Hormone therapy enhances anti-PD1 efficacy in premenopausal estrogen receptor-positive and HER2-negative advanced breast cancer.

The efficacy of immunotherapy for estrogen receptor-positive/HER2-negative (ER+/HER2-) metastatic breast cancer (MBC) has not been proven. We conduct a phase 1b/2 trial to assess the efficacy of combining pembrolizumab (anti-PD1 antibody), exemestane (nonsteroidal aromatase inhibitor), and leuprolide (gonadotropin-releasing hormone agonist) for 15 patients with premenopausal ER+/HER2- MBC who had failed one to two lines of hormone therapy (HT) without chemotherapy. The primary endpoint of progression-free survival rate at 8 months (i.

Porcine reproductive and respiratory syndrome virus activates lipid synthesis through a ROS-dependent AKT/PCK1/INSIG/SREBPs axis.

The porcine reproductive and respiratory syndrome virus (PRRSV) is a highly contagious pathogen in pigs. This study aimed to investigate the impact of PRRSV infection on cellular metabolism, particularly focusing on lipid metabolism to understand its role in promoting viral replication. We conducted a metabolic analysis on MARC-145 cells before and after PRRSV infection.

A transcription-independent role for HIF-1α in modulating microprocessor assembly.

Microprocessor is an essential nuclear complex responsible for the initial RNase-mediated cleavage of primary miRNA, which is a tightly controlled maturation process that requires the proper assembly of Drosha and DGCR8. Unlike previously identified mechanisms directly targeting the enzymatic subunit Drosha, current knowledge about the biological ways of controlling miRNA nuclear maturation through DGCR8 is less addressed. In this study, we unveiled that the microprocessor assembly is governed by a master gene regulator HIF-1α irrespective of its canonical transcriptional activity.

In situ HER2 RNA expression as a predictor of pathologic complete response of HER2-positive breast cancer patients receiving neoadjuvant chemotherapy and anti-HER2 targeted treatment.

Background: Immunohistochemistry (IHC) and in situ hybridization (ISH) remain standard biomarkers for therapeutic decisions in human epidermal growth factor 2 (HER2)-positive breast cancers (BCs); however, they are insufficient to explain the heterogeneous anti-HER2 response.

Methods: We aimed to investigate the correlation of in situ HER2 RNA expression (isHRE), using RNAscope, with HER2 biomarkers and the impact of isHRE on the pathological complete response (pCR) rates of 278 patients with HER2 IHC/fluorescence ISH (FISH)-positive BC receiving neoadjuvant chemotherapy and anti-HER2 targeted treatment (NCTT).

Results: We validated HER2 RNAscope scoring as a semiquantitative method to determine isHRE and showed a positive correlation between RNAscope scores and pCR rates, with particularly different rates between patients with a score of 5 versus 1-4 BCs (66.

Umpolung-Enabled Divergent Dearomative Carbonylations.

Although dearomative functionalizations enable the direct conversion of flat aromatics into precious three-dimensional architectures, the case for simple arenes remains largely underdeveloped owing to the high aromatic stabilization energy. We herein report a dearomative sequential addition of two nucleophiles to arene π-bonds through umpolung of chromium-arene complexes. This mode enables divergent dearomative carbonylation reactions of benzene derivatives by tolerating various nucleophiles in combination with alcohols or amines under CO-gas-free conditions, thus providing modular access to functionalized esters or amides.

Pseudorabies virus manipulates mitochondrial tryptophanyl-tRNA synthetase 2 for viral replication.

The pseudorabies virus (PRV) is identified as a double-helical DNA virus responsible for causing Aujeszky's disease, which results in considerable economic impacts globally. The enzyme tryptophanyl-tRNA synthetase 2 (WARS2), a mitochondrial protein involved in protein synthesis, is recognized for its broad expression and vital role in the translation process. The findings of our study showed an increase in both mRNA and protein levels of WARS2 following PRV infection in both cell cultures and animal models.

A novel computer-assisted tool for 3D imaging of programmed death-ligand 1 expression in immunofluorescence-stained and optically cleared breast cancer specimens.

Background: Programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) are the two most common immune checkpoints targeted in triple-negative breast cancer (BC). Refining patient selection for immunotherapy is non-trivial and finding an appropriate digital pathology framework for spatial analysis of theranostic biomarkers for PD-1/PD-L1 inhibitors remains an unmet clinical need.

Methods: We describe a novel computer-assisted tool for three-dimensional (3D) imaging of PD-L1 expression in immunofluorescence-stained and optically cleared BC specimens (n = 20).

Jeans and language: kin networks and reproductive success are associated with the adoption of outgroup norms.

Traditional norms of human societies in rural China may have changed owing to population expansion, rapid development of the tourism economy and globalization since the 1990s; people from different ethnic groups might adopt cultural traits from outside their group or lose their own culture at different rates. Human behavioural ecology can help to explain adoption of outgroup cultural values. We compared the adoption of four cultural values, specifically speaking outgroup languages/mother tongue and wearing jeans, in two co-residing ethnic groups, the Mosuo and Han.

Loss of LECT2 promotes ovarian cancer progression by inducing cancer invasiveness and facilitating an immunosuppressive environment.

Leukocyte cell-derived chemotaxin 2 (LECT2) is a multifunctional cytokine that can bind to several receptors and mediate distinct molecular pathways in various cell settings. Changing levels of LECT2 have been implicated in multiple human disease states, including cancers. Here, we have demonstrated reduced serum levels of LECT2 in patients with epithelial ovarian cancer (EOC) and down-regulated circulating Lect2 as the disease progresses in a syngeneic mouse ID8 EOC model.

Lifestyle Factors and Energy Intakes with Risks of Breast Cancer among Pre- and Post- Menopausal Women in Taiwan.

Although the incidence of invasive breast cancer (BC) among women in Asian is generally lower than that in Western countries, the incidence of BC has been on the rise in the past three decades in Asian countries. This hospital-based case-control study aimed to explore the relationship between dietary and metabolic factors and BC risk in pre- and post-menopausal women. We enrolled 285 patients with newly diagnosed BC at the National Taiwan University Hospital and 297 controls from the local community and hospital staff.

Plasma cell-free tumor DNA, PIK3CA and TP53 mutations predicted inferior endocrine-based treatment outcome in endocrine receptor-positive metastatic breast cancer.

Purpose: How to factor both tumor burden and oncogenic genomic mutations as variables to predict the outcome of endocrine-based therapy (ET) in ER-positive/HER2-negative metastatic breast cancer patients (MBC) remains to be explored.

Method: Blood samples prospectively collected from 163 ER-positive/HER2-negative female MBC patients, before ET, were used for cell-free tumor DNA (cfDNA) analysis. cfDNA was subjected to next-generation sequencing (NGS) to interrogate oncogenic PIK3CA hotspot and TP53 DNA-binding domain (DBD) mutations, including single nucleotide variants (SNVs) or small insertions and deletions (InDels).

Intermolecular Dearomative 1,2-Amination/Carbonylation via Nucleophilic Addition of Simple Amines to Arene π-Bonds.

The incorporation of the privileged amino functionality is of paramount importance in organic synthesis. In contrast to the well-developed amination methods for alkenes, the dearomative amination of arenes is largely underexplored due to the inherently inert reactivity of arene π-bonds and selectivity challenges. Herein, we report an intermolecular dearomative aminofunctionalization via direct nucleophilic addition of simple amines to chromium-bound arenes.

Investigation of the material basis of Xiexin Tang to alleviate type 2 diabetes mellitus based on spectrum-effect analysis by UPLC-Q-TOF/MS.

Xiexin Tang (XXT) is a classic prescription for treating diabetes in clinical practices for thousands of years in China, which has been also proved by a large number of modern pharmacological studies. However, due to its complex composition, the bioactive ingredients of XXT is still unclear. In present researches, spectrum-effect relationship analysis is widely used to explore the material basis of traditional medical herbs, so this method was adopted in this study.

Chemoselective 1,2-Reduction and Regiodivergent Deuteration of Chromium-Bound Arenes.

Herein, a general strategy for chemo- and regioselective 1,2-reduction of chromium-bound arenes was developed, thus providing rapid access to 1,3-cyclohexadienes. Selective arene activation via π-complexation along with the use of mild hydride Ph SiH can overcome the inherently low reactivity of arene π-bonds while tolerating various reduction-sensitive functional groups. Its versatility further enables a regiodivergent deuteration.

High rate of postoperative upstaging of ductal carcinoma in situ when prioritizing ultrasound evaluation of mammography-detected lesions: a single-center retrospective cohort study.

Background: The initial diagnosis of ductal carcinoma in situ (DCIS) can be upstaged to invasive cancer after definitive surgery. This study aimed to identify risk factors for DCIS upstaging using routine breast ultrasonography and mammography (MG) and to propose a prediction model.

Methods: In this single-center retrospective study, patients initially diagnosed with DCIS (January 2016-December 2017) were enrolled (final sample size = 272 lesions).

MSIr: Automatic Registration Service for Mass Spectrometry Imaging and Histology.

Mass spectrometry imaging (MSI) is a powerful tool that can be used to simultaneously investigate the spatial distribution of different molecules in samples. However, it is difficult to comprehensively analyze complex biological systems with only a single analytical technique due to different analytical properties and application limitations. Therefore, many analytical methods have been combined to extend data interpretation, evaluate data credibility, and facilitate data mining to explore important temporal and spatial relationships in biological systems.

Estrogen-DNA Adducts and Breast Cancer Risk in Premenopausal Asian Women.

Unlabelled: The incidence of breast cancer among premenopausal women has been increasing rapidly in recent decades in East Asia. This case-control study investigated whether estrogen-DNA adducts were associated with breast cancer risk in Taiwan. The control group (n = 146) comprised healthy female volunteers and women with non-proliferative breast disease.

Dearomative Aminocarbonylation of Arenes via Bifunctional Coordination to Chromium.

Amides are ubiquitous in physical and life sciences. Given the significant abundance of arenes, dearomative aminocarbonylation of arenes would lead to a large and underexplored chemical space for amide discovery. However, such reactions are challenging due to the high degree of resonance stabilization and selectivity issues.

Neoadjuvant afatinib with paclitaxel for triple-negative breast cancer and the molecular characteristics in responders and non-responders.

Background: The prognosis of triple-negative breast cancer (TNBC) is worse and a major proportion of TNBC expresses epidermal growth factor receptor (EGFR). Afatinib can inhibit EGFR signal pathway; however, its treatment effect for TNBC is unknown. Thus, we aimed to assess the efficacy and biomarkers of afatinib in combination with paclitaxel in a neoadjuvant setting.

Impact of BRCA mutation on the survival and risk of contralateral breast cancer in Asian breast cancer patients.

Purpose: Breast cancer is increasing around the globe, including Asia. We aimed to examine the survival and risk of contralateral breast cancer (CBC) in Asian breast cancer patients with BRCA mutations.

Methods: A total of 128 breast cancer patients with germline BRCA mutations and 4,754 control breast cancer patients were enrolled.

TARBP2 Suppresses Ubiquitin-Proteasomal Degradation of HIF-1α in Breast Cancer.

TAR (HIV-1) RNA binding protein 2 (TARBP2) is an RNA-binding protein participating in cytoplasmic microRNA processing. Emerging evidence has shown the oncogenic role of TARBP2 in promoting cancer progression, making it an unfavorable prognosis marker for breast cancer. Hypoxia is a hallmark of the tumor microenvironment which induces hypoxia-inducible factor-1α (HIF-1α) for transcriptional regulation.

Circulating Tumor DNA as a Predictive Marker of Recurrence for Patients With Stage II-III Breast Cancer Treated With Neoadjuvant Therapy.

Background: Patients with stage II to III breast cancer have a high recurrence rate. The early detection of recurrent breast cancer remains a major unmet need. Circulating tumor DNA (ctDNA) has been proven to be a marker of disease progression in metastatic breast cancer.