Purpose: A widely distributed cell cycle inhibitor, p27, regulates cyclin-dependent kinase-cyclin complexes. Although the prognostic value of p27 has been established for various types of carcinomas, its role in luminal breast cancer remains poorly understood. This study aimed to explore the functional enrichment of p27 and identify potential drug targets in patients with luminal-type breast cancer. Methods: Clinicopathological data were collected from 868 patients with luminal-type breast cancer. Additionally, publicly available data from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset (1,500 patients) and the Gene Expression Omnibus database (855 patients) were included in the analysis. Immunohistochemical staining for p27, differential gene expression analysis, disease ontology analysis, survival prediction modeling using machine learning (ML), and in vitro drug screening were also performed. Results: Low p27 expression correlated with younger age, advanced tumor stage, estrogen receptor/progesterone receptor negativity, decreased cluster of differentiation 8+ T cell count, and poorer survival outcomes in luminal-type breast cancer. The METABRIC data revealed that reduced cyclin-dependent kinase inhibitor 1B (CDKN1B) expression (encoding p27) was associated with cell proliferation-related pathways and epigenetic polycomb repressive complex 2. Using ML, p27 emerged as the second most significant survival factor after N stage, thereby enhancing survival model performance. Additionally, luminal-type breast cancer cell lines with low CDKN1B expression demonstrated increased sensitivity to specific anticancer drugs such as voxtalisib and serdemetan, implying a potential therapeutic synergy between CDKN1B-targeted approaches and these drugs. Conclusion The integration of ML and bioinformatic analyses of p27 has the potential to enhance risk stratification and facilitate personalized treatment strategies for patients with breast cancer.

Purpose: A widely distributed cell cycle inhibitor, p27, regulates cyclin-dependent kinase-cyclin complexes. Although the prognostic value of p27 has been established for various types of carcinomas, its role in luminal breast cancer remains poorly understood. This study aimed to explore the functional enrichment of p27 and identify potential drug targets in patients with luminal-type breast cancer. Methods: Clinicopathological data were collected from 868 patients with luminal-type breast cancer. Additionally, publicly available data from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset (1,500 patients) and the Gene Expression Omnibus database (855 patients) were included in the analysis. Immunohistochemical staining for p27, differential gene expression analysis, disease ontology analysis, survival prediction modeling using machine learning (ML), and in vitro drug screening were also performed. Results: Low p27 expression correlated with younger age, advanced tumor stage, estrogen receptor/progesterone receptor negativity, decreased cluster of differentiation 8+ T cell count, and poorer survival outcomes in luminal-type breast cancer. The METABRIC data revealed that reduced cyclin-dependent kinase inhibitor 1B (CDKN1B) expression (encoding p27) was associated with cell proliferation-related pathways and epigenetic polycomb repressive complex 2. Using ML, p27 emerged as the second most significant survival factor after N stage, thereby enhancing survival model performance. Additionally, luminal-type breast cancer cell lines with low CDKN1B expression demonstrated increased sensitivity to specific anticancer drugs such as voxtalisib and serdemetan, implying a potential therapeutic synergy between CDKN1B-targeted approaches and these drugs. Conclusion The integration of ML and bioinformatic analyses of p27 has the potential to enhance risk stratification and facilitate personalized treatment strategies for patients with breast cancer.

Purpose: A widely distributed cell cycle inhibitor, p27, regulates cyclin-dependent kinase-cyclin complexes. Although the prognostic value of p27 has been established for various types of carcinomas, its role in luminal breast cancer remains poorly understood. This study aimed to explore the functional enrichment of p27 and identify potential drug targets in patients with luminal-type breast cancer. Methods: Clinicopathological data were collected from 868 patients with luminal-type breast cancer. Additionally, publicly available data from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset (1,500 patients) and the Gene Expression Omnibus database (855 patients) were included in the analysis. Immunohistochemical staining for p27, differential gene expression analysis, disease ontology analysis, survival prediction modeling using machine learning (ML), and in vitro drug screening were also performed. Results: Low p27 expression correlated with younger age, advanced tumor stage, estrogen receptor/progesterone receptor negativity, decreased cluster of differentiation 8+ T cell count, and poorer survival outcomes in luminal-type breast cancer. The METABRIC data revealed that reduced cyclin-dependent kinase inhibitor 1B (CDKN1B) expression (encoding p27) was associated with cell proliferation-related pathways and epigenetic polycomb repressive complex 2. Using ML, p27 emerged as the second most significant survival factor after N stage, thereby enhancing survival model performance. Additionally, luminal-type breast cancer cell lines with low CDKN1B expression demonstrated increased sensitivity to specific anticancer drugs such as voxtalisib and serdemetan, implying a potential therapeutic synergy between CDKN1B-targeted approaches and these drugs. Conclusion The integration of ML and bioinformatic analyses of p27 has the potential to enhance risk stratification and facilitate personalized treatment strategies for patients with breast cancer.

Background: Tumor spread through air spaces (STAS) is a recently discovered risk factor for lung adenocarcinoma (LUAD). The aim of this study was to investigate specific genetic alterations and anticancer immune responses related to STAS. By using a machine learning algorithm and drug screening in lung cancer cell lines, we analyzed the effect of Janus kinase 2 (JAK2) on the survival of patients with LUAD and possible drug candidates. Methods: This study included 566 patients with LUAD corresponding to clinicopathological and genetic data. For analyses of LUAD, we applied gene set enrichment analysis (GSEA), in silico cytometry, pathway network analysis, in vitro drug screening, and gradient boosting machine (GBM) analysis. Results: The patients with STAS had a shorter survival time than those without STAS (P < 0.001). We detected gene set-related downregulation of JAK2 associated with STAS using GSEA. Low JAK2 expression was related to poor prognosis and a low CD8+ T-cell fraction. In GBM, JAK2 showed improved survival prediction performance when it was added to other parameters (T stage, N stage, lymphovascular invasion, pleural invasion, tumor size). In drug screening, mirin, CCT007093, dihydroretenone, and ABT737 suppressed the growth of lung cancer cell lines with low JAK2 expression. Conclusion In LUAD, low JAK2 expression linked to the presence of STAS might serve as an unfavorable prognostic factor. A relationship between JAK2 and CD8+ T cells suggests that STAS is indirectly related to the anticancer immune response. These results may contribute to the design of future experimental research and drug development programs for LUAD with STAS.

BACKGROUND/AIMS: Fabry disease is an X-linked recessive and progressive disease caused by alpha-galactosidase A (alpha-GaL A) deficiency. We sought to assess the prevalence of unrecognized Fabry disease in dialysis-dependent patients and the efficacy of serum globotriaosylceramide (GL3) screening. METHODS: A total of 480 patients of 1,230 patients among 17 clinics were enrolled. Serum GL3 levels were measured by tandem mass spectrometry. Additionally, we studied the association between increased GL3 levels and cardiovascular disease, cerebrovascular disease, or left ventricular hypertrophy. RESULTS: Twenty-nine patients had elevated serum GL3 levels. The alpha-GaL A activity was determined for the 26 patients with high GL3 levels. The mean alpha-GaL A activity was 64.6 nmol/hr/mg (reference range, 45 to 85), and no patient was identified with decreased alpha-GaL A activity. Among the group with high GL3 levels, 15 women had a alpha-GaL A genetics analysis. No point mutations were discovered among the women with high GL3 levels. No correlation was observed between serum GL3 levels and alpha-GaL A activity; the Pearson correlation coefficient was 0.01352 (p = 0.9478). No significant correlation was observed between increased GL3 levels and the frequency of cardiovascular disease or cerebrovascular disease. CONCLUSIONS: Fabry disease is very rare disease in patients with end-stage renal disease. Serum GL3 measurements as a screening method for Fabry disease showed a high false-positive rate. Thus, serum GL3 levels determined by tandem mass spectrometry may not be useful as a screening method for Fabry disease in patients with end stage renal disease.
Adult ; Aged ; Fabry Disease/blood/*diagnosis ; Female ; Humans ; Kidney Failure, Chronic/blood/*therapy ; Male ; Middle Aged ; *Renal Dialysis ; Trihexosylceramides/*blood ; alpha-Galactosidase/genetics/metabolism

Although most of pseudocysts as one of complications of pancreatitis occur primarily within the pancreas, the extrapancreatic locations of pseudocysts, especially in the liver, are rare events. With advanced technology of imaging studies including abdominal computed tomography, ultrasonography, and magnetic resonance imaging, their frequency seems to be increasing. We report here a case of left intrahepatic pancreatic pseudocyst following acute pancreatitis. Percutaneous puncture revealed a high level of amylase and lipase in the collection, confirming the diagnosis of intrahepatic pseudocyst. Symptomatic intrahepatic pseudocysts can be managed surgically, transcutaneously or endoscopically, and asymptomatic intrahepatic pseudocysts can be treated conservatively. We report this case with a review of literature.
Acute Disease ; Aged ; Humans ; Liver Diseases/*diagnosis/etiology/ultrasonography ; Magnetic Resonance Imaging ; Male ; Pancreatic Pseudocyst/*diagnosis/etiology/ultrasonography ; Pancreatitis, Alcoholic/complications/*diagnosis/ultrasonography ; Tomography, X-Ray Computed

BACKGROUND/AIMS: The failure rates of first and second line therapies of Helicobacter pylori (H. pylori) eradication range from 15 to 20%. This study was aimed to evaluate the efficacy and safety of levofloxacin based triple therapy compared with standard triple or quadruple therapy for H. pylori eradication in Korea. METHODS: We enrolled two hundred and sixty seven patients with presence of H. pylori infection. One hundred and forty-one patients were treated with levofloxacin based triple therapy (LAP; levofloxacin, amoxicillin, proton pump inhibitor; PPI), and 126 patients were treated with standard triple therapy (CAP; clarithromycin, amoxicillin, PPI). We retreated the patients who had failed in H. pylori eradication with standard quadruple second-line therapy (MTPB; metronidazole, tetracycline, PPI, bismuth subcitrate) or levofloxacin based therapy (LAP or LCP; levofloxacin, clarithromycin, PPI). RESULTS: In first line therapy of H. pylori eradication, the eradication rates of levofloxacin based triple therapy and standard triple therapy were 69.8% and 74.0% respectively (p=0.52). In second-line therapy, the eradication rate of levofloxacin based triple therapy and standard quadruple therapy were 62.5% and 40.0% respectively (p=0.34). CONCLUSIONS: Levofloxacin based triple therapy is effective as standard regimen to eradicate H. pylori infection and is useful for an alternative rescue therapy as well.
Adult ; Aged ; Anti-Bacterial Agents/*administration & dosage ; Drug Therapy, Combination ; Female ; Helicobacter Infections/*drug therapy ; *Helicobacter pylori ; Humans ; Male ; Middle Aged ; Ofloxacin/*administration & dosage

BACKGROUND: Corticosteroids in combination with cytotoxic drugs are the mainstays of therapy for idiopathic pulmonary fibrosis (IPF). However, there has been no regimen showing any survival benefit. The aim of this study was to describe a short-term clinical experience on interferon gamma-1b (IFN-gamma1b) therapy for IPF, as an antifibrotic agent. METHODS: Medical records of 27 patients who were treated with IFN-gamma1b (2 million IU, 3 times a week, subcutaneous injection) were retrospectively reviewed. Treatment response was assessed using ATS/ERS criteria in 17 patients who received IFN-gamma1b for more than 6 months. In addition, we compared the efficacy of IFN-gamma1b therapy with that of cyclophosphamide+/-prednisolone therapy (n=26). RESULTS: The median age of IFN-gamma treated group (M:F=19:8) was 59 years (44-74 years). Compared to the patients who showed a stable response at 6 months (n=12), the deteriorated group (n=5) had worse baseline lung function (FVC, 55.4+/-11.3% vs. 70.7+/-10.9%, p=0.019; DLco, 50.3+/-7.3% vs. 76.9+/-19.6%, p=0.014). Lower baseline PaO2 on room air breathing was observed in the deteriorated group (68.6+/-7.8mmHg vs. 91.4+/-6.6mmHg p=0.001). Subcutaneous IFN-gamma1b did not show better efficacy than prednisolone. Five patients discontinued IFN-gamma because of severe side effects. ARDS developed in one patient, who eventually died. CONCLUSION: The administration of IFN-gamma1b is not desirable for patients diagnosed with IPF with poor lung function. Long-term and large-scaled clinical studies are needed for its efficacy in IPF.
Adrenal Cortex Hormones ; Humans ; Idiopathic Pulmonary Fibrosis* ; Interferon-gamma ; Interferons* ; Lung ; Medical Records ; Prednisolone ; Pulmonary Fibrosis ; Respiration ; Retrospective Studies

BACKGROUND: The tuberculin skin test has been used to diagnose latent tuberculosis infection, but is not widely used to diagnose or exclude pulmonary tuberculosis. The objective of this study was to evaluate the diagnostic utility of the tuberculin test in diagnosing and excluding pulmonary tuberculosis, and differentiating pulmonary tuberculosis from nontuberculous mycobacteria (NTM) pulmonary disease, when a sputum acid-fast bacilli (AFB) smear was positive. MATERIAL AND METHODS: From October 2002 to August 2003, among all the inpatients of the Division of Pulmonary and Critical Care Medicine at Samsung Medical Center, 258 patients with clinical suspicion of pulmonary tuberculosis were enrolled and underwent a tuberculin test. RESULTS: 156 males and 102 females were included, with a mean age of 57.5 years. The final diagnoses included lung cancer in 89 cases (34.5%), pulmonary tuberculosis in 59 cases (22.9%), bacterial pneumonia in 33 cases (12.8%) and NTM pulmonary disease in 24 cases (9.3%). The positive tuberculin test rate was higher in the tuberculosis than non-tuberculosis group; 81.4 (48/59) vs. 42.4% (81/199). (p<0.001). In 208 patients with a negative sputum AFB smear, the result of the tuberculin test was positive in 69.4% (25/36) of the tuberculosis group and in 44.8% (77/172) of the non-tuberculosis group (p=0.007), so a positive result of the tuberculin test could predict pulmonary tuberculosis with 69.4% sensitivity, 55.2% specificity, a 24.5% positive predictive value and a 89.6% negative predictive value. In 50 patients with a positive sputum AFB smear, the positive rates of the tuberculin test were 83.9% (26/31) in tuberculosis group and 21.1% (4/19) in NTM pulmonary disease group (p<0.001), so a positive result of the tuberculin skin test could predict pulmonary tuberculosis with 83.9% sensitivity, 78.9% specificity, a 86.7% positive predictive value and a 75.0% negative predictive value. CONCLUSION: The tuberculin test could be useful in excluding pulmonary tuberculosis when the sputum AFB smear is negative, and to differentiate pulmonary tuberculosis from NTM pulmonary disease when the sputum AFB smear is positive.
Adult* ; Critical Care ; Diagnosis ; Female ; Humans ; Inpatients ; Korea ; Latent Tuberculosis ; Lung Diseases ; Lung Neoplasms ; Male ; Nontuberculous Mycobacteria ; Pneumonia, Bacterial ; Skin Tests ; Sputum ; Tuberculin Test* ; Tuberculin* ; Tuberculosis ; Tuberculosis, Pulmonary*

BACKGROUND: As an effective regimen for isoniazid (INH)-resistant pulmonary tuberculosis, several treatment regimens have been recommended by many experts. In Korea, a standard regimen has not been established for INH-resistant tuberculosis, and the treatment by individual physicians has been performed on an empirical bases. The purpose of the present study was to retrospectively describe the treatment characteristics and evaluate the treatment outcomes of patients with INH-resistant tuberculosis. MATERIALS AND METHODS: Sixty of 69 patients reported to have INH-resistant tuberculosis from 1994 to 2001 were retrospectively analyzed. Exclusion criteria included: death from other causes, with the exceptions of tuberculosis and incomplete treatment, including a patient's transfer-out. RESULTS: A previous tuberculosis history was found in 28 (46.7%) patients. The sputum smear for acid-fast bacilli was positive in 44 (73.3%) patients, and 30 (50.0%) had cavitary disease. Streptomycin resistance coexisted in 25.0% of isolates. INH was to be prescribed continuously, even after INH resistance was reported, in 86.0% of patients. The treatment regimens were diverse between the patients according to drug regimen composition and treatment duration. The most frequent prescribed regimen included rifampin, ethambutol and pyrazinamide, with and without INH, for the full 12-month term of treatment. Treatment failure occurred in 13 (21.7%) patients. Cavitary disease (p=0.005) and a treatment regimen with second-line drugs, excluding rifampin (p=0.015), were associated with treatment failure. One patient experienced a relapse. CONCLUSIONS: Standardized treatment guidelines will be needed in Korea to improve the treatment efficacy for INH-resistant tuberculosis.
Drug Resistance ; Ethambutol ; Humans ; Isoniazid ; Korea ; Pyrazinamide ; Recurrence ; Retrospective Studies ; Rifampin ; Sputum ; Streptomycin ; Treatment Failure ; Treatment Outcome ; Tuberculosis ; Tuberculosis, Pulmonary*