NCI-H460 Lung Research Articles

Self-microemulsifying drug delivery system-based gastroretentive in situ raft of pazopanib with enhanced solubility and bioavailability.

Pazopanib hydrochloride (PZH) is a Biopharmaceutics Classification System class II drug that faces challenges at the formulation forefront including low aqueous solubility (0.043 mg/mL) and poor oral bioavailability (14-39%). The present investigation aimed to develop a self-microemulsifying drug delivery system (SMEDDS) of PZH using a blend of Capryol® 90, Labrasol®, and propylene glycol to improve its solubility. Furthermore, a sustained-release SMEDDS-based gastroretentive floating system was developed and optimized using the Central Composite Design approach of DoE. The optimized SMEDDS-based in situ gelling raft, R-SM-PZH, exhibited minimal floating lag time (3.09 ± 0.8 s), optimal viscosity (1229.4 ± 20.9 cP) and density (0.327 ± 0.15 g/mL) as compared to other formulations under study. Additionally, R-SM-PZH was evaluated for its in vitro dissolution in FaSSGF and FeSSGF, pharmacokinetic profile, and MTT assay (against NCI-H460 lung cancer cells) compared to pure PZH. A 12 h sustained release, three-fold augmentation in dissolution rate and bioavailability, and 15-fold enhancement in cytotoxicity were observed in comparison to pure PZH. Thus, the SMEDDS-based in situ gelling raft presents a promising approach to advancing the developability potential of PZH.

Suppression of Metastasis and Angiogenesis by Taxifolin Ruthenium-p-cymene Loaded PLGA Nanoparticles in Lung Carcinoma.

Flavonoid-based organometallic complexes were revealed to be novel bioactive compounds. The taxifolin ruthenium-p-cymene nanoparticle (TaxRu-NPs) was produced in this study, and the toxicological assessment was done prior to in vivo chemotherapeutic research. Furthermore, the in vitro chemotherapeutic investigation used the A549 and NCI-H460 lung cancer cell lines. The in vitro study found that TaxRu-NPs induced apoptosis in lung cancer cells and hindered their ability to form colonies and migrate. The in vivo study showed that treatment with TaxRu-NPs restored the histological structure of a normal lung with less hyperplasia and lymphocytic infiltration. Furthermore, the treatment downregulated the angiogenic marker VEGF and the cell survival protein β-catenin and upregulated apoptotic markers like p53 and caspase-3. TaxRu-NPs treatment additionally raised the apoptotic index and decreased cancer cell growth. Finally, TaxRu-NPs effectively alleviate lung cancer by activating p53-mediated apoptosis and preventing angiogenesis and metastasis by decreasing the VEGF/β-catenin pathway.

Surface-modified nanoparticles based on ibuprofen prodrug and exploring its anti-inflammatory and anti-cancer potential

Cancer aggressiveness and metastases represent a major cause of death worldwide. Cyclooxygenase-2 (COX-2), and its metabolites significantly influence the tumor development, and metastatic processes. The design and synthesis of prodrugs intended for nonsteroidal anti-inflammatory drugs (NSAIDs) have garnered considerable attention from medicinal chemists, particularly in the last decade. A pH-sensitive drug delivery carrier based on TEG-derivatized ibuprofen Ibu-TEG was synthesized to serve as a dual-delivery system for anti-inflammatory and anticancer agents. The successful synthesis was confirmed through various spectroscopic techniques. This amphiphilic and biodegradable prodrug was self-assembled into micellar nanoparticles (Ibu-TEG-NPs). Their surface was subsequently modified with biocompatible molecules, chitosan (Ibu-TEG-NPs-CHI), and poly-dopamine (Ibu-TEG-NPs-PDA), to enhance the drug efficacy and thermal stability. As-prepared NPs were characterized through FT-IR, DLS, TGA, AFM, and SEM. These surface-modified NPs were significantly active against ROS and NO generation, and showed a lower IC50 value than ibuprofen. Moreover, Ibu-TEG-NPs, Ibu-TEG-NPs-CHI, and Ibu-TEG-NPs-PDA revealed significant therapeutic activity against lung–NCI–H460, and hepato-HepG2 cancer cell lines, demonstrating low IC50 values.

Ginsenoside Rb1 Inhibits the Proliferation of Lung Cancer Cells by Inducing the Mitochondrial-mediated Apoptosis Pathway.

Lung cancer is one of the more common malignant tumors posing a great threat to human life, and it is very urgent to find safe and effective therapeutic drugs. The antitumor effect of ginsenosides has been reported to be a treatment with a strong effect and a high safety profile. This paper aimed to investigate the inhibitory effect of ginsenoside Rb1 on 95D and NCI-H460 lung cancer cells and its pathway to promote apoptosis. We performed the CCK-8 assay, fluorescence staining assay, flow cytometry, scratch healing assay, and Transwell assay to detect the effects of different concentrations of ginsenoside Rb1 on the antitumor activity of 95D and NCI-H460 cells and Western Blot detected the mechanism of antitumor effect. Ginsenoside Rb1 treatment significantly increased the inhibition and apoptosis rates of 95D and NCIH460 cells and inhibited the cell cycle transition from S phase to G2/M. Rb1 induces apoptosis by altering the levels of P53, Bax, Cyto-c, Caspase-8, Caspase-3, Cleaved Caspase-3, Bcl-2, MMP-2, and MMP-9 proteins and activating the external apoptotic pathway. Ginsenoside Rb1 inhibits proliferation and migration and induces apoptosis of 95D and NCI-H460 lung cancer cells by regulating the mitochondrial apoptotic pathway to achieve antitumor activity.

3D tumor spheroids promote activation, expansion, and anti-tumor effects of tumor-infiltrating lymphocytes in vitro

The adoptive immunotherapy mediated by tumor-infiltrating lymphocytes (TILs) has shown definite efficacy against various solid tumors. However, the inefficiency of the conventional method based on in vitro expansion of TILs fails to achieve the cell count and high tumor-killing activity required for therapeutic purposes. This study investigated the effect of 3D tumor spheroids on the activation and expansion of TILs in vitro, aiming to provide a novel approach for the expansion of TILs. We procured TILs and primary tumor cells from surgical samples of lung cancer patients and then compared the impacts of lung cancer cell line NCI-H1975 and primary lung cancer cells cultured under 2D and 3D conditions on the activation, expansion, and anti-tumor activity of TILs. Furthermore, we added the programmed cell death protein 1 (PD-1) antibody into the co-culture of primary tumor cells and TILs within a 3D environment to assess the effects of the antibody on TILs. The results showed that compared with 2D cultured tumor cells, the 3D cultured H1975 cells significantly enhanced the expansion of TILs, increasing the proportion of CD3+/CD8+ cells in TILs to 61.6%. The 3D primary tumor model also enhanced the proportion of CD3+/CD8+ cells in TILs (45.5%, 54.4%), induced apoptosis of tumor epithelial cells and decreased the overall tumor cells survival rate (16.7%) after co-culture. PD-1 antibodies further improved the in vitro expansion capacity of TILs mediated by 3D tumor spheroids, resulting in the proportions of 50.9% and 57.0% for CD3+/CD8+ cells and enhancing the antitumor activity significantly (reducing the overall tumor survival rate to 9.36%). In summary, the use of 3D tumor spheroids significantly promoted the expansion and improved the anti-tumor effect of TILs, and the use of the PD-1 antibody further promoted the expansion and tumor-killing effect of TILs.

Evaluation of Anti-Cancer Potential of Homeopathic Medicines by In-Vitro Study on Human Breast, Lung and Colorectal Cancer Cells

The purpose of this study is to assess the cytotoxic effects of homoeopathic drugs on cancer cell lines by In-vitro experiment. Background: Homoeopathy is a renowned therapeutic approach in many nations across the world. However, the approach has sparked much scientific discussion concerning its efficacy and methods of action. This is particularly true when it comes to the application of homeopathy in cancer treatment. Objective: The purpose of this study was to evaluate the cytotoxic effect of homoeopathic remedies on cancer cells and to emphasise the therapeutic effects of 50 Millesimal potencies. Materials & Methods: Carcinosinum, Conium maculatum, and Asterias rubens were the drugs used in 0/1 potency against the MCF 7 breast cancer cell line. Carcinosinum, Nitric acid, and Ruta were the drugs in 0/1 potency used against the HCT 116 colorectal cancer cell line and the NCI-H460 lung cancer cell line. 90% alcohol medicated on poppy-sized globules, dried fully and used as a control for all cell lines. The cytotoxicity has been assessed using the standard MTT test. Results: The LC50 values of the medicines tested on breast and lung cancer cells were not obtained up to 40000 ppm concentrations, as a result, cytotoxicity evaluation was not possible. The LC50 values of the medicines tested on Colo-rectal cancer cells were obtained around 20,000 ppm concentration and showed a gradual increase in Cell Death with increasing Concentration of exposure of the drugs. As a result, these drugs revealed cytotoxic qualities as well as anti-cancer actions. Conclusion: Despite the objective facts, we cannot reach a definite conclusion about the anti-cancer effectiveness of these drugs in vitro because several aspects of homeopathy's action are unlikely to be replicated in In-vitro study. Determination of reasons for the same or understanding the molecular mechanism of resistance of the cell lines to the cytotoxic effects of the drugs were not within the purview of the study and these can be addressed in future studies. Keywords: Homeopathy, Cancer, MCF-7, HCT 116, NCI-H 460, In-Vitro, Carcinosinum, Conium maculatum, Asteria rubens, Ruta graveolens, Nitric acid, 50 Millesimal Potency, MTT Assay.

Host-specific endophytes of Momordica charantia: A promising source for affordable lung cancer therapeutics

Endophyte-host interactions lead to the production of various bioactive compounds. Thus, endophytes from a medicinal plant such as Momordica charantia, can be promising candidates for producing pharmacological compounds. Our study therefore aims to evaluate these endophytes as sustainable sources of potential low-cost lung cancer drugs. We determined the endophytes associated with M. charantia (fruit and leaf) and assessed anti-inflammatory, antioxidant and antiproliferative potential against NCI-H23 lung cancer cells. LC-Q-TOF-MS of the endophyte extracts was conducted to determine the metabolite profile.Leaf endophyte F. circinatum showed anti-inflammatory (114.29 %), antioxidant (IC50=27.39 µg/ml) and antiproliferative activity (IC50=98.62 µl/ml) with decreased Beclin1 expression (autophagy regulator) in NCI-H23 cells. It produced five anticancer compounds namely linamarin, xestoaminol C, phytosphingosine, cucurbitacin E and margarolic acid. Fruit endophyte E. fergusonii also showed significant antiproliferative potential (IC50=170.8 µl/ml) with upregulated apoptosis regulator Bcl2 expression. It produced compounds such as eplerenone, kuguacin C and H. With the production of triterpenoids momordicine I, cucurbitacin E and kuguaglycoside A, leaf endophyte A. faecalis showed antioxidant potential (IC50=29.65 µg/ml) but limited antiproliferative activity. This is the first report of endophytes-mediated biosynthesis of host-specific compounds in M. charantia including momordicine I, cucurbitacin E and kuguacins, which are known to have anti-cancer properties. Thus, these medicinal plant endophytes can be low-cost sustainable candidates with anti-cancerous potential, especially against lung cancer.

Pachira aquatica: biological activity and chemical composition of leaves, flowers, and seeds

The chemical composition of Pachira aquatica crude extracts flowers, leaves, and seeds was obtained by UHPLC-ESI/qTOF and GC/MS. The antiproliferative activity was evaluated against the human tumour cell lines AGS (gastric), CaCo-2 (colorectal), MCF-7 (breast), and NCI-H460 (lung). The anti-inflammatory and cellular antioxidant activities were also studied. Flavonoids, phenolic acids, coumarins, and saturated fatty acids were identified in the samples. The concentration of extracts responsible for inhibiting 50% of nitric oxide production ranged from (149 to > 400 µg mL−1). Antiproliferative activity against the tumour cell lines was: AGS (GI50 175 to > 400 µg mL−1), Caco-2 (GI50 215 to > 400 µg mL−1), MCF7 (GI50 232 to > 400 µg mL−1) and NCI-H460 (GI50 208 to > 400 µg mL−1). Cellular antioxidant activity remained between 73% to > 2000%. The selectivity index (SI) ranged from 1.00 to 2.78, indicating low antiproliferative activity.

Cytotoxic constituents from the fruit of Solanum aculeastrum

A new triterpene, aculeastrumone A (1), a new triterpene saponin aculeastrumoside A (2), and eleven known compounds (3–13) were isolated from MeOH/Water (80/20) extract of the fruits of Solanum aculeastrum (Solanaceae). Their structures were established by detailed 1D and 2D NMR spectroscopic studies and mass spectrometry. The isolated compounds were evaluated against three human cancer cells ((MCF-7 (breast cancer), NCI-H460 (lung cancer), and Hela (cervical cancer)) and normal human fibroblast (BJ) cell lines. Among them, saponins 2–5, 7–8, and Carpesterol 10 possess significant cytotoxic activity with IC50 ≤ 10 µM against the three cancer cell lines.

Anti-cancer activity and mechanism of flurbiprofen organoselenium compound RY-1-92 in non-small cell lung cancer.

Lung cancer is one of the malignancies with the highest incidence and mortality rates worldwide, and non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancer types. In this study, the anti-cancer activities of a novel flurbiprofen organic selenium compound, RY-1-92, on NSCLC cells and a mouse model and the underlying molecular mechanisms were explored. We found that compound RY-1-92 can significantly inhibit the viability, colony formation and migration of A549, NCI-H460 lung cancer cells. Flow cytometry analysis showed that RY-1-92 also can lead to G2/M cell cycle arrest and apoptosis induced in lung cancer cells. Further, RY-1-92 can decrease the tumor size in the Lewis lung cancer tumor-bearing mouse model. The protein levels of cell cycle-related proteins CDK1/cyclinB1 were decreased, while the apoptosis-related protein BAX was increased dramatically after RY-1-92 treatment in vitro and in vivo. Impressively, it was found that TRPV1 might act as a potential molecular target of RY-1-92 using the SEA search server. Furthermore, down-regulation on TRPV1 and its downstream associated factors including p-AKT protein and MAPK signaling pathway-related proteins after RY-1-92 treatment was observed in A549, NCI-H460 lung cancer cells. Taken together, our findings shed light on the potential of RY-1-92 as a novel small molecular drug for NSCLC, and it is of great significance for its further in-depth research and development.

3,3',5,5'-Tetramethoxybiphenyl-4,4'diol triggers oxidative stress, metabolic changes, and apoptosis-like process by reducing the PI3K/AKT/NF-κB pathway in the NCI-H460 lung cancer cell line

Lung cancer is one of the leading causes of cancer-related deaths in men and women worldwide. Current treatments have limited efficacy, cause significant side effects, and cells can develop drug resistance. New therapeutic strategies are needed to discover alternative anticancer agents with high efficacy and low-toxicity. TMBP, a biphenyl obtained by laccase-biotransformation of 2,6-dimethoxyphenol, possesses antitumor activity against A549 adenocarcinoma cells. Without causing damage to sheep erythrocytes and mouse peritoneal macrophages of BALB/c mice. In addition to being classified as a good oral drug according to in-silico studies. This study evaluated the in-vitro cytotoxic effect of TMBP on lung-cancer cell-line NCI-H460 and reports mechanisms on immunomodulation and cell death. TMBP treatment (12.5–200 μM) inhibited cell proliferation at 24, 48, and 72 h. After 24-h treatment, TMBP at IC50 (154 μM) induced various morphological and ultrastructural changes in NCI-H460, reduced migration and immunofluorescence staining of N-cadherin and β-catenin, induced increased reactive oxygen species and nitric oxide with reduced superoxide radical-anion, increased superoxide dismutase activity and reduced glutathione reductase. Treatment also caused metabolic stress, reduced glucose-uptake, intracellular lactate dehydrogenase and lactate levels, mitochondrial depolarization, increased lipid droplets, and autophagic vacuoles. TMBP induced cell-cycle arrest in the G2/M phase, death by apoptosis, increased caspase-3/7, and reduced STAT-3 immunofluorescence staining. The anticancer effect was accompanied by decreasing PI3K, AKT, ARG-1, and NF-κB levels, and increasing iNOS. These results suggest its potential as a candidate for use in future lung anticancer drug design studies.

α-Conotoxin recombinant protein ImI-AFP3 efficiently inhibits the growth and migration of lung cancer cells

α-Conotoxin ImI is a selective antagonist of alpha7 nicotinic acetylcholine receptor (α7 nAChR) that is involved in cancer development. Human alpha fetoprotein domain 3 (AFP3) is a prototype of anticancer agents. In an effort to design drugs for anticancer treatments, we fused the ImI peptide to AFP3 as a fusion protein for testing. The fusion protein (ImI-AFP3) was highly expressed in the insect Bac-to-Bac system. The purified fusion protein was found to have improved anticancer activity and synergized with the drug gefitinib to inhibit the growth and migration of A549 and NCI-H1299 lung cancer cells. Our data have demonstrated that the recombinant protein ImI-AFP3 is a promising candidate for drug development to suppress lung cancer cell growth, especially to suppress hepatoid adenocarcinoma of the lung (HAL) cell growth.

Schweinfurthiamide, a new alkaloid isolated from the tuber roots of Asparagus flagellaris Baker (Liliaceae)

The phytochemical investigations of the tuber roots of Asparagus flagellaris led to the isolation of a new alkaloid, schweinfurthiamide (1) and eight known compounds. The structures of the isolated compounds were elucidated using spectroscopic techniques 1D and 2D NMR (1H, 13C, COSY, HMBC, HMQC, HSQC-TOCSY). The absolute configuration of 1 was unambiguously determined using DP4+ calculations. Compound 1 showed significant cytotoxicity against MCF-7 (breast cancer), NCI-H460 (lung cancer), and Hela (cervical cancer) cancer cell lines with IC50 values of 1.18 ± 0.02 µM, 2.25 ± 0.19 µM, and 4.23 ± 0.26 µM, respectively and no toxicity against normal human fibroblast (BJ).

Regulation of cytokinesis and necroptosis pathways by diosgenin inhibits the proliferation of NCI-H460 lung cancer cells

AimOvercoming resistance to apoptosis and antimitotic chemotherapy is crucial for effective treatment of lung cancer. Diosgenin (DG), a promising phytochemical, can regulate various molecular pathways implicated in tumor formation and progression. However, the precise biological activity of DG in lung cancer remains unclear. This study aimed to investigate the antiproliferative activity of DG in NCI-H460 lung carcinoma cells to explore the underlying antimitotic mechanisms and alternative cell death pathways. Materials and methodsIn a 2D culture system, we analyzed cell viability, multinucleated cell frequency, cell concentration, cell cycle changes, cell death induction, intracellular reactive oxygen species (ROS) production, and nuclear DNA damage, particularly in relation to target gene expression. We also evaluated the antiproliferative activity of DG in a 3D culture system of spheroids, assessing volume changes, cell death induction, and inhibition of proliferation recovery and clonogenic growth. Key findingsDG reduced cell viability and concentration while increasing the frequency of cells with multiple nuclei, particularly binucleated cells resulting from daughter cell fusion. This effect was associated with genes involved in cytokinesis regulation (RAB35, OCRL, BIRC5, and AURKB). Additionally, DG-induced cell death was linked to necroptosis, as evidenced by increased intracellular ROS production and RIPK3, MLKL, TRAF2, and HSPA5 gene expression. In tumor spheroids, DG increased spheroid volume, induced cell death, and inhibited proliferation recovery and clonogenic growth. SignificanceOur study provides new insights into the biological activities of DG in lung cancer cells, contributing to the development of novel oncological therapies.

Platinum-Acridine Agents with High Activity in Cancers Expressing the Solute Carrier MATE1 (SLC47A1).

Platinum-acridine anticancer agents (PAs) containing acyclic (1 and 3) and heterocyclic (R)-3-aminopiperidine (2) and 2-iminopyrrolidine (4) based linker moieties were studied. Similar to 1, rigidified 2 shows a strong positive correlation between potency and SLC47A1 (multidrug and toxin extrusion protein 1, MATE1) gene expression levels across the NCI-60 panel of cancer cell lines. All derivatives show nanomolar activity in HepG2 (liver), NCI-H460 (lung), and MDA-MB-436 (breast), which express high levels of SLC47A1 (Cancer Cell Line Encyclopedia, CCLE). The PAs are up to 350-fold more potent than cisplatin. In a MATE1 inhibition assay, a significant reduction in activity is observed in the three cancer cell lines (4000-fold lower for HepG2). Molecular docking experiments provide insight into the compatibility of the structurally diverse set of PAs with MATE1-mediated transport. MATE1 is a predictive marker and actionable target that sensitizes cancer cells regardless of the tissue of origin to PAs.

TL-532, a novel specific Toll-like receptor 3 agonist rationally designed for targeting cancers: discovery process and biological characterization.

Toll-like receptor 3 (TLR3) is an innate immune receptor that recognizes double-stranded RNA (dsRNA) and induces inflammation in immune and normal cells to initiate anti-microbial responses. TLR3 acts also as a death receptor only in cancer cells but not in their normal counterparts, making it an attractive target for cancer therapies. To date, all of the TLR3-activating dsRNAs used at preclinical or clinical stages have major drawbacks such as structural heterogeneity, toxicity, and lack of specificity and/or efficacy. We conducted the discovery process of a new family of TLR3 agonists that are chemically manufactured on solid-phase support and perfectly defined in terms of sequence and size. A stepwise discovery process was performed leading to the identification of TL-532, a 70 base pair dsRNA that is potent without transfection reagent and is highly specific for TLR3 without activating other innate nucleic sensors such as RIG-I/MDA5, TLR7, TLR8, and TLR9. TL-532 induces inflammation in murine RAW264.7 myeloid macrophages, in human NCI-H292 lung cancer cells, and it promotes immunogenic apoptosis in tumor cells in vitro and ex vivo without toxicity towards normal primary cells. In conclusion, we identified a novel TLR3 agonist called TL-532 that has promising anticancer properties.

Abstract ND02: CTX112 and CTX131: Next-generation CRISPR/Cas9-engineered allogeneic (allo) CAR T cells incorporating novel edits that increase potency and efficacy in the treatment of lymphoid and solid tumors

Abstract Allo CAR T cells represent an “off-the-shelf” treatment option that addresses the unmet need for immediately available, potentially curative therapies. CRISPR Therapeutics’ first generation allo CAR T cell products, CTX110® (CD19-directed) and CTX130TM (CD70-directed), have shown encouraging efficacy in ongoing clinical trials (NCT04035434, NCT04502446, NCT04438083), including complete and durable responses in B- and T-cell lymphoma and renal cell carcinoma (RCC). However, T cell exhaustion, occurring even prior to CAR T cell clearance by the immune system, can result in diminished efficacy and loss of response, especially in patients with high tumor burden. To address this challenge, we performed a CRISPR screen to discover potency edits to incorporate into next-generation CAR T programs. Herein, we describe two novel allo CAR T cell therapies, CTX112TM and CTX131TM, that incorporate the synergistic potency edits Regnase-1 and TGFBR2. CTX112 (CD19-directed) and CTX131 (CD70-directed) are produced from healthy donor T cells modified ex vivo using CRISPR/Cas9 gene editing. Regnase-1 and TGFBR2 have been added to edits in our first-generation programs: TRAC (T-cell receptor to prevent GvHD), B2M (MHC class I to reduce T-cell mediated rejection), and CD70 (to eliminate fratricide and increase potency), and site-specific CAR insertion at the TRAC locus using an AAV template. These modifications result in next-generation CAR-T therapies that have demonstrated increased potency, prolonged persistence, and sustained antitumor activity. Disruption of Regnase-1 improves functional persistence by increasing cellular expansion potential, correlating with central memory phenotype. TGFBR2 disruption allows CAR T cells to avoid tumor microenvironment suppression. In combination, these edits increase potency at least 10-fold. In addition, long-term maintenance of CM phenotype enables efficient manufacturing. CTX112 and CTX131 demonstrated increased expansion, resistance to exhaustion, and elevated effector cytokine release when tested using in vitro and in vivo models. CTX112 increased survival and tumor regression in CD19+ Nalm6-Luciferase leukemia and Jeko-1 lymphoma models relative to control CAR T cells with only Regnase-1 or TGFBR2 disruption. Similarly, in a “rechallenge model” in which xenografts were serially implanted following a single dose of CAR T cells, CTX131 caused complete regression of NCI-H1975 lung, A498 RCC, and Caki-2 RCC tumors. No evidence of clonal expansion nor cytokine independent growth occurred, suggesting multiplex edited CTX112 and CTX131 cells are safe for clinical use. In summary, CTX112 and CTX131 are the first CAR T programs to incorporate novel Regnase-1 and TGFBR2 edits, with the potential to increase expansion and functional persistence, which may translate clinically to deeper, more durable responses. CTX112 will be developed in patients with B cell malignancies, and CTX131 will be developed in patients with advanced solid tumors, including RCC. Citation Format: Jonathan A. Terrett, Demetrios Kalaitzidis, Mary-Lee Dequeant, Sushant Karnik, Mohammed Ghonime, Changan Guo, Robert Chain, Heidi Heath, Nivedita Jaishankar, Rachel Yuen, Davis Settipane, Zinkal Padalia, Lauren Zakas, Meghna Kuppuraju, Paul Tetteh, Chandirasegaran Massilamany, Brigid McEwan, Glenn Leary, Henia Dar, Daniel Ferulo, Melanie Allen, Kimberley Tipton, Laura Serwer, Thao Nguyen, Melanie Butler-Gauthier, Parin Sripakdeevong, Shashwat D. Nagar, Yin Tang, Hemangi Chaudhari, Nicole Flanagan, Elaine Huang, Shashwant Phuyal, Elizabeth Koch, Andrew Dunn, Erisa Sula, Jacob Waldman, Cristian Loaiza, Maria Lei Zhang, Erin Thorstensen, Keith Steiger, Katie Schum, Kayla Urbaez, Mark Benton, Anna Ma, Sarah Cohen, Annie Weaver, Christopher Finch, Phuong Khanh Morrow. CTX112 and CTX131: Next-generation CRISPR/Cas9-engineered allogeneic (allo) CAR T cells incorporating novel edits that increase potency and efficacy in the treatment of lymphoid and solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr ND02.

Acyclic enediynes fused to triazole and benzothiophene containing propargylamine moieties

Synthesis of 3-(5-triazolyl)- and 3-(3-benzothienyl)-propargylamines includes the Mannich reaction of the corresponding ethynyl derivatives with diaminomethanes. The MTT test of the synthesized compounds toward the viability of NCI-H460 lung carcinoma cells and WI-26 VA4 normal lung fibroblast cells reveals one of them possessing a notable cytotoxic activity.

Screening of Anti-cancer Activity of rGO–Bi2O3 Nanocomposite on Apoptosis in A549 and NCI-H460 Lung Cancer Cell Lines

Screening of Anti-cancer Activity of rGO–Bi2O3 Nanocomposite on Apoptosis in A549 and NCI-H460 Lung Cancer Cell Lines

Antiproliferative activity from five Myrtaceae essential oils

The Myrtaceae plants are cultivated for their edible fruits and folk medicinal uses. Likewise, their leaves, flowers, and fruit essential oils (EOs) are described to have antiproliferative, antimicrobial, and antioxidant activities. This work analyzed the chemical compositions and evaluated the antiproliferative activities of essential oils (EO) of Myrcia bella Cambess, Myrcia fallax (Rich.) DC., Myrcia guianensis (Aubl.) DC., Eugenia aurata O. Berg, and Eugenia punicifolia (Kunth) DC, from the Brazilian Cerrado. EOs were obtained by leaf hydrodistillation and analyzed by Gas Chromatography-Mass Spectrometry (GC-MS) plus Gas Chromatography-Flame Ionization Detector (GC-FID). The major component in M. bella was α-cadinol (14.4%); in Myrcia fallax (Rich.) DC., guaiol acetate (14.4%); and in M.guianensis, (E)-iso-g‑bisabolene (17.5%). For E. aurata and E. punicifolia, bicyclogermacrene (25.3%) and (E)-caryophyllene (18%), respectively, were the most relevant chemical constituents. The EOs were tested against the human tumor cell lines UACC-62 (melanoma), MCF7 (breast), 786-0 (kidney), NCI-H460 (lung), OVCAR-3 (ovarian), HT29 (colon), and K562 (leukemia) and one non-tumor cell line (VERO). Eugenia aurata presented the most promising effect against HT29 (TGI = 1.5 mg/mL), K562 (TGI = 5.0 mg/mL), and no toxicity against non-tumor VERO cells (TGI> 250 mg/mL). For the other EOs, moderate to no activity was observed. So, in conclusion, E. aurata EOs revealed a good potential for anticancer applications.