600 Ranch Rd Lower Umpqua Hospital
Reedsport OR 97467
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miR-1182 inhibits growth and mediates the chemosensitivity of bladder cancer by targeting hTERT. - Biochemical and biophysical research communications
microRNAs (miRNAs) have been demonstrated to contribute to tumor progression and metastasis and proposed to be key regulators of diverse biological processes. In this study, we report that miR-1182 is deregulated in bladder cancer tissues and cell lines. To characterize the role of miR-1182 in bladder cancer cells, we performed functional assays. The overexpression of miR-1182 significantly inhibits bladder cancer cell proliferation, colony formation, and invasion. Moreover, its up-regulation induced cell cycle arrest and apoptosis and mediated chemosensitivity to cisplatin in bladder cancer. Furthermore, a luciferase reporter assay and a rescue experiment indicated that miR-1182 directly targets hTERT by binding its 3'UTR. In conclusion, these results demonstrate that miR-1182 acts as a tumor suppressor and may be a potential biomarker for bladder cancer diagnosis and treatment.Copyright Â© 2016 Elsevier Inc. All rights reserved.
Primary central nervous system extranodal NK/T cell lymphoma, nasal type, with antecedent hemophagocytic syndrome in a child. - Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society
Primary central nervous system (CNS) extranodal natural killer (NK)/T-cell lymphoma, nasal type (NKTCL), is an exceedingly uncommon entity. Here, we present a case of CNS NKTCL that manifested initially as hemophagocytic syndrome 4 months earlier in a 13-year-old girl. Histological examination revealed the cerebellum mass was composed of large-sized and atypical tumor cells, with an angiocentric and angiodestructive growth pattern and prominent necrosis. The tumor cells exhibited marked pleomorphism with conspicuous nucleoli and prominent mitotic activity. Immunohistochemical staining showed the tumor cells were positive for CD45, CD2, CD3Îµ, CD30, CD43, CD56, and granzyme B. Epstein-Barr virus--encoded ribonucleic acid was expressed in almost all of the nuclei of the lymphoma cells. The T-cell receptor Î³ chain gene rearrangement study showed no evidence of a clonal rearrangement. The patient was treated with etoposide and dexamethasone and died a few days after the operation. As far as we know, this case is the 1st pediatric and female patient of primary CNS NKTCL with antecedent hemophagocytic syndrome, which highlights the clinical data and is helpful for the diagnosis of this tumor.
CD117-positive cells and mast cells in adult human cardiac valves--observations and implications for the creation of bioengineered grafts. - Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology
There is no report to date of stem cells in human cardiac valves. We examined their possible presence, number, and distribution in valves removed at cardiac surgery from patients with a variety of underlying valve pathologies.Grossly normal aortic and mitral valves were obtained from live heart transplant patients. Surgically excised valves with rheumatic mitral stenosis, aortic valve age-related degeneration, aortic valve changes of aortoannular ectasia, and mitral valves with myxomatous degeneration were studied. Immunohistochemical and histochemical studies were performed on sequential valve sections, including hematoxylin and eosin, hematoxylin phloxine saffron, Movat pentachrome, toluidine blue, CD31, CD34, and CD117.There were small clusters of CD117-positive cells in the fibrosa and spongiosa of mitral and aortic valves from all groups of valves. Sequential sectioning and staining showed that almost all of these cells were mast cells. However, in the mitral myxomatous valves and the mitral rheumatic valves, there were rare CD117-positive cells that did not have corresponding toluidine blue staining and thus could be valve mesenchymal stem cells.Most of the CD117-positive cells in normal and diseased adult heart valves are mast cells. These valve cells could play a role in valve pathology and injury. A very small number of possible valve stem cells were also identified. It is unlikely that these valve stem cells are sufficient in number to allow isolation and expansion for tissue engineering purposes.
Effects of off-pump versus on-pump coronary artery bypass grafting on function and viability of circulating endothelial progenitor cells. - The Journal of thoracic and cardiovascular surgery
Off-pump coronary artery bypass grafting may result in fewer myocardial and vascular complications than on-pump. Although differences in aortic manipulations likely play a role, the systemic responses of endothelial progenitor cells to both types of operations have not been examined. We sought to examine endothelial progenitor cell characteristics after off-pump versus on-pump coronary artery bypass grafting.Twenty patients undergoing off-pump or on-pump coronary artery bypass grafting were prospectively enrolled and had endothelial progenitor cells isolated and cultured from their peripheral blood before and 24 hours after surgery. Endothelial progenitor cells were identified by fluorescent dual lectin/low-density lipoprotein binding. Their number, phenotype characteristics, proliferation, migratory function, and viability were determined in a blinded fashion.Patient characteristics and numbers of grafts were equivalent. Endothelial progenitor cells had similar phenotypes between groups before and after surgery. Off-pump and on-pump coronary artery bypass grafting resulted in similar increases in endothelial progenitor cell numbers and showed equivalent proliferation activity. However, endothelial progenitor cell migratory function was higher in off-pump patients (25.3 +/- 5.0 vs 5.0 +/- 1.0 cells per high-powered field for off-pump vs on-pump coronary artery bypass grafting, respectively; P = .04). Postoperative endothelial progenitor cell viability adjusted for preoperative baseline was also higher after off-pump than on-pump coronary artery bypass grafting by 72.4% +/- 14.6% (P = .01). Endothelial progenitor cells of on-pump patients were less viable after surgery than before surgery, whereas the reverse was observed in off-pump patients.Both on-pump and off-pump coronary artery bypass grafting elicit mobilization of endothelial progenitor cells into the peripheral blood. On-pump coronary artery bypass grafting, however, impairs the migratory function and viability of these vascular repair cells, which are conversely preserved after off-pump surgery. Further work is necessary to determine whether the function and viability of endothelial progenitor cells correlate with vascular outcomes and whether their therapeutic modulation may one day benefit coronary artery bypass grafting patients.
Lithotripter shockwave-induced enhancement of mouse melanoma lung metastasis: dependence on cavitation nucleation. - Journal of endourology / Endourological Society
To confirm a previous report of metastasis enhancement by lithotripter shockwaves (LSW) and to test the hypothesis that this effect is attributable to cavitation.The metastatic B16-D5 melanoma cell line was implanted on the hind legs of female C57/b16 mice 12 days before tumor treatment. The tumors were treated with 500 LSW in a waterbath arrangement. The effect of augmented cavitation nucleation was tested by intratumor injection of air bubbles or ultrasound contrast agent gas bodies (UCAGB). The primary tumor was surgically removed on day 1 after treatment. The six groups of mice were sham, LSW, sham + air bubbles, LSW + air bubbles, sham + UCAGB, and LSW + UCAGB. Data were collected for the 113 mice that survived at least 25 days. Lung evaluations were performed blind after 2 weeks of bleaching in Fekete's solution.The outcomes of the three sham groups were very similar and indicated that the simple injection of material into the tumor did not increase metastasis. In comparison with the pooled shams, both the LSW + air bubbles and LSW + UCAGB groups had statistically significant increases in metastasis counts. Only the LSW + UCAGB group had a significant increase in incidence of metastasis relative to the pooled shams. The LSW + UCAGB also had significantly reduced survival.Shockwaves can enhance metastasis from tumors, and this effect is attributable to cavitation.
Protein-, gene-, and cell-based therapeutic angiogenesis for the treatment of myocardial ischemia. - Molecular and cellular biochemistry
Therapeutic angiogenesis aims at restoring perfusion to chronically ischemic myocardial territories by using growth factors or cells, without intervening on the epicardial coronary arteries. Despite angiogenesis having received considerable scientific attention over the last decade, it has not yet been shown to provide clinical benefit and is still reserved for patients who have failed conventional therapies. Nevertheless, angiogenesis is a very potent physiologic process involved in the growth and development of every animal and human, and it is likely that its use for therapeutic purposes, once its underlying mechanistic basis is better understood, will one day become an important modality for patients with CAD and other types of organ ischemia. This review summarizes current knowledge in therapeutic angiogenesis research.
Tumor growth reduction and DNA transfer by cavitation-enhanced high-intensity focused ultrasound in vivo. - Ultrasound in medicine & biology
The potential application of high-intensity focused ultrasound (US), HIFU, was investigated for nonthermal gene transfer and tumor ablation. Renal carcinoma (RENCA) tumors were implanted on the hind leg of BALB/c mice and injected with a marker plasmid. Optison US contrast agent was also injected into the tumor (IT) or into the venous (IV) circulation. HIFU at 1.55 MHz was applied to the tumors with guidance from diagnostic US images. One test of transfection was also performed with lithotripter shock waves. In one set of exposures, tumor volume was followed for 4 days and a beta-galactosidase marker plasmid was used for localization of transfected cells. A second set of exposures employed a luciferase marker plasmid for assessing overall transfection after 2 days. Use of 100-ms bursts at 8-MPa peak rarefactional pressure amplitude stopped tumor growth during the 4-day period, compared to a 2.8-fold growth in shams and yielded luciferase expression 34-fold greater than in shams. Longer bursts or higher pressure amplitudes led to decreases in tumor growth, but did not yield increases in transfection. The HIFU results were similar to those of shock waves for cavitation enhanced by IT Optison. These results should aid in optimizing the application of HIFU for nonthermal tumor treatment.
DNA transfer and cell killing in epidermoid cells by diagnostic ultrasound activation of contrast agent gas bodies in vitro. - Ultrasound in medicine & biology
DNA transfer by sonoporation and cell killing in monolayer cells were examined by contrast-aided low-power diagnostic ultrasound (US). Culture chambers with epidermoid cell monolayers were scanned at about 1 mm/s with a 1.5-MHz scan head aimed upward at the chamber in a 37 degrees C water bath. For DNA transfer tests, plasmids coding for green fluorescent protein (GFP) were added to the medium, and GFP expression was assessed by flow cytometry after 2 days. In separate tests, cell killing was determined immediately after treatment. GFP-positive cell counts were 0.4% (0.7% SD) for shams and 3.7% (1.2% SD) of cells for exposure at 2.3 MPa with 2% Optison contrast agent. The fraction of dead cells was 3.4% (1.7% SD) in shams and 28.6% (6.3% SD) in exposed chambers. Both effects increased for increasing Optison concentration and increasing peak rarefactional pressure amplitude. Contrast-aided diagnostic US has a potential therapeutic application for gene transfer, but a trade-off appears to exist with cell killing.
pcDNAL1 genetic immunization can induce specific cell-mediated immune responses in C57BL/6 mice. - Chinese medical journal
To investigate the specific cell-mediated immune efficacy of the an HPV16 prophylactic vaccine.C57BL/6 mice were randomly divided into 3 groups: experimental group I (treated with pcDNA L1), control group II (treated with pcDNA3.1) and control group III (treated with PBS buffer). The mice were immunized three times during a three-week interval. Ten to fourteen days after the third inoculation, a footpad swelling test was used to detect delayed-type hypersensitivity (DTH) responses. Antigen-specific splenocyte proliferation assay and quantitation of IFN-gamma cells in splenocytes were performed by FACS assay.In the experimental group, splenocytes actively proliferated after stimulation with HPV16 VLP, and had developed a markedly larger amount of CD8(+) IFN-gamma(+) cells, which is an index for special CTL. Also, the footpad was significantly thickened upon inoculation with HPV16 VLP.Naked DNA vaccine of HPV16 L1 can induce specific cell-mediated immune responses in mice, which should be considered for evaluation of HPV16 DNA vaccine feasibility.
Lithotripter shock waves with cavitation nucleation agents produce tumor growth reduction and gene transfer in vivo. - Ultrasound in medicine & biology
Cavitation nucleation agents (CNA) can greatly enhance DNA transfer and cell killing for therapeutically useful applications of nonthermal bioeffects of ultrasound (US). Renal carcinoma (RENCA) tumor cells were implanted and grown to about 400 microL tumor volumes on the hind legs of syngeneic Balb/c mice. Before treatment, mice were anesthetized, the tumor region was shaved and depilated, and a DNA plasmid coding for marker proteins was injected into the tumor. Two sets of tests were completed: the first set involved measurement of tumor growth for 4 days and use of a beta-galactosidase marker plasmid for localization of transfection, and the second set involved 2 days of growth and use of a luciferase marker plasmid for assessing overall protein expression. Either saline, Optison US contrast agent, a vaporizing perfluoropentane droplet suspension (SDS) or air bubble was also injected intratumorally at 10% of tumor volume as a CNA. In some tests, droplets or contrast agent were injected IV. Shock waves (SW) were generated from a spark-gap lithotripter at 7.4 MPa peak negative pressure amplitude. For sham exposure, tumor volume increased by a factor of 3.6 in 4 days. With 500-SW treatment, all the CNA reduced 4-day tumor growth about the same amount (to factors of 1.2 to 1.9). Marker gene expression was generally localized to the region around the needle injection path. All the agents, except saline, produced statistically significant increases of 11.8- to 14.6-fold in luciferase expression after 2 days, relative to sham exposure. IV injection of Optison or droplet nucleation agents before SW treatment reduced tumor growth to factors of 1.0 and 0.7, but did not increase transfection. These results demonstrate the efficacy of CNA in vivo and should lead to improved strategies for simultaneous SW tumor ablation and cancer gene therapy.
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600 Ranch Rd Lower Umpqua Hospital Reedsport, OR 97467
600 Ranch Road