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1.
Mar Pollut Bull ; 203: 116421, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38713927

ABSTRACT

Intensive aquaculture production generates large amounts of sludge. This waste could be considered as a potential source of nutrients that can be recovered and utilized. Little attention has been paid to nutrient recovery from fish sludge. In this study, bioconversion of sludge was evaluated in lab scale under anaerobic (AN), facultative anaerobic (FA) and aerobic (AE) conditions. After 40 days of fermentation, AN recovered the highest values of dissolved total nitrogen (82.7 mg L-1), while AE showed the highest dissolved total phosphorus (11.8 mg L-1) and the highest reduction of total suspended solids (36.0 %). Microbial analysis showed that AN exhibited a distinct bacterial community than that of FA and AE. Furthermore, C. sorokiniana grown in AN effluents collected after 12 days of fermentation achieved the highest biomass production (1.96 g L-1). These results suggest that AN has the best potential to recover nutrients from sludge for production of C. sorokiniana.


Subject(s)
Chlorella , Microalgae , Nitrogen , Nutrients , Phosphorus , Sewage , Chlorella/growth & development , Animals , Fishes , Aquaculture , Waste Disposal, Fluid/methods , Biomass , Anaerobiosis , Fermentation
2.
PLoS One ; 19(5): e0292978, 2024.
Article in English | MEDLINE | ID: mdl-38728307

ABSTRACT

Endosalpingiosis (ES) and endometriosis (EM) refer to the growth of tubal and endometrial epithelium respectively, outside of their site of origin. We hypothesize that uterine secretome factors drive ectopic growth. To test this, we developed a mouse model of ES and EM using tdTomato (tdT) transgenic fluorescent mice as donors. To block implantation factors, progesterone knockout (PKO) tdT mice were created. Fluorescent lesions were present after oviduct implantation with and without WT endometrium. Implantation was increased (p<0.05) when tdt oviductal tissue was implanted with endometrium compared to oviductal tissue alone. Implantation was reduced (p<0.0005) in animals implanted with minced tdT oviductal tissue with PKO tdT endometrium compared to WT endometrium. Finally, oviductal tissues was incubated with and without a known implantation factor, leukemia inhibitory factor (LIF) prior to and during implantation. LIF promoted lesion implantation. In conclusion, endometrial derived implantation factors, such as LIF, are necessary to initiate ectopic tissue growth. We have developed an animal model of ectopic growth of gynecologic tissues in a WT mouse which will potentially allow for development of new prevention and treatment modalities.


Subject(s)
Endometriosis , Endometrium , Uterus , Animals , Female , Mice , Endometriosis/metabolism , Endometriosis/pathology , Endometriosis/genetics , Uterus/metabolism , Endometrium/metabolism , Leukemia Inhibitory Factor/metabolism , Leukemia Inhibitory Factor/genetics , Secretome/metabolism , Mice, Transgenic , Disease Models, Animal , Fallopian Tubes/metabolism , Progesterone/metabolism , Mice, Knockout , Embryo Implantation/physiology
3.
JMIR Res Protoc ; 13: e48069, 2024 Feb 09.
Article in English | MEDLINE | ID: mdl-38335019

ABSTRACT

BACKGROUND: Ovarian cancer ranks 12th in cancer incidence among women in the United States and 5th among causes of cancer-related death. The typical treatment of ovarian cancer focuses on disease management, with little attention given to the survivorship needs of the patient. Qualitative work alludes to a gap in survivorship care; yet, evidence is lacking to support the delivery of survivorship care for individuals living with ovarian cancer. We developed the POSTCare survivorship platform with input from survivors of ovarian cancer and care partners as a means of delivering patient-centered survivorship care. This process is framed by the chronic care model and relevant behavioral theory. OBJECTIVE: The overall goal of this study is to test processes of care that support quality of life (QOL) in survivorship. The specific aims are threefold: first, to test the efficacy of the POSTCare platform in supporting QOL, reducing depressive symptom burden, and reducing recurrence worry. In our second aim, we will examine factors that mediate the effect of the intervention. Our final aim focuses on understanding aspects of care platform design and delivery that may affect the potential for dissemination. METHODS: We will enroll 120 survivors of ovarian cancer in a randomized controlled trial and collect data at 12 and 24 weeks. Each participant will be randomized to either the POSTCare platform or the standard of care process for survivorship. Our population will be derived from 3 clinics in Texas; each participant will have received some combination of treatment modalities; continued maintenance therapy is not exclusionary. RESULTS: We will examine the impact of the POSTCare-O platform on QOL at 12 weeks after intervention as the primary end point. We will look at secondary outcomes, including depressive symptom burden, recurrence anxiety, and physical symptom burden. We will identify mediators important to the impact of the intervention to inform revisions of the intervention for subsequent studies. Data collection was initiated in November 2023 and will continue for approximately 2 years. We expect results from this study to be published in early 2026. CONCLUSIONS: This study will contribute to the body of survivorship science by testing a flexible platform for survivorship care delivery adapted for the specific survivorship needs of patients with ovarian cancer. The completion of this project will contribute to the growing body of science to guide survivorship care for persons living with cancer. TRIAL REGISTRATION: ClinicalTrials.gov NCT05752448; https://clinicaltrials.gov/study/NCT05752448. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/48069.

4.
Int J Surg Pathol ; 31(5): 651-655, 2023 Aug.
Article in English | MEDLINE | ID: mdl-35946122

ABSTRACT

Epithelioid trophoblastic tumor (ETT) is a rare neoplasm derived from chorionic intermediate trophoblast cells, representing less than 2% of all gestational trophoblastic neoplasms. Classically, ETT presents as a uterine mass in women of reproductive age following a term pregnancy. The time from pregnancy to tumor development varies from months to several years. ETT most often arises in the endometrium, followed by the cervix. Extrauterine ETT are extremely infrequent, with few cases reported in the literature. We report a case of a 41-year-old woman, with history of three term pregnancies who presented with abdominal pain and elevated beta human chorionic gonadotropin (ß-hCG) level, ten years after her last pregnancy. Imaging reported a 3.5 cm adnexal mass, suspicious for ectopic pregnancy. Hysterectomy and mass resection revealed a 4.7 cm, tan-yellow, necrotic mass adjacent to the broad ligament. Histologic evaluation in conjunction with immunohistochemical stains revealed a tumor consistent with ETT. No connection to the endometrium was found grossly or microscopically. DNA fingerprinting analysis revealed the tumor to have two copies of paternal alleles, as seen in molar gestations. One of the primary differential diagnoses for ETT is squamous cell carcinoma due to similar morphologic features. In challenging cases, genetic analysis demonstrating paternally derived genes can establish the diagnosis. In this report, we discuss the challenges in the diagnosis of extrauterine ETT, due to its rarity and highly variable presentation, given that appropriate diagnosis is critical for correct patient management.


Subject(s)
Gestational Trophoblastic Disease , Pregnancy, Ectopic , Trophoblastic Neoplasms , Uterine Neoplasms , Pregnancy , Humans , Female , Adult , Uterine Neoplasms/pathology , Gestational Trophoblastic Disease/pathology , Chorionic Gonadotropin, beta Subunit, Human , Diagnosis, Differential , Trophoblastic Neoplasms/diagnosis , Epithelioid Cells/pathology
5.
Brachytherapy ; 20(1): 284-289, 2021.
Article in English | MEDLINE | ID: mdl-32891569

ABSTRACT

PURPOSE: The COVID-19 pandemic presents serious challenges for brachytherapists, and in the time-sensitive case of locally advanced cervical cancer, the need for curative brachytherapy (BT) is critical for survival. Given the high-volume of locally advanced cervical cancer in our safety-net hospital, we developed a strategy in close collaboration with our gynecology oncology and anesthesia colleagues to allow for completely clinic-based intracavitary brachytherapy (ICBT). METHODS AND MATERIALS: This technical report will highlight our experience with the use of paracervical blocks (PCBs) and oral multimodal analgesia (MMA) for appropriately selected cervical ICBT cases, allowing for completely clinic-based treatment. RESULTS: 18 of 19 (95%) screened patients were eligible for in-clinic ICBT. The excluded patient had significant vaginal fibrosis. 38 of 39 intracavitary implants were successfully transitioned for entirely in-clinic treatment utilizing PCBs and oral MMA (97% success rate). One case was aborted due to inadequate analgesia secondary to a significantly delayed case start time (PO medication effect diminished). 95% of patients reported no pain at the conclusion of the procedure. The median (IQR) D2cc for rectum and bladder were 64.8 (58.6-70.2) Gy and 84.1 (70.9-89.4) Gy, respectively. Median (IQR) CTV high-risk D90 was 88.0 (85.6-89.8) Gy. CONCLUSIONS: In a multidisciplinary effort, we have successfully transitioned many ICBT cases to the clinic with the use of PCB local anesthesia and oral multimodality therapy in direct response to the current pandemic, thereby mitigating exposure risk to patients and staff as well as reducing overall health care burden.


Subject(s)
Ambulatory Surgical Procedures/methods , Analgesics/therapeutic use , Anesthesia, Local/methods , Anesthesia, Obstetrical/methods , Brachytherapy/methods , Pain, Procedural/prevention & control , Uterine Cervical Neoplasms/radiotherapy , Anti-Anxiety Agents/therapeutic use , Antiemetics/therapeutic use , COVID-19 , Female , Gabapentin/therapeutic use , Humans , Hydromorphone/therapeutic use , Ibuprofen/therapeutic use , Lorazepam/therapeutic use , Organs at Risk , Pain, Procedural/drug therapy , Pandemics , Promethazine/therapeutic use , Radiotherapy Dosage , Rectum , SARS-CoV-2 , Urinary Bladder , Uterine Cervical Neoplasms/pathology
6.
PLoS One ; 15(5): e0232487, 2020.
Article in English | MEDLINE | ID: mdl-32401810

ABSTRACT

Endosalpingiosis, traditionally regarded as an incidental pathological finding, was recently reported to have an association with gynecologic malignancies. To determine the prevalence of endosalpingiosis, we evaluated all benign appearing adnexal lesions using the Sectioning and Extensively Examining-Fimbria (SEE-Fim) protocol, and queried the pathology database for the presence of endosalpingiosis, gynecologic malignancy, endometriosis, Walthard nests, and paratubal cysts. Using the SEE-Fim protocol, the prevalence of endosalpingiosis, endometriosis, Walthard nests, and paratubal cysts were 22%, 45%, 33%, and 42% respectively, substantially higher than previously reported. All lesions were observed to increase with age except endometriosis which increased until menopause then decreased dramatically. Among specimens including ovarian tissue, the prevalence of implantation of at least one lesion type was ubiquitous in patients age 51 and older (93%). The clinical significance of endosalpingiosis should be a continued area of research with larger trials assessing prevalence, factors affecting incidence, and association with malignancy. Our findings contribute to elucidating the origin of ectopic lesions and gynecologic disease risk.


Subject(s)
Fallopian Tube Diseases/epidemiology , Genital Diseases, Female/epidemiology , Adnexal Diseases/epidemiology , Adnexal Diseases/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Child , Choristoma/epidemiology , Choristoma/pathology , Endometriosis/epidemiology , Endometriosis/pathology , Fallopian Tube Diseases/pathology , Fallopian Tubes/pathology , Female , Genital Diseases, Female/pathology , Genital Neoplasms, Female/epidemiology , Genital Neoplasms, Female/pathology , Humans , Middle Aged , Prevalence , Retrospective Studies , Young Adult
7.
Theriogenology ; 151: 58-65, 2020 Jul 15.
Article in English | MEDLINE | ID: mdl-32311601

ABSTRACT

Artificial fertilization is increasingly used in aquaculture, mostly applying short-term cold stored milt. Large scale cryopreservation of milt could be valuable for increased flexibility and acceleration of breeding progress. The aim of this study was to assess viability, motility and ATP content of sperm from Atlantic salmon as a function of storage time, before and after cryopreservation. The objective was also to investigate whether in vitro parameters were associated with sperm fertilizing ability after cryopreservation. Milt from six mature Atlantic salmon males were collected twice, one week apart. The milt was stored undiluted at 5 °C in cell culture flasks for six days. Samples were taken on days 1, 3 and 6 of storage for cryopreservation. In total, 36 batches were diluted to a standardized sperm concentration of 2 × 109 spermatozoa/mL, filled into 0.5 mL French medium straws and cryopreserved. In vitro analyses were assessed on the same sample for the 72 combinations of male, collection week, days of storage and cold stored or frozen-thawed. Fertilization trials with cryopreserved milt were carried out for all 36 batches in triplicate for each combination of male, collection week, storage time and sperm:egg ratios of either 2 or 4 × 106 sperm per egg, respectively, totally 218 experimental units, including two egg controls. There was a significant influence of storage and collection week on sperm quality parameters, both cold stored and cryopreserved, and cryopreservation had a significant effect on all tested sperm quality parameters. High correlations for cold stored vs cryopreserved samples was demonstrated for ATP content (p < 0.00001), motility and velocity parameters (p < 0.001), but not for viability, straightness and linearity. The overall percentage of fertilization achieved was 73.9 ± 1.7%. Sperm collected in week 2 showed significantly lower fertility when cryopreserved after six days of storage than after 1 or 3 days for sperm to egg ratios of 2 × 106 (p < 0.005), while there was no such effect for milt collected in week 1. Several post-thaw sperm parameters were correlated to fertilization rates, while curvilinear velocity best explained variations in fertilization by modelling. Our results suggest that cryopreservation of Atlantic salmon milt should be performed soon after milt collection to maximize the cryopreserved sperm quality. Fertilization results seems not to be compromised by storage for three days before cryopreservation.


Subject(s)
Cell Survival , Cryopreservation/veterinary , Salmo salar/physiology , Semen Preservation/veterinary , Sperm Motility , Spermatozoa/physiology , Animals , Cell Membrane , Cold Temperature , Fertilization , Freezing , Male , Ovum , Semen Preservation/methods , Specimen Handling
8.
Theriogenology ; 84(3): 413-20, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25922170

ABSTRACT

To make timing of artificial insemination (AI) relative to ovulation less critical, methods for prolonging shelf life of spermatozoa in vivo after AI have been attempted to be developed. Encapsulation of sperm cells is a documented technology, and recently, a technology in which sperm cells are embedded in alginate gel has been introduced and commercialized. In this study, standard processed semen with the Biladyl extender (control) was compared with semen processed by sperm immobilization technology developed by SpermVital AS in a blind field trial. Moreover, in vitro acrosome and plasma membrane integrity was assessed and compared with AI fertility data for possible correlation. Semen from 16 Norwegian Red young bulls with unknown fertility was collected and processed after splitting the semen in two aliquots. These aliquots were processed with the standard Biladyl extender or the SpermVital extender to a final number of 12 × 10(6) and 25 × 10(6) spermatozoa/dose, respectively. In total, 2000 semen doses were produced from each bull, divided equally by treatment. Artificial insemination doses were set up to design a blinded AI regime; 5 + 5 straws from each extender within ejaculates in ten-straw goblets were distributed to AI technicians and veterinarians all over Norway. Outcomes of the inseminations were measured as 56-day nonreturn rate (NRR). Postthaw sperm quality was assessed by flow cytometry using propidium iodide and Alexa 488-conjugated peanut agglutinin to assess the proportion of plasma membrane and acrosome-intact sperm cells, respectively. In total, data from 14,125 first inseminations performed over a 12-month period, 7081 with Biladyl and 7044 with SpermVital semen, were used in the statistical analyses. There was no significant difference in 56-day NRR for the two semen categories, overall NRR being 72.5% and 72.7% for Biladyl and SpermVital, respectively. The flow cytometric results revealed a significant higher level of acrosome-intact live spermatozoa in Biladyl-processed semen compared to SpermVital semen. The results indicate that the level of acrosome-intact live spermatozoa in the AI dose did not affect the 56-day NRR for the two semen processing methods. In conclusion, this study has showed that immobilized spermatozoa provide equal fertility results as standard processed semen when AI is performed in a blinded field trial, although the immobilization procedure caused increased sperm damage evaluated in vitro compared to standard semen processing procedure.


Subject(s)
Cattle , Insemination, Artificial/veterinary , Semen Preservation/veterinary , Acrosome/physiology , Alginates , Animals , Flow Cytometry/veterinary , Insemination, Artificial/methods , Male , Semen Analysis/veterinary , Semen Preservation/methods
9.
Mil Med ; 179(4): e461-2, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24690973

ABSTRACT

A 54-year-old woman with a history of in-utero diethylstilbestrol (DES) exposure, who had a prior hysterectomy for symptomatic leiomyomata and dysmenorrhea, presented for vaginal bleeding. Vaginal biopsies showed a non-clear-cell adenocarcinoma, and the patient was subsequently treated with radiation therapy. We present a case of primary vaginal non-clear-cell adenocarcinoma in a patient with in-utero DES exposure. Continued monitoring of older DES-exposed women for vaginal lesions is warranted because of reported cases of non-clear-cell adenocarcinoma and persistent risk of clear cell adenocarcinoma.


Subject(s)
Adenocarcinoma, Mucinous/chemically induced , Diethylstilbestrol/adverse effects , Vaginal Neoplasms/chemically induced , Adenocarcinoma, Mucinous/pathology , Adenocarcinoma, Mucinous/radiotherapy , Biopsy , Diethylstilbestrol/therapeutic use , Estrogens, Non-Steroidal/adverse effects , Estrogens, Non-Steroidal/therapeutic use , Female , Humans , Hysterectomy , Leiomyoma, Epithelioid/drug therapy , Leiomyoma, Epithelioid/surgery , Middle Aged , Uterine Neoplasms/drug therapy , Uterine Neoplasms/surgery , Vaginal Neoplasms/pathology , Vaginal Neoplasms/radiotherapy
10.
Gynecol Oncol Case Rep ; 8: 14-6, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24567888

ABSTRACT

•Perivascular epithelioid cell tumors (PEComas) are a family of rare, poorly defined mesenchymal tumors of uncertain malignant potential.•Treatment for PEComas has most commonly involved excisional biopsy or surgical resection.•The use of mTOR inhibitors may provide the best medical treatment as well as a fertility-sparing treatment option.

11.
Int J Gynecol Cancer ; 20(6): 1079-81, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20683421

ABSTRACT

BACKGROUND: Many different techniques that require the surgeon to harvest autologous tissue to create a neovagina have been described in the literature. TECHNIQUE: We describe a technique for creating a neovagina with the use of an acellular dermal allograft as a replacement for split-thickness skin graft. Three patients are presented who had a successful creation of a neovagina with this technique. The indications for vaginoplasty include vaginal agglutination from lichen planus, squamous cell carcinoma of the vagina, and vaginal agenesis. CONCLUSION: The creation of a neovagina using an acellular dermal allograft can be successfully accomplished in patients undergoing constructive and exenterative procedures. The use of an acellular dermal allograft decreases operative time and decreases the incidence of postoperative morbidity because harvesting autologous tissue for the neovagina is not required.


Subject(s)
Genitalia, Female/surgery , Plastic Surgery Procedures/methods , Skin Transplantation/methods , Tissue Scaffolds , Female , Follow-Up Studies , Genitalia, Female/pathology , Graft Survival , Gynecologic Surgical Procedures/methods , Humans , Middle Aged , Quality of Life , Sampling Studies , Transplantation, Homologous , Treatment Outcome , Vagina/surgery , Vulva/surgery , Wound Healing/physiology
12.
Obstet Gynecol ; 115(2 Pt 2): 434-436, 2010 Feb.
Article in English | MEDLINE | ID: mdl-20093871

ABSTRACT

BACKGROUND: Multiple viruses have been associated with carcinogenesis in solid-organ transplant patients. Although Epstein-Barr virus (EBV) has been associated with lymphomas in immunocompromised patients, an association with smooth muscle tumors recently has been described. CASE: An EBV immunoglobulin G-positive woman underwent bilateral lung transplant for sarcoidosis. She was placed on immunosuppression and prophylaxis for opportunistic infections. She presented 5 months later with an EBV-positive uterine leiomyosarcoma. Postoperative therapy included a decrease in immunosuppression and antiviral therapy. Recurrence was noted after 1 year; the patient developed sepsis while undergoing chemotherapy and declined further therapy. CONCLUSION: Epstein-Barr virus-associated leiomyosarcoma can occur in the uterus in immunosuppressed patients.


Subject(s)
Herpesvirus 4, Human/isolation & purification , Immunocompromised Host , Leiomyosarcoma/virology , Lung Transplantation/immunology , Neoplasm Recurrence, Local/virology , Uterine Neoplasms/virology , Adult , Fatal Outcome , Female , Humans , Leiomyosarcoma/immunology , Leiomyosarcoma/pathology , Uterine Neoplasms/immunology , Uterine Neoplasms/pathology
13.
Fish Physiol Biochem ; 35(2): 255-72, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19343521

ABSTRACT

This study comprised the results of three different seawater trials using unique combination of techniques to study protease digestive efficiency and growth performance quality to illustrate the effects of light regimes and vaccine types in Atlantic salmon (Salmo salar L.). Fish with higher growth had higher trypsin (T) and chymotrypsin (C) specific activities with higher T/C ratio or slope T/C ratio [calculated from the regression between trypsin (y) and chymotrypsin (x) specific activities] in the pyloric caeca. The T/C ratios indicated fish growth rates over a period of 1-2 months, while the slope T/C ratios indicated fish growth rates at sampling. Adaptation period for adjustment to the new environment of continuous light was 70 days, indicated by the differences in trypsin specific activities and the crossing of slope T/C ratio regressions following with the changes in growth rate directions between the control and the treated group. Vaccine types affected fish vertebral growth, and additional continuous light enhanced the impact of vaccines on fish growth during springtime, indicated by differences in slope T/C ratios. Continuous light stimulated fish growth during winter to spring, when the natural day length was short, without significantly changing white muscle and oocyte qualities in the fish of about 500 g, except for significantly increased white muscle RNA concentration. Continuous light also reduced fish growth rate later during summer, when the natural day length was long, by precedently decreasing the T/C ratio in late spring. Interestingly, plasma levels of free lysine related to tryptic digestion were correlated with trypsin specific activity levels. Continuous light caused higher levels of most free amino acids (FAA) involved in nitrogen metabolism, higher incorporation of essential FAA for protein synthesis, and higher protein turnover rate (free hydroxyproline levels) in both plasma and white muscle. However, continuous light did not affect higher protein content, intracellular buffering capacity and RNA levels in the white muscle of the fish of about 1 kg, probably due to limitation of FAA available for protein synthesis. It is therefore suggested that enhancing fish growth by continuous light stimulation should be accompanied by increasing availability or content of dietary protein (and probably minerals), which in turn would improve the quality of fish growth performance through increasing fillet protein concentration, strengthening vertebral growth, and delaying oocyte development.


Subject(s)
Amino Acids/metabolism , Digestion/physiology , Photoperiod , Salmo salar/physiology , Vaccination/veterinary , Animals , Bacterial Vaccines/administration & dosage , Body Weight , Chymotrypsin/metabolism , Muscle, Skeletal/physiology , Oocytes/physiology , Salmo salar/growth & development , Salmo salar/metabolism
14.
Gynecol Oncol ; 104(2): 422-7, 2007 Feb.
Article in English | MEDLINE | ID: mdl-16996118

ABSTRACT

OBJECTIVE: Oxaliplatin and topotecan have demonstrated activity as single agents against recurrent platinum-sensitive and -resistant ovarian cancer, as well as synergy in vitro. This was a dose-finding study of combination therapy with weekly topotecan and alternating-week oxaliplatin in patients with recurrent epithelial ovarian cancer. METHODS: Eligible patients had a diagnosis of recurrent ovarian or primary peritoneal carcinoma, a performance status of 0-2, and normal bone marrow, renal, and hepatic function. On days 1 and 15 of a 28-day cycle, patients received a fixed dose of oxaliplatin (85 mg/m2) via intravenous infusion. On days 1, 8, and 15, patients received an escalating dose of intravenous topotecan (2.0-4.0 mg/m2). Five dose levels were planned with a minimum cohort of 3 patients at each level. RESULTS: Thirteen patients were enrolled and received a total of 50 cycles of chemotherapy. The maximum tolerated dose was 85 mg/m2 of oxaliplatin and 3.0 mg/m2 of topotecan, and grade 3 neutropenia was the dose-limiting toxicity. Four of nine (44%) evaluable patients had stable disease or a partial response to the drug combination as assessed by cancer antigen-125 levels. CONCLUSIONS: A 28-day schedule of oxaliplatin and topotecan is safe and well tolerated. Because of the in vitro synergy observed between topoisomerase I inhibitors and platinum derivatives and the tolerability reported in the current study, this regimen warrants further investigation.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Ovarian Neoplasms/drug therapy , Adult , Aged , Dose-Response Relationship, Drug , Drug Administration Schedule , Drug Synergism , Female , Humans , Middle Aged , Organoplatinum Compounds/administration & dosage , Organoplatinum Compounds/adverse effects , Ovarian Neoplasms/pathology , Oxaliplatin , Topotecan/administration & dosage , Topotecan/adverse effects
15.
Cancer Res ; 66(17): 8404-12, 2006 Sep 01.
Article in English | MEDLINE | ID: mdl-16951150

ABSTRACT

Ovarian cancer is resistant to the antiproliferative effects of transforming growth factor-beta (TGF-beta); however, the mechanism of this resistance remains unclear. We used oligonucleotide arrays to profile 37 undissected, 68 microdissected advanced-stage, and 14 microdissected early-stage papillary serous cancers to identify signaling pathways involved in ovarian cancer. A total of seven genes involved in TGF-beta signaling were identified that had altered expression >1.5-fold (P < 0.001) in the ovarian cancer specimens compared with normal ovarian surface epithelium. The expression of these genes was coordinately altered: genes that inhibit TGF-beta signaling (DACH1, BMP7, and EVI1) were up-regulated in advanced-stage ovarian cancers and, conversely, genes that enhance TGF-beta signaling (PCAF, TFE3, TGFBRII, and SMAD4) were down-regulated compared with the normal samples. The microarray data for DACH1 and EVI1 were validated using quantitative real-time PCR on 22 microdissected ovarian cancer specimens. The EVI1 gene locus was amplified in 43% of the tumors, and there was a significant correlation (P = 0.029) between gene copy number and EVI1 gene expression. No amplification at the DACH1 locus was found in any of the samples. DACH1 and EVI1 inhibited TGF-beta signaling in immortalized normal ovarian epithelial cells, and a dominant-negative DACH1, DACH1-Delta DS, partially restored signaling in an ovarian cancer cell line resistant to TGF-beta. These results suggest that altered expression of these genes is responsible for disrupted TGF-beta signaling in ovarian cancer and they may be useful as new and novel therapeutic targets for ovarian cancer.


Subject(s)
Gene Expression Profiling , Ovarian Neoplasms/genetics , Transforming Growth Factor beta/physiology , Female , Genes, Reporter , Humans , Neoplasm Staging , Neoplasms, Cystic, Mucinous, and Serous/genetics , Neoplasms, Cystic, Mucinous, and Serous/pathology , Oligonucleotide Array Sequence Analysis , Ovarian Neoplasms/pathology , Polymerase Chain Reaction , RNA, Neoplasm/genetics , RNA, Neoplasm/isolation & purification , Signal Transduction
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