PURPOSE: The aim of this study was to evaluate local control and long-term survival of concurrent hyperfractionated radiotherapy with CDDP/VP-16 chemotherapy in limited stage small cell lung cancer. MATERIALS AND METHODS: From April 1992 to April 1997, twenty-nine patients with limited stage small cell lung cancer received cisplatin 25 mg/m plus etoposide 120 mg/m(2) on day 1, 2 and 3. Chemotherapy was repeated every 4 weeks for a total of 4 courses. Radiation was given to 60 Gy in 50 twice-daily fractionation separated by at least 6 hours, 5 days per week Thoracic radiotherapy was started with first coese of chemotherapy for 28.8 Gy. After 12 days break, radiotherapy was resumed with second course of chemotherapy for another 31,2 Gy. RESULTS: Twenty-eight patients (96.6%) were evaluable. Patient characteristics include: median age 58.4 years (range 45-67); clinical stage 1IIa 13 pts, stage IIIb 15 pts; ECOG performance status 0 (8 pts), 1 (16 pts) and 2 (4 pts). Objective responses were 21 complete response, 6 partial response, 1 stable disease with overall response rate of 96.4%. Grade III and IV toxicities were leukopenia in 23/28 pts, thrombocytopenia in 8/28 pts, stomatitis in 10/28 pts, and alopecia in 8/28 pts. The median survival time was 19.2 months with 1 year, 2 year, 3 year, and 4 year actuarial survival rates and RFS are 65.6%, 30.6%, 30.6%, 24.5%, and 65.3%, 52.8%, 52.8%, 42.2%, respectively. Overall survival rate according to TNM stage, weight loss, age and sex were not statistically significant. Pattems of relapse were local only in 2 pts, systemic only in 7 pts, and local plus systemic in 1 pt, and brain was the most frequent systemic recurrent site (4 pts). CONCLUSION: Concurrent hyperfractionated radiotherapy with CDDP/VP-16 chemotherapy seems to produce better local contml and survival rates in limited stage small cell lung cancer.
Alopecia ; Brain ; Cisplatin ; Drug Therapy* ; Etoposide* ; Humans ; Leukopenia ; Radiotherapy* ; Recurrence ; Small Cell Lung Carcinoma* ; Stomatitis ; Survival Rate ; Thrombocytopenia ; Weight Loss

PURPOSE: Alterations of the p15(INK4B) and p16(INK4A) gene which are separated by 25 kb on chromosome 9p21 have been reported in various tumor derived cell lines and primary tumors, but the role of these genes in cervical cancer is unknown. MATERIAL AND METHOD: To determine the frequency of deletions and point mutations of these genes in human cervical cancer, we examined 57 primary tumors and matched normal tissues, and 3 cervical cancer derived cell lines. All the tumor tissues and cell lines were human papil- INK48 lomavirus (HPV)-positive. Deletions or point mutations of exon 2 of the pl5 gene and exons 1, 2, and 3 of the p16(INK4A) gene were examined by polymerase chain reaction (PCR) and direct sequencing, respectively. RESULT: Our data indicate no evidence for intragenic homozygous deletion or point mutation in the cervical cancer or cervical cancer derived cell lines. INK48 INK4A CONCLUSION: Deletions or point mutations in the p15 or p16 gene may not be required for the development of HPV-positive cervical cancer or for establishment of cervical cancer cell lines.
Cell Line* ; Cyclin-Dependent Kinase Inhibitor p16 ; Exons ; Genes, p16 ; Humans ; Point Mutation ; Polymerase Chain Reaction ; Uterine Cervical Neoplasms

PURPOSE: Hepatocellular carcinoma (HCC) is one of the most common malignancy with high mortality in Korea. A new therapeutic modality such as gene therapy is necessary to improve the prognosis of hepatoma patients. Therefore we investigated the preclinical significance of Herpes simplex virus - thymidine kinase/ganciclovir (HSV-tk/GCV) gene therapy model using the retroviral vector for HCC cell lines. MATERIALS AND METHODS: LNC/HSV-tk retroviral vector and PA317/LNC/HSV-tk pro- ducer cell line were constructed. HSV-tk transduced HCC cells using the LNC/HSV-tk retrovirus were selected by the G418 containing media. In vitro GCV sensitivity test of the HCC cells was performed by MTT assay. To evaluate in vivo GCV sensitivity, GCV was intraperitoneally injected after subcutaneous administration of HCC cells into each flank of the nude mouse. RESULTS: HSV-tk gene transduction and expression in HCC cells were confirmed by RT-PCR. HSV-tk transduced HCC cell lines (SK-Hepl/HSV-tk and Hep-3B/HSV-tk) showed the marked GCV sensitivity comparing with the parental cell lines (SK-Hepl and Hep-3B) by MTT assay (p<0.001). The MTT test revealed that SK-Hepl/HSV-tk cells were more sensitive to GCV compare with that of Hep-3B/H5V-tk cells, and the parent cell line showed minimal growth suppression by the GCV treatment. In 12 nude mice received tumor cell mixtures of Hep-3B and Hep-3B/HSV-tk cells which contained more than 50% of HSV-tk transduced cells, the tumor was not developed in ll mice by the intraperitoneal administration of GCV. The tumors developed in 1 of 6 mice and 5 of 6 mice when mixtures contained 30% and 10% of HSV-tk transduced cells, respectively. Five mice out of 6 mice received inoculum containing the mixtures of 70% and 50% of HSV-tk transduced cells into each flank survived more than 6 month after HSV-tk/GCV treatment. Conelusion: HSV-tk gene transduced HCC cells showed the enhanced sensitivity to GCV. In nude mice HSV-tk/GCV strategy for HCC seemed to be more effective when tumor cell inoculum contained more than 30% of HSV-tk transduced HCC cells.
Animals ; Carcinoma, Hepatocellular* ; Cell Line* ; Ganciclovir* ; Genetic Therapy ; Herpes Simplex* ; Humans ; Korea ; Mice ; Mice, Nude ; Mortality ; Parents ; Prognosis ; Retroviridae* ; Simplexvirus* ; Thymidine Kinase* ; Thymidine* ; Zidovudine

PURPOSE: The replacement of functional genes into cells that lack genes or mutant genes is the basis of gene therapy. In cancer, where cells often have multiple genetic defects, the replacement of critical genes may suffice to suppress cell growth or induce cell death. In malignant brain tumors, p53 mutation are among the most frequently observed genetic findings and inactivation p53 suggests that p53 plays a critical role in carcinogenesis and tumor progression. Therefore, we study the successful transfer of the wild-type p53 gene using a replicative deficient adenovirus vector into human glioma and medulloblastoma c~ell lines. Meterials and Methods: The human glioma cell line T-98G, U-87MG, U-373MG were used. To determine the efficiency of the adenovirus vector, cell lines were transfected with the Ad-p gal and analysed with X-Gal staining. Cell viability was determined by trypan blue exclusion every day after infection and Westem blot analysis was used to conform the expression of the exogenous p53 protein. RESULTS: Cell growth of the Ad-CMV-p53 infected U-373MG, and U-87MG was significantly suppressed. It appeared that exogenous p53 protein expression had an earlier ad more profound suppressive effect on U-373MG having a mutated p53 gene than on U-87MG having a wild-type p53. The expression of the exogenous p53 was more than 10 times higher than the expression of the endogenous p53. To examine the decreased viability, U-373MG was stained with Hochest 33258 and detected nuclear condensation and apoptic body. Staining results suggest that cells undergo apoptosis. CONCLUSION: The replicative deficient adenoviral vector can transfer and express p53 in human glioma cell lines in vitro, restoring wild-type p53 tumor suppressor functions. The restoration of normal p53-encoded protein in the mutant ceil lines induced cell death. The high expression of the newly transduced protein had different effects on the growth rate of the infected cell lines depending on the p53 status of the cells.
Adenoviridae* ; Apoptosis ; Brain Neoplasms ; Carcinogenesis ; Cell Death ; Cell Line* ; Cell Survival ; Genes, p53 ; Genetic Therapy ; Glioma* ; Humans ; Medulloblastoma ; Trypan Blue

Invasive aspergillosis is a life-threatening infectious disease in immunocompromised patients. Prolonged neutropenia is the most important predisposing factor. Bronchial casts are generally associated with pneumonia, bronchiectasis, asthma, chronic bronchitis, allergic bronchopulmonary aspergillosis and mucoviscidosis. We experienced.a case of invasive aspergillosis characterized by the formation of large bronchial cast in patient with acute myelogenous leukemia(AML) during induction chemotherapy. The patient expectorated a large bronchial cast without airway obstruction. Aspergillus was disclosed in intraluminal surface of bronchial cast. The patient's conditions improved after amphotericin B therapy and expectoration of a large bronchial cast.
Airway Obstruction ; Amphotericin B ; Aspergillosis* ; Aspergillosis, Allergic Bronchopulmonary ; Aspergillus ; Asthma ; Bronchiectasis ; Bronchitis, Chronic ; Causality ; Communicable Diseases ; Cystic Fibrosis ; Humans ; Immunocompromised Host ; Induction Chemotherapy ; Leukemia, Myeloid, Acute* ; Neutropenia ; Pneumonia

PURPOSE: The purpose of this study was to investigate the possibilities for serial in vivo localized proton magnetic resonance spectroscopy (MRS) examination of bone marrow in patients with acute le,ukemia. MATERIALS AND METHODS: Selective measurements of the relaxation times Tl and T2 for the water and fat resonance in the bone marrow spectra were performed (1.5 Tesla whole body magnetic resonance scanner). Six patients with acute leukemia were examined at diagnosis. Follow-up examinations of four patients with acute leukemia in complete remission were also examined. Six normal control subjects were examined with identical methods for comparison. RESULTS: Significant differences could be detected in the spectral patterns from lumbar spine in patients with leukemia at diagnosis compared to healthy normal controls. The relative water content was increased in leukemic patients compared to normal subjects, which indicate an increase in the amount of hemopoietic tissue and a corresponding decrease in marrow fat content. A significant correlation was found between cellularity assessments derived from conventional bone marrow core biopsies and relative water content of proton MRS data. The Tl relaxation time of the water resonance in leukemic patients were significantly prolonged at diagnosis compared to normal controls. After chemotherapeutic induction of remission, the spectra from the bone marrow of lumbar spine resembled normal subjects. CONCLUSIONS: This method provide the possibility for serial measurements of bone marrow in patients with leukemia, and may provide information from regions inaccessible to bone marrow biopsy. This therefore appears to be a promising application of proton MRS that can be performed on a routine basis in a clinical setting.
Biopsy ; Bone Marrow* ; Diagnosis ; Drug Therapy* ; Follow-Up Studies ; Humans ; Leukemia ; Magnetic Resonance Spectroscopy* ; Protons* ; Relaxation ; Remission Induction ; Spine ; Water

No abstract available.
Proportional Hazards Models* ; Survival Analysis*

No abstract available.
Urinary Bladder Neoplasms* ; Urinary Bladder*

No abstract available.
Bacillus* ; Humans ; Urinary Bladder Neoplasms* ; Urinary Bladder*

No abstract available.
Urinary Tract*