5 results on '"LeRoy SC"'
Search Results
2. Methylome analysis of extreme chemoresponsive patients identifies novel markers of platinum sensitivity in high-grade serous ovarian cancer
- Author
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Tushar Tomar, Nicolette G. Alkema, Leroy Schreuder, Gert Jan Meersma, Tim de Meyer, Wim van Criekinge, Harry G. Klip, Heidi Fiegl, Els van Nieuwenhuysen, Ignace Vergote, Martin Widschwendter, Ed Schuuring, Ate G. J. van der Zee, Steven de Jong, and G. Bea A. Wisman
- Subjects
DNA methylation ,Integrated methylome analysis ,Ovarian cancer ,Platinum-based chemotherapy ,Extreme chemoresponders ,Medicine - Abstract
Abstract Background Despite an early response to platinum-based chemotherapy in advanced stage high-grade serous ovarian cancer (HGSOC), the majority of patients will relapse with drug-resistant disease. Aberrant epigenetic alterations like DNA methylation are common in HGSOC. Differences in DNA methylation are associated with chemoresponse in these patients. The objective of this study was to identify and validate novel epigenetic markers of chemoresponse using genome-wide analysis of DNA methylation in extreme chemoresponsive HGSOC patients. Methods Genome-wide next-generation sequencing was performed on methylation-enriched tumor DNA of two HGSOC patient groups with residual disease, extreme responders (≥18 months progression-free survival (PFS), n = 8) and non-responders (≤6 months PFS, n = 10) to platinum-based chemotherapy. DNA methylation and expression data of the same patients were integrated to create a gene list. Genes were validated on an independent cohort of extreme responders (n = 21) and non-responders (n = 31) using pyrosequencing and qRT-PCR. In silico validation was performed using publicly available DNA methylation (n = 91) and expression (n = 208) datasets of unselected advanced stage HGSOC patients. Functional validation of FZD10 on chemosensitivity was carried out in ovarian cancer cell lines using siRNA-mediated silencing. Results Integrated genome-wide methylome and expression analysis identified 45 significantly differentially methylated and expressed genes between two chemoresponse groups. Four genes FZD10, FAM83A, MYO18B, and MKX were successfully validated in an external set of extreme chemoresponsive HGSOC patients. High FZD10 and MKX methylation were related with extreme responders and high FAM83A and MYO18B methylation with non-responders. In publicly available advanced stage HGSOC datasets, FZD10 and MKX methylation levels were associated with PFS. High FZD10 methylation was strongly associated with improved PFS in univariate analysis (hazard ratio (HR) = 0.43; 95% CI, 0.27–0.71; P = 0.001) and multivariate analysis (HR = 0.39; 95% CI, 0.23–0.65; P = 0.003). Consistently, low FZD10 expression was associated with improved PFS (HR = 1.36; 95% CI, 0.99–1.88; P = 0.058). FZD10 silencing caused significant sensitization towards cisplatin treatment in survival assays and apoptosis assays. Conclusions By applying genome-wide integrated methylome analysis on extreme chemoresponsive HGSOC patients, we identified novel clinically relevant, epigenetically-regulated markers of platinum-sensitivity in HGSOC patients. The clinical potential of these markers in predictive and therapeutic approaches has to be further validated in prospective studies.
- Published
- 2017
- Full Text
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3. Long-term blood product transfusion support for patients with myelodysplastic syndromes (MDS): cost analysis and complications.
- Author
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Gupta P, LeRoy SC, Luikart SD, Bateman A, and Morrison VA
- Subjects
- Costs and Cost Analysis, Humans, Transfusion Reaction, Blood Transfusion economics, Myelodysplastic Syndromes economics, Myelodysplastic Syndromes therapy
- Abstract
Patients with myelodysplastic syndromes (MDS) frequently become dependent on blood transfusions. We analyzed the total transfusion support required, and its complications and cost, following the diagnosis of MDS (total period = 79.7 patient-years) in 50 patients followed at the Minneapolis VA Medical Center. From diagnosis of MDS to transformation to AML or death (the MDS phase), 41 patients (82%) required transfusions. The median numbers of transfused blood products per patient per year of follow-up in the MDS phase were: packed red blood cells (pRBC), 11.1 (range, 0-91.3) units, random donor platelets (RDP), 6.8 (range, 0-581) units, and single donor apheresis platelet packs (SDP): 0 (range, 0-40) collections. In the AML phase (time from diagnosis of secondary AML to death or last follow-up), median transfusion requirements per patient (n = 5) were 24 (range, 8-88) units pRBC, 94 (range, 24-480) units RDP and 3 (range, 0-19) collections of SDP. Overall, 80% of patients required either special processing or selection of blood products, had reactions to blood products or required premedications (specified/complicated transfusions); 94% of all pRBC and 97% of all platelet transfusions were specified/complicated. The median cost of transfusions per patient was $4048 (range, $0-73210) during the MDS phase and $13210 (range, $5288-59010) during the AML phase. During the MDS phase, the median cost was $4877 (range, $0-67050) per patient-year of follow-up; the major proportion of this cost was for pRBC transfusions. Long-term support with frequent transfusions for MDS usually requires specially selected or processed blood products, and is associated with a high incidence of transfusion reactions. This study provides baseline data on the costs of transfusion support for MDS, and can be used for comparing resource utilization and costs of long-term transfusion support (supportive care) with growth factor therapy or disease-modifying modalities such as allogeneic transplantation.
- Published
- 1999
- Full Text
- View/download PDF
4. Vibratory stimulation for treatment of anejaculation in quadriplegic men.
- Author
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Pryor JL, LeRoy SC, Nagel TC, and Hensleigh HC
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- Adult, Female, Humans, Insemination, Artificial, Homologous, Male, Sexual Dysfunction, Physiological etiology, Sperm Count, Sperm Motility, Ejaculation, Quadriplegia complications, Sexual Dysfunction, Physiological therapy, Vibration therapeutic use
- Abstract
Sexual dysfunction and infertility are common problems following spinal cord injury. Most men with complete spinal cord lesions do not ejaculate during coitus. Vibratory stimulation applied to the frenulum of the penis in six quadriplegic male subjects produced ejaculates for intrauterine inseminations. Pregnancies occurred in five of the six partners. Vibratory stimulation is a relatively safe and effective means to produce an ejaculation in men with quadriplegia.
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- 1995
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5. Severe penile erosion after use of a vacuum suction device for management of erectile dysfunction in a spinal cord injured patient. Case report.
- Author
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LeRoy SC and Pryor JL
- Subjects
- Adult, Alprostadil therapeutic use, Cellulitis drug therapy, Cellulitis etiology, Humans, Male, Paraplegia complications, Patient Education as Topic, Penile Diseases etiology, Suction adverse effects, Suction instrumentation, Penile Diseases therapy, Penis injuries, Spinal Cord Injuries complications
- Abstract
We report a case of severe erosion and cellulitis at the base of the penis as a result of vacuum suction device constriction bands left on for 4 hours in a spinal cord injured patient with paraplegia and hypesthesia of the genital area. All patients using vacuum suction devices need to be properly educated regarding usage and risks with adequate follow up; patients with hypesthesias and spinal cord injuries need information specifically related to their decreased or absent level of sensation. Only two out of seven vacuum suction device brochures reviewed warn of the risk to patients with decreased sensation in the penis, but none specifically address usage or risks to men with spinal cord injuries.
- Published
- 1994
- Full Text
- View/download PDF
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