orabase and Ovarian-Neoplasms

Long peptides are efficiently presented to both CD4(+) and CD8(+) T cells after intracellular processing by antigen-presenting cells. To investigate the safety and in vivo immunogenicity of synthetic overlapping long peptides (OLP) from a human tumor self-antigen, we conducted a phase I clinical trial with OLP from cancer-testis antigen NY-ESO-1 in various adjuvant combinations.. Twenty-eight patients with advanced ovarian cancer in second or third remission were enrolled sequentially in three cohorts and received at least one vaccination. Patients in Cohort 1 (n = 4) received 1.0 mg OLP, Cohort 2 (n = 13) received OLP in Montanide-ISA-51, and Cohort 3 (n = 11) received OLP + 1.4 mg Poly-ICLC in Montanide-ISA-51 on weeks 1, 4, 7, 10, and 13. Humoral and cellular responses were evaluated by standardized immunomonitoring techniques (ELISA, ELISPOT assay, intracellular cytokine staining, and tetramer staining).. The vaccine was generally well tolerated with injection site reactions and fatigue that resolved. NY-ESO-1-specific antibody and CD8(+) T cells were undetectable after vaccination with OLP alone, but were found in 6 of 13 (46%) and 8 of 13 (62%) patients, respectively, after vaccination with OLP+Montanide, and in 10 of 11 (91%) and 10 of 11 (91%) patients, respectively, after vaccination with OLP+Montanide+Poly-ICLC. NY-ESO-1-specific CD4(+) T cells were detected in all patients with greater frequency and polyclonality when Montanide-ISA-51 was used for vaccination. Inclusion of Poly-ICLC as an adjuvant further accelerated the induction of NY-ESO-1-specific immune responses.. The current study shows that NY-ESO-1 OLP vaccine is safe and rapidly induces consistent integrated immune responses (antibody, CD8(+) and CD4(+)) in nearly all vaccinated patients when given with appropriate adjuvants.

Topics: Adult; Aged; Antibodies; Antigens, Neoplasm; Autoantigens; Cancer Vaccines; Carboxymethylcellulose Sodium; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Female; Follow-Up Studies; Humans; Immunity, Humoral; Middle Aged; Neoplasm Staging; Ovarian Neoplasms; Peptides; Poly I-C; Polylysine; T-Lymphocytes, Regulatory; Treatment Outcome; Vaccines, Subunit

To evaluate the efficacy of a hyaluronate-carboxymethylcellulose (HA-CMC) barrier for prevention of pelvic adhesion formation in women undergoing primary cytoreductive surgery with radical oophorectomy for locally advanced epithelial cancer.. Between 3/1/01 and 3/1/02, all patients undergoing primary surgery for locally advanced FIGO Stage III-IV epithelial ovarian cancer were prospectively offered study enrollment. Radical oophorectomy (en bloc rectosigmoid colectomy) with total pelvic peritonectomy was performed as clinically indicated. Intestinal continuity was reestablished via stapled anastomosis following complete cytoreduction of pelvic disease. The entire pelvic peritoneal defect was covered with subdivided sheets of HA-CMC (6.5 cm x 5.0 cm) using a 'quilting' technique. The abdominal wall incision site was not treated with adhesion preventive measures. At second-look surgery, four-quadrant pelvic (treated area) and abdominal wall (untreated internal control) adhesion scores were assigned using a previously validated scoring system. Statistical analysis for differences in mean pelvic and abdominal wall adhesion scores was performed using Student's t test.. Fourteen patients satisfied all inclusion criteria. Abdominal wall adhesions were noted in 92.9% of patients. In the pelvis, the dorsal peritoneal surfaces were the most common sites of adhesion formation (42.9%). Overall, the mean pelvic (treated) adhesion score was statistically significantly lower (0.91, SD +/- 1.04) than the mean abdominal wall (untreated control) score (5.56, SD +/- 4.55, P = 0.02). There were no instances of intestinal anastomotic leak, and no peri-operative complications directly attributable to HA-CMC were observed.. Placement of a HA-CMC barrier is associated with a significant reduction in the extent and density of pelvic adhesion formation following radical oophorectomy and pelvic peritonectomy for locally advanced epithelial ovarian cancer.

Topics: Abdominal Wall; Aged; Carboxymethylcellulose Sodium; Female; Humans; Hyaluronic Acid; Membranes, Artificial; Middle Aged; Neoplasm Staging; Ovarian Neoplasms; Ovariectomy; Peritoneal Diseases; Prospective Studies; Tissue Adhesions

Topics: Animals; Antineoplastic Agents; Carboxymethylcellulose Sodium; Cell Line, Tumor; Delayed-Action Preparations; Drug Liberation; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Female; Humans; Lung Neoplasms; Mice, Inbred BALB C; Nanoparticles; Ovarian Neoplasms; Podophyllotoxin; Polyethylene Glycols

Endometriosis is a chronic disease of women in the reproductive age, defined as endometrial cells growing outside of the uterine cavity and associated with relapses. Relapses are hypothesized to correlate with incomplete surgical excision or result from nonrandom implantation of new endometrial implants in adjacent peritoneum. Thus, surgical excision could lead to free endometriotic cells or tissue residues, which readhere, grow, and invade into recurrent lesions. Barrier agents are frequently used to prevent postoperative adhesions. We tested if the absorbable cell adhesion barrier gel Intercoat consisting of polyethylene oxide and sodium carboxymethyl cellulose could inhibit cellular adhesion, proliferation, and invasion of primary endometriosis and endometrial cells. Due to an association of endometriosis with ovarian carcinoma, we tested two ovarian carcinoma cell lines. Prior to cell seeding, a drop of the barrier gel was placed in cell culture wells in order to test inhibition of adherence and proliferation or coated over a polymerized collagen gel to assay for prevention of invasion. Results showed that the barrier gel significantly inhibited cell adherence, proliferation, and invasion of endometriosis and endometrial stromal cells as well as ovarian carcinoma cells in culture. Our findings could help to prevent local cell growth/invasion and possible consequent recurrences.

Topics: Adult; Carboxymethylcellulose Sodium; Cell Adhesion; Cell Line, Tumor; Cell Proliferation; Collagen; Endometriosis; Female; Gels; Humans; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Ovarian Neoplasms; Peritoneum; Polyethylene Glycols; Sarcoma, Endometrial Stromal

Hyaluronic acid is a prognostic factor in ovarian cancers. It is also a component of Hyaluronic Acid-Carboxymethyl Cellulose (HA-CMC) barrier, an anti-adhesion membrane widely used during abdominal surgeries in particular for ovarian carcinosis. 70% of patients who undergo ovarian surgery will relapse due to the persistence of cancer cells. This study's objective was to determine the oncological risk from use of this material, in the presence of residual disease, despite the benefit gained by it decreasing post-surgical adhesions in order to provide an unambiguous assessment of its appropriateness for use in ovarian surgical management.. We assessed the effects of HA-CMC barrier on the in vitro proliferation of human ovarian tumor cell lines (OVCAR-3, IGROV-1 and SKOV-3). We next evaluated, in vivo in nude mice, the capacity of this biomaterial to regulate the tumor progression of subcutaneous and intraperitoneal models of ovarian tumor xenografts.. We showed that HA-CMC barrier does not increase in vitro proliferation of ovarian cancer cell lines compared to control. In vivo, HA-CMC barrier presence with subcutaneous xenografts induced neither an increase in tumor volume nor cell proliferation (Ki67 and mitotic index). With the exception of an increased murine carcinosis score in peritoneum, the presence of HA-CMC barrier with intraperitoneal xenografts modified neither macro nor microscopic tumor growth. Finally, protein analysis of survival (Akt), proliferation (ERK) and adhesion (FAK) pathways highlighted no activation on the xenografts imputable to HA-CMC barrier.. For the most part, our results support the lack of tumor progression activation due to HA-CMC barrier. We conclude that the benefits gained from using HA-CMC barrier membrane during ovarian cancer surgeries seem to outweigh the potential oncological risks.

Topics: Absorbable Implants; Animals; Carboxymethylcellulose Sodium; Cell Line, Tumor; Cell Proliferation; Evaluation Studies as Topic; Extracellular Matrix Proteins; Female; Humans; Hyaluronan Receptors; Hyaluronic Acid; Mice, Nude; Neoplasm Transplantation; Ovarian Neoplasms; Signal Transduction; Tissue Adhesions

To evaluate the risk of postoperative complications related to HA-CMC use in patients undergoing optimal cytoreductive surgery for primary and recurrent ovarian, fallopian tube, and peritoneal cancers.. A single institution retrospective review identified all patients undergoing optimal (≤1 cm) cytoreductive surgery for primary or recurrent ovarian, fallopian tube, and peritoneal cancers between 1/95 and 12/08. Operative details and post-operative complications (<30 days) were extracted from the medical record. Fisher's exact test, Mann-Whitney-U, and multiple regression analyses were performed to identify factors, including HA-CMC use, associated with post-operative complications.. Three hundred seventy-five cases were analyzed: HA-CMC was utilized in 168 debulking procedures. There was no difference in the incidence of overall morbidity for patients with HA-CMC compared to those without HA-CMC (OR 1.07; 95% CI: 0.68-1.67). On univariate analysis, application of HA-CMC increased the risk of pelvic abscess (OR 2.66; 95% CI: 1.21-5.86), particularly in the primary surgery setting (OR 4.65; 95% CI: 1.67-12.98) and in patients undergoing hysterectomy (OR 3.36; 95% CI: 1.18-9.53). After controlling for confounding factors using multiple linear regression, HA-CMC use approached statistical significance in predicting an increased risk of pelvic abscess but not major postoperative morbidity.. HA-CMC adhesion barrier placement at the time of optimal cytoreductive surgery for ovarian, fallopian tube, and peritoneal cancer is not associated with major postoperative complications but may be associated with increased risk of pelvic abscess.

Topics: Carboxymethylcellulose Sodium; Fallopian Tube Neoplasms; Female; Gynecologic Surgical Procedures; Humans; Middle Aged; Ovarian Neoplasms; Peritoneal Neoplasms; Retrospective Studies

To determine whether HA-CMC was associated with the development of postoperative intra-abdominal collections in patients undergoing laparotomy for ovarian, fallopian tube, or primary peritoneal malignancies.. We retrospectively identified all laparotomies performed for these malignancies from March 1, 2005 to December 31, 2007. The use of HA-CMC was identified. Laparotomies for malignant bowel obstruction or repair of fistulae were excluded. Intra-abdominal collections, non-infected and infected, were defined as localized intraperitoneal fluid accumulations in the absence of re-accumulating ascites. All other complications were also captured. Appropriate statistical tests were applied using SPSS 15.0.. We identified 219 laparotomies with HA-CMC and 204 without HA-CMC. Upper abdominal resections were performed in 65/219 (30%) HA-CMC cases compared to 39/204 (19%) cases without HA-CMC (P=0.01). The rates of large bowel and/or rectal resections were similar in both cohorts. Intra-abdominal collections were seen in 18/219 (8.2%) HA-CMC cases compared to 5/204 (2.5%) cases without HA-CMC (P=0.009). HA-CMC was independently associated with the diagnosis of a postoperative intra-abdominal collection (P=0.01). All but 2 collections developed in patients undergoing debulking procedures.. HA-CMC appears to be associated with a higher rate of postoperative intra-abdominal collections. This seems to be greatest in patients who are undergoing a debulking procedure.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Ascites; Carboxymethylcellulose Sodium; Cohort Studies; Fallopian Tube Neoplasms; Female; Humans; Hyaluronic Acid; Laparotomy; Membranes, Artificial; Middle Aged; Ovarian Neoplasms; Peritoneal Neoplasms; Retrospective Studies; Tissue Adhesions; Young Adult

Eight patients with advanced ovarian cancer were treated with polyinosinic-polycytidylic lysine carboxymethylcellulose (poly(ICLC]. Toxicity was substantial. No responses were seen in this small group of patients. Further clinical trials utilizing poly(ICLC) at the doses described in patients with advanced ovarian cancer do not appear to be warranted.

Topics: Adult; Aged; Carboxymethylcellulose Sodium; Female; Humans; Methylcellulose; Middle Aged; Ovarian Neoplasms; Pilot Projects; Poly I-C; Polylysine