PURPOSE: Vascular endothelial growth factor (VEGF) is a major positive effector of angiogenesis. We investigated the mechanism of tumor growth inhibition by adenoviral transfer of antisense- VEGF in glioma and the role of VEGF for in vivo growth of human glioma cells according to the stage of the tumor growth. MATERIALS AND METHODS: Replication-deficient adenoviral vector containing the VEGF cDNA in an antisense orientation (Ad5CMV-alphaVEGF) were constructed to increase the in vivo applicability of antisense sequence. The effect of Ad5CMV-alphaVEGF was studied in vitro and in vivo with human glioma cell line U-87 MG. Immunohistochemical staining of the subcutaneous tumor with anti-VEGF antibody and CD34 antibody were performed to compare VEGF protein expression and the microvessel count respectively. RESULTS: The growth curve of U-87 MG cells treated with Ad5CMV-alphaVEGF remained as same as that of mock-infected and Ad5(dl312)-infected U-87 MG cells in vitro, suggesting that Ad5CMV-alphaVEGF does not have direct cytotoxic effect. The growth of subcutaneous human glioma xenografts was inhibited by early intratumoral injection of Ad5CMV-alphaVEGF. Immuno histochemical staining of tumors showed that VEGF protein expression and mean microvessel counts were decreased in early Ad5CMV-alphaVEGF treatment group. CONCLUSION: The efficient down-regulation of VEGF produced by tumor cells using Ad5CMV- alphaVEGF in early stage of glioma growth has an antitumor effect in vivo through antiangiogenic mechanism.
Adenoviridae ; Cell Line ; DNA, Complementary ; Down-Regulation ; Genetic Therapy* ; Glioblastoma* ; Glioma ; Heterografts ; Humans ; Microvessels ; Vascular Endothelial Growth Factor A

PURPOSE: Brain metastases are the most frequent metastatic neurologic complication of systemic cancer. Even if the prognosis of brain metastases is grave, with available treatments, most patients experience effective palliation of neurologic symptoms and meaningful extension of life. We evaluated the clinical features and prognostic factors of the patients who were diagnosed as solid tumors with brain metastasis and received radiotherapy for brain metastases. MATERIALS AND METHODS: Between January 1987 and January 1998, 71 patients with brain metastases from solid malignancy were included. We reviewed neurologic symptoms and signs of patients and evaluated improvememt of neurologic symptoms and signs. Survival durations after brain metastasis were analysed according to several factors such as age, performance status, primary malignancies, the presence of brain metastasis at initial diagnosis of primary tumor, multiplicity of brain metastass, the presence of metastases other than brain, and treatment method. RESULTS: Frequent symptoms associated with brain metastasis were headache (47.9%), motor weakness (40.8%), nausea and vomiting (19.7%) and mental change (19.7%). Palliation of these symptoms was accomplished in 64.9% of cases. The overall median survival time was 16 weeks and 1- and 2-year survival rates were 15.0% and 5.1% respectively. Patients without extracranial metastases (n=27) had longer median survival than patients with extracranial metastases (33 weeks vs 10 weeks, p=0.0018). In patients with single brain metastasis (n=37), the median survival time was longer in patients treated with surgery plus radiotherapy than in patients treated with radiotherapy alone (40 weeks vs 16 weeks, p=0.0438). CONCLUSION: Patients who has brain metastases only constitute a prognostically favorable group and they may be benefited from radiotherapy and surgery if indicated.
Brain* ; Diagnosis ; Headache ; Humans ; Nausea ; Neoplasm Metastasis* ; Neurologic Manifestations ; Prognosis ; Radiotherapy* ; Survival Rate ; Vomiting

Methotrexate is the most widely used intrathecal antineoplastic agent and is potentially neurotoxic. Accidental intrathecal overdose of methotrexate can produce severe and life-threatening toxicities. A 17-year-old girl with acute lymphocytic leukemia, in complete remission, inadvertently received a 10-fold overdose of intrathecal methotrexate instead of intended dose (100mg vs 10mg). Exchange of lumbar cerebrospinal fluid with normal saline via intrathecal indwelling catheter was started 2 hours later. Leucovorin and dexamethasone were given intravenously. After exchange of cerebrospinal fluid, the total amount of methotrexate removed was about 37mg. Cerebrospinal fluid and plasma methotrexate levels at 18 hours were about 3- to 5- fold higher than those previously reported in patients following standard dose of intrathecal methotrexate who did not develop neurotoxicity. But no methotrexate induced neurologic sequelae were observed in this patient. CSF exchange is a simple and effective method for the treatment of acute intrathecal methotrexate overdose.
Adolescent ; Catheters, Indwelling ; Cerebrospinal Fluid ; Dexamethasone ; Female ; Humans ; Leucovorin ; Methotrexate* ; Plasma ; Precursor Cell Lymphoblastic Leukemia-Lymphoma*

POEMS syndrome is a rare multisystemic syndrome characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes. We report a case of POEMS syndrome associated with unclassifiable myeloproliferative disorder presenting with polyneuropathy, hepatosplenomegaly, hypothyroidism, hyperprolactinemia, monoclonal gammopathy, hyperpigmentation, hypertrichosis, ascites, peripheral edema, and pulmonary hypertension.
Ascites ; Edema ; Hyperpigmentation ; Hyperprolactinemia ; Hypertension, Pulmonary ; Hypertrichosis ; Hypothyroidism ; Myeloproliferative Disorders* ; Paraproteinemias ; POEMS Syndrome* ; Polyneuropathies ; Skin

PURPOSE: Most medical schools in Korea do not provide adequate education in end-of-life care. This study was designed to illustrate the need to improve end-of-life care education and to assess the effect of the education on fourth-year medical students' awareness and attitude towards hospice and palliative care for terminally ill patients. METHODS: One hundred sixty six fourth-year medical students were surveyed with questionnaires on end-of-life care before and after they received the education. RESULTS: Before receiving the education, students most frequently answered "at the end of life" (33.6%) was appropriate time to write an advance medical directive. After the education, the most frequent answer was "in healthy status" (58.7%). More students agreed to withholding or withdrawing futile life-sustaining treatment increased after the education (48.1% vs. 92.5% (P<0.001) for cardiopulmonary resuscitation, 38.3% vs. 92.5% (P<0.001) for intubation and mechanical ventilation, 39.1% vs. 85.8% (P<0.001) for inotropics, 60.9% vs. 94.8% (P<0.001) for dialysis and 27.8% vs. 56.0% (P<0.001) for total parenteral nutrition). Significantly more students opposed euthanasia after the education (46.6% vs. 82.1%, P<0.001). All students agreed to the need for education in end-of-life care. CONCLUSION: After reflecting on the meaning of death through the end-of-life care education, most students recognized the need for the education. The education brought remarkable changes in students' awareness and attitude towards patients at the end of life. We suggest end-of-life care education should be included in the regular curriculum of all medical schools in Korea.
Cardiopulmonary Resuscitation ; Curriculum ; Dialysis ; Euthanasia ; Hospice Care ; Hospices ; Humans ; Intubation ; Korea ; Palliative Care ; Respiration, Artificial ; Schools, Medical ; Students, Medical ; Terminal Care ; Terminally Ill

Objectives: This study aimed to examine the correlations between the regional characteristics of counties in Gangwon Province, Republic of Korea and the ratio of intracounty to extracounty sources of coronavirus disease 2019 (COVID-19) infection. Methods: The region of the infectious contact was analysed for each COVID-19 case reported in Gangwon Province between February 22, 2020 and February 7, 2022. The population, population density, area, the proportion of urban residents, the proportion of older adults (>65 years), financial independence, and the number of adjacent counties were assessed for each of the 18 counties in Gangwon Province. Correlation coefficients between regional characteristics and the ratio of intracounty to extracounty infections were calculated. Results: In total, 19,645 cases were included in this study. The population, population density, proportion of older adults, and proportion of urban residents were significantly correlated with the ratio of intracounty to extracounty infections. A stratified analysis with an age cut-point of 65 years showed that the proportion of older adults had a significant negative correlation with the ratio of intracounty to extracounty infections. In other words, the proportions of extracounty infections were higher in countries with higher proportions of older adults. Conclusion Regions with ageing populations should carefully observe trends in infectious disease outbreaks in other regions to prevent possible transmission.

PURPOSE: Previous epidemiologic studies have demonstrated that nonsteroidal anti-inflammatory drugs can reduce the risk of breast cancer, and this possibly happens via cyclooxygenase (COX) inhibition. Moreover, growth factor-inducible COX-2, which is overexpressed in neoplastic tissue, is an attractive therapeutic target. Thus, we evaluated the expression of COX-2 in breast cancer tissues, and we assessed the association between COX-2 expression and HER-2/neu expression and also with several clinicopathological features. MATERIALS AND METHODS: We analyzed the surgical specimens from 112 women with breast cancer who had undergone lumpectomy or mastectomy. The expressions of COX-2, HER-2/neu, MMP-2 and TIMP-2 were determined immunohistochemically. The correlations between COX-2 expression and several variables, including clinicopathological factors, HER-2/neu expression, MMP-2 expression and TIMP-2 expression were analyzed. Survival analysis was also performed with respect to COX-2 overexpression. RESULTS: The overexpression of COX-2 protein was observed in 28.6% of the breast cancer tissues. Tumors with lymph node metastasis more frequently showed COX-2 overexpression than did those tumors without metastasis (p=0.039), and the increased COX-2 expression correlated positively with HER-2/neu overexpression (p=0.000). No significant differences were found for the MMP-2 or TIMP-2 expression rates in the COX-2 positive and negative groups. The survival analysis revealed no significant differences according to the COX-2 expression. CONCLUSION: This study results suggest that increased COX-2 expression is related with the progression of breast cancer, e.g., with lymph node invasion. COX-2 overexpression found to be related with HER-2/neu overexpression, but not with MMP-2 or TIMP-2 expression. These results support the potential use of selective agents that inhibit COX-2 or HER-2/neu for the management of breast cancer.
Breast Neoplasms* ; Breast* ; Cyclooxygenase 2* ; Epidemiologic Studies ; Female ; Humans* ; Lymph Nodes ; Mastectomy ; Mastectomy, Segmental ; Neoplasm Metastasis ; Prostaglandin-Endoperoxide Synthases ; Tissue Inhibitor of Metalloproteinase-2

BACKGROUND: Angiogenesis plays a key role in the growth and metastasis of solid tumor. But it is not known whether the hematopoietic tumor depends on angiogenesis. To evaluate the prognostic roles of vascular endothelial growth factor (VEGF) expression and angiogenesis in patients with acute myelogenous leukemia, we analyzed the relationships between the level of VEGF expression, microvessel counts (MVC) in the bone marrow specimen of acute myelogenous leukemia patient and remission, relapse, and overall survival. METHODS: We evaluated bone marrow biopsy from 32 adult patients with newly diagnosed acute myelogenous leukemia and 16 controls with normal bone marrow. VEGF expression and MVC were assessed by immunohistochemical stain with monoclonal antibody to VEGF and polyclonal antibody to factor VIIIRAg, respectively. RESULTS: VEGF expression was higher in acute myelogenous leukemia than that of control (56.4+/-32.8% vs 19.0+/-25.9%, P=0.004). MVC was also higher in acute myelogenousleukemia than that of control (14.7+/-10.3 vs 6.2+/-3.8, P<0.001). Between high VEGF expression group and low VEGF expression group, there were no significant differences in the complete remission (CR), relapse and overall survival. There was no significant difference of MVC between CR group and non- CR group. Relapse group tends to have higher MVC than non-relapse group without statistical significance (P=0.06). There were no significant differences of MVC between hypervascular group and hypovascular group in remission, relapse and overall survival. CONCLUSION: In patients with acute myelogenous leukemia, VEGF expression and MVC were significantly higher than those of control. These findings suggest angiogenesis may play an important role in the pathogenesis of acute myelogenous leukemia. But there was no clinical correlation between the level of VEGF expression, MVC and remission, relapse and overall survival in this study. Further study willbe necessary for the establishment of prognostic role of VEGF expression and angioge-nesis and clinical efficacy of angiogenic inhibitors in acute myelogenous leukemia.
Adult ; Angiogenesis Inhibitors ; Biopsy ; Bone Marrow ; Humans ; Leukemia, Myeloid, Acute* ; Microvessels ; Neoplasm Metastasis ; Recurrence ; Vascular Endothelial Growth Factor A*

Neurofibromatosis type 1 (von Recklinghausen's disease, NF-1) is an autosomal-dominant neurocutaneous disorder characterized by abnormal skin pigmentation (cafe au lait spots and axillary freckling), cutaneous and plexiform neurofibromas, skeletal dysplasias, and Lisch nodules (pigmented iris hamartomas). Gastrointestinal stromal tumors (GISTs) are the most common tumors of mesenchymal origin in the gastrointestinal tract, mesentery, omentum, and retroperitoneum. Here, we report a case of GIST in the ileum of a 76-year-old woman previously diagnosed as NF-1. She was admitted due to sudden onset of abdominal pain. Contrast enhanced CT scan revealed a moderately defined, peripherally enhanced soft tissue mass of about 8.8 x 7.3 cm, originating from the small bowel in the left of the abdomen. Surgical excision was performed and the tumor was found to be composed of tumor cells that were positive for c-kit protein. The patient started imatinib treatment a month later, but stopped medication due to dyspepsia after a few months and eventually progressed after 18 months.
Risk Factors ; Neurofibromatosis 1/*diagnosis/pathology/surgery ; Humans ; Gastrointestinal Stromal Tumors/*diagnosis/pathology/surgery ; Female ; Aged ; Abdominal Pain

PURPOSE: Many end-of-life care studies are based on the assumption that there is a shared definition of language concerning the stage of cancer. However, studies suggest that patients and their families often misperceive patients' cancer stages and prognoses. Discrimination between advanced cancer and terminal cancer is important because the treatment goals are different. In this study, we evaluated the understanding of the definition of advanced versus terminal cancer of the general population and determined associated socio-demographic factors. MATERIALS AND METHODS: A total of 2,000 persons from the general population were systematically recruited. We used a clinical vignette of a hypothetical advanced breast cancer patient, but whose cancer was not considered terminal. After presenting the brief history of the case, we asked respondents to choose the correct cancer stage from a choice of early, advanced, terminal stage, and don't know. Multinomial logistic regression analysis was performed to determine sociodemographic factors associated with the correct response, as defined in terms of medical context. RESULTS: Only 411 respondents (20.6%) chose "advanced," while most respondents (74.5%) chose "terminal stage" as the stage of the hypothetical patient, and a small proportion of respondents chose "early stage" (0.7%) or "don't know" (4.4%). Multinomial logistic regression analysis found no consistent or strong predictor. CONCLUSION: A large proportion of the general population could not differentiate advanced cancer from terminal cancer. Continuous effort is required in order to establish common and shared definitions of the different cancer stages and to increase understanding of cancer staging for the general population.
Breast Neoplasms ; Data Collection ; Delivery of Health Care* ; Discrimination (Psychology) ; Humans ; Logistic Models ; Neoplasm Staging ; Prognosis