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Biomedical subjects

A Garofalo

Publications and source records attributed to A Garofalo.

At least 55 records · Page 3Linked to original sources

Endothelial leukocyte adhesion molecule-1-dependent adhesion of colon carcinoma cells to vascular endothelium is inhibited by an antibody to Lewis fucosylated type I carbohydrate chain.

Endothelial leukocyte adhesion molecule-1 (ELAM-1) has been determined to be the mediator of adhesion of colon carcinoma cells to interleukin-1 (IL-1)-activated endothelial cells. To identify ELAM-1 ligand in colon carcinoma cells, we have screened a series of 11 monoclonal antibodies directed to these cells and found that only one MBr8 was able to inhibit the IL-1-induced increment in adhesion of HT29 and of SW948 colon carcinoma lines to endothelial cells. In contrast, MBr8 did not bind to polymorphonuclear cells, monocytes, and lymphocytes and did not inhibit polymorphonuclear adhesion to IL-1-activated endothelial cells. As expected, an ELAM-1 monoclonal antibody strongly inhibited IL-1 induced increment of adhesion of HT29, SW948, and polymorphonuclear cells. As negative control, MG63 osteosarcoma cells were used. These cells adhere more efficiently to IL-1 activated endothelial cells but MBr8 and ELAM-1 monoclonal antibodies did not affect their adhesion. The effect of MBr8 was also tested in an experimental system in vivo. As described previously, radiolabeled HT29 cell retention in the lung of nude mice was increased in animals given IL-1. MBr8 administration to nude mice or pretreatment of tumor cells with it inhibited this effect. These data suggest that cell adhesion to ELAM-1 might be mediated by different, cell type specific, sugar ligands.

Antibodies, Monoclonal↗

Effect of interleukin-1-beta on metastasis formation in different tumor systems.

Experiments were done to determine the effect of interleukin-1-beta (IL-1 beta) on metastasis formation in different tumor systems. Intravenous administration of 1 microgram of human recombinant IL-1 beta given 1 hour before tumor cell injection augmented lung colony formation (experimental metastases) by the human A375 melanoma variants, the human HT-29M colon carcinoma, the SN12-K1 renal carcinoma in nude mice, the murine B16 melanoma variants, and the murine UV-2237M fibrosarcoma in syngeneic recipients. The same treatment did not induce lung colony formation by a human rectal carcinoma (HCC-P2988) or by a murine reticulum cell sarcoma (M5076), both of which are not metastatic to the lung. Spontaneous metastases were studied in C57BL/6 mice bearing the B16-BL6 melanoma (metastatic to the lung) in their footpad and the M5076 reticulum cell sarcoma (metastatic to the liver) subcutaneously. Daily intraperitoneal treatment with 1 microgram of IL-1 beta increased lung and liver metastases. These findings indicate that treatment of mice with IL-1 beta can increase the number of artificial or spontaneous metastases and that this effect is not limited to a single tumor type or to a specific organ.

Animals↗

Early gastric cancer: total gastrectomy vs. distal resection. Results of a study of 271 cases. The Italian Stomach Cancer Group (A.C.O.I.-I.S.C.G.).

Two hundred and seventy-one (271) patients with early gastric cancer from 26 different hospitals were examined in a retrospective study conducted by the I.S.C.G. (Italian Stomach Cancer Group). The patients were divided into two series: the first, comprising 234 patients with negative lymph nodes (Stage ITNM-UICC), had 5-year survival rates of 85%. The second group comprised 37 patients with positive lymph nodes (Stage III TNM-UICC) with a 72% five-year survival rate. Both results appear to be of great significance when compared with the five-year survival rate for advanced gastric cancer, namely 29.3%. As far as the difference between the late results of total gastrectomy and subtotal distal resection are concerned, the latter was associated with a higher five-year survival rate in the case of tumors located in the lower third and in the middle third of the stomach.

Adult↗

[Multicenter retrospective study of 3,024 patients operated on for stomach cancer in Italy. Epidemiology, surgical treatment and survival].

This study presents the results achieved in 2,000 patients who underwent gastric resection and who had been selected from amongst 3,074 cases of gastric neoplasia included in the Retrospective Study of Carcinoma of the Stomach, carried out by the "Italian Stomach Cancer Group" of the Association of Italian Hospital Surgeons (ACOI). In terms of the UICC TNM classification, these patients consisted of 234 stage I patients, 494 stage II patients 1,011 stage III patients and 261 stage IV patients. The overall operative mortality was 7.1 percent. This was lower after subtotal distal resection. The long-term survival tended to fall in proportion with the stage of the illness, whereas the degree of the exeresis did not appear to have any impact. The overall survival at 5 years in the patients who survived the operation was 45%, that following distal resection was 54% and that after total gastrectomy was 33%. The survival rate in terms of the stage ranged from 86% for Early Gastric Cancers to 28% for the patients who underwent surgery at stage III i.e. when they had metastatic lymph nodes.

Adult↗

Interleukin 1-induced augmentation of experimental metastases from a human melanoma in nude mice.

This study has examined the effect of the cytokine interleukin 1 (IL-1) on metastasis formation by the human melanoma A375M in nude mice. We have found that human recombinant IL-1 beta (a single injection greater than 0.01 micrograms per mouse i.v. given before tumor cells) induced an augmentation of experimental lung metastases from the A375M tumor cells in nude mice. This effect was rapidly induced and reversible within 24 h after IL-1 injection. A similar effect was induced by human recombinant IL-1 alpha and human recombinant tumor necrosis factor, but not by human recombinant interleukin 6. 5-[125I]odo-2'-deoxyuridine-radiolabeled A375M tumor cells injected i.v. remained at a higher level in the lungs of nude mice receiving IL-1 than in control mice. In addition, IL-1 injected 1 h, but not 24 h, after tumor cells enhanced lung colonization as well, thus suggesting an effect of IL-1 on the vascular transit of tumor cells. These findings may explain the observation of enhanced secondary localization of tumor cells at inflammatory sites and suggest that modulation of secondary spread should be carefully considered when assessing the ability of this cytokine to complement cytoreductive therapies.

Animals↗

Research on compounds with psychotropic activity. IX--Synthesis of 6-p-methoxyphenylpyrrolo[2,1-d][1,5]benzothiazepines and evaluation of their affinities for BDZ and GABA receptor subtypes.

6-p-Methoxyphenylpyrrolo[2,1-d][1,5]benzothiazepin-7(6H)-one (IV), cis-7-acetoxy-6,7-dihydro-6-p-methoxyphenylpyrrolo[2,1-d] [1,5]benzothiazepine (V) and some significant 7-acyloxy-6-p-methoxyphenylpyrrolo[2,1-d][1,5]benzothiazepines (VI a-g) were synthesized and tested in vitro for inhibition of the specific binding of 3H-Flunitrazepam, 3H-PK 11195, 3H-Muscimol and 3H-(-)Baclofen to central and peripheral benzodiazepine, GABA-A and GABA-B receptors, respectively. The compounds (IV), VI a) and (VI c) were active on the peripheral benzodiazepine receptor; in particular (VI a) and (VI c) were very active. The compound (VI g) showed an affinity, even though scanty, for the central benzodiazepine receptor.

Animals↗

[Clinical study of the efficacy and tolerability of nimesulide in suppositories compared to flurbiprofen in gynecology].

The efficacy and tolerability of nimesulide in a new pharmaceutical suppository form were assessed in a double blind study versus flurbiprofen in pain-inflammatory pathologies of obstetrico-gynecological nature. One hundred patients with pelvic inflammatory disease were randomly assigned to treatment with nimesulide or flurbiprofen. Both drugs, administered in a dose of 2 suppositories a day for 7 days, evidenced speedy, effective analgesic and anti-inflammatory activity combined with good tolerability. Specifically, as regards the pain component, nimesulide demonstrated a significantly more marked analgesic effect than flurbiprofen in the first two hours of treatment.

Analgesics↗

Synthesis of disubstituted tetrahydrocarbazoles with potential antidepressive activity.

A new series of disubstituted tetrahydrocarbazoles were synthesized. They are tested for antidepressive activity by the Porsolt's forced swimming test (one of the acute stress methods) and by the prevention of reserpine induced hypothermia and ptosis in mice. 3-Morpholino-1-[N-(6-methoxy-1,2,3,4- tetrahydrocarbozolyl)2-propanol, fumarate (XI) was demonstrated to be the most promising compound of this series. Besides, this series did not present the most common adverse effects of the conventional tricyclic-antidepressants (loss of locomotor coordination, ataxia and anticholinergic activity).

Animals↗

The nude mouse for the study of human colorectal carcinoma.

The tumorigenicity and metastatic behaviour of human colorectal tumors have been assessed in athymic nude mice. Surgical specimens were obtained from colorectal carcinomas or from metastases of different patients. Primary colorectal tumors and their synchronous liver metastases were obtained from three patients. After intramuscular (i.m.) injection into nude mice, tumor cells originating from metastases showed a higher take than those from primary tumors. In general, metastasis-derived tumors had a shorter doubling time than primary-derived tumors. This growth pattern was not associated with the production of spontaneous metastases in nude mice. To investigate the malignant potential of colorectal neoplasms in the nude mouse, tumor cells were injected intravenously (i.v.) (artificial lung metastases) and in the spleen (artificial liver metastases). Colorectal-derived tumor cells produced lung colonies after i.v. injection, but the most dramatic expression of malignancy was the tumor cells' ability to grow in the liver after intrasplenic (i.s.) injection. The ability to grow in the liver of nude mice appeared to be a distinct characteristic of each tumor cell population. Human colorectal tumors were maintained as continuous lines subcutaneously (s.c.) in nude mice. Phenotypic differences, including malignant potential, were generally maintained at different passages. Human colorectal tumors with a definite pattern of malignant behaviour (i.e. to the liver) in the nude mouse provide a unique experimental system for the study of the biology and the therapy of cancer metastases.

Animals↗

Response to flavone acetic acid (NSC 347512) of primary and metastatic human colorectal carcinoma xenografts.

The antitumour activity of flavone acetic acid (FAA) was evaluated against two human colorectal carcinoma (HCC) lines, HCC-P2988 and HCC-M1410, transplanted into nude mice. On repeated i.v. injection of 200 mg kg-1 every 4 days FAA was moderately active against the s.c. growing HCC-P2988. HCC-M1410 transplanted s.c. was almost unresponsive in the same experimental conditions. In contrast, FAA (200 mg kg-1 i.v. every 4 days, repeated three times) significantly reduced liver tumour colonies produced by the HCC-M1410 cells injected intrasplenically into nude mice. These findings suggest that FAA has potential activity against human colorectal carcinoma, particularly against liver metastases.

Animals↗

Effects of estriol administration on human postmenopausal endometrium.

Forty eight women with atrophic endometrium were treated with estriol, 1 mg twice daily, by mouth for a minimum of 10 days and a maximum of 25 days. Vaginal hysterectomy was then performed and specimens were examined histologically. Results showed that estriol produces endometrial hyperplasia in 70.8% of the examined women; only 29.2% of the patients retained atrophic endometrium after treatment.

Aged↗

Serum aldosterone and plasma renin activity in normal and toxaemic pregnancies.

The present study was performed to examine serum aldosterone and plasma renin activity variations in normal and toxaemic pregnancy. Blood samples were collected by 166 normal pregnant women and 196 toxaemic women. Results don't show important differences between normal and toxaemic pregnancies concerning either serum aldosterone or plasma renin activity.

Aldosterone↗

Double circuit esophagojejunoduodenal plasty in reconstruction of the alimentary tract after total gastrectomy.

The results of a new reconstructive technique of the digestive tract after total gastrectomy with a double circuit EDDP were reviewed. Since 1976, 141 patients with carcinoma of the stomach have been surgically treated at our hospital. Of the 68 patients who had undergone total gastrectomy, 17 had a double circuit EDDP performed. In this short series, no postoperative complications occurred. The results of clinical, laboratory and instrumental assessments in the eight patients available for follow-up study were quite satisfactory. Weight loss was moderate, if not absent. All patients assessed were content with their quality of life and were able to resume their previous work activities again.

Body Weight↗

A human acute lymphoblastic leukemia line with the T(4;11) translocation as a model of minimal residual disease in SCID mice.

This study describes a new human acute lymphoblastic leukemia (ALL) cell line (ALL-PO) with the t(4;11) translocation established in SCID mice. The ALL-PO line can be maintained by serial transplant in SCID mice with stable immunophenotypic, molecular and karyotypic features. After intravenous (i.v.) injection ALL-PO spread systemically involving the hematopoietic organs and the central nervous system (CNS) of all mice. The homing and the progression of the disease are evaluated by histological analysis and reverse-transcriptase polymerase chain reaction (RT-PCR) amplification of the t(4;11) translocation in the bone marrow, spleen and CNS of SCID mice at different times after engraftment. Occult leukemia was detectable by PCR in the bone marrow of SCID mice as early as three days after the i.v. injection of leukemic cells whereas the first signs of involvement of the spleen and CNS appeared after 14 days; after 24 days all the mice were euthanized because they were moribund and the bone marrow, spleen and CNS showed ample infiltration by leukemic cells. The sensitivity to conventional chemotherapy was tested in this model. ALL-PO in SCID mice did not respond to treatment with vincristine or idarubicin but cyclophosphamide (150 mg kg(-1) i.v., single injection) significantly increased the survival of the mice. The efficacy of such a treatment was more evident when cyclophosphamide was given in the early stages of the disease (detectable only by molecular analysis) but much less effective when the drug was administered when the disease could be detected by conventional histological analysis. The biological behavior and molecular characteristics of ALL-PO make it a good model for studying novel therapeutic strategies for a better control of minimal residual disease.

Animals↗

Increase in beta-galactosidase activity in a non-isothermal bioreactor utilizing immobilized cells of Kluyveromyces fragilis: fundamentals and applications.

The beta-galactosidase activity of Kluyveromyces fragilis cells immobilized in a kappa carrageenan gel was studied in a bioreactor functioning under isothermal and non-isothermal conditions. We observed an increase in enzyme activity which was found to be proportional to the intensity of the temperature gradient applied across the biocatalytic membrane, as well as to the average temperature of the bioreactor. The efficiency of such a non-isothermal bioreactor was calculated with respect to the yield of a bioreactor working under comparable isothermal conditions and was evaluated in terms of reduction of processing times in industrial applications. The possibility that enzyme activity in living cells is affected by non-isothermal conditions naturally existing owing to metabolic heat production is also discussed.

Bioreactors↗