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The Dysoxylum genus that belongs to the Meliaceae family is widely distributed from India and Sri Lanka throughout Malaysia and Indonesia to Australia and New Zealand. Numerous types of compounds have been reported, including sesquiterpenoids, limonoids, triterpenoids, and alkaloids. One of the members of this genus is Dysoxylum alliaceum. Reports on the phytochemical constituents of this species are limited. During our search for naturally occurring tropical plant compounds with intriguing structures and biological properties, the stembark of D. alliaceum, which showed cytotoxic activity against MCF-7, A549 and CV-1 cell lines, was investigated. This paper also describes the chemical structure of the isolated compounds using HR-ESI-MS, FTIR, and NMR. As a result, eight triterpenoid compounds belonging to tirucallane-type (1-8) were identified, including cneorin-NP36 (1) toonapubesin A (2), toonapubesin B (3), chisopanin M (4), 21 α-methylmelianodiol (5), 21 β-methylmelianodiol (6), hispidone (7), and odoratone (8). These compounds are newly discovered in this plant. Furthermore, toonapubesin A (2) showed the highest selectivity against A549 cancer cell lines with IC50 value of 7.81±0.02 μM, resulting in no activity towards CV-1 cells. The current result could indicate that this plant produces potential natural product compounds with anticancer properties. [ABSTRACT FROM AUTHOR]

This paper reports for the first time the immunomodulatory and cytotoxic effects of two previously isolated compounds from the stem of Peltophorum pterocarpum and characterized as bergenin (1) and cinchonain Ia (2). The immunomodulatory capacity of these two compounds was assessed based on their ability to inhibit IL-2 release from RAW264.7 cells. The results demonstrated that cinchonain Ia (2) possesses distinctly immunomodulatory effects in vitro since this compound strongly inhibited IL-2 cytokine level (at concentrations of 4.0 and 0.8 μg/mL) (P<0.01 and P<0.05), while it was increased up to 8.84 time at the 100 μg/mL concentration. Additionally, compound 2 showed a weak cytotoxic effect against 5 human cancer cells (A549, Huh-7, T24, 8505, and SNU-1) with the IC50 values between 39.19 g/mL and 60.44 μg/mL. [ABSTRACT FROM AUTHOR]

Metastasis, the spread of cancer cells from a primary tumor to secondary location(s) in the human organism, is the ultimate cause of death for the majority of cancer patients. Although studied for more than 180 years, increasing efforts in recent years have significantly contributed to a better understanding of this aspect of tumor development. Adding to this understanding, our current paper proposes a multi-type branching process model, through which various topics, such as extinction of cancer cell clones, occurrence of successful mutants, and immediate risk of escaping extinction, are investigated. More specifically, the relationship between the lifespan distribution of cancer cells with subcritical reproduction and the waiting time until the occurrence of a mutant (having supercritical reproduction) cancer cell, escaping extinction, is highlighted. The theoretical studies formulated in this paper may allow our model to be tailored to real data available for particular kinds of cancer and chemotherapy. [ABSTRACT FROM AUTHOR]

This paper intended to study RBPMS-AS1 in lung cancer (LC) radiosensitivity. LC cells were transfected with RBPMS-AS1 overexpression plasmid and miR-19a-3p mimic and treated with radiation. PTEN, AKT, p-AKT, RBPMS-AS1, and miR-19a-3p expressions were detected via Western blot and qRT-PCR. The localization of RBPMS-AS1 in cells was determined through fluorescence in situ hybridization assay. The targeting relationships of RBPMS-AS1 and miR-19a-3p/miR-19a-3p and PTEN were determined through RIP and dual luciferase reporter analysis. Cell survival, viability, and apoptosis were assessed through colony formation, CCK-8, and flow-cytometry assays. RBPMS-AS1 was downregulated in LC and mainly distributed in cytoplasm. RBPMS-AS1 targeted miR-19a-3p in LC cells. Radiation suppressed LC cell survival, viability, and induced apoptosis, as overexpressed RBPMS-AS1 performed the similar effects and enhanced those effects induced by radiation. MiR-19a-3p mimic reversed the effect of overexpressed RBPMS-AS1 on enhancing radiation-induced LC cell apoptosis. MiR-19a-3p targeted PTEN and miR-19a-3p mimic reversed the effect of overexpressed RBPMS-AS1 on PTEN and phosphorylation of AKT in LC cells. Overexpressed RBPMS-AS1 sponged miR-19a-3p to increase cell radiosensitivity in LC via regulating PTEN/AKT axis. [ABSTRACT FROM AUTHOR]

Long non-coding RNA LIFR-AS1 is low-expressed in many cancers, but its functions in papillary thyroid carcinoma (PTC) were not defined and require further study. The relationship between LIFR-AS1 expression and clinicopathological characteristics of patients with PTC was statistically analyzed. The downregulation of LIFR-AS1 in PTC tissues and cell lines was predicted by bioinformatics analysis and verified by qRT-PCR. After overexpressing or silencing LIFR-AS1, the regulatory role of LIFR-AS1 in PTC was examined by performing MTT, colony formation, wound healing, Transwell, ELISA, tube formation and xenograft tumor experiment. MiR-31-5p and SID1 transmembrane family member 2 (SIDT2) expressions in PTC tissues or cell lines were detected by qRT-PCR, Western blot, or in situ hybridization. The relationship between miR-31-5p and LIFR-AS1/SIDT2 was predicted by LncBase, TargetScan or Pearson correlation test and then verified by Dual-Luciferase Reporter assay, RNA pull-down assay and qRT-PCR. The regulatory effect of LIFR-AS1/miR-31-5p/SIDT2 axis on the biological behaviors of PTC cells was confirmed by functional experiments and rescue experiments mentioned above. The tumor size and lymphatic metastasis were correlated with LIFR-AS1 overexpression. Overexpressed LIFR-AS1 suppressed tumorigenesis in vivo. LIFR-AS1 and SIDT2 expressions were suppressed in PTC tissues, while that of miR-31-5p was elevated in PTC tissues. LIFR-AS1 was negatively correlated with miR-31-5p. LIFR-AS1 sponged miR-31-5p to upregulate SIDT2, thereby inhibiting the viability, proliferation, migration, invasion, and the secretion of vascular endothelial growth factor (VEGF) of PTC cells and angiogenesis of human umbilical vein endothelial cells (HUVECs). This paper demonstrates that LIFR-AS1/miR-31-5p/SIDT2 axis modulated the development of PTC. [ABSTRACT FROM AUTHOR]

Biological populations under stress often face certain extinction unless they adapt toward unfavorable circumstances. In some scenarios such adaptation can assume the form of mutations within the genome of the population (e.g., cancer cells resisting chemotherapy, viruses developing resistance toward a vaccine), while in other scenarios adaptation can be in the form of movement toward some physical location (e.g., spreading of cancer cells to parts of the organism unaffected by treatment, animal populations fleeing polluted areas or areas struck by disaster). Regardless of the particular situation, it is often the case that cells/individuals with different levels of adaptation (which we may group into types) emerge among the cells/individuals of a stressed population. We propose a decomposable multi-type Sevastyanov branching process (possibly with multiple supercritical types) for modeling relevant aspects of the dynamics of such populations. The branching process developed within this paper is a generalization of the decomposable multi-type age-dependent branching process with a single supercritical type considered in Slavtchova-Bojkova and Vitanov. With respect to Slavtchova-Bojkova and Vitanov, we introduce additional, possibly supercritical, types into the interaction scheme between types, further, we incorporate possible dependence of the reproductive capabilities of cells/individuals from their age. We obtain a system of integral equations for the probability generating function of the new process and accordingly expand previous results from Slavtchova-Bojkova and Vitanov concerning probabilities of extinction, number of occurred mutations, waiting time to escape mutant, and immediate risk of escaping extinction. We also provide a general numerical scheme for calculating obtained systems of integral equations. [ABSTRACT FROM AUTHOR]

Phytochemical investigation of the seeds of Coix lacryma-jobi var. lacryma-jobi resulted in the isolation of eight compounds, including two new structures, coixdines A-B (1-2) and six known compounds (3-8). The structures of these compounds were determined by 1 D and 2 D NMR spectra referring to the literatures, together with HR-MS analysis. Coixdine A and B are first examples of spermidine skeleton in genus Coix. In the present paper, all compounds were evaluated for the cytotoxicity against two cancer cell lines (CT-26 and BxPC-3) in vitro, and none of the compounds exhibited obvious cytotoxic activity. The present investigation suggests that these amides seem to be of great chemotaxonomic value for C. lacryma-jobi. [ABSTRACT FROM AUTHOR]

Differential analysis techniques are commonly used to offer scientists a dimension reduction procedure and an interpretable gateway to variable selection, especially when confronting high-dimensional genomic data. Huanget al.used a gene expression profile of breast cancer cell lines to identify genomic markers which are highly correlated with in vitro sensitivity of a drug Dasatinib. They considered three statistical methods to identify differentially expressed genes and finally used the results from the intersection. But the statistical methods that are used in the paper are not sufficient to select the genomic markers. In this paper we used three alternative statistical methods to select a combined list of genomic markers and compared the genes that were proposed by Huanget al.We then proposed to use sparse principal component analysis (Sparse PCA) to identify a final list of genomic markers. The Sparse PCA incorporates correlation into account among the genes and helps to draw a successful genomic markers discovery. We present a new and a small set of genomic markers to separate out the groups of patients effectively who are sensitive to the drug Dasatinib. The analysis procedure will also encourage scientists in identifying genomic markers that can help to separate out two groups. [ABSTRACT FROM AUTHOR]

Cell lines have been considered excellent research models in many areas of biomedicine and, specifically, in the study of carcinogenesis. However, they cease to be effective models if their behavior changes. Although studies on the cross-contamination of cell lines originating from different tissues have been performed, little is known about cell lines derived from cervical neoplasia. We know that high-risk HPV (HR-HPV) is associated with the development of this type of cancer. This link between HPV infection and cancer was first established over 35 years ago when HPV16 DNA was found to be present in a large proportion of cervical cancer biopsies. The present review paper aims to report the status of the establishment, authenticity, and characterization of cervical cancer (CC) cell lines. This is a systematic review of articles on the establishment, authenticity, and characterization of CC cell lines, published from 1960 to date in the databases and in cell repository databases. 52 cell lines were identified in the literature. Only 25 cell lines were derived from cervical neoplasia, of which only 45.8% have a reported identity test (genomic fingerprint). Despite the increase in the establishment of cell lines of cervical neoplasia and the standards for the regulation of these study models, the criteria for their characterization continue to be diverse. [ABSTRACT FROM AUTHOR]

Introduction: Currently, basic understanding of heterogeneity and complexity of tumors is depicted at molecular, cellular, genetic, epigenetic and metabolic adaptations levels. Areas covered: There are appreciable numbers of views to pinpoint signaling axis that support metabolic adaptations of cancer cells in response to environmental pressures including nutritional factors and drug treatments. Specifically, nutritional deprivation and autophagy in certain types of cancer are linked to the abilities of cancer cells to use arginine in an auxotrophic or prototrophic manner. Expert opinion: Hence, this paper highlights the current scope of arginine- and autophagy-centered metabolic adaptations across tumor types and possible avenues to bring tumors towards cytotoxic or cytostatic death. [ABSTRACT FROM AUTHOR]

In this paper, we study a distributed optimal control problem of a coupled nonlinear system of reaction-diffusion equations. The system consists of three partial differential equations to represent cancer cell density, matrix-degrading enzymes concentration and oxygen concentration, and an ordinary differential equation to describe the extracellular matrix concentration. Our aim is to minimize the growth of cancer cells by controlling the production of matrix-degrading enzymes. First, we prove the existence and uniqueness of solutions of the direct problem. Then, we prove the existence of an optimal control. Finally, we derive the first-order optimality conditions and prove the existence of weak solutions of the adjoint problem. [ABSTRACT FROM AUTHOR]

Nanomaterials are frequently demonstrating advantages for drug delivery applications due to their high potential in treatment of variety of cancers. This paper reports the development of termoresponsive nanocomposites from graphene/(β-Cyclodextrin)-star poly(methyl methacrylate)-block-poly(N-Isopropylacrylamide) GO/β-Cyclodextrin-star-PMMA-b-PNiPAM via reversible addition fragmention chain transfer (RAFT) polymerization. The drug loading efficiency of GO/nanocomposites for DTX was high and 85% efficiency was obtained. The cytotoxicity of the DTX against breast cancer cell line (MCF7) was exhibited by using the cytotoxicity assays (MTT), DAPI staining, and cellular uptake. These intelligent GO/nanocomposites with increased anticancer activity could be chosen as an ideal nanocarrier for anticancer therapy. [ABSTRACT FROM AUTHOR]

Resistance to anti-cancer therapy is a major challenge for cancer treatment. Many studies revealed that macroautophagy/autophagy inhibition can overcome autophagy-mediated therapy resistance, but these efforts have not yet led to the success of clinical applications. In a recent paper, we established a 37-gene autophagy signature to estimate the autophagy status of approximately 10,000 tumor samples across 33 cancer types from The Cancer Genome Atlas, and muti-omics characterization reveals that autophagy induction may also sensitize cancer cells to anti-cancer drugs. These findings provide a comprehensive resource of molecular alterations associated with autophagy and highlight the potential to utilize drug sensitivity induced by autophagy to overcome the resistance of cancer therapy. [ABSTRACT FROM AUTHOR]

In this paper, we developed a novel strategy of preparing doxorubicin (DOX) nanocrystal (NC) exerting spherical particles with a diameter of 102 nm, which experienced following coating of chondroitin sulphate derivative (CSOA) shell via electrostatic and hydrophobic interactions. Such multifunctional outerwear resulted in drug nanocapsules with high drug loading content up to 70% and high colloidal stability under physiological conditions. It exhibited accelerated drug release behaviour when dispersing in hyaluronidase (HAase) containing medium or incubated with cancer cells. CSOA/NCs were effectively taken up by cancer cells via CD44 receptor-mediated endocytosis, but were rarely internalised into normal fibroblasts. With the comparison of typical drug-loaded micelles system (DOX/PEG-PCL), CSOA/NCs showed greater inhibition to cancer cells due to the targeted and sensitive drug delivery. [ABSTRACT FROM AUTHOR]

Found in various natural food products, many in vitro evidence indicated that resveratrol (RES) has been linked to neuroprotective and cardioprotective effects and prevent cancer development. However, human clinical trials have been conducted with varying results, making the usage of RES controversial. In this paper, we demonstrated that the drug RES could be conjugated with the high levels of endogenous GS• in cancer cells. 5,5-Dimethyl-1-Pyrroline-N-Oxide (DMPO) was employed to capture the GS•. The molecular mechanism of the reaction between RES and GS• was further studied by UV-Vis spectrometry, mass spectrometry and Density Functional Theory (DFT) calculations. Besides, the formation of the adduct GS-RES in cancer cell was obtained when RES was added during incubation. Further study indicated that over 77.6% of the RES was consumed in cancer cells. This study suggested that endogenous GS• may be one of the important factors to cause the depletion of anti-tumour drugs during chemotherapy, which should be paid special attention in clinical therapeutics and drug development. [ABSTRACT FROM AUTHOR]

Active research is invested in early diagnosis of malignant cells in order to allow scope for effective treatment. The electrical impedance measurements and the modeling techniques used to perform the calculation for dielectric permittivity, conductivity and relaxation frequency aids in the differentiation of malignant and healthy cells. The literature showed a general trend in data with malignant cells having higher electrical conductivity and lower dielectric permittivity than its surrounding healthier cells. However, the relaxation frequency that correlates with the dielectric loss factor was found twice in magnitude for cancer cells than healthy cells. The water content of a cancer cell is found higher and hence correlates with the shift in the relaxation time. The intracellular sodium ion concentration is also realized to be higher for malignant cells than normal cells and accounts for the depolarized transmembrane potential. Hence, this paper forms the framework for future technological innovation that can be taken into account to actively diagnose cancer cell. [ABSTRACT FROM AUTHOR]

In this paper, the synthesis, antiproliferative activity in vitro and structure–activity relationship of N-methylated 2-benzimidazoles related to 2,3-acrylonitriles and benzimidazo [1,2-a]quinolines bearing halogeno or amino substituent is described. Amino-substituted N-methylated benzimidazo[1,2-a]quinolines were prepared by using microwave-assisted amination from corresponding halogeno-substituted precursors. All newly prepared compounds were tested against tree human cancer cells to assess their antiproliferative activity in vitro. Compounds 4a and 4b display certain selective activity against MCF-7 cells together with the N,N-dimethylamino-substituted derivative 4e with IC50 0.4 µM. Cyclic derivatives 7a, 7b, and 8 were more active with IC50 in micromolar range of concentrations but without any selectivity among tested cells. Among the most active compounds, 2-amino-substituted derivatives 9a and 9b were also selective against HCT116 cells with IC50 values 0.2 µM and 0.4 µM, respectively. The influence of compounds 9a and 9b on the cell cycle of HCT 116 revealed that both compounds induced a strong reduction of the percentage of cells in S phase, along with the induction of cell death. [ABSTRACT FROM AUTHOR]

In this paper, the self-assembled folate-biotin-quaternized starch nanoparticles (FBqS NPs) were used as carrier system of doxorubicin (DOX) and siRNAIGF1R for the codelivery of both into human lung adenocarcinoma cell lines (A549 cells) in vitro. The cytotoxicity, targeted ligand competition, cell proliferation inhibition, cellular uptake, endocytosis mechanism and target protein suppression of drug-loaded FBqS NPs were evaluated in detail. Compared with several other drug formulations under same condition, siRNAIGF1R/DOX/FBqS NPs exhibited the greatest cytotoxicity to A549 cells and the cytotoxicity was competitively inhibited by free folate in dose-dependent manner. The A549 cells treated by siRNAIGF1R/DOX/FBqS NPs showed the lowest cell proliferation capacity. The energy-dependent clathrin- and caveolae-mediated endocytosis might be the primary cellular uptake mechanism of drug-loaded FBqS NPs. The expression of IGF1R protein in A549 cells treated by siRNAIGF1R/FBqS NPs declined dramatically. So the FBqS NPs were expected as the co-carrier system of chemotherapeutants and siRNAs for future clinical application. [ABSTRACT FROM AUTHOR]

In paper preparation and characterization of hydrogels based on chitosan of bees' origin and modified with caffeine have been reported. Surface morphology of hydrogel materials including their average porosity has been determined. Furthermore, study of the release of caffeine from hydrogels in different environments was determined. Subsequently, studies on cytotoxicity of hydrogels to fibroblasts and cancer cells has been defined. Based on the research it can be stated that honeybees constitute an interesting material that could be a valuable source of chitosan. Prepared hydrogels had a significant negative impact on the cancer cells and did not affect negatively on fibroblasts. [ABSTRACT FROM AUTHOR]

Despite the success of immunotherapies for melanoma in recent years, there remains a significant proportion of patients who do not yet derive benefit from available treatments. Immunotherapies currently licensed for clinical use target the adaptive immune system, focussing on Tcell interactions and functions. However, the most prevalent immune cells within the tumor microenvironment (TME) of melanoma are macrophages, a diverse immune cell subset displaying high plasticity, to which no current therapies are yet directly targeted. Macrophages have been shown not only to activate the adaptive immune response, and enhance cancer cell killing, but, when influenced by factors within the TME of melanoma, these cells also promote melanoma tumorigenesis and metastasis. We present a review of the most up-to-date literatureavailable on PubMed, focussing on studies from within the last 10 years. We also include data from ongoing and recent clinical trials targeting macrophages in melanoma listed on clinicaltrials.gov. Understanding the multifaceted role of macrophages in melanoma, including their interactions with immune and cancer cells, the influence of current therapies on macrophage phenotype and functions and how macrophages could be targeted with novel treatment approaches, are all critical for improving outcomes for patients with melanoma. [ABSTRACT FROM AUTHOR]

This paper presents a method to inhibit B16F10 cancer cells using extremely low-frequency electromagnetic fields (ELF-EMFs) and to evaluate cell viability using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay. The study examined the effect of a natural EMF resonance frequency (7.83 Hz) and a power line frequency (60 Hz) on B16F10 cancer cells for 24 and 48 h. The B16F10 cancer cells were also exposed to sweep frequencies in several sweep intervals to quantitatively analyze the viability of cancer cells. The results yielded a 17% inhibition rate under 7.83 Hz compared with that of the control group. Moreover, sweep frequencies in narrow intervals (7.83 ± 0.1 Hz for the step 0.05 Hz) caused an inhibition rate of 26.4%, and inhibitory effects decreased as frequency sweep intervals increased. These results indicate that a Schumann resonance frequency of 7.83 Hz can inhibit the growth of cancer cells and that using a specific frequency type can lead to more effective growth inhibition. [ABSTRACT FROM AUTHOR]

Resistance to chemo-immunotherapy is a major issue for the treatment of non-small cell lung cancer. In a recent paper we unravel the role of MAPK in the capacity of restraining the therapeutic efficacy of chemo-immunotherapy. Inhibition of the MAPK pathway using a MAP2K/MEK inhibitor in combination with chemotherapy could promote OPTN (optineurin)-dependent mitophagy of cancer cells. Mitochondria then degrade via autophagosomes and amphisomes and release mitochondrial DNA, which interacts with TLR9 located in these compartments. TLR9 activation promotes the production of the chemokine CXCL10 by cancer cells, which could further improve T cell recruitment and improve the efficacy of immunotherapy. [ABSTRACT FROM AUTHOR]

Propyl gallate (PG) has been found to exert an inhibitory effect on the growth of different cell types, including lung cancer cells. However, little is known about the cytotoxicological effects of PG specifically on normal primary lung cells. The current study examined the cellular effects and cell death resulting from PG treatment in human pulmonary fibroblast (HPF) cells. DNA flow cytometry results demonstrated that PG (100-1,600 µM) had a significant impact on the cell cycle, leading to G1 phase arrest. Notably, 1,600 µM PG slightly increased the number of sub-G1 cells. Additionally, PG (400-1,600 µM) resulted in the initiation of cell death, a process that coincided with a loss of mitochondrial membrane potential (MMP; ΔΨm). This loss of MMP (ΔΨm) was evaluated using a FACS cytometer. In PG-treated HPF cells, inhibitors targeting pan-caspase, caspase-3, caspase-8, and caspase-9 showed no significant impact on the quantity of annexin V-positive and MMP (ΔΨm) loss cells. The administration of siRNA targeting Bax or caspase-3 demonstrated a significant attenuation of PG-induced cell death in HPF cells. However, the use of siRNAs targeting p53, Bcl-2, or caspase-8 did not exhibit any notable effect on cell death. Furthermore, none of the tested MAPK inhibitors, including MEK, c-Jun N-terminal kinase (JNK), and p38, showed any impact on PG-induced cell death or the loss of MMP (ΔΨm) in HPF cells. In conclusion, PG induces G1 phase arrest of the cell cycle and cell death in HPF cells through apoptosis and/or necrosis. The observed HPF cell death is mediated by the modulation of Bax and caspase-3. These findings offer insights into the cytotoxic and molecular effects of PG on normal HPF cells. [ABSTRACT FROM AUTHOR]

Context: Rice bran arabinoxylan compound (RBAC) is a natural immunomodulator with anticancer properties. Objective: this study critically evaluates the available evidence on the biological pathways of RBAC and its effects on cancer treatment. Methods: this secondary analysis of a scoping review includes studies evaluating the mechanisms of RBAC on healthy or malignant cells, animal models, or humans for cancer prevention or treatment. Data from randomized controlled trials on survival and quality of life outcomes were subjectd to meta analysis. Results: the evidence synthesis was based on 38 articles. RBAC exhibited antitumor properties by promoting apoptosis and restoring immune function in cancer patients to enhance inflammatory and cytotoxic responses to block tumorigenesis. RBAC works synergistically with chemotherapeutic agents by upregulating drug transport. in a clinical trial, combining RBAC with chemoembolization in treating liver cancer showed improved response, reduced recurrence rates, and prolonged survival. RBAC also augments the endogenous antioxidant system to prevent oxidative stress and protect against radiation side effects. in addition, RBAC has chemoprotective effects. Animals and humans have exhibited reduced toxicity and side effects from chemotherapy. Meta analysis indicates that RBAC treatment increases the survival odds by 4.02-times (95% ci: 1.67, 9.69) in the first year and 2.89-times (95% ci: 1.56, 5.35) in the second year. Conclusion: RBAC is a natural product with immense potential in cancer treatment. Additional research is needed to characterize, quantify, and standardize the active ingredients in RBAC responsible for the anticancer effects. More well-designed, large-scale clinical trials are required to substantiate the treatment efficacies further. [ABSTRACT FROM AUTHOR]

Context: Pileostegia tomentella hand. Mazz (saxifragaceae) total coumarins (TCPT) show antitumour activity in colorectal cancer (CRC) with unknown mechanism of action. tumour angiogenesis mediated by exosomes-derived miRNa exhibits the vital regulation of endothelial cell function in metastasis of CRC. Objective: to investigate the effect of TCPT on exosomal miRNA expression and angiogenesis of CRC cells. Materials and methods: HT-29-derived exosomes were generated from human CRC cells (HT-29) or either treated with TCPT (100 μg/ml) for 24 h, followed by identification by transmission electron microscope, nanoparticle tracking analysis (NTA) and Western blot. co-culture experiments for human umbilical vein endothelial cells (HUVECS) and exosomes were performed to detect the uptake of exosomes in HUVECs and its influence on HUVECs cells migration and lumen formation ability. Potential target miRNas in exosomes were screened out by sequencing technology. Rescue assays of angiogenesis were performed by the transfecting mimics or inhibitors of targeted miRNa into HUVECs. Results: HT-29-derived exosomes, after TCPT treatment (Exo-TCPT), inhibited the migration and lumen formation of HUVECs, reduced the expression levels of vascular marker (FLT-1, VCAM-1 AND VEGFR-2) in HUVECs. Furthermore, the level of miR-375-3p was significantly upregulated in exo-tcPt. Rescue assays showed that high expression of miR-375-3p in hUVecs inhibited migration and lumen formation abilities, which was consistent with the effects of Exo-TCPT, whereas applying miR-375-3p inhibitors displayed opposite effects. Discussion and conclusion: TCPT exhibits anti-angiogenesis in CRC, possibly through upregulating exosomal miR-375-3p. Our findings will shed light on new target exosomes miRNA-mediated tumour microenvironment and the therapeutic application of Pileostegia tomentella in CRC. [ABSTRACT FROM AUTHOR]

When the orthologue of tumor suppressor protein p53 (TP53), cep-1, is inactivated in Caenorhabditis elegans, the nematodes manifest an autophagy-dependent increase in lifespan. A recent paper by Yang et al. demonstrates that accelerated aging phenotype of autophagy-deficient mice can be reduced by the knockout (KO) of Trp53. These findings point to a complex bidirectional crosstalk between autophagy and TP53 that has vast implications for the aging process. [ABSTRACT FROM AUTHOR]

There are growing interests in the health benefits associated with consumption of fruits and vegetables, especially for the prevention of cancer, cardiovascular, or other chronic diseases. Epidemiological studies and clinical trials suggest that these health benefits are strongly associated with phytochemicals found in fruits and vegetables. Ursolic acid is a naturally synthesized pentacyclic triterpenoid, widely distributed in different fruits and vegetables. Current research suggested that ursolic acid and its derivatives exhibited anticancer activity, anti-inflammatory effects, and induction of apoptosis in several human cancer cells. In particular, ursolic acid inhibited breast cancer proliferation by inducing cell G1/G2 arrest and regulating the expression of key proteins in signal transduction pathways. In addition, ursolic acid induced apoptosis in human breast cancer cells through intrinsic and extrinsic apoptotic pathways. Ursolic acid was also determined to scavenge free radicals and have potent anti-inflammation activity. The purpose of this paper is to review recent literature on anticancer activity of ursolic acid and focus on its mechanisms of action. [ABSTRACT FROM AUTHOR]

The established molecular heterogeneity of human cancers has had profound effects on the design of cancer therapeutics. Most cancer drugs are today targeted to molecular alterations present in cancer cells. Tumors of the same primary site, however, often differ with regard to the alterations that they harbor. Consequently, this heterogeneity has required the development of new paradigms for clinical development. In this paper, we review some clinical trial designs finding active use in co-development of therapeutics and predictive biomarkers to inform their use in oncology. [ABSTRACT FROM AUTHOR]

How to overcome drug resistance and prevent tumor metastasis is key to the success of malignant tumor therapy. In this paper, ADH-1 peptide-modified liposomes (A-LP) have been successfully constructed for restoring chemosensitivity and suppressing cancer cell migration. With a particle size of about 90 nm, this functionalized nanocarrier was loaded with fluorescent probe or paclitaxel (PTX). Cellular uptake studies showed that A-LP facilitated the delivery of anticancer drug to tumor cells undergoing EMT. Interestingly, this nanocarrier enhanced chemosensitivity by assessing the cell activity using CCK-8 assay. Further, the results of Wound scratch assay and Transwell migration assay showed the inhibition effect of this nanocarrier on tumor cell migration. Moreover, this nanocarrier exhibited significant tumor-targeting ability and anti-tumor efficacy in vivo. Collectively, A-LP might be a novel targeted drug delivery system to enhance the efficacy of chemotherapy and prevent tumor metastasis. [ABSTRACT FROM AUTHOR]

In this paper, novel folate-conjugated and redox-responsive crosslinked block copolymer was successfully synthesized for targeted and controlled release of doxorubicin (DOX) to cancer cells. Folate-conjugated poly(ethylene glycol)-b-copolycarbonates (FA-PEG-b-P(MAC-co-DTC)) and methoxy poly(ethylene glycol)-b-copolycarbonates (mPEG-b-P(MAC-co-DTC)) were firstly synthesized by enzymatic method. FA-PEG/mPEG-b-P(MAC-co-DTC)-SS was then obtained by further crosslinking reaction with cystamine. Non-conjugated crosslinked copolymer mPEG-b-P(MAC-co-DTC)-SS- and non-conjugated uncrosslinked copolymer mPEG-b-P(MAC-co-DTC) were also synthesized for comparison. All the amphiphlic copolymers could self-assemble to form nano-sized micelles which dispersed in spherical shape before and after DOX loading. The core crosslinking structure of FA-PEG/mPEG-b-P(MAC-co-DTC)-SS could improve the micellar stability and drug loading capacity, while in vitro release studies also showed more sustained drug release behavior which could be accelerated in reductive condition. Moreover, confocal laser scanning microscopy indicated that the conjugation of FA could enhance the cellular uptake efficiency obviously via FA-receptor-mediated endocytosis, and MTT assays demonstrated highly potent cytotoxic activity of FA-PEG/mPEG-b-P(MAC-co-DTC)-SS. [ABSTRACT FROM AUTHOR]

In this paper, we report the conjugation of the humanized monoclonal antibody nimotuzumab with cisplatin-loaded liposomes and thein vitroevaluation of its affinity for tumor cells. The conjugation procedure was performed through derivatization of nimotuzumab with N-succinimidyl S-acetylthioacetate (SATA) followed by a covalent attachment with maleimide groups at the end of PEG-DSPE chains located at the membrane of pre-formed liposomes. Confocal microscopy was performed to evaluate the immunoliposome affinity for EGFR antigens from human epidermoid carcinoma (A-431) and normal lung (MRC-5) cell lines. Results showed that the procedures implemented in this work do not affect the capability of the nimotuzumab-immunoliposomes to recognize the tumor cells, which overexpress the EGFR antigens. [ABSTRACT FROM PUBLISHER]

The aim of this work is to assist pathologists in the evaluation of tumour cells in microscopic breast images where we distinguish three kinds of cells: positive tumour cells for oestrogen receptor, negative tumour cells for oestrogen receptor, and non-tumour cells. This work has proven to be very difficult because of the variability of cells' size, shape (morphology) and distribution. Conventional methods for segmentation like thresholding and edge detection are unable to resolve this problem. The herein proposed method is a hybrid approach combining segmentation and classification to ensure better results. While the morphological processes are used for artefact elimination and cell segmentation, the classification algorithm is used to automatically classify all existing cells in the image. The paper contains also a comparative study between fuzzy c-means clustering algorithm and neural network-based classification. The proposed approach was applied on several microscopic breast cancer cells images corresponding to eight patients. The experimental results are efficient and the found values are near to those announced by experts. To better interpret these results, we performed a statistical analysis in terms of sensitivity, specificity and accuracy of detected tumour cells. The statistics proved the efficacy of the proposed approach since a percentage exceeding 90% was recorded for sensitivity, specificity and accuracy for the totality of the studied images. When using neural networks, the statistics are slightly above those gathered with fuzzy c-means. We recorded over 97% for sensitivity, specificity and accuracy of detected cells, reaching an error rate below 3%. Furthermore, it should be kept in mind that analysing breast cells images using the proposed approach gives us important information such as number of tumour cells, and number and percentage of positive tumour cells. Moreover, it is so much less time-consuming than experts' evaluation. [ABSTRACT FROM AUTHOR]

Percutaneous Hot Saline Injection Therapy (PSIT) has recently been proved to be a powerful minimally invasive way to destroy malignant tumor cells. However, this approach may also possibly cause thermal injury to the surrounding normal tissues during the treatment. For example, an excessive or insufficient injection would lead to very undesirable results. The main reasons can be attributed to the lack of a flexible monitoring method. In this paper, we propose to implement thermal infrared imaging to guide the whole process of performing PSIT to treat superficial tumors. Conceptual experiments were performed in vivo on the left thigh of an anaesthetized rabbit. It was demonstrated that the infrared temperature mapping across the skin surface clearly reflects the heating status of the target tissues. Along with the mathematical simulation, such information can easily be incorporated into the computer code to reconstruct the spatial and transient temperature field around the subject. The obtained data will serve as an important index for effectively administering the thermal dose on the target tissues while preserving the surrounding normal tissues from burning during PSIT. [ABSTRACT FROM AUTHOR]

A new mini-invasive hyperthermia probe using high-temperature water vapour for deep regional tumour treatment was developed in this paper. The vacuum insulation mechanism was incorporated into the probe to avoid heating damage to the normal tissues around the edge of the insertion path. To better understand the heat transfer behaviour in living tissues due to operation of the probe, theoretical models based on the Pennes' equation were established and two closed form analytical solutions under constant flux or temperature heating at the tip of probe were obtained. Parametric studies were performed to investigate the influence of various parameters on the temperature response of tissues heated by the probe. Further, several simulating experiments on the actual heating performance of the probe fabricated in this paper were conducted on the in vitro biological materials (fresh pork) and phantom gel. It was demonstrated that the probe can cause a high enough temperature over the treatment area to thermally destroy the tumour tissue in due time, while the temperature over the surrounding healthy tissues can be kept below a safe threshold value. This mini-invasive heating probe may have significant applications in future clinical tumour hyperthermia. [ABSTRACT FROM AUTHOR]

Purpose:Gene therapy combined with radiation has shown promising potential for the treatment of tumors. This paper aimed to clarify the synergistic effect of radiotherapy combined with the bladder cancer tissue-specific oncolytic adenovirus (Ad-PSCAE-UPII-E1A) on bladder cancer cells and to study the underlying synergy mechanisms of the combined treatment. Materials and methods:The Adenovirus carrying E1A under control of UPII promoter and prostate stem cell antigen enhancer (PSCAE) were successfully constructed. The viability of bladder cancer cells BIU-87 and EJ was determined by MTT assay. The apoptotic assay was demonstrated by flow cytometry and TEM. Virus titer was determined by TCID50 assay, and proteins Mre11, Chk2-Thr68, and E1A were analyzed by Western blot method. Results:Oncolytic adenovirus combined with radiotherapy improved antitumor efficacy compared with the single treatment at a time and was X-ray dosage-dependent. When the adenovirus infection was scheduled at 24 h after irradiation, cancer cells had the lowest viability. Adenovirus and irradiation induced cell death through the caspase-3 related apoptotic pathway, and bladder cancer cells were arrested at the G1 (BIU-87) or S phase (EJ). Autophagic vacuoles were observed in bladder cancer cells treated with radiation and adenovirus. After irradiation, more virus particles were observed in the BIU-87 and EJ cells. However, by a TCID50 assay, there was no difference in virus titter between irradiated bladder cancer cells and unirradiated cells. The proteins Mre11, Chk2-Thr68 which involved in the DNA break repair pathway were decreased while γ-H2AX-Ser139 increased; at the same time, the E1A gene and the hexon proteins of oncolytic adenovirus were increased after irradiation. Conclusions:Our results proved synergistic antitumor effect of adenovirus Ad-PSCAE-UPII-E1A and radiation, which might be a potential therapeutic strategy for bladder cancer. [ABSTRACT FROM PUBLISHER]

Recently, genkwanin (GKA) has been shown to displayin vitroantitumor activity against some cancer cells, but its poor solubility restricted thein vivostudy and further investigation of its antitumor therapeutic efficacy. In this paper, genkwanin nanosuspensions (GKA-NSps) were successfully prepared using D-alpha tocopherol acid polyethylene glycol succinate (TPGS) as a stabilizer using the precipitation-homogenization method. The obtained GKA-NSps had an average particle size of 183.1 ± 4.4 nm, a PDI value of 0.16 ± 0.07, a zeta potential of −16.2 ± 0.1 mV, and a drug loading content of 49.36 ± 0.14%. GKA-NSps showed spherical morphology and very good stability in normal saline, phosphate buffer saline (PBS, pH 7.4), 5% glucose, artificial gastric juice, artificial intestinal juice and plasma; thus, it is suitable for both oral and intravenous administration. The resultant GKA-NSps displayed sustained drug release behavior and strongerin vitrocytotoxicity against 4T1, MCF-7, MDA-MB-453, HeLa, HepG2, BT474, and A549 cells than free GKA. Thein vivostudy in MCF-7 tumor-bearing nude mice indicated that GKA-NSps (60 mg/kg, i.v.) achieved similar therapeutic efficacy as PTX injection (8 mg/kg, i.v.) (62.09% vs. 61.27%), while the minimal lethal dose was more than 320 mg/kg, indicating good safety. By using nanotechnology, our study suggested that some antitumor flavonoids of low potency, such as GKA, are promising as safe but effective anticancer drugs. [ABSTRACT FROM AUTHOR]

Purpose: A challenge for single-cell dosimetry of internalized Auger electron-emitting (AE) radiopharmaceuticals remains how best to elucidate their spatial distribution. To this end, a method, photoresist autoradiography (PAR), was previously developed to identify the lateral spatial distribution of AE-emitting radionuclides internalized in single cancer cells. In this paper, we present a simple mathematical model based on the radius and depth of radiation-induced patterns in photoresist material to identify the location in the z-plane of an 111In source capable of generating the pattern. Materials and methods: SQ20B cells, derived from a head and neck squamous cell carcinoma, were exposed to 111In-labeled epidermal growth factor (EGF) (8 MBq/μg). The integrated electron fluence after four half-lives from the internalized radionuclide-containing construct was detected by a photoresist layer that was placed in close proximity to the cells. The resultant latent patterns were chemically developed and analyzed by atomic force microscopy (AFM). The features in the patterns were matched to locations of electrons emitted from simulated point sources, thereby determining the likely locations of internalized radionuclides. Results: The modeling procedure was validated using simple patterns. The model relates the depth and radius (in the x-y plane) of a pattern to the location and fluence of the source giving rise to the pattern. This point source modeling method provided a good fit to experimental data and can be expanded to analyze more complex patterns. Conclusions: We have demonstrated the utility of the modelling technique to identify the location of internalized AE-emitting radionuclides. This methodology now needs to be extended to predict the source positions in more complex PAR patterns. [ABSTRACT FROM AUTHOR]

Article title: Assessment of redox homeostasis via genotoxicity, cytotoxicity, apoptosis and NRF-2 in colorectal cancer cell lines after treatment with Ganoderma lucidum extractAuthors: Yasin Tülüce, Ahmet Yasin Keleş, Sedat KöstekciJournal:Drug and Chemical ToxicologyDOI:https://doi.org/10.1080/01480545.2023.2257403When the article has been previously published, the Graphical Abstract has not been included.Below is the Graphical Abstract of this paper:Graph [Extracted from the article]

A series of new disulfides incorporating naphthalimide moiety were designed, synthesized and biologically evaluated against three human cancer cell lines (MCF-7, SMMC-7721 and Hela). Most of target compounds exhibited some degrees of anticancer activities, and some compounds displayed better effects than reference drugs PX-12 and 5-FU against the tested three cancer cells. Especially, compound 7d showed the most potent antiproliferative activity against MCF-7 cell lines with IC50 value of 3.19 μM. Compound 8a displayed prominent anticancer property against SMMC-7721 cell lines with IC50 value of 1.84 μM. Compound 6c possessed the most effective proliferation inhibitory activity against Hela cell lines with IC50 value of 2.14 μM. In addition, cytotoxicity evaluation indicated that most of the compounds had weak cytotoxicity to L929 cell lines. [ABSTRACT FROM AUTHOR]

The antipsychotic drug pimozide has been demonstrated to inhibit cancer. However, the precise anticancer mechanism of pimozide remains unclear. The purpose of this study was to investigate the effects of pimozide on human MCF-7 and MDA-MB-231 breast cancer cell lines, and the potential involvement in the RAF/ERK signaling. The effects of pimozide on cells were examined by 4,5-dimethylthiazol-2-yl-3,5-diphenylformazan, wound healing, colony formation, transwell assays, and caspase activity assay. Flow cytometry and acridine orange and ethidium bromide staining were performed to assess changes in cells. Transmission electron microscopy and monodansylcadaverine staining were used to observe autophagosomes. The cyclic adenosine monophosphate was evaluated using the FRET system. Immunohistochemistry, immunofluorescence, RNA interference, and western blot investigated the expression of proteins. Mechanistically, we focus on the RAF1/ERK signaling. We detected pimozide was docked to RAF1 by Schrodinger software. Pimozide down-regulated the phosphorylation of RAF1, ERK 1/2, Bcl-2, and Bcl-xl, up-regulated Bax, and cleaved caspase-9 to induce apoptosis. Pimozide might promote autophagy by up-regulating cAMP. The enhancement of autophagy increased the conversion of LC3-I to LC3-II and down-regulated p62 expression. But mTOR signaling was not involved in promoting autophagy. The knockdown of RAF1 expression induced autophagy and apoptosis in breast cancer cells, consistent with the results of pimozide or sorafenib alone. Blocked autophagy by chloroquine resulted in the impairment of pimozide-induced apoptosis. These data showed that pimozide inhibits breast cancer by regulating the RAF/ERK signaling pathway and might activate cAMP-induced autophagy to promote apoptosis and it may be a potential drug for breast cancer treatment. [ABSTRACT FROM AUTHOR]

DIRAS family GTPase 1 (DIRAS1) has been reported as a potential tumor suppressor in other human cancer. However, its expression pattern and role in cervical cancer remain unknown. Knockdown of DIRAS1 significantly promoted the proliferation, growth, migration, and invasion of C33A and SiHa cells cultured in vitro. Overexpression of DIRAS1 significantly inhibited the viability and motility of C33A and SiHa cells. Compared with normal cervical tissues, DIRAS1 mRNA levels were significantly lower in cervical cancer tissues. DIRAS1 protein expression was also significantly reduced in cervical cancer tissues compared with para-cancerous tissues. In addition, DIRAS1 expression level in tumor tissues was significantly negatively correlated with the pathological grades of cervical cancer patients. DNA methylation inhibitor (5-Azacytidine) and histone deacetylation inhibitor (SAHA) resulted in a significant increase in DIRAS1 mRNA levels in C33A and SiHa cells, but did not affect DIRAS1 protein levels. FTO inhibitor (FB23-2) significantly down-regulated intracellular DIRAS1 mRNA levels, but significantly up-regulated DIRAS1 protein levels. Moreover, the down-regulation of METTL3 and METTL14 expression significantly inhibited DIRAS1 protein expression, whereas the down-regulation of FTO and ALKBH5 expression significantly increased DIRAS1 protein expression. In conclusion, DIRAS1 exerts a significant antioncogenic function and its expression is significantly downregulated in cervical cancer cells. The m6A modification may be a key mechanism to regulate DIRAS1 mRNA stability and protein translation efficiency in cervical cancer. [ABSTRACT FROM AUTHOR]

Objective: This study aims to investigate the effect of red ginseng polysaccharide (RGP) on gastric cancer (GC) development and explore its mechanism. Methods: GC cell lines AGS were treated with varying concentrations of RGP (50, 100, and 200 µg/mL). AGS cells treated with 200 µg/mL RGP were transfected with aquaporin 3 (AQP3) overexpression vector. Cell proliferation, viability, and apoptosis were evaluated by MTT, colony formation assay, and flow cytometry, respectively. Real-time quantitative reverse transcription PCR (qRT-PCR) was used to detect the expression of AQP3. The levels of Fe2+, malondialdehyde, and lactate dehydrogenase were measured using their respective detection kits, and the reactive oxygen species levels was determined by probe 2',7'-dichlorodihydrofluorescein diacetate. The expression of ferroptosis-related protein and PI3K/Akt pathway-related protein were assessed by western blot. In vivo experiments in nude mice were performed and the mice were divided into four groups (n = 5/group) which gavage administrated with 150 mg/kg normal saline, and 75, 150, 300 mg/kg RGP, respectively. Their tumor weight and volume were recorded. Results: RGP treatment effectively inhibited the proliferation and viability of AGS cells in a dosagedependent manner and induced apoptosis. It induced ferroptosis in AGS cells, as well as inhibiting the expression of PI3K/Akt-related proteins. AQP3 overexpression could reversed the effect of RGP treatment on ferroptosis. Confirmatory in vivo experiments showed that RGP could reduce the growth of implanted tumor, with increased RGP concentration resulting in greater tumor inhibitory effects. Conclusion: RGP might have therapeutic potential against GC, effectively inhibiting the proliferation and viability of AGS cells. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the most lethal cancers. Single-cell RNA sequencing (scRNA-seq) and protein-protein interactions (PPIs) have enabled the systematic study of CRC. In our research, the activation of the AKT pathway in CRC was analyzed by KEGG using single-cell sequencing data from the GSE144735 dataset. The correlation and PPIs of MDFI and ITGB4/LAMB3 were examined. The results were verified in the TCGA and CCLE and further tested by coimmunoprecipitation experiments. The effect of MDFI on the AKT pathway via ITGB4/LAMB3 was validated by knockdown and lentiviral overexpression experiments. The effect of MDFI on oxaliplatin/fluorouracil sensitivity was probed by colony formation assay and CCK8 assay. We discovered that MDFI was positively associated with ITGB4/LAMB3. In addition, MDFI was negatively associated with oxaliplatin/fluorouracil sensitivity. MDFI upregulated the AKT pathway by directly interacting with LAMB3 and ITGB4 in CRC cells, and enhanced the proliferation of CRC cells via the AKT pathway. Finally, MDFI reduced the sensitivity of CRC cells to oxaliplatin and fluorouracil. In conclusion, MDFI promotes the proliferation and tolerance to chemotherapy of colorectal cancer cells, partially through the activation of the AKT signaling pathway by the binding to ITGB4/LAMB3. Our findings provide a possible molecular target for CRC therapy. [ABSTRACT FROM AUTHOR]

Emerging evidence has provided considerable insights into the integral function of reprogramming fatty acid metabolism in the carcinogenesis and progression of endometrial cancer. Linoleic acid, an essential fatty acid with the highest consumption in the Western diet regimen, has shown pro-tumorigenic or antitumorigenic effects on tumor cell growth and invasion in multiple types of cancer. However, the biological role of linoleic acid in endometrial cancer remains unclear. In the present study, we aimed to investigate the functional impact of linoleic acid on cell proliferation, invasion, and tumor growth in endometrial cancer cells and in a transgenic mouse model of endometrial cancer. The results showed that Linoleic acid significantly inhibited the proliferation of endometrial cancer cells in a dose-dependent manner. The treatment of HEC-1A and KLE cells with linoleic acid effectively increased intracellular reactive oxygen species (ROS) production, decreased mitochondrial membrane potential, caused cell cycle G1 arrest, and induced intrinsic and extrinsic apoptosis pathways. The anti-invasive ability of linoleic acid was found to be associated with the epithelial-mesenchymal transition process in both cell lines, including the decreased expression of N-cadherin, snail, and vimentin. Furthermore, treatment of Lkb1fl/flp53fl/fl transgenic mice with linoleic acid for four weeks significantly reduced the growth of endometrial tumors and decreased the expression of VEGF, vimentin, Ki67, and cyclin D1 in tumor tissues. Our findings demonstrate that linoleic acid exhibits anti-proliferative and anti-invasive activities in endometrial cancer cell lines and the Lkb1fl/flp53fl/fl mouse model of endometrial cancer, thus providing a pre-clinical basis for future dietary interventions with linoleic acid in endometrial cancer. [ABSTRACT FROM AUTHOR]

Background: Lung cancer is the deadliest form of malignancy and the most common subtype is non-small cell lung cancer (NSCLC). Hypoxia is a typical feature of solid tumor microenvironment. In the current study, we clarified the effects of hypoxia on stemness and metastasis and the molecular mechanism. Methods: The biological functions were assessed using the sphere formation assay, Transwell assay, and XF96 extracellular flux analyzer. The protein levels were detected by western blot. The lactylation modification was assessed by western blot and immunoprecipitation. The role of SOX9 in vivo was explored using a xenografted tumor model. Results: We observed that hypoxia promoted sphere formation, migration, invasion, glucose consumption, lactate production, glycolysis, and global lactylation. Inhibition of glycolysis suppressed cell stemness, migration, invasion, and lactylation. Moreover, hypoxia increased the levels of SOX9 and lactylation of SOX9, whereas inhibition of glycolysis reversed the increase. Additionally, knockdown of SOX9 abrogated the promotion of cell stemness, migration, and invasion. In tumor-bearing mice, overexpression of SOX9 promoted tumor growth, and inhibition of glycolysis suppressed tumor growth. Conclusion: Hypoxia induced the lactylation of SOX9 to promote stemness, migration, and invasion via promoting glycolysis. The findings suggested that targeting hypoxia may be an effective way for NSCLC treatment and reveal a new mechanism of hypoxia in NSCLC. [ABSTRACT FROM AUTHOR]

Tumor heterogeneity contributes significantly to chemoresistance, a leading cause of treatment failure. To better personalize therapies, it is essential to develop tools capable of identifying and predicting intraand inter-tumor heterogeneities. Biology-inspired mathematical models are capable of attacking this problem, but tumor heterogeneity is often overlooked in in-vivo modeling studies, while phenotypic considerations capturing spatial dynamics are not typically included in in-vitro modeling studies. We present a data assimilation-prediction pipeline with a two-phenotype model that includes a spatiotemporal component to characterize and predict the evolution of in-vitro breast cancer cells and their heterogeneous response to chemotherapy. Our model assumes that the cells can be divided into two subpopulations: surviving cells unaffected by the treatment, and irreversibly damaged cells undergoing treatment-induced death. MCF7 breast cancer cells were previously cultivated in wells for up to 1000 hours, treated with various concentrations of doxorubicin and imaged with time-resolved microscopy to record spatiotemporally-resolved cell count data. Images were used to generate cell density maps. Treatment response predictions were initialized by a training set and updated by weekly measurements. Our mathematical model successfully calibrated the spatiotemporal cell growth dynamics, achieving median [range] concordance correlation coefficients of > .99 [.88, >.99] and .73 [.58, .85] across the whole well and individual pixels, respectively. Our proposed data assimilationprediction approach achieved values of .97 [.44, >.99] and .69 [.35, .79] for the whole well and individual pixels, respectively. Thus, our model can capture and predict the spatiotemporal dynamics of MCF7 cells treated with doxorubicin in an in-vitro setting. [ABSTRACT FROM AUTHOR]

Redox adaptation causes poor prognosis by adapting cancer cells to excessive oxidative stress. Previously, we introduced an oxidative stress-resistant metastatic prostate cancer (mPC) model (LNCaPHPR) that redox adaptation reduced the effect of Cabazitaxel (Cab), the last taxane-derivative for metastatic castration-resistant PC (mCRPC). Whereas, we investigated for the first time whether there is an association between the altered apoptotic effect and pro-oxidant efficacy of Cab on the redox adaptation in PC cells with different phenotypes, including LNCaP mPC, LNCaP-HPR, C4-2 mCRPC, and RWPE-1 cells. Cab was shown pro-oxidant efficacy proportionally with the apoptotic effect, more prominent in the less aggressive LNCaP cells, by increasing the endogenous ROS, mitochondrial damage, and inhibiting nuclear ROS scavengers, p-Nrf2 and HIF-1a. However, the pro-oxidant and apoptotic effect was lower in the LNCaP-HPR and C4-2 cells, indicating that the drug sensitivity of the cells adapted to survive with more ROS was reduced via altered regulation of redox adaptation. Additionally, unlike LNCaP, Cab caused an increase in the p-NF-κB activation, suggesting that the p-NF-κB might accompany maintaining survival with the increased ROS in the aggressive PC cells. Moreover, the cytotoxic and apoptotic effects of Cab were less on RWPE-1 cells compared to LNCaP but were closer to those on the more aggressive LNCaP-HPR and C4-2 cells, except for the changing pro-oxidant effect of Cab. Consequently, this study indicates the variable pro-oxidant effects of Cab on redox-sensitive proteins, which could be a target for improving Cab's apoptotic effect more in aggressive PC cells. [ABSTRACT FROM AUTHOR]

This study investigated the inhibitory effects of lncRNA HLA Complex Group 11 (HCG11) on non-small cell lung cancer (NSCLC) and the molecular mechanisms. Bioinformatics analysis was conducted to determine the downstream targeted gene miR-17-5p/p21 and predict their binding sites. qRT-PCR and Western blot were used to detect expression levels, and dual luciferase and RIP assays were adopted to verify binding relationship. The lncRNA HCG11/miR-17-5p/p21 axis was found to regulate drug resistance, proliferation, apoptosis, and cell cycle of A549 and A549-Gemcitabine (GEM) cells. HCG11 acted as a ceRNA binding to miR-17-5p, which repressed p21 expression in turn. In vivo experiments demonstrated that HCG11 hindered tumor growth. Therefore, lncRNA HCG11, by targeting the miR-17-5p/p21 axis, suppressed GEM resistance and malignant progression of NSCLC cells. This study provides a reference for investigating the potential value of lncRNA HCG11 in the diagnosis of NSCLC and finding potential targets against clinical chemotherapeutic resistance in NSCLC. [ABSTRACT FROM AUTHOR]

In this paper, we propose a method to optimise a theoretical control on a mathematical model of interactions between cancer cells and the immune system. The model consists of five ordinary differential equations describing the behaviour of a tumour cell population interacting with populations of immune cells, all cells being submitted to the effects of chemotherapy. Two constraints were added to reflect the biological specificity of the problem. The first one asserts that the number of cytotoxic T lymphocytes must remain above a given threshold at the terminal point in time. The second one keeps the drug concentration in the bloodstream below a threshold to reduce toxic side effects resulting from the damages of chemotherapy to healthy cells. Using Pontryagin’s Maximum Principle and approximation methods for optimal control, we obtain bang–bang solutions for different scenarios. [ABSTRACT FROM PUBLISHER]

Immunogenic cell death (ICD) involves the release of ATP, which can be destroyed by ectonucleotidases, converting it into immunosuppressive adenosine. Hence, inhibition of such ectonucleotidases is a strategy for enhancing ICD-elicited anticancer immunity. In a recent paper in Science Translational Medicine, Mao et al. report the construction of reactive oxygen-labile nanoparticles that bear two functionalities, namely (i) the capacity to sensitize cancer cells to near-infrared light (NIL) irradiation, hence inducing ICD in the context of photodynamic therapy, and (ii) the peculiarity to respond to NIL by releasing a pharmacological inhibitor of ectonucleotidases, hence enhancing intratumoral concentrations of ATP. In preclinical models, these nanoparticles are highly efficient in inducing anticancer immune responses. [ABSTRACT FROM AUTHOR]