Targeting the KDM4B-AR-c-Myc axis promotes sensitivity to androgen receptor-targeted therapy in advanced prostate cancer.

The histone demethylase KDM4B functions as a key co-activator for the androgen receptor (AR) and plays a vital in multiple cancers through controlling gene expression by epigenetic regulation of H3K9 methylation marks. Constitutively active androgen receptor confers anti-androgen resistance in advanced prostate cancer. However, the role of KDM4B in resistance to next-generation anti-androgens and the mechanisms of KDM4B regulation are poorly defined.

Targeting USP1-dependent KDM4A protein stability as a potential prostate cancer therapy.

The histone demethylase lysine-specific demethylase 4A (KDM4A) is reported to be overexpressed and plays a vital in multiple cancers through controlling gene expression by epigenetic regulation of H3K9 or H3K36 methylation marks. However, the biological role and mechanism of KDM4A in prostate cancer (PC) remain unclear. Herein, we reported KDM4A expression was upregulation in phosphatase and tensin homolog knockout mouse prostate tissue.

Hyperpolarized C magnetic resonance imaging, using metabolic imaging to improve the detection and management of prostate, bladder, and kidney urologic malignancies.

Approximately 25% of the 2 million new cancer diagnoses in the United States in 2018 were comprised of malignancies of the urogenital system. Of these cancers, 75% occurred in the kidney/renal pelvis, prostate, and urinary bladder. Early diagnosis is beneficial to long-term survival.

Linking cellular metabolism and metabolomics to risk-stratification of prostate cancer clinical aggressiveness and potential therapeutic pathways.

Prostate cancer treatment is based on the stratification of disease as low-, intermediate- or high-risk. This stratification has been largely based on anatomic pathology of the disease, as well as through the use of prostate specific antigen (PSA). However, despite this stratification, there remains heterogeneity within the current classification schema.

[High Throughput Screening Analysis of Preservatives and Sweeteners in Carbonated Beverages Based on Improved Standard Addition Method].

Simulated water samples of 3 kinds of preservatives and 4 kinds of sweeteners were formulated by using orthogonal design. Kernel independent component analysis (KICA) was used to process the UV spectra of the simulated water samples and the beverages added different amounts of the additive standards, then the independent components (ICs), i. e.

Metabolic targets for potential prostate cancer therapeutics.

Purpose Of Review: Prostate cancer (PCa) demonstrates characteristic changes in metabolism and bioenergetics in the transition from benign to malignant tissue. It is feasible that some of these changes may be targetable for therapeutic purposes. This review will highlight some of the current metabolically targeted therapies being investigated for the treatment of prostate cancer.

Metabolic perturbation sensitizes human breast cancer to NK cell-mediated cytotoxicity by increasing the expression of MHC class I chain-related A/B.

Cleavage or shedding of the surface antigen, MHC class I chain-related (MIC) protein (A/B) has been known to be one of the mechanisms by which tumor cells escape host immune surveillance. Thus, any strategy to augment the surface expression of MICA/B could facilitate anticancer immune response. Here, we demonstrate that metabolic perturbation by the glycolytic inhibitor, 3-bromopyruvate (3-BrPA) augments the surface expression of MICA/B in human breast cancer cell lines, MDA-MB-231 and T47D.

Reversal of anchorage-independent multicellular spheroid into a monolayer mimics a metastatic model.

Lack of an in vitro model of metastasis has been a major impediment in understanding the molecular regulation of metastatic processes, and identification of specific therapeutic targets. We have established an in vitro model which displayed the signatures of metastatic phenotype such as migration, invasiveness, chemoresistance and expression of cancer stem-cell markers. This in vitro model was developed by the induction of reversal of multicellular spheroids that were generated by anchorage-independent growth.

Digitoxin analogues with improved anticytomegalovirus activity.

Cardiac glycosides are potent inhibitors of cancer cell growth and possess antiviral activities at nanomolar concentrations. In this study we evaluated the anticytomegalovirus (CMV) activity of digitoxin and several of its analogues. We show that sugar type and sugar length attached to the steroid core structure affects its anticytomegalovirus activity.

Three-dimensional fluorescence characteristics of white chrysanthemum flowers.

White chrysanthemum flower is one of the most popular plants found everywhere in China and used as herbs. In the present work, three-dimensional fluorescence technique was used to discriminate species of white chrysanthemum flowers. Parameters affecting extraction efficiency were investigated.

Growth properties of SF188/V+ human glioma in rats in vivo observed by magnetic resonance imaging.

SF188/V+ is a highly vascular human glioma model that is based on transfection of vascular endothelial growth factor (VEGF) cDNA into SF188/V- cells. This study aims to assess its growth and vascularity properties in vivo in a rat model. Thirty-two adult rats were inoculated with SF188/V+ tumor cells, and, for comparison, five were inoculated with SF188/V- tumor cells.

Assessment of MRI parameters as imaging biomarkers for radiation necrosis in the rat brain.

Purpose: Radiation necrosis is a major complication of radiation therapy. We explore the features of radiation-induced brain necrosis in the rat, using multiple MRI approaches, including T(1), T(2), apparent diffusion constant (ADC), cerebral blood flow (CBF), magnetization transfer ratio (MTR), and amide proton transfer (APT) of endogenous mobile proteins and peptides.

Methods And Materials: Adult rats (Fischer 344; n = 15) were irradiated with a single, well-collimated X-ray beam (40 Gy; 10 × 10 mm(2)) in the left brain hemisphere.

A model of cellular dosimetry for macroscopic tumors in radiopharmaceutical therapy.

Purpose: In the radiopharmaceutical therapy approach to the fight against cancer, in particular when it comes to translating laboratory results to the clinical setting, modeling has served as an invaluable tool for guidance and for understanding the processes operating at the cellular level and how these relate to macroscopic observables. Tumor control probability (TCP) is the dosimetric end point quantity of choice which relates to experimental and clinical data: it requires knowledge of individual cellular absorbed doses since it depends on the assessment of the treatment's ability to kill each and every cell. Macroscopic tumors, seen in both clinical and experimental studies, contain too many cells to be modeled individually in Monte Carlo simulation; yet, in particular for low ratios of decays to cells, a cell-based model that does not smooth away statistical considerations associated with low activity is a necessity.

Differentiation between glioma and radiation necrosis using molecular magnetic resonance imaging of endogenous proteins and peptides.

It remains difficult to distinguish tumor recurrence from radiation necrosis after brain tumor therapy. Here we show that these lesions can be distinguished using the amide proton transfer (APT) magnetic resonance imaging (MRI) signals of endogenous cellular proteins and peptides as an imaging biomarker. When comparing two models of orthotopic glioma (SF188/V+ glioma and 9L gliosarcoma) with a model of radiation necrosis in rats, we could clearly differentiate viable glioma (hyperintense) from radiation necrosis (hypointense to isointense) by APT MRI.

Determination of endpoint of procedure for radix rehmanniae steamed based on ultraviolet spectrophotometry combination with continuous wavelet transform and kernel independent component analysis.

A method for determination of the endpoint of the procedure for radix rehmanniae steamed was proposed based on UV spectrophotometry combination with continuous wavelet transform and kernel independent component analysis (UV-CWT-KICA). In the proposed method, the raw UV spectra of the rehmanniae samples during steamed procedure were measured. The raw UV spectral data were firstly pretreated by CWT for elimination of the noise signal and enrichment of the spectral resolution, then the independent components (ICs) were estimated from the mixed CWT coefficient matrix.

[Determination and comparison of metal elements in Huai radix rehmanniae at different grades by ICP-MS].

The Huai radix rehmanniae at different grades was pretreated by wet digestion, and then the metal elements in the radix rehmanniae and the prepared sample by steaming method were determined using ICP-MS. The results indicate that there is no obvious difference in the metal elements between the different grades and between the dried radix rehmanniae and its corresponding prepared product. There are elements Zn, Cu, Cr, Fe, Mn, Sn, Ni, Mo, Go, etc.

[Theoretical study on infrared vibration spectrum of catalpol by DFT].

The catalpol, which can be isolated from the Chinese traditional herbs Rehmannia glutinosa as an effective and active ingredient, is an iridoid glycoside with many pharmacological functions. The molecular structure and the infrared (IR) spectrum of catalpol were calculated using density-functional theory (B3LYP) at 6-311G** level, and the theoretical frequency was scaled by 0. 96.

Characterization of radix rehmanniae processing procedure using FT-IR spectroscopy through nonnegative independent component analysis.

A method is proposed for monitoring the radix rehmanniae proparate processing procedure and determining the endpoint of the process using attenuated total reflectance (ATR) FT-IR through nonnegative independent component analysis (ICA). In the proposed method, ATR FT-IR spectra of the samples were firstly measured at different steaming periods. Then, nonnegative ICA was used for direct estimation of the feature spectra of the pure components in the mixture without pre-separation and other prior information.

Imaging virus-associated cancer.

Cancer remains an important and growing health problem. Researchers have made great progress in defining genetic and molecular alterations that contribute to cancer formation and progression. Molecular imaging can identify appropriate patients for targeted cancer therapy and may detect early biochemical changes in tumors during therapy, some of which may have important prognostic implications.

Bortezomib-induced enzyme-targeted radiation therapy in herpesvirus-associated tumors.

We investigated the possibility of using a pharmacologic agent to modulate viral gene expression to target radiotherapy to tumor tissue. In a mouse xenograft model, we had previously shown targeting of [(125)I]2'-fluoro-2'-deoxy-beta-D-5-iodouracil-arabinofuranoside ([(125)I]FIAU) to tumors engineered to express the Epstein-Barr virus thymidine kinase (EBV-TK). Here we extend those results to targeting of a therapeutic radiopharmaceutical [(131)I]FIAU to slow or stop tumor growth or to achieve tumor regression.

Estimation of source spectra profiles and simultaneous determination of polycomponent in mixtures from ultraviolet spectra data using kernel independent component analysis and support vector regression.

A method that use kernel independent component analysis (KICA) and support vector regression (SVR) was proposed for estimation of source ultraviolet (UV) spectra profiles and simultaneous determination of polycomponents in mixtures. In KICA-SVR procedure, the UV source spectra profiles were estimated using KICA, then the mixing matrix of the components were calculated using the estimated sources, and the calibration model was build using SVR based on the calculated mixing matrix. A simulated UV dataset of three-component mixtures was used to test the ability of KICA for estimating source spectra profiles from spectra data of mixtures.

Virus-associated tumor imaging by induction of viral gene expression.

Purpose: EBV and other herpesviruses are associated with a variety of malignancies. The EBV thymidine kinase (TK) is either not expressed or is expressed at very low levels in EBV-associated tumors. However, EBV-TK expression can be induced in vitro with several chemotherapeutic agents that promote viral lytic induction.

A p105-based inhibitor broadly represses NF-kappa B activities.

An IkappaBalpha-based NF-kappaB super repressor (sr) has been used widely for studying genes regulated by NF-kappaB transcription factors. Repression of NF-kappaB by IkappaBalpha(sr) also facilitates tumor necrosis factor alpha-induced apoptosis in the cell. However, IkappaBalpha primarily targets RelA and c-Rel-containing complexes, leaving other NF-kappaB/Rel protein complexes, such as p50 and p52 homodimers, and RelB heterodimers uninhibited.

Human T-lymphotropic virus type I tax activates I-kappa B kinase by inhibiting I-kappa B kinase-associated serine/threonine protein phosphatase 2A.

I-kappa B kinase (IKK) is a serine/threonine kinase that phosphorylates I-kappa B alpha and I-kappa B beta and targets them for polyubiquitination and proteasome-mediated degradation. IKK consists of two highly related catalytic subunits, alpha and beta, and a regulatory gamma subunit, which becomes activated after serine phosphorylation of the activation loops of the catalytic domains. The human T-lymphotropic retrovirus type-I trans-activator, Tax, has been shown to interact directly with IKK gamma and activates IKK via a mechanism not fully understood.