMCs by PCR revealed sequence homology to HTLV-I only in these two patients. On the contrary, PCR with primer pairs specific for HTLV-II showed no beta-thalassemic patient was infected by this retrovirus. Surprisingly, Western blot analysis for detecting anti-HIV1 antibodies in these polytransfused subjects showed a seropositivity in two patients (not the same found to be infected with HTLV-I) in spite of a screening for HIV1 antibodies in the blood bank. CONCLUSIONS: These findings suggest that in Italy polytransfused people should still be considered at risk for HIV1 as well as HTLV-I infection, even if the incidence cannot be evaluated from such a small sample. The authors stress the importance of a through medical history of potential blood donors to eliminate possibly infected subjects.
Adolescent↗
Temozolomide in radio-chemotherapy combined treatment for newly-diagnosed glioblastoma multiforme: phase II clinical trial.
BACKGROUND: Continuous research into new strategies and chemotherapy agents for the treatment of malignant high-grade gliomas have led to the synthesis of a new chemotherapy drug, temozolomide (TMZ), with a lower toxicity profile compared to conventional chemotherapy agents, such as nitrosoureas. Temozolomide is an oral alkylating chemotherapy agent licensed for the treatment of recurrent high-grade gliomas, anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM). Because of its favorable pharmacokinetic and pharmacodynamic properties and improved tolerability, TMZ is now under investigation for concomitant use with radiotherapy in patients with newly-diagnosed GBM. We present a phase II clinical trial investigating the efficacy and safety of radio-chemotherapy combined treatment using TMZ, followed by six cycles of adjuvant chemotherapy with TMZ, in patients with newly-diagnosed GBM who have undergone debulking surgery or biopsy only. PATIENTS AND METHODS: Twenty-one patients with newly histologically-diagnosed GBM were enrolled into this phase II clinical trial. In phase I of the study, TMZ (75 mg/m2/day per 7 days/wk for 6 weeks) was orally administered to patients concomitantly with radiotherapy (RT) (2 Gy per fraction once daily, per 5 days/wk for 6 weeks). In phase II of the study, four weeks after completion of RT, a monochemotherapy using TMZ was administered at the dosage of 200 mg/m2/day per 5 days every 28 days for 6 cycles. Primary end-points were the safety and tolerability profile of this two-phase combined treatment and secondary end-points were the objective response and survival rates at twelve months and eighteen months from study entry. RESULTS: The one-year survival rate of patients treated with the investigated multimodality treatment was 58% and median survival time was 15.7 months. Concomitant RT plus TMZ (phase I) followed by adjuvant TMZ (phase 2) were well-tolerated; indeed, nonhematological adverse events were rare and mild to moderate in severity; grade 3 and 4 neutropenia and thrombocytopenia were the major-related hematological side-effects observed in only 2 and 3 of all patients in phase I and 4 patients in phase II. We found that the combination of radio- and chemo-therapy, in phase I of the study did not significantly increase the incidence and severity of hematological toxicity caused by the adjuvant TMZ-based chemotherapy administered in phase II of the study. CONCLUSION: The investigated multimodality treatment regimen was well-tolerated and prolonged survival while improving patients' quality of life.
Adult↗
Antigenic expression changes occurring in adriamycin resistant MCF-7 mammary carcinoma cells.
The antigenic phenotypic repertoire of MCF-7 human breast carcinoma cell line variants that display different sensitivity to adriamycin (Adr) was analyzed using monoclonal antibodies (MoAbs) recognizing five different tumor associated antigens (TAAs) and the external domain of the epidermal growth factor receptor (EGF-R). ELISA and cytofluorimetry determinations were used and results indicate a diminished expression of one antigenic determinant of the carcinoembryonic antigen (CEA) molecule, the disappearance of all the other TAAs and the de novo expression of the EGF-R in the MCF-7 AdrR (IC50/Adr:10 uM). Treatment with recombinant alfa-Interferon (alfa-IFN) did not enhance antigenic expression in MCF-7 AdrR cells.
Antibodies, Monoclonal↗