CSMed® wound dressing for prophylaxis and management of radiation dermatitis in breast and head-neck cancer patients: a single hospital prospective clinical trial.

PURPOSE: CSMed® wound dressing, a dressing with various herb extracts, was tested for its therapeutic effect in radiation dermatitis of breast and head-and-neck cancer patients. METHODS: This study included 20 breast cancer patients and 10 head-and-neck cancer patients. Half of the irradiated area was covered with CSMed® and the other half was under routine treatment. The severity of radiation dermatitis was evaluated with radiation therapy oncology group (RTOG) grade throughout the treatment and the follow-up period. The RTOG grade between the dressed and undressed area were compared to illustrate the therapeutic effect of CSMed® dressing. RESULTS: The results showed that CSMed® dressed area had significant lower RTOG score at 3-7 weeks and final record during the treatment, and 1-3 weeks during follow-up than undressed area. CONCLUSIONS: This indicated that CSMed® can delay the onset, reduce the severity, and enhance healing of radiation dermatitis. CSMed® can be used for prophylaxis and management of radiation dermatitis.

Radiomic biomarkers for platinum-refractory head and neck cancer in the era of immunotherapy.

OBJECTIVE: Immune checkpoint inhibitors (ICI) are recommended as the first-line therapy for platinum-refractory head and neck squamous cell carcinoma (HNSCC), a disease with a poor prognosis. However, biomarkers in this situation are rare. The objective was to identify radiomic features-associated biomarkers to guide the prognosis and treatment opinions in the era of ICI. METHODS: A total of 31 platinum-refractory HNSCC patients were retrospectively enrolled. Of these, 65.5% (20/31) received ICI-based therapy and 35.5% (11/31) did not. Radiomic features of the primary site at the onset of recurrent metastatic (R/M) status were extracted. Prognostic and predictive radiomic biomarkers were analysed. RESULTS: The median overall survival from R/M status (R/M OS) was 9.6 months. Grey-level co-occurrence matrix-associated texture features were the most important in identifying the patients with or without 9-month R/M death. A radiomic risk-stratification model was established and equally separated the patients into high-, intermittent- and lower-risk groups (1-year R/M death rate, 100.0% vs. 70.8% vs. 27.1%, p = 0.001). Short-run high grey-level emphasis (SRHGE) was more suitable than programmed death ligand 1 (PD-L1) expression in selecting whether patients received ICI-based therapy. CONCLUSIONS: Radiomic features were effective prognostic and predictive biomarkers. Future studies are warranted.

FDG PET/CT Demonstrated Unilateral Striatum Hypometabolism in a Case of Advanced Nasopharyngeal Cancer.

ABSTRACT: A 79-year-old man with nasopharyngeal cancer (NPC) presented with diplopia symptom and a history of diabetes mellitus was referred for an FDG PET/CT scan to determine the pretreatment staging. The FDG PET/CT scan revealed NPC with skull base invasion and decreased FDG uptake at the left striatum. A review of his clinical history and a brain MRI conducted 5 months ago confirmed a previous diagnosis of left hyperglycemic hemichorea. In this NPC patient with inadequate blood sugar control, unilateral striatum hypometabolism may persist for up to 5 months after the initial clinical symptoms.

Effectiveness of multimedia courses in improving self-care among patients with breast cancer undergoing radiotherapy.

BACKGROUND: Ninety percent of patients receiving radiation therapy experience side effects. Busy schedules and intensive health education programs may lead to incomplete education content delivery and inaccurate patient self-care implementation. This study investigated whether multimedia health education improves the accuracy of patient self-care implementation compared with paper-based education. METHODS: From March 11, 2020 to February 28, 2021, 110 patients were randomly divided into experimental and control groups, each comprising 55 participants. Paper-based materials were used along with multimedia materials. Radiology self-care awareness questionnaires were administered to both groups before the first treatment and on day 10. The differences in radiology self-care awareness between the two groups was analyzed with inferential statistics, independent t tests, categorical data, and Pearson's chi-squared test. Differences between the two groups were considered significant at a p value of < 0.05. RESULTS: The treatment accuracy rate improved from 10.9 to 79.1% in the control group and from 24.8 to 98.5% in the experimental group, indicating an improvement in both groups. The difference was significant. These results indicate that the intervention could improve the effectiveness of self-care. CONCLUSIONS: Participants who used pretreatment multimedia health education exhibited a higher rate of having a correct understanding of treatment self-care than did the control group. These findings can inform the development of a patient-centered cancer treatment knowledge base for improved quality of care.

Effects of the individual three-dimensional printed craniofacial bones with a quick response code on the skull spatial knowledge of undergraduate medical students.

Understanding the three-dimensional (3D) structure of the human skull is imperative for medical courses. However, medical students are overwhelmed by the spatial complexity of the skull. Separated polyvinyl chloride (PVC) bone models have advantages as learning tools, but they are fragile and expensive. This study aimed to reconstruct 3D-printed skull bone models (3D-PSBs) using polylactic acid (PLA) with anatomical characteristics for spatial recognition of the skull. Student responses to 3D-PSB application were investigated through a questionnaire and tests to understand the requirement of these models as a learning tool. The students were randomly divided into 3D-PSB (n = 63) and skull (n = 67) groups to analyze pre- and post-test scores. Their knowledge was improved, with the gain scores of the 3D-PSB group (50.0 ± 3.0) higher than that of the skull group (37.3 ± 5.2). Most students agreed that using 3D-PSBs with quick response codes could improve immediate feedback on teaching (88%; 4.41 ± 0.75), while 85.9% of the students agreed that individual 3D-PSBs clarified the structures hidden within the skull (4.41 ± 0.75). The ball drop test revealed that the mechanical strength of the cement/PLA model was significantly greater than that of the cement or PLA model. The prices of the PVC, cement, and cement/PLA models were 234, 1.9, and 10 times higher than that of the 3D-PSB model, respectively. These findings imply that low-cost 3D-PSB models could revolutionize skull anatomical education by incorporating digital technologies like the QR system into the anatomical teaching repertoire.

Hepatoprotective Activity of Nelumbo nucifera Gaertn. Seedpod Extract Attenuated Acetaminophen-Induced Hepatotoxicity.

The aim is to investigate the effect of lotus (Nelumbo nucifera Gaertn.) seedpod extract (LSE) on acetaminophen (APAP)-induced hepatotoxicity. LSE is rich in polyphenols and has potent antioxidant capacity. APAP is a commonly used analgesic, while APAP overdose is the main reason for drug toxicity in the liver. Until now, there has been no in vitro test of LSE in drug-induced hepatotoxicity responses. LSEs were used to evaluate the effect on APAP-induced cytotoxicity, ROS level, apoptotic rate, and molecule mechanisms. The co-treatment of APAP and LSEs elevated the survival rate and decreased intracellular ROS levels on HepG2 cells. LSEs treatment could significantly reduce APAP-induced HepG2 apoptosis assessed by DAPI and Annexin V/PI. The further molecule mechanisms indicated that LSEs decreased Fas/FasL binding and reduced Bax and tBid to restore mitochondrial structure and subsequently suppress downstream apoptosis cascade activation. These declines in COX-2, NF-κB, and iNOS levels were observed in co-treatment APAP and LSEs, which indicated that LSEs could ameliorate APAP-induced inflammation. LSE protected APAP-induced apoptosis by preventing extrinsic, intrinsic, and JNK-mediated pathways. In addition, the restoration of mitochondria and inflammatory suppression in LSEs treatments indicated that LSEs could decrease oxidative stress induced by toxic APAP. Therefore, LSE could be a novel therapeutic option for an antidote against overdose of APAP.

Preoperative prediction model to evaluate salvage surgery in patients with recurrent or second primary oral cavity squamous cell carcinoma.

OBJECTIVE: In approximately 50% of patients with oral cavity squamous cell carcinoma (OCSCC), the disease progresses after curative surgery. However, the role of salvage surgery (SS) is controversial, and life expectancy after SS is unknown. METHODS: In this study, 262 patients with OCSCC with locoregional recurrence and second primary OCSCC were retrospectively enrolled and divided into a resectable (55.0%, 144/262) and unresectable (45.0%, 118/262) groups. After excluding neck recurrence only, SS had been performed 195 times in the resectable group. The corresponding preoperative clinicopathologic factors and postsurgery survival (PSS) of each SS were pooled for analysis. RESULTS: Median survival after disease progression was 64.2 and 10.4 months for the resectable and unresectable groups, respectively. In the resectable group, one-fifth (19.5%, 37/190) of the patients died within 1 year of SS (PSS < 1 year), and one-third (32.8%, 64/195) of the patients had undergone SS two or more times. The interval from the last surgery ≤ 12 months, depth of invasion of the last surgery > 1 cm, and clinical evidence of nodal disease at the preoperative evaluation were independent predictors of poor PSS. A scoring prediction model was established with 1 point for each factor. The results revealed 1-year postsurgery death rates of 10.3% in the low-risk group (score: 0-1) and 48.6% in the high-risk group (score: 2 or 3) (P < 0.001). CONCLUSIONS: In conclusion, an effective scoring model predicting life expectancy after SS for patients with OCSCC was established.

Evaluating photoneutron dose equivalents for lung cancer using PMMA phantoms undergoing 15 MV IMRT.

BACKGROUND: According to statistics of the Ministry of Health and Welfare in 2017, the second leading cause of death in Taiwan was lung cancer. OBJECTIVE: Routine treatment planning does not consider photoneutron dose equivalent (PNDE) of patient induced secondary radiation resulting from primary exposure of lung cancer. However, such treatment is potentially important for improving estimates of health risks. METHODS: This study used 10, 30, 50, 70, and 90 kg of polymethylmethacrylate (PMMA) phantoms as patient to measure PNDE varying anatomical area during lung cancer of intensity modulated radiotherapy (IMRT) treatment. Paired thermoluminescent dosimeters (TLD-600 and 700) were calibrated using university reactor neutrons. TLDs were inserted into phantom which was closely corresponded of the represented tissues or organs. RESULTS: Neutron doses (ND) of organ or tissue (N⁢DT) were determined in these phantoms using paired TLDs approach. The risks of incurring fatal secondary malignancies, maximum statistical and total errors were estimated. Evaluated PNDE ranged from 0.80 ± 0.12 to 0.56 ± 0.08 mSv/Gy for these phantoms. CONCLUSION: The estimated N⁢DT decreased with increasing distance that is from the central axis. Evaluated PNDE and N⁢D𝑠𝑘𝑖𝑛 for these phantoms were discussed. This investigation also identified secondary risks associated with PNDE relating to radiation protection.

Evaluating dose distributions of normal organs for patients undergoing VMAT therapy of nasopharyngeal carcinoma using Rando phantom and TLD-100H.

BACKGROUND: The routine radiation therapy treatment planning does not include secondary radiation and peripheral doses resulting from radiotherapy exposure in patients with nasopharyngeal carcinoma (NPC) undergoing Volumetric Modulated Arc Therapy (VMAT) using an linear accelerator (linac) of Axesse (Elekta 2538). OBJECTIVE: VMAT has a better dose conformity of the tumor and is also operated by adjusting the shapes of mulileaf collimator. However, such treatment is potentially important to improve the accuracy of estimated health risks. METHODS: This study aimed to evaluate the equivalent dose of organ or tissue (DT) and effective dose (E) for normal organs using the Alderson Rando phantom as an equivalent of the human body. Thermoluminescent dosimeters (TLD-100H) were calibrated by 6 MV X-ray originated by the linac. A total of 252 TLDs were used. These TLDs were inserted into phantom organ or tissue which closely approximated to these places. RESULTS: The thyroid dose (D𝑡ℎ𝑦) had the highest dose, 1840 ± 202 mSv/treatment. The E of the Rando was 7.11 ± 0.61 mSv/treatment, as estimated using ICRP 103. The skin doses (D𝑠𝑘𝑖𝑛) varied significantly outside the treatment field and decreased as the distance from the treatment field increased. CONCLUSIONS: This study can be referred to practical guidance regarding radiation protections of the public.

Prediction Model of Distant Metastasis in Oral Cavity Squamous Cell Carcinoma With or Without Regional Lymphatic Metastasis.

Patients with oral cavity squamous cell carcinoma (OCSCC) who develop distant metastasis (DM) face poor outcomes, and effective prediction models of DM are rare. A total of 595 patients with OCSCC were retrospectively enrolled in this study. Because pathological N staging significantly influences the development and mechanisms of DM, the patients were divided into nodal-negative (pN-) and -positive (pN+) groups. Clinical outcomes, prognoses, and prediction models were analyzed separately for both groups. Overall, 8.9% (53/595) of these patients developed DM. Among the DM cases, 84.9% (45/53) of them developed DM within the first 3 years. The median overall survival, locoregional recurrence-free survival, time until DM development, and postmetastatic survival were 19.8, 12.7, 14.6, and 4.1 months, respectively. Distinguishing patients who only developed locoregional recurrence from those with DM according to locoregional conditions was difficult. Age, surgical margin, and early locoregional recurrence were predictors of DM that were independent of time until DM in the pN- group; the lymphocyte-to-monocyte ratio, presence of lymphovascular invasion, and early locoregional recurrence in the pN+ group were determined. If one point was scored for each factor, then two scoring systems were used to classify the patients into low- (score = 0), intermittent- (score = 1), or high- (score = 2 or 3) risk for the pN- and pN+ groups. According to this scoring system, the 3-year DM rates for the low, intermittent, and high risk subgroups were 0.0%, 5.9%, and 17.8% for the pN- group and 7.1%, 44.9%, and 82.5% for the pN+ group, respectively. These systems also effectively predicted DM, and the areas under the curve predicted DM occurring within the first 3 years were 0.744 and 0.820 for the pN- and pN+ groups, respectively. In conclusion, effective scoring models were established for predicting DM.

Predictors of early progression after curative resection followed by platinum-based adjuvant chemoradiotherapy in oral cavity squamous cell carcinoma.

OBJECTIVES: Early progression, defined as a disease-free interval (DFI) of less than 6 months after completion of adjuvant platinum-based chemoradiotherapy (CRT), leads to poor outcomes in locally advanced oral cavity squamous cell carcinoma (OCSCC). However, appropriate biomarkers for predicting early progression remain unknown. METHODS: In this study, 346 patients with OCSCC, who underwent curative surgical resection and platinum-based adjuvant CRT at the Taipei Veterans General Hospital (202 patients, training cohort) and Chung Shan Medical University Hospital (144 patients, validation cohort) were enrolled. The clinical-pathological variables were compared using the χ2 test. Cox proportional-hazards analyses were performed for DFIs. Survival was estimated using the Kaplan-Meier method and log-rank tests, and a scoring system for predicting early progression was established. RESULTS: One-fifth (20.5%, 71/346) of all patients experienced progression within 6 months. Each of the independent factors for the DFI in the training cohort, including pT3-4, extracapsular spread, and perineural invasion, were assigned a score of one point to establish a scoring system. The 6-month DFIs of the low-risk (score 0-1), intermediate-risk (score 2), and high-risk (score 3) groups were 97.8%, 78.7%, and 35.7% and 88.2%, 77.6%, and 42.1% in the training and validation cohorts, respectively. If the cutoff level was ≥2 or <2, the sensitivity/specificity/area under the curve for the training and validation cohorts were 94.4%/56.1%/0.837, and 73.3%/56.6%/0.703, respectively. CONCLUSIONS: The established scoring system effectively predicted early progression after adjuvant CRT for locally advanced OCSCC.

Radiation doses with various body weights of phantoms in brain 128-slice MDCT examination.

The effective dose (HE) and organ or tissue equivalent dose (HT) for use in brain computed tomography (CT) examinations with various body weights were evaluated. Thermoluminescent dosimeters (TLD-100H) were inserted into Rando and five anthropomorphic phantoms. These phantoms were made of polymethylmethacrylate (PMMA), according to the specifications of ICRU 48, with masses from 10 to 90 kg. Brain CT examinations were conducted, scanning the maxillae from the external auditory meatus to the parietal bone using a 128-slice multi-detector CT (MDCT) scanner. To reduce errors, three independent trials were conducted. Calculated HE,TLD, based on the weighting factor recommended by ICRP 103, was 1.72 ± 0.28 mSv, which slightly exceeds the HE,DLP of 1.70 mSv, that was calculated from the dose-length product (DLP) of the Rando phantom. This experiment yielded HE,TLD values of ICRP 103 from the highest 1.85 ± 0.28 (90 kg) to the lowest 1.47 ± 0.22 (10 kg) mSv. HE,TLD (mSv) = 5.45×10-3 W(kg) + 1.361, with an R2 of 0.87667. Using the DLP protocol, HE,DLP was estimated from CTDIvol that was recorded directly from the console display of the CT unit and multiplied by the conversion coefficient (k) recommended by the ICRP 103. Finally, the experimental results obtained herein are compared with those in the literature. Physicians should choose and adjust protocols to prevent the exposure of patients to unnecessary radiation, satisfying the as low as reasonably achievable (ALARA) principle. These findings will be valuable to patients, physicians, radiologists and the public.

In Vitro and In Vivo Protective Effects of Flavonoid-Enriched Lotus Seedpod Extract on Lipopolysaccharide-Induced Hepatic Inflammation.

Endotoxin lipopolysaccharide (LPS) plays an important role in the acceleration of hepatic inflammation. Natural medicinal plants that can prevent inflammation by targeting LPS have potential therapeutic clinical application. The aim of the study is to examine the anti-inflammatory effects of lotus seedpod extract (LSE), used as a traditional Chinese herbal medicine with hemostasis function and for eliminating bruise, on the LPS-induced hepatic inflammation and its underlying molecular mechanisms in vitro and in vivo. In vitro, LSE and its purified compound (-)-epigallocatechin (EGC) dose-dependently inhibited the expressions of pro-inflammatory cytokines and mediators, including tumor necrosis factor (TNF)- α , interleukin (IL)-6, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), without affecting cell viability in LPS-stimulated human hepatoma cell line HepG2. Molecular studies showed the anti-LPS effect of HLP or EGC might be mediated via downregulation of Toll-like receptor 4. (TLR4)-mediated both NF- κ B and p38 signaling, as demonstrated by the usage of pyrrolidine dithiocarbamate (PDTC), a specific NF- κ B inhibitor. In vivo, LPS-induced hepatic inflammation was significantly ameliorated in LSE-fed mice as gauged by dose-dependent inhibition of serum levels of biochemical markers of liver damage, the changes of hepatic lobular architecture and the secretion of pro-inflammatory mediators, as well as induction of anti-oxidant enzymes. As a result, our data presented the first evidence of EGC-enriched LSE as an anti-inflammatory agent in LPS-stimulated HepG2 cells and mice, and these findings may open interesting perspectives to the strategy in treatment for hepatic inflammation.

Tribbles Homolog 3 Involved in Radiation Response of Triple Negative Breast Cancer Cells by Regulating Notch1 Activation.

Breast cancer is the most common cancer for women in Taiwan and post-lumpectomy radiotherapy is one of the therapeutic strategies for this malignancy. Although the 10-year overall survival of breast cancer patients is greatly improved by radiotherapy, the locoregional recurrence is around 10% and triple negative breast cancers (TNBCs) are at a high risk for relapse. The aim of this paper is to understand the mechanisms of radioresistance in breast cancers which may facilitate the development of new treatments in sensitizing breast cancer toward radiation therapy. Tribbles homolog 3 (TRIB3) is a pseudokinase protein and known to function as a protein scaffold within cells. It has been reported that higher TRIB3 expression is a poor prognostic factor in breast cancer patients with radiotherapy. In this study, we investigate the involvement of TRIB3 in the radiation response of TNBC cells. We first found that the expression of TRIB3 and the activation of Notch1, as well as Notch1 target genes, increased in two radioresistant TNBC cells. Knockdown of TRIB3 in radioresistant MDA-MB-231 TNBC cells decreased Notch1 activation, as well as the CD24-CD44⁺ cancer stem cell population, and sensitized cells toward radiation treatment. The inhibitory effects of TRIB3 knockdown in self-renewal or radioresistance could be reversed by forced expression of the Notch intracellular domain. We also observed an inhibition in cell growth and accumulated cells in the G0/G¹ phase in radioresistant MDA-MB-231 cells after knockdown of TRIB3. With immunoprecipitation and mass spectrometry analysis, we found that, BCL2-associated transcription factor 1 (BCLAF1), BCL2 interacting protein 1 (BNIP1), or DEAD-box helicase 5 (DDX5) were the possible TRIB3 interacting proteins and immunoprecipitation data also confirmed that these proteins interacted with TRIB3 in radioresistant MDA-MB-231 cells. In conclusion, the expression of TRIB3 in radioresistant TNBC cells participated in Notch1 activation and targeted TRIB3 expression may be a strategy to sensitize TNBC cells toward radiation therapy.

Neural response to betel quid cues in chewers: a functional magnetic resonance imaging study.

The World Health Organization regards betel quid (BQ) as a human carcinogen. The current study analyzes whether the BQ cues can elicit activity in the chewers' craving-related brain areas. We adopted a cue-reactivity paradigm to examine the changes in the brain activities. The urge intensity was also included to examine whether it can moderate the brain areas stimulated by BQ cues. Sixteen male BQ chewers and 16 healthy male controls were recruited and analyzed. Four types of cues were adopted: BQ cues, matched food cues, visual control cues, and resting crosshair cued. The most direct and important comparison was between the brain activities elicited by the BQ cues versus those by the food cues. Furthermore, to test the current urge intensity effect, we compared BQ chewers with a strong urge versus those with a weak urge. All of the three-dimension anatomical and multi-slice task-based functional images were acquired using 3 T MRI. We found that (1) the BQ chewers and the healthy controls had similar brain activation patterns when comparing any two cue types, (2) the high-urge (not the low-urge) chewers showed craving-related activations (e.g., anterior cingulate cortex, medial orbitofrontal gyrus, and superior frontal gyrus) in the critical BQ cues vs. the food cue comparisons. (3) The high-urge chewers had larger contrast activations (BQ - Food) in many craving-related brain areas than low-urge chewers did (e.g., frontal gyrus). The urge states endorsed by the chewers can moderate the neural responses to BQ cues. Multisensory cues should be considered to elicit more intense and consistent cravings.

Induction of Mitotic Catastrophe via Inhibition of Aurora B by Ionizing Radiation With Additive of Mulberry Water Extract in Human Bladder Cancer Cells.

Mulberry fruit water extract (MWE) has been reported to synergistically enhance the cytotoxic effect of paclitaxel by promoting mitotic catastrophe to induce apoptosis in bladder cancer cells in our previous work. The aim of this study was to evaluate and to mechanistically explore the effects of MWE on bladder cancer responses to ionizing radiation (IR) by treating TSGH 8301 bladder carcinoma cells with MWE after exposing to IR. The results of MTT assay showed a synergistic cytotoxicity of IR with the co-treatment of MWE (IR/MWE) by inducing G2/M phase arrest as demonstrated by flow cytometry analysis in TSGH 8301, HT1367 and HT1197 bladder carcinoma cells lines. The IR/MWE-treated cells expressed increased levels of the G2/M phase arrest-related proteins cdc2/cyclin B1 and displayed giant multinucleated morphology, a typical characteristic of mitotic catastrophe. Immunofluorescent confocal microscopy revealed that the combined strategy inhibited Aurora B phosphorylation through Ras/Raf/MEK/ERK signaling cascade as demonstrated by Western blotting analysis. IR/MWE also caused an inhibitory effect on Plk1 and the subsequent downstream regulator RhoA repression and Cep55 induction, which would influence cell cycle progression in the early steps of cytokinesis. A profound tumor growth suppression and inactivation of Aurora B activity in the tumor tissues by IR/MWE treatment were confirmed in the TSGH 8301 xenograft model in vivo. These data demonstrated that MWE could be an effective auxiliary to synergize with radiation on the anticancer efficacy by promoting mitotic catastrophe through inhibition of Aurora B, providing a novel and effective therapeutic option for bladder cancer management.

Evaluating doses of multi-slice CT in brain examinations using various methods.

PURPOSE: The effective dose (HE) and organ or tissue equivalent dose (HT) of a Rando phantom undergoing two brain computed tomography (CT) examination protocols were evaluated using thermoluminescent dosimeters (TLD-100H) and dose length product (DLP) methods. MATERIALS AND METHODS: TLDs were inserted into the correlated positions of an organ or tissue of Rando phantom, such as thyroid, brain, and salivary gland, using (A) axial scan: scanning the maxillae ranging from external auditory meatus to the parietal bone, and (B) helical scan: scanning from the mandible to the parietal bone. CT examinations were performed on a Philips computer tomography (Brilliance CT) at Lukang Christian Hospital. TLDs were measured using a Harshaw 3500 TLD reader. The HT of organ and tissue during the two protocols was discussed. RESULTS AND CONCLUSION: HE were calculated using ICRP 60 and 103 at 2.67 ± 0.18 and 1.89 ± 0.23 mSv based on an axial scan, and 4.70 ± 0.38 and 4.39 ± 0.37 mSv based on a helical scan, respectively. In the DLP method, HE was estimated from CTDIvol that was recorded directly from the console display of the CT unit and then calculated using AAPM 96. Finally, experimental results are compared with those in literature. Radiologists should choose and adjust protocols to prevent unnecessary radiation to patients and satisfying the as low as reasonably achievable (ALARA) principle. These findings will be valuable to patients, physicians, radiologists, and the public.

Hsp90α Mediates BMI1 Expression in Breast Cancer Stem/Progenitor Cells through Facilitating Nuclear Translocation of c-Myc and EZH2.

Heat shock protein 90 (Hsp90) is a molecular chaperone that facilitates the correct folding and functionality of its client protein. Numerous Hsp90-client proteins are involved in cancer development. Thus, Hsp90 inhibitors have potential applications as anti-cancer drugs. We previously discovered that Hsp90α expression increased in breast cancer stem cells (BCSCs), which can initiate tumorigenesis and metastasis and resist treatment. In the present study, we further demonstrated that 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), an inhibitor of Hsp90, could suppress the self-renewal of BCSCs by downregulating B lymphoma Mo-MLV insertion region 1 homolog (BMI1), a polycomb family member with oncogenic activity in breast cancer. Through immunoprecipitation analysis, we found that BMI1 did not interact with Hsp90α and that the downregulation of BMI1 by 17-DMAG was mediated by the inhibition of c-Myc and enhancement of zeste homolog 2 (EZH2) expression. The transcriptional and BMI1 promoter-binding activities of c-Myc in BCSCs were inhibited by 17-DMAG treatment. The overexpression of EZH2 attenuated the inhibitory effect of 17-DMAG on BMI1 and c-Myc expression. Furthermore, Hsp90α could be co-immunoprecipitated with c-Myc and EZH2 and bind to the BMI1 promoter. Treatment with 17-DMAG decreased the nuclear expression of EZH2 and c-Myc but not that of Hsp90α. In conclusion, our data suggested that Hsp90α could positively regulate the self-renewal of BCSCs by facilitating the nuclear translocation of c-Myc and EZH2 to maintain BMI1 expression.

Evaluation of structural connectivity changes in betel-quid chewers using generalized q-sampling MRI.

RATIONALE: Betel quid (BQ) is a common addictive substance in many Asian countries. However, few studies have focused on the influences of BQ on the brain. It remains unclear how BQ can affect structural brain abnormalities in BQ chewers. OBJECTIVES: We aimed to use generalized q-sampling imaging (GQI) to evaluate the impact of the neurological structure of white matter caused by BQ. METHODS: The study population comprised 16 BQ chewers, 15 tobacco and alcohol controls, and 17 healthy controls. We used GQI with voxel-based statistical analysis (VBA) to evaluate structural brain and connectivity abnormalities in the BQ chewers compared to the tobacco and alcohol controls and the healthy controls. Graph theoretical analysis (GTA) and network-based statistical (NBS) analysis were also performed to identify the structural network differences among the three groups. RESULTS: Using GQI, we found increases in diffusion anisotropy in the right anterior cingulate cortex (ACC), the midbrain, the bilateral angular gyrus, the right superior temporal gyrus (rSTG), the bilateral superior occipital gyrus, the left middle occipital gyrus, the bilateral superior and inferior parietal lobule, and the bilateral postcentral and precentral gyrus in the BQ chewers when compared to the tobacco and alcohol controls and the healthy controls. In GTA and NBS analyses, we found more connections in connectivity among the BQ chewers, particularly in the bilateral anterior cingulum. CONCLUSIONS: Our results provided further evidence indicating that BQ chewing may lead to brain structure and connectivity changes in BQ chewers.

Promotion of mitotic catastrophe via activation of PTEN by paclitaxel with supplement of mulberry water extract in bladder cancer cells.

Paclitaxel is a mitotic inhibitor used in cancer chemotherapy. Mulberry fruit is rich in phenolic compounds and flavonoids and exhibits chemopreventive activities. In this study, mulberry water extract (MWE) was used as a supplement to synergize with the effects of paclitaxel in the treatment of the TSGH 8301 human bladder cancer cell line. Treatment with paclitaxel combined with MWE (paclitaxel/MWE) enhanced the cytotoxicity of paclitaxel and induced severe G2/M arrest, mitotic catastrophe and subsequent apoptosis, as shown by MTT assay, HE staining and flow cytometry analyses. Differences in the expression and activation of Aurora A and Plk1 between cells treated with paclitaxel/MWE and paclitaxel alone suggested that the combined treatment caused a defect in the early steps of cytokinesis. Paclitaxel/MWE decreased EEA1 immunofluorescence staining and increased the expression of PTEN, indicating that the regimen inhibited the formation of the recycling endosome, which is required for cytokinesis. Paclitaxel/MWE also retarded tumor growth in a TSGH 8301 xenograft model via activation of PTEN and Caspase 3. These data demonstrated a synergistic effect on the anticancer efficacy of paclitaxel through MWE supplementation by promoting mitotic catastrophe through the activation of PTEN, providing a novel and effective therapeutic option for bladder cancer treatment strategies.