Negative correlations of psychological distress with quality of life and immunotherapy efficacy in patients with advanced NSCLC

xlomafota13 shared this article with you from Inoreader Negative correlations of psychological distress with quality of life and immunotherapy efficacy in patients with advanced NSCLC Via American Journal of Cancer Research Am J Cancer Res. 2022 Feb 15;12(2):805-815. eCollection 2022. ABSTRACT To evaluate the relationships between psychological distress and immunotherapy efficacy, adverse reactions and quality of life scores in patients with advanced non-small cell lung cancer (NSCLC). A total of 104 NSCLC patients who received 4-6 cycles of standard immunotherapy were enrolled and evaluated with the Distress Thermometer (DT) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). The aim was to analyze the correlation between psychological distress and quality of life and to analyze whether psychological distress affects the efficacy of and adverse reactions to immunotherapy. The objective response rate (ORR) and disease control rate (DCR) of the psychological distress group were 6% and 50%, respectively, and those of the no psychological distress group were 18.5% and 83.3%, respectively. The differen ces were statistically significant (χ2=14.131, P<0.05). The progression-free survival (PFS) of advanced NSCLC patients who received comprehensive immunotherapy and had no psychological distress was significantly better than that of the psychological distress group (HR, 0.338; 95% CI, 0.192-0.592; P<0.05). The PFS of advanced NSCLC patients who received immunotherapy combined with chemotherapy in the no psychological distress group was significantly better than that in the psychological distress group (HR, 0.458; 95% CI, 0.296-0.709; P<0.05). Psychological distress in advanced NSCLC patients affects the efficacy of immunotherapy, and psychological distress is negatively correlated with quality of life during immunotherapy. PMID:35261803 | PMC:PMC8899984 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

ONC206 has anti-tumorigenic effects in human ovarian cancer cells and in a transgenic mouse model of high-grade serous ovarian cancer

xlomafota13 shared this article with you from Inoreader ONC206 has anti-tumorigenic effects in human ovarian cancer cells and in a transgenic mouse model of high-grade serous ovarian cancer Via American Journal of Cancer Research Am J Cancer Res. 2022 Feb 15;12(2):521-536. eCollection 2022. ABSTRACT ONC206, a dopamine receptor D2 (DRD2) antagonist and imipridone, is a chemically modified derivative of ONC201. Recently, ONC206 and other imipridones were identified as activators of the mitochondrial protease ClpP, inducing downstream pathways that allow them to selectively target cancer cells. Clinical trials showed that ONC201, the first in class imipridone, was well tolerated and exhibited tumor regression in some solid tumors. Our goal was to evaluate the effect of ONC206 on cell proliferation and tumor growth in ovarian cancer cell lines and in a transgenic mouse model of high grade serous ovarian cancer (KpB model). ONC206 was more potent than ONC201 in inhibiting cell proliferation, as evidenced by a 10-fold decrease in IC50 for the SKOV3 and OVCAR5 cell lines. This was accompanied by the results that ONC206 significantly inhibited cellular proliferation, i nduced cell cycle G1 arrest and apoptosis, caused cellular stress, and inhibited adhesion and invasion in vitro. Treatment of obese and non-obese KpB mice with ONC206 elevated Bip and ClpP expression and reduced KI67, BCL-XL and DRD2 expression in the ovarian tumors. Our findings demonstrate that ONC206 has anti-tumorigenic effects in ovarian cancer as previously demonstrated by ONC201 but appears to be as well tolerated and more potent. Thus, ONC206 deserves further evaluation in clinical trials. PMID:35261784 | PMC:PMC8900003 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

MUC20 as a novel prognostic biomarker in ccRCC correlating with tumor immune microenvironment modulation

xlomafota13 shared this article with you from Inoreader MUC20 as a novel prognostic biomarker in ccRCC correlating with tumor immune microenvironment modulation Via American Journal of Cancer Research Am J Cancer Res. 2022 Feb 15;12(2):695-712. eCollection 2022. ABSTRACT Tumor microenvironment (TME) broadly participates in genesis development of clear cell renal cell carcinoma (ccRCC). To recognize the immune and stromal modulation in TME, we screened the differentially expressed TME-related genes generated by the ESTIMATE algorithm in ccRCC specimens. Following the construction of protein-protein interaction (PPI) network and univariate COX regression, mucin 20 (MUC20) was judged to be a predictive factor. Further analysis, including immunohistochemistry (IHC) showed that MUC20 was positively correlated with survival and negatively correlated with the clinicopathologic characteristics (grade, clinical and TNM stages) in ccRCC patients. Gene Set Enrichment Analysis suggested that the low-expression MUC20 group was primarily enriched in immune-related activities, inflammation and epithelial-mesenchymal transition. Based on the CIBERS ORT analysis for tumor-infiltrating immune cells (TICs), MUC20 was positively correlated with CD8+ T cells and resting mast cells and negatively correlated with activated CD4+ memory T cells, Treg cells, and plasma cells, implying that MUC20 may contribute to immune component in TME. Additionally, the patients with low MUC20 expression had better response to immune checkpoint blockades (ICBs) and 17 potential anticancer drugs were screened regarding calculating IC50 value. Thus, MUC20 may contain a value of prognosis assessment for ccRCC patients and indicate the immune modulation status of TME, which provided a novel insight for comprehensive immunotherapy. PMID:35261796 | PMC:PMC8899979 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

A novel HDAC11 inhibitor potentiates the tumoricidal effects of cordycepin against malignant peripheral nerve sheath tumor through the Hippo signaling pathway

xlomafota13 shared this article with you from Inoreader A novel HDAC11 inhibitor potentiates the tumoricidal effects of cordycepin against malignant peripheral nerve sheath tumor through the Hippo signaling pathway Via American Journal of Cancer Research Am J Cancer Res. 2022 Feb 15;12(2):873-892. eCollection 2022. ABSTRACT Neurofibromatosis type 1 (NF1) is an autosomal dominant neurocutaneous disorder. Clinically, the hallmarks of NF1 include skin pigmentation and cutaneous neurofibroma. Some NF1 patients develop plexiform neurofibroma (PN) since early childhood. Pathologically, PN contains abundant Schwann cells, blood vessels and connective tissues, which may transform into a malignant peripheral nerve sheath tumor (MPNST). MPNST is a highly invasive sarcoma without any effective therapy. Recently, both in vitro and in vivo studies showed that cordycepin can inhibit the growth of MPNST cells. Cordycepin causes cell cycle arrest at G2/M phase and downregulates the protein levels of α-tubulin, p53 and Sp1. Herein, the present study revealed that the HDAC11 inhibitor, FT895, can synergistically enhance the tumoricidal effect of cordycepin against MPNST cells in vitro< /i>. Treatment with the combination of cordycepin and FT895 reduced the size of MPNST in the xenograft mouse model. The combined treatment decreased the protein levels of α-tubulin and KIF18A, which may disrupt the microtubule organization leading to the mis-segregation of chromosomes and aneuploidy. Moreover, the expression levels of TEAD1 and its co-activator TAZ, the candidate proteins in hippo signaling pathway, were suppressed after combined treatment. Sequence analysis found a few binding sites for the transcription factor, TEAD1 in the promoter regions of TUBA1B, KIF18A, TEAD1, TAZ, YAP, TP53 and SP1 genes. ChIP-qPCR assay showed that the combined treatment decreases the binding of TEAD1 to the promoters of TUBA1B, KIF18A, TEAD1, TAZ and YAP genes in STS26T cells. The reduced binding to TP53 and SP1 promoters was also found in S462TY cells, which was further confirmed by immunoblotting. The down-regulation of these important transcri ptional factors may contribute to the vulnerability of MPNST. In summary, HDAC11 inhibitor, FT895 can potentiate the tumoricidal effect of cordycepin to suppress the MPNST cell growth, which was probably mediated by the dysfunction of hippo-signaling pathway. PMID:35261809 | PMC:PMC8899988 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.

Decreased RNA m6A methylation enhances the process of the epithelial mesenchymal transition and vasculogenic mimicry in glioblastoma

xlomafota13 shared this article with you from Inoreader Decreased RNA m<sup>6</sup>A methylation enhances the process of the epithelial mesenchymal transition and vasculogenic mimicry in glioblastoma Via American Journal of Cancer Research Am J Cancer Res. 2022 Feb 15;12(2):893-906. eCollection 2022. ABSTRACT RNA N6-methyladenosine (m6A) modification is gradually thought to be an active participant in the considerable biological processes of glioblastoma (GB), providing us with a novel insight for exploring this disease. However, the role of RNA m6A modification during the epithelial mesenchymal transition (EMT) or vasculogenic mimicry (VM) progression has not been investigated in GB. Here we performed a research to validate the impact exerted by AlkB homolog 5 (ALKBH5), one of "erasers" for RNA m6A and methyltransferase-like 3 (METTL3) which adds m6A modification to the RNAs on the progression of EMT and VM in GB. In this study, we demonstrate that the m6A levels of RNAs were reduced in GB cells and glioma tissues. Patients with high mRNA expression of ALKBH5 acquired relatively shorter median overall sur vival (OS) time, while patients with relatively high expression of MEETL3 prolonged their disease free survival. ALKBH5 enhanced GB cell proliferation and influenced cell cycle in vitro. Decreased RNA m6A methylation enhanced the progression of the EMT and VM in glioblastoma cells. ALKBH5 strengthened glioblastoma growth and enhanced the EMT and VM process of glioblastoma in vivo. Our study uncovers that RNA m6A methylation suppresses the process of EMT and VM in glioblastoma, providing a new perspective to seek for a potential therapeutic target for GB. PMID:35261810 | PMC:PMC8899976 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Outcomes and recurrence patterns following curative hepatectomy for hepatocellular carcinoma patients with different China liver cancer staging

xlomafota13 shared this article with you from Inoreader Outcomes and recurrence patterns following curative hepatectomy for hepatocellular carcinoma patients with different China liver cancer staging Via American Journal of Cancer Research Am J Cancer Res. 2022 Feb 15;12(2):907-921. eCollection 2022. ABSTRACT This study aimed to investigate outcomes and recurrence patterns after hepatectomy for hepatocellular carcinoma (HCC) patients with different China Liver Cancer staging (CNLC), and then analyze the risk factors of different recurrence patterns. A total of 731 HCC patients undergoing curative resection were reviewed from 6 independent institutions. Data on preoperative and clinicopathological parameters, operation and tumor recurrence information, recurrence management and long-term outcomes were analyzed. Our results showed that 1-, 3-, and 5-year OS rate for Ia was 96.6%, 88.5%, and 77.4%, while 1-, 3-, and 5-year of Ib was 84.2%, 65.5%, and 51.3%, respectively. Compared to Ia, the patients in IIa and IIb staging had poorer 1-, 3-, and 5-year OS and DFS. Furthermore, the 1-, 3-, and 5-year OS rate in IIIa was 59.3%, 37.3%, and 27.7%, while the 1-, 3-, and 5-year OS of IIIb was 25.6%, 12.8%, and 0%, respectively. The mostly site of recurrence after liver surgery was intrahepatic recurrence (CNLC Ia: 89.4%; Ib: 65.9%; IIa: 68.9%; IIb: 91.7%; IIIa: 63.8%). However, the CNLC IIIb patients have higher percentage of extrahepatic recurrence (56.5%). The main recurrence pattern of time course was late recurrence in CNLC Ia patients (61.1%). However, the rate of early recurrence in Ib, IIa, IIb, IIIa, IIIb patients was 69.0%, 62.2%, 62.5%, 78.3% and 95.7% respectively. In conclusion, the outcomes and recurrence patterns of HCC patients after resection vary with different CNLC staging, which defined the prognosis of patients with HCC after resection. The HCC patients with CNLC IIIa can also benefit from liver resection. The CNLC staging could be considered in forming management strategies, treatment choice and surveillance for HCC patients. PMID:35261811 | PMC:PMC8899998 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.