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(searched for: doi:10.4103/jcrt.JCRT_1053_16)
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Haoqi Wang, Yuntao Li, Yixin Qi, Erbao Zhao, Xiangshun Kong, Chao Yang, QiQi Yang, Chengyuan Zhang, Yueping Liu, Zhenchuan Song
Published: 8 July 2022
Frontiers in Oncology, Volume 12; https://doi.org/10.3389/fonc.2022.909426

Abstract:
Background: Combined neoadjuvant chemotherapy with trastuzumab and pertuzumab is the standard regimen for human epidermal growth receptor 2 (HER2)-positive breast cancer (BC). However, pertuzumab is not available because it is not on the market or covered by medicare in some regions or poor economy. Anthracyclines and taxanes are cornerstones in BC chemotherapy, and their combination contributes to satisfactory efficiency in neoadjuvant settings. Nonetheless, concomitant administration of trastuzumab and an anthracycline is generally avoided clinically due to cardiotoxicity. Pegylated liposomal doxorubicin (PLD) is less cardiotoxic compared with traditional anthracyclines. Here, we conducted this prospective study to evaluate the efficacy, safety, and potential biomarkers for PLD plus trastuzumab and docetaxel as neoadjuvant treatment in HER2-positive BC.Patients and Methods: Patients with stage II or III HER2-positive BC were recruited in this multicenter, open-label, single-arm, phase II study. Eligible patients were given 6 cycles of PLD plus docetaxel and trastuzumab. Primary endpoint was total pathological complete response (tpCR, ypT0/is ypN0). Secondary endpoints were breast pathological complete response (bpCR, ypT0/is), objective response rate (ORR), operation rate, breast-conserving surgery rate, and safety. Metadherin (MTDH), glutaminyl-peptide cyclotransferase (QPCT), topoisomerase II alpha (TOP2A), programmed death ligand 1 (PD-L1), and tumor-infiltrating lymphocytes (TILs) were evaluated in BC tissues pre-neoadjuvant for potential biomarkers.Results: Between March 2019 and February 2021, 54 patients were enrolled, 50 were included in the analysis, and 35 (70.0%) completed 6 cycles of neoadjuvant treatment. Forty-nine (98.0%) patients underwent surgery with a breast-conserving rate of 44.0%. The tpCR rate, bpCR rate, and ORR were 48.0% (95% CI, 33.7%–62.6%), 60.0% (95% CI, 45.2%–73.6%), and 84.0% (95% CI, 70.9%–92.8%), respectively. tpCR was associated with MTDH (p = 0.002) and QPCT (p = 0.036) expression but not with TOP2A (p = 0.75), PD-L1 (p = 0.155), or TILs (p = 0.76). Patients with HR-negative status were more likely to achieve bpCR compared with those with HR-positive status (76.2% vs. 48.3%, p = 0.047). Grade ≥3 adverse events occurred in 38.0% of patients. Left ventricular ejection fraction decline by ≥10% was reported in 18.0% of patients, and no patient experienced congestive heart failure.Conclusions: PLD plus docetaxel and trastuzumab might be a potential neoadjuvant regimen for HER2-positive BC with a high tpCR rate and manageable tolerability. MTDH and QPCT are potential predictive markers for tpCR.
, Ha X. Dang, Nicole M. White, Matthew S. Strand, Bradley A. Krasnick, Emily B. Rozycki, Gejae G. L. Jeffers, Julie G. Grossman, Maureen K. Highkin, , et al.
Published: 1 May 2020
Nature Communications, Volume 11, pp 1-13; https://doi.org/10.1038/s41467-020-15547-8

Abstract:
Colorectal cancer (CRC) is the most common gastrointestinal malignancy in the U.S.A. and approximately 50% of patients develop metastatic disease (mCRC). Despite our understanding of long non-coding RNAs (lncRNAs) in primary colon cancer, their role in mCRC and treatment resistance remains poorly characterized. Therefore, through transcriptome sequencing of normal, primary, and distant mCRC tissues we find 148 differentially expressed RNAs Associated with Metastasis (RAMS). We prioritize RAMS11 due to its association with poor disease-free survival and promotion of aggressive phenotypes in vitro and in vivo. A FDA-approved drug high-throughput viability assay shows that elevated RAMS11 expression increases resistance to topoisomerase inhibitors. Subsequent experiments demonstrate RAMS11-dependent recruitment of Chromobox protein 4 (CBX4) transcriptionally activates Topoisomerase II alpha (TOP2α). Overall, recent clinical trials using topoisomerase inhibitors coupled with our findings of RAMS11-dependent regulation of TOP2α supports the potential use of RAMS11 as a biomarker and therapeutic target for mCRC.
Ying-Jie Hao, Hui-Bo Sun, Hong-Wei Li, Bing-Jie Chen, Xiu-Li Chen, Lin Ma,
Published: 26 February 2020
World Journal of Clinical Cases, Volume 8, pp 689-699; https://doi.org/10.12998/wjcc.v8.i4.689

Abstract:
As a radical treatment, breast cancer surgery has a positive psychological impact on most patients. However, some patients do not have a clear understanding of the disease, which requires a more scientific and comprehensive consideration during clinical intervention and are based on cognition. The positive behavior management model is based on this kind of background-derived new interventions, which can better serve the clinical rehabilitation process of patients. The positive behavior management model based on cognitive architecture is a new type of intervention derived from this background, which can better serve the clinical rehabilitation process of patients. To analyze the influence of a positive behavior management model based on cognitive framework on the degree of hope and self-efficacy of patients with breast cancer surgery. Eighty-four patients with breast cancer who underwent surgical treatment in our hospital from August 2016 to December 2018 were included in the study. The patients were divided into the experimental group (n = 42) and control group (n = 42) by random number table grouping. The control group received traditional nursing intervention, while the experimental group received a positive behavior management model based on cognitive framework based on the traditional intervention of the control group. General Self-efficacy Scale, Herth Hope Scale, Self-Rating Anxiety Scale, Self-Rating Depression Scale and Cancer Patient Specific Scale were used to evaluate the two groups before and 1 wk after intervention. After the intervention, self-efficacy and hope level of the experimental group were significantly higher than those of the control group (P < 0.05). The Self-Rating Anxiety Scale and Self-Rating Depression Scale scores in the experimental group were significantly lower than those in the control group (P < 0.05). There was no significant difference in the quality of life scores between the two groups before intervention (P > 0.05). The quality of life scores in all aspects in the experimental group after intervention were significantly higher than those in the control group (P < 0.05). The positive behavior management model based on cognitive framework applied to patients with breast cancer surgery improved hope for treatment and self-efficacy, reduced negative emotion, and improved quality of life.
Alexandra Bomane, Anthony Gonçalves,
Published: 25 October 2019
Frontiers in Genetics, Volume 10; https://doi.org/10.3389/fgene.2019.01041

Abstract:
To address the problem of resistance to paclitaxel treatment, we have investigated to which extent is possible to predict Breast Cancer (BC) patient response to this drug. We carried out a large-scale tumor-based prediction analysis using data from the US National Cancer Institute’s Genomic Data Commons. These data sets comprise the responses of BC patients to paclitaxel along with six molecular profiles of their tumors. We assessed 10 Machine Learning (ML) algorithms on each of these profiles and evaluated the resulting 60 classifiers on the same BC patients. DNA methylation and miRNA profiles were the most informative overall. In combination with these two profiles, ML algorithms selecting the smallest subset of molecular features generated the most predictive classifiers: a complexity-optimized XGBoost classifier based on CpG island methylation extracted a subset of molecular factors relevant to predict paclitaxel response (AUC = 0.74). A CpG site methylation-based Decision Tree (DT) combining only 2 of the 22,941 considered CpG sites (AUC = 0.89) and a miRNA expression-based DT employing just 4 of the 337 analyzed mature miRNAs (AUC = 0.72) reveal the molecular types associated to paclitaxel-sensitive and resistant BC tumors. A literature review shows that features selected by these three classifiers have been individually linked to the cytotoxic-drug sensitivities and prognosis of BC patients. Our work leads to several molecular signatures, unearthed from methylome and miRNome, able to anticipate to some extent which BC tumors respond or not to paclitaxel. These results may provide insights to optimize paclitaxel-therapies in clinical practice.
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