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Biomedical subjects

A Gallo

Publications and source records attributed to A Gallo.

At least 19 recordsLinked to original sources
PubMed1992

v-ras and protein kinase C dedifferentiate thyroid cells by down-regulating nuclear cAMP-dependent protein kinase A.

Ras proteins are membrane-associated transducers of eternal stimuli to unknown intracellular targets. The constitutively activated v-ras oncogene induces dedifferentiation in thyroid cells. v-Ras appears to act by stimulating protein kinase C (PKC), which inhibits the nuclear migration of the catalytic subunit of the cAMP-dependent protein kinase A (PKA). Nuclear tissue-specific and housekeeping trans-acting factors that are dependent on phosphorylation by PKA are thus inactivated. Exclusion of the PKA subunit from the nucleus could represent a general mechanism for the pleiotropic effects of Ras and PKC on cellular growth and differentiation.

Animals↗
PubMed1992

Neoplastic infiltration of laryngeal cartilages: histocytochemical study.

The relationship between cartilage and invading neoplastic cells was studied in 32 cases of laryngeal cancer by histological and cytochemical methods. Cartilage invasion was present in 12 cases, 10 of which were in proximity or in contact with areas of calcification and ossification. It was significantly correlated only to tobacco consumption (P less than .05) and, in regard to glottic tumors, to tumor diameter greater than 3 cm (P less than .01). Histologically, neoplastic invasion in cartilage was massive in 2 cases, occurred in areas of ossification in 4, between cartilage and bone in 4, and in epiglottic cartilage in 2. In 3 of the cases with bone invasion, there was also new bone formation. Hyaline cartilage and bone resorption was due to tartrate-resistant acid phosphatase (TRAP)-positive giant cells; in epiglottic cartilage only mononuclear cells were present, some of which were TRAP-positive. These results show that neoplastic cells can promote not only resorption and formation of bone, but also resorption of cartilage, which is considered resistant to neoplastic invasion. The different types of resorbing cells in contact with hyaline cartilage and bone in laryngeal cancer, and elastic cartilage in epiglottic cancer, suggest that the structure of the tissue being resorbed can influence the type of resorbing cells.

Acid Phosphatase↗
PubMed1991

Recombinant alpha-2b-interferon dynamic test as a potential tool in predicting disease status during second look in ovarian cancer. A preliminary report.

The circulating levels of a 90-kilodalton (KD) tumor-associated antigen were measured in the blood of 26 patients with ovarian cancer in clinical remission who received a short course of recombinant alpha-2b-interferon (rIFN-alpha-2b, 3 million U/m2/d intramuscularly for 3 days) before second-look procedures. The administration of rIFN-alpha-2b to 90-KD antigen-positive patients produced a slight increase of the marker. However, in patients without the marker but with evidence of disease, a remarkable increase above the cutoff level was observed. Less pronounced modifications of 90-KD antigen serum levels were found in patients with no disease at second look. Moreover, considering the 90-KD antigen mean percentage increase, the dynamic test with rIFN-alpha-2b was able to eliminate five of six false-negative results obtained with the 90-KD antigen basal assay alone. The sensitivity of the assay increased to 92% after IFN compared with 54% for the 90-KD antigen assay alone. An increase (greater than 100% above pretreatment titer) of 90-KD antigen levels during the test also was observed in four patients with no evidence of disease at second look. In two of these false-positive cases, recurrence of disease was observed 13 and 24 months later. At the time of this analysis, none of the patients with a negative second look and negative dynamic test had relapsed. These results suggest that the dynamic test with rIFN-alpha-2b might be a new tool to assess disease status in patients with ovarian cancer before second-look procedures.

Adult↗
PubMed1991

Neoadjuvant chemotherapy and radical surgery in locally advanced cervical cancer. Prognostic factors for response and survival.

Between January 1986 and September 1988, 75 patients with locally advanced cervical carcinoma (International Federation of Gynecology and Obstetrics [FIGO] Stages IB-III) received three courses of neoadjuvant chemotherapy (NAC), including cisplatin, bleomycin, and methotrexate (PBM). Fifteen percent of patients achieved a complete response (CR) and 68% a partial response (PR). Pretreatment characteristics were analyzed for response to NAC. Significantly lower response rates were found in patients with tumor size more than 5 cm in diameter and bilateral parametrial involvement to the pelvic side wall. None of the biological parameters studied was related to chemoresponsiveness. Patients achieving CR or PR had a significantly improved 3-year survival rate compared with those who did not respond. After NAC, radical surgery was possible in all responding patients. The median number of lymph nodes removed was 60. A lower than expected incidence of lymph node metastases was detected. None of the clinical and pathologic features considered was significantly correlated with the lymph node status. Twelve of the 62 operated patients had disease recurrence. Pathologic parametrial involvement and cervical infiltration equal to or deeper than 5 mm were found to be significant prognostic factors for recurrence. A 3-year, disease-free survival of 89%, 73%, and 43% for Stage IB-IIA, IIB, and III, respectively, was found. Among the operated patients these rates increased to 100%, 81%, and 66% for Stage IB-IIA, IIB, and III, respectively. A prospective randomized trial comparing NAC and surgery with radiotherapy alone is in progress.

Adenocarcinoma↗
PubMed1991

Effect of recombinant human interferon-alpha 2b on receptors for steroid hormones and epidermal growth factor in patients with endometrial cancer.

Interferons (IFNs) may modulate oestrogen (ER), progesterone (PR) and epidermal growth factor (EGFR) receptor expression in vitro. ER, PR and EGFR levels in tumour specimens taken from 13 patients with endometrial adenocarcinomas before and after 5 days' intramuscular treatment with 5 x 10(6) U per recombinant human leucocyte interferon-alpha 2b (rh IFN-alpha 2b). After treatment, ER (P less than 0.01) and PR (P less than 0.05) levels were significantly increased with a simultaneous reduction of EGFR content (P less than 0.05). Since the expression of ER and PR characterises more differentiated hormono-sensitive tumours, while EGFR are preferentially expressed in less differentiated tumours, the increase of steroid hormone receptor levels with the reduction of EGFR expression suggests that rh IFN-alpha 2b may induce endometrial cancer cell differentiation. Moreover, the decrease of EGFR levels may explain the antiproliferative effect of IFNs.

Adenocarcinoma↗
PubMed1991

Improvement of cardiac contractile response to beta-adrenergic stimulation in normal and two-kidney, one-clip hypertensive rats treated with nitrendipine.

To evaluate the effect of nitrendipine on cardiac hypertrophy and inotropic response to isoproterenol in two-kidney, one-clip (2K,1C) renovascular hypertension, male Wistar rats (n = 56) were divided into a clipped group (K) (n = 28) and a sham group (S) (n = 28). Twenty-one days after surgery, the rats were placed in metabolic cages where they received either a normal diet (S and K rats) or a similar one containing N (18 mg/day) (SN and KN rats) during 3 weeks. Arterial pressure and body weight were measured twice a week. At the end of the experimental period, the hearts were excised, the ventricles were weighed, and cardiac proteins were measured by the Lowry method in seven hearts of each group. In the remaining hearts, the left ventricular papillary muscle was excised and mounted in a bath where the developed tension (dt) and the maximal rate of rise of developed tension (+T) were recorded in basal conditions, and after cumulative doses of isoproterenol (10(-11) to 10(-4) M). The arterial pressure, ventricular weight, and cardiac proteins were similar in S, SN, and KN groups and were significantly higher in the K group (p less than 0.05). No difference in the basal values of +T and dt were observed among the four groups. The increment in +T after isoproterenol was higher in treated (KN and SN) than in nontreated (K and S) groups (p less than 0.05). In conclusion, nitrendipine enhances the contractile response to isoproterenol and reverses the cardiac hypertrophy in the 2K, 1C model.

Animals↗
PubMed1991

Reversible inhibition of a thyroid-specific trans-acting factor by Ras.

Exposure of rat thyroid cells for 1 week to a temperature-sensitive variant of Kirsten murine sarcoma virus (KiMSV) Ras inactivated the thyroglobulin promoter (pTg). Cellular dedifferentiation was paralleled by the loss of the thyroid-specific trans-acting factor, TgTF1, which binds to pTg. When Ras was denatured by shifting cells to 39 degrees C, TgTF1 binding and pTg function recovered rapidly without the synthesis of new protein. TgTF1 could be reactivated in vitro by treating nuclear extracts with protein kinase A. After 4 weeks of exposure to the oncogene, denaturation of Ras no longer restored TgTF1 binding or reactivated pTg. Incubation of nuclear extracts with protein kinase A likewise did not reactivate TgTF1. Cells chronically exposed to Ras did, however, yield differentiated clones after treatment with 5-azacytidine. We suggest that Ras induces dedifferentiation in two sequential steps: (1) Ras reduces PKA activity; TgTF1 (or an auxiliary protein) becomes dephosphorylated, and binding to pTg is abolished. (2) The effects of Ras become imprinted by methylation, possibly of the TgTF1 gene.

Animals↗
PubMed1990

Serum levels of tumour associated glycoprotein (TAG 72) in patients with gynaecological malignancies.

Serum levels of TAG 72 were measured in 726 serum samples from patients with benign and malignant gynaecological conditions in order to evaluate the clinical usefulness of TAG 72 alone or in combination with other tumour markers. Sixty-six per cent of patients with ovarian cancer showed abnormal concentrations of TAG 72 antigen. A good correlation was also found between serial TAG 72 values and the clinical course of disease during chemotherapy and follow-up. In cervical and endometrial cancer abnormal TAG 72 values occurred in 23% and 14% of cases, while none of the patients with breast cancer had abnormal TAG 72 levels. Among patients with benign disease only one out of 12 patients (8%) with benign ovarian tumours and one of 15 patients with uterine fibromyomatosis (7%) showed high TAG 72 serum levels. However, the determination of TAG 72 did not increase the sensitivity of CA 125 and squamous cell carcinoma antigen (SCC), in ovarian and cervical cancer, respectively. The systemic administration of recombinant interferon alpha-2b to 15 patients with ovarian cancer and different basal levels of TAG 72 did not increase serum levels of the antigen.

Adenocarcinoma↗
PubMed1990

Extinction and activation of the thyroglobulin promoter in hybrids of differentiated and transformed thyroid cells.

Thyroglobulin gene expression was repressed in a rat thyroid cell line transformed with Kirsten murine sarcoma virus. Expression of a dominant selectable marker driven by the thyroglobulin promoter was also inhibited. Somatic cell hybridization of transformed and differentiated thyroid cells resulted in extinction of thyroglobulin gene expression. When transformed cells carrying a dominant selectable marker driven by the thyroglobulin promoter were fused to differentiated cells and expression of this marker was selected, we obtained stable hybrid cell lines expressing both the endogenous and the exogenous thyroglobulin promoters. Although the expression of v-ras remained unchanged compared with expression in the parental transformed cells, transformation was suppressed in the hybrid cell lines. The other thyroid differentiation markers, iodide uptake and thyroid-stimulating hormone-dependent growth, were inhibited in all the hybrids tested. We show that activity of the thyroglobulin promoter correlates with the presence of a thyroid nuclear factor that binds the promoter at position -60 from the transcription start site. Loss of this factor accompanies the extinction of thyroglobulin gene expression in hybrids selected for expression of a non-thyroid-specific promoter.

Animals↗
PubMed1990

Sodium intake modulates the development of cardiac hypertrophy in two-kidney, one clip rats.

Sodium homeostasis exerts a powerful influence on the cardiovascular system in normotensive and hypertensive animals. Previous studies indicate that factors other than blood pressure can influence cardiac hypertrophy. In the present experiments, we evaluated the effects of different sodium diets in the two-kidney, one clip hypertension model in the rat. After the renal artery had been clipped, the rats received a normal sodium (177 meq/kg), high sodium (517 meq/kg), and low sodium (7 meq/kg) diet during 4 weeks. The final blood pressure was almost the same in the three groups (normal sodium 170 +/- 12 mm Hg; low sodium 168 +/- 4 mm Hg; and high sodium 162 +/- 7 mm Hg). Sodium restriction significantly reduced the development of cardiac hypertrophy as compared with rats on normal or high sodium diets. Thus, ventricular weight and ventricular weight/body weight ratio were significantly higher in rats subjected to a normal or high sodium diet (p less than 0.01). The hypertrophied hearts of rats on normal and high sodium diets showed a larger increase in the number of cardiac beta-adrenergic receptors than those observed in hearts from low sodium diet, clipped rats. These results show that sodium modulates the development of cardiac hypertrophy in two-kidney, one clip hypertensive rats. Similarly, the cardiac beta-adrenergic receptors appear to be influenced by dietary sodium intake. A possible role of the sympathetic nervous system is suggested.

Animals↗
PubMed1990

Effect of enalaprilic acid on cardiac contractile response to beta-adrenergic stimulation.

Studies in two-kidney--one clip hypertensive rats have demonstrated that long-term treatment with enalapril induced regression of cardiac hypertrophy, but the cardiac contractile response to beta-adrenergic stimulation remained depressed. In the present study, we evaluate the contractile response to beta-adrenergic stimulation of isolated papillary muscle in normal rats with isoproterenol (10(-11) M to 10(-4) M) in the presence of enalaprilic acid (10(-6) M or 10(-4) M) or enalaprilic acid (10(-4) M) and angiotensin II (10(-6) M). Myocardial contractility was characterized by maximal developed tension and maximal rate of rise of tension (+T), and the relaxant effect of isoproterenol by the ratio of (+T), and the maximal velocity of relaxation (-T)(+T/-T ratio). The rest tension (g/mm2) and the cross-sectional area (mm2) were similar in all the muscles studied. Enalaprilic acid (either 10(-6) M or 10(-4) M) in the bath did not induce any change in contractile and relaxation parameters. The increment in +T and -T (expressed as percentage) in response to cumulative doses of isoproterenol (10(-11) M to 10(-4) M) was significantly depressed in the presence of enalaprilic acid (10(-4) M) when compared with control hearts in which only vehicle was added before isoproterenol (p less than 0.05). The addition of angiotensin II after enalaprilic acid (10(-4) M) did not normalize the response in +T and -T. Enalaprilic acid diminishes the contractile response of the papillary muscle to beta-adrenergic stimulation. The inhibition of the local angiotensin II does not seem to be involved in this result.

Adrenergic beta-Agonists↗
PubMed1990

[Effect of alpha methyldopa on heart in renovascular hypertension].

Previous studies from our laboratory, have demonstrated that 21 days after unclipping the decrease in arterial pressure (AP) was followed by a regression of cardiac hypertrophy (CH) and a normalization of contractile response to Isoproterenol (I) stimulation in two kidney one clip (2K1C) hypertension. The purpose in this study was to reexamine the effects of Alpha Methyl Dopa (AMD) treatment on AP, CH and cardiac response to I stimulation in this model. A total of 43 male rats, ten weeks old, were used. In 19 rats a silver clip was placed under ether anaesthesia in the left renal artery (clip group) (K). The remaining 24 animals constituted the control group (C). Twenty one days later, in 9 and in 17 animals from K and C groups, treatment with AMD 100 mg/kg/day per os was started and maintained during the three week-follow-up period (K alpha and C alpha groups). AP was measured twice a week by the tail cuff method and body weight was registered once a week. We defined hypertension when the systolic pressure was 150 mmHg or more. Three weeks after clipping and 21 days after treatment, in the clipped animals, simultaneously with matched controls (C alpha and K alpha) the cardiac response to Isoproterenol stimulation was studied. For this purpose, under pentobarbital anesthesia the carotid artery and the femoral artery and vein were cannulated in order to measure mean arterial pressure (MAP), left ventricular systolic pressure, heart rate (HR) and DP/DT+ Max in basal conditions and after I (0.001, 0.02, 0.04, 0.12 and 0.24 microgram/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Digestive disturbances in shift-workers: a clinical statistical investigation.

In order to give a clarifying contribution about the probable relationship between shift-work and digestive diseases the authors have conducted a clinical and anamnestical investigation on digestive disturbances and alimentary habits of shift-workers comparing them with non shift-workers. The former group of subjects is engaged in very different activities conducted in variable working environments, with shift rhythms which are always disordered, sometime are imposed by the working Companies and sometimes chosen on the basis of personal necessities. The most interesting result of this study is represented by the confirmation of statistical significance among the larger incidence percentage of digestive disturbances between shift and non shift-workers. Moreover, statistical differences have been remarked among the different groups of shift-workers examinated. For these reasons the authors believe that shift-work is per se responsible of digestive diseases in the workers engaged to it and they also think that it is very important to distinguish the kind of shift work which may produce environmental, psychological and motivational differences.

Adaptation, Physiological↗
PubMed1990

Fatal breast rhabdomyosarcoma in a 15 year old primigravida.

A fatal case of rhabdomyosarcoma, occurring in a 15 year old primigravida is described. Difficulties in early and correct diagnosis, the problems of management, and whether this cancer is due to the pregnant condition are discussed. The ethical dilemma is: should the pregnancy be allowed to continue or not, causing delay in the beginning of chemotherapy yet permitting the delivery of a healthy fetus--since the mother was certainly condemned by the widespread diffusion of the rhabdomyosarcoma.

Adolescent↗
PubMed1989

[Carcinoma of the breast and conservative surgical therapy. Current approaches and presentation of a personal case series].

After re-emphasising the concept of breast cancer as a systemic disease whose prognosis depends more on biological activity than the local evolution of the tumour, the paper compares tumour size and axillary lymph node involvement in 2 groups of patients with Stage PT1 and PT2 breast cancer, in order to justify a preference for conservative surgery (QU.A.RT) even for tumours over 2 cm in diameter.

Adult↗
PubMed1989

Reactivation of thyroglobulin gene expression in transformed thyroid cells by 5-azacytidine.

Transformed rat thyroid cells fail to express thyroglobulin. Cells transformed with a Kirsten murine sarcoma virus carrying a temperature-sensitive ras allele lose their transformation phenotype when shifted to the nonpermissive (39 degrees C) temperature. The thyroglobulin promoter, however, remains inactive. Similarly, transfection of these cells with a thyroglobulin promoter fused to a neomycin resistance reporter gene does not produce clones resistant to G418. Treatment of the transfected cells with the DNA demethylating agent 5-azacytidine reactivates the thyroglobulin promoter and yields stable G418-resistant clones. We show that thyroglobulin promoter activity is correlated with the presence of a thyroid-specific nuclear factor, TgTF1. TgTF1 cannot be detected in transformed cells but reappears after treatment with 5-azacytidine at 39 degrees C. Restoration of Ras activity at 33 degrees C leads to the rapid loss of TgTF1 and G418 resistance.

Animals↗
PubMed1989

Protein binding domains of the rat thyroglobulin promoter.

We have previously shown that DNA elements controlling tissue specific expression of the rat thyroglobulin gene extend 170 bp upstream of the cap site and have identified a thyroid specific nuclear factor which binds the promoter in the -60 region (site C). Here we report that the distal portion of the promoter, extending from -160 to -120, contains two contiguous DNA elements (sites A and B) which interact with the same thyroid-specific factor binding to proximal site C. A second nuclear factor, ubiquitously distributed, binds to the distal site A. Transient cotransfection-competition studies show that all the three binding sites A, B and C titrate a trans-acting factor(s) which is necessary for the transcription of the thyroglobulin gene.

Animals↗