Comparative assessment of established and deep learning-based segmentation methods for hippocampal volume estimation in brain magnetic resonance imaging analysis.

In this study, our objective was to assess the performance of two deep learning-based hippocampal segmentation methods, SynthSeg and TigerBx, which are readily available to the public. We contrasted their performance with that of two established techniques, FreeSurfer-Aseg and FSL-FIRST, using three-dimensional T1-weighted MRI scans (n = 1447) procured from public databases. Our evaluation focused on the accuracy and reproducibility of these tools in estimating hippocampal volume. The findings suggest that both SynthSeg and TigerBx are on a par with Aseg and FIRST in terms of segmentation accuracy and reproducibility, but offer a significant advantage in processing speed, generating results in less than 1 min compared with several minutes to hours for the latter tools. In terms of Alzheimer's disease classification based on the hippocampal atrophy rate, SynthSeg and TigerBx exhibited superior performance. In conclusion, we evaluated the capabilities of two deep learning-based segmentation techniques. The results underscore their potential value in clinical and research environments, particularly when investigating neurological conditions associated with hippocampal structures.

Virtual MOLLI Target: Generative Adversarial Networks Toward Improved Motion Correction in MRI Myocardial T1 Mapping.

BACKGROUND: The modified Look-Locker inversion recovery (MOLLI) sequence is commonly used for myocardial T1 mapping. However, it acquires images with different inversion times, which causes difficulty in motion correction for respiratory-induced misregistration to a given target image. HYPOTHESIS: Using a generative adversarial network (GAN) to produce virtual MOLLI images with consistent heart positions can reduce respiratory-induced misregistration of MOLLI datasets. STUDY TYPE: Retrospective. POPULATION: 1071 MOLLI datasets from 392 human participants. FIELD STRENGTH/SEQUENCE: Modified Look-Locker inversion recovery sequence at 3 T. ASSESSMENT: A GAN model with a single inversion time image as input was trained to generate virtual MOLLI target (VMT) images at different inversion times which were subsequently used in an image registration algorithm. Four VMT models were investigated and the best performing model compared with the standard vendor-provided motion correction (MOCO) technique. STATISTICAL TESTS: The effectiveness of the motion correction technique was assessed using the fitting quality index (FQI), mutual information (MI), and Dice coefficients of motion-corrected images, plus subjective quality evaluation of T1 maps by three independent readers using Likert score. Wilcoxon signed-rank test with Bonferroni correction for multiple comparison. Significance levels were defined as P < 0.01 for highly significant differences and P < 0.05 for significant differences. RESULTS: The best performing VMT model with iterative registration demonstrated significantly better performance (FQI 0.88 ± 0.03, MI 1.78 ± 0.20, Dice 0.84 ± 0.23, quality score 2.26 ± 0.95) compared to other approaches, including the vendor-provided MOCO method (FQI 0.86 ± 0.04, MI 1.69 ± 0.25, Dice 0.80 ± 0.27, quality score 2.16 ± 1.01). DATA CONCLUSION: Our GAN model generating VMT images improved motion correction, which may assist reliable T1 mapping in the presence of respiratory motion. Its robust performance, even with considerable respiratory-induced heart displacements, may be beneficial for patients with difficulties in breath-holding. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 1.

Baicalein suppresses HER2-mediated malignant transformation of HER2-overexpressing ovarian cancer cells by downregulating HER2 gene expression.

The upregulation of the HER2 oncogene is associated with a variety of human cancers and is associated with poor prognosis. Baicalein is reported to have anti-tumor activity, but the molecular mechanism of this effect in HER2-positive cancer cells has not been studied. In this study, our data showed that baicalein can inhibit the proliferation and transformation potential of ovarian cancer cells overexpressing HER2. Baicalein treatment caused a dose-dependent inhibition of HER2 gene expression at the transcriptional level. Baicalein acted on ovarian cancer cells overexpressing HER2 to downregulate the PI3K/Akt signaling pathway downstream of HER2 and inhibit the expression or activity of downstream targets, such as VEGF and cyclin D1 and MMP2. Oral administration of baicalein supplemented with a pharmaceutical excipient significantly inhibited the growth of HER2-overexpressing ovarian SKOV-3 cancer xenografts in mice. These results suggest that downregulation of HER2 gene expression by baicalein at the transcriptional level contributes to inhibit the in vitro and in vivo proliferation and HER2-mediated malignant transformation of HER2-overexpressing ovarian cancer cells.

Baicalein Induces G2/M Cell Cycle Arrest Associated with ROS Generation and CHK2 Activation in Highly Invasive Human Ovarian Cancer Cells.

Ovarian cancer is a lethal gynecological cancer because drug resistance often results in treatment failure. The CHK2, a tumor suppressor, is considered to be an important molecular target in ovarian cancer due to its role in DNA repair. Dysfunctional CHK2 impairs DNA damage-induced checkpoints, reduces apoptosis, and confers resistance to chemotherapeutic drugs and radiation therapy in ovarian cancer cells. This provides a basis for finding new effective agents targeting CHK2 upregulation or activation to treat or prevent the progression of advanced ovarian cancer. Here, the results show that baicalein (5,6,7-trihydroxyflavone) treatment inhibits the growth of highly invasive ovarian cancer cells, and that baicalein-induced growth inhibition is mediated by the cell cycle arrest in the G2/M phase. Baicalein-induced G2/M phase arrest is associated with an increased reactive oxygen species (ROS) production, DNA damage, and CHK2 upregulation and activation. Thus, baicalein modulates the expression of DNA damage response proteins and G2/M phase regulatory molecules. Blockade of CHK2 activation by CHK2 inhibitors protects cells from baicalein-mediated G2/M cell cycle arrest. All the results suggest that baicalein has another novel growth inhibitory effect on highly invasive ovarian cancer cells, which is partly related to G2/M cell cycle arrest through the ROS-mediated DNA breakage damage and CHK2 activation. Collectively, our findings provide a molecular basis for the potential of baicalein as an adjuvant therapeutic agent in the treatment of metastatic ovarian cancer.

Dual down-regulation of EGFR and ErbB2 by berberine contributes to suppression of migration and invasion of human ovarian cancer cells.

The overexpression of EGFR and/or ErbB2 occurs frequently in ovarian cancers and is associated with poor prognosis. The purpose of this study was to examine the anticancer effects and molecular mechanisms of berberine on human ovarian cancer cells with different levels of EGFR and/or ErbB2. We found that berberine reduced the motility and invasiveness of ovarian cancer cells. Berberine depleted both EGFR and ErbB2 in ovarian cancer cells. Furthermore, berberine suppressed the activation of the EGFR and ErbB2 downstream targets cyclin D1, MMPs, and VEGF by down-regulating the EGFR-ErbB2/PI3K/Akt signaling pathway. The berberine-mediated inhibition of MMP-2 and MMP-9 activity could be rescued by co-treatment with EGF. Finally, we demonstrated that berberine induced ErbB2 depletion through ubiquitin-mediated proteasome degradation. In conclusion, the suppressive effects of berberine on the ovarian cancer cells that differ in the expression of EGFR and ErbB2 may be mediated by the dual depletion of EGFR and/or ErbB2.

Discriminating pyogenic brain abscesses, necrotic glioblastomas, and necrotic metastatic brain tumors by means of susceptibility-weighted imaging.

OBJECTIVES: To investigate the feasibility of using susceptibility-weighted imaging (SWI) to discriminate abscesses and necrotic tumours. METHODS: Twenty-one patients with pyogenic abscesses, 21 patients with rim-enhancing glioblastomas and 23 patients with rim-enhancing metastases underwent SWI. Intralesional susceptibility signal (ILSS) was analyzed employing both qualitative (QL) and semi-quantitative (SQ) methods. Logistic regression models and receiver operating characteristic analysis were used to demonstrate the discriminating power. RESULTS: In QL analysis, ILSSs were seen in 12 of 21 abscesses, in 20 of 21 glioblastomas, and in 16 of 23 metastases. In SQ analysis, a low degree of ILSS (85.8 %) was in the majority of abscesses and a high degree of ILSS (76.2 %) was in the majority of glioblastomas. SQ model was significantly better than QL model in distinguishing abscesses from glioblastomas (P < .001). A derived ILSS cutoff grade of 1 or less was quantified as having a sensitivity of 85.7 %, specificity of 90.5 %, accuracy of 88.1 %, PPV of 90.0 %, and NPV of 86.4 % in distinguishing abscesses from glioblastomas. CONCLUSIONS: A high-grade ILSS may help distinguish glioblastomas from abscesses and necrotic metastatic brain tumours. The lack of ILSS or low-grade ILSS can be a more specific sign in the imaging diagnosis of abscesses. KEY POINTS: • ILSS of SWI can contribute to differential diagnosis of rim-enhanced mass. • Low-grade ILSS can be a more specific sign in abscesses. • High-grade ILSS may help distinguish necrotic glioblastomas from abscesses. • ILSS spreads across the four ILSS categories in metastases.

Automatic calibration of trigger delay time for cardiac MRI.

This study aimed to automatically identify the cardiac rest period using a rapid free-breathing (FB) calibration scanning procedure, and to determine the optimal trigger delay for cardiac imaging. A standard deviation (SD) method was used to rapidly identify cardiac quiescent phases employing multiphase cine cardiac images. The accuracy of this method was investigated using 46 datasets acquired from 22 healthy volunteers. The possibility of using a low-resolution FB method to rapidly acquire cine images was also evaluated. The reproducibility and accuracy of the trigger delay obtained using the rapid calibration scanning process were assessed before its application to a real-time feedback system. The real-time trigger delay calibration system was then used to perform T1 -weighted, short-axis imaging at the end of the cardiac systolic period. Linear regression analysis of the trigger times obtained using the SD method and a reference method indicated that the SD algorithm accurately identified the cardiac rest period (linear regression: slope = 0.94-1, R(2) = 0.68-0.84). Group analysis showed that the number of pixels in the left ventricular blood pool in images acquired at the end-systolic time calculated in real time was significantly lower than in those acquired 50 ms in advance or later (p < 0.01, paired t-test). The low-resolution FB imaging method was reproducible for the calibration scanning of an image in a vertical long-axis slice position (average SD of trigger times, 16-39 ms). Combined with rapid FB calibration scanning, the real-time feedback system accurately adjusted the trigger delay for T1 -weighted short-axis imaging. The real-time feedback method is rapid and reliable for trigger time calibration, and could facilitate cardiac imaging during routine examination.

Quantitative comparison of post-processing methods for reduction of frequency modulation sidebands in non-water suppression 1H MRS.

Non-water suppression MRS (NWS MRS) has several advantages. First, the unsuppressed water signal can be used as internal calibration for metabolite quantification and as a reliable frequency/phase reference for retrospective motion correction. Second, it avoids the potential artifacts caused by incomplete water suppression (WS) and extra radiofrequency deposition from WS pulses. However, the frequency modulation (FM) sidebands originating from a large water signal will distort the spectrum. Among the methods proposed to solve the problems caused by FM sidebands, post-acquisition processing methods are superior in flexibility for general use compared with experimental methods. In this study, we propose two algorithms based on advanced matrix decomposition to remove the FM sidebands. These methods, the simultaneous diagonalization (QZ) algorithm and its subsequent variant, the simultaneously generalized Schur decomposition (SGSD) algorithm, were numerically evaluated using computer simulations. In addition, we quantitatively compared the performance of these methods and the modulus method in an in vitro experiment and in vivo NWS MRS against conventional WS data. Our results show that the proposed SGSD algorithm can reduce the FM sidebands to achieve superior estimation of concentration on three major metabolites. This method can be applied directly to spectra pre-acquired under various experimental conditions without modifying the acquisition sequences.

Multilayer appearance on contrast-enhanced susceptibility-weighted images on patients with brain abscesses: Possible origins and effects of postprocessing.

PURPOSE: To demonstrate the presence of a multilayer appearance of the capsule on contrast-enhanced (CE) susceptibility-weighted imaging (SWI) in patients with pyogenic brain abscesses. Possible origins for the appearance and effects of postprocessing settings are discussed. MATERIALS AND METHODS: Fourteen patients with pyogenic brain abscesses underwent post gadolinium-enhanced SWI at 1.5 T. All SWI images were postprocessed with various filter and mask settings to compare the image appearance. Computer simulations using a paramagnetic spherical shell model were performed to verify the clinical findings. RESULTS: Pyogenic brain abscesses demonstrated a multilayer appearance with a darkened ring within the enhanced capsule on CE-SWI in all patients. The multilayer appearance was slice-orientation-dependent, decreased with larger widths of the high-pass filter, and increased with larger numbers of phase mask multiplication operations, consistently on both simulation results and the clinical images. CONCLUSION: CE-SWI shows the multilayer appearance of the capsule in pyogenic brain abscesses, which may arise from postprocessing procedures originally designed to enhance susceptibility contrast. Although SWI may provide additional information valuable in the diagnosis of pyogenic brain abscesses, image interpretation should be exercised with caution, particularly for CE-SWI.

Intra-tumoral susceptibility signal: a post-processing technique for objective grading of astrocytoma with susceptibility-weighted imaging.

BACKGROUND: Susceptibility-weighted imaging (SWI) is sensitive to the accumulation of paramagnetic substances, such as hemorrhage and increased venous vasculature, both being frequently found in high-grade tumors. The purpose of this retrospective study is to differentiate high-grade and low-grade astrocytoma by objectively measuring quantitative intra-tumoral susceptibility signals (qITSS) on SWI. METHODS: Precontrast SWI and 3D contrast-enhanced T1WI of 65 patients with astrocytoma were collected at 1.5 Tesla. All tumors were histologically confirmed and classified into two groups: high grade (WHO grade III and IV, n=50) and low grade (WHO grade II, n=15). After manual delineation of the tumor on T1WI, normalized contrast (NC) was calculated voxel by voxel within the tumor by using the concept of contrast to noise ratio. Thresholding on NC was applied to detect qITSS, and the volumetric percentage of qITSS can be obtained for each tumor. Two-sample t-test was applied to examine significant difference of qITSS percentage between high-grade and low-grade astrocytoma for different NC thresholds, ranging from 4 to 20. Receiver operating characteristic analysis was performed to evaluate the performance of differentiation. RESULTS: P value was less than 0.01 for a large range of NC thresholds [4-20], reflecting significant difference of qITSS percentage between high-grade and low-grade astrocytoma. The area under the receiver operating characteristic curve was larger than 0.9 at NC thresholds from 8 to 16 and peaks at 0.949 with a NC threshold of 14. It was shown that astrocytoma grading by qITSS percentage is successful for a wide range of NC threshold, demonstrating robustness on threshold selection. CONCLUSIONS: Without relying on the selection of slice position and at the same time providing objective identification of hypointense signal in SWI, the qITSS percentage can be used to distinguish high-grade and low-grade astrocytoma reliably.

Ile/Ile homozygosity at codon 655 of HER2 in schwannoma.

PURPOSE: This study aimed to determine the genetic role of HER2, one of the epidermal growth factor receptor (EGFR) family, in schwannoma. The latter is a neogrowth of myelin-producing Schwann cells in peripheral nerves, inducible by N-nitrosoethylurea in animals with mutation in the neu gene (homologous gene of human HER2 protein). METHODS: In this study we obtained genomic DNA samples from tissue blocks of schwannoma, initially by xylene treatment and alcohol extraction, followed by use of the DNA extraction kit. Evaluation of this genetic polymorphism in our subjects was conducted by direct nucleotide sequencing or restriction enzyme analyses after PCR work. RESULTS: There were thirty extracted DNA samples from tissue blocks of schwannoma, and all were Ile/Ile homozygotes after genotype analyses. Two individuals received the leukocyte DNA extraction after peripheral blood sampling, both showing Ile/Ile homozygosity. This study gave the impression of an association of the HER2 polymorphism at codon 655 with tumorigenesis of schwannoma. Although the majority of the Taiwanese showed Ile/Ile homozygosity (about 83%), the present study revealed a 100% carriage rate among the tissue blocks from our subjects with schwannoma. CONCLUSION: Ile/Ile homozygosity at codon 655 of HER2 in schwannoma may imply some role in tumorigenesis of Ile655Val allele of HER2 in this nerve tumor.

Stimulated echo induced misestimates on diffusion tensor indices and its remedy.

PURPOSE: To report possible erroneous estimates of diffusion parameters in the twice-refocused spin-echo (TRSE) technique, proposed to eliminate eddy-current-induced geometric distortions in diffusion-weighted echo-planar imaging, when stimulated echo signals are inappropriately included. MATERIALS AND METHODS: Eleven subjects were included for imaging experiments on two 1.5 Tesla systems using the TRSE sequence. Three versions, two with unbalanced crusher gradients inserted to dephase the stimulated echo from the b = 0 images and one with balanced crusher gradients, were implemented. The apparent diffusion coefficients (ADC) and fractional anisotropy (FA) were derived and compared. RESULTS: The ADCs obtained with unbalanced crusher gradients were closer to values reported in the literature. Stimulated echo led to ADC over-estimations by 34.2%, 50.4%, 54.0%, 51.5%, 24.0%, and 41.9% in the genu of corpus callosum, splenium of corpus callosum, bilateral corona radiata, internal capsule, mediofrontal gyrus, and the cuneus, respectively (P < 0.01), with concomitant reduction in FA in highly anisotropic regions. Over-estimations of diffusion coefficients were found to be roughly equal along all directions. CONCLUSION: Formation of stimulated echo in the TRSE technique can lead to erroneous estimations of the diffusion parameters, even if no prominent morphological artifacts are seen.

Effective dose for multiple and repeated radiation examinations in donors and recipients of adult-to-adult living donor liver transplants at a single center.

PURPOSE: To evaluate the effective doses received by donors and recipients, identify effective dose contributions, and make risk assessments. MATERIALS AND METHODS: It was a retrospective study. 100 Donors and 100 recipients were enrolled with an operative day from March 2016 to August 2017. The dose was analyzed for all radiation-related examinations over a period of 2 years, 1 year before and 1 year after the LDLT procedure. The effective doses of plain X-rays, CT, fluoroscopy, and nuclear medicine per patient were simulated by a Monte Carlo software, evaluated by the dose-length product conversion factors, evaluated by the dose-area product conversion factors, and evaluated by the activity conversion factors, respectively. The risks of radiation-induced cancer were assessed on the basis of the ICRP risk model. RESULTS: The median effective doses were 71 (range: 30-186) mSv for donors and 147 (32-423) mSv for recipients. The radiation examinations were mainly performed in the last three months of preoperative period to first month of postoperative period for recipients and donors. The HCC recipients received a higher effective dose, 195 (64-423) mSv, than those with other indications. The median radiation-induced cancer risk was 0.38 % in male and 0.48 % in female donors and was 0.50 % in male and 0.58 % in female recipients. CONCLUSION: Donors and recipients received a large effective dose, mainly from the CT scans. To reduce effective doses should be included in future challenges in some living donor liver transplants centers that often use CT examinations.

Octarepeat changes of prion protein in Parkinson's disease.

Polymorphism in prion protein (PrP) is related to different phenotypes of spongiform encephalopathies and some mental illnesses. The octarepeat region of PrP, encompassing the codon 51 through 91, is related to cellular anti-oxidation function and may play a role in genetic contribution of PrP polymorphism to neurodegeneration, such as Parkinson's disease (PD). We analyzed the genomic patterns of PrP gene from 528 subjects and found a predominance of Met/Met variant at codon 129 of PD subjects without significant difference (97.3%, and 96.5% in controls). But among PD subjects there were one with heterozygosity of silent nucleotide substitution (NS) on octarepeats (R1-2-3g-3-4/R1-2-2-3-4) and three with heterozygosity of single copy deletion (CD) on octarepeats (R1-2-3-4/R1-2-2-3-4). Consistent genomic DNA and cDNA sequences were found in a PD subject without any octarepeat changes and the one with NS, but R1-2-3g-3-4/R1-2-2-3-4 of cDNA pattern occurred in the one with genomic CD. This is the first report of the polymorphic PrP octarepeat change among those with parkinsonism. We proposed a hypothesis about an initial secondary hairpin structure of the template strand followed by the transcript "shift backward" due to the high homology of the sequences between R2 and R3 motifs while synthesizing RNA. This phenomenon may be a key step of neurodegeneration resulting from PrP polymorphism and require further studies.

Deriving and validating biomarkers associated with autism spectrum disorders from a large-scale resting-state database.

Resting-state functional magnetic resonance imaging (MRI) has been used to investigate the brain activity related to autism spectrum disorder (ASD). In this study, we applied information from a large-scale dataset, the Autism Brain Imaging Data Exchange (ABIDE), to clinical applications. We recruited 21 patients with ASD and 23 individuals with neurotypical development (TD). We applied ASD biomarkers derived from ABIDE datasets and subsequently investigated the relationship between the MRI biomarkers and indicators from clinical screening questionnaires, the social responsiveness scale (SRS), and the Swanson, Nolan, and Pelham Questionnaire IV. The results indicated that the biomarkers generated from the default mode and executive control networks significantly differed between the participants with ASD and TD. In particular, the biomarkers derived from the default mode network were negatively correlated with the raw scores and model factors of the SRS. In summary, this study transferred the efforts of the global autism research community to clinical applications and identified connectivity-based biomarkers in ASD.

Susceptibility-weighted imaging provides complementary value to diffusion-weighted imaging in the differentiation between pyogenic brain abscesses, necrotic glioblastomas, and necrotic metastatic brain tumors.

PURPOSE: The purpose of this retrospective study was to investigate the differentiation of abscess and necrotic tumors, using susceptibility-weighted imaging (SWI) and apparent diffusion coefficients (ADC) either separated or combined. METHODS: Imaging was performed on 26 patients with pyogenic brain abscesses, 31 patients with rim-enhancing glioblastomas, and 21 patients with rim-enhancing metastases. The degree of intralesional susceptibility signal (ILSS) was independently assessed by three observers. Average ADC in the lesion core was calculated. After receiver operating characteristic (ROC) analysis, the area under the ROC curve was compared using three different analytical models (ILSS, ADC, and ILSS-ADC combined) to differentiate abscess from the two rim-enhancing necrotic tumors. RESULTS: The ILSS-ADC combined model had greater area under the ROC curves than ILSS or ADC used alone. In this study, the ILSS-ADC combined model showed 100% diagnostic accuracy differentiating abscesses from glioblastoma. The ADC model and the ILSS-ADC combined model performed equally well in distinguishing abscesses from metastases. CONCLUSION: It is concluded that SWI and ADC are complementary, and the combination of SWI and ADC may improve results compared with the use of only one model. Validation by an independent cohort is the next necessary step to broaden its applicability in routine clinical settings.

Downregulation of HER2 by RIG1 involves the PI3K/Akt pathway in ovarian cancer cells.

Interferon-gamma (IFN-gamma) is known to downregulate HER2 oncoprotein (p185(HER2) or briefly p185) in prostate cancer cells. We demonstrate that the IFN-gamma-induced retinoid-inducible gene 1 (RIG1) acts as a transrepressor of p185. Furthermore, we exhibit that RIG1 downregulates the activated (phosphorylated) form of p185 and phosphoinositide-3 kinase (PI3K)/serine/threonine-specific protein kinase (Akt) and the mammalian target of rapamycin (mTOR), downstream substrates of HER2. We also elucidate that heregulin (HRG) specifically restores the activation of p185 and Akt after their activities are reduced by RIG1. Additionally, expression of vascular endothelial growth factor (VEGF) increases through the HER2- and Akt/mTOR-signaling pathways, indicating that VEGF is downregulated by RIG1 within the cell. These findings suggest that RIG1 plays a role in IFN-gamma-mediated therapy by downregulating p185 and its downstream PI3K/Akt/mTOR/VEGF-signaling pathway. These results may provide a new therapeutic mechanism for the clinical use of IFN-gamma and RIG1.

Ganoderma tsugae extracts inhibit colorectal cancer cell growth via G(2)/M cell cycle arrest.

ETHNOPHARMACOLOGICAL RELEVANCE: Ganoderma, known as Lingzhi or Reishi, has been traditionally administered throughout Asia for centuries as a cancer treatment and for other medicinal purposes. AIM OF THE STUDY: To investigate the inhibitory activity and explore the molecular mechanisms of anti-tumor effect on colorectal cancer cells in vitro and in vivo as well as to test the side effects of Ganoderma tsugae. MATERIALS AND METHODS: Methanol fraction was obtained from dried fruiting bodies of Ganoderma. TLC and HPLC were performed to differentiate and confirm the identification of different species as well as to quantify the bioactive molecules in methanol extracts of Ganoderma species. MTT and Trypan blue exclusion assay as well as tumorigenesis study were used to assess the anti-tumor effect in vitro and in vivo. Using flow cytometry and Western Blots, we examined further the molecular mechanisms of anti-tumor effect. Finally, biochemical and hematological profiles and pathological examinations were used to evaluate the safety. RESULTS: The Ganoderma tsugae extracts inhibit colorectal cancer cell proliferation caused by accumulating cells in G(2)/M phase, and it may be through downregulation of cyclin A and B1 and upregulation of p21 and p27. Tumorigenesis study in nude mice revealed the extracts caused tumor shrinkage. Additionally, safety assay showed Ganoderma tsugae extracts caused no significant side effects in an animal model. CONCLUSIONS: This study provides molecular evidence that Ganoderma tsugae extracts exert anti-tumor effects both in vitro and in vivo on colorectal adenocarcinoma cells by inducing G(2)/M cell cycle arrest. More importantly, no significant physiological changes resulting from treatment with Ganoderma tsugae extracts were observed in the animal model. Therefore, these data provide new insights into the possible therapeutic use of Ganoderma tsugae for treating colorectal cancer.

Human manganese superoxide dismutase suppresses HER2/neu-mediated breast cancer malignancy.

The up-regulation of HER2/neu is associated with human malignancies and is a useful target for developing anticancer drugs. Overexpression of human manganese superoxide dismutase (MnSOD) has been demonstrated to effectively suppress various carcinoma cells, including breast carcinomas, in vitro and in vivo. This study demonstrates that MnSOD effectively suppresses HER2/neu oncogene expression at the transcriptional level. Additionally, stable transfection was used and the MnSOD-transfected human breast cancer clones were found to be able to down-regulate the endogenous production of p185(HER2/neu). Furthermore, the MnSOD-overexpressing stable transfectants exhibited reduced soft-agarose colony-forming ability and metastatic properties, unlike control cell lines. These data suggest that MnSOD may be useful in treating HER2/neu-mediated human breast tumor malignancy.

Gene transfer mediated by sphingosine/ dioleoylphosphatidylethanolamine liposomes in the presence of poloxamer 188.

A cationic liposome system consisting of sphingosine (SP) and dioleoylphosphatidylethanolamine (DOPE) was developed for in vitro and in vivo gene transfer. A nonionic surface active agent of poloxamer 188 was incorporated in the formulations to stabilize the DNA/liposome complex. Comparison of the results obtained from systems with and without the effect of poloxamer 188 was made to investigate the efficiency of gene expression. In vitro transfection study of the DNA/liposome complex showed that with the effect of poloxamer 188, gene transfer into some cell lines was enhanced. In vivo systemic delivery of the DNA/liposome complex with poloxamer 188 demonstrated gene expression with improved luciferase activity in all major organs including lung, spleen, heart, liver, and kidney. High level transgene activity was found in lung and spleen with prolonged gene expression. This was attributed to poloxamer 188 that stabilized the liposome system and produced homogeneous DNA/liposome complex for enhancement of gene delivery.