I kappa B kinase beta (IKK beta) subunit of IKK complex is essential for the activation of NF-kappa B in response to various proinflammatory signals. Cys-179 in the activation loop of IKK beta is known to be the target site for IKK inhibitors such as cyclopentenone prostaglandins, arsenite, and antirheumatic gold compounds. Here we show that a mutant IKK beta in which Cys-179 is substituted with alanine had decreased activity when it was expressed in HEK-293 cells, and TNF stimulation did not restore the activity. Phosphorylation of activation loop serines (Ser-177 and Ser-181) which is required for IKK beta activation was reduced in the IKK beta (C179A) mutant. The activity of IKK beta (C179A) was partially recovered when its phosphorylation was enforced by coexpression with mitogen-activated protein kinase kinase kinases (MAPKKK) such as NF-kappa B inducing kinase (NIK) and MAPK/extracellular signal-regulated kinase kinase kinase 1(MEKK1) or when the serine residues were replaced with phospho-mimetic glutamate. The IKK beta (C179A) mutant was normal in dimer formation, while its activity abnormally responded to the change in the concentration of substrate ATP in reaction mixture. Our results suggest that Cys-179 of IKK beta plays a critical role in enzyme activation by promoting phosphorylation of activation-loop serines and interaction with ATP.
Transfection ; Serine/*metabolism ; Protein Binding ; Phosphorylation ; Mutant Proteins/chemistry ; MAP Kinase Kinase Kinases/metabolism ; I-kappa B Kinase/*chemistry ; Humans ; Hela Cells ; Enzyme Activation/*physiology ; Cysteine/*physiology ; Cells, Cultured ; Catalytic Domain ; Amino Acid Substitution/physiology ; Adenosine Triphosphate/metabolism

Background: A cervical transforaminal epidural (TFE) steroid injection is a useful treatment option for cervical radicular pain, but it carries a small risk of catastrophic complications.Several studies have reported that cervical facet joint (FJ) steroid injection can reduce cervical radicular pain through an indirect epidural spread. The aim of this retrospective comparative study was to evaluate the pain scores and functional disability in subjects receiving cervical FJ or TFE steroid injection for the treatment of cervical radicular pain due to foraminal stenosis (FS). Methods: We selected 278 patients 18 years of age and older who underwent cervical FJ (n = 130) or TFE (n= 148) steroid injection for cervical radicular pain. The primary outcomes included pain scores and functional disability during hospital visits one, three, and six months after the initial injection. Secondary outcomes were the proportion of responders and Medication Quantification Scale (MQS) scores. Adverse events and variables correlating with effectiveness one month after the initial injection were also evaluated. Results: The Numeric Rating Scale and Neck Disability Index scores showed a significant improvement one, three, and six months after the initial injection in both groups, with no significant differences between the groups. No significant differences were observed in the success rates of the procedure one, three, and six months after the initial injection for either group. There were no significant differences in MQS between the groups during the followup period. Univariate and multivariate logistic regression analyses revealed that the injection method, age, sex, number of injections, FS severity, MQS, pain duration, and the presence of cervical disc herniation were not independent predictors of treatment success. Conclusion The efficacy of FJ steroid injection may not be inferior to that of TFE steroid injection in patients with cervical radicular pain due to FS.

PURPOSE: A phase II study of vinorelbine and ifosfamide combination chemotherapy in patients with advanced or recurrent non-small cell lung cancer (NSCLC) was conducted to assess response rate, response duration, and toxicites. MATERIALS AND METHODS: Patients with advanced NSCLC who had no prior systemic chemotherapy were eligible. They have no central nervous system metastasis and recurrent or progressive disease after surgery or radiotherapy. Each cycle consisted of vinorelbine 25 mg/m' i.v. days 1 & 8, and ifosfamide 2 g/m i.v. days 1, 2 & 3 with Mesna and treatments were repeated every 21 days. RESULTS: Forty patients with advanced or recurrent NSCLC were treated at multi center between March, 1997 and March, 1998. Six patients were not evaluable because five patients refused therapy after the first course and one patient was protocol violation. Of 34 evaluable patients, objective responses were seen in 11 (32.4%) patients (CR 0%, PR 32.4%). The median duration of response was 16.4 weeks. The median overall survival was 9.5 months. The toicities of this regimen were acceptable without treatment related toxic death. CONCLUSION: We concluded that combination regimen of vinorelbine and ifosfamide was effective and tolerable in the treatment of advanced non-small cell lung cancer.
Carcinoma, Non-Small-Cell Lung ; Central Nervous System ; Drug Therapy ; Drug Therapy, Combination ; Humans ; Ifosfamide* ; Mesna ; Neoplasm Metastasis ; Radiotherapy ; Small Cell Lung Carcinoma*

Thirty eight women with recurrent breast carcinoma involving chest wall and/or regional lymph nodes after surgery with or without systemic therapy were treated with radiation between 1979 and 1986. Among them, 5 patients were excluded from analysis because of incomplete treatment. The median follow up of survivors was 30 months (randged 1-79 months). Fifteen (45%) patients had their disease confined to the chest wall and eighteen patients had lymph node involvement as some of their locoregional recurrent disease. Within 36 months after the initial treatment, 87% of recurrences manifested themselves. All patients had radiotherapy to at least the site of involvement. In 8 patients, recurrent tumors were treated with complete excision followed by radiation. Of the remaining 25 patients, 18(72%) had complete response (CR) following radiotherapy. The actuarial 3-year survival of all patients following locoregional recurrence was 50%. Three year survival was 24% in those 25 patients who had recurrences within 24 months of the initial treatment. For those 8 patients whose recurrences occurred after more than 24 month disease free interval, the 3-year survival was 100%. For those patients with recurrences confined to chest wall alone, 3-year survival was 57%. The patients who had lymph node involvement as part of their locoregional recurrences had a 43% 3-year survival. The majority of them developed distant metastases. Those patients who had a CR showed 63% 3-year survival. On the other hand, 1 year survival was only 33% for those patients who had a less than CR. Three patients developed carcinoma of the contralateral breast following radiotherapy. Three year survival following locoregional recurrence was 40% for patients whose initial treatment for their primary breast carcinoma was surgery and adjuvant systemic therapy. For those patients whose primary breast carcinoma was treated by surgery alone, the 3-year survival following locoregional recurrence was 71%. In patients who had subsequent recurrence after radiotherapy, the actuarial survival was 25% at 2 years.
Breast Neoplasms* ; Breast* ; Female ; Follow-Up Studies ; Hand ; Humans ; Lymph Nodes ; Neoplasm Metastasis ; Radiotherapy* ; Recurrence ; Survivors ; Thoracic Wall

PURPOSE: Adenoid cystic carcinoma (ACC) is a high-grade malignant tumor of the salivary glands, clinically characterized by multiple recurrences and late distant metastasis. Biological markers for assessing the prognosis of ACC have remained elusive. The purpose of this study was to investigate whether the protein expressions of ataxia telangiectasia mutated (ATM), p53, and ATM-mediated phosphorylated p53 are related to patient survival in ACC. MATERIALS AND METHODS: In this study, 48 surgical samples were used to assess the expressions of ATM and its downstream target p53. Fisher's exact test and Kaplan-Meier analysis were conducted to evaluate the role of ATM, p53, and phospho-p53 (S15) protein expressions in predicting patient survival and distant metastasis. RESULTS: Myb expression was positive in 85.4% of ACCs, but did not reflect patient survival rate. In contrast, low expression of ATM in cancer cells was significantly correlated with poor survival rate (p=0.037). Moreover, under positive p53 expression, low expression of ATM was highly predictive of poor survival in ACC (p=0.017). CONCLUSION: These data indicate that combined assessment of ATM and p53 expression can serve as a useful prognostic marker for assessing survival rate in patients with ACC of the salivary glands.
Adenoids* ; Ataxia Telangiectasia ; Biomarkers ; Carcinoma, Adenoid Cystic* ; Humans ; Kaplan-Meier Estimate ; Neoplasm Metastasis ; Prognosis ; Recurrence ; Salivary Glands* ; Survival Rate

Adenoid cystic carcinoma (ACC) is one of the high grade malignant tumors in salivary glands, prognosticallycharacterized by multiple recurrences and late distant metastasis. Recently, Myb-NFIB fusion or rearrangements of Myb have been detected as a hallmark of ACC. However, no biological marker estimating the outcome of ACC has been proven yet. Purpose of this study was to investigate whether the protein expression of ATM gene is related to patients’ survival in ACC. This study consists of 48 surgical samples for detecting expression of ATM and its downstream p53. Kaplan-Meier plots were used to evaluate the relationship between the protein expression ratios of ATM, p53 and its ATM-mediated phosphorylation and the overall survival rate of patients with ACC. low expression of ATM in cancer cells correlated with poor survival rate (p = 0.037). However, low expression of ATM in stromal fibroblasts was not significantly associated with patient outcome. Moreover, this study evaluated ATM expression stratified by p53 and its ATM-mediated phosphorylation status. ATM loss was associated with a significantly decreased overall survival in patients simultaneously showing overexprssion of p53 (p = 0.01) and low expression of p53 phospho S15 (p = 0.05). These data supported that loss of ATM and its functional status in p53 pathway is an important factor associated with poor outcome of patients in ACC of salivary glands.

Chronic spontaneous urticaria (CSU) is defined as the occurrence of spontaneous wheals, angioedema, or both for >6 weeks in the absence of specific causes. It is a common condition associated with substantial disease burden both for affected individuals and societies in many countries, including Korea. CSU frequently persists for several years and requires high-intensity treatment; therefore, patients experience deteriorations in quality of life and medication-associated complications. During the last decade, there have been major advances in the pharmacological treatment of CSU and there is an outstanding need for evidence-based guidelines that reflect clinical practice in Korea. The guidelines reported here represent a joint initiative of the Korean Academy of Asthma, Allergy and Clinical Immunology and the Korean Dermatological Association, and aim to provide evidence-based guidance for the management of CSU in Korean adults and children. In Part 1, disease definition, guideline scope and development methodology as well as evidence-based recommendations on the use of antihistamines and corticosteroids are summarized.

Chronic spontaneous urticaria (CSU) is defined as the occurrence of spontaneous wheals, angioedema, or both for >6 weeks in the absence of specific causes. It is a common condition associated with substantial disease burden both for affected individuals and societies in many countries, including Korea. CSU frequently persists for several years and requires high-intensity treatment; therefore, patients experience deteriorations in quality of life and medication-associated complications. During the last decade, there have been major advances in the pharmacological treatment of CSU and there is an outstanding need for evidence-based guidelines that reflect clinical practice in Korea. The guidelines reported here represent a joint initiative of the Korean Academy of Asthma, Allergy and Clinical Immunology and the Korean Dermatological Association, and aim to provide evidence-based guidance for the management of CSU in Korean adults and children. In Part 1, disease definition, guideline scope and development methodology as well as evidence-based recommendations on the use of antihistamines and corticosteroids are summarized.