Purpose: The introduction of immune checkpoint inhibitors represents a major advance in the treatment of lung cancer, allowing sustained recovery in a significant proportion of patients. Nivolumab is a monoclonal anti–programmed death cell protein 1 antibody licensed for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) after prior chemotherapy. In this study, we describe the demographic and clinical outcomes of patients with advanced NSCLC treated with nivolumab in the Korean expanded access program. Materials and Methods: Previously treated patients with advanced non-squamous and squamous NSCLC patients received nivolumab at 3 mg/kg every 2 weeks up to 36 months. Efficacy data including investigator-assessed tumor response, progression data, survival, and safety data were collected. Results: Two hundred ninety-nine patients were treated across 36 Korean centers. The objective response rate and disease control rate were 18% and 49%, respectively; the median progression-free survival was 2.1 months (95% confidence interval [CI], 1.87 to 3.45), and the overall survival (OS) was 13.2 months (95% CI, 10.6 to 18.9). Patients with smoking history and patients who experienced immune-related adverse events showed a prolonged OS. Cox regression analysis identified smoking history, presence of immune-related adverse events as positive factors associated with OS, while liver metastasis was a negative factor associated with OS. The safety profile was generally comparable to previously reported data. Conclusion This real-world analysis supports the use of nivolumab for pretreated NSCLC patients, including those with an older age.

PURPOSE: To determine the patterns of evaluation and treatment in the patient with early breast cancer treated with conservative surgery and radiotherapy and to improve the radiotherapy techiniques, nationwide survey was performed. MATERIALS AND METHODS: A web-based database system for Korean Patterns of Care Study (PCS) for 6 common cancers was developed. Two hundreds sixty-one randomly selected records of eligible patients treated between 1998~999 from 15 hospitals were reviewed. RESULTS: The patients ages ranged from 24 to 85 years(median 45 years). Infiltrating ductal carcinoma was most common histologic type (88.9%) followed by medullary carcinoma (4.2%) and infiltrating lobular carcinoma (1.5%). Pathologic T stage by AJCC was T1 in 59.7% of the casses, T2 in 29.5% of the cases, Tis in 8.8% of the cases. Axillary lymph node dissection was performed in 91.2% of the cases and 69.7% were node negative. AJCC stage was 0 in 8.8% of the cases, stage I in 44.9% of the cases, stage IIa in 33.3% of the cases, and stage IIb in 8.4% of the cases. Estrogen and progesteron receptors were evaluated in 71.6%, and 70.9% of the patients, respectively. Surgical methods of breast-conserving surgery was excision/lumpectomy in 37.2%, wide excision in 11.5%, quadrantectomy in 23% and partial mastectomy in 27.5% of the cases. A pathologically confirmed negative margin was obtained in 90.8% of the cases. Pathological margin was involved with tumor in 10 patients and margin was close (less than 2 mm) in 10 patients. All the patients except one recieved more than 90% of the planned radiotherapy dose. Radiotherapy volume was breast only in 88% of the cases, breast+supraclavicular fossa (SCL) in 5% of the cases, and breast+SCL+posterior axillary boost in 4.2% of the cases. Only one patient received isolated internal mammary lymph node irradiation. Used radiation beam was Co-60 in 8 cases, 4 MV X-ray in 115 cases, 6 MV X-ray in 125 cases, and 10 MV X-ray in 11 cases. The radiation dose to the whole breast was 45~9.4 Gy (median 50.4) and boost dose was 8~20 Gy (median 10 Gy). The total radiation dose delivered was 50.4~70.4 Gy (median 60.4 Gy). CONCLUSION: There was no major deviation from current standard in the patterns of evaluation and treatment for the patients with early breast cancer treated with breast conservation method. Some varieties were identified in boost irradiation dose. Separate analysis for the datails of radiotherapy planning will be followed and the outcome of treatment is needed to evaluate the process.
Breast Neoplasms ; Breast* ; Carcinoma, Ductal ; Carcinoma, Lobular ; Carcinoma, Medullary ; Estrogens ; Humans ; Korea* ; Lymph Node Excision ; Lymph Nodes ; Mastectomy, Segmental* ; Radiotherapy

Local cutaneous reactions have been reported at injection sites of interferon therapy, but these are usually erythema or rarely induration. Skin necrosis at the injection site is rare. We describe here a patient with multiple sclerosis who presented with cutaneous necrosis at the injection sites of interferon-β. Biopsy of the necrotic lesion showed dermal vessel thrombosis and complete ischemic coagulative necrosis of epidermis and dermis.
Biopsy ; Dermis ; Epidermis ; Erythema ; Humans ; Interferon-beta* ; Interferons ; Multiple Sclerosis ; Necrosis* ; Skin* ; Thrombosis

Lung cancer is the leading cause of cancer deaths. Non-small cell lung cancer constitutes approximately 75% of lung cancers, and 40% will present as advanced stage IIIa or IIIb, which are ineffectively treated by primary surgery. Radiation of a primary tumor, and the regional lymphatics, has been the traditional treatment for an unresectable locally advanced disease, but few patients achieved a complete response. Due to the limited benefits provided by radiation therapy, we explored the use of combined chemoradiotherapy in patients with locally advanced, unresectable NSCLC. Combined chemoradiotherapy appears to have improved the outcome of patients with locally advanced unresectable stage III NSCLC, with a median survival of 13 to 14 months, with 5 year survival rates as high as 15 to 20%, nearly three times that reported with radiation therapy alone. Various agents have been used either sequentially or concomitantly in clinical trials of combined chemoradiotherapy for NSCLC. The interactions of chemotherapy and radiation therapy are complex, and Texanes interact with radiation at many levels. Cell-cycle synchronization, through mitotic arrest, has been consistently shown to play a major role in radiation enhancement, but increased apoptosis and tumor reoxygenation may be additional mechanisms. Clearly, the interaction is multifactorial, and the dominant mechanism may be affected by specific settings, which include drug exposure and concentration, tumor type and radiation dosimetry. Recent studies have demonstrated that shorter, high-dose, radiotherapy schedules cause a statistically significant increase in the control of a local tumor in NSCLC. Radiation dose escalation, utilizing conventional fractionation techniques, would be likely to cause prohibitive toxicity. Threedimensional conformal radiation therapy (3-DCRT) has the potential to deliver high dose radiation >70 Gy), with minimal under-dosing and concomitant relative sparing of normal tissues. This technical demonstration of the enhanced therapeutic ratio is used as the basis for the evolving clinical utilization of 3-DCRT for NSCLC. Preliminary experience of the technique has resulted in promising survival rates, following three-dimensional conformal radiation therapy alone, for locally advanced NSCLC. A greater follow-up and experience will help determine its late toxicity, maximum dose and efficacy of dose escalation. Strategies should be developed to integrate this modality into combined treatments for locally advanced NSCLC. Biotechnological developments within the last decade have resulted in the identification of important biological and biophysiological pathways in lung carcinogenesis, and new agents are being developed to target difficult levels of these important pathways. Preclinical and clinical studies using these specific targeted therapies in lung cancer have been very promising. Targeted therapies in lung cancer, and the potential of combining these agents with chemotherapy and radiotherapy, are under investigation.
Apoptosis ; Appointments and Schedules ; Carcinogenesis ; Carcinoma, Non-Small-Cell Lung ; Chemoradiotherapy ; Drug Therapy ; Follow-Up Studies ; Humans ; Lung Neoplasms* ; Lung* ; Radiometry ; Radiotherapy* ; Survival Rate

A 26-year-old man with intermittent lower, abdominal, cramping pain, nausea, vomiting, and diarrhea was found to have intussusception by computed tomography. Whole emergency laparotomy was performed, intus-susception reduced spontaneously. Postoperately, familial adenomatous polyposis (FAP) was diagnosed by colonoscopy and barium enema. Innumerous polyps were found in the entire colon and one of these was presumed to have caused sigmoid invagination. If is believed that FAP is quite a rare cause of colonic intus-susception. This case of a 26-year-old man with an intussusception of the colon due to FAP is herein reported. It is important that surgeons and internists are aware of this rare cause of intussusception due to FAP because of the therapeutic implications.
Adenomatous Polyposis Coli* ; Adult ; Barium ; Colon* ; Colon, Sigmoid ; Colonoscopy ; Diarrhea ; Emergencies ; Enema ; Humans ; Intussusception* ; Laparotomy ; Muscle Cramp ; Nausea ; Polyps ; Vomiting

PURPOSE: To gain insight on transcriptional repression of Topo II a in HL-60 cells arrested to G2/M and M phase, the levels of Topo IIa mRNA and the binding activity of ATF have been investigated with Northern blot hybridization and DNA mobility shift assay, respectively. MATERIALS AND METHODS: HL-60 cells were grown in RPMI 1640 medium supplemented with 10% heat-mactivated fetal bovine serum and antibiotics in a humidified 5% CO2 at 37C degree. Total RNA was prepared by a modification of the method of Karlinsey et al. Northern blot hybridization was performed by the method of Virca et al. A Xho I-Mlu I fragment of phTOP2 was used as probe for Northern blot analysis of Topo II a mRNA. DNA mobility shift assay was performed by the method of Lim et al. End labeled DNA oligomer (upper strand, 5-TCTCCGCTATGACGCCGAGTGGTG-3) for ATF binding activity was mixed with nuclear extracts in a 20 pl reaction volume containing 60 mM KC1, 12 mM HEPES, pH 7.9, 5 mM MgCl2, 0.2 mM EDTA, 0.2 mM DTT, 12% glycerol, and 2 ug of poly [dI-dC]. RESULTS: HL-60 cells were arrested at G2/M phase and M phase after taxol or nocodazole treatment. The levels of Topo II a mRNA were reduced at 24 hours after exposure with nocodazole or taxol but the unknotting activities were not changed. DNA mobility shift assay using oligonucleotide containing the ATF binding site showed that ATF binding activity was reduced after pretreatment of nododazole or taxol. CONCLUSIONS: These results suggest that the reduction of ATF binding activity may be important to transcriptional repression of Topo II a gene by nocodazole and taxol in HL- 60 cells.
Anti-Bacterial Agents ; Binding Sites ; Blotting, Northern ; Cell Division* ; DNA Topoisomerases, Type I* ; DNA Topoisomerases, Type II* ; DNA* ; Edetic Acid ; Electrophoretic Mobility Shift Assay ; Genes, vif ; Glycerol ; HEPES ; HL-60 Cells ; Humans ; Hydrogen-Ion Concentration ; Magnesium Chloride ; Nocodazole ; Paclitaxel ; Repression, Psychology ; RNA ; RNA, Messenger

PURPOSE: Alteration of p53 and telomerase activity may be responsible for gastric carcino- genesis. In this study, we tried to observe modulation of telomerase activity by wild type p53 in gastric cancer cell lines. MATERIALS AND METHODS: We used five gastric cancer cell lines (KATO-III, AGS, SNU-1, SNU-5, SNU-16). In order to find p53 mutation, we used western blot and PCR-SSCP. The TRAP-eze kit which supplied by Oncor (Gaithersburg, MD) was used to detect telomerase activity of the five gastric carcinoma cell lines. The wild type p53 gene was transfected by electroporation method. RESULTS: The expression of p53 protein was increased in four gastric carcinoma cell lines and one cell line (KATO-III) did not express. We found p53 point mutation in exon 5 and 8, and the p53 gene was deleted in KATO-III. The telomerase activity were observed in all five gastric carcinoma cell lines and there were no difference in telomere repeat length among five cell lines. After transfection with wild type p53, we could not find the change of telomerase activity in KATO-III. CONCLUSION: Although activation of telomerase activity and mutation of p53 gene may be needed in gastric carcinogenesis, the telomerase activity was not affected by restoration of p53 function in gastric carcinoma cell lines.
Blotting, Western ; Carcinogenesis ; Cell Line* ; Electroporation ; Exons ; Genes, p53* ; Point Mutation ; Stomach Neoplasms ; Telomerase* ; Telomere ; Transfection

BACKGROUND AND OBJECTIVE: Eosinophil is a major inflammatory cell in allergic diseases and parasitic infestations. Various cytokines such as GM-CSF, IL-3 and IL-5 are known to activate eosinophils and prolong their survival. Among them, IL-5 is the most potent stimulator of eosinophil survival. Recently, it was reported that increased expression of Bcl-2 is related to prolonged survival of IL-5 stimulated eosinophil. Theophylline is a useful drug in bronchial asthma, due not only to bronchial dilation but also to its anti-inflammatory effects. It has been suggested that anti inflammatory action of theophylline derives from the reduction of inflammatory cells in the airways which is mechated by stimulat on of apoptosis of inflammatory cells. In this study, we investigated, by measuring Bcl-2 expression of IL-5 stimulated eosinophil, the effect of theophylline on apoptosis as one of the anti-inflammatory action. MATERIAL AND METHOD: Peripheral eosinophils were isolated from atopic patients by using Perco- 11 discontinuous gradient and purified by negative selection technique using MACS. Eosinophil viability and apoptosis were measured by FACscan. Expression of Bcl-2 protein in eosinophils was detected by Western blot and ELISA. RESULTS: IL-5 increased the percentage of viable eosinophils and reduced the apoptosis of eosinophils in a dose dependent manner. The increased survival of IL-5 stimulated eosinophils was reduced by theophylline via activation of apoptosis. Bcl-2 was increased when eosinophils were cultured with IL-5 only, but when theophylline was cocultured, reduced Bcl-2 was seen with Western blot and ELISA. CONCLUSION: IL-5 increases the survival of eosinophil through the enhanced expression of Bcl- 2. Theophylline has counter action against IL-5 via inhibition of Bcl-2 induced by IL-5. Inhibiting the prolongation of eosinophil survival caused by IL-5 might be one possible mechanism of antiinflammatory effects of theophylline.
Apoptosis ; Asthma ; Blotting, Western ; Cytokines ; Enzyme-Linked Immunosorbent Assay ; Eosinophils* ; Granulocyte-Macrophage Colony-Stimulating Factor ; Humans ; Interleukin-3 ; Interleukin-5 ; Theophylline*

In order to investigate the clinical results of clear lens extraction for high myopia, the effects of 5.5mm sutureless corneoscleral procedure with low power IOL insertion on 21 patients (31 eyes) who were followed up averagely for 9.43 months were analyzed retrospectively. Prophylactic retinal treatment with argon laser was performed in 23 eyes to prevent retinal detachment. Eighty-seven percent (25/31 eyes) of eyes were within +/-1D of targeted refractive error and all eyes were within +/-2D of targeted refractive error. The postoperative corrected visual acuities were increased in 96.8% (30/31 eyes) and 80.7% (25/31 eyes) among them gained two or more lines. the corrected visual acuity of 20/40 or better were increased from 35.5%(11/31 eyes) preoperatively to 93.6% (29/31 eyes) postoperatively. Posterior capsular opacification was developed in two eyes and YAG laser posterior capsulotomy was performed at 2 and 7 months postoperatively. No retinal break, no cystoid macular edema were developed during the follow up period. In conclusion, the clear lens extraction was effective method for correction of severe high myopia but longer follow-up is needed to evaluate it`s complications.
Argon ; Follow-Up Studies ; Humans ; Lasers, Solid-State ; Macular Edema ; Myopia* ; Posterior Capsulotomy ; Refractive Errors ; Retinal Detachment ; Retinal Perforations ; Retinaldehyde ; Retrospective Studies ; Visual Acuity

OBJECTIVES: The poor survival rates among patients receiving surgery alone for stages II and III non-small cell lung cancer prompted several trials of adjuvant therapy after resection. We performed a prospective phase II study in patients with stage II-IIIA non-small cell lung cancer after resection to evaluate the feasibility, activity and toxicity of the postoperative sequential MVP chemotherapy and radiotherapy. METHODS: Between February 1991 and May 1995, 60 patients with resected stage II, IIIA non-small cell lung cancer received 2 cycles of MVP combination chemotherapy (Mitomycin-C 6 mg/m2, Vinblastine 6 mg/m2, Cisplatin 60 mg/m2) within 3 weeks after surgery, followed by thoracic irradiation (5,040 cGy after complete resection and 900 cGy booster to microscopically positive resection margin at 1.8 Gy per fraction) within 3-4 weeks after chemotherapy. RESULTS: Forty nine men and 11 women with a median age of 60.5 years (range 33-81 years) were included. During the median follow-up period of 828 days (61-2,015 days), 25 patients had developed recurrence. Among the 25 failures, 3 were local relapse only and 20 were distant metastasis only and 2 had both local and distant sites of recurrence. Three-year overall survival and event-free survival were 43% and 37%, respectively. Neutropenia of grade I-II was observed only in 13 patients. Eleven patient showed grade I-II radiation pneumonitis and 32 had grade I-II radiation esophagitis. CONCLUSION: Postoperative sequential MVP chemotherapy and radiotherapy in resected stage II-IIIA non-small cell lung cancer is well-tolerated and shows interesting activity.
Carcinoma, Non-Small-Cell Lung* ; Cisplatin* ; Disease-Free Survival ; Drug Therapy* ; Drug Therapy, Combination ; Esophagitis ; Female ; Follow-Up Studies ; Humans ; Male ; Mitomycin* ; Neoplasm Metastasis ; Neutropenia ; Prospective Studies ; Radiation Pneumonitis ; Radiotherapy* ; Recurrence ; Survival Rate ; Vinblastine*