Recent advances in caspase-3, breast cancer, and traditional Chinese medicine: a review.

Caspases (cysteinyl aspartate-specific proteinases) are a group of structurally similar proteases in the cytoplasm that can be involved in cell differentiation, programmed death, proliferation, and inflammatory generation. Experts have found that caspase-3 can serve as a terminal splicing enzyme in apoptosis and participate in the mechanism by which cytotoxic drugs kill cancer cells. Breast cancer (BC) has become the most common cancer among women worldwide, posing a severe threat to their lives. Finding new therapeutic targets for BC is the primary task of contemporary physicians. Numerous studies have revealed the close association between caspase-3 expression and BC. Caspase-3 is essential in BC's occurrence, invasion, and metastasis. In addition, Caspase-3 exerts anticancer effects by regulating cell death mechanisms. Traditional Chinese medicine acting through caspase-3 expression is increasingly used in clinical treatment. This review summarizes the biological mechanism of caspase-3 and research progress on BC. It introduces a variety of traditional Chinese medicine related to caspase-3 to provide new ideas for the clinical treatment of BC.

Chemical and Biological Strategies for Profiling Protein-Protein Interactions in Living Cells.

Protein-protein interactions (PPIs) play critical roles in almost all cellular signal transduction events. Characterization of PPIs without interfering with the functions of intact cells is very important for basic biology study and drug developments. However, the ability to profile PPIs especially those weak/transient interactions in their native states remains quite challenging. To this end, many endeavors are being made in developing new methods with high efficiency and strong operability. By coupling with advanced fluorescent microscopy and mass spectroscopy techniques, these strategies not only allow us to visualize the subcellular locations and monitor the functions of protein of interest (POI) in real time, but also enable the profiling and identification of potential unknown interacting partners in high-throughput manner, which greatly facilitates the elucidation of molecular mechanisms underlying numerous pathophysiological processes. In this review, we will summarize the typical methods for PPIs identification in living cells and their principles, advantages and limitations will also be discussed in detail.

Randomized Trial of First-Line Tyrosine Kinase Inhibitor With or Without Radiotherapy for Synchronous Oligometastatic EGFR-Mutated Non-Small Cell Lung Cancer.

BACKGROUND: Adding radiotherapy (RT) to systemic therapy improves progression-free survival (PFS) and overall survival (OS) in oligometastatic non-small cell lung cancer (NSCLC). Whether these findings translate to epidermal growth factor receptor (EGFR)-mutated NSCLC remains unknown. The SINDAS trial (NCT02893332) evaluated first-line tyrosine kinase inhibitor (TKI) therapy for EGFR-mutated synchronous oligometastatic NSCLC and randomized to upfront RT vs no RT; we now report the prespecified interim analysis at 68% accrual. METHODS: Inclusion criteria were biopsy-proven EGFR-mutated adenocarcinoma (per amplification refractory mutation system or next generation sequencing), with synchronous (newly diagnosed, treatment naïve) oligometastatic (≤5 metastases; ≤2 lesions in any one organ) NSCLC without brain metastases. All patients received a first-generation TKI (gefitinib, erlotinib, or icotinib), and randomization was between no RT vs RT (25-40 Gy in 5 fractions depending on tumor size and location) to all metastases and the primary tumor/involved regional lymphatics. The primary endpoint (intention to treat) was PFS. Secondary endpoints included OS and toxicities. All statistical tests were 2-sided. RESULTS: A total of 133 patients (n = 65 TKI only, n = 68 TKI with RT) were enrolled (2016-2019). The median follow-up was 23.6 months. The respective median PFS was 12.5 months vs 20.2 months (P < .001), and the median OS was 17.4 months vs 25.5 months (P < .001) for TKI only vs TKI with RT. Treatment yielded no grade 5 events and a 6% rate of symptomatic grade 3-4 pneumonitis in the TKI with RT arm. Based on the efficacy results of this prespecified interim analysis, the ethics committee recommended premature cessation of this trial. CONCLUSIONS: As compared with a first-line TKI alone, addition of upfront local therapy using RT statistically significantly improved PFS and OS for EGFR-mutated NSCLC.

Longitudinal Association of Universal Screening and Treatment for Major Depressive Disorder with Survival in Cancer Patients.

Evidence for clinical screening and intervention for depression in cancer and the effect of this intervention on cancer prognosis is suboptimal. This study substantialized a complete model with universal screening and intervention for major depressive disorder (MDD) and explored its effect on survival in patients. This longitudinal study recruited cancer patients routinely screened for MDD with a two-stage model. Data including sex, age, cancer diagnosis, first diagnosis date, date of death, cancer stage, and MDD diagnosis and treatment were collected from medical records and the national registration system for cancer. Kaplan−Meier's survival analysis and the Cox proportional hazards regression model were applied to analyze the effects of associated factors on survival. Further subgroup analysis for 14 types of cancer primary site was also performed. Overall, the hazard for patients adhering to psychiatric treatment for MDD before cancer diagnosis was not statistically different from that for patients without MDD (hazard ratio (HR) = 1.061, 95% CI: 0.889−1.267, p = 0.512). The hazard for patients adhering to psychiatric treatment after cancer diagnosis was significantly lower than that for patients without MDD (HR = 0.702, 95% CI: 0.607−0.812, p < 0.001). Those who were diagnosed with MDD after cancer diagnosis and adhered poorly to psychiatric treatment had the greatest hazard (HR = 1.829, 95% CI: 1.687−1.984, p < 0.001). The effect of intervention for MDD varied across different primary cancer types.

Structural, spectroscopic and DFT theoretical studies of phosphorescent CuIP2S-containing cuprous complexes.

Luminescent cuprous complexes are important coordination compounds due to their relative abundance, low cost and ability to display excellent luminescence. The structures of two CuIP2S-type cuprous complexes, namely, iodido(thiourea-κS)bis(triphenylphosphane-κP)copper(I), [CuI(CH4N2S)(C18H15P)2] or [CuI(TU)(TPP)2] (I), and (2,3-dihydrobenzimidazole-2-thione-κS)iodidobis(triphenylphosphane-κP)copper(I), [CuI(C7H6N2S)(C18H15P)2] or [CuI(DHBIT)(TPP)2] (II), are described. In these two structures, the complex molecules of both are constructed by one copper(I) centre, one iodide ion, two TPP ligands and one thione ligand (TU for I and DHBIT for II). The copper(I) centres of I and II are both located in a distorted CuIP2S tetrahedron and are coordinated by two P atoms from two TPP ligands, one S atom from the thione ligand and the I atom. The UV-Vis absorption and photoluminescence properties of these CuIP2S-type cuprous complexes have been studied using crystalline powder samples. Detailed time-dependent density functional theory (TD-DFT) calculations and wavefunction analysis reveal that the pale-blue-green phosphorescence emission should originate from intra-ligand (TPP for I and DHBIT for II) charge transfer, with a small component of the metal-to-ligand charge transfer 3(IL+ML)CT excited state.

A new heteroleptic phosphorescent cuprous complex supported by a BINAP ligand: synthesis, structure, luminescence properties and theoretical analyses.

Luminescent cuprous complexes are an important class of coordination compounds due to their relative abundance, low cost and ability to display excellent luminescence. The heteroleptic cuprous complex solvate rac-(acetonitrile-κN)(3-aminopyridine-κN)[2,2'-bis(diphenylphosphanyl)-1,1'-binaphthyl-κ2P,P']copper(I) hexafluoridophosphate dichloromethane monosolvate, [Cu(C5H6N2)(C2H3N)(C44H32P2)]PF6·CH2Cl2, conventionally abbreviated as [Cu(3-PyNH2)(CH3CN)(BINAP)]PF6·CH2Cl2, (I), where BINAP and 3-PyNH2 represent 2,2'-bis(diphenylphosphanyl)-1,1'-binaphthyl and 3-aminopyridine, respectively, is described. In this complex solvate, the asymmetric unit consists of a cocrystallized dichloromethane molecule, a hexafluoridophosphate anion and a complete racemic heteroleptic cuprous complex cation in which the cuprous centre, in a tetrahedral CuP2N2 coordination, is coordinated by two P atoms from the BINAP ligand, one N atom from the 3-PyNH2 ligand and another N atom from a coordinated acetonitrile molecule. The UV-Vis absorption and photoluminescence properties of this heteroleptic cuprous complex have been studied on polycrystalline powder samples, which had been verified by powder X-ray diffraction before recording the spectra. Time-dependent density functional theory (TD-DFT) calculations and a wavefunction analysis reveal that the orange-yellow phosphorescence emission should originate from intra-ligand (BINAP) charge transfer mixed with a little of the metal-to-ligand charge transfer 3(IL+ML)CT excited state.

HOXB5 promotes malignant progression in pancreatic cancer via the miR-6732 pathway.

Background: Homeobox B5 (HOXB5) is associated with the poor prognosis of various cancer types. However, the specific mechanism by which HOXB5 promotes the malignant progression of pancreatic cancer (PC) remains to be determined.Methods: The Cancer Genome Atlas database indicated HOXB5 expression level correlated to PC prognosis. The biological functions of HOXB5 was confirmed by colony formation, migration, and invasion assays. The effects of HOXB5 on the expression of cancer stem cell and epithelial-mesenchymal transition markers were evaluated. The downstream target of HOXB5 was miR-6723, which was detected by transcriptional assay. A xenograft tumor model was established in nude mice for the assessment of the role of HOXB5 in tumor growth and metastasis.Results: PC tissues had higher HOXB5 expression levels than noncancerous tissues, and high HOXB5 expression was significantly associated with poor PC prognosis. HOXB5 knockdown suppressed clone formation and the proliferation, invasion, and migration of PC cells in vitro. Conversely, these activities were enhanced by HOXB5 overexpression. The HOXB5 that bound two synergy motifs regulated miR-6723 expression and contributed to PC malignant progression. The role of HOXB5 in promoting tumor growth and metastasis was verified in vivo. Further investigation revealed that Twist1 and Zeb1 expression levels were increased by HOXB5.Conclusions: HOXB5 overexpression was significantly correlated with poor PC prognosis. HOXB5 accelerated the malignant progression of PC by up-regulating miR-6723, which afforded PC cells stem-like properties and facilitated the epithelial-mesenchymal transition of PC cells.

In vivo magnetic resonance imaging tracking of transplanted superparamagnetic iron oxide-labeled bone marrow mesenchymal stem cells in rats with myocardial infarction.

Superparamagnetic iron oxide (SPIO) nanoparticles generate superparamagnetism, thereby resulting in an inhomogeneous local magnetic field, which shortens the T2 value on magnetic resonance imaging (MRI). The purpose of the present study was to use MRI to track bone marrow mesenchymal stem cells (BMSCs) labeled with SPIO in a rat model of myocardial infarction. The BMSCs were isolated from rats and labeled with SPIO. The anterior descending branch of the coronary artery was ligated under anesthesia. Two weeks later, the rats received, at random, 5 x 10(7) SPIO-labeled BMSCs, 5 x 10(7) unlabeled BMSCs or a vehicle (100 µl phosphate-buffered saline) via direct injection into the ischemic area (20 animals/group). MRI was used to track the SPIO­labeled BMSCs and the rats were then sacrificed to verify the presence of BMSCs using immunohistochemistry with an anti-CD90 antibody. The procedure labeled 99% of the BMSCs with SPIO, which exhibited low-intensity signals on T2 and T2* MRI imaging. At 24 h post-BMSC transplantation, low-intensity MRI signals were detected on the T2 and T2* sequences at the infarction margins. After 3 weeks following transplantation, low-intensity signals started to appear within the infarcted area; however, the signal intensity subsequently decreased and became indistinct. Immunohistochemistry revealed that the SPIO-labeled BMSCs migrated from the margin into the infarcted region. In conclusion, the BMSCs were readily labeled with SPIO and in vivo and MRI tracking demonstrated that the SPIO-labeled BMSCs established and grew in the infarcted myocardium.