In several human tumors, signal transducer and activator of transcription 3 (STAT3) and nuclear factor κB (NFκB) are activated and interact; how these STAT3–NFκB complexes are transported to the nucleus is not fully understood. In this study, we found that Rac1 was activated in starved cancer cells and that activated Rac1 coexisted with STAT3 and NFκB. Rac1 knockdown and overexpression of the dominant-negative mutant Rac1N19 inhibited the degradation of IκBα, an inhibitor of NFκB. MG132, an inhibitor of the ubiquitin proteasome pathway, increased the amount of non-phosphorylated IκBα, but not serine-phosphorylated IκBα, indicating that IκBα degradation by Rac1 in starved cancer cells is independent of IκBα serine phosphorylation by IKK. Rac1 knockdown also inhibited the nuclear translocation of STAT3–NFκB complexes, indicating that this translocation requires activated Rac1. We also demonstrated that the mutant STAT3 Y705F could form complexes with NFκB, and these unphosphorylated STAT3–NFκB complexes translocated into the nucleus and upregulated the activity of NFκB in starved cancer cells, suggesting that phosphorylation of STAT3 is not essential for its translocation. To our knowledge, this is the first study demonstrating the crucial role of Rac1 in the function of STAT3–NFκB complexes in starved cancer cells and implies that targeting Rac1 may have future therapeutic significance in cancer therapy.
Humans ; Phosphorylation ; Proteasome Endopeptidase Complex ; Serine ; STAT3 Transcription Factor ; Ubiquitin

PURPOSE: When murine myeloma cells P3-X63-Ag8.653 (V653) of this model treated with amin opterin, an anticancer drug, they can't synthesize nucleic acid via de novo or salvage pathway and selectively eliminated due to apoptosis. This study was aimed to clone specific known and novel genes preferentially expressed in aminopteirn-treated tumor cell apoptosis. MATERIALS AND METHODS: This study was aimed to clone specific known and novel genes pre ferentially expressed in aminopteirn-treated tumor cell apoptosis by using subtraction-PCR technique. RESULTS: By using this technique 868 clones were obtained. Of these 427 clones were positive with insert DNA. By using cross-hybridization Southern blotting, final 101 clones were selected. All of these genes were sequenced and analyzed by using genebank DNA database. Total 101 clones of genes preferentially expressed in apoptotic tumor cells were classified into 10 groups, which included ribosomal proteins, nuclear proteins, mitdegrees Chondrial proteins, signal transductional proteins, retroviral proteins, cell surface receptor proteins, cell structural proteins, unclassified miscellaneous proteins, and novel genes. Especially, Unknown novel genes preferentially ex pressed in this apoptotic tumor cells included clone numbers S1-63, 1-1, 1-3, 1-16, 1-18, 1-20, 3-33, 3-41, 3-44, 3-48, 3-55, 3-60, 6-17, 6-25, 8-12, 50-7, 50-23, and 100-35. CONCLUSION: It seemed that known and unknown novel genes cloned in this study would con tribute to the future studies regarding apoptosis of tumor cells and cancer treatment therepy.
Aminopterin ; Apoptosis* ; Blotting, Southern ; Clone Cells* ; Cloning, Organism* ; Databases, Nucleic Acid ; DNA ; Mass Screening* ; Membrane Proteins ; Nuclear Proteins ; Ribosomal Proteins ; Zidovudine

Background: Periocular dark circles (PDCs) are a common cosmetic complaint. Grading systems based on objective measures have been used but no standard system is in place. Objective: To determine factors associated with subjective and objective PDC severity. Methods: Enrolled patients (n=100) completed a questionnaire comprised of demographic variables, medical history, and self-perception of PDC. Those perceiving PDC graded dissatisfaction on a 10-point scale. Clinical severity (grades 0∼4) and subtype (constitutional, post-inflammatory, vascular, shadow effects, or others) were determined. A Konica Minolta CR-400 chromameter was used to obtain colorimetry measurements (L*a*b* values). The objective average difference in darkness (ΔL*) between the periocular region and the cheek was determined. Comparisons were made using Spearman correlation coefficients (r). Results: Patient dissatisfaction correlated with both clinical severity (r=0.46,p＜0.001) and the ΔL* by colorimetry (r=0.35, p=0.004). Factors associated with subjective dissatisfaction were female sex (r=0.38, p=0.002), higher Fitzpatrick skin type (r=0.42, p=0.001), fewer hours of sleep (r=–0.28, p=0.03), and use of concealer (r=0.35, p=0.004). Factors associated with objective measures were higher Fitzpatrick skin type (r=0.36, p= 0.0007 and r=0.28, p=0.009, respectively), family history of PDC (r=0.34, p＜0.001 and r=0.20, p=0.05), and history of eczema (r=0.45, p＜0.001 and r=0.20, p=0.0504). Clinical severity grading correlated with colorimetric severity (r=0.36, p=0.0003). Conclusion Overall, subjective dissatisfaction was associated with clinical severity. However, factors associated with subjective severity did not necessarily overlap with factors associated with objective severity. These findings highlight the importance of patient-reported grading. There may be added value in incorporating a component of subjective grading into the traditionally objective PDC grading scales.

Background: Periocular dark circles (PDCs) are a common cosmetic complaint. Grading systems based on objective measures have been used but no standard system is in place. Objective: To determine factors associated with subjective and objective PDC severity. Methods: Enrolled patients (n=100) completed a questionnaire comprised of demographic variables, medical history, and self-perception of PDC. Those perceiving PDC graded dissatisfaction on a 10-point scale. Clinical severity (grades 0∼4) and subtype (constitutional, post-inflammatory, vascular, shadow effects, or others) were determined. A Konica Minolta CR-400 chromameter was used to obtain colorimetry measurements (L*a*b* values). The objective average difference in darkness (ΔL*) between the periocular region and the cheek was determined. Comparisons were made using Spearman correlation coefficients (r). Results: Patient dissatisfaction correlated with both clinical severity (r=0.46,p＜0.001) and the ΔL* by colorimetry (r=0.35, p=0.004). Factors associated with subjective dissatisfaction were female sex (r=0.38, p=0.002), higher Fitzpatrick skin type (r=0.42, p=0.001), fewer hours of sleep (r=–0.28, p=0.03), and use of concealer (r=0.35, p=0.004). Factors associated with objective measures were higher Fitzpatrick skin type (r=0.36, p= 0.0007 and r=0.28, p=0.009, respectively), family history of PDC (r=0.34, p＜0.001 and r=0.20, p=0.05), and history of eczema (r=0.45, p＜0.001 and r=0.20, p=0.0504). Clinical severity grading correlated with colorimetric severity (r=0.36, p=0.0003). Conclusion Overall, subjective dissatisfaction was associated with clinical severity. However, factors associated with subjective severity did not necessarily overlap with factors associated with objective severity. These findings highlight the importance of patient-reported grading. There may be added value in incorporating a component of subjective grading into the traditionally objective PDC grading scales.

PURPOSE: The current study investigated whether the combined effects of soy intake and genetic polymorphisms of interleukin (IL) genes modify gastric cancer risk. MATERIALS AND METHODS: A total of 377 cases and 754 controls of Korean origin were included in the analysis. Soy consumption was assessed using a semi-quantitative food frequency questionnaire. Seven variants of IL10 (rs1800871), IL2 (rs2069763 and rs2069762), IL13 (rs6596090 and rs20541), and IL4R (rs7205663 and rs1805010) were genetically analyzed. To analyze the combined effect of soy intake and genetic polymorphisms, a low-intake group and high-intake group of each type of soy were categorized based on the intake level of the control group. Interactions between soy products and these genetic variants were analyzed by a likelihood ratio test, in which a multiplicative interaction term was added to the logistic regression model. RESULTS: A higher intake of nonfermented soy products was associated with a reduced cancer risk (odds ratio [OR], 0.62; 95% confidence interval [CI], 0.43 to 0.90), and the reduced risk was only apparent in males (OR, 0.44; 95% CI, 0.27 to 0.71). None of the IL genetic polymorphisms examined were independently associated with gastric cancer risk. Individuals with a minor allele of IL2 rs2069762 and a higher intake of nonfermented soy food had a decreased risk of gastric cancer (OR, 0.46; 95% CI, 0.31 to 0.68) compared to those with a lower intake (p(interaction)=0.039). CONCLUSION: Based on the genetic characteristics of the studied individuals, the interaction between IL2 rs2069762 and nonfermented soy intake may modify the risk of gastric cancer.
Alleles ; Case-Control Studies* ; Gene-Environment Interaction ; Humans ; Interleukin-10 ; Interleukin-13 ; Interleukin-2 ; Interleukins* ; Korea* ; Logistic Models ; Male ; Polymorphism, Genetic* ; Soy Foods ; Stomach Neoplasms*

We present a case of primary malignant melanoma of the thoracic spine mimicking intradural extramedullary meningioma or schwannoma. In 2010, a 55-year-old man presented with hypesthesia below the T4 dermatome level and bilateral leg weakness. Magnetic resonance imaging (MRI) of the thoracic spine revealed an approximately 1.5 cm well marginated mass lesion in the intradural extramedullary area at the level of T4-5. Preoperative MRI findings suggested benign spinal cord tumor such as meningioma or calcified schwannoma. Surgery revealed a well marginated black-colored tumor. After removal of the tumor, we observed pigmented seeding along the leptomeninges. According to the pathology report, the final diagnosis was malignant melanoma. No evidence of primary malignant tumor, abnormal lymphadenopathy or distant metastatic lesion was found on the PET-CT scan. As a result, the lesion was compatible with primary spinal malignant melanoma. Even if spinal melanoma was suspected in the thoracic spine, it is easy to simply diagnosis the finding as schwannoma or meningioma based on the preoperative radiological findings. Therefore, preoperative diagnosis should be decided carefully, especially for masses in the thoracic spinal tumor.
Humans ; Hypesthesia ; Leg ; Lymphatic Diseases ; Magnetic Resonance Imaging ; Melanoma ; Meningioma ; Middle Aged ; Neurilemmoma ; Seeds ; Spinal Cord ; Spinal Cord Neoplasms ; Spine

OBJECTIVE: To compare the detection performance of the automated whole breast ultrasound (AWUS) with that of the hand-held breast ultrasound (HHUS) and to evaluate the interobserver variability in the interpretation of the AWUS. MATERIALS AND METHODS: AWUS was performed in 38 breast cancer patients. A total of 66 lesions were included: 38 breast cancers, 12 additional malignancies and 16 benign lesions. Three breast radiologists independently reviewed the AWUS data and analyzed the breast lesions according to the BI-RADS classification. RESULTS: The detection rate of malignancies was 98.0% for HHUS and 90.0%, 88.0% and 96.0% for the three readers of the AWUS. The sensitivity and the specificity were 98.0% and 62.5% in HHUS, 90.0% and 87.5% for reader 1, 88.0% and 81.3% for reader 2, and 96.0% and 93.8% for reader 3, in AWUS. There was no significant difference in the radiologists' detection performance, sensitivity and specificity (p > 0.05) between the two modalities. The interobserver agreement was fair to good for the ultrasonographic features, categorization, size, and the location of breast masses. CONCLUSION: AWUS is thought to be useful for detecting breast lesions. In comparison with HHUS, AWUS shows no significant difference in the detection rate, sensitivity and the specificity, with high degrees of interobserver agreement.
Aged ; Breast Neoplasms/pathology/*ultrasonography ; Chi-Square Distribution ; *Clinical Competence ; Diagnosis, Differential ; Female ; Humans ; Image Interpretation, Computer-Assisted/methods ; Magnetic Resonance Imaging ; Middle Aged ; Neoplasm Staging ; Observer Variation ; Sensitivity and Specificity ; Ultrasonography, Mammary/*methods

Purposes: Although the standard management of limited stage small cell lung cancer is concurrent platinum-based chemotherapy with thoracic radiotherapy (TRT), the optimal timing of the TRT remains controversial. We investigated the feasibility of concurrent chemoradiation for the patients with limited stage small cell lung cancer after 2 cycles of combination chemotherapy with Etoposide/Cisplatin (EP). MATERIALS AND METHODS: EP consisted of Etoposide 100 mg/m2 on day 1 to 3 and Cisplatin 70 mg/m2 on day 1. Six cycles were given to the responders every 4 weeks. Total 55 Gy (1.8 Gy once-daily or 1.2 Gy twice-daily, 5 days per week) of TRT were given to the patients who showed at least a partial response after 2 cycles of EP. The other patients were treated by the physician's decision. The patients with complete remission were recommended to receive prophylactic cranial irradiation. RESULTS: Fifty patients were enrolled. Thirty-five (70%) of them showed responses (2 complete remissions and 33 partial remissions) after 2 cycles of EP. Thirty-three of the responders were given TRT starting with the 3rd cycle of EP. The nonresponders were treated with salvage chemotherapy and TRT. After completion of treatment for 50 patients, the overall response rate was 86% (29 complete remissions, 14 partial remissions). One patient (2%) showed stable disease, and 6 (12%) showed a progressive disease. The median progression free survival was 326 days and the median survival time was 410 days. One-, 2-, 3-, 4- and 5-year survival rates were 62%, 24%, 14%, 9% and 6%, respectively. As hematologic toxicities during chemoradiation, 35.1% with grade III/IV neutropenia and 18.9% with grade III/IV thrombocytopenia were noted. Grade II/III radiation pneumonitis and radiation esophagitis were noted in 5/1 and 13/1 patients (15.2%/ 3.0% and 39.4%/3.0%), respectively. One patient died of septicemia during chemoradiation. CONCLUSION: The concurrent EP and TRT after 2 cycles of EP was feasible in limited stage small cell lung cancer. Further study is required for the indentification of optimum timing of TRT during combination chemotherapy.
Chemoradiotherapy ; Cisplatin ; Cranial Irradiation ; Disease-Free Survival ; Drug Therapy ; Drug Therapy, Combination* ; Esophagitis ; Etoposide ; Humans ; Neutropenia ; Radiation Pneumonitis ; Radiotherapy* ; Sepsis ; Small Cell Lung Carcinoma* ; Survival Rate ; Thrombocytopenia

PURPOSE: Breast cancer treatment has progressed significantly over the past 20 years. However, knowledge regarding male breast cancer (MBC) is sparse because of its rarity. This study is an investigation of the clinicopathologic features, treatments, and clinical outcomes of MBC. MATERIALS AND METHODS: Clinical records of 59 MBC patients diagnosed during 1995-2014 from seven institutions in Korea were reviewed retrospectively. RESULTS: Over a 20-year period, MBC patients accounted for 0.98% among total breast cancer patients, and increased every 5 years. The median age of MBC patientswas 66 years (range, 24 to 87 years). Forty-three patients (73%) complained of a palpable breast mass initially. The median symptom duration was 5 months (range, 1 to 36 months). Mastectomy was performed in 96% of the patients. The most frequent histology was infiltrating ductal carcinoma (75%). Ninety-one percent of tumors (38/43) were estrogen receptor–positive, and 28% (11/40) showed epidermal growth factor receptor 2 (HER-2) overexpression. After curative surgery, 42% of patients (19/45) received adjuvant chemotherapy; 77% (27/35) received hormone therapy. Five out of ten patients with HER-2 overexpressing tumors did not receive adjuvant anti–HER-2 therapy, while two out of four patients with HER-2 overexpressing tumors received palliative trastuzumab for recurrent and metastatic disease. Letrozole was used for one patient in the palliative setting. The median overall survival durations were 7.2 years (range, 0.6 to 17.0 years) in patients with localized disease and 2.9 years (range, 0.6 to 4.3 years) in those with recurrent or metastatic disease. CONCLUSION: Anti–HER-2 and hormonal therapy, except tamoxifen, have been underutilized in Korean MBC patients compared to female breast cancer patients. With the development of precision medicine, active treatment with targeted agents should be applied. Further investigation of the unique pathobiology of MBC is clinically warranted.
Breast ; Breast Neoplasms ; Breast Neoplasms, Male* ; Carcinoma, Ductal ; Chemotherapy, Adjuvant ; Estrogens ; Female ; Humans ; Korea ; Male ; Male* ; Mastectomy ; Precision Medicine ; Prognosis ; Receptor, Epidermal Growth Factor ; Retrospective Studies ; Tamoxifen ; Trastuzumab