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.

Diagnostic and therapeutic biomarkers in colorectal cancer: a review

xlomafota13 shared this article with you from Inoreader Diagnostic and therapeutic biomarkers in colorectal cancer: a review Via American Journal of Cancer Research Am J Cancer Res. 2022 Feb 15;12(2):661-680. eCollection 2022. ABSTRACT Colorectal cancer (CRC) is a public health concern and the second most common type of cancer among men and women causing a significant mortality. Biomarkers closely linked to the disease morbidity could holds potential as diagnostic and/or prognostic biomarker for the disease. This review provides an overview of recent advances in the search for colorectal cancer biomarkers through genomics and proteomics according to clinical function and application. Specifically, a number of biomarkers were identified and discussed. Emphasis was placed on their clinical applications relative to the diagnosis and prognosis of CRC. The discovery of more sensitive and specific markers for CRC is an urgent need, and the study of molecular targets is extremely important in this process, as they will allow for a better understanding of colorectal carcinogenesis, identification and vali dation of potential genetic signatures. PMID:35261794 | PMC:PMC8900002 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.