Deciphering the Multifaceted Immune Landscape of Unresectable Primary Liver Cancer to Predict Immunotherapy Response.

Immunotherapies employing PD-1/PD-L1 immune checkpoint inhibitors (ICIs) are vital for primary liver cancer (PLC), but response rates remain unsatisfying. Accurate differentiation of responders from non-responders to immunotherapy is imperative. Here, single-cell-scaled mass cytometry analysis on sequential peripheral blood mononuclear cells (PBMCs) from ICI-treated PLC patients is conducted, and tissue residence of immune subpopulations is assessed via multiplex immunohistochemistry.

Advances in Targeted Drug Resistance Associated with Dysregulation of Lipid Metabolism in Hepatocellular Carcinoma.

Hepatocellular carcinoma is the prevailing malignant neoplasm affecting the liver, often diagnosed at an advanced stage and associated with an unfavorable overall prognosis. Sorafenib and Lenvatinib have emerged as first-line therapeutic drugs for advanced hepatocellular carcinoma, improving the prognosis for these patients. Nevertheless, the issue of tyrosine kinase inhibitor (TKI) resistance poses a substantial obstacle in the management of advanced hepatocellular carcinoma.

SHC4 orchestrates β-catenin pathway-mediated metastasis in triple-negative breast cancer by promoting Src kinase autophosphorylation.

Triple-negative breast cancer (TNBC) is highly aggressive and metastatic, and has the poorest prognosis among all breast cancer subtypes. Activated β-catenin is enriched in TNBC and involved in Wnt signaling-independent metastasis. However, the underlying mechanisms of β-catenin activation in TNBC remain unknown.

Lysosomal cyst(e)ine storage potentiates tolerance to oxidative stress in cancer cells.

Cyst(e)ine is a key precursor for the synthesis of glutathione (GSH), which protects cancer cells from oxidative stress. Cyst(e)ine is stored in lysosomes, but its role in redox regulation is unclear. Here, we show that breast cancer cells upregulate major facilitator superfamily domain containing 12 (MFSD12) to increase lysosomal cyst(e)ine storage, which is released by cystinosin (CTNS) to maintain GSH levels and buffer oxidative stress.

Overexpressed FAM111B degrades GSDMA to promote esophageal cancer tumorigenesis and cisplatin resistance.

Background: Chemotherapeutic agents such as cisplatin are commonly used in patients with clinically unresectable or recurrent esophageal cancer (ESCA). However, patients often develop resistance to cisplatin, which in turn leads to a poor prognosis. Studies have shown that FAM111B may be involved in the development of tumors as an oncogene or tumor suppressor gene.

Inhibition of DPAGT1 suppresses HER2 shedding and trastuzumab resistance in human breast cancer.

Human epidermal growth factor receptor 2-targeted (HER2-targeted) therapy is the mainstay of treatment for HER2+ breast cancer. However, the proteolytic cleavage of HER2, or HER2 shedding, induces the release of the target epitope at the ectodomain (ECD) and the generation of a constitutively active intracellular fragment (p95HER2), impeding the effectiveness of anti-HER2 therapy. Therefore, identifying key regulators in HER2 shedding might provide promising targetable vulnerabilities against resistance.

The YTHDC1/GLUT3/RNF183 axis forms a positive feedback loop that modulates glucose metabolism and bladder cancer progression.

Aberrant glucose metabolism is a characteristic of bladder cancer. Hyperglycemia contributes to the development and progression of bladder cancer. However, the underlying mechanism by which hyperglycemia promotes the aggressiveness of cancers, especially bladder cancer, is still incompletely understood.

ZDHHC2-Mediated AGK Palmitoylation Activates AKT-mTOR Signaling to Reduce Sunitinib Sensitivity in Renal Cell Carcinoma.

Unlabelled: Tyrosine kinase inhibitors (TKI) that can suppress the VEGF signaling pathway and angiogenesis have been developed to impede the progression of malignant tumors and have been approved as first-line targeted agents for clear cell renal cell carcinoma (ccRCC). Dysregulation of lipid metabolism is a major driver of TKI resistance in renal cancer. In this study, we showed that the palmitoyl acyltransferase ZDHHC2 is abnormally upregulated in tissues and cell lines resistant to TKIs, such as sunitinib.

Global crotonylome reveals hypoxia-mediated lamin A crotonylation regulated by HDAC6 in liver cancer.

Lysine crotonylation is a recently discovered post-translation modification involved in transcription regulation, cell signal transduction, and other processes. Scientists have identified several crotonylases and decrotonylases of histones, including P300/CBP, HDACs, and SIRTs. However, the regulation of non-histone protein crotonylation remains unclear.

E3 ubiquitin ligase RNF180 reduces sensitivity of triple-negative breast cancer cells to Gefitinib by downregulating RAD51.

Background: Gefitinib (Gef) is an EGFR inhibitor and its resistance in triple negative breast cancer (TNBC) is a critical concern. E3 ubiquitin ligases are pivotal for mediation of TNBC metastasis. However, the role of E3 ubiquitin ligase Ring Finger Protein 180 (RNF180) in EGFR inhibitor resistance of TNBC remains unclear.

Tripartite motif-containing 3 (TRIM3) enhances ER signaling and confers tamoxifen resistance in breast cancer.

Tamoxifen resistance remains a clinical problem in estrogen receptor (ER)-positive breast cancer. SUMOylation of ERα enhances ERα-induced transcription activity. Tripartite motif-containing (TRIM) proteins are a new class of SUMO E3 ligases, which regulate the SUMOylation of proteins.

Prognostic Factors of Survival of Advanced Liver Cancer Patients Treated With Palliative Radiotherapy: A Retrospective Study.

Aims: Survival benefit of liver cancer patients who undergo palliative radiotherapy varies from person to person. The present study aims to identify indicators of survival of advanced liver cancer patients receiving palliative radiotherapy.

Patients And Methods: One hundred and fifty-nine patients treated with palliative radiotherapy for advanced liver cancer were retrospectively assessed.

Microstructure-Induced Anisotropic Optical Properties of YF Columnar Thin Films Prepared by Glancing Angle Deposition.

Yttrium fluoride (YF) columnar thin films (CTFs) were fabricated by electron beam evaporation with the glancing angle deposition method. The microstructures and optical properties of YF CTFs were studied systematically. The YF films grown at different deposition angles are all amorphous.

Zinc finger protein 367 promotes metastasis by inhibiting the Hippo pathway in breast cancer.

Circulating tumor cells (CTC) disseminating is an important cause of distant metastasis. However, the mechanism involved in increasing the numbers of CTCs in breast cancer is unclear. Herein, Zinc finger protein 367 (ZNF367) was identified as a potential prometastatic gene in an integrative breast cancer datasets.

Oridonin inhibits aberrant AKT activation in breast cancer.

Aberrant activation of phosphatidylinosito-4,5-bisphosphate 3-kinase/protein kinase B (PI3K/AKT) signaling in cancer has led to pursuit of inhibitors for targeting this pathway. However, inhibitors of PI3K and AKT have failed to yield efficacious results without adverse effects. Here, we screened a library containing 441 authenticated traditional chinese medicine (TCM) plant extracts by examining their effect on cell viability of a human mammary epithelial cell line HMEC-PIK3CA, which expresses mutant PIK3CA and has constitutively active AKT signaling.

Age-specific sex difference in the incidence of hepatocellular carcinoma in the United States.

Background: Hepatocellular carcinoma possesses a notable sex difference in incidence, and a protective role of estrogens has been hypothesized.

Methods: Using data from 13 cancer registries in the Surveillance, Epidemiology, and End Results Program, we describe the age-specific sex difference in the incidence of hepatocellular carcinoma in the United States during 1992-2013. We used a curve fitting by non-linear regression to quantitatively characterize the age-specific incidence rate of hepatocellular carcinoma by sex.

HN1 contributes to migration, invasion, and tumorigenesis of breast cancer by enhancing MYC activity.

Background: Hematological and neurological expressed 1 (HN1) is upregulated in many tumors, but the role of HN1 in breast cancer progression and its regulatory mechanism have not been well understood.

Methods: To study the role of HN1 in the initiation and progression of breast cancer, we examined HN1 levels in breast cancer cells and tissues and analyzed the relationship between HN1 levels and patient survival. We used mammosphere formation assay, side population analysis, wound healing assay, transwell assay, soft agar formation assay, and xenografted tumor model to determine the effect of HN1 on the expansion of breast cancer stem cells, and the migration, invasion and tumorigenesis of breast cancer.

Digitalis Use and the Risk of Breast Cancer: A Systematic Review and Meta-Analysis.

Introduction: Previous epidemiological studies have indicated an increased risk of breast cancer associated with digitalis medication, though results are inconsistent. We performed this systematic review of available epidemiological studies to clarify the association between digitalis use and the risk of breast cancer.

Methods: A search of studies published through May 2016 in MEDLINE and EMBASE databases was performed, supplemented by manual searches of reference lists.

Addition of the p110α inhibitor BYL719 overcomes targeted therapy resistance in cells from Her2-positive-PTEN-loss breast cancer.

Breast cancer is one of the leading causes of death for women worldwide. Among various subtypes of breast cancer, human epidermal growth factor receptor 2 (HER2)-positive and phosphatase and tensin homolog (PTEN) loss breast cancer is a cause of great concern in terms of its resistance to HER2-targeted therapies and its poor prognosis. Phosphatidylinositol 3-kinase (PI3K)/AKT hyperphosphorylation is considered one of key mechanisms leading to this resistance, thus combination therapy of PI3K inhibitors and HER2 antibodies is promising for overcoming this problem, and more specific regimens should be designed in this age of precision medicine.

Gold nanorods as the saturable absorber for a diode-pumped nanosecond Q-switched 2 μm solid-state laser.

Gold nanorods (GNRs) with an average aspect ratio of 15 were experimentally exploited as the 2 μm saturable absorber in a laser diode pumped Tm:YAG laser for the first time, to the best of our knowledge. Q-switched pulses with a maximum average output power of 380 mW, a minimum pulse width of 796 ns, and a pulse repetition rate of 77 kHz were achieved under the LD pump power of 6.2 W.

High efficiency Tm:YAG slab laser with hundred-watts-level output power.

We report on a hundred-watts-level high power Tm:YAG slab laser system operating at room temperature. The laser has a threshold pump power of 46.7 W, benefiting from the good mode matching of an end-pumping scheme and the excellent heat-dissipation capability of our cooling system.

Encapsulation of single cells into monodisperse droplets by fluorescence-activated droplet formation on a microfluidic chip.

Random compartmentalization of cells by common droplet formation methods, i.e., T-junction and flow-focusing, results in low occupancy of droplets by single cells.