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S Bellone

Publications and source records attributed to S Bellone.

At least 73 records · Page 4Linked to original sources
PubMed1999

[Giant benign gastric ulcer penetrating into the liver, pancreas and mesocolon].

Penetration of the liver, pancreas and transverse mesocolon by a giant benign gastric ulcer is relatively uncommon, and literature contains a few reports of this complication. The preoperative histological diagnosis may be difficult or impossible. A 63-year-old female patient with a history of seven months of lack of appetite, asthenia, epigastric pain, a remarkable weight decrease, presenting at physical examination a large, smooth margins, not pulsating, quite fixed abdominal mass, is reported. Echography confirmed the presence of a mass of approximately 14 x 19 cm, with solid and liquid content. Biopsy showed inflammatory elements and cellular detriti. Barium enema showed that the mass compressed the descendent colon, which appeared dislocated. Tumor markers (CEA, CA 19-9, alpha-fetoprotein) where in the normal range. Endoscopy showed a giant angular ulcer whose bottom was represented by necrotic material (after the definitive histological examination it proved to be hepatic tissue). At TC scan of the abdomen, a remarkable thickening of the gastric wall was present. At surgery the stomach appeared increased in volume, with remarkably thickened walls, tenaciously sticking to II and III hepatic segments, to the pancreas and transverse mesocolon. A total gastrectomy was performed because of the depth of the ulcer penetration and the extension of the alteration of the gastric wall, even if the giant gastric ulcer, in the literature, is more frequently benign than malignant.

Anastomosis, Roux-en-Y↗
PubMed1998

Hexarelin, a synthetic GH-releasing peptide, is a powerful stimulus of GH secretion in pubertal children and in adults but not in prepubertal children and in elderly subjects.

GH-releasing peptides (GHRPs) and their non-peptidly mimetics are synthetic molecules which possess marked, dose-related and reproducible GH-releasing effect even after oral administration. Their potent stimulatory effect on GH secretion suggested that GHRP could be useful as provocative test on the diagnosis of GH deficiency. We compared the GH response to the maximal effective dose of Hexarelin (2 micrograms/kg i.v.), an hexapeptide belonging to GHRP family, with that of GHRH (1 microgram/kg i.v.) alone and combined with arginine (ARG, 0.5 g/kg i.v.), which likely acts via inhibition of hypothalamic somatostatin release. We studied 6 prepubertal (4 boys and 2 girls, age 2.6-12.2 yr) and 6 pubertal children with normal short stature (3 boys and 3 girls, age 10.3-14.4 yr) as well as 12 normal young adults (6 males and 6 females, age 22-30 yr) and 12 normal elderly subjects (6 males and 6 females, age 53-79 yr). In prepubertal children, the GH response to HEX (19.0 +/- 4.6 micrograms/l; 611.5 +/- 121.4 micrograms/l/h) was lower than that to GHRH (27.4 +/- 12.7 micrograms/l; 1209.0 +/- 590.9 micrograms/l/h) but this difference did not attain statistical significance. Both these responses were, in turn, lower (p < 0.05) than that to ARG + GHRH (57.9 +/- 15.1 micrograms/l; 2483.6 +/- 696.6 micrograms/l/h). In pubertal children, the GH response to HEX (67.6 +/- 12.7 micrograms/l; 2755.3 +/- 547.3 micrograms/l/h) was higher than that to ARG + GHRH (49.1 +/- 8.9 micrograms/l; 2554.1 +/- 356.6 micrograms/l/h) but this difference did not attain statistical significance; both these responses were, in turn, clearly higher (p < 0.05) than that to GHRH alone (23.1 +/- 7.9 micrograms/l; 1004.8 +/- 214.3 micrograms/l/h). In young adults, the GH response to HEX 60.9 +/- 8.0 micrograms/l; 2401.0 +/- 376.2 micrograms/l/h) was similar to that to ARG + GHRH (68.9 +/- 11.7 micrograms/l; 3035.7 +/- 466.6 micrograms/l/h) and both were clearly higher (p < 0.001) than that to GHRH alone (21.6 +/- 3.6 micrograms/l; 790.0 +/- 137.0 micrograms/l/h). In elderly subjects, the GH response to HEX (22.4 +/- 4.9; 855.0 +/- 199.0 micrograms/l/h) was higher (p < 0.01) than that to GHRH (3.6 +/- 0.8 micrograms/l; 151.8 +/- 24.6 micrograms/l/h) but lower (p < 0.05) than that to ARG + GHRH (48.1 +/- 4.6 micrograms/l; 1758.2 +/- 149.1 micrograms/l/h). In conclusion, GHRPs are a powerful stimulus of GH secretion in pubertal children and young adults only. On the other hand, the age-related variations in the GH response to GHRPs probably limit their reliability for the evaluation of GH releasable pool in prepubertal children and elderly subjects.

Adolescent↗
PubMed1998

Usefulness of IGF-I assay for the diagnosis of GH deficiency in adults.

IGF-I is the best marker of GH secretory status but it also depends on the nutritional status and peripheral hormones such as insulin, glucocorticoids, thyroid hormones and gonadal steroids. Though monitoring IGF-I levels is the best way for evaluating appropriate GH replacement, the usefulness of IGF-I assay in the diagnosis of adult GH deficiency (GHD) is still matter of debate. To clarify this point in a large population of GHD adults (no. = 135, 61 women and 74 men; age, mean +/- SE: 43.8 +/- 1.4 yr, range 20-80 yr) we studied IGF-I levels, their reproducibility and association to peak GH response to GHRH + arginine (GHRH + ARG) test and insulin tolerance test (ITT). The results in GHD were compared with those in a large population of normal subjects (no. = 336, 233 women and 103 men, aged 20-80 yr). Mean IGF-I levels in GHD (77.8 +/- 4.9 micrograms/l) were clearly lower (p < 0.001) than those in normal subjects (170.2 +/- 4.7 micrograms/l). In Childhood Onset GHD (CO-GHD; no. = 40; age, mean +/- SE: 27.8 +/- 1.5 yr) IGF-I levels were lower than those in Adult Onset GHD (AO-GHD; no. = 95, age, mean +/- SE: 50.7 +/- 1.4 yr) (56.6 +/- 9.7 vs 87.1 +/- 5.4 micrograms/l, p < 0.0003). In both GHD and normal subjects IGF-I levels showed good, reproducibility (r = 0.92, p < 0.00001 and r = 0.62, p < 0.00001, respectively). In GHD, but not in normal subjects, IGF-I levels were positively associated to peak GH responses to GHRH + ARG (r = 0.57, p < 0.00001); on the other hand, the GH peak after ITT was not associated to IGF-I in GHD. In normal subjects, but not in GHD, IGF-I levels were negatively associated to age (r = -0.60, p < 0.00001). Considering individual IGF-I levels there was a clear overlap between GHD and normal subjects. However, this overlap was strongly dependent on age. In fact, in the third and fourth decade of life 83.6% of GHD had IGF-I levels below the 3rd centile of normal values; on the other hand, in the fifth-sixth decade and in ageing 47% and only 12% of GHD, respectively, had IGF-I levels low for age. In conclusion, our results demonstrate that IGF-I levels represent a reproducible marker of GH status and are reduced more in CO-GHD than in AO-GHD adults. An overlap exists between GHD and normal subjects, however this is small up to the 4th decade of life. Thus, though normal IGF-I levels do not rule out the existence of GHD, up to 40 yr low IGF-I levels strongly point to GHD if malnutrition and liver disease have been ruled out.

Adult↗
PubMed1998

Comparison between insulin-induced hypoglycemia and growth hormone (GH)-releasing hormone + arginine as provocative tests for the diagnosis of GH deficiency in adults.

There is now wide consensus that, within an appropriate clinical context, GH deficiency (GHD) in adults must be shown biochemically by provocative testing of GH secretion and that appropriate cut-off limits have to be defined for each provocative test. Insulin-induced hypoglycemia (ITT) is indicated as the test of choice, and severe GHD, to be treated with recombinant human GH replacement, is defined by a GH peak response to ITT of less than 3 micrograms/L. GHRH + arginine (GHRH + ARG) is one of the most promising tests in alternative to ITT. In fact, it has been reported as a potent, reproducible, and age-independent test and that it is able to distinguish between GHD and normal adults. The aim of the present study was to compare the GH response to ITT and GHRH + ARG in a large group of hypopituitary adults (n = 40; 29 male and 11 female; age: 36.4 +/- 2.1 yr). The third centile limit of the peak GH response to ITT has been reported as 5 micrograms/L, whereas in our lab, that to GHRH + ARG is 16.5 micrograms/L. In hypopituitary adults, the mean peak GH response to ITT (1.5 +/- 0.2 micrograms/L, range: 0.1-8.5 micrograms/L) was lower (P < 0.001) than that to GHRH + ARG (3.0 +/- 0.4 micrograms/L, range 0.1-12.0 micrograms/L), though there was positive correlation (r = 0.61, P < 0.001) between the GH responses to the 2 tests. The peak GH response to GHRH + ARG, but not that to ITT, was positively (though weakly) associated with insulin-like growth factor-I levels (r = 0.35, P < 0.03). Childhood and adult onset GHD patients, as well as patients with single and multiple pituitary insufficiencies, had similar peak GH responses to ITT or GHRH + ARG. Analyzing individual GH responses, 4/40 (10%) of the hypopituitary patients had GH peaks higher than 5 micrograms/L after ITT; moreover, 3 other patients (7%) had GH peaks, after ITT, higher than 3 micrograms/L. On the other hand, after GHRH + ARG, all patients had GH peaks lower than 16.5 micrograms/L, whereas 21/40 (52.5%) had GH peaks higher than 3 micrograms/L. Because 3 micrograms/L is the arbitrary cut-off for ITT, the third centile limit of which is 5 micrograms/L, we arbitrarily considered 9 micrograms/L as the cut-off point for GHRH + ARG. It is noteworthy that 37/40 (92.5%) patients had a GH peak, after GHRH + ARG, below this limit. In conclusion, our present results confirm that the ITT test is a reliable provocative test for the diagnosis of adult GHD, whereas they show that the GHRH + ARG test is, at least, as sensitive as the ITT test (provided that appropriate cut-off limits are considered). Note that even the arbitrary cut-off point below which severe GHD is demonstrated has to be appropriate to the potency of the test.

Adult↗
PubMed1998

[Clear cell renal carcinoma metastatic to the thyroid. A case report].

A case of clear cell renal carcinoma metastatic to the thyroid 5 years after surgical removal of the primary tumor is presented. The differential diagnosis related to cyto-histologic findings, the uncommon occurrence and the unpredictable behaviour of clear cell renal carcinoma are discussed.

Adenocarcinoma, Clear Cell↗
PubMed1997

Is the persistence of isolated GH deficiency in adulthood predicted by anatomical hypothalamic-pituitary alterations?

The aim of this study was to verify the persistence in adulthood of GH deficiency diagnosed in childhood and treated with hGH in childhood and to study whether anatomical hypothalamic-pituitary alterations evaluated by magnetic resonance (MR) imaging could predict it. To this goal, in six GHD adults (3 males and 3 females aged 17.2-24.5 yr, BMI 21.8 +/- 1.3), we studied anterior pituitary hormone response to GHRH (1 microgram/kg iv)+pyridostigmine (120 mg po)+ GnRH (100 micrograms iv) +TRH (400 micrograms iv)+hCRH (100 micrograms iv) as well as brain MR imaging. In childhood, the diagnosis of severe isolated GHD had been done based on auxological findings as well as on GH response < 7 micrograms/L after two classical provocative stimuli. In the present study, hormonal responses showed the persistence of severe isolated GHD in 4 out of 6 patients (peak, mean +/- SEM: 3.8 +/- 0.6, range 2.6-4.8 micrograms/L). In these patients, IGF-I levels were found low or low-normal. In other 2 patients, a clear GH response to stimulation (peak: 51.3 and 43.0 micrograms/L, respectively) together with normal IGF-I levels were found. No other anterior pituitary hormone deficiency was present in all subjects. MR imaging showed pituitary hypoplasia in all patients with persistent GHD; in 2 out of them, pituitary stalk interruption and ectopic neurohypophysis was also present. On the other hand, MR imaging showed normal hypothalamo-pituitary morphology in the 2 subjects with normal somatotrope response. In conclusion, our present data indicate that testing with a potent stimulus such as GHRH+pyridostigmine is a reliable method to assess the persistence of GH deficiency which associates with anatomical hypothalamic-pituitary alterations at the MR imaging. Patients with transient GH deficiency in childhood and normal pituitary GH reserve in adulthood have normal hypothalamic-pituitary MR imaging.

Adolescent↗
PubMed1997

Methionine potentiates both basal and GHRH-induced GH secretion in children.

OBJECTIVE: It is widely accepted that arginine is a potent GH secretagogue in man, probably acting via inhibition of hypothalamic somatostatin release. Although many other amino acids are known to stimulate GH secretion, their effects and mechanisms of action have not been extensively studied in humans. The aim of the present study was to clarify the effect, if any, of methionine (MET) on GH secretion in children with normal short stature (normal height velocity and IGF-1 > 100 micrograms/l). DESIGN: We studied the effect of MET (0.2 g/kg intravenously (i.v.) over 30 min) on both basal and GHRH (1 microgram/kg i.v. at 0 min)-induced GH secretion (group A) comparing its effect with that of arginine (ARG) at low and classical doses 0.2 and 0.5 g/kg i.v. over 30 min) (groups B and C). The effect of the combined administration of MET and ARG (0.5 g/kg i.v. over e0 min) (group D) on GH secretion was also studied. PATIENTS: Thirty-four children (20 male and 14 female, age 12.8-14.0 years), divided into four groups. MEASUREMENTS: Serum Gh was measured in duplicate by immunoradiometric assay. RESULTS: In group A, MET increased basal Gh levels (peak, mean +/- SEM 14.6 +/- 2.6 vs 2.6 +/- 0.6 mU/l; P < 0.01) and potentiated the GH response to 1 microgram/kg i.v. GHRH (78.0 +/- 17.6 vs 41.6 +/0 9.8 mU/I; P < 0.02). In group B, ARG (0.2 g/kg) increased basal GH levels (16.2 +/- 5.2 vs 2.4 +/- 0.6 mU/I; P < 0.03) and potentiated the GH response to GHRH (119.6 +/- 20.4 vs 48.8 +/- 14.2 mU/I; P < 0.01). In group C, ARG (0.5 g/kg) induced a clear GH rise (28.0 +/- 3.8 vs 2.0 +/- 0.6 mU/I; P < 0.001) and potentiated the GH response to GHRH (93.4 +/- 10.0 vs 34.2 +/- 4.6 mU/I; P < 0.001). The GH responses to MET and ARG alone in groups A and B were similar and lower than that to ARG in group C. The GH responses to MET or ARG combined with GHRH in groups A, B and C were similar. In group D MET failed to modify the GH response to 0.5 g/kg i.v. ARG (10.8 +/- 6.4 vs 9.6 +/- 6.0 mU/I). CONCLUSION: Methionine potentiates both basal and GHRH-induced Gh secretion in children as effectively as arginine. As methionine has no interaction with arginine, our data suggest that these amino acids act via a common mechanism.

Adolescent↗
PubMed1997

[Television and eating disorders. Study of adolescent eating behavior].

BACKGROUND: The media, mainly TV, play a significant social and cultural role and may affect the prevalence and incidence of eating disorders such as bulimia and anorexia nervosa. Their influence acts mainly by favoring a tall and thin body as the only fashionable for female adolescents: your social success depends primarily and totally by your physical appearance and you can, (and must), shape your body as you like better. Our research aims t analyze the attitude of adolescent people toward the TV and to investigate on: 1) time spent watching TV programs; 2) the influence of TV on the personal choices of goods to buy; 3) the ideal body images; 4) choice of TV programs. METHODS: Sixty-seven healthy adolescents (36 F-31 M) were included in our study as controls together with 24 female adolescents with eating disorders (DCA) diagnosed according to the DSM-IV and EAT/26 criteria. RESULTS: Our results show a psychological dependence of DCA adolescents from the TV (longer period of time spent watching TV programs, buying attitudes more influenced by TV advertising). The thin and tall body image is preferred by the DCA girls as well as by the controls; however the body appearance and proportions have a predominant and utmost importance only for the eating disorder females. The masculine subjects instead have a preference for a female and masculine opulent body appearance. CONCLUSIONS: To prevent the observed increase in prevalence and incidence of eating disorders among adolescents, it is appropriate to control the messages, myths and false hood propagated by media, TV in particular.

Adolescent↗
PubMed1996

Reliability of provocative tests to assess growth hormone secretory status. Study in 472 normally growing children.

The reliability of provocative stimuli of GH secretion in the diagnosis of GH deficiency is still controversial. Until now, normative values of GH response to various stimuli have not been established properly. In 472 children and adolescents with normal stature (n = 295, height SDS range -1.5 to 1.2) or normal short stature (n = 177, height SDS range -3.7 to -1.8), we studied the GH response to physical exercise, insulin-induced hypoglycemia, arginine (ARG), clonidine, levodopa, glucagon, pyridostigmine (PD), GHRH, PD + GHRH, and ARG + GHRH. The peak GH responses (range) to various stimuli were: 1) physical exercise: 3.0-28.3 micrograms/L; 2) insulin-induced hypoglycemia: 2.7-46.4 micrograms/L; 3) ARG: 0.5-48.4 micrograms/L; 4) clonidine: 3.8-86.0 micrograms/L; 5) levodopa: 1.9-40.0 micrograms/L; 6) glucagon: 1.9-49.5 micrograms/L; 7) PD: 2.5-35.0 micrograms/L; 8) GHRH: 2.7-102.7 micrograms/L; 9)PD + GHRH: 19.6-106.0 micrograms/L; and 10) ARG + GHRH: 19.4-120.0 micrograms/L. Our results show that all conventional stimuli of GH secretion frequently failed to increase GH levels, showing values lower than that arbitrarily assumed, so far, as minimum normal GH peak, i.e. 7 or 10 micrograms/L. When combined with PD or ARG (substances inhibiting hypothalamic somatostatin release), GHRH becomes the most powerful test to explore the secretory capacity of somatotrope cells (the GH response being always higher than 19 micrograms/L). Therefore, only GHRH combined with PD or ARG may be able to clearly differentiate normal children from patients with GH deficiency, though a normal GH response to these tests cannot rule out the existence of GH hyposecretory state because of hypothalamic dysfunction.

Adolescent↗
PubMed1996

Acute administration of recombinant human growth hormone inhibits the somatotrope responsiveness to growth hormone-releasing hormone in childhood.

In adulthood the growth hormone (GH) response to growth hormone-releasing hormone (GHRH) is inhibited by previous acute administration of either GH or GHRH and it is restored by substances that inhibit hypothalamic somatostatin release. Because in children the GH response to GHRH is not affected by previous neurohormone administration, it has been suggested that in childhood a GH increase is not able to trigger the somatostatin-mediated negative GH autofeedback mechanism. To verify this hypothesis, in 25 children (8 girls and 17 boys; 15 prepubertal and 10 in pubertal stages II-IV) with familial short stature (normal height velocity and insulin-like growth factor I levels) we studied the effect of acute i.v. administration of different recombinant human GH doses (group 1, N = 5, 0.06 U/kg; group 2, N = 6, 0.01 U/kg; group 3, N = 7, 0.005 U/kg at - 150 min) or saline on the GH response to GHRH (1 microgram/kg i.v. at 0 min). In another group (N = 7), we studied the effect of 0.005 U/kg iv recombinant human GH or saline on the GH response to GHRH combined with arginine (0.5 g/kg i.v. over 30 min), which likely inhibits hypothalamic somatostatin release. Serum GH increases after recombinant human GH were dose-dependent (GH peak, mean +/- SEM, 171.7 +/- 24.4, 33.3 +/- 3.9 and 21.8 +/- 5.1 micrograms/l, respectively). The administration of recombinant human GH strongly inhibited the GHRH-induced GH rise in all groups (group 1, 7.1 +/- 1.7 vs 23.1 +/- 7.6 micrograms/l, p < 0.05; group 2, 9.5 +/- 2.8 vs 26.9 +/- 8.5 micrograms/l, p < 0.05; group 3, 9.1 +/- 2.7 vs 34.8 +/- 7.2 micrograms/l, p < 0.02). The GH response to arginine + GHRH (56.9 +/- 13.3 micrograms/l) was higher than that to GHRH alone recorded in group 1 (p < 0.005), group 2 (p < 0.01) and group 3 (p < 0.01), while exogenous recombinant human GH failed to inhibit it (45.0 +/- 9.4 micrograms/l). Our results demonstrate that in childhood, as well as in adulthood, recombinant human GH administration inhibits the somatotrope responsiveness to GHRH. This inhibitory effect is likely to be mediated by hypothalamic somatostatin release.

Arginine↗
PubMed1994

[Lymph node myofibroblastoma: report of a submandibular case with peculiar morphologic and immunohistochemical characteristics].

The Authors describe a case of intranodal myofibroblastoma presenting in the submandibular region as a firm, indolent and freely mobile rounded nodule of about 3 cm. in diameter. The nature of this uncommon benign lesion is discussed. The observed histological features are partly different from the cases originally described. A proliferation of moderately pleomorphic spindle cells, which are vimentin and muscle specific actin positive, occupies a large part of a lymph node, sharply separated from the normal tissue. The so called "amianthoid fibres" are however absent and the inflammatory cells are almost exclusively eosinophils, mainly localized at the border between the lesion and the residual lymph node. Some spindle cells also show an unexplained positivity for the S-100 protein. In addition, extranodal extension of inflammation with few spindle cells is present. Such a complex picture has many features in common with the inflammatory pseudotumor of lymph node, another benign cause of lymphadenopathy. For this reason, the Authors suggest the possibility that myofibroblastoma is not a true neoplasm, but, together with the inflammatory pseudotumor, a peculiar type or a different stage of an abnormal lymph node reactivity.

Humans↗
PubMedDate not supplied

Puberty onset in Northern Italy: a random sample of 3597 Italian children.

Entering puberty is one of the most important milestones in life. Studies from around the world have shown that age of pubertal changes onset can vary with race and ethnicity, environmental conditions, geographical location and nutrition. In the last century, the onset of puberty progressively shifted back towards younger ages in several European countries, with a levelling off in the last decades. The aim of our study was to describe the prevalence of secondary sexual characteristics in a group of children living in Northern Italy comparing them with the percentile values published by Tanner in 1976. We enrolled 3496 children drawn from public schools and evaluated height, weight and pubertal stages. The analysis of our data evidenced that the 50th percentile age of puberty onset in both sexes decreased by about 1 yr compared to data published by Tanner. Mean body mass index (BMI) z-score was significantly higher (p = 0.01) in pubertal than in pre-pubertal girls, on the contrary it was higher (p = 0.005) in pre-pubertal than in pubertal boys. In conclusion, our study found that girls and boys of our region are beginning pubertal development about 1 yr earlier than Tanner's British population. Taking into consideration the 3rd percentile age for Tanner's breast stage 2 in girls and testicular volume (TV) of 4 ml in boys, the current internationally used cut-off age for precocious puberty, i.e. 8 yr for girls and 9 yr for boys, can be maintained in our population.

Age Factors↗
PubMedDate not supplied

Ghrelin: a link between eating disorders, obesity and reproduction.

Ghrelin, a 28-amino acid acylated peptide predominantly produced by the stomach, displays strong GH-releasing activity mediated by the hypothalamic-pituitary GH secretagogues (GHS) receptors (GHS-R) which had been shown specific for a family of synthetic, orally active molecules known as GHS. However, ghrelin and GHS, acting on central and peripheral receptors, also exert other actions. These include influence on pituitary functions, orexigenic action, influence on exocrine and endocrine gastro-entero-pancreatic functions, cardiovascular and anti-proliferative effects. In particular, the effect of ghrelin in promoting food intake and modulating energy metabolism strongly suggested that ghrelin has a key role in managing the neuroendocrine and metabolic response to starvation and that could be involved in the pathogenesis and/or in the metabolic and neuro-hormonal alterations of obesity and eating disorders. Although specific alterations in ghrelin secretion and/or action in obesity and anorexia nervosa (AN) have already been reported, the possibility that ghrelin analogues acting as agonists or antagonists has clinical perspectives for treatment of eating disorders presently remains a dream.

Adrenocorticotropic Hormone↗
PubMedDate not supplied

Restoration of tumor specific human leukocyte antigens class I-restricted cytotoxicity by dendritic cell stimulation of tumor infiltrating lymphocytes in patients with advanced ovarian cancer.

Despite the large number of potentially cytotoxic tumor-infiltrating (TIL) and tumor-associated (TAL) lymphocytes accumulated in the peritoneal cavity ascitic fluid and tumor tissue, advanced ovarian cancer is a progressive disease, suggesting that TIL and TAL populations eventually become functionally suppressed in vivo. Dendritic cells (DC) are the most powerful professional antigen presenting cells known in humans and recently, ovarian tumor antigen pulsed DC have been shown to elicit tumor specific human leukocyte antigens (HLA)-class I-restricted cytotoxicity from the peripheral blood of advanced ovarian cancer patients. In this study, we have evaluated the potential of tumor antigen-pulsed fully mature DC stimulation in restoring tumor-specific cytotoxicity in anergic TIL populations from advanced ovarian cancer patients. In addition, we have compared tumor-specific T-cell responses induced by tumor antigen-loaded DC in TIL to those induced in TAL and peripheral blood lymphocytes (PBL). DC stimulation induced powerful cytotoxicity against autologous tumor target cells in TIL-derived CD8+ T-cells from all patients tested, while autologous Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCL) were not lysed. Killing of autologous tumor cells was higher by CD8+ T-cells from TIL compared to PBL and TAL (P < 0.01) and was more strongly inhibited by anti-HLA class I MAb (P < 0.05 compared to PBL and TAL). Phenotypically, all cytotoxic T lymphocyte (CTL) populations were CD3+/CD8+, with variable levels of CD56 expression. Finally, although a marked Type 1 cytokine bias [ie, interferon-gamma/interleukin-4 (IFN-gammahigh/IL-4low)] was observable in all DC-stimulated CD8+ T-cell populations, TIL derived CD8+ T-cells showed a higher percentage of IFN-gamma positive cells compared to TAL and PBL. Taken together, these data show that tumor lysate-pulsed DC can consistently restore strong CD8+ CTL responses from TIL against autologous ovarian cancer cells. DC-stimulated TIL may represent a superior source of tumor-specific CTL for adoptive T-cell immunotherapy for advanced ovarian cancer.

Aged↗