Combined OX40 Agonist and PD-1 Inhibitor Immunotherapy Improves the Efficacy of Vascular Targeted Photodynamic Therapy in a Urothelial Tumor Model

Purpose: Vascular targeted photodynamic therapy (VTP) is a nonsurgical tumor ablation approach used to treat early-stage prostate cancer and may also be effective for upper tract urothelial cancer (UTUC) based on preclinical data. Toward increasing response rates to VTP, we evaluated its efficacy in combination with concurrent PD-1 inhibitor/OX40 agonist immunotherapy in a urothelial tumor-bearing model. Experimental design: In mice allografted with MB-49 UTUC cells, we compared the effects of combined VTP with PD-1 inhibitor/OX40 agonist with those of the component treatments on tumor growth, survival, lung metastasis, and antitumor immune responses. Results: The combination of VTP with both PD-1 inhibitor and OX40 agonist inhibited tumor growth and prolonged survival to a greater degree than VTP with either immunotherapeutic individually. These effects result from increased tumor infiltration and intratumoral proliferation of cytotoxic and helper T cells, depletion of Treg cells, and suppression of myeloid-derived suppressor cells. Conclusions: Our findings suggest that VTP synergizes with PD-1 blockade and OX40 agonist to promote strong antitumor immune responses, yielding therapeutic efficacy in an animal model of urothelial cancer.     

Nutritional Value and Preventive Role of Nigella sativa L. and Its Main Component Thymoquinone in Cancer: An Evidenced-Based Review of Preclinical and Clinical Studies

In recent times, scientific attention has been paid to different foods and their bioactive components for the ability to inhibit the onset and progress of different types of cancer. Nigella sativa extract, powder and seed oil and its main components, thymoquinone and α-hederin, have showed potent anticancer and chemosensitizing effects against various types of cancer, such as liver, colon, breast, renal, cervical, lung, ovarian, pancreatic, prostate and skin tumors, through the modulation of various molecular signaling pathways. Herein, the purpose of this review was to highlight the anticancer activity of Nigella sativa and it constitutes, focusing on different in vitro, in vivo and clinical studies and projects, in order to underline their antiproliferative, proapoptotic, cytotoxic and antimetastatic effects. Particular attention has been also given to the synergistic effect of Nigella sativa and it constitutes with chemotherapeutic drugs, and to the synthesized analogs of thymoquinone that seem to enhance the chemo-sensitizing potential. This review could be a useful step towards new research on N. sativa and cancer, to include this plant in the dietary treatments in support to conventional therapies, for the best achievement of therapeutic goals.     

Clinical Perspectives of Theranostics

Theranostics is a precision medicine which integrates diagnostic nuclear medicine and radionuclide therapy for various cancers throughout body using suitable tracers and treatment that target specific biological pathways or receptors. This review covers traditional theranostics for thyroid cancer and pheochromocytoma with radioiodine compounds. In addition, recent theranostics of radioimmunotherapy for non-Hodgkin lymphoma, and treatment of bone metastasis using bone seeking radiopharmaceuticals are described. Furthermore, new radiopharmaceuticals for prostatic cancer and pancreatic cancer have been added. Of particular, F-18 Fluoro-2-Deoxyglucose (FDG) Positron Emission Tomography (PET) is often used for treatment monitoring and estimating patient outcome. A recent clinical study highlighted the ability of alpha-radiotherapy with high linear energy transfer (LET) to overcome treatment resistance to beta--particle therapy. Theranostics will become an ever-increasing part of clinical nuclear medicine.     

A Novel N-Tert-Butyl Derivatives of Pseudothiohydantoin as Potential Target in Anti-Cancer Therapy

Tumors are currently more and more common all over the world; hence, attempts are being made to explain the biochemical processes underlying their development. The search for new therapeutic pathways, with particular emphasis on enzymatic activity and its modulation regulating the level of glucocorticosteroids, may contribute to the development and implementation of new therapeutic options in the treatment process. Our research focuses on understanding the role of 11β-HSD1 and 11β-HSD2 as factors involved in the differentiation and proliferation of neoplastic cells. In this work, we obtained the 9 novel N-tert-butyl substituted 2-aminothiazol-4(5H)-one (pseudothiohydantoin) derivatives, differing in the substituents at C-5 of the thiazole ring. The inhibitory activity and selectivity of the obtained derivatives in relation to two isoforms of 11β-HSD were evaluated. The highest inhibitory activity for 11β-HSD1 showed compound 3h, containing the cyclohexane substituent at the 5-position of the thiazole ring in the spiro system (82.5% at a conc. 10 µM). On the other hand, the derivative 3f with the phenyl substituent at C-5 showed the highest inhibition of 11β-HSD2 (53.57% at a conc. of 10 µM). A low selectivity in the inhibition of 11β-HSD2 was observed but, unlike 18β-glycyrrhetinic acid, these compounds were found to inhibit the activity of 11β-HSD2 to a greater extent than 11β-HSD1, which makes them attractive for further research on their anti-cancer activity.     

Novel nonperipheral octa-3-hydroxypropylthio substituted metallo-phthalocyanines: synthesis,characterization, and investigation of their electrochemical,photochemical and computational properties

The current study describes the synthesis, electrochemical, computational, and photochemical properties of octa (3-hydroxypropylthio) substituted cobalt (II) ( 4 ), copper (II) ( 5 ), nickel (II) ( 6 ) and zinc(II) ( 7 ) phthalocyanine derivatives. These novel compounds were characterized by elemental analysis,¹H,¹³C NMR, FT-IR, UV-Vis, and MS. The redox behaviors of these metallo-phthalocyanines were investigated by the cyclic voltammetric method. The optimized molecular structure and gauge-including atomic orbital (GIAO)¹H and¹³C NMR chemical shift values of these phthalocyanines in the ground state had been calculated by using B3LYP/6–31G(d,p) basis set. The outcomes of the optimized molecular structure were given and compared with the experimental NMR values. The photochemical properties including photodegradation and singlet oxygen generation of zinc(II) phthalocyanine were studied in DMSO solution for the determination of its photosensitizer behaviors.     

Surfactant-mediated wetting and spreading: Recent advances and applications

Surfactant-mediated wetting and spreading are ubiquitous. Understanding of these phenomena in-depth allows precise tailoring of wetting performance which can contribute to global challenges in the food supply chain, healthcare, ecology and industrial processes. The first part of this review shows how surfactants can be used to improve the efficacy of fertilisers and pesticides in agriculture, enhanced oil recovery, treatment of lung diseases and extinguishing fires involving flammable liquids. The second part provides analysis of recent studies on wetting and spreading over solid substrates. It includes discussion on the effect of surfactants on the outcome of the impact of liquid drops, the wetting state after impact, autophobic effect and spreading kinetics for both partial and complete wetting, including superspreading. Perspectives of future development in the area of surfactant-assisted wetting and spreading on solid substrates are outlined.     

New Quinoxaline Derivatives as Dual Pim-1/2 Kinase Inhibitors: Design,Synthesis and Biological Evaluation

Proviral integration site for Moloney murine leukemia virus (Pim)-1/2 kinase overexpression has been identified in a variety of hematologic (e.g., multiple myeloma or acute myeloid leukemia (AML)) and solid (e.g., colorectal carcinoma) tumors, playing a key role in cancer progression, metastasis, and drug resistance, and is linked to poor prognosis. These kinases are thus considered interesting targets in oncology. We report herein the design, synthesis, structure–activity relationships (SAR) and in vitro evaluations of new quinoxaline derivatives, acting as dual Pim1/2 inhibitors. Two lead compounds (5c and 5e) were then identified, as potent submicromolar Pim-1 and Pim-2 inhibitors. These molecules were also able to inhibit the growth of the two human cell lines, MV4-11 (AML) and HCT-116 (colorectal carcinoma), expressing high endogenous levels of Pim-1/2 kinases.     

A Cyanine-based Liposomal Nanophotosensitizer for Enhanced Cancer Chemo-Photodynamic Therapy

Currently, chemotherapy is one of the most important treatment modalities for malignant tumors in the clinic, however, it exhibits some shortcomings, such as poor selectivity, limited efficacy and serious adverse effects. Therefore, synergistic therapy and accurate drug delivery at tumor sites become a promising strategy for achieving tumor eradication. Herein, a smart NIR fluorescence imaging-guided nanoliposome was fabricated by encapsulating a chemotherapeutic drug(doxorubicin, DOX), liposomes(L) and a near-infrared(NIR) photosensitizer(CY) to form L@CY@DOX, which could realize enhanced therapeutic efficacy of chemo-PDT in cancer therapy(PDT=photodynamic therapy). L@CY@DOX can induce mitochondrial apoptosis and produce severe toxicity at the cellular level, and L@CY@DOX can enrich in the tumor site, which significantly induces tumor death. In vitro and in vivo studies demonstrated that L@CY@DOX exhibited great antitumor efficacy compared with each one of these monotherapies, indicating that the combination of chemotherapy and PDT possessed potential development prospects and is anticipated in clinical application.     

Built-in piezoelectric field improved photocatalytic performance of nanoflower-like Bi2WO6 using low-power white LEDs

Photocatalysis technology has been proved to be a potential strategy for removal of organic dyes, however high-power light sources are generally necessary to initiate photocatalytic reaction. In this work, we employed an excellent photocatalyst of Bi₂WO₆ with visible light harvest and meanwhile an intrinsic ferroelectricity, which realized the efficient degradation of organic dye via the synergetic photopiezocatalysis. Through coupling the illumination by a low-power (9 W) LED and the ultrasonic vibration (120 W) by an ultrasonic cleaner, the nanoflower-like Bi₂WO₆ composed of ultrathin nanosheets showed a much more enhanced photopiezocatalysis performance for purification of organic dye than the individual photocatalysis and piezocatalysis. Furthermore, the high mineralization efficiency and the good durability of the Bi₂WO₆ catalyst were demonstrated. The possible mechanism of photopiezocatalysis was finally proposed, where the ultrasound-induced piezoelectric field in Bi₂WO₆ drove photo-generated electrons and holes to diffuse along opposite directions, consequently promoting the separation efficiency of charge carriers. This work indicates that the synergetic photopiezocatalysis by coupling irradiation and ultrasonic vibration is a promising strategy to purify organic pollutants in wastewater.