Pleiotropic anti-cancer activities of novel non-covalent thioredoxin reductase inhibitors against triple negative breast cancer.

Mounting evidence shows that tumor growth and progression rely on thioredoxin reductase 1 (TXNRD1)-mediated detoxification of oxidative stress that results from deregulated metabolism and mitogenic signaling in tumors. TXNRD1 levels are significant higher in triple negative breast cancer (TNBC) compared to normal tissue, making TXNRD1 a compelling TNBC therapeutic target. Despite the many attempts to generate TXNRD1 inhibitors, all known and reported compounds inhibiting TXNRD1 are problematic; they interact with TXNRD1 irreversibly and non-specifically resulting in numerous adverse side effects.

A Randomized Controlled Trial Comparing STREAMLINE Canaloplasty to Trabecular Micro-Bypass Stent Implantation in Primary Open-Angle Glaucoma.

Purpose: To report interim results of the VENICE study, a multi-center, randomized, controlled trial (RCT) comparing STREAMLINE Surgical System (STREAMLINE) canaloplasty with iStent inject W (iStent W) implantation in patients with mild-to-moderate primary open-angle glaucoma (POAG) undergoing phacoemulsification.

Patients And Methods: Safety and efficacy analyses involving the first 72 randomized eyes are included in this report. Following pre- (Screening) and post-medication washout (Eligibility) visits, one eye per subject was randomized 1:1 to STREAMLINE or iStent W after undergoing uncomplicated phacoemulsification.

Estimation of genotype by environmental interaction for litter traits by reaction norm model in Taiwan Landrace sows.

The negative effects of heat stress on swine reproduction have been well documented and the recent global warming trend caused by climate change is leading to more days with high temperatures every year. This has caused a reduction in litter trait performance of Landrace sows in Taiwan, a country extending across tropical and subtropical oceanic zones. Therefore, this study developed a modified model to determine which stages of pregnancy, before, early, middle, and late, had the largest impacts of heat stress on litter traits.

Targeting Unique Ligand Binding Domain Structural Features Downregulates DKK1 in Y537S Mutant Breast Cancer Cells.

Resistance to endocrine therapies remains a major clinical hurdle in breast cancer. Mutations to estrogen receptor alpha (ERα) arise after continued therapeutic pressure. Next generation selective estrogen receptor modulators and degraders/downregulators (SERMs and SERDs) show clinical efficacy, but responses are often non-durable.

Targeting Unique Ligand Binding Domain Structural Features Downregulates DKK1 in Y537S Mutant Breast Cancer Cells.

Resistance to endocrine therapies remains a major clinical hurdle in breast cancer. Mutations to estrogen receptor alpha (ERα) arise after continued therapeutic pressure. Next generation selective estrogen receptor modulators and degraders/downregulators (SERMs and SERDs) show clinical efficacy, but responses are often non-durable.

Epigenetic priming targets tumor heterogeneity to shift transcriptomic phenotype of pancreatic ductal adenocarcinoma towards a Vitamin D susceptible state.

As a highly heterogeneous tumor, pancreatic ductal adenocarcinoma (PDAC) exhibits non-uniform responses to therapies across subtypes. Overcoming therapeutic resistance stemming from this heterogeneity remains a significant challenge. Here, we report that Vitamin D-resistant PDAC cells hijacked Vitamin D signaling to promote tumor progression, whereas epigenetic priming with glyceryl triacetate (GTA) and 5-Aza-2'-deoxycytidine (5-Aza) overcame Vitamin D resistance and shifted the transcriptomic phenotype of PDAC toward a Vitamin D-susceptible state.

Two-Year Performance and Safety Results of the MINIject Supraciliary Implant in Patients With Primary Open-Angle Glaucoma: Meta-Analysis of the STAR-I, II, III Trials.

Purpose: To evaluate the performance and safety of minimally invasive glaucoma surgery with a supraciliary drainage device (MINIject; iSTAR Medical, Wavre, Belgium) in primary open-angle glaucoma (POAG) as a stand-alone procedure.

Design: Meta-analysis.

Methods: At 11 sites in Colombia, France, Germany, India, Panama, and Spain, 82 patients were treated in 3 prospective, multicenter, interventional, nonrandomized trials (STAR-I, II, III).

36-Month Outcomes from the Prospective GEMINI Study: Canaloplasty and Trabeculotomy Combined with Cataract Surgery for Patients with Primary Open-Angle Glaucoma.

Purpose: To provide long-term intraocular pressure (IOP) and ocular hypotensive medication usage outcomes through 36 months for patients treated with canaloplasty and trabeculotomy (OMNI Surgical System) combined with cataract surgery as participants in the GEMINI study.

Setting: Eleven ophthalmology practices in 10 US states.

Design: Non-interventional 36-month extension of the 12-month, prospective, multicenter, GEMINI study.

Ab-Externo MicroShunt versus Trabeculectomy in Primary Open-Angle Glaucoma: Two-Year Results from a Randomized, Multicenter Study.

Purpose: To compare the effectiveness and safety of the MicroShunt (Santen Inc) versus trabeculectomy in patients with primary open-angle glaucoma (POAG).

Design: Prospective, randomized, multicenter trial conducted in the United States and Europe.

Participants: Adult patients (aged 40-85 years) with mild to severe POAG inadequately controlled on maximum tolerated medical therapy and intraocular pressure (IOP) ≥ 15 mmHg and ≤ 40 mmHg.

SELENOF Controls Proliferation and Cell Death in Breast-Derived Immortalized and Cancer Cells.

SELENOF expression is significantly lower in aggressive breast tumors compared to normal tissue, indicating that its reduction or loss may drive breast tumorigenesis. Deletion of SELENOF in non-tumorigenic immortalized breast epithelial MCF-10A cells resulted in enhanced proliferation, both in adherent culture and matrix-assisted three-dimmensional (3D) growth. Modulation of SELENOF in vitro through deletion or overexpression corresponded to changes in the cell-cycle regulators p21 and p27, which is consistent with breast tumor expression data from the METABRIC patient database.

Distinct Roles of SELENOF in Different Human Cancers.

SELENOF, previously known as SEP15, is a selenoprotein that contains selenium in the form of the amino acid selenocysteine. Like other selenoproteins, the role for SELENOF in carcinogenesis has been investigated due to its altered expression compared to the corresponding normal tissue, its molecular function, and the association of genetic variations in the gene to cancer risk or outcome. This review summarizes SELENOF's discovery, structure, cellular localization, and expression.

Multifaceted role for p53 in pancreatic cancer suppression.

The vast majority of human pancreatic ductal adenocarcinomas (PDACs) harbor mutations, underscoring p53's critical role in PDAC suppression. PDAC can arise when pancreatic acinar cells undergo acinar-to-ductal metaplasia (ADM), giving rise to premalignant pancreatic intraepithelial neoplasias (PanINs), which finally progress to PDAC. The occurrence of mutations in late-stage PanINs has led to the idea that p53 acts to suppress malignant transformation of PanINs to PDAC.

Selenium and breast cancer - An update of clinical and epidemiological data.

There is an urgent need for new and improved therapeutic strategies in breast cancer, which is the most common malignancy affecting women in the United States and worldwide. Selenium (Se) is an essential trace element of the human diet and plays a critical role in many aspects of human health. Clinical and epidemiological studies summarized here clearly demonstrate that Se status correlates with breast cancer survival.

Canaloplasty and Trabeculotomy Combined with Phacoemulsification for Glaucoma: 12-Month Results of the GEMINI Study.

Purpose: To report 12-month efficacy outcomes of 360° canaloplasty and 180° trabeculotomy using the OMNI surgical system in combination with phacoemulsification in patients with mild-moderate open-angle glaucoma (OAG) and visually significant cataract.

Setting: Fifteen multi-subspecialty ophthalmology practices and surgery centers located in 14 US states.

Design: Prospective, multicenter, IRB approved study of patients treated with canaloplasty (360°) and trabeculotomy (180°).

Long-term Outcomes from the HORIZON Randomized Trial for a Schlemm's Canal Microstent in Combination Cataract and Glaucoma Surgery.

Purpose: To present the 5-year results of the HORIZON trial comparing cataract surgery (CS) combined with an intracanalicular microstent with CS alone.

Design: Prospective, multicenter, controlled randomized clinical trial.

Participants: Patients with cataract and primary open-angle glaucoma treated with 1 or more glaucoma medications, washed-out diurnal intraocular pressure (DIOP) of 22 to 34 mmHg, and no prior incisional glaucoma surgery.

Suppression of Diurnal (9AM-4PM) IOP Fluctuations with Minimally Invasive Glaucoma Surgery: An Analysis of Data from the Prospective, Multicenter, Single-Arm GEMINI Study.

Purpose: This study analyzes diurnal IOP data (9AM, 12PM, 4PM) from a prospective 12-month trial of the OMNI Surgical System in open-angle glaucoma (OAG) patients with the aim of evaluating effect of MIGS surgery on the amplitude of the diurnal IOP profile pre- and postoperatively.

Setting: Fifteen ophthalmology practices and surgery centers located in 14 states in the United States.

Design: Prospective, multicenter, IRB approved study.

RAS induced senescence of skin keratinocytes is mediated through Rho-associated protein kinase (ROCK).

Cellular senescence is a well-documented response to oncogene activation in many tissues. Multiple pathways are invoked to achieve senescence indicating its importance to counteract the transforming activities of oncogenic stimulation. We now report that the Rho-associated protein kinase (ROCK) signaling pathway is a critical regulator of oncogene-induced senescence in skin carcinogenesis.

Ab-Externo MicroShunt versus Trabeculectomy in Primary Open-Angle Glaucoma: One-Year Results from a 2-Year Randomized, Multicenter Study.

Purpose: To compare the effectiveness and safety of the MicroShunt versus trabeculectomy in patients with primary open-angle glaucoma (POAG).

Design: One-year results from a 2-year, prospective, randomized, multicenter, noninferiority study (NCT01881425) conducted in the United States and Europe.

Participants: Eligible patients were aged 40-85 years with intraocular pressure (IOP) ≥15 and ≤40 mmHg and mild-to-severe POAG inadequately controlled on maximum tolerated medical therapy.

Cell of Origin Influences Pancreatic Cancer Subtype.

Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease with a 5-year survival rate of approximately 9%. An improved understanding of PDAC initiation and progression is paramount for discovering strategies to better detect and combat this disease. Although transcriptomic analyses have uncovered distinct molecular subtypes of human PDAC, the factors that influence subtype development remain unclear.

Canaloplasty and Trabeculotomy Combined with Phacoemulsification in Open-Angle Glaucoma: Interim Results from the GEMINI Study.

Purpose: To report interim 6-month safety and efficacy outcomes of 360° canaloplasty and 180° trabeculotomy using the OMNI Surgical System concomitantly with phacoemulsification in patients with open-angle glaucoma (OAG).

Setting: Fifteen multi-subspecialty ophthalmology practices and surgery centers located in 14 states (Alabama, Arizona, Arkansas, Florida, Georgia, Iowa, Kansas, Montana, Nebraska, North Dakota, Oklahoma, Pennsylvania, Texas, and Wisconsin).

Design: Prospective, multicenter, IRB approved study of patients treated with canaloplasty (360°) and trabeculotomy (180°).

American Glaucoma Society Position Paper: Microinvasive Glaucoma Surgery.

In 2018, the American Glaucoma Society (AGS), the world’s largest professional society of glaucoma subspecialists, convened a 12-member task force of experts to craft a position statement about microinvasive glaucoma surgery (MIGS). The main objective of this position statement is to provide a succinct overview of these procedures and to address some misconceptions about MIGS. The members of the task force were selected by the AGS Board of Directors and include AGS members with expertise in developing MIGS, teaching MIGS, performing research on use and outcomes of these procedures, and working with the United States Food and Drug Administration (FDA) and other regulatory agencies about developing criteria to evaluate the efficacy and safety of these devices.

Performance evaluation of ozone and particulate matter sensors.

As public awareness and concern about air quality grows, companies and researchers have begun to develop small, low-cost sensors to measure local air quality. These sensors have been used in citizen science projects, in distributed networks within cities, and in combination with public health studies on asthma and other air-quality-associated diseases. However, sensor long-term performance under different environmental conditions and pollutant levels is not fully understood.

Topical Application of a Dual ABC Transporter Substrate and NF-κB Inhibitor Blocks Multiple Sources of Cutaneous Inflammation in Mouse Skin.

Among the molecular signals underlying cutaneous inflammation is the transcription complex NF-κB, its upstream modulators, and cytokines and chemokines that are the downstream proinflammatory effectors. Central to NF-κB activation is IκB kinase (IKK), which phosphorylates IκBα, releasing NF-κB to the nucleus. In a screening of a kinase inhibitor library, we identified two IKK inhibitors that were high-affinity substrates for p-glycoprotein (ABCB1), the multidrug resistance protein known to facilitate transdermal drug delivery.