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Purpose@#The treatment of male breast cancer (MBC) has been extrapolated from female breast cancer (FBC) because of its rarity despite their different clinicopathologic characteristics. We aimed to investigate the distribution of intrinsic subtypes based on immunohistochemistry, their clinical impact, and treatment pattern in clinical practice through a multicenter study in Korea. @*Materials and Methods@#We retrospectively analyzed clinical data of 248 MBC patients from 18 institutions across the country from January 1995 to July 2016. @*Results@#The median age of MBC patients was 63 years (range, 25 to 102 years). Among 148 intrinsic subtype classified patients, 61 (41.2%), 44 (29.7%), 29 (19.5%), and 14 (9.5%) were luminal A, luminal B, human epidermal growth factor receptor 2, and triple-negative breast cancer, respectively. Luminal A subtype showed trends for superior survival compared to other subtypes. Most hormone receptor-positive patients (166 patients, 82.6%) received adjuvant endocrine treatment. Five-year completion of adjuvant endocrine treatment was associated with superior disease-free survival (DFS) in patients classified with an intrinsic subtype (hazard ratio [HR], 0.15; 95% confidence interval [CI], 0.04 to 0.49; p=0.002) and in all patients (HR, 0.16; 95% CI, 0.05 to 0.54; p=0.003). @*Conclusion@#Distribution of subtypes of MBC was similar to FBC and luminal type A was most common. Overall survival tended to be improved for luminal A subtype, although there was no statistical significance. Completion of adjuvant endocrine treatment was associated with prolonged DFS in intrinsic subtype classified patients. MBC patients tended to receive less treatment. MBC patients should receive standard treatment according to guidelines as FBC patients.
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Background@#Music is regarded as a beneficial tool for assessing the clinical symptoms and communication skills in individuals with autism spectrum disorder (ASD) or autism. The present study developed a music-based attention test (MAT) for individuals with autism using music parameters and the algorithm of the comprehensive attention test (CAT). @*Methods@#We recruited 51 autistic individuals and 50 neurotypical individuals to participate in the CAT, MAT, and social intelligence tests. The reliability and validity of the MAT were assessed using exploratory factor analysis, concurrent validity, and criterion-related validity. @*Results@#The MAT had sound internal consistency (high Cronbach’s α = 0.948). In addition, the MAT had suitable concurrent validity in the correlation between CAT and MAT, as well as good criterion validity when attention was measured using the MAT and was compared between autistic individuals and neurotypical individuals. Attention evaluated using the MAT was associated with the social quotient in individuals with autism. @*Conclusions@#The MAT could be a relevant tool for gauging attention in individuals with ASD.Furthermore, attention determined using the MAT may be correlated with social quotient in autistic individuals. Future studies should consider that using music in the field of attention could improve the social quotient of individuals with autism.
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Purpose@#: The study aimed to identify relationship among intensive care unit (ICU) nurses’ critical thinking disposition, medication error risk level of high-alert medication, and medication safety competency, as well as the factors affecting medication safety competency. @*Methods@#: The participants were 266 ICU nurses of one higher-tier general hospital and one general hospital in Province. The data were collected using structured self-administered questionnaire from August 10 to August 31, 2021. Measurements included the critical thinking disposition questionnaire, nurses’s knowledge of high-alert medication questionnaire, the medication safety competency scale. Data were analyzed using hierarchical multiple regressions using SPSS/WIN 28.0. @*Results@#: In the multiple regression analysis, the medication safety competence has a statistically significant correlation with the working department, the critical thinking disposition, and medication error risk level of high-alert medication. @*Conclusion@#: Based on the results of this study, it is suggested to develop and apply an educational strategy that can strengthen the knowledge and skills of critical thinking disposition and medication error risk level of high-alert medication to improve the ICU nurse’s medication safety competency.
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Purpose@#: This study aimed to identify intensive care units (ICU) nurses’ experience of traumatic events, deliberate rumination, self-disclosure, social support, and post-traumatic growth (PTG), and to explore relationships among the variables. @*Methods@#: Participants were 157 nurses who have provided direct patient care for six months or more in ICUs at a university hospital. Collected data were analyzed using descriptive statistics, independent t-tests, one-way ANOVAs, Pearson correlations, and multiple linear regressions using the SPSS/WIN version 23.0. @*Results@#: The PTG was found to be significantly associated with deliberate rumination (r=0.36, p<.001), self-disclosure (r=0.39, p<.001), and social support (r=0.54, p<.001). Factors that affect PTG significantly were found in the order of social support (β=0.40, p<.001), self-disclosure (β=0.25, p<.001), and deliberate rumination (β=0.24, p<.001). The final regression model explained 40.1% of the variance of PTG (F=26.33, p<.001). @*Conclusion@#: The influencing factors identified in this study on PTG, including social support, self-disclosure, and deliberate rumination should be included in programs to promote PTG for ICU nurses who may experience traumatic events repeatedly.
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Purpose@#This study aimed to identify the major keywords and the structure of the networks for each major topic to gain knowledge on factors influencing the quality of life of cancer survivors using Text Network Analysis (TNA) and topic modeling. @*Methods@#The study was conducted in four steps:(1) collecting abstracts, (2) text preprocessing in Python, (3) building a co-occurrence matrix, and (4) analyzing network features and clustering topic groups. From 2010 to 2020, 133 studies related to factors affecting the quality of life of cancer survivors were collected from several databases (PubMed, Embase, Cochrane, CINAHL RISS, KoreaMed, KISS). @*Results@#As a result of analyzing 9,968 evaluation results on “breast cancer,” “female,” “depression,” “treatment,” “age,” “questionnaire,” “symptom,” and “diagnosis,” five topics were derived after topic modeling considering coherence score and perplexity score. The main themes were breast cancer survivor, symptom experience, colon cancer survivor, psycho-social factors, and lifestyle and health management. @*Conclusion@#Based on the results of this study, symptoms such as depression, physical activity, and lifestyle and health management are significant factors affecting the quality of life of cancer survivors.
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In 2017, Korean Society of Medical Oncology (KSMO) published the Korean management guideline of metastatic prostate cancer. This paper is the 2nd edition of the Korean management guideline of metastatic prostate cancer. We updated recent many changes of management in metastatic prostate cancer in this 2nd edition guideline. The present guideline consists of the three categories: management of metastatic hormone sensitive prostate cancer; management of metastatic castration resistant prostate cancer; and clinical consideration for treating patients with metastatic prostate cancer. In category 1 and 2, levels of evidence (LEs) have been mentioned according to the general principles of evidence-based medicine. And grades of recommendation (GR) was taken into account the quality of evidence, the balance between desirable and undesirable effects, the values and preferences, and the use of resources and GR were divided into strong recommendations (SR) and weak recommendations (WR). A total of 16 key questions are selected. And we proposed recommendations and described key evidence for each recommendation. The treatment landscape of metastatic prostate cancer is changing very rapid and many trials are ongoing. To verify the results of the future trials is necessary and should be applied to the treatment for metastatic prostate cancer patients in the clinical practice. Especially, many prostate cancer patients are old age, have multiple underlying medical comorbidities, clinicians should be aware of the significance of medical management as well as clinical efficacy of systemic treatment.
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Background@#Liver fibrosis is defined as the accumulation of the extracellular matrix and scar formation. The receptor for advanced glycation end products (RAGE) has been demonstrated to participate in fibrogenesis. S100B is a ligand of RAGE and exerts extracellular functions by inducing a series of signal transduction cascades. However, the involvement of S100B and RAGE in cholestasis-induced liver fibrosis remains unclear. In this study, we investigated S100B and RAGE expression during liver fibrosis in mice that underwent common bile duct ligation (BDL). @*Methods@#BDL was performed in 10-week-old male C57BL/6J mice with sham control (n = 26) and BDL (n = 26) groups. Expression levels of S100B, RAGE and fibrotic markers in the livers from both groups at week 1 and 3 after BDL were examined by western blot and quantitative real-time reverse transcription polymerase chain reaction analysis. Liver fibrotic changes were examined by histological and ultrastructural analysis. @*Results@#Histological staining with Sirius Red and the evaluation of the messenger RNA expression of fibrotic markers showed noticeable periportal fibrosis and bile duct proliferation. S100B was mainly present in bile duct epithelial cells, and its expression was upregulated in proportion to the ductular reaction during fibrogenesis by BDL. RAGE expression was also increased, and interestingly, triple immunofluorescence staining and transmission electron microscopy showed that both S100B and RAGE were expressed in proliferating bile duct epithelial cells and activated hepatic stellate cells (HSCs) of the BDL livers. In addition, in rat HSCs (HSC-T6), treatment with recombinant S100B protein significantly increased fibrotic markers in a dose-dependent manner, and RAGE small interfering RNA (siRNA) suppressed S100B-stimulated upregulation of fibrotic markers compared with cells treated with scramble siRNA and S100B. @*Conclusion@#These findings suggest that the increased expression of S100B and RAGE and the interaction between S100B and RAGE may play an important role in ductular reaction and liver fibrosis induced by BDL.
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In 2017, Korean Society of Medical Oncology (KSMO) published the Korean management guideline of metastatic prostate cancer. This paper is the 2nd edition of the Korean management guideline of metastatic prostate cancer. We updated recent many changes of management in metastatic prostate cancer in this 2nd edition guideline. The present guideline consists of the three categories: management of metastatic hormone sensitive prostate cancer; management of metastatic castration resistant prostate cancer; and clinical consideration for treating patients with metastatic prostate cancer. In category 1 and 2, levels of evidence (LEs) have been mentioned according to the general principles of evidence-based medicine. And grades of recommendation (GR) was taken into account the quality of evidence, the balance between desirable and undesirable effects, the values and preferences, and the use of resources and GR were divided into strong recommendations (SR) and weak recommendations (WR). A total of 16 key questions are selected. And we proposed recommendations and described key evidence for each recommendation. The treatment landscape of metastatic prostate cancer is changing very rapid and many trials are ongoing. To verify the results of the future trials is necessary and should be applied to the treatment for metastatic prostate cancer patients in the clinical practice. Especially, many prostate cancer patients are old age, have multiple underlying medical comorbidities, clinicians should be aware of the significance of medical management as well as clinical efficacy of systemic treatment.
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Background@#Liver fibrosis is defined as the accumulation of the extracellular matrix and scar formation. The receptor for advanced glycation end products (RAGE) has been demonstrated to participate in fibrogenesis. S100B is a ligand of RAGE and exerts extracellular functions by inducing a series of signal transduction cascades. However, the involvement of S100B and RAGE in cholestasis-induced liver fibrosis remains unclear. In this study, we investigated S100B and RAGE expression during liver fibrosis in mice that underwent common bile duct ligation (BDL). @*Methods@#BDL was performed in 10-week-old male C57BL/6J mice with sham control (n = 26) and BDL (n = 26) groups. Expression levels of S100B, RAGE and fibrotic markers in the livers from both groups at week 1 and 3 after BDL were examined by western blot and quantitative real-time reverse transcription polymerase chain reaction analysis. Liver fibrotic changes were examined by histological and ultrastructural analysis. @*Results@#Histological staining with Sirius Red and the evaluation of the messenger RNA expression of fibrotic markers showed noticeable periportal fibrosis and bile duct proliferation. S100B was mainly present in bile duct epithelial cells, and its expression was upregulated in proportion to the ductular reaction during fibrogenesis by BDL. RAGE expression was also increased, and interestingly, triple immunofluorescence staining and transmission electron microscopy showed that both S100B and RAGE were expressed in proliferating bile duct epithelial cells and activated hepatic stellate cells (HSCs) of the BDL livers. In addition, in rat HSCs (HSC-T6), treatment with recombinant S100B protein significantly increased fibrotic markers in a dose-dependent manner, and RAGE small interfering RNA (siRNA) suppressed S100B-stimulated upregulation of fibrotic markers compared with cells treated with scramble siRNA and S100B. @*Conclusion@#These findings suggest that the increased expression of S100B and RAGE and the interaction between S100B and RAGE may play an important role in ductular reaction and liver fibrosis induced by BDL.
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Purpose@#The purpose of this study was to evaluate clinical characteristics and treatment pattern of ovarian clear cell carcinoma (OCCC) in Korea and the role of adjuvant chemotherapy in earlystage. @*Materials and Methods@#Medical records of 308 cases of from 21 institutions were reviewed and data including age, performance status, endometriosis, thromboembolism, stage, cancer antigen 125, treatment, recurrence, and death were collected. @*Results@#Regarding stage of OCCC, it was stage I in 194 (63.6%), stage II in 34 (11.1%), stage III in 66 (21.6%), and stage IV in 11 (3.6%) patients. All patients underwent surgery. Optimal surgery (residual disease ≤ 1 cm) was achieved in 89.3%. Majority of patients (80.5%) received postoperative chemotherapy. The most common regimen was taxane-platinum combination (96%). Median relapse-free survival (RFS) was 138.5 months for stage I, 33.4 for stage II, 19.3 for stage III, and 9.7 for stage IV. Median overall survival (OS) were not reached, 112.4, 48.7, and 18.3 months for stage I, II, III, and IV, respectively. Early-stage (stage I), endometriosis, and optimal debulking were identified as favorable prognostic factors for RFS. Early-stage and optimal debulking were also favorable prognostic factors for OS. Majority of patients with early-stage received adjuvant chemotherapy. However, additional survival benefit was not found in terms of recurrence. @*Conclusion@#Majority of patients had early-stage and received postoperative chemotherapy regardless of stage. Early-stage and optimal debulking were identified as favorable prognostic factors. In stage IA or IB, adding adjuvant chemotherapy did not show difference in survival. Further study focusing on OCCC is required.
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PURPOSE: We investigated whether irinotecan plus capecitabine improved progression-free survival (PFS) compared with capecitabine alone in patients with human epidermal growth factor 2 (HER2) negative and anthracycline and taxane pretreated metastatic breast cancer (MBC). MATERIALS AND METHODS: A total of 221 patients were randomly assigned to irinotecan (80 mg/m2, days 1 and 8) and capecitabine (1,000 mg/m2 twice a day, days 1-14) or capecitabine alone (1,250 mg/m2 twice a day, days 1-14) every 3 weeks. The primary endpoint was PFS. RESULTS: There was no significant difference in PFS between the combination and monotherapy arm (median, 6.4 months vs. 4.7 months; hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.63 to 1.11; p=0.84). In patients with triple-negative breast cancer (TNBC, n=90), the combination significantly improved PFS (median, 4.7 months vs. 2.5 months; HR, 0.58; 95% CI, 0.37 to 0.91; p=0.02). Objective response rate was numerically higher in the combination arm, though it failed to reach statistical significance (44.4% vs. 33.3%, p=0.30). Overall survival did not differ between arms (median, 20.4 months vs. 24.0 months; p=0.63). While grade 3 or 4 neutropenia was more common in the combination arm (39.6% vs. 9.0%), hand-foot syndrome was more often observed in capecitabine arm. Quality of life measurements in global health status was similar. However, patients in the combination arm showed significantly worse symptom scales especially in nausea/vomiting and diarrhea. CONCLUSION: Irinotecan plus capecitabine did not prove clinically superior to single-agent capecitabine in anthracycline- and taxane-pretreated HER2 negative MBC patients. Toxicity profiles of the two groups differed but were manageable. The role of added irinotecan in patients with TNBC remains to be elucidated.
Subject(s)
Humans , Arm , Breast Neoplasms , Breast , Capecitabine , Diarrhea , Disease-Free Survival , Epidermal Growth Factor , Global Health , Hand-Foot Syndrome , Neutropenia , Quality of Life , Triple Negative Breast Neoplasms , Weights and MeasuresABSTRACT
BACKGROUND/OBJECTIVES: Although anaplastic thyroid carcinoma (ATC) is rare, it is one of the deadliest forms of thyroid cancer. The fatality rate for ATC is high, and the survival rate at one year after diagnosis is <20%. The present study aimed to investigate the anti-tumor activities of paclitaxel, radiation, and tyrosine kinase inhibitor (TKI) combined therapy in anaplastic thyroid cancer cells both in vitro and in vivo and explore its effects on apoptotic cell death pathways.MATERIALS #SPCHAR_X0026; METHODS: ATC cell line was exposed to TKI, lenvatinib in the presence or absence of paclitaxel with radiation, and cell viability was determined by MTT assay. Effects of the combined treatment on cell cycle and intracellular signaling pathways were assessed by flow cytometry and western blot analysis. The ATC cell line xenograft model was used to examine the anti-tumor activity in vivo.RESULTS: Our data revealed that the combined administration of paclitaxel, TKI, and radiation decreased cell viability in ATC cells, and also significantly increased apoptotic cell death in these cells, as demonstrated by the cleavage of caspase-3 and DNA fragmentation. This combination therapy reduced anti-apoptotic factor levels in ATC cells, while significantly decreasing tumor volume and increasing survival in ATC xenografts.CONCLUSION: These results indicate that administering the combination of paclitaxel, TKI, and radiation therapy may exert significant anticancer effects in preclinical models, potentially suggesting a new clinical approach for treating patients with ATC.
Subject(s)
Humans , Blotting, Western , Caspase 3 , Cell Cycle , Cell Death , Cell Line , Cell Survival , Diagnosis , DNA Fragmentation , Flow Cytometry , Heterografts , In Vitro Techniques , Paclitaxel , Protein-Tyrosine Kinases , Survival Rate , Thyroid Carcinoma, Anaplastic , Thyroid Neoplasms , Tumor BurdenABSTRACT
Occult breast cancer (OBC) is an asymptomatic condition. We report a case of OBC in a 72-year-old male patient who presented with severe dyspnea and upper extremity swelling. Computed tomography scan showed multiple lymph node enlargements in the supraclavicular and infraclavicular areas, and ultrasound scan showed multiple axillary lymph node enlargements. Based on the radiological findings, clinicians suspected lymphoma or disseminated metastasis from unknown primary malignancies. However, the axillary biopsy specimen revealed invasive breast cancer with hormonal receptor positivity.
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OBJECTIVE: Unrecognized left main coronary artery disease (LMCD) is often fatal; however, accuracy of non-invasive tests for diagnosing LMCD is still unsatisfactory. This study was performed to elucidate single-photon emission computed tomography (SPECT) detection of LMCD using quantitative coronary angiography (QCA) data. MATERIALS AND METHODS: Fifty-five patients (39 men; mean age, 68.1 ± 10.9 years) diagnosed with significant left main (LM) stenosis (≥ 50%) by invasive coronary angiography (ICA) were retrospectively reviewed. All study patients underwent SPECT with pharmacologic stress within 30 days of ICA. All coronary lesions were quantified via QCA, and SPECT findings were compared with QCA results. RESULTS: Only four patients (7.3%) had isolated LMCD; all others had combined significant stenosis (≥ 70%) of one or more other epicardial coronary arteries. Patients with more severe coronary artery disease tended to have higher values for summed difference scores in a greater number of regions, but the specific pattern was not clearly defined. Summed stress score of SPECT did not differ according to LM stenosis severity. Only three patients (5.4%) had a typical LM pattern of reversible perfusion defect on SPECT. A significant negative linear correlation between stenosis severity and stress perfusion percent was found in the left anterior descending artery region (r = −0.455, p < 0.001) but not in the left circumflex artery. CONCLUSION: Single-photon emission computed tomography findings were heterogeneous, not specific and poorly correlated to QCA data in patients with significant LMCD. This may be due to highly prevalent significant stenosis of other epicardial coronary arteries.
Subject(s)
Humans , Male , Arteries , Constriction, Pathologic , Coronary Angiography , Coronary Artery Disease , Coronary Vessels , Myocardial Ischemia , Perfusion , Retrospective Studies , Tomography, Emission-Computed , Tomography, Emission-Computed, Single-PhotonABSTRACT
PURPOSE: This study aimed to evaluate the efficacy and safety of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) chemotherapy beyond standard treatment for anthracycline- and taxane-pretreated metastatic breast cancer (MBC). METHODS: We consecutively enrolled 158 MBC patients who underwent CMF chemotherapy in a palliative setting at two academic hospitals in Korea between 2002 and 2016. RESULTS: The median age of the 158 enrolled patients was 51 years (range, 30–77 years). The enrolled patients were treated with a median of 5 lines of systemic treatment (range, 2–11) before CMF therapy, and the median time from diagnosis of MBC to CMF administration was 36.0 months (range, 7.1–146.7 months). The median number of cycles of CMF treatment was 3 (range, 1–19), and the relative dose intensity was 90.4%. The toxicity profile was mild, with an observed 3.1% of grade 2 and 5.0% of grade 3/4 neutropenia. Among 147 patients (93.0%) whose response to CMF was evaluated, the response rate was 10.9% (16/147), with complete response (CR) in one and partial response (PR) in 15. In addition, the disease control rate (calculated as CR+PR+stable disease) was 44.2% (65/147). The median progression-free survival and overall survival were 3.1 months (95% confidence interval [CI], 2.7–3.6) and 9.4 months (95% CI, 7.1–11.6), respectively. CONCLUSION: CMF therapy is effective and tolerable as salvage treatment for heavily pretreated MBC.
Subject(s)
Humans , Breast Neoplasms , Breast , Cyclophosphamide , Diagnosis , Disease-Free Survival , Drug Therapy , Fluorouracil , Korea , Methotrexate , Neutropenia , Palliative Care , Retrospective Studies , Salvage TherapyABSTRACT
The aim of this study was to investigate the correlation between physical activity (PA) level and mental health status in a population-based sample of Korean female patients with breast cancer. Our analysis included 76 patients with breast cancer and 44 healthy controls. The Korean versions of the International Physical Activity Questionnaire (IPAQ), Beck Depressive Inventory (BDI), State-Trait Anxiety Inventory-KY (STAI-KY), and Somatosensory Amplification Scale (SSAS), and Quality of Life (QOL) scale were assessed. The frequency of moderate PA level in breast cancer patients was significantly lower than that of healthy control subjects (t = −2.6; P = 0.011). In turn, the incidence of low PA level in breast cancer patients was significantly higher than that observed in healthy controls (t = 2.85; P = 0.005). A moderate PA level was inversely correlated with BDI score (r = −0.35; P = 0.008) and was positively correlated with QOL score (r = 0.38; P = 0.011). A low level of PA was inversely correlated with SSAS score (r = −0.39; P < 0.001). In healthy controls, a high level of PA was positively correlated with QOL score (r = 0.50; P = 0.043). Moderate PA level was inversely correlated with SSAS score (r = −0.59; P < 0.001). A low level of PA was also positively correlated with BDI score (r = 0.35; P = 0.008). A moderate or low intensity of PA was inversely correlated with depression and somatosensory amplification and was positively correlated with QOL in breast cancer patients. Finally, we suggest that progressively low-to-moderate levels of PA can be well adapted to positively impact several measures of mental health.
Subject(s)
Female , Humans , Anxiety , Breast Neoplasms , Breast , Depression , Incidence , Mental Health , Motor Activity , Quality of LifeABSTRACT
Neurofibromas can occur anywhere in the body, but they usually involve the head, neck, pelvis, and extremities. Abdominal visceral involvement is rare, and intrahepatic involvement is even less common. We describe a patient who suffered from plexiform neurofibromatosis with liver involvement. A 49-year-old man, who had previously been diagnosed with neurofibromatosis, underwent esophagogastroduodenoscopy and abdominal ultrasonography for screening purposes. Esophagogastroduodenoscopy showed grade 2 esophageal varices and abdominal ultrasonography showed conglomerated nodules with echogenic appearances in the perihepatic space. Magnetic resonance imaging showed presumed plexiform neurofibroma involving the lesser sac and hepatic hilum and encasing the common hepatic artery celiac trunk and superior mesenteric artery left portal triad. We report an unusual case of portal hypertension attributed to the compressive narrowing of the portal vein by presumed as plexiform neurofibroma at the lesser sac and hepatic hilum.
Subject(s)
Humans , Male , Middle Aged , Abdomen/diagnostic imaging , Endoscopy, Digestive System , Esophageal and Gastric Varices/pathology , Hepatic Artery/diagnostic imaging , Hypertension, Portal/diagnosis , Liver/diagnostic imaging , Magnetic Resonance Imaging , Neurofibroma, Plexiform/diagnosis , Tomography, X-Ray Computed , UltrasonographyABSTRACT
PURPOSE: Overexpression of cyclooxygenase 2 (COX-2) is thought to promote survival of transformed cells. Transforming growth factor beta (TGF-beta) exerts anti-proliferative effects on a broad range of epithelial cells. In the current study, we investigated whether TGF-beta can regulate COX-2 expression in A549 human lung adenocarcinoma cells, which are TGF-beta-responsive and overexpress COX-2. MATERIALS AND METHODS: Western blotting, Northern blotting, and mRNA stability assays were performed to demonstrate that COX-2 protein and mRNA expression were suppressed by TGF-beta. We also evaluated the effects of tristetraprolin (TTP) on COX-2 mRNA using RNA interference. RESULTS: We demonstrated that COX-2 mRNA and protein expression were both significantly suppressed by TGF-beta. An actinomycin D chase experiment demonstrated that COX-2 mRNA was more rapidly degraded in the presence of TGF-beta, suggesting that TGF-beta-induced inhibition of COX-2 expression is achieved via decreased mRNA stability. We also found that TGF-beta rapidly and transiently induced the expression of TTP, a well-known mRNA destabilizing factor, before suppression of COX-2 mRNA expression was observed. Using RNA interference, we confirmed that increased TTP levels play a pivotal role in the destabilization of COX-2 mRNA by TGF-beta. Furthermore, we showed that Smad3 is essential to TTP-dependent down-regulation of COX-2 expression in response to TGF-beta. CONCLUSION: The results of this study show that TGF-beta down-regulated COX-2 expression via mRNA destabilization mediated by Smad3/TTP in A549 cells.
Subject(s)
Humans , Adenocarcinoma , Blotting, Northern , Blotting, Western , Cyclooxygenase 2 , Dactinomycin , Down-Regulation , Epithelial Cells , Lung , Lung Neoplasms , RNA Interference , RNA Stability , RNA , RNA, Messenger , Transforming Growth Factor beta , TristetraprolinABSTRACT
PURPOSE: We investigated the relationships between metastasis-free interval (MFI) and tumor characteristics, and assessed the prognostic value of MFI for survival after metastasis in patients with metastatic breast cancer. Furthermore, we compared MFI among the subtypes. METHODS: We identified 335 patients with postoperative tumor recurrence at distant site(s). All patients underwent curative resection and had a MFI of at least 6 months. MFI was categorized as short ( or =2 years and or =5 years). Overall survival after metastasis (OSM) was estimated. RESULTS: Patients with a shorter MFI were younger, more likely to have initial metastasis to visceral organs, and had a larger tumor with a higher stage and grade as well as a higher rate of nodal involvement at initial diagnosis. Among 136 patients with known disease subtypes, shorter MFI was associated with the triple-negative subtype while longer MFI was associated with the hormone receptor-positive/human epidermal growth factor receptor 2 negative subtype. Mortality after metastasis declined sharply with increasing MFI up to approximately 2 years, and continued gradually declining between 2 and 5 years. An MFI longer than 5 years did not add any survival benefit. MFI was a significant prognostic factor for OSM independent of nodal status, stage, metastatic site, and hormone receptor status of the metastasized cancer. CONCLUSION: MFI is closely related to biological characteristics of both primary tumors and their metastases, and has a prognostic value for survival after metastasis. We therefore suggest investigation into treatments targeting improvement of MFI as a potential novel strategy.
Subject(s)
Humans , Breast Neoplasms , Breast , Diagnosis , Mortality , Neoplasm Metastasis , Population Characteristics , ErbB Receptors , RecurrenceABSTRACT
PURPOSE: This study aimed to evaluate the clinical significance of Ki-67 and p53 expressions in patients with pancreatic head cancer. METHODS: Between May 2008 and April 2013, immunohistochemical staining for Ki-67 and p53 was performed in 34 patients with pancreatic head cancer (ductal adenocarcinoma). All 34 patients underwent pancreaticoduodenectomy at Chonnam National University Hwasun Hospital, Hwasun, Korea. Clinical and histopathological characteristics were analyzed, relative to p53 expression. RESULTS: Thirty (88.2%) and twenty-one (61.7%) of the 34 pancreatic head cancers exhibited positive expression of Ki-67 and p53, respectively. Patients expressing Ki-67 and p53 experienced more frequent tumor recurrences within 1 year after surgical resection (P = 0.003 and P = 0.030, respectively). However, no correlation was detected between Ki-67 and p53 expression. Ki-67 expression was correlated with pathological grade, lymph node metasatsis, and clinical stage (P < 0.05). Importantly, Ki-67 was the independent predictive factor for postoperative recurrence within 1 year in both univariable and multivariable analyses (odds ratio, 27.219; 95% confidence interval, 1.403-528.135; P = 0.029). CONCLUSION: The expression of Ki-67 and p53 are significantly related to early postoperative recurrence within 1 year after surgical resection in pancreatic head cancer. Especially, Ki-67 was the independent predictive factor for postoperative recurrence within 1 year. Therefore, immunohistochemical staining for Ki-67 and p53 may be applied as a predictive marker for early postoperative recurrence in pancreatic head cancer.