Radiosensitization of non-small cell lung cancer by kaempferol.

The aim of the present study was to determine whether kaempferol has a radiosensitization potential for lung cancer in vitro and in vivo. The in vitro radio-sensitization activity of kaempferol was elucidated in A-549 lung cancer cells by using an MTT (3-(4 5-dimethylthiazol-2-yl)-25-diphenyl-tetrazolium bromide) assay, cell cycle analysis and clonogenic assay. The in vivo activity was evaluated in the BALB/c nude mouse xenograft model of A-549 cells by hematoxylin and eosin staining and immunohistochemistry, and the tumor volume was recorded. Protein levels of the apoptotic pathway were detected by western blot analysis. Treatment with kaempferol inhibited the growth of A-549 cells through activation of apoptotic pathway. However, the same doses did not affect HFL1 normal lung cell growth. Kaempferol induced G2/M cell cycle arrest and the enhancement of radiation-induced death and clonogenic survival inhibition. The in vivo data showed that kaempferol increased tumor cell apoptosis and killing of radiation. In conclusion, the findings demonstrated that kaempferol increased tumor cell killing by radiation in vitro and in vivo through inhibition of the AKT/PI3K and ERK pathways and activation of the mitochondria apoptosis pathway. The results of the present study provided solid evidence that kaempferol is a safe and potential radiosensitizer.

Automated feature set selection and its application to MCC identification in digital mammograms for breast cancer detection.

We propose a fully automated algorithm that is able to select a discriminative feature set from a training database via sequential forward selection (SFS), sequential backward selection (SBS), and F-score methods. We applied this scheme to microcalcifications cluster (MCC) detection in digital mammograms for early breast cancer detection. The system was able to select features fully automatically, regardless of the input training mammograms used. We tested the proposed scheme using a database of 111 clinical mammograms containing 1,050 microcalcifications (MCs). The accuracy of the system was examined via a free response receiver operating characteristic (fROC) curve of the test dataset. The system performance for MC identifications was Az = 0.9897, the sensitivity was 92%, and 0.65 false positives (FPs) were generated per image for MCC detection.

Quantification of blood flow in internal cerebral artery by optical flow method on digital subtraction angiography in comparison with time-of-flight magnetic resonance angiography.

OBJECTIVE: This study compared data on the blood flow velocity in the internal carotid artery, which was obtained using the optical flow method (OFM) with digital subtraction angiography (DSA) and the time-of-flight (TOF) technique using magnetic resonance angiography (MRA). MATERIALS AND METHODS: Images were obtained from 12 cerebrovascular patients who underwent both brain DSA and MRA imaging. The OFM was applied on the DSA images to determine the average blood flow velocity. The calculated results were compared with the values obtained from the TOF-MRA data. A linear fit was performed on the data and Bland-Altman plots were analyzed. RESULTS: The blood flow velocity was closely associated with vascular diseases. Color-coding of the OFM measurements were superimposed on to the DSA images, which quantitatively illustrated the relative flow in the vessels. The average blood flow velocity was calculated using OFM and DSA, which demonstrated a high correlation with the MRA measurements in the anterior-posterior (AP) view (R = 0.71). In contrast, the average blood flow velocity was low in the lateral view (R = 0.28). The consistency between the high and low blood velocity in the AP view was better compared to the lateral view. The blood flow velocity distribution in the AP view was statistically closer to the MRA measurement compared to the lateral view. CONCLUSIONS: This study evaluated the correlation of blood flow measured using DSA and TOF-MRA in a small heterogeneous group of patients with cerebrovascular lesions. OFM with DSA imaging reveals hemodynamic information and TOF-MRA.

Computed tomographic imaging in determining the need of embolization for high-grade blunt renal injury.

BACKGROUND: It is well documented that transarterial embolization (TAE) can successfully stop bleeding in renal trauma patients and reduce the failure rate of conservation treatment. However, there is no consensus on the indications for TAE. The aim of this study was to evaluate the criteria for computed tomography (CT) to predict the need for TAE for patients with high-grade blunt renal trauma. METHODS: Of the 137 patients with blunt renal trauma between 2005 and 2010, 81 had a high-grade injury (grade ≥ 3) with stable hemodynamics, who were treated conservatively, were included in the study. CT criteria included contrast extravasation (CE), perirenal hematoma rim distance (PRD), and extent of hematoma. The patients were divided into two groups according to the extent of hematoma on CT, as either Group 1 with localized hematomas or Group 2 with extensive hematomas. We compared the CT and angiographic findings and examined the correlation between patient management and outcome. The CT criteria, alone or in combination, for predicting the subsequent requirement for TAE were evaluated. RESULTS: Of the 81 patients, 35 were in Group 1 and 46 were in Group 2, with 35 having CE. The 22 patients who received TAE were all in Group 2 and had CE. Mean PRD was larger for the patients who received TAE than for those who did not. CE, extent of hematoma, and PRD correlated significantly with the need for TAE (all p < 0.001). Overall, the combination of CT criteria for CE and extent of hematoma showed the highest accuracy for predicting the need for TAE. CONCLUSION: CE, extent of hematoma, and PRD were simple and sensitive indicators of patients who required TAE. The combination of CE criteria and extent of hematoma markedly increased the predictive value for predicting the need for TAE. LEVEL OF EVIDENCE: Prognostic study, level III; therapeutic study, level IV.

Quantitative portal vein velocity of liver cancer patients with transcatheter arterial chemoembolization on angiography.

OBJECTIVE: We applied optical flow method (OFM) to quantify relative velocities of blood flow using digital subtraction angiography (DSA) in the vascular analysis of hepatocellular carcinoma (HCC) patients who underwent transarterial chemoembolization (TACE) treatment. METHODS: A total of 40 HCC patients treated by TACE were analyzed in this study. DSA imaging with a 12-inch field of view, 1024 × 1024 pixels and 4 frames/second was acquired. OFM developed for motion estimation is applied for blood flow estimation. Two acrylic phantoms were built to validate the method. RESULTS: The relationship between the OFM and Doppler measurements was found linear with R(2) = 0.99 for both straight and curved tube phantoms. Quantitative blood flow distribution images of the portal vein region were presented. After TACE, the minimum, maximum and mean velocities in the portal vein all decreased (P < 0.05). Additionally, the velocity in the portal vein is significantly lower with a higher Child-Pugh score (P < 0.01). CONCLUSIONS: The present technique provides add-on quantitative information of flows to DSA and the hemodynamic analysis in relative quantifications of blood flow in portal vein of hepatocellular carcinoma patients using DSA.

Intramesosigmoid hernia: preoperative diagnostic MDCT findings.

Internal hernias, protrusion of abdominal viscera into an intraperitoneal fossa, are uncommon causes of bowel obstruction, and preoperative diagnoses are difficult. We report a rare case of a 47-year-old female with strangulated small bowel obstruction secondary to an intramesosigmoid hernia preoperative diagnosis by multi-detector row computed tomography. We highlight the preoperatively diagnosed value and findings of MDCT in intramesosigmoid hernia.

Hemodynamic analysis of vascular stenting treatment outcome: computational fluid dynamics method vs optical flow method.

BACKGROUND AND PURPOSE: Computational fluid dynamics method (CFDM) and optical flow method (OFM) effectively provide the hemodynamic information based on the digital subtraction angiogram (DSA). However, the quantitative analysis in comparison of CFDM and OFM is still absent. The goal of this study is to apply CFDM and OFM in quantitative analysis of stenting treatment. MATERIAL AND METHOD: A left carotid stenosis patient underwent stenting of percutaneous transluminal angioplasty was analyzed as an example. CFDM and OFM for hemodynamic analysis on digital subtraction angiography before and after stenting treatment were presented. RESULTS: Improvement gains of blood flow velocities on left internal carotid artery after stenting treatment for different initial conditions on the common carotid artery were 1.91 ∼ 2.13, 1.62 ∼ 2.09, and 0.69 by CFDM with Newtonian and non-Newtonian fluids and OFM, respectively. With the CFDM analysis, the flow mapping by OFM using time resolved DSA data on the fly to estimate hemodynamic significance of a cervical carotid stenosis was explained. CONCLUSION: Quantificative blood flow estimations by CFDM and OFM to evaluate the treatment outcomes to patient with carotid stenosis are practical. Both methods are able to provide quantitative information of blood flow for stenting treatment. It is advantagious to use both methods in treatment evaluation.

Proteomic approaches to study epigallocatechin gallate-provoked apoptosis of TSGH-8301 human urinary bladder carcinoma cells: roles of AKT and heat shock protein 27-modulated intrinsic apoptotic pathways.

Epigallocatechin-3-gallate (EGCG), a polyphenol constituent present in green tea, has been shown to inhibit the growth of cancer cells in vitro and in vivo. However, studies regarding human bladder carcinoma cells are limited and not well investigated. Hence, our study focused on the evaluation of EGCG-triggered apoptosis in TSGH-8301 human urinary bladder carcinoma cells in vivo and in vitro as well as its related molecular mechanisms. In an in vivo study, EGCG inhibited xenograft tumor size of TSGH-8301 cells in a nude mouse model. Based on an in vitro study, EGCG resulted in morphological changes and increased growth inhibition in a dose- and time-dependent manner in TSGH-8301 cells. Furthermore, sub-G1 populations were shown and caspase-9 and -3 activities were stimulated in EGCG-treated TSGH-8301 cells. Moreover, a caspase-9 inhibitor (Z-LEHD-FMK) and a caspase-3 inhibitor (Z-DEVD-FMK) were able to reduce EGCG-stimulated caspase-9 and -3 activities, respectively. Loss of mitochondrial membrane potential (∆Ψm) resulted in an increase of protein levels of cytochrome c, Apaf-1, caspase-9 and -3 in TSGH-8301 cells following exposure to EGCG. Proteomic analysis revealed that EGCG affected the expression levels of various proteins, including HSP27, porin, tropomyosin 3 isoform 2, prohibitin and keratin 5, 14, 17 in TSGH-8301 cells. EGCG also suppressed AKT kinase activity and protein levels and also altered the expression levels of Bcl-2 family-related proteins such as Bcl-2, Bax, BAD and p-BAD. Based on the above findings, this study suggests that EGCG-provoked apoptotic death in TSGH-8301 cells is mediated through targeting AKT and HSP27 and modulating p-BAD, leading to activation of the intrinsic apoptotic pathway.

Induction of the mitochondria apoptosis pathway by phytohemagglutinin erythroagglutinating in human lung cancer cells.

BACKGROUND: Deregulation of apoptosis will influence the balance of cell proliferation and cell death, resulting in various fatal diseases that can include cancer. In prior research reports related to cancer therapy, phytohemagglutinin, a lectin extracted from red kidney beans, demonstrated the ability to inhibit the growth of human cancer cells. However, one of its isoforms, erythroagglutinating, has yet to be evaluated on its anticancer effects. METHODS: PHA-E was used to induce apoptosis of A-549 lung cancer cells and the possible signal transduction pathway was elucidated, as measured by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, G6PD release assay, flow cytometry, and Western blot analysis. RESULTS: PHA-E treatment caused a dose-dependent increase of cell growth inhibition and cytotoxicity on A-549 cells. In annexin V/propidium iodide [i.e., PI] and TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling)/PI assay, we found that the rate of apoptotic cells was raised as the concentration of PHA-E increased. Treatment of A-549 cells with PHA-E resulted in enhancing the release of cytochrome c, which thus activated an increase in caspase 9 and caspase 3, the upregulation of Bax and Bad, the downregulation of Bcl-2 and phosphorylated Bad, and finally the inhibition of the epidermal growth factor receptor and its downstream signal pathway PI3K/Akt and MEK/ERK. CONCLUSIONS: PHA-E can induce growth inhibition and cytotoxicity of lung cancer cells, which is mediated through an activation of the mitochondria apoptosis pathway. These results suggest that PHA-E can be developed into a new therapeutic treatment that can be applied as an effective anti-lung cancer drug in the near future.

Quantitative analysis in clinical applications of brain MRI using independent component analysis coupled with support vector machine.

PURPOSE: To effectively perform quantification of brain normal tissues and pathologies simultaneously, independent component analysis (ICA) coupled with support vector machine (SVM) is investigated and evaluated for effective volumetric measurements of normal and lesion tissues using multispectral MR images. MATERIALS AND METHODS: Synthetic and real MR data of normal brain and white matter lesion (WML) data were used to evaluate the accuracy and reproducibility of gray matter (GM), white matter (WM), and WML volume measurements by using the proposed ICA+SVM method to analyze three sets of MR images, T1-weighted, T2-weighted, and proton density/fluid-attenuated inversion recovery images. RESULTS: The Tanimoto indexes of GM/WM classification in the normal synthetic data calculated by the ICA+SVM method were 0.82/0.89 for data with 0% noise level. As for clinical MR data experiments, the ICA+SVM method clearly extracted the normal tissues and white matter hyperintensity lesions from the MR images, with low intra- and inter-operator coefficient of variations. CONCLUSION: The experiments conducted provide evidence that the ICA+SVM method has shown promise and potential in applications to classification of normal and pathological tissues in brain MRI.

Langerhans cell histiocytosis with thyroid and lung involvement in a child: a case report.

SUMMARY: Langerhans cell histiocytosis (LCH), a monoclonal disease of histiocytes, may involve several organ systems but rarely primarily involves the thyroid gland. This report presents an extremely rare case of LCH of the thyroid and lungs in a 3-year-old boy who presented with a neck mass for several weeks. The patient subsequently underwent chemotherapy with resolution of the goiter and lung findings, and the patient remained in complete remission 1 year after chemotherapy. LCH of the thyroid should be considered in the differential diagnosis of a child with a thyroid mass. Pulmonary examination should be done in these patients.

Alobar holoprosencephaly associated with cebocephaly and craniosynostosis.

Cebocephaly is a very rare congenital midline facial anomaly characterized by a blind-ended single nostril and ocular hypotelorism, and is usually combined with alobar holoprosencephaly. We report here a case of alobar holoprosencephaly with cebocephaly and craniosynostosis. Chromosomal analysis revealed normal karyotyping. The facial dysmorphism was characterized by the single nostril, hypotelorism, absence of philtrum and small head girth. The failure of cleavage of the prosencephalon and the fusion of all cranial sutures except for the sagittal suture were documented by computed tomography (CT) and magnetic resonance image (MRI). Early detection by the prenatal ultrasound examination is important because of poor prognosis of alobar holoprosencephaly.

Children presenting at the emergency department with right lower quadrant pain.

Right lower quadrant (RLQ) pain is a common complaint in children presenting at emergency departments. This study analyzed the etiologies of RLQ pain, and compared the clinical presentations, laboratory test results and imaging findings in patients with appendicitis with those in other groups of patients. We also investigated if active observation resulted in delayed diagnosis, to the detriment of patients. Medical records for the period January 2006 to July 2006 were reviewed for children (age < 18 years) who presented to the emergency department of one medical center, complaining of RLQ pain. Out of a total of 100 patients (age range: 2-17 years; mean: 11 years), 46 patients presented with only one symptom of RLQ pain, while 32 patients had >/= 2 associated signs or symptoms, including fever, nausea/vomiting, diarrhea, or rebound tenderness. Imaging studies, including abdominal sonography and/or computed tomography, were performed in 73 patients; 44 underwent surgery for presumed appendicitis and one received surgery for a right paraduodenal hernia. Eleven patients underwent surgery because of peritoneal signs, and eight because of persistent or aggravated RLQ pain. Postoperative pathologic examinations revealed 53 cases of appendicitis, six normal appendices, and other morbidities (1 perforated peptic ulcer, 1 pelvic inflammatory disease, 1 ovarian cyst, 1 diverticulitis, and 1 right paraduodenal hernia). Thirty-three patients were discharged after several hours of observation (range: 0.5-18 hours; mean: 4 hours), and three patients were admitted for further observations. All were discharged without operation. There were significant differences in the incidences of fever (p = 0.004) and rebound tenderness (p = 0.019), and in white cell counts (p < 0.001), neutrophil percentages (p < 0.001), and C-reactive protein levels (p < 0.001) between patients with appendicitis and patients with other causes of RLQ pain. Clinical signs and symptoms, laboratory tests, and imaging studies can be used to differentiate between the causes of RLQ pain. Patients without the classical features of appendicitis or peritonitis can be safely managed by active observation and repeated physical examinations.

Reappraisal of the management and outcome of emphysematous pyelonephritis.

This study compared the management, prognostic factors and outcomes of patients with emphysematous pyelonephritis (EPN). Twenty-one patients with EPN were studied between September 1996 and August 2005, and were assigned to two groups. Patients in Group 1 received conservative treatment with/without percutaneous catheter drainage (PCD) while patients in Group 2 underwent nephrectomy following medical treatment and PCD. A post hoc analysis of the prognostic factors was performed between survivors and nonsurvivors, and between the survivors in Group 1 and Group 2. There were 14 patients in Group 1, and seven in Group 2. The mortality in Group 1 was 35.7% (5/14) and in Group 2 was 0% (p = 0.12). There were no statistically significant differences in prognostic factors between the two groups, though patients in Group 1 had relatively lower platelet counts (p = 0.07) and Group 2 patients had a higher incidence of dialysis after nephrectomy (p = 0.03). Comparing the survivors and nonsurvivors, patients with comorbid congestive heart failure and patients initially presenting with consciousness disturbances had higher mortalities (p = 0.02 and p < 0.01, respectively). Nonsurvivors also had lower platelet counts (p = 0.06). In conclusion, medical treatment with/without PCD can be used to manage patients with EPN. More agressive drainage is needed in patients with congestive heart failure who initially present with consciousness disturbances or thrombocytopenia.

Children with chest pain visiting the emergency department.

BACKGROUND: Chest pain is a common complaint in children visiting the emergency department (ED). True organic problems like cardiac disease are rare. We assess and analyze the etiology of chest pain among children visiting a pediatric ED in one medical center. METHODS: We retrospectively reviewed the medical records of children with chest pain who visited our ED between September 2002 and June 2005. Any case of trauma-associated chest pain was excluded from this study. RESULTS: A total of 103 patients (64 boys, 39 girls; mean age, 13 years; age range, 4-17 years) were enrolled into this study; 101 patients had chest radiograms (98.1%). Pneumonia was identified in five patients and pneumothorax in three. Eighty-seven patients had electrocardiogram study (84.5%) and four of them showed abnormalities. Additional diagnostic tests were performed in 64 patients (62.1%), including complete blood count analysis and echocardiography. Echocardiograms were performed in 15 (14.6%) patients. Six of them showed minor abnormality. Panendoscopy was done in six (5.8%) patients, and gastroesophageal reflux was found in three. Eleven (10.7%) patients were admitted to hospital because of pneumonia, pneumothorax or arrhythmia. Overall, idiopathic chest pain was the most common diagnosis (59.2%). Other associated disorders were pulmonary (24.3%), musculoskeletal (6.7%), gastrointestinal (5.8%), cardiac (2.0%) and miscellaneous (2.0%). CONCLUSION: The most common cause of chest pain prompting a child to visit the ED is idiopathic chest pain. Careful physical examination can reveal important clues and save much unnecessary examinations.

Preoperative diagnosis of right paraduodenal hernia by multidetector computed tomography.

Right paraduodenal hernia is an unusual congenital malformation that causes intestinal obstruction. It is seldom diagnosed preoperatively and a small bowel follow-through series is the best diagnostic method. However, multidetector computed tomography (MDCT) can be an alternative diagnostic method. We report the first case of right paraduodenal hernia that was diagnosed preoperatively by MDCT. A 15-year-old boy presented with right lower abdominal pain, nausea and vomiting. Abdominal MDCT with coronal reformation images clearly revealed encapsulated small bowel loops in the right side of the abdomen and displacement of the ascending colon to the left side. He received surgical repair and recovered uneventfully.

Clinical outcome and prognostic factors of patients with pyogenic liver abscess requiring intensive care.

OBJECTIVE: Despite improvements in diagnosis and treatment, pyogenic liver abscess remains a life-threatening disease. This study evaluated clinical outcome and prognostic factors in patients with pyogenic liver abscess admitted to the intensive care unit. DESIGN: Retrospective study. SETTING: Medical and surgical intensive care unit in a 1,700-bed university-based hospital. PATIENTS: Four hundred and thirty-six adult patients (> or = 18 yrs) with a diagnosis of pyogenic liver abscess were reviewed, and 72 patients with pyogenic liver abscess who required intensive care were enrolled in the study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Twenty of 72 enrolled patients died, yielding an intensive care unit mortality rate of 28%. The most common underlying disease was diabetes mellitus (51%), and the most common microorganism was Klebsiella pneumoniae (74%). Compared with survivors, nonsurvivors had higher Acute Physiology and Chronic Health Evaluation (APACHE) II scores (22.2 +/- 9 vs. 13.7 +/- 6, p < .001), higher serum creatinine levels (2.9 +/- 2 vs. 1.9 +/- 2 mg/dL, p = .02), and longer prothrombin times (21 +/- 5 vs. 16 +/- 5 s, p = .01) on the first day of intensive care unit admission. In addition, factors associated with mortality included inadequate antibiotic therapy (p = .026), septic shock (p = .002), acute respiratory failure (p < .001), and acute renal failure (p = .043) on the first day of intensive care unit admission. On multivariate logistic regression analysis, factors that independently correlated with mortality were the presence of acute respiratory failure (p = .003, relative risk = 18.7) and APACHE II score > 16 (p = .026, relative risk = 7.43). CONCLUSIONS: In patients with pyogenic liver abscess requiring intensive care, variables including size of liver abscess, pathogens, comorbidity, and most laboratory data were not associated with mortality. Only the presence of acute respiratory failure and APACHE II score >16 on the first day of intensive care unit admission were significant prognostic factors.

Emergent transcatheter arterial embolization in hemodynamically unstable patients with blunt splenic injury.

RATIONALE AND OBJECTIVES: Splenic preservation is currently the trend for treatment of patients with splenic trauma to avoid complications of splenectomy. This study aimed to evaluate the feasibility of emergent transcatheter arterial embolization (TAE) for hemodynamically unstable patients with blunt splenic injury. MATERIALS AND METHODS: In a period of 2 years, 65 patients of blunt splenic trauma were studied. Patients with initial systolic blood pressure < 90 mmHg and showed initial response including rapid response and transient response to the emergent fluid resuscitation were included. Angiography and TAE was undertaken if contrast medium extravasation or pseudoaneurysm formation was noted in the computed tomography (CT) images, according to the criteria of American Association for the Surgery of Trauma. All patients who underwent TAE were admitted for observation of the possibility of delayed rupture. RESULTS: Thirteen hemodynamically unstable patients who were responsive to initial fluid resuscitation received angiography due to abnormal CT findings including contrast agent extravasation in 12 patients, 2 patients with arteriovenous fistula, and 8 patients with pseudoaneurysm formation. TAE was successfully performed in all of these 13 patients, including 2 patients with associated left renal injuries and 1 patient associated with bilateral internal mammary arteries injuries, without complications. CONCLUSIONS: TAE is a safe and effective procedure for treating blunt splenic injury even in hemodynamically unstable patients who responded to initial fluid resuscitation.