Serum soluble interleukin-2 receptors in epithelial ovarian cancer patients

1995 ◽  
Vol 10 (2) ◽  
pp. 75-80 ◽  
Author(s):  
N.A. Pavlidis ◽  
E. Bairaktari ◽  
J. Kalef-Ezra ◽  
C. Nicolaides ◽  
C. Seferiadis ◽  
...  

The levels of soluble interleukin-2 receptors (sIL-R2) were measured in the serum of 52 patients with epithelial ovarian carcinoma as well as in 25 age and sex-matched normal controls. The mean serum level of sIL-2R was increased in 37 patients (71.2%). Comparison of these levels to those of normal controls showed a highly statistically significant difference (p<0.001). Serum sIL-2R levels were not related to histology, clinical stage or the presence of ascites (p-0.58, p=0.32 and p=0.67, respectively), nor did they follow disease activity or response to chemotherapy. However, patients with higher pretreatment sIL-2R levels (more than 1200 U/ml) were found to have a longer survival (p<0.02), possibly explained by the presence of activated lymphocytes and a better immune surveillance. We conclude that the serum level of sIL-2R: a) is elevated in ovarian cancer patients, b) has no relationship with histological subtypes, tumor burden or the presence of ascites, c) cannot serve as a valuable tumor marker for the monitoring of patient treatment, and d) has a prognostic value for survival.

2006 ◽  
Vol 16 (Suppl 1) ◽  
pp. 179-182 ◽  
Author(s):  
M. Ueda ◽  
Y. Terai ◽  
K. Kanda ◽  
M. Kanemura ◽  
M. Takehara ◽  
...  

Single-nucleotide polymorphism at −670 of Fas gene promoter (A/G) was examined in a total of 354 blood samples from normal healthy women and gynecological cancer patients. They consisted of 95 normal, 83 cervical, 108 endometrial, and 68 ovarian cancer cases. Eighty-three patients with cervical cancer had statistically higher frequency of GG genotype and G allele than 95 controls (P= 0.0353 and 0.0278, respectively). There was no significant difference in the genotype or allele prevalence between control subjects and endometrial or ovarian cancer patients. The Fas −670 GG genotype was associated with an increased risk for the development of cervical cancer (OR = 2.56, 95% CI = 1.08–6.10) compared with the AA genotype. The G allele also increased the risk of cervical cancer (OR = 1.60, 95% CI = 1.05–2.43) compared with the A allele. Germ-line polymorphism of Fas gene promoter −670 may be associated with the risk of cervical cancer in a Japanese population.


1990 ◽  
Vol 8 (10) ◽  
pp. 1618-1629 ◽  
Author(s):  
R G Steis ◽  
W J Urba ◽  
L A VanderMolen ◽  
M A Bookman ◽  
J W Smith ◽  
...  

Autologous lymphokine-activated killer (LAK) cells and recombinant human interleukin-2 (rIL-2) were administered intraperitoneally (IP) to 24 patients with malignancies limited to the peritoneal space. Ten patients had ovarian cancer, 12 had colorectal cancer, and one patient each had endometrial carcinoma and primary small-bowel adenocarcinoma. All ovarian cancer patients, three of twelve colorectal cancer patients, and one patient with endometrial carcinoma had received prior therapy. Patients received IL-2 100,000 U/kg every 8 hours intravenously (IV) for 3 days, and 2 days later underwent daily leukapheresis for 5 days. LAK cells were generated in vitro by incubating the peripheral blood mononuclear cells in IL-2 for 7 days and were then administered IP daily for 5 days through a Tenckhoff catheter (Davol, Inc, Cranston, RI) together with IL-2 25,000 U/kg IP every 8 hours. All but one patient completed at least one cycle of therapy. Toxic side effects included minor to moderate hypotension, fever, chills, rash, nausea, vomiting, abdominal pain and distension, diarrhea, oliguria, fluid retention, thrombocytopenia, and minor elevations of liver function tests; all of these rapidly improved after discontinuation of IL-2. One patient had a grand mal seizure, and one suffered a colonic perforation; these were felt to be treatment-related. IP fibrosis developed in 14 patients and limited repeated cyclic administration of this therapy in five patients. Two of 10 (20%) ovarian cancer patients and five of 12 (42%) colorectal cancer patients had laparoscopy- or laparotomy-documented partial responses. We conclude that LAK cells and rIL-2 can be administered IP to cancer patients, resulting in moderate to severe short-term toxicity and modest therapeutic efficacy. Further investigation of this form of adoptive immunotherapy modified to address the problem of IP fibrosis and with lower IP IL-2 doses is justified by these initial results.


Blood ◽  
1993 ◽  
Vol 81 (2) ◽  
pp. 424-429 ◽  
Author(s):  
DP Barton ◽  
DK Blanchard ◽  
B Michelini-Norris ◽  
SV Nicosia ◽  
D Cavanagh ◽  
...  

Abstract This study was undertaken to determine if advanced epithelial ovarian cancer was associated with increased serum and ascitic levels of soluble interleukin-2 receptor alpha (sIL-2R alpha). Serum and ascitic fluid samples from 23 ovarian cancer patients were analyzed for sIL-2R alpha using an enzyme-linked immunosorbent assay and compared with the serum and peritoneal levels in 18 normal females. The samples were analyzed for CA-125 levels using a radioimmunoassay and the total protein was also measured. Normal individuals had low serum levels of sIL-2R alpha (367.5 +/- 44.6 U/mL), with similar levels of sIL-2R alpha in the normal peritoneal fluid (438.6 +/- 48.8 U/mL). In contrast, the serum and ascitic fluid levels in ovarian cancer patients were significantly higher (746.7 +/- 82.9 U/mL, P = .0006; 2,656.7 +/- 373.7 U/mL, P = .00002, respectively). The results for sIL-2R alpha were also significant when the levels were expressed per milligram of total protein. More importantly, in almost every ovarian cancer patient the ascitic sIL-2R alpha level far exceeded the serum level, a pattern also observed for CA-125. There was no correlation between the serum and ascitic sIL-2R alpha levels, or between the serum and ascitic CA-125 levels. Although the serum levels of sIL-2R alpha and CA-125 were elevated in the same patient, overall there was no correlation between the serum sIL-2R alpha and serum CA-125 levels, either when the levels were expressed in absolute units or per milligram of total protein. Similarly, there was no correlation between sIL-2R alpha and CA-125 levels in individual ascitic samples. While CA-125 levels may reflect an independent index of tumor burden, these results suggest that selective accumulation of sIL-2R alpha in the ascites may be one of the factors associated with the known nonresponsiveness of the infiltrating lymphocytes against ovarian carcinoma cells.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 15009-15009
Author(s):  
F. Legge ◽  
V. Salutari ◽  
A. Paglia ◽  
A. Testa ◽  
D. Lorusso ◽  
...  

15009 Background: Cyclooxygenase-2 (COX-2) has been shown to be involved in several steps of ovarian onset and progression and its overepression is associated with a poor chance of response to chemotherapy and poor prognosis in ovarian cancer. Celecoxib, an orally active selective COX-2 inhibitor, has been tested for its ability to potentiate the activity of carboplatin in treatment of heavily pretreated recurrent ovarian cancer patients. Methods: A phase II study was planned, considering the regimen active if at least 12 responses were observed among the 43 enrolled patients. Celecoxib (400 mg/die), and carboplatin (5 AUC) q28 were administered, until progression or unacceptable toxicity. Response was assessed by RECIST and also by Rustin criteria. Results: 34 pts (median age: 60 yrs, range 28–74) and an ECOG performance status (0/1/2) of (21/12/1), were enrolled. 58.8% of patients were platinum resistant (progressing during or < 6 months from primary treatment). Median number of previous chemotherapy regimens was 3 (range 2–6). Currently 27 patients are evaluable for response. The overall response rate (CR and PR) was 25.9% (2 CR, 5 PR) with stabilization of disease in 8 patients (29.6%). Four responses occurred in platinum sensitive and 3 in platinum resistant group Median time to response was 11 weeks (range 9–19) and median duration of response was 23 weeks (range 12–39). According to Rustin criteria 10 patients out of 25 (40%) were considered responsive to treatment (return of CA125 levels to normal level or >50% reduction). Overall, 143 cycles were administered with a median value of 3 cycles (range = 1–10). Moderate/severe toxicities were as follows: G3 anemia occurred in 2.3% cycles, G3 neutropenia in 4.6% cycles, G3 thrombocytopenia in 1.5% cycles, G3/4 gastrointestinal toxicity occurred in 4.6% cycles. Cutaneous diffuse erithema was observed in 2 patients, in both cases recovered with a short period of antihistaminic treatment; 2 cases of hypertension were documented, G2 hypersensitivity reactions during carboplatin infusion were observed in 4 cases. Conclusions: Celecoxib combined with carboplatin is well tolerated and has promising activity as salvage treatment in heavily pretreated recurrent ovarian cancer patients. No significant financial relationships to disclose.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16521-e16521
Author(s):  
F. AbuShain ◽  
P. Escobar ◽  
S. Shahabi ◽  
C. Michener ◽  
R. Drake ◽  
...  

e16521 Background: Small published series suggested that three progressively rising CA-125 values, doubling of CA-125, and an absolute rise of 5 U/mL from the nadir, all while remaining in the normal range were highly associated with disease recurrence. This study aims to validate these proposed criteria in a larger population. Methods: We conducted a retrospective review of the records of patients with stages IIIC and IV epithelial ovarian cancer treated with primary surgery and adjuvant chemotherapy between 1994 and 2006. Only patients who had a complete response to chemotherapy verified by normal CT scan, CA-125 and physical examination were included. Nadir CA-125 level was defined as the first CA-125 measurement after completing chemotherapy. Available CA-125 values from diagnosis to recurrence or to last follow up were collected and evaluated for meeting any of the criteria above. Results: 91 patients with a median age of 59 (42 - 88) met the inclusion criteria. 82 patients had stage IIIC (90%) and 9 patients (10%) had stage IV. 86 patients (94.5%) had papillary serous histology and 88 patients had grade 3 (96.7%) disease. Median follow up was 43.7 months (12.6 - 156). Table 1 shows the number of patients who met any of the above CA-125 criteria in total and divided by the presence or absence of recurrence. There was no statistically significant difference in meeting any of the CA-125 criteria between the recurrence and no recurrence groups. Meeting at least one of the CA-125 criteria had 50% sensitivity, 65% specificity, and 86% positive predictive value for recurrence. The median time to recurrence in patients who met at least one CA-125 criteria was 3.8 months (0.2 - 12.4) and the median follow up time after meeting one of the CA 125 criteria in patients who did not recur was 88.5 months (10.4 - 188) Conclusions: Rising CA-125 levels within the normal range that meet any of the above criteria are highly predictive (86%) of recurrence within 12 months and closer observation is warranted. [Table: see text] No significant financial relationships to disclose.


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