Young Seon Hong

High dose concentration administration of ascorbic acid inhibits tumor growth in BALB/C mice implanted with sarcoma 180 cancer cells via the restriction of angiogenesis.

To test the carcinostatic effects of ascorbic acid, we challenged the mice of seven experimental groups with 1.7 × 10-4 mol high dose concentration ascorbic acid after intraperitoneal administrating them with sarcoma S-180 cells. The survival rate was increased by 20% in the group that received high dose concentration ascorbic acid, compared to the control. The highest survival rate was observed in the group in which 1.7 × 10-4 mol ascorbic acid had been continuously injected before and after the induction of cancer cells, rather than just after the induction of cancer cells. The expression of three angiogenesis-related genes was inhibited by 0.3 times in bFGF, 7 times in VEGF and 4 times in MMP2 of the groups with higher survival rates. Biopsy Results, gene expression studies, and wound healing analysis in vivo and in vitro suggested that the carcinostatic effect induced by high dose concentration ascorbic acid occurred through inhibition of angiogenesis.

Chemotherapy use and associated factors among cancer patients near the end of life.

Objectives: We investigated the frequency of chemotherapy use and its associated factors in patients in all age groups in the last year of life. Methods: We identified cancer patients who died in 2004 in any of 17 hospitals. We used demographic and treatment characteristics by computerized hospital information systems and by linking the identification numbers to the 2004 death registry. Results: 48.7% of patients in the last 6 months of life, 43.9% in the last 3 months, and 30.9% in the last month of life received chemotherapy. The frequency of chemotherapy use was lower for older patients. In those ≧65 years old, there was no difference between women and men in the proportion that received chemotherapy. For patients <65 years of age, a larger proportion of women than men received chemotherapy, and chemotherapy use was significantly less frequent for patients with refractory disease than for those with responsive disease. Patients dying at a relatively small hospital without a hospice inpatient unit were significantly more likely to receive chemotherapy. Conclusions: Despite the fact that most cancer patients are resistant to chemotherapy at the end of life, it was administered often to all age groups.

Primary radiation therapy in patients with localized orbital marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT Lymphoma).

PURPOSE To evaluate the outcomes of patients with localized orbital marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT lymphoma) who were treated with radiotherapy (RT). METHODS AND MATERIALS We retrospectively reviewed the records of 46 patients who were treated with RT for pathologically confirmed localized stage IE marginal zone B-cell lymphoma of MALT. The radiation dose ranged from 21.6 to 45 Gy (median, 30.6 Gy) at 1.8-2.0 Gy per fraction. Median follow-up duration was 32.3 months (range, 3.1-113.6 months). RESULTS Forty-three patients (93%) achieved complete remission (CR), and three patients (7%) achieved partial remission (PR). Five-year relapse-free survival, cause-specific survival, and overall survival were 93%, 100%, and 100%, respectively. Among the patients with CR, two had recurrence at three sites. One patient relapsed locally and was successfully salvaged with reirradiation. The other patient relapsed in a distant site and was successfully treated with six cycles of CHOP chemotherapy. Late complications were noted in four patients. Two patients developed cataracts at 26 and 37 months after completion of RT. The other two patients developed nasolacrimal duct obstructions at 4 and 11 months after completion of RT. CONCLUSION Our study showed that a modest dose of RT is an excellent treatment modality with low complication and recurrence rates. We suggest that a dose of 30.6 Gy is tolerable and sufficient for treating orbital MALT lymphoma. Even following recurrence, successful salvage is possible with RT or chemotherapy.

Impact of caregivers’ unmet needs for supportive care on quality of terminal cancer care delivered and caregiver’s workforce performance

Goals of workFamily caregivers play an important role in caring for cancer patients, but the impact of caregivers’ unmet needs on the quality of end-of-life (EOL) care they deliver and on their workplace performance are less understood.Patients and methodsWe identified 1,662 family caregivers of cancer patients who had died at any of 17 hospitals in Korea during 2004. The caregivers answered a telephone questionnaire about needs that were not met when they delivered terminal cancer care and how those unmet their needs affected their workplace performance; they also answered the Quality Care Questionnaire-End of Life (QCQ-EOL).ResultsCompared with caregivers who did not have unmet needs, caregivers who had unmet needs for symptom management, financial support, or community support showed poorer QCQ-EOL scores (P < 0.01). Caregivers who had unmet needs for financial support (adjusted odds ratio (aOR) = 7.55; 95% confidential interval (CI) 3.80–15.00), psychosocial support (aOR = 6.24; 95% CI 2.95–13.05), symptom management (aOR = 3.21; 95% CI 2.26–4.54), community support (aOR = 3.82; 95% CI 2.38–6.11), or religious support (aOR = 4.55; 95% CI 1.84–11.26) were more likely to experience work limitations. Caregivers of patients receiving conventional hospital care were more likely to have unmet needs for symptom management (aOR = 1.21; 95% CI 1.00–1.47), psychosocial support (aOR = 1.99; 95% CI 1.37–2.88), and religious support (aOR = 1.73; 95% CI 1.08–2.78) than those of patients receiving palliative hospice care.ConclusionsCaregivers’ unmet needs negatively affected both the quality of EOL care they delivered and their workplace performance. More investment in caregiver support and public policies that meet caregiver needs are needed, and hospice use should be encouraged.

Comprehensive DNA methylation and extensive mutation analyses reveal an association between the CpG island methylator phenotype and oncogenic mutations in gastric cancers

Recent development of personal sequencers for extensive mutation analysis and bead array technology for comprehensive DNA methylation analysis have made it possible to obtain integrated pictures of genetic and epigenetic alterations on the same set of cancer samples. Here, we aimed to establish such pictures of gastric cancers (GCs). Comprehensive methylation analysis of 30 GCs revealed that the number of aberrantly methylated genes was highly variable among individual GCs. Extensive mutation analysis of 55 known cancer-related genes revealed that 19 of the 30 GCs had 24 somatic mutations of eight different genes (CDH1, CTNNB1, ERBB2, KRAS, MLH1, PIK3CA, SMARCB1, and TP53). Integration of information on the genetic and epigenetic alterations revealed that the GCs with the CpG island methylator phenotype (CIMP) tended to have mutations of oncogenes, CTNNB1, ERBB2, KRAS, and PIK3CA. This is one of the first studies in which both genetic and epigenetic alterations were extensively analyzed in the same set of samples. It was also demonstrated for the first time in GCs that the CIMP was associated with oncogene mutations.

Death receptor 5 and Bcl-2 protein expression as predictors of tumor response to gemcitabine and cisplatin in patients with advanced non-small-cell lung cancer.

The cytotoxic effects of gemcitabine (G) and cisplatin (C) seem to occur through induction of apoptosis. To examine whether the efficacy of GC chemotherapy might be influenced by the expression of death receptor 5 (DR5) and Bcl-2 of the tumor, we investigated the correlation between the tumor response rate and DR5 and Bcl-2 expression in a series of patients prospectively treated with GC. Thirty-four chemotherapy naïve patients with advanced non-small-cell lung cancer (NSCLC) received intravenously 1000 mg/m2 gemcitabine on d 1 and 8 along with 80 mg/m2 cisplatin on d 2, every 21 d. Tumor specimens were analyzed for DR5 and Bcl-2 expression by immunohistochemistry. The objective response rate was 56% (19 of 34 patients). With median follow-up of 10 mo, the predicted median survival time was 12 mo (95% confidence interval [CI], 9–15 mo). Eleven (32%) and 14 (41%) NSCLC cases were found positive for DR5 and Bcl-2, respectively. The response rate was significantly higher in patients with DR5 expression than those without DR5 expression (91% vs 39%; p=0.008). Patients with Bcl-2 expression were apparently less responsive than those without Bcl-2 expression (21% vs 80%; p=0.001). DR5 and Bcl-2 expression was significantly associated with response to GC chemotherapy. Therefore, DR5 and Bcl-2 status are useful factors for predicting the efficacy of GC.

Adoptive Transfer of Epstein-Barr Virus-Specific Cytotoxic T-Lymphocytes for the Treatment of Angiocentric Lymphomas

Angiocentric lymphoma, known as natural killer (NK)/T-cell non-Hodgkin’s lymphoma, has been reported to be associated with the Epstein-Barr virus (EBV). We performed adoptive transfer of EBV-specific polyclonal T-cell lines in 3 patients with extranodal NK/T-cell lymphoma, nasal type, and evaluated the treatment for safety, immunologic reconstitution, and clinical outcomes. The tissue samples collected from the 3 patients were confirmed by polymerase chain reaction analysis to be EBV positive. In the cases of the first and second patients, EBV-transformed B-lymphoblastoid cell lines (LCLs) and T-cell lines were generated from peripheral lymphocytes of HLA-matched sibling donors. The third patient’s T-cell lines were induced with autologous lymphocytes. Polyclonal T-cell infusion was carried out after high-dose radiotherapy because active relapsed disease remained in all of the patients. The first patient received 4 weekly infusions of 2 X 107 cells/m2, and the second and third patients underwent treatment with 2 cycles of infusions of the same dosage. All T-cell lines showed >60% NK activity, cytotoxic T-lymphocyte (CTL) responses of >40% against autologous LCLs, and no CTL activity against patient-derived lym-phoblasts. The level of cytotoxicity increased substantially in all patients after cell infusion. The 2 patients who received T-cell therapy twice had stabilized disease for more than 3 years. These safe treatments exhibited no severe inflammatory response, and no serious toxicity developed during T-cell therapy. Our findings demonstrate that adoptively transferred cells may provide reconstitution of EBV-specific CTL responses in patients with active relapsed angiocentric lymphoma. These results provide a rationale for the immunotherapy of angiocentric lymphoma.

Validation of the Edmonton Symptom Assessment System in Korean Patients With Cancer

CONTEXT The Edmonton Symptom Assessment System (ESAS) is a brief, widely adopted, multidimensional questionnaire to evaluate patient-reported symptoms. OBJECTIVES To develop a Korean version of the ESAS (K-ESAS) and to perform a psychometric analysis in Korean patients with advanced cancer. METHODS We tested the K-ESAS in two pilot studies with 15 patients each. We assessed internal consistency, test-retest reliability, and concurrent validity in 163 Korean patients, who completed the K-ESAS along with the Korean versions of the M. D. Anderson Symptom Inventory (K-MDASI) and the Hospital Anxiety and Depression Scale (K-HADS) twice. A total of 38 patients completed the questionnaires again seven days later to assess responsiveness. RESULTS The K-ESAS scores had good internal consistency, with a Cronbachs alpha coefficient of 0.88, indicating that no questions had undue influence on the score. Pearson correlation coefficients for K-ESAS symptom scores between baseline and after two to four hours ranged from 0.72 (95% CI 0.64-0.79) to 0.87 (95% CI 0.82-0.90), indicating strong test-retest reliability. For concurrent validity, Pearson correlation coefficients between K-ESAS symptom scores and corresponding K-MDASI symptom scores ranged from 0.70 (95% CI 0.62-0.77) to 0.83 (95% CI 0.77-0.87), indicating good concurrent validity. For the K-HADS, concurrent validity was good for anxiety (r=0.73, 95% CI 0.65-0.79) but moderate for depression (r=0.4, 95% CI 0.26-0.52). For responsiveness, changes in K-ESAS scores after seven days were moderately correlated with changes in K-MDASI scores but weakly correlated with changes in K-HADS scores. CONCLUSION The K-ESAS is a valid and reliable tool for measuring multidimensional symptoms in Korean patients with cancer.

Complementary and alternative medicine use among cancer patients at the end of life: Korean national study.

OBJECTIVES To investigate in depth the use of complementary and alternative medicines (CAMs) by cancer patients at the end-of-life (EOL) and how they communicate with physicians about them. DESIGN AND LOCATION: In 17 hospitals in Korea between January and December 2004 we identified 4,042 families of cancer patients. RESULTS The prevalence of CAM use among cancer patients at the EOL was 37.0%, and 93.1% had used pharmacologic types of agents. The most frequent motive for CAM use was the recommendation of friends or a close relative (53.4%) or a physician (1.6%). Only 42.5% discussed CAM use with their physicians. Satisfaction with CAMS was recalled for 37.1% . The most common reason given for that satisfaction was improvement of emotional or physical well-being, while ineffectiveness was the most common reason given for dissatisfaction. The average cost of CAM during the last month of life was

Long-term Outcome of Extranodal NK/T Cell Lymphoma Patients Treated With Postremission Therapy Using EBV LMP1 and LMP2a-specific CTLs

US 900. CAM use was associated with longer disease periods, primary cancers other than liver, biliary, and pancreatic, and need of support from physicians or religion. CONCLUSIONS CAM use among cancer patients at the EOL was common, not discussed with physicians, and associated with expectation of cure. Expectations were generally unmet while the treatments were a financial burden. Further studies evaluating the effects of CAM at the EOL and factors that enhance communication with the physician are needed.