Exceptional Response to Trastuzumab Deruxtecan in a Patient With Recurrent Ovarian Clear Cell Carcinoma With Human Epidermal Growth Factor Receptor 2 Expression.

Case report of a HER2-expressed ovarian clear cell carcinoma with exceptional response to trastuzumab deruxtecan.

QTL and PACE analyses identify candidate genes for anthracnose resistance in tomato.

Anthracnose, caused by the fungal pathogen spp., is one of the most significant tomato diseases in the United States and worldwide. No commercial cultivars with anthracnose resistance are available, limiting resistant breeding.

Steroidal glycoalkaloids contribute to anthracnose resistance in Solanum lycopersicum.

Anthracnose is a widespread plant disease caused by various species of the fungal pathogen Colletotrichum. In solanaceous plants such as tomato (Solanum lycopersicum), Colletotrichum infections exhibit a quiescent, asymptomatic state in developing fruit, followed by a transition to necrotrophic infections in ripe fruit. Through analysis of fruit tissue extracts of 95L368, a tomato breeding line that yields fruit with enhanced anthracnose resistance, we identified a role for steroidal glycoalkaloids (SGAs) in anthracnose resistance.

An omic and multidimensional spatial atlas from serial biopsies of an evolving metastatic breast cancer.

Mechanisms of therapeutic resistance and vulnerability evolve in metastatic cancers as tumor cells and extrinsic microenvironmental influences change during treatment. To support the development of methods for identifying these mechanisms in individual people, here we present an omic and multidimensional spatial (OMS) atlas generated from four serial biopsies of an individual with metastatic breast cancer during 3.5 years of therapy.

Exploration into natural variation for genes associated with fruit shape and size among Capsicum chinense collections.

Phenotype diversity within cultivated Capsicum chinense is particularly evident for fruit shape and size. We used this diversity in C. chinense to further unravel the genetic mechanisms underlying fruit shape variation in pepper and related Solanaceous species.

Identification of miRNAs and Their Targets Involved in Flower and Fruit Development across Domesticated and Wild Species.

MicroRNAs (miRNAs) are regulators of the post-transcription stage of gene activity documented to play central roles in flower and fruit development in model plant species. However, little is known about their roles and differences in domesticated and wild species. In this study, we used high-throughput sequencing to analyze the miRNA content at three developmental stages (flower, small fruit, and middle fruit) from two cultivated ( and ) and two wild ( and ) pepper species.

The ankyrin repeat gene family in Capsicum spp: Genome-wide survey, characterization and gene expression profile.

The ankyrin (ANK) repeat protein family is largely distributed across plants and has been found to participate in multiple processes such as plant growth and development, hormone response, response to biotic and abiotic stresses. It is considered as one of the major markers of capsaicin content in pepper fruits. In this study, we performed a genome-wide identification and expression analysis of genes encoding ANK proteins in three Capsicum species: Capsicum baccatum, Capsicum annuum and Capsicum chinense.

Integrated Metabolomic and Transcriptomic Analysis to Characterize Cutin Biosynthesis between Low- and High-Cutin Genotypes of Jacq.

Habanero peppers constantly face biotic and abiotic stresses such as pathogen/pest infections, extreme temperature, drought and UV radiation. In addition, the fruit cutin lipid composition plays an important role in post-harvest water loss rates, which in turn causes shriveling and reduced fruit quality and storage. In this study, we integrated metabolome and transcriptome profiling pertaining to cutin in two habanero genotypes: PI 224448 and PI 257145.

LXRβ controls glioblastoma cell growth, lipid balance, and immune modulation independently of ABCA1.

Cholesterol is a critical component of membranes and a precursor for hormones and other signaling molecules. Previously, we showed that unlike astrocytes, glioblastoma cells do not downregulate cholesterol synthesis when plated at high density. In this report, we show that high cell density induces ABCA1 expression in glioblastoma cells, enabling them to get rid of excess cholesterol generated by an activated cholesterol biosynthesis pathway.

Cholesterol Metabolism: A Potential Therapeutic Target in Glioblastoma.

Glioblastoma is a highly lethal adult brain tumor with no effective treatments. In this review, we discuss the potential to target cholesterol metabolism as a new strategy for treating glioblastomas. Twenty percent of cholesterol in the body is in the brain, yet the brain is unique among organs in that it has no access to dietary cholesterol and must synthesize it de novo.

CRISPR/Cas9-mediated gene knockout is insensitive to target copy number but is dependent on guide RNA potency and Cas9/sgRNA threshold expression level.

CRISPR/Cas9 is a powerful gene editing tool for gene knockout studies and functional genomic screens. Successful implementation of CRISPR often requires Cas9 to elicit efficient target knockout in a population of cells. In this study, we investigated the role of several key factors, including variation in target copy number, inherent potency of sgRNA guides, and expression level of Cas9 and sgRNA, in determining CRISPR knockout efficiency.

Global Inhibition with Specific Activation: How p53 and MYC Redistribute the Transcriptome in the DNA Double-Strand Break Response.

In response to stresses, cells often halt normal cellular processes, yet stress-specific pathways must bypass such inhibition to generate effective responses. We investigated how cells redistribute global transcriptional activity in response to DNA damage. We show that an oscillatory increase of p53 levels in response to double-strand breaks drives a counter-oscillatory decrease of MYC levels.

Exploiting Radiation-Induced Signaling to Increase the Susceptibility of Resistant Cancer Cells to Targeted Drugs: AKT and mTOR Inhibitors as an Example.

Implementing targeted drug therapy in radio-oncologic treatment regimens has greatly improved the outcome of cancer patients. However, the efficacy of molecular targeted drugs such as inhibitory antibodies or small molecule inhibitors essentially depends on target expression and activity, which both can change during the course of treatment. Radiotherapy has previously been shown to activate prosurvival pathways, which can help tumor cells to adapt and thereby survive treatment.

Disabled cell density sensing leads to dysregulated cholesterol synthesis in glioblastoma.

A hallmark of cellular transformation is the evasion of contact-dependent inhibition of growth. To find new therapeutic targets for glioblastoma, we looked for pathways that are inhibited by high cell density in astrocytes but not in glioma cells. Here we report that glioma cells have disabled the normal controls on cholesterol synthesis.

Genome-wide Diversity and Association Mapping for Capsaicinoids and Fruit Weight in Capsicum annuum L.

Accumulated capsaicinoid content and increased fruit size are traits resulting from Capsicum annuum domestication. In this study, we used a diverse collection of C. annuum to generate 66,960 SNPs using genotyping by sequencing.

Genome-Wide Divergence and Linkage Disequilibrium Analyses for Revealed by Genome-Anchored Single Nucleotide Polymorphisms.

Principal component analysis (PCA) with 36,621 polymorphic genome-anchored single nucleotide polymorphisms (SNPs) identified collectively for and was used to characterize population structure and species domestication of these two important incompatible cultivated pepper species. Estimated mean nucleotide diversity (π) and Tajima's D across various chromosomes revealed biased distribution toward negative values on all chromosomes (except for chromosome 4) in cultivated , indicating a population bottleneck during domestication of . In contrast, chromosomes showed positive π and Tajima's D on all chromosomes except chromosome 8, which may be because of domestication at multiple sites contributing to wider genetic diversity.

Genetic diversity in Capsicum baccatum is significantly influenced by its ecogeographical distribution.

Background: The exotic pepper species Capsicum baccatum, also known as the aji or Peruvian hot pepper, is comprised of wild and domesticated botanical forms. The species is a valuable source of new genes useful for improving fruit quality and disease resistance in C. annuum sweet bell and hot chile pepper.

Pancreatic cancers require autophagy for tumor growth.

Macroautophagy (autophagy) is a regulated catabolic pathway to degrade cellular organelles and macromolecules. The role of autophagy in cancer is complex and may differ depending on tumor type or context. Here we show that pancreatic cancers have a distinct dependence on autophagy.

Phosphorylation by casein kinase I promotes the turnover of the Mdm2 oncoprotein via the SCF(beta-TRCP) ubiquitin ligase.

Mdm2 is the major negative regulator of the p53 pathway. Here, we report that Mdm2 is rapidly degraded after DNA damage and that phosphorylation of Mdm2 by casein kinase I (CKI) at multiple sites triggers its interaction with, and subsequent ubiquitination and destruction, by SCF(beta-TRCP). Inactivation of either beta-TRCP or CKI results in accumulation of Mdm2 and decreased p53 activity, and resistance to apoptosis induced by DNA damaging agents.

Targeting EGFR induced oxidative stress by PARP1 inhibition in glioblastoma therapy.

Despite the critical role of Epidermal Growth Factor Receptor (EGFR) in glioblastoma pathogenesis, EGFR targeted therapies have achieved limited clinical efficacy. Here we propose an alternate therapeutic strategy based on the conceptual framework of non-oncogene addiction. A directed RNAi screen revealed that glioblastoma cells over-expressing EGFRvIII, an oncogenic variant of EGFR, become hyper-dependent on a variety of DNA repair genes.

Mig-6 controls EGFR trafficking and suppresses gliomagenesis.

Glioblastoma multiforme (GBM) is the most common and lethal primary brain cancer that is driven by aberrant signaling of growth factor receptors, particularly the epidermal growth factor receptor (EGFR). EGFR signaling is tightly regulated by receptor endocytosis and lysosome-mediated degradation, although the molecular mechanisms governing such regulation, particularly in the context of cancer, remain poorly delineated. Here, high-resolution genomic profiles of GBM identified a highly recurrent focal 1p36 deletion encompassing the putative tumor suppressor gene, Mig-6.

First Report of Leveillula taurica Causing Powdery Mildew on Pepper in Maryland.

Pepper plants in large experimental plots in Beltsville, MD developed widespread powdery mildew during the late summer of 2008. Infection was observed in a diversity of accessions that included Capsicum annuum, C. baccatum, C.

Pten and p53 converge on c-Myc to control differentiation, self-renewal, and transformation of normal and neoplastic stem cells in glioblastoma.

Glioblastoma (GBM) is a highly lethal primary brain cancer with hallmark features of diffuse invasion, intense apoptosis resistance and florid necrosis, robust angiogenesis, and an immature profile with developmental plasticity. In the course of assessing the developmental consequences of central nervous system (CNS)-specific deletion of p53 and Pten, we observed a penetrant acute-onset malignant glioma phenotype with striking clinical, pathological, and molecular resemblance to primary GBM in humans. This primary, as opposed to secondary, GBM presentation in the mouse prompted genetic analysis of human primary GBM samples that revealed combined p53 and Pten mutations as the most common tumor suppressor defects in primary GBM.