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1.  Enhanced cytotoxic effect of radiation and temozolomide in malignant glioma cells: targeting PI3K-AKT-mTOR signaling, HSP90 and histone deacetylases 
BMC Cancer  2014;14:17.
Despite aggressive treatment with radiation therapy and concurrent adjuvant temozolomide (TMZ), glioblastoma multiform (GBM) still has a dismal prognosis. We aimed to identify strategies to improve the therapeutic outcome of combined radiotherapy and TMZ in GBM by targeting pro-survival signaling from the epidermal growth factor receptor (EGFR).
Glioma cell lines U251, T98G were used. Colony formation, DNA damage repair, mode of cell death, invasion, migration and vasculogenic mimicry as well as protein expression were determined.
U251 cells showing a low level of methyl guanine transferase (MGMT) were highly responsive to the radiosensitizing effect of TMZ compared to T98G cells having a high level of MGMT. Treatment with a dual inhibitor of Class I PI3K/mTOR, PI103; a HSP90 inhibitor, 17-DMAG; or a HDAC inhibitor, LBH589, further increased the cytotoxic effect of radiation therapy plus TMZ in U251 cells than in T98G cells. However, treatment with a mTOR inhibitor, rapamycin, did not discernibly potentiate the radiosensitizing effect of TMZ in either cell line. The mechanism of enhanced radiosensitizing effects of TMZ was multifactorial, involving impaired DNA damage repair, induction of autophagy or apoptosis, and reversion of EMT (epithelial-mesenchymal transition).
Our results suggest possible strategies for counteracting the pro-survival signaling from EGFR to improve the therapeutic outcome of combined radiotherapy and TMZ for high-grade gliomas.
PMCID: PMC3910677  PMID: 24418474
Glioblastoma; Radiosensitization; Temozolomide; Pro-survival signaling
3.  The Revolving Door of Resident Continuity Practice: Identifying Gaps in Transitions of Care 
It is well documented that transitions of care pose a risk to patient safety. Every year, graduating residents transfer their patient panels to incoming interns, yet in our practice we consistently find that approximately 50% of patients do not return for follow-up care within a year of their resident leaving.
To examine the implications of this lapse of care with respect to chronic disease management, follow-up of abnormal test results, and adherence with routine health care maintenance.
Retrospective chart review
We studied a subset of patients cared for by 46 senior internal medicine residents who graduated in the spring of 2008. 300 patients had been identified as high priority requiring follow-up within a year. We examined the records of the 130 of these patients who did not return for care.
Main Measures
We tabulated unaddressed abnormal test results, missed health care screening opportunities and unmonitored chronic medical conditions. We also attempted to call these patients to identify barriers to follow-up.
Key Results
These patients had a total of 185 chronic medical conditions. They missed a total of 106 screening opportunities including mammogram (24), Pap smear (60) and colon cancer screening (22). Thirty-two abnormal pathology, imaging and laboratory test results were not followed-up as the graduating senior intended. Among a small sample of patients who were reached by phone, barriers to follow-up included a lack of knowledge about the need to see a physician, distance between home and our office, difficulties with insurance, and transportation.
This study demonstrates the high-risk nature of patient handoffs in the ambulatory setting when residents graduate. We discuss changes that might improve the panel transfer process.
PMCID: PMC3157520  PMID: 21559852
patient safety; resident continuity practice; transitions of care
5.  The influence of adjuvant radiotherapy on patterns of failure and survivals in uterine carcinosarcoma 
Radiation Oncology Journal  2011;29(4):228-235.
To evaluate the impact of postoperative radiotherapy (PORT) on patterns of failure and survivals in uterine carcinosarcoma patients treated with radical surgery.
Materials and Methods
Between October 1998 and August 2010, 19 patients with stage I-III uterine carcinosarcoma received curative hysterectomy and bilateral salpingo-oophorectomy with or without PORT at Seoul National University Hospital. Their hospital medical records were retrospectively reviewed. PORT and non-PORT groups included 11 and 8 patients, respectively. They were followed for a mean of 22.7 months (range, 7.8 to 126.6 months).
At 5 years, the overall survival rates were 51.9% for entire, 61.4% for PORT, and 41.7% for non-PORT groups, respectively. There was no statistical difference between PORT and non-PORT groups with regard to overall survival (p = 0.682). Seven out of 19 (36.8%) patients showed treatment failures, which all happened within 12 months. Although the predominant failures were distant metastasis in PORT group and loco-regional recurrence in non-PORT group, there was no statistically significant difference in loco-regional recurrence-free survival (LRRFS) (p = 0.362) or distant metastasis-free survival (DMFS) (p = 0.548). Lymph node metastasis was found to be a significant prognostic factor in predicting poor LRRFS (p = 0.013) and DMFS (p = 0.021), while the International Federation Gynecology and Obstetrics (FIGO) stage (p = 0.043) was associated with LRRFS.
Considering that adjuvant radiotherapy after surgical resection was effective to decrease loco-regional recurrence and most treatment failures were distant metastasis, multimodal therapy including surgery, radiotherapy, and chemotherapy might be an optimal treatment for uterine carcinosarcoma patients.
PMCID: PMC3429907  PMID: 22984675
Uterus; Carcinosarcoma; Adjuvant radiotherapy; Treatment failure; Survival
6.  Endovascular management of the patent inferior mesenteric artery in two cases of uncontrolled type II endoleak after endovascular aneurysm repair 
Endovascular aneurysm repair (EVAR) has well documented advantages over traditional open repair and has been widely adopted as the alternative treatment modality for abdominal aortic aneurysm. However, endoleaks specifically type II can be a significant problem with this technique leading to aortic sac expansion and potential rupture. A large number of type II endoleaks are caused by persistent inferior mesenteric artery (IMA) retrograde bleeding. Various methods to try to manage this complication have been previously described. IMA embolization via the marginal artery of Drummond, however, has not been adequately popularized as an alternative less invasive approach to the treatment of type II endoleak.
Case Report:
Two men, ages 77 and 81, underwent uneventful EVAR for 5.5 and 5.0 cm infrarenal abdominal aortic aneurysms, respectively, using Zenith Cook® bifurcated stent grafts. Computed tomography angiography at 1 and 6 months postoperatively demonstrated small type II endoleaks in both cases which were followed clinically. Subsequent follow-up tomography scan at 12 months revealed persistent type II endoleaks related to retrograde filling from the IMA with significant enlargement of the aneurysm sacs. Both patients underwent successful IMA coil embolization via the marginal artery of Drummond.
Percutaneous IMA embolization using standard endovascular techniques to access the marginal artery of Drummond is an alternative, and in our opinion, preferred technique for controlling type II endoleaks caused by a persistently patent IMA.
PMCID: PMC3234148  PMID: 22171248
Endoleak; marginal artery; drummond; coil embolization

Results 1-6 (6)