[Show abstract][Hide abstract] ABSTRACT: In an effort to identify cell surface targets and single short-chain antibody (scFv) for ovarian cancer therapy, we used a phage display approach to isolate an antibody with high reactivity against ovarian cancer.
A phage scFv library was subjected to panning against human SK-OV-3 ovarian cancer cells. A clone with high reactivity was selected and tested in immunoperoxidase staining on a panel of normal tissues and ovarian carcinoma. Using immunoprecipitation, a differentially expressed band was analyzed by mass spectrometry. The antigen subclass was characterized with reverse transcription-PCR on cDNA library of normal tissues, and 91 ovarian cancer specimens, and correlated with clinicohistopathologic characteristics.
Ninety-six individual scFv clones were screened in ELISA following panning. scFv F7 revealed high reactivity with ovarian cancer cell lines and showed intense staining of 15 fresh ovarian cancer specimens and no staining of a panel of normal tissues. A 40-kDa protein was identified to be translation elongation factor 1alpha1 (EEF1A1; P < 0.05). The expression of EEF1A2, a highly homologous and functionally similar oncogene, was found to be restricted only to the normal tissues of the heart, brain, and skeletal muscle. Aberrant EEF1A2 mRNA expression was found in 21 of 91 (23%) of ovarian cancer specimens and significantly correlated with increased likelihood of recurrence (P = 0.021).
scFv F7 may represent an ovarian cancer-specific antibody against translation EEF1A family of translational factors. We propose that EEF1A2 may be a useful target for therapy of human ovarian cancer.
Clinical Cancer Research 11/2007; 13(19):5889-96. DOI:10.1158/1078-0432.CCR-07-0703 · 8.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Limited information is available on the incidence and characteristics of neutropenic fever (NF) in patients receiving contemporary regimens for epithelial ovarian cancer (EOC). We examined this issue in patients receiving first-line adjuvant chemotherapy with platinum- and paclitaxel-based regimens at a major cancer institute.
Charts of patients with EOC at a single institute from 1998 through 2002 were reviewed. Data were collected on the incidence and duration of NF, duration of hospitalization and fever, cultures, antibiotic and chemotherapy regimen, and type of debulking procedure.
140 patients were treated for EOC. 125 patients received first line chemotherapy. 15 episodes of NF were observed. Mean duration of neutropenia and fever was 2.33 and 3.07 days respectively. 9 of 15 (60%) NF episodes occurred after cycle 1. Cultures were positive in 7 of 15 patients (47%). Organisms most frequently recovered were bowel-derived. 8 patients (53%) had bowel resections, and 15 patients (100%) had radical or supraradical procedures. There was a correlation between incidence of NF and type of procedure (P = 0.01) and stage of EOC (P = 0.04). There was no correlation between NF and elderly age, medical comorbidities, and postoperative complications.
The rate of NF was higher than previously reported. NF occurred most frequently after cycle 1. NF patients were of advanced stage that had undergone more aggressive surgery and had bowel resections. Our data suggest that patients with advanced EOC who undergo more radical procedures should be identified as high risk for developing NF in early cycles.
[Show abstract][Hide abstract] ABSTRACT: OY-TES-1 is a novel target that belongs to the family of 'cancer/testis' (CT) antigens. Our goal was to examine the expression and immunogenicity of OY-TES-1 in epithelial ovarian cancer (EOC) to determine its potential as a target for vaccine therapy. OY-TES-1 expression was determined by one-step reverse transcriptase PCR on 100 EOC samples, 5 EOC cell lines, and a panel of normal tissues. Immunohistochemistry (IHC) was performed on the same panel of EOC tissues. Sera from a sub-group of patients were tested for OY-TES-1 antibody by ELISA. Thymus and leukocytes were weakly positive for OY-TES-1 while the remaining 5 normal tissues were negative. Expression of OY-TES-1 by either RT-PCR and/or IHC was demonstrable in 69/100 (69%) tumors. Humoral immunity to OY-TES-1 was demonstrated in 1/10 (10%) serum samples from patients whose tumors expressed the antigen. The median follow-up of the patient population was 34 months. There was no correlation between antigen expression and stage, grade, histology and survival. OY-TES-1 is expressed in 69% of patients with EOC, is absent from normal ovarian tissue, and a proportion of patients show evidence of a specific humoral immune response. These findings make OY-TES-1 an attractive target for antigen-specific immunotherapy in EOC.
International Journal of Oncology 11/2006; 29(4):903-10. DOI:10.3892/ijo.29.4.903 · 3.03 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Surgery is the cornerstone of management in ovarian cancer. However, in high-risk and elderly patients there is a tendency for less aggressive surgery upfront. The aim of this study was to review cytoreductive surgery, with focus on complications and outcomes in patients with multiple surgical risk factors.
Charts of patients with ovarian cancer from 1998 to 2002 were retrospectively reviewed.
One hundred and forty patients were treated for ovarian cancer. Sixty-three patients (45%) were elderly (> or =65 years), and 69 patients (49%) had comorbidities. Optimal debulking (< or =1 cm) was achieved in 123 patients (88%). There was no significant relation between complications and type of procedure, elderly age, comorbidities, or transfusions. Optimally debulked patients had a significantly longer survival than patients with suboptimal debulking (P < .001).
Aggressive optimal cytoreduction can be achieved in the majority of patients with multiple surgical risk factors and is associated with a low complication rate.
American journal of obstetrics and gynecology 12/2005; 193(6):2077-82. DOI:10.1016/j.ajog.2005.06.074 · 3.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cancer-testis (CT) antigens are expressed in tumors but not normal tissues except the testis and could be targets for vaccine therapy in epithelial ovarian cancer (EOC). A-kinase anchoring protein 3 (AKAP-3) is a novel member of the CT antigen family. The aim of this study was to examine the expression of AKAP-3 in EOC and correlate with clinico-pathologic characteristics.
One step RT-PCR was performed with RNA from normal and ovarian cancer cell lines and 74 epithelial ovarian tumor tissues. AKAP-3-specific PCR product was amplified. The distribution of AKAP-3 expression and clinico-pathologic variables was analyzed. Survival distributions were estimated, and multivariate analyses were performed.
AKAP-3 mRNA expression was demonstrated in 43/74 (58%) of the ovarian cancer specimens. AKAP-3 was expressed in normal testis, but not in other normal tissues. AKAP-3 expression significantly correlated with increased likelihood of residual tumor (P = 0.005), but no increase in the likelihood of recurrence or persistent disease (P = 0.06). Patients with AKAP-3 mRNA expression were found to have a significantly poorer overall survival (median 50 months) compared with patients without AKAP-3 expression (median not reached) (P = 0.007). Multivariate analysis of AKAP-3 expression, residual disease, and response to frontline chemotherapy found response to be the strongest predictor of overall survival (P = 0.012).
Our data demonstrate that AKAP-3 is expressed at high frequency in patients with EOC. Since AKAP-3 demonstrates tumor-restricted expression and appears to be associated with worse overall survival, it could represent an attractive target for antigen-specific immunotherapy in EOC.
[Show abstract][Hide abstract] ABSTRACT: Ovarian cancer is the leading cause of death in women with gynecological malignancies and overall survival for patients with advanced epithelial ovarian cancer (EOC) remains poor. The majority of patients recur after initial treatment. A strategy for improving outcome is to minimise recurrence via targeted therapy in patients after front-line therapy, or more appropriately as consolidation therapy. EOC represents an attractive target because of the biology of the disease and that the bulk of disease occurs in the peritoneal cavity. To initiate targeted therapy, a candidate target must be identified. Innovative approaches via targeted therapy to control metastatic residual EOC are currently under investigation. The targets are molecules and pathways, on which cancer cells depend to proliferate, invade, metastasise and prevent apoptosis. Potential targeted therapies include: proapoptototic therapy, suicide gene therapy, signal transduction, antiangiogenesis, immunotherapy and cytokine therapy. The utilisation of these targets in the clinic demands carefully conducted, well-coordinated but discovery-oriented translational research in the form of clinical trials that can quickly assess alternative strategies or combination of strategies that could result in clinical benefit. Therefore, targeted therapy for epithelial ovarian cancer, especially after complete response to standard regimens, represents a paradigm whose time has come to be nurtured.
[Show abstract][Hide abstract] ABSTRACT: The granular cell tumor (GCT) of vulva is a rare female genital tract tumor.
A 59-year-old female was incidentally noted to have a 1-cm sized lump in her left labium majus that subsequently increased in size to approximately 4 cm. The mass was totally excised under general anesthesia. Her postoperative follow-up was uneventful. Histologic examination of the tumor showed sheets and clusters of infiltrating tumor cells with morphologic features consistent with granular cell tumor.
Although benign and slow growing, it has a tendency for recurrence and can cause morbidity and mortality when presenting with multicentric or multiple organ involvement due to the lack of effective systemic therapy. Therefore, clinicians and pathologists should be aware of its clinical and histopathologic features.