Protein Complex of Fibrinogen Gamma Chain and Complement Factor H in Ovarian Cancer Patient Plasma.

BACKGROUND: In the plasma of an advanced cancer patient, fibrinogen is sometimes increased with possible effects on red blood cells (RBCs). MATERIALS AND METHODS: The plasma fraction deteriorating osmotic resistance of RBCs was separated from a patient's plasma with advanced ovarian cancer by phenyl-sepharose column chromatography and analyzed with gel filtration chromatography. RESULTS: In the plasma fraction, we found a protein reactive against whole fibrinogen with a molecular weight higher than that of intact fibrinogen from a healthy volunteer. The-high molecular weight protein was immunoractive to an antibody against fibrinogen gamma chain but not to an antibody against alpha or beta chain. Complement factor H, identified by N-terminal sequencing of a 150-kDa protein separated from the protein, was also eluted from anti-fibrinogen gamma immunoaffinity column. CONCLUSION: Fibrinogen gamma chain and complement factor H were found to be bound as a protein complex in the plasma of a patient with advanced ovarian cancer.

Zymosan Induces Immune Responses Comparable with Those of Adults in Monocytes, Dendritic Cells, and Monocyte-Derived Dendritic Cells from Cord Blood.

OBJECTIVE: To investigate the differences in toll-like receptor (TLR)-mediated immune responses between human neonates and adults, focusing on the cytokine profiles of monocytes, dendritic cells (DCs), and monocyte-derived DCs (MoDCs) in cord and adult blood. STUDY DESIGN: Purified monocytes, DCs, and MoDCs were stimulated with the following TLR ligands: lipopolysaccharide (TLR4), Pam3CSK4 (TLR1/2), flagellin (TLR5), zymosan (TLR2), polyinosinic:polycytidylic acid (TLR3), imiquimod (TLR7), and CpG (TLR9). Interleukin (IL)-8, IL-6, tumor necrosis factor, IL-1ß, and IL-10 concentrations were analyzed in culture supernatants. RESULTS: Compared with the effects in adult blood, lipopolysaccharide-, Pam3CSK4-, flagellin-, and polyinosinic:polycytidylic acid-stimulated inflammatory cytokine production in cord blood was generally weak in monocytes, comparable in DCs, and elevated in MoDCs. CpG- and imiquimod-stimulated cytokine production in DCs was comparable in cord blood and adult blood, but cytokine production was almost absent in monocytes and MoDCs in both cord blood and adult blood. In contrast, zymosan stimulation produced comparable inflammatory cytokine profiles in the monocytes, DCs, and MoDCs of cord blood and adult blood. CONCLUSION: The immaturity of TLR-mediated innate immunity in neonates depends on monocytes rather than on DCs. Our results indicate that zymosan-mediated TLR2 signaling may be useful for developing a neonatal vaccine adjuvant.

Human Papillomavirus E6 Knockdown Restores Adenovirus Mediated-estrogen Response Element Linked p53 Gene Transfer in HeLa Cells.

The p53 gene is inactivated by the human papillomavirus (HPV) E6 protein in the majority of cervical cancers. Treatment of HeLa S3 cells with siRNA for HPV E6 permitted adenovirus-mediated transduction of a p53 gene linked to an upstream estrogen response element (ERE). Our previous study in non-siRNA treated HHUA cells, which are derived from an endometrial cancer and express estrogen receptor ß, showed enhancing effects of an upstream ERE on adenovirus-mediated p53 gene transduction. In HeLa S3 cells treated with siRNA for HPV E6, adenovirus-mediated transduction was enhanced by an upstream ERE linked to a p53 gene carrying a proline variant at codon 72, but not for a p53 gene with arginine variant at codon 72. Expression levels of p53 mRNA and Coxsackie/adenovirus receptor (CAR) mRNA after adenovirus-mediated transfer of an ERE-linked p53 gene (proline variant at codon 72) were higher compared with those after non-ERE-linked p53 gene transfer in siRNA-treated HeLa S3 cells. Western blot analysis showed lower ß-tubulin levels and comparatively higher p53/ß-tubulin or CAR /ß-tubulin ratios in siRNA-treated HeLa S3 cells after adenovirus-mediated ERE-linked p53 gene (proline variant at codon 72) transfer compared with those in non-siRNA-treated cells. Apoptosis, as measured by annexin V binding, was higher after adenovirus-mediated ERE-linked p53 gene (proline variant at codon 72) transfer compared with that after non-ERE-linked p53 gene transfer in siRNA-treated cells.

Pegylated liposomal doxorubicin for platinum-resistant or refractory Müllerian carcinoma (epithelial ovarian carcinoma, primary carcinoma of Fallopian tube and peritoneal carcinoma): A single-institutional experience.

The aim of the present study was to evaluate the efficacy and safety of pegylated liposomal doxorubicin (PLD) in patients with Müllerian carcinoma treated at our hospital. Nineteen patients with platinum-resistant Müllerian carcinoma were treated with intravenous PLD 50 mg/m(2) every 4 weeks. Tumor response was assessed by MRI following every 2-3 cycles of treatment. The severity of adverse events was assessed according to the Common Terminology Criteria for Adverse Events (v3.0). The best overall responses in the 19 patients were identified as 5 partial responses (PR), 6 stable diseases (SD) and 8 progressive diseases (PD). Response rate was 26.3%. The proportion of patients with CR, PR or SD was 57.9%. The median time to progression was 188.0 days. The median survival time was 381.0 days. Toxicity grades were identified as one grade III hand-foot syndrome, two grade III neutropenia, one grade IV hand-foot syndrome, one grade IV stomatitis and one grade IV neutropenia. The present study confirmed that PLD is an effective drug when administered as a salvage therapy for the treatment of Müllerian carcinoma and is associated with a reduced toxicity profile compared with current therapeutic options.

Expression of the mitotic-arrest deficiency 2 is associated with chemotherapy resistance in ovarian serous adenocarcinoma.

Mitotic-arrest deficiency 2 (MAD2) is a key component of spindle assembly checkpoint (SAC) function; SAC mediates spindle microtubule attachment to kinetochores on chromosomes and chromosomal segregation during mitosis. To determine whether MAD2 expression is associated with chemotherapy resistance in ovarian serous adenocarcinoma, we reviewed tumor samples from 41 cases of ovarian serous adenocarcinoma at Osaka City University Medical School Hospital (Osaka, Japan), 2000-2007. Of the 41 cases, 24 were recurrent and 17 were not recurrent. Expression of MAD2 was investigated in paraffin-embedded sections using a MAD2 antibody. Quantitative analysis of MAD2 expression gave mean weighted scores of 4.3 for the relapsed group and 7.2 for the relapse-free group; the expression was, thus, significantly greater in the relapse-free group compared to the relapsed group (P=0.023). When the 41 cases were classified into low- and high-expression, these classifications showed no significant difference in terms of progression-free survival (P=0.0685), however, overall survival for the low-expression group was significantly shorter than that of the high-expression group (P=0.0188). The present study implies that MAD2 expression levels can indicate sensitivity to anticancer agents, and risk for recurrence.