Recombinant cell-detecting RaDR-GFP in mice reveals an association between genomic instability and radiation-induced-thymic lymphoma

xlomafota13 shared this article with you from Inoreader Recombinant cell-detecting RaDR-GFP in mice reveals an association between genomic instability and radiation-induced-thymic lymphoma Via American Journal of Cancer Research Am J Cancer Res. 2022 Feb 15;12(2):562-573. eCollection 2022. ABSTRACT In this study, we aimed to investigate how homologous recombinant (HR)-related genomic instability is involved in ionizing radiation (IR)-induced thymic lymphoma in mice. We divided five-week-old Rosa26 Direct Repeat-GFP (RaDR-GFP) transgenic mice into non-IR control and IR groups and exposed the mice in the IR group to a 7.2 Gy dose of γ-rays, delivered in 1.8 Gy fractions, once a week for four weeks. We then estimated mouse survival and recorded their body, thymus, and spleen weights. The frequency of HR events in the chromosomes of the thymus, bone marrow, and spleen cells and the phenotype of thymic lymphoma cells were analyzed using fluorescence-activated cell sorting (FACS). We found that most mice in the IR group developed thymic lymphoma, their survival rate decreasing to 20% after 180 days of IR exposure, whereas no mice died in the non-IR control group un til day 400. The thymus and spleen weighed significantly more in the IR-4-month group than that in the non-IR group; however, we observed no significant differences between the body weights of the control and IR mice. FACS analysis indicated that the frequency of HR events significantly increased at two and four months after the last IR dose in the bone marrow and thymus cells, but not in the spleen cells of RaDR-GFP transgenic mice, suggesting that recombinant cells accumulated in the thymus upon IR exposure. This suggests that IR induces genome instability, revealed as increased HR, that drives the development of thymic lymphoma. Additionally, phenotypic analysis of lymphoma cells showed an increase in the CD4-/CD8+ (CD8SP) cell population and a decrease in the CD4+/CD8- (CD4SP) cell population in the IR-4-month group compared to that in the non-IR group, indicating that IR induces an aberrant cell phenotype characteristic of lymphoma. I n conclusion, we observed a significant increase in HR events and abnormal phenotype in thymic lymphoma cells at two and four months after IR exposure in both the thymus and bone marrow tissues, suggesting that genomic instability is involved in the early stages of thymic lymphomagenesis. Our study indicates that HR-visualizing RaDR-GFP transgenic mice can help explore the links between the molecular mechanisms of genome instability and IR-induced tumorigenesis. PMID:35261787 | PMC:PMC8899999 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Multimodality imaging in the assessment of bone marrow-derived mesenchymal stem cell therapy for doxorubicin-induced cardiomyopathy

xlomafota13 shared this article with you from Inoreader Multimodality imaging in the assessment of bone marrow-derived mesenchymal stem cell therapy for doxorubicin-induced cardiomyopathy Via American Journal of Cancer Research Am J Cancer Res. 2022 Feb 15;12(2):574-584. eCollection 2022. ABSTRACT Due to their broad-spectrum effects and high antitumor efficacies, anthracycline-based chemotherapies are commonly prescribed in various solid and hematological malignancies. Doxorubicin (DOX) is one of the most highly used anthracyclines but has been shown to cause lethal cardiomyopathy in clinical practice. Studies have demonstrated that bone marrow-derived mesenchymal stem cells (BMSCs) have the ability to rescue DOX-induced cardiomyopathy (DIC). However, novel molecular imaging techniques are required to explore the biological behaviors, safety, eventual viability, and environmental interactions of transplanted stem cells during therapy. To investigate the biological behaviors of transplanted BMSCs, we applied bioluminescence imaging (BLI) and magnetic resonance imaging (MRI) techniques to trace firefly luciferase (Fluc) and ultrasmall superparamagnetic iron oxi de (USPIO) double-labeled mouse BMSCs after injection into the heart apex in a chronic DIC mouse model. Then, we determined the optimal BMSC number for transplantation into the heart and optimized MRI parameters to evaluate transplanted BMSCs in vitro and in vivo. Our results showed that the BLI trace signal could last 7 days in the DIC mouse model, whereas the MRI signal lasted up to 3 days. However, MRI provided more detailed pathophysiological information on DIC than BLI, such as inflammation and fibrosis signs. The optimal in vivo cell number for BLI and MRI was determined to be 1×106. In conclusion, BLI combined with multimodality MRI could be used to monitor the biological behavior of BMSCs transplanted into a chronic DIC mouse model in a visual and dynamic manner. PMID:35261788 | PMC:PMC8899982 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Trastuzumab in combination with PEGylated interferon-α1b exerts synergistic antitumor activity through enhanced inhibition of HER2 downstream signaling and antibody-dependent cellular cytotoxicity

xlomafota13 shared this article with you from Inoreader Trastuzumab in combination with PEGylated interferon-α1b exerts synergistic antitumor activity through enhanced inhibition of HER2 downstream signaling and antibody-dependent cellular cytotoxicity Via American Journal of Cancer Research Am J Cancer Res. 2022 Feb 15;12(2):549-561. eCollection 2022. ABSTRACT The anti-HER2 monoclonal antibody trastuzumab is the mainstay of treatment for HER2-positive breast and gastric cancer, and its combination with multiple chemotherapeutic agents has represented an effective and rational strategy in the clinic. In this study, we report that trastuzumab in combination with PEGylated interferon-α1b (IFN-α1b), a polyethylene glycol (PEG)-conjugated form of a subtype of interferon alpha (IFN-α), synergistically inhibited the proliferation of HER2-positive cells, including BT-474 and SK-BR-3 breast cancer cells and NCI-N87 gastric cancer cells, and also induced their apoptosis, but had no effect on HER2-negative MDA-MB-231 breast cancer cells. Trastuzumab inhibited phosphorylation of HER2, AKT and ERK, an effect that was enhanced by PEGylated IFN-α1b, likely owing to PEGylated IFN-α1b-mediated downregulation of HER2 through the lysos omal degradation pathway. Moreover, PEGylated IFN-α1b significantly enhanced trastuzumab-mediated antibody-dependent cellular cytotoxicity (ADCC) in HER2-positive cells. Importantly, trastuzumab combined with PEGylated IFN-α1b exhibited significant synergistic antitumor activity in HER2-positive BT-474 xenografts, an effect that was associated with enhanced inhibition of HER2 expression and AKT and ERK phosphorylation. Strikingly, depletion of natural killer cells with anti-Asialo GM1 antibody abrogated the synergistic antitumor activity, indicating that augmented ADCC is essential for this synergy. Taken together, our findings indicate that both enhanced inhibition of HER2 downstream signaling and augmented ADCC contribute to the synergistic antitumor activity of trastuzumab with PEGylated IFN-α1b, and imply that combining trastuzumab with PEGylated IFN-α1b could be a promising strategy for HER2-positive cancers. PMID:35261786 | PMC:PMC8899978 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Significant association between serum Wisteria floribunda agglutinin-positive Mac-2-binding protein and prognosis of hepatocellular carcinoma after surgical treatment

xlomafota13 shared this article with you from Inoreader Significant association between serum Wisteria floribunda agglutinin-positive Mac-2-binding protein and prognosis of hepatocellular carcinoma after surgical treatment Via American Journal of Cancer Research Am J Cancer Res. 2022 Feb 15;12(2):601-614. eCollection 2022. ABSTRACT Serum Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA+-M2BP) is a novel marker for evaluating fibrosis and predicting the development of hepatocellular carcinoma (HCC). However, the role of WFA+-M2BP in the prognosis of HCC patients after curative surgery remains unknown. In this study, we aimed to evaluate the prognostic role of serum WFA+-M2BP in HCC patients after curative resection and liver transplantation. We enrolled 460 HCC patients (357 resection and 103 transplantation) to analyze the risk factors for HCC recurrence and patient's survival. We employed time-to-event models using univariate and multivariable Cox proportional hazards regression analyses and calculated the hazard ratios (HRs) and adjusted HRs with their corresponding 95% confidence intervals (CIs). The levels of WFA+-M2BP were 0.19 -14.51 COI (median 1.08) in patients of hepatectomy and 0.47-19.90 COI (median 6.0) in transplant patients. The levels of WFA+-M2BP in liver transplant patients is much higher than that of hepatectomy patients. Overall, liver fibrotic stage was positively correlated to WFA+-M2BP levels (P<0.0001). This study demonstrated that elevated WFA+-M2BP level (COI ≥0.75) was associated with a higher HCC recurrence rate in the resection group (P<0.001). Survival analysis showed that an elevated WFA+-M2BP level (COI ≥1.43) is associated with a higher mortality risk after surgical resection (P=0.0088) in the univariate analysis only. In liver transplant patients, WFA+-M2BP level (COI ≥3.81) did not predict HCC recurrence at all, but was associated poor survival after transplantation, with a borderline significance (P=0.0943). Serum WFA+-M2BP is a reliable marker for liver fibrosis in the present study. It is also reli able marker to predict prognosis of HCC after surgical resection. However, the prognostic role of WFA+-M2BP in HCC related transplants is equivocal, which is different from that of surgical resection. PMID:35261790 | PMC:PMC8899980 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Chronic Cough: Evaluation of Patients’ Motivation to Undergo Cough Suppression Therapy

xlomafota13 shared this article with you from Inoreader Chronic Cough: Evaluation of Patients' Motivation to Undergo Cough Suppression Therapy Via Journal of Voice Chronic cough is a persistent cough lasting greater than eight weeks. The prevalence rate is estimated to be 9% to 33% in the United States. There are several treatment modalities described in current literature including medical, surgical, and behavioral interventions. Behavioral intervention with a speech-language pathologist (SLP) includes education on laryngeal hygiene and the voluntary control of cough as well as respiratory retraining to suppress or reduce the duration of cough. Cough suppression therapy, like other behavioral therapies, requires patient motivation and commitment to participation and completion in therapy. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Entwicklung auditiver Verarbeitungs- und Wahrnehmungsleistungen mit und ohne AVWS im Grundschulalter

xlomafota13 shared this article with you from Inoreader Entwicklung auditiver Verarbeitungs- und Wahrnehmungsleistungen mit und ohne AVWS im Grundschulalter Via Sprache · Stimme · Gehör Sprache · Stimme · Gehör 2022; 46: 44-50 DOI: 10.1055/a-1745-7502 Hintergrund Ob sich die an unauffälligen Kindern beschriebenen Reifungsprozesse des zentralen Hörsystems auch an Kindern mit auditiven Verarbeitungs- und Wahrnehmungsstörungen (AVWS) im Grundschulalter nachweisen lassen, sollte an 2 Schülerjahrgängen (1. und 4. Klasse) im Kontrollgruppenvergleich untersucht werden. Material und Methoden In die Auswertung gingen 7 Testergebnisse von 82 Erstklässlern (40 mit AVWS; 42 unauffällige Kinder) und 65 Viertklässlern (35 mit AVWS; 30 unauffällige Kinder) ein. Es wurde eine ANOVA mit dem Gesamtsummenwert aus folgenden 7 Untersuchungen sowie anschließend eine MANOVA mit den Einzeltestergebnissen durchgeführt: Göttinger Sprachaudiometrie II im Störgeräusch; dichotisches Wortpaarverstehen (Uttenweiler-Test); Phonemdifferenzierung, Phonemidentifikation, Phonemanalyse (Subtests aus Heidelberger Lautdifferenzierungstest); Zahlenfolgen-Gedächtnis (Subtest aus psycholinguistischem Entwicklungstest); Mottier-Test. Ergebnisse Die ANOVA zeigte signifikante Haupteffekte von „Schuljahr" (p < 0,001; η² = 0,418) und „Gruppe" (p < 0,001; η² = 0,690), jedoch keine Interaktionseffekte zwischen beiden. Das Ergebnis der MANOVA war ähnlich bzgl. der o. g. Haupteffekte; nur für 2 Tests (Phonemidentifikation, Phonemanalyse) wurde die Interaktion der Faktoren Schuljahr und Gruppe mit jeweils geringen Effektstärken von 3 bzw. 6 % statistisch signifikant. Diskussion Gemäß dieser Querschnittsstudie scheint der Unterschied zwischen den beiden Gruppen unabhängig vom Schuljahr zu sein. Fazit Im Grundschulalter gibt es nicht nur für unauffällige Kinder, sondern auch für solche mit AVWS Hinweise auf eine Reifung des zentralen Hörsystems. [...] Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany Article in Thieme eJournals: Table of contents  |  Abstract  |  Full text View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Full coverage path planning algorithm for MRgFUS therapy

xlomafota13 shared this article with you from Inoreader Full coverage path planning algorithm for MRgFUS therapy Via The International Journal of Medical Robotics and Computer Assisted Surgery ABSTRACT Background High-quality methods for Magnetic Resonance guided Focused Ultrasound (MRgFUS) therapy planning are needed for safe and efficient clinical practices. Herein, an algorithm for full coverage path planning based on preoperative MR images is presented. Methods The software functionalities of an MRgFUS robotic system were enhanced by implementing the developed algorithm. The algorithm's performance in accurate path planning following a Zig-Zag pathway was assessed on MR images. The planned sonication paths were performed on acrylic films using the robotic system carrying a 2.75 MHz single element transducer. Results Ablation patterns were successfully planned on MR images and produced on acrylic films by overlapping lesions with excellent match between the planned and experimental lesion shapes. Conclusions The advanced software was proven efficient in planning and executing full ablation of any segmented target. The reliability of the algorithm could be enhanced through the development of a fully automated segmentation procedure. This article is protected by copyright. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.