Novel Systemic Treatment Modalities Including Immunotherapy and Molecular Targeted Therapy for Recurrent and Metastatic Head and Neck Squamous Cell Carcinoma

Head and neck squamous cell carcinomas (HNSCCs) are the sixth most common cancers worldwide. More than half of patients with HNSCC eventually experience disease recurrence and/or metastasis, which can threaten their long-term survival. HNSCCs located in the oral cavity and larynx are usually associated with tobacco and/or alcohol use, whereas human papillomavirus (HPV) infection, particularly HPV16 infection, is increasingly recognized as a cause of oropharyngeal HNSCC. Despite clinical, histologic, and molecular differences between HPV-positive and HPV-negative HNSCCs, current treatment approaches are the same. For recurrent disease, these strategies include chemotherapy, immunotherapy with PD-1-inhibitors, or a monoclonal antibody, cetuximab, that targets epidermal growth factor; these therapies can be administered either as single agents or in combination. However, these treatment strategies carry a high risk of toxic side effects; therefore, more effective and less toxic treatments are needed. The landscape of HNSCC therapy is changing significantly; numerous clinical trials are underway to test novel therapeutic options like adaptive cellular therapy, antibody-drug conjugates, new targeted therapy agents, novel immunotherapy combinations, and therapeutic vaccines. This review helps in understanding the various developments in HNSCC therapy and sheds light on the path ahead in terms of further research in this field.     

GWO‐C: Grey wolf optimizer‐based clustering scheme for WSNs

A wireless sensor network (WSN) is a prominent technology that could assist in the fourth industrial revolution. Sensor nodes present in the WSNs are functioned by a battery. It is impossible to recharge or replace the battery, hence energy is the most important resource of WSNs. Many techniques have been devised and used over the years to conserve this scarce resource of WSNs. Clustering has turned out to be one of the most efficient methods for this purpose. This paper intends to propose an efficient technique for election of cluster heads in WSNs to increase the network lifespan. For the achievement of this task, grey wolf optimizer (GWO) has been employed. In this paper, the general GWO has been modified to cater to the specific purpose of cluster head selection in WSNs. The objective function for the proposed formulation considers average intra‐cluster distance, sink distance, residual energy, and CH balancing factor. The simulations are carried out in diverse conditions. On comparison of the proposed protocol, ie, GWO‐C protocol with some well‐known clustering protocols, the obtained results prove that the proposed protocol outperforms with respect to the consumption of the energy, throughput, and the lifespan of the network. The proposed protocol forms energy‐efficient and scalable clusters.     

In vitro evaluation of Pediococcus acidilactici NCDC 252 for its probiotic attributes

In vitro probiotic attributes of Pediococcus acidilactici, viz. tolerance to acidity and bile salt, phenol resistance, lactic acid production, antioxidant activity, cell surface hydrophobicity, lysozyme resistance and the presence of β‐galactosidase, proteolytic, lipase and peptidoglycan hydrolase activities, were studied. The strain was found to be rich in different proteolytic activities, β‐galactosidase and antioxidant activities, and produced lactic acid. The studies conducted support that P. acidilactici national collection of dairy cultures (NCDC) 252 is a potential probiotic for humans with all the essential basic probiotic properties. This testing is useful to gain insight into this strain and its mechanism of action. All these attributes add to its therapeutic importance and industrial significance.     

THZ531 Induces a State of BRCAness in Multiple Myeloma Cells: Synthetic Lethality with Combination Treatment of THZ 531 with DNA Repair Inhibitors

Multiple myeloma (MM) is a hematological disease marked by abnormal growth of B cells in bone marrow. Inherent chromosomal instability and DNA damage are major hallmarks of MM, which implicates an aberrant DNA repair mechanism. Studies have implicated a role for CDK12 in the control of expression of DNA damage response genes. In this study, we examined the effect of a small molecule inhibitor of CDK12–THZ531 on MM cells. Treatment of MM cells with THZ531 led to heightened cell death accompanied by an extensive effect on gene expression changes. In particular, we observed downregulation of genes involved in DNA repair pathways. With this insight, we extended our study to identify synthetic lethal mechanisms that could be exploited for the treatment of MM cells. Combination of THZ531 with either DNA-PK inhibitor (KU-0060648) or PARP inhibitor (Olaparib) led to synergistic cell death. In addition, combination treatment of THZ531 with Olaparib significantly reduced tumor burden in animal models. Our findings suggest that using a CDK12 inhibitor in combination with other DNA repair inhibitors may establish an effective therapeutic regimen to benefit myeloma patients.     

Coumarin‐based polymer and its silver nanocomposite as advanced antibacterial agents: Synthetic path,kinetics of polymerization,and applications

A novel polymer bearing coumarin pendants of 4‐allyloxy‐2H‐chromen‐2‐one (ACO) was synthesized by atom transfer radical polymerization (ATRP) in toluene at 110°C using 2‐Bromoisobutyryl bromide (BIBB), Cu (I) Br, and 2,2′‐bipyridyl (bpy) as initiator, catalyst, and ligand, respectively. The most appropriate molar concentration ratio of [ACO] : [BIBB] : [Cu (I) Br] : [bpy] was found to be 40 : 1 : 1 : 2 for controlled polymerization. Successful chain extension polymerization of poly (4‐allyloxy‐2H‐chromen‐2‐one) (PACO) confirms the livingness of the process. The activation energy (E_a) (76.26 kJ mol^?1) and enthalpy of activation (ΔH^?) (73.07 kJ mol^?1) were in good agreement to each other proving the feasibility of the reaction and negative value of entropy of activation (ΔS^?) (?320 J mol^?1 K^?1) supported the highly restricted movement of reacting species in transition state during polymerization. Initial polymer decomposition temperature of PACO was found to be 130°C. SEM analysis revealed that polymer surface is not smooth with pointed rod like shapes. The polymer/Ag nanocomposite was synthesized and examined in view of antibacterial effect against Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Proteus mirabilis, and Klebsiella pneumonae. PACO and its Ag nanocomposite (PACON) have been found to be active selectively against bacterial pathogen E. fecalis with minimum inhibitory concentration of 50 and 32 μg mL^?1, respectively. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Immunogenic Cell Death of Breast Cancer Stem Cells Induced by an Endoplasmic Reticulum-Targeting Copper(II) Complex

Immunogenic cell death (ICD) offers a method of stimulating the immune system to attack and remove cancer cells. We report a copper(II) complex containing a Schiff base ligand and a polypyridyl ligand, 4 , capable of inducing ICD in breast cancer stem cells (CSCs). Complex 4 kills both bulk breast cancer cells and breast CSCs at sub-micromolar concentrations. Notably, 4 exhibits greater potency (one order of magnitude) towards breast CSCs than salinomycin (an established breast CSC-potent agent) and cisplatin (a clinically approved anticancer drug). Epithelial spheroid studies show that 4 is able to selectively inhibit breast CSC-enriched HMLER-shEcad spheroid formation and viability over non-tumorigenic breast MCF10 A spheroids. Mechanistic studies show that 4 operates as a Type II ICD inducer. Specifically, 4 readily enters the endoplasmic reticulum (ER) of breast CSCs, elevates intracellular reactive oxygen species (ROS) levels, induces ER stress, evokes damage-associated molecular patterns (DAMPs), and promotes breast CSC phagocytosis by macrophages. As far as we are aware, 4 is the first metal complex to induce ICD in breast CSCs and promote their engulfment by immune cells.     

Investigation of structural,optical, electrical,and magnetic properties of Fe-doped La0.7Sr0.3MnO3 manganites

In this work, the physical properties of nanocrystalline samples of La_0.7Sr_0.3Mn_1−xFe_xO₃ (0.0 ≤ x ≤ 0.20) perovskite manganites synthesized by the reverse micelle (RM) technique were explored in detail. The phase purity, crystal structure, and crystallite size of the samples were determined using X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy. All the samples had rhombohedral crystal structure and crystallite size increased with increase in Fe content in La_0.7Sr_0.3MnO₃. The scanning electron micrographs (SEMs) exhibited smooth surface morphology and nonuniform shape of the particles. The optical properties studied using UV-visible absorption spectroscopy revealed a decrease in the absorbance and optical band gap with an increase in Fe content in La_0.7Sr_0.3MnO₃ compound. The temperature-dependent resistivity measurements revealed semiconducting nature of x = 0 and 0.1 samples up to the studied temperature range, while a metal-to-insulator transition was observed at higher Fe doping. Magnetic studies revealed weak ferromagnetism in all the samples and a reduction in the maximum magnetization with an increase in Fe content. A close correlation between electrical transport and magnetic properties was observed with the doping of Fe ion in La_0.7Sr_0.3MnO₃ at Mn site. These results advocate strong interactions associated with the double exchange mechanism among Fe³⁺ and Mn³⁺ ions.     

Polyphosphazenes—A Promising Candidate for Drug Delivery,Bioimaging, and Tissue Engineering: A Review

Synthetic polymer materials have been surged to the forefront of research in the fields of tissue engineering, drug delivery, and biomonitoring in recent years. Biodegradable synthetic polymers are increasingly needed as transient substrates for tissue regeneration and medicine delivery. In contrast to commonly used polymers including polyesters, polylactones, polyanhydrides, poly(propylene fumarates), polyorthoesters, and polyurethanes, biodegradable polyphosphazenes (PPZs) hold great potential for the purposes indicated above. PPZ's versatility in the synthetic process has enabled the production of a variety of polymers with various physico-chemical, and biological properties have been produced, making them appropriate for biomedical applications. Biocompatible PPZs are often used as scaffolds in the regeneration of skeleton, bones, and other tissues. PPZs have also received special attention as potential drug vehicles of high-value biopharmaceuticals such as anticancer drugs. Additionally, by incorporating fluorophores into the PPZ backbone to produce photoluminescent biodegradable PPZs, the utility of polyphosphazenes is further expanded as they are used in tracking the regeneration of the target tissue as well as the fate of PPZ based scaffolds or drug delivery vehicles. This review provides a summary of the evolution of PPZ applications in the fields of tissue engineering, drug delivery, and bioimaging in recent 5 years.     

A Novel Highly Sensitive Humidity Sensor Based on ZnO/SBA‐15 Hybrid Nanocomposite

This work deals with the study of hydrothermally synthesized zinc oxide (ZnO) loaded mesoporous SBA‐15 hybrid nanocomposite for relative humidity sensing (RH) at room temperature. The sensor exhibits an excellent ~5 orders impedance change along with excellent linearity, quick response time (17 s), rapid recovery time (18 s), negligible hysteresis (1.2%), good repeatability, and stability (1.8%) in 11%–98% RH range. In addition, complex impedance spectra of the sensor at different RHs were analyzed to understand the humidity sensing mechanism. Our study can open a new way for realizing ZnO/SBA‐15 hybrid nanocomposite for fabrication of high‐performance RH sensors.     

Indole‐based polymer and its silver nanocomposite as advanced antibacterial agents: synthetic path,kinetics of polymerization and applications

Atom transfer radical polymerization of 1‐allylindole‐3‐carbaldehyde (AIC) was studied by employing 2‐bromoisobutyryl bromide as initiator in toluene. It led to controlled radical polymerization of AIC, with an increase of molecular weight along with the conversion of the monomer, and a relatively narrow molar mass distribution was obtained, as determined by gel permeation chromatography. The living nature of poly(1‐allylindole‐3‐carbaldehyde) (PAIC) was confirmed by the chain extension polymerization whereas ¹H NMR analysis showed that the major population of PAIC retained the chain‐end functional group. PAIC and its silver nanocomposite were found to be biologically active against some tested bacterial pathogens. Minimum inhibitory concentration tests revealed that PAIC exhibited antibacterial activity against Staphylococcus aureus, Proteus mirabilis and Klebsiella pneumonae whereas PAIC/Ag nanocomposite showed antibacterial activity against Enterococcus faecalis and K. pneumonae. © 2012 Society of Chemical Industry