Modulation of microRNA associated with ovarian cancer cells by genistein.

PURPOSE: Role of microRNAs in malignancies is well established due their regulatory role in cellular differentiation, proliferation and cell cycle control. Our purpose was to determine miRNA profiles of serially established ovarian cancer cell lines and the effect of genistein treatment. METHODS: Cell lines (UL-3A, UL-3B) were established from one patient during progression of disease. miRNA profiling was performed in untreated and genistein-treated cells. Estrogen receptors (ER) were studied with real-time polymerase chain reaction (RT-PCR) and Western immunoblotting. In vitro migration and invasion assays were utilized. RESULTS: While 108 miRNAs were expressed equally in both cell lines and their genistein-treated counterparts, an additional 53 miRNAs were differentially expressed. Genistein resulted in induction of ERalpha and ERbeta in ovarian cancer cells. A significant reduction in migration and invasion of UL-3A and UL-3B was demonstrated in genistein-treated cells. CONCLUSION: Common and unique miRNA profiles were demonstrated between the two cell lines, some of which were altered by genistein.

Systematic effects from an ambient-temperature, continuously rotating half-wave plate.

We present an evaluation of systematic effects associated with a continuously rotating, ambient-temperature half-wave plate (HWP) based on two seasons of data from the Atacama B-Mode Search (ABS) experiment located in the Atacama Desert of Chile. The ABS experiment is a microwave telescope sensitive at 145 GHz. Here we present our in-field evaluation of celestial (Cosmic Microwave Background (CMB) plus galactic foreground) temperature-to-polarization leakage. We decompose the leakage into scalar, dipole, and quadrupole leakage terms. We report a scalar leakage of ∼0.01%, consistent with model expectations and an order of magnitude smaller than other CMB experiments have been reported. No significant dipole or quadrupole terms are detected; we constrain each to be <0.07% (95% confidence), limited by statistical uncertainty in our measurement. Dipole and quadrupole leakage at this level lead to systematic error on r ≲ 0.01 before any mitigation due to scan cross-linking or boresight rotation. The measured scalar leakage and the theoretical level of dipole and quadrupole leakage produce systematic error of r < 0.001 for the ABS survey and focal-plane layout before any data correction such as so-called deprojection. This demonstrates that ABS achieves significant beam systematic error mitigation from its HWP and shows the promise of continuously rotating HWPs for future experiments.

Adenoviral-mediated gene therapy with Ad5CMVp53 and Ad5CMVp21 in combination with standard therapies in human breast cancer cell lines.

Our objective was to determine the efficacy of adenoviral-mediated gene therapy with wild-type p53 or p21 in human breast cancer cells and investigate interactions with radiation and chemotherapy. Two human breast cancer cell lines, MDA-MB-231 and MDA-MB-435, both with p53 mutations, were transduced with adenoviral vectors containing wild-type p53 (Ad5CMV-p53) or p21/WAF1/Cip1 (Ad5CMV-p21), and the effects on growth were determined. Infection was combined with low-dose (1.4 - 3.7 Gy) irradiation to see if this would improve transduction efficiency and enhance numbers of cells killed. Transduction with either vector resulted in expression of p21WAF1/cip1 and growth inhibition, although Ad5CMV-p53 transduction produced greater growth inhibition than did Ad5CMV-p21. The cell lines differed in sensitivity to the vectors. The Ad5CMV-p53 vector in a multiplicity of infection (MOI) of 125 resulted in 50% to 80% inhibition of MDA-MB-231, while MOI 250 of the same vector resulted in 27% inhibition of MDA-MB-435. Infection with Ad5CMV-p21 produced modest growth inhibition in both cell lines (< or = 40% at MOI 200), although protein expression was detected at lower viral doses. Low dose gamma-irradiation (1.4 to 3.7 Gy) was used to try and improve the rate of gene transfer. Modest increases in transduction efficiency and duration of expression of a vector containing beta-galactosidase occurred in irradiated breast cancer cells. Radiation 24 hr before transduction with Ad5CMV-p53 increased the proportions of apoptotic MDA-MB-231 cells. The cells transduced with Ad5CMV-p21 were arrested in G1, yet when they were irradiated before adenoviral transduction, the overexpression of p21 protected the cells from the cytotoxic effects of the radiation. Clonogenic assays showed that Ad5CMV-p21 reduced the sensitivity of MDA-MB-231 to VP-16 and paclitaxel. Combining these drugs with Ad5CMV-p53 did not consistently or significantly decrease clonogenic survival.

Rhinomanometry in children.

During the period January 1982 to December 1985 nasal resistance (NR) was measured by computer-assisted 'head-out' plethysmography in 986 patients aged 4-18 years referred to the Airflow Laboratory at the Hospital for Sick Children, Toronto. Nasal resistance was found to decline with increasing age, and it was elevated in the presence of mucosal swelling, adenoid enlargement and other significant nasal pathology. Studies of variance on the equipment used indicated that in the assessment of NR results of the head-out volume displacement plethysmographic method of active posterior rhinometry were highly reproducible.

Desmoplastic small round cell tumor: report of a case presenting as a primary ovarian neoplasm.

BACKGROUND: Desmoplastic small round cell tumor (DSRCT) is an intra-abdominal malignancy that typically has extensive peritoneal spread at the time of diagnosis. We report a case of DSRCT with involvement of the ovary and omentum as well as an elevated CA-125 level at presentation. CASE: A 23-year-old female presented to another institution with a pelvic mass and a CA-125 level of 140 U/ml. During tumor reductive surgery the right ovary, omentum, and liver were found to be involved. Initial histologic examination favored an undifferentiated small cell carcinoma of the ovary. The patient received two cycles of Taxol and cisplatin chemotherapy and was referred to the University of Texas M. D. Anderson Cancer Center. Upon review of the pathology material at the time of the referral, a diagnosis of DSRCT was made. Despite two additional cycles of chemotherapy, the tumor progressed, and the patient returned home. CONCLUSION: DSRCT may mimic an ovarian primary tumor by presenting with involvement of the ovary and an elevated CA-125 level, and should be included in the differential diagnosis of ovarian neoplasms in young patients.

Modulation of cosmic microwave background polarization with a warm rapidly rotating half-wave plate on the Atacama B-Mode Search instrument.

We evaluate the modulation of cosmic microwave background polarization using a rapidly rotating, half-wave plate (HWP) on the Atacama B-Mode Search. After demodulating the time-ordered-data (TOD), we find a significant reduction of atmospheric fluctuations. The demodulated TOD is stable on time scales of 500-1000 s, corresponding to frequencies of 1-2 mHz. This facilitates recovery of cosmological information at large angular scales, which are typically available only from balloon-borne or satellite experiments. This technique also achieves a sensitive measurement of celestial polarization without differencing the TOD of paired detectors sensitive to two orthogonal linear polarizations. This is the first demonstration of the ability to remove atmospheric contamination at these levels from a ground-based platform using a rapidly rotating HWP.

Retraction of an intraperitoneal chemotherapy port: a case report and literature review.

Delivery of chemotherapy directly into the peritoneal cavity is becoming part of the standard frontline management of patients with optimally cytoreduced ovarian carcinoma. Traditionally, the peritoneal access devices used for this have had relatively high complication rates including infection, blockage, leakage, and difficulties with port access. In order to reduce the risk of infection, we have been using a Bard 9.6F silastic infusaport that does not have a Dacron cuff to secure it into the tissues of the anterior abdominal wall. It has the added advantage of being more easily removed at the end of treatment. We report a case of spontaneous retraction of such a port out of the peritoneal cavity into the subcutaneous tissues. This complication associated with a silastic cuffless port is presented to raise awareness of this possible complication and suggest ways of preventing it.

Cytoreduction and intraperitoneal heated chemotherapy for the treatment of endometrial carcinoma recurrent within the peritoneal cavity.

Our experience with hyperthermic intraperitoneal chemotherapy (IPHC) in conjunction with surgical resection for endometrial cancer recurrent within the abdominal cavity was reviewed. Eligible patients underwent exploratory laparotomy with the aim of resecting disease to < or =5 mm maximum dimension followed immediately by intraperitoneal perfusion of cisplatin (100 mg/m(2)) heated to 41-43 degrees C (105.8-109.4 degrees F) for 1.5 h. Data for analysis was extracted from retrospective chart review. Five patients underwent surgery and IPHC between September 2002 and January 2005 for abdomino-pelvic recurrence. Original stage and histology were 1A papillary serous (1), 1C endometrioid with clear cell features (1), and 1B endometrioid (3). Mean age was 61 (41-75) years, mean prior laparotomies were 1.4 (1-2), and mean chemotherapy agent exposure was 1.6 (0-4). Mean time from initial treatment to surgery and IPHC was 47 (29-66) months. Mean length of surgery was 9.8 (7-11) h after which three patients had no residual disease and two had < or =5 mm disease. The mean duration of hospital stay was 12.6 (6-20) days. Postoperative surgical complications included wound infection with septicemia in one patient. Mean maximum postoperative serum creatinine was 1.02 (0.6-1.70) mg/dL. There was no ototoxicity or neuropathy and no perioperative mortality. No patients have been lost to follow-up. Two are living disease free at 28 and 32 m and two are living with disease at 12 and 36 m. One patient died at 3 m without evidence of cancer. Two patients who had no residual macroscopic disease at the end of surgery are alive at 32 and 36 m. The combination of IPHC with surgery for recurrent endometrial carcinoma is relatively well tolerated. The unexpectedly long survival seen in this cohort supports a phase II trial of IPHC with cisplatin for recurrent endometrial cancer.

Inherited C2 deficiency and systemic lupus erythematosus: studies on a family.

A patient is described in which an inherited defect in the synthesis of C2 complement component coexisted with the disease systemic lupus erythematosus. The family studies show evidence of the autosomal recessive nature of the inheritance of the C2 synthesis defect. Of particular interest was the finding of a great-aunt who also had homozygous C2 deficiency. This great-aunt suffered from discoid lupus erythematosus as well. The occurrence of various autoantibodies in the serum from the family members, the typing for blood groups, HL-A antigens, and some serum protein markers are reported and discussed. The C2 deficiency may be a critical defect in the host defenses to infection that predisposed to the development of autoimmune disease.

Low-grade ovarian cancer in an adolescent patient.

BACKGROUND: Ovarian tumors in the pediatric population are most likely to be of germ cell origin. However, serous tumors have also been reported in adolescent patients. CASE: A 14-year-old girl was diagnosed with stage IIIc low-grade ovarian cancer. Her serum CA-125 was elevated preoperatively and was a marker for recurrence of disease. Five months after completing standard chemotherapy, she developed recurrent disease, which progressed despite hormonal therapy. She then developed toxicity on liposomal doxorubicin (Doxil) and is now receiving hospice care. CONCLUSION: Low-grade serous adenocarcinoma of the ovary can present as advanced disease and should be considered in the differential diagnosis of an ovarian mass in an adolescent patient.

Paget's disease of the vulva: pathology, pattern of involvement, and prognosis.

OBJECTIVE: The aim of this study was to determine prognostic factors and risk factors for recurrence in patients with Paget's disease of the vulva. METHODS: The medical records of 76 patients with a diagnosis of Paget's disease of the vulva were retrospectively reviewed. The diagnosis in each case was confirmed by reviewing the pathology. Patients were then divided into four groups by diagnosis: intraepithelial Paget's disease (IEP) (n = 46), invasive Paget's disease (IP) (n = 9), intraepithelial Paget's disease with underlying adenocarcinoma (IEPUA) (n = 13), and intraepithelial Paget's disease with a coexisting cancer (CCA) (n = 8). Comorbid conditions, location of disease, pathologic diagnosis, method of treatment, margin status, and current status of the patient were evaluated. Descriptive statistical data and univariate analysis were generated using the Statview statistical package. RESULTS: A diagnosis of IEPUA, IP, or CCA predicted a poor survival (P = 0. 0017). Patients who had received chemotherapy or radiation as treatment had a poor survival (P < 0.0001 and 0.0002). Patients with clitoral Paget's disease had a higher incidence of death from disease (P = 0.026). When death from all causes was considered, patients treated with wide local excision (WLE) had a significantly longer survival than patients treated with other more radical treatments (P = 0.02). Risk factors for recurrence included treatment with WLE (P = 0.004). CONCLUSIONS: Patients with IP, IEPUA, or CCA have a poorer prognosis than patients with IEP. Location of Paget's disease is important for prognosis; and patients with clitoral Paget's disease may require more aggressive treatment. WLE is associated with a higher risk of recurrence, but overall patients with WLE tend to survive longer than patients treated more radically.

Survey of female gynecologic oncologists and fellows: balancing professional and personal life.

OBJECTIVE: The aim of this study was to determine how female gynecologic oncologists have dealt with the challenge of combining childbearing and a career in gynecologic oncology and to identify other issues which need to be addressed to improve job satisfaction. METHODS: This survey of female members of the Society of Gynecologic Oncologists and fellows addressed demographics, timing of childbearing, type and cost of childcare, satisfaction with childcare choices, and mentorship. Those without children were queried about plans and reservations. Open-ended questions investigated how female gynecologic oncologists felt job satisfaction could be improved. RESULTS: A total of 65/110 (59%) attendings and 18/36 (50%) fellows responded. Three-fourths of respondents felt that the ideal time to have children was postfellowship. Timing of childbearing caused moderate to severe stress in the personal relationships of 23% of respondents. Median maternity leave was 6 weeks (1-120 days). Seventy-eight percent of female gynecologic oncologists with children employed a nanny. Over half of the respondents estimated weekly childcare cost at over $400. A successful balance between family and full-time practice was the most commonly cited quality of an ideal mentor. Sixty-six percent of the respondents replied to open-ended questions with narrative answers, revealing three major areas for improvement: childcare issues, increased flexibility in hours and duties (clinical, surgical, and research), and the need for more female mentoring. CONCLUSIONS: This survey highlighted the concerns of female gynecologic oncologists about achieving a successful balance between family and professional duties. It also revealed the ways in which women have responded and identified other issues that may be targeted to improve job satisfaction.