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Pharmaceuticals: Some General Aspects
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
The understanding of cancer pathogenesis has significantly improved in the recent past which has led to new therapeutic concepts such as targeted agents designed to inhibit molecular pathways that are crucial for tumor growth, or immunotherapeutic approaches (Vanneman and Dranoff, 2012; Gotwals et al., 2017; Banchereau and Palucka, 2018) including immune checkpoint inhibitors (Dine et al., 2017). Another recent example is Yescarta, a chimeric antigen receptor (CAR) T cell therapy, approved as the second gene therapy by the FDA for treating diffuse large B-cell lymphoma (DLBCL, the most common type of non-Hodgkin lymphoma; FDA, 2018c); Yescarta has received the orphan drug status (see next section). This has led to an improved survival of patients suffering from certain types of cancer and finds expression, too, in a trend towards an increased share of oncologic drugs as part of the number of drugs approved per year as shown in the following figure (see also Centerwatch, 2018).
Opportunities and challenges in radiomics and radiogenomics
Published in Ruijiang Li, Lei Xing, Sandy Napel, Daniel L. Rubin, Radiomics and Radiogenomics, 2019
Ruijiang Li, Yan Wu, Michael Gensheimer, Masoud Badiei Khuzani, Lei Xing
Beyond radiogenomics association studies, one important emerging direction is to leverage the complementary power of imaging and molecular data and integrate them into a unifying model to further improve prediction accuracy of clinical outcomes. This is particularly relevant for improving the value of imaging for precision medicine. Cottereau et al.51 showed that combination of molecular profile and metabolic tumor volume at FDG-PET imaging improved patient stratification for progression-free and overall survival in diffuse large B-cell lymphoma. Grossmann et al.38 combined gene expression and CT radiomic signatures to enhance the accuracy of survival prediction in lung cancer. Cui et al.52 showed that integrating O-6-Methylguanine-DNA Methyltransferase (MGMT) methylation status and volume of the high-risk subregion at multiparametric MRI improved survival stratification in glioblastoma. Recently, Lee et al. developed a CT image-based prognostic signature and validated it in an external cohort of patients with stage I NSCLC.53 Further, it was shown that a composite imaging and genomic signature improved prognostic accuracy upon either one used alone. While still preliminary, these studies provide the initial evidence that image-based biomarkers can provide additional information beyond molecular analysis alone and integrating both will provide more accurate assessment of prognosis and outcomes for individual patients.
Immuno-cancer therapy
Published in Rachel Kim, Economics and Management in the Biopharmaceutical Industry in the USA, 2018
Kite Pharma was the first company to seek approval to treat some cancers with CAR-T therapy in Europe (Taylor, August 1, 2017). Kite focused on obtaining approval to use axicabtagene ciloleucel (KTE-C19) (later Yescarta®) to treat two types of non-Hodgkin’s lymphoma. Right now, it appears Kite Pharma and its acquirer, Gilead Sciences, is ahead of Novartis in CAR-T cell therapeutics in the European Union. However, in the United States, Novartis is a bit ahead regarding CAR-T cell therapeutics. Novartis already applied for FDA approval on tisagenlecleucel-T for relapsed and refractory B-cell acute lymphoblastic leukemia in August 2017 and refractory diffuse large B-cell lymphoma by the end of 2017. Both Yescarta® and Kymriah® aim to treat patients with hard-to-treat cancers. The market value of these personalized cancer treatments is estimated to be several billion dollars per year (Taylor, 2017).
Serum microRNA profiles among dioxin exposed veterans with monoclonal gammopathy of undetermined significance
Published in Journal of Toxicology and Environmental Health, Part A, 2020
Weixin Wang, Youn K. Shim, Joel E. Michalek, Emily Barber, Layla M. Saleh, Byeong Yeob Choi, Chen-Pin Wang, Norma Ketchum, Rene Costello, Gerald E. Marti, Robert F. Vogt, Ola Landgren, Katherine R. Calvo
In this case-series study of 47 male veterans with MGUS who served in Vietnam or other Southeast Asian countries during the Vietnam War, serum levels of 13 miRNAs associated with a number of cancers including MM or nonmalignant conditions such as MGUS were measured (Bouyssou et al. 2018; Calvo et al. 2011; Kubiczkova et al. 2014; Pichiorri, Suh, and Ladetto 2008; Sun et al. 2013; Wang et al. 2015). In univariate analysis, the strongest associations with increasing age were reduction in the tumor suppressor let-7a and elevation in miR-181a. Decreased let-7a levels were reported in plasma samples from early-stage colorectal carcinoma (Ghanbari et al. 2016). Let-7a was noted to target oncogenes and genes related to tumor migration such as MYC and HMGA2 (Liu et al. 2012; Wu et al. 2015). Liu et al. (2019) found that miR-181a was upregulated in multiple myeloma cell lines. Further, Neu et al. (2017) demonstrated that miR-181 was inhibited cutaneous squamous cell carcinoma proliferation by targeting KRAS and Kozloski et al. (2016) reported that miR-181 blocked proliferation and survival of diffuse large B-cell lymphoma by targeting NF-κB.
Analysis of Proposed and Traditional Boosting Algorithm with Standalone Classification Methods for Classifying Gene Expresssion Microarray Data Using a Reject Option
Published in Applied Artificial Intelligence, 2022
Adil Aslam Mir, Lal Hussain, Muhammad Hammad Waseem, Amjad Aldweesh, Saim Rasheed, El Sayed Yousef, Malik Sajjad Ahmed Nadeem, Elsayed Tag Eldin
In this analysis, the gene expression microarray data of lymphoid cancer (Shipp et al. 2002) is used. This dataset contains data about the patients of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) patients. The dataset contains information for 58 DLBCL patients and 19 FL patients. For analysis, we split our dataset into train and test sets in such a way that the test set is independent of the train set as mentioned above.
Trichoderma after crossing kingdoms: infections in human populations
Published in Journal of Toxicology and Environmental Health, Part B, 2023
Uener Ribeiro dos Santos, Jane Lima dos Santos
AMB MIC values in vitro, ranging from 0.09–4 µg/ml, whereas only 6 isolates exhibited higher MICs ranging from 5–32 µg/ml. As exceptions, treatment of two of these patients with intravenous and peritoneal AMB exerted no marked effect, for T. longibrachiatum (Myoken et al. 2002) and T. viride (De Miguel et al. 2005) in patients with diffuse large B cell lymphoma and acute myeloid leukemia, respectively.