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Biomedical subjects

G Rasi

Publications and source records attributed to G Rasi.

At least 19 recordsLinked to original sources
PubMed2006

Rhinitis and asthma in athletes: an ARIA document in collaboration with GA2LEN.

This consensus document is aimed at reviewing evidence that the rhinitis-asthma links have peculiar features in athletes. Beside a review of epidemological data on the high prevalence of rhinitis and asthma in athletes, the effects on intense physical exercise on the immune system and repiratory functions are discussed, with special reference to the role of allergens and pollutants. In extending the Allergic Rhinitis and its Impact on Asthma (ARIA) recommendations to athletes, the issue is addressed of adapting diagnosis and management to criteria set by the International Olympic Committee (IOC) and regulations adopted by the World Anti-Doping Agency (WADA).

Asthma↗
PubMed2003

Combination therapy in the treatment of chronic viral hepatitis and prevention of hepatocellular carcinoma.

Treatment of chronic hepatitis B and C viruses (HBV and HCV) is still disappointing, and both are the major causes of liver cirrhosis and hepatocarcinoma. Interferon and lamivudine are the registered drugs for chronic HBV but are scarcely effective on HBeAg-negative patients, and resistance due to virus mutation is the rule with lamivudine. Interferon and ribavirine represent the standard treatment for chronic HCV but less than the half of the infected population is eligible for this treatment and less of the half of treated patients will experience a sustained response. No single new drug to date has shown the potential to overcome this dismal picture. Combined strategies are thus the currently most available approach to improve the response rate of chronic HBV and HCV infection, with a subsequent decrease in the number of patients developing hepatocellular carcinoma (HCC). Combination of thymosin alpha 1 with interferon or antiviral agents is currently the most promising option, but nontoxic immunomodulants, such as oral MIMP, should be explored. This review focuses on the difficulties with current therapy and the rationale for use of combination therapy with thymosin alpha 1 for both HBV and HCV therapies.

Adjuvants, Immunologic↗
PubMed2003

Nerve growth factor: neurotrophin or cytokine?

Nerve growth factor (NGF) is a neutrophin exerting an important role in the development and functions of the central and peripheral nervous system. However, it has recently been documented that several immune cells - such as mast cells, lymphocytes and eosinophils - produce, store and release NGF. Moreover, NGF high and low affinity receptors are widely expressed in the immune system, thus indicating the potential of responding to this neurotrophin through an autocrine mechanism. In fact, NGF influences development differentiation, chemotaxis and mediator release of inflammatory cells as well as fibroblast activation through a complex network influenced by other pro-inflammatory cytokines. Finally, NGF is increased in biological fluids of several allergic, immune and inflammatory diseases. Data reviewed suggest, therefore, that NGF might also be viewed as a (Th2?) cytokine with a modulatory role in allergic inflammation and tissue remodeling.

Cytokines↗
PubMed2002

Nerve growth factor and asthma.

An increasing body of evidence shows that nerve growth factor (NGF) exerts biological activity not only on the central and peripheral nervous system, but also on the immune system thereby influencing allergic diseases and asthma. (1) NGF circulating levels are increased in patients with allergic diseases and asthma, and are related to the severity of the inflammatory process and disease. In vernal keratoconjunctivitis, NGF plasma levels correlate with the number of mast cells infiltrating the conjunctiva, and NGF mRNA is increased in nasal mucosal scrapings of patients with allergic rhinitis who have high levels of NGF in serum and nasal fluids; NGF is further increased in nasal fluids after specific allergen challenge. (2) NGF is produced and released by several modulatory and effector cells of allergic inflammation and asthma, for example T-helper 2 lymphocytes, mast cells and eosinophils. (3) NGF receptors are expressed on the conjunctival epithelium of patients with allergic conjunctivitis and the number of NGF-receptor positive cells is increased in the conjunctiva of these patients. Indeed, local administration of NGF induces fibroblast activation and healing processes of human corneal ulcers, which suggests that NGF plays a role in tissue remodelling processes occurring in asthma. (4) NGF increases airway hyperreactivity to histamine in an animal model of asthma, while anti-NGF treatment reduces airway hyperreactivity induced by ovalbumin topical challenge in the sensitized mouse.

Animals↗
PubMed2001

The heterogeneity of allergic phenotypes: genetic and environmental interactions.

OBJECTIVE: This article reinforces the reader's knowledge of the multifactorial nature of allergic diseases and of the heterogeneity of allergic phenotypes. DATA SOURCES: Personal studies and an evidence-based approach is used to support the assumption that three major abnormalities concur in the pathophysiology of allergic diseases: 1) enhanced allergen recognition and specific immune response; 2) a T helper 2 cytokine profile that results in polyclonal immunoglobulin E activation and mast cell-eosinophilic inflammation; and 3) organ hyperreactivity. STUDY SELECTION: Examples of genetic and environmental factors that preferentially influence each of these distinct pathophysiologic abnormalities are provided. RESULTS: Data presented indicate that allergic diseases distribute along a wide spectrum depending on the preferential pathophysiologic abnormalities operating in the individual patient. CONCLUSIONS: Categorization of allergic patients into distinct clinical phenotypes might result in a more patient-oriented (rather than disease-oriented) approach, and hence, better management.

Allergens↗
PubMed2000

A new human tumor-associated antigen (TLP) is naturally expressed in rat DHD-K12 colorectal tumor cells.

Renewed interest in cancer immunotherapy has been raised by the availability of a variety of tumor-associated antigens and animal models. We have recently described the presence of a new antigen, TLP, in sera and cancer tissue from lung and colorectal cancer patients. In order to develop an experimental model suitable for preclinical studies on cancer vaccines, we investigated the presence of TLP antigen in vitro, in the DHD-K12 cell line and in vivo, in metastases induced in syngeneic BDIX rats by DHD-K12 cell injection. TLP was not detected in any tissue of healthy rats nor in normal tissues of tumor-bearing rats. This is in agreement with our previous studies, in which we had demonstrated that TLP is expressed in human colorectal cancer and adenomas but not in normal colonic mucosa. Our results indicate TLP as a possible human tumor-specific antigen naturally expressed in DHD-K12 tumor syngeneic to immunocompetent BDIX rats.

Animals↗
PubMed2000

Thymosin alpha 1 in the treatment of cancer: from basic research to clinical application.

Many studies have explored the effects of immunotherapy, alone or in combination with conventional therapies, on both experimental and human cancers. Evidence has been provided that combined treatments with thymosin alpha 1 (T alpha 1) and low doses of interferon (IFN) or interleukin (IL)-2 are highly effective in restoring several immune responses depressed by tumor growth and/or cytostatic drugs. In addition, when combined with specific chemotherapy, they are able to increase the anti-tumor effect of chemotherapy while markedly reducing the general toxicity of the treatment. The advantages of using this combined chemo-immunotherapeutic approach in experimental and human cancers are reviewed in this issue.

Adjuvants, Immunologic↗
PubMed1999

Efficacy of repeated cycles of chemo-immunotherapy with thymosin alpha1 and interleukin-2 after intraperitoneal 5-fluorouracil delivery.

We have used chemo-immunotherapy with 5-fluorouracil (5-FU), thymosin alpha1 (T alpha1) and interleukin-2 (IL-2) to treat multiple liver metastases from colorectal cancer induced by DHD/K12 cells in syngeneic BDIX rats, comparing one and two cycles of treatment, and different treatment combinations. 5-FU was delivered loco-regionally as a continuous infusion via an intraperitoneal (i.p.) catheter from a subcutaneously implanted mini-pump, a method we developed for this study. We show here that two cycles of a triple chemo-immunotherapy regimen significantly increased the average survival time compared to one cycle, and compared to untreated controls or those treated with two cycles of 5-FU alone. At 150 days, two rats treated with two cycles of triple therapy were cured, showing no signs of cancer at autopsy; all the other rats died before this time. Triple chemo-immunotherapy resulted in significantly fewer extra-hepatic metastases than in the controls and in those treated with 5-FU only. Further, we found that two cycles of triple treatment significantly increased the absolute number of peripheral T cells expressing IL-2 receptor, CD4 and CD8 compared to controls. We conclude that two cycles of chemo-immunotherapy with 5-FU, T alpha1 and IL-2 were superior to one cycle of treatment and to other treatments tested. Our results suggest that the triple therapy acts by increasing numbers of effector T cells. This method shows promise for the use of multi-cycle chemo-immunotherapy in the treatment of unresectable metastases of colorectal cancer in humans.

Animals↗
PubMed1999

Differential expression of a new tumor-associated antigen, TLP, during human colorectal cancer tumorigenesis.

Tumour liberated particles (TLP) have been proposed as a potential new serum tumor marker. In particular, a high percentage of patients with early stages of lung cancer scored positive for serum TLP, suggesting its possible role as a marker for early diagnosis of disease. The aim of the present study was to analyze the expression of TLP in the colorectal adenoma-carcinoma sequence in order to determine whether its expression correlates with the various stages of cancer transformation. TLP distribution was assessed by immunohistochemistry in normal, premalignant, and malignant colorectal lesions. Normal colonic mucosa and hyperplastic polyps showed no positive staining, whereas adenomas and adenocarcinomas reacted to anti-TLP serum. The percentage of positive tumor cells increased from adenomas with mild dysplasia to adenomas with severe dysplasia. Moreover, a supranuclear staining pattern was observed mainly in adenomas with mild dysplasia, whereas adenomas with severe dysplasia as well as adenocarcinomas showed a characteristic diffuse staining pattern and a strong staining intensity. Only a few cases of adenocarcinoma were found to be TLP-negative and all were poorly differentiated. Our results suggest that TLP antigen expression may be considered as a marker of epithelial atypia in the colorectal tract and as a potential target for new diagnostic and/or therapeutic approaches to human colorectal cancer.

Adenocarcinoma↗
PubMed1999

Expression profile of saccharide epitope CaMBr1 in normal and neoplastic tissue from dogs, cats, and rats: implication for the development of human-derived cancer vaccines.

CaMBr1 is a blood group-related tumour-associated antigen, whose pattern of expression provides a therapeutic window for passive or active immunotherapy and points to the promise of a vaccine against carcinomas overexpressing this antigen. In this context, an animal model that closely mimics the human situation would be extremely useful. We, therefore, utilised the murine monoclonal antibody MBr1, which defines CaMBr1, as a useful probe to detect the molecule targeted for vaccine development on canine and feline spontaneous breast and uterus tumours and on their normal counterparts, and on rat normal tissues and carcinoma cell lines. Immunoperoxidase staining of cryostat sections revealed homogeneous CaMBr1 expression only in normal feline uterus and a uterus papilloma, whereas MBr1 reactivity was very weak and heterogeneous in normal (1/3 and 1/3) and tumour (1/10 and 1/6) breast tissues from dogs and cats, respectively. In contrast, the data obtained in rat tissues were reproducible in the strains tested and showed that CaMBr1 was expressed in all epithelial tissues of the digestive tract, although with variable intensities. Monoclonal antibody staining appeared to correspond to membrane-bound structures as well as mucinous secretions. Similarly, secretion products of lactating mammary glands expressed CaMBr1. The spectrum of expression on rat digestive tract was broader than that in humans but the specificity of MBr1 reactivity was confirmed by competition assay with a synthetic tetrasaccharide that mimics the CaMBr1 antigen. On FACS analysis, only one of two clonal derivatives of the rat breast carcinoma line RAMA 25 expressed CaMBr1, and a negative cell subset was evident in repeated experiments. By contrast, both colon carcinoma lines, DHD/K12 and CC531, showed staining with MBr1, albeit at different levels of intensity, and no evidence of a negative subset. The cell line CC531 maintained or even increased CaMBr1 expression levels following transplantation in syngeneic immunocompetent animals. Our data suggest the usefulness of the rat as a test model for vaccines against human cancers overexpressing the CaMBr1 antigen.

Animals↗
PubMed1999

Microfabricated biocapsules provide short-term immunoisolation of insulinoma xenografts.

This study examines the viability and functionality of two insulinoma cell lines, RIN (1048) and betaTC6F7, encapsulated within microfabricated biocapsules. Surface and bulk micromachining are integrated in the biocapsule fabrication process, resulting in a diffusion membrane with uniform pore size distribution as well as mechanical and chemical stability, surrounded by an anisotropically-etched silicon wafer, which serves as the encapsulation cavity. Insulinoma cells (4500 cells/biocapsule) were enclosed within these microfabricated biocapsules and subjected to a static incubation study after either implantation in BALB-C mice or incubation in vitro. Examination of retrieved microfabricated biocapsules revealed an insulin stimulatory index of approximately 1.5 for encapsulated RIN cells and 3.6 for encapsulated betaTC6F7 cells for biocapsules with 18 nm pore sized microfabricated membranes, similar to indices of biocapsules incubated in vitro. There was an 80% decrease in cell stimulatory response between in vitro and in vivo 66 nm-biocapsules as compared to 20% for 18 nm-biocapsules, indicating that the immunoisolatory effectiveness depends greatly on achieving uniform pore sizes in the size range of 18 nm or smaller. The present study demonstrates the feasibility of using microfabricated biocapsules for the immunoisolation of insulinoma cells lines. The microfabricated biocapsule may serve as an alternative to conventional polymeric based biocapsules for possible use as in vivo insulin secreting bioreactor.

Journal Article↗
PubMed1997

Combination therapy with BRMs in cancer and infectious diseases.

In recent years many studies have stressed the importance of using biological response modifiers (BRMs) in the treatment of different conditions of immune-impairment correlated with ageing, cancer and infectious diseases. In particular, the use of different BRMs in conjunction with conventional therapies has been extensively explored. Our studies have demonstrated that treatment with Thymosin alpha-1 and low doses of IFN or IL-2 exert powerful biological effects both in vitro and in vivo. They are highly effective in restoring cytotoxic activities in immunosuppression induced by tumors and/or cytostatic drugs. In addition, when combined with specific chemotherapy, they are able to induce a dramatic inhibition of tumor growth in both experimental models and in humans. Immunotherapeutic treatment also has an application in controlling infectious diseases, especially those occurring in the immuno-compromised host. The advantage of using the combined immunotherapy treatment with antiviral drugs has been recently demonstrated by our group both in a murine experimental influenza model and in patients infected with HBV, HCV and HIV.

Bacterial Infections↗
PubMed1996

Combination low-dose lymphoblastoid interferon and thymosin alpha 1 therapy in the treatment of chronic hepatitis B.

This open label study was initiated to assess the safety and efficacy of lymphoblastoid interferon-alpha (IFN-alpha) and thymosin alpha 1 (T alpha 1) in the treatment of 11 patients with chronic hepatitis B, who had failed to respond to standard IFN-alpha 2b therapy, and in four interferon naive patients. These fifteen hepatitis B surface antigen (HBsAg) positive and serum hepatitis B virus (HBV) DNA positive patients were given T alpha 1 (1 mg) subcutaneously (s.c.) on 4 consecutive days. Low-dose lymphoblastoid IFN-alpha (3 MU) was administered intramuscularly (i.m.) on the fourth day. Beginning with the second and for the subsequent 25 weeks, patients self-administered T alpha 1 twice weekly in the morning followed, 12 h later, by 3 million units (MU) lymphoblastoid IFN-alpha. Patients were followed-up for 12 months. Nine (60%) of the 15 patients, including six (55%) of the 11 patients previously treated with IFN-alpha 2b, responded by losing serum HBV DNA and normalizing alanine aminotransferase (ALT) values. Six of the nine responders seroconverted to HBsAg negativity. Significant improvements in the Knodell histological activity index were observed in the responders and no significant adverse effects were observed. Combination low-dose lymphoblastoid IFN-alpha and T alpha 1 treatment may provide a safe and potentially effective therapeutic approach in chronic hepatitis B. These results require confirmation in future randomized controlled studies.

Adult↗
PubMed1996

Combination thymosin alpha 1 and lymphoblastoid interferon treatment in chronic hepatitis C.

BACKGROUND: Monotherapy for chronic hepatitis C using interferon (IFN) results in a very small proportion of patients exhibiting a sustained response. Clinical trials assessing the benefit of combination drug therapy may provide evidence of improved treatment response over that seen with single drug treatment. AIM: To assess the response in patients with chronic hepatitis C to one year of combination treatment: thymosin alpha 1 (T alpha 1), 1 mg twice weekly, and lymphoblastoid (L)-IFN, 3 MU thrice weekly. PATIENTS AND METHODS: Fifteen patients with serum HCV RNA positive chronic hepatitis C were studied. Eleven patients were treatment naive and four had failed previous standard IFN therapy. Thirteen patients were HCV RNA serotype 1b. All patients were given combination T alpha 1 and L-IFN therapy for one year with a six month follow up period. RESULTS: Six months after initiation of treatment seven patients (47%) were sera HCV RNA negative and at completion of the one year treatment 11 (73%), including two who had failed previous standard IFN treatment, had negative serum HCV RNA. Six months after treatment, six patients (40%), including five with HCV type 1b, showed a sustained response characterized by a negative serum HCV RNA. CONCLUSIONS: The results of this open label trial suggest that there may be a potential benefit to combining an immune modulator (T alpha 1) with an antiviral (IFN) in the treatment of chronic hepatitis C. Verification of the observations in this study require completion of a randomised controlled study.

Adult↗