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The purpose of this study is to determine the applicability of Radio Frequency Identification (RFID) technology and commercial cellular networks to provide an online triage system for handling mass casualty situations. This was tested by a using a pilot system for a simulated mass casualty situation during a military field exercise. The system proved to be usable. Compared to the currently used system, it also dramatically improves the general view of mass casualty situations and enhances medical emergency readiness in a military medical setting. The system can also be adapted without any difficulties by the civilian sector for the management of mass casualty disasters.

Purpose: 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., Experimental Design: 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., Results: 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)., Conclusions: 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.

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.

Currently available serum biomarkers are insufficiently reliable to distinguish patients with epithelial ovarian cancer (EOC) from healthy individuals. Metabonomics, the study of metabolic processes in biologic systems, is based on the use of (1)H-NMR spectroscopy and multivariate statistics for biochemical data generation and interpretation and may provide a characteristic fingerprint in disease. In an effort to examine the utility of the metabonomic approach for discriminating sera from women with EOC from healthy controls, we performed (1)H-NMR spectroscopic analysis on preoperative serum specimens obtained from 38 patients with EOC, 12 patients with benign ovarian cysts and 53 healthy women. After data reduction, we applied both unsupervised Principal Component Analysis (PCA) and supervised Soft Independent Modeling of Class Analogy (SIMCA) for pattern recognition. The sensitivity and specificity tradeoffs were summarized for each variable using the area under the receiver-operating characteristic (ROC) curve. In addition, we analyzed the regions of NMR spectra that most strongly influence separation of sera of EOC patients from healthy controls. PCA analysis allowed correct separation of all serum specimens from 38 patients with EOC (100%) from all of the 21 premenopausal normal samples (100%) and from all the sera from patients with benign ovarian disease (100%). In addition, it was possible to correctly separate 37 of 38 (97.4%) cancer specimens from 31 of 32 (97%) postmenopausal control sera. SIMCA analysis using the Cooman's plot demonstrated that sera classes from patients with EOC, benign ovarian cysts and the postmenopausal healthy controls did not share multivariate space, providing validation for the class separation. ROC analysis indicated that the sera from patients with and without disease could be identified with 100% sensitivity and specificity at the (1)H-NMR regions 2.77 parts per million (ppm) and 2.04 ppm from the origin (AUC of ROC curve = 1.0). In addition, the regression coefficients most influential for the EOC samples compared to postmenopausal controls lie around delta3.7 ppm (due mainly to sugar hydrogens). Other loadings most influential for the EOC samples lie around delta2.25 ppm and delta1.18 ppm. These findings indicate that (1)H-NMR metabonomic analysis of serum achieves complete separation of EOC patients from healthy controls. The metabonomic approach deserves further evaluation as a potential novel strategy for the early detection of epithelial ovarian cancer., ((c) 2004 Wiley-Liss, Inc.)

Epithelial ovarian cancer (EOC) is the leading cause of death from gynecological malignancies in the United States. Most patients with EOC will respond to surgical debulking followed by platinum and paclitaxel based chemotherapy. Unfortunately, the relapse rate within 2 years is more than 70%. The molecular events leading to the development of EOC and the molecular factors that may predict response to treatment are not well established. Such knowledge would not only improve the understanding of the biology of EOC, but may help in the identification of new tumor markers and the design of molecular therapies for EOC. A literature review was conducted using MEDLINE to delineate studies that investigated gene expression in ovarian cancer correlated with outcome. A review is presented of the expression and role of the BRCA1 and 2 genes, p53, amplification of Her2/neu, PIK3CA, AKT2, K-ras, c-myc, BRCA1, p53, p16, and p27 in ovarian cancer. Additionally, a review of the use of microarray technology is presented and its use in determining expression patterns in ovarian cancer. The accumulation of data derived from new technologies, as well as that obtained from well-established methods, has provided new insights into gene expression profiles in EOC. The utilization of novel technologies that allow high throughput analysis of thousands of genes may lead to the development of new biomarkers or novel therapies that are urgently needed in this deadly disease.

SCP-1 is a novel tumor antigen that belongs to the growing family of cancer/testis (CT) antigens, and it is a potential target for immunotherapy. In an effort to determine the expression of SCP-1 in epithelial ovarian cancer (EOC), one-step RT-PCR was performed with RNA from epithelial ovarian tumor tissues and with two normal ovarian surface epithelial cell lines. We used immunohistochemistry (IHC) to investigate SCP-1 expression in paraffin-fixed EOC samples and ELISA to test sera from a subgroup of patients for SCP-1 antibody. SCP-1 was expressed in 15 out of 100 (15%) primary tumors, as determined by RT-PCR. The normal ovarian surface epithelial cell lines were negative for SCP-1 expression, as were a panel of other normal tissues. None of the patients whose tumors were determined to be SCP-1 positive by RT-PCR expressed the antigen by IHC or demonstrated a humoral immune response by ELISA. Tumors that expressed SCP-1 mRNA tended to have a higher grade than those that did not (P = 0.03). There was a significant decrease in survival time (P = 0.004) for patients with SCP-1 mRNA-positive tumors compared to those with SCP-1 mRNA-negative tumors [median 25 mo, 95% confidence interval (CI) 0-56 mo; and median 97 mo, CI 32-162 mo, respectively]. The present study shows that SCP-1 mRNA expression in patients with EOC is associated with a poorer chance of survival. These findings imply that further evaluation of SCP-1 as a potential target for vaccine therapy in EOC is warranted.

Purpose of Review: The vast majority of women diagnosed with ovarian cancer and subsequently treated with debulking surgery and adjuvant chemotherapy will ultimately relapse. As is the case with primary diagnosis, detection of recurrent ovarian cancer is limited due to lack of sensitivity and specificity. Specific guidelines for surveillance of this disease are controversial, partly because evidence to support such guidelines is scant and partly because the management of identified recurrences continues to be of minimal success. Subsequently, whether early detection actually can make a difference is not necessarily made clear in the literature. However, there are advances in radiological and molecular biology technology that may offer new possibilities in cancer surveillance. This review will outline the latest evidence to address their use in ovarian cancer., Recent Findings: Most of the recent literature involving detection of recurrent ovarian cancer addresses the use of positron emission tomography. There are also some data addressing the use of magnetic resonance imaging and computed tomography in this arena. Data pertaining to other modalities such as biological markers are limited. Ca-125 is the accepted assay used for ovarian cancer surveillance, but other options are introduced that may hold promise for the future., Summary: A review of the recent literature concerning ovarian cancer surveillance techniques offers few new definitive avenues. While radiological technology and discoveries in detection assays are noteworthy, their potential impact on surveillance appears to be minimal at this time. Low sensitivity and specificity, along with expense, continue to be limiting factors.

Objective: Heat shock protein 27 (HSP27) is produced in response to pathophysiologic stress in animal cells. The authors have previously shown that HSP27 is an independent prognostic indicator in patients with ovarian carcinoma. The present study was performed to see whether HSP27 remained an independent prognostic indicator with longer follow-up., Methods: One hundred and three consecutive patients with epithelial ovarian carcinoma were studied. Slides were prepared from fresh tissue. HPS27 staining was performed as previously described. Patient records were examined for FIGO stage, grade, histology, level of cytoreduction and survival., Results: One hundred and three patients were followed for a mean of 60 months. Twenty patients had FIGO Stage I disease, four Stage II, 59 Stage III, and 20 Stage IV. Immunohistochemical (IHC) staining for HSP27 was not related to histologic grade, level of cytoreduction or histologic subtype. A statistically significant decrease in HSP27 staining was found to correlate with increased FIGO stage (p = 0.008). Using cox-regression analysis, HSP27 staining (p = 0.025), stage (p = 0.0012), and level of cytoreduction (p < 0.0001) were independent predictors of survival in these patients., Conclusion: Cox-regression analysis found HSP27 to be an independent indicator of prognosis and survival in patients with ovarian carcinoma who had longer follow-up. Decreased HSP27 staining was related to decreased survival. This study confirms the authors' earlier report on the importance of HSP27 as a prognostic indicator in ovarian carcinoma.

Background: Although not fully understood, heat shock proteins (HSP) are well known stress response proteins. The purpose of this analysis was to determine whether staining for HSP27 was different between placentas from pregnancies complicated by severe pre-eclampsia with intrauterine growth restriction (IUGR) as compared to controls., Methods: Sterile placental tissue was collected from ten women whose pregnancies were complicated by severe preeclampsia with IUGR and from ten women with uncomplicated by severe pre-eclampsia with IUGR and from ten women with uncomplicated term pregnancies. The tissue was then stained for HSP27., Results: The median age of the patients was 27 years (mean 27, range 17-37). The median estimated gestational age at delivery was 38 weeks (mean 37, range 29-41). Overall 12 of 20 placentas stained positively for HSP27 (nuclear and/or cytoplasmic). Eight of ten placentas from women with pre-eclampsia and IUGR stained positively for HSP27 (p = 0.046)., Conclusion: HSP27 staining of the placenta is twice as common in patients with severe preeclampsia as compared to patients with normal term gestations. These preliminary results warrant the inauguration of a similar but larger study to examine the significance of these findings.

Cancer-testis (CT) antigens are expressed in a variety of cancers, but not in normal adult tissues, except for germ cells of the testis, and hence appear to be ideal targets for immunotherapy. In an effort to examine the potential of NY-ESO-1 and LAGE-1 CT antigens for immunotherapy in epithelial ovarian cancer (EOC), we examined the expression of these antigens by reverse transcription-PCR (RT-PCR) and immunohistochemistry (IHC) in a large panel of EOC tissues and cell lines. Sera from a subgroup of the patients were tested for NY-ESO-1/LAGE-1 antibody by ELISA. The data indicated that four ovarian cancer cell lines were positive for one or both CT antigens. Expression of NY-ESO-1 in EOC was demonstrated by RT-PCR and/or IHC in 82 of 190 (43%) specimens. NY-ESO-1 expression by IHC ranged from homogeneous to heterogeneous pattern. LAGE-1 mRNA expression was present in 22 of 107 (21%) tumor tissues. Overall, the expression of either NY-ESO-1 or LAGE-1 mRNA was present in 42 of 107 (40%) EOC specimens and coexpression of both antigens was demonstrated in 11% of specimens. Antibody to NY-ESO-1/LAGE-1 was present in 11 of 37 (30%) patients whose tumors expressed either NY-ESO-1 or LAGE-1. Detectable antibodies were present for up to 3 years after initial diagnosis. Although there was no statistically significant relation between expression of NY-ESO-1/LAGE-1 antigen and survival, the data showed aberrant expression of NY-ESO-1 and LAGE-1 by IHC/RT-PCR in a significant proportion of EOC patients. These findings indicate that NY-ESO-1 and LAGE-1 are attractive targets for antigen-specific immunotherapy in EOC.

Objective: Heat shock protein 27 (HSP27) is a relatively small protein produced in response to pathophysiologic stress. The purpose of this study was to determine prospectively whether HSP27 was associated with known prognostic factors in patients with endometrial carcinoma., Methods: One hundred fifty-three consecutive patients with endometrial carcinoma were studied. Slides were prepared from fresh tissue. HSP27 was analyzed using a semiquantitative measurement. Patient records were examined for FIGO stage, grade, depth of myometrial invasion, histology, lymphovascular space invasion, time to recurrence, and survival., Results: The mean follow-up was 53 months (median 56 months, range 30-68 months). Endometrioid tumors showed significantly higher HSP27 staining than nonendometrioid tumors (P = 0.005). Patients alive at the conclusion of this study had significantly higher mean HSP27 staining than patients who were deceased (P < 0.001). Logistic regression revealed HSP27 staining (P = 0.02), FIGO stage (P = 0. 014), and lymphovascular space invasion (P = 0.046) to be independently predictive of survival., Conclusion: HSP27 staining is significantly higher in endometrioid than nonendometrioid tumors. HSP27 staining is an independent prognostic indicator in patients with endometrial carcinoma, the most common gynecologic malignancy in the United States., (Copyright 1999 Academic Press.)

Objective: Heat shock protein 27 (HSP27) is produced in response to pathophysiologic stress in animal cells. The purpose of this study was to determine prospectively whether HSP27 was associated with known prognostic factors as well as survival in patients with epithelial ovarian carcinoma., Methods: Ninety-nine patients with epithelial ovarian carcinoma were studied. Slides were prepared from fresh tissue. Patient records were examined for FIGO stage, grade, histology, level of cytoreduction, and survival., Results: Immunohistochemical staining for HSP27 was not related to histologic grade, level of cytoreduction or histologic subtype. A statistically significant difference in HSP27 staining was found in relation to FIGO stage (P = 0.013). HSP27 staining was found to be an independent predictor of 2-year survival in these patients (P = 0.041)., Conclusion: The level of HSP27 significantly decreases as the FIGO stage increases and is an independent prognostic indicator of survival in patients with epithelial ovarian carcinoma.

Background: A review of literature comparing the survival of patients with clear cell carcinoma of the ovary to patients with serous carcinoma reveals divided opinions. No studies of statistical significance have demonstrated worse survival in a cohort of patients with clear cell carcinoma matched stage for stage with patients with serous carcinoma of the ovary. The purpose of this study was to compare survival in a cohort of clear cell carcinoma patients to a cohort of serous carcinoma patients matched for stage, age, treatment, and cytoreduction., Methods: All cases of clear cell carcinoma and serous carcinoma of the ovary operated on by the gynecology oncology service from January 1, 1981 to December 31, 1989 were evaluated for patient age, length of survival and level of primary cytoreduction, as well as FIGO stage and histology., Results: Twenty-two patients with clear cell carcinoma found in the years noted were compared to a cohort of 22 patients with serous carcinoma matched for stage (I, 18.2%; II, 9.1%; III, 63.6%; IV, 9.1%), age (clear cell carcinoma 58 years, serous carcinoma 60 years (p = 0.330)), and level of primary cytoreduction (optimal in 63.6% of both clear cell carcinoma and serous carcinoma cohorts and non-optimal in 36.4% of both groups). Survival in the clear cell carcinoma cohort (16 months) was worse than in the serous carcinoma cohort (36 months) (p = 0.045)., Conclusion: Patients with clear cell carcinoma have a significantly worse prognosis than patients with serous carcinoma when matched for age, stage, and level of primary cytoreduction.