Perceived communication efficacy and unmet needs for chemotherapy-associated symptom management in patients with lung and colorectal cancer: a cross-sectional study.

BACKGROUND: Understanding cancer patients' unmet needs for chemotherapy-related symptom management will assist clinicians in developing tailored intervention programs. Little is known about the association between perceived communication efficacy and unmet care needs for symptom management in patients with lung and colorectal cancer. OBJECTIVES: To examine the unmet care needs for symptom management of patients with lung and colorectal cancer and their association with perceived communication efficacy. METHODS: A cross-sectional survey was conducted in a tertiary hospital in China from July to November 2020. A convenience sample of 203 patients with lung and colorectal cancer undergoing chemotherapy completed survey questionnaires, including the MD Anderson Symptom Inventory Scale and the Perceived Efficacy in Patient‒Physician Interactions Scale. RESULTS: Approximately 43% of participants had at least one symptom with unmet needs. Fatigue was reported as the symptom with the highest occurrence (66%), the highest demand for supportive care (36%), and the highest prevalence of unmet needs (19%). Low levels of perceived communication efficacy independently predicted participants' unmet needs for symptom management (ß=-0.13, p = 0.011). CONCLUSIONS: This study highlights the necessity of introducing clinical assessment tools and guidelines to address fatigue and other chemotherapy-induced symptoms in patients with lung and colorectal cancer. Clinical programs designed to actively engage cancer patients to voice their needs and strengthen their communication efficacy are also warranted.

Rapid and ratiometric fluorescent detection of hypochlorite by glutathione functionalized molybdenum disulfide quantum dots.

We proposed a rapid and ratiometric fluorescent detection method for hypochlorite by glutathione functionalized molybdenum disulfide quantum dots (G-MoS2 QDs). The G-MoS2 QDs were obtained through a hydrothermal method and the maximum fluorescence intensity was obtained at 430 nm under excitation of 360 nm. The fluorescence of G-MoS2 QDs at 430 nm can be weakened by curcumin through the inner filter effect, meanwhile the fluorescence of curcumin at 540 nm appeared. Hypochlorite can fast oxidize curcumin and weaken the inner filter effect, thus the fluorescence of curcumin at 540 nm decreased and the fluorescence of G-MoS2 QDs at 430 nm increased. This process takes only 30 s at room temperature. This is the rationale behind our rapid ratiometric fluorescent detection model for hypochlorite. Two linear detection ranges for hypochlorite are obtained with concentration from 1 to 20 µM and 20 to 30 µM, the limit of detection (LOD) was 11.5 nM. The standard spike recovery tests on milk and tap water samples showed satisfactory results, which extended the application of G-MoS2 QDs in the field of ratiometric fluorescence detection assays.

pH-responsive Ag2S nanodots loaded with heat shock protein 70 inhibitor for photoacoustic imaging-guided photothermal cancer therapy.

Heat-treated cancer cells have thermo-resistance due to the up-regulated levels of heat shock proteins (HSP) resulting in low therapeutic efficiency and ineffective ablation of tumors. In this work, we report pH-responsive Ag2S nanodots (Ag2S NDs) loaded with HSP70 inhibitor (QE-PEG-Ag2S) for enhanced photothermal cancer therapy. QE-PEG-Ag2S was easily prepared via self-assembly of hydrophobic Ag2S NDs, amphiphilic pH-responsive PEG5k-PAE10k polymer, and an HSP70 inhibitor quercetin (QE). QE-PEG-Ag2S has ideal water-solubility and biocompatibility, can rapidly enter cells, and preferentially accumulate in cell lysosomes. The slightly acidic environment of tumor cells and the acidity of lysosomes as well as the high temperature generated by photothermal therapy under irradiation of NIR light (808 nm) promote the release of the inhibitor molecules to reduce the heat resistance of cancer cells and improve the in vivo photothermal therapy efficiency. Moreover, QE-PEG-Ag2S has good photoacoustic imaging (PAI) ability; this QE-PEG-Ag2S concentration dependent signal can precisely follow the accumulation of the nanomaterials in tumors and dictate the correct time for light therapy. As a result, QE-PEG-Ag2S achieved complete tumor ablation effect with no recurrence when only irradiated with NIR light for 10 min. This approach offers a new approach for the theranostic applications of Ag2S NDs. STATEMENT OF SIGNIFICANCE: In this work, pH-responsive Ag2S nanodots loaded with the heat shock protein inhibitor for enhanced photothermal cancer therapy have been simply prepared via self-assembly process. This nanoagent possesses ideal water-solubility and biocompatibility, can rapidly enter cells, and preferentially accumulate in cell lysosomes. The acidic environment of tumor cells and the acidity of lysosomes, as well as the high temperature generated by photothermal therapy under irradiation of NIR light promote the release of the inhibitor molecules from the nanoagent to improve the in vivo photothermal therapy efficiency. Moreover, the photoacoustic imaging (PAI) of the nanoagent can precisely follow the accumulation of the nanomaterials in tumors and dictate the light therapy time to guarantee the complete tumor ablation effect with no recurrence.

Furin substrate as a novel cell-penetrating peptide: combining a delivery vector and an inducer of cargo release.

We have developed a new cell-penetrating peptide (CPP) using a repeated protease (furin) substrate. This CPP can not only deliver cargo into cells but can also be cleaved by furin in cells and release the cargo. Cell-impermeable antitumor pro-apoptotic peptide KLAKLAKKLAKLAK (KLA) and chemotherapy drug chlorambucil were chosen to be delivered by the CPP into live cancer cells and their cytotoxicity was greatly enhanced for in vivo cancer treatment.

Suppression of HSP70 inhibits the development of acute lymphoblastic leukemia via TAK1/Egr-1.

Acute lymphoblastic leukemia (ALL), usually treated with chemotherapy, has limited therapeutic effects and high toxicity. Upregulation of HSP70 induces tumor development, however, the molecular mechanism of HSP70 in ALL remains unclear. In our research, we aimed to investigate the role of HSP70 in ALL, specifically the molecular mechanisms underlying cell apoptosis and proliferation. We found that HSP70 expression in leukomonocytes from ALL patients was increased compared with the control group. HSP70 expression in NALM-6 and BE-13 was also up-regulated contrast with AHH-1. Inhibition of HSP70 significantly promoted cell apoptosis and suppressed cell proliferation in ALL cell lines. Suppression of HSP70 decreased TAK1 and increased Egr-1 protein expression. Further experiments indicated that overexpression of TAK1 ameliorated the effect of HSP70 inhibition on Egr-1 protein expression, cell apoptosis and proliferation. In order to determine whether the effect of HSP70 inhibition on apoptosis and proliferation of ALL cell lines could be achieved via regulation of Egr-1, we performed a loss-of-function experiment for Egr-1. Egr-1 suppression was found to reverse the effect of HSP70 inhibition on cell apoptosis and proliferation in ALL. Taken together, our results suggest that HSP70 inhibition upregulates Egr-1 via TAK1, inducing apoptosis and restricting proliferation in ALL cells.

Self-Assembly of Amphiphilic Peptides for Recognizing High Furin-Expressing Cancer Cells.

Self-assembled nanostructures of amphiphilic peptides have a wide range of applications in bioimaging and delivery systems. In this study, we design and synthesize a biocompatible amphiphilic peptide (C-3) consisting of an RVRRFFF sequence and a nitrobenzoxadiazole fluorophore that can self-assemble into stable micelles for specifically detecting furin, a kind of proprotein convertase with promoting tumor progression. The self-assembly of C-3 with a ß-sheet nanostructure is capable of a rapid and specific response to furin in only 5 min in aqueous solution because of the existence of the RVRR motif in the C-3 molecule. The C-3 nanostructures thus can selectively distinguish high furin-expressing cancer cells, like MDA-MB-231 cells, a kind of human breast cancer cells, from normal cells. Furthermore, the C-3 self-assembly can stay in living cells for a long time and are capable of durable detection of intracellular furin, being good for tracer analysis. To our knowledge, this is the first example of self-assembly of a soluble amphiphilic peptide that can selectively detect furin in high furin-expressing live cells.

Release of Amino- or Carboxy-Containing Compounds Triggered by HOCl: Application for Imaging and Drug Design.

The overproduction of HOCl is highly correlated with diseases such as atherosclerosis, rheumatoid arthritis, and cancer. Whilst acting as a marker of these diseases, HOCl might also be used as an activator of prodrugs or drug delivery systems for the treatment of the corresponding disease. In this work, a new platform of HOCl probes has been developed that integrates detection, imaging, and therapeutic functions. The probes can detect HOCl, using both NIR emission and the naked eye in vitro, with high sensitivity and selectivity at ultralow concentrations (the detection limit is at the nanomolar level). Basal levels of HOCl can be imaged in HL-60 cells without special stimulation. Moreover, the probes provided by this platform can rapidly release either amino- or carboxy-containing compounds from prodrugs, during HOCl detection and imaging, to realize a therapeutic effect.

Polydopamine-Based Tumor-Targeted Multifunctional Reagents for Computer Tomography/Fluorescence Dual-Mode Bioimaging-Guided Photothermal Therapy.

Development of multifunctional diagnosis and treatment reagents is very meaningful in clinical application. Herein, we developed a polydopamine-based (PDA-based) tumor targeted multifunctional reagent by surface-initiated atom transfer radical polymerization (ATRP) strategy. First, the targeted PDA nanoparticles were prepared via combining with folic acid (FA) and dopamine. Then ATRP technology was used to graft the europium(III) complexes onto PDA surface (defined as FEDA). A series of detections revealed that the FEDA nanoparticles had been successfully prepared and exhibited a bright X-ray computer tomography (CT) and photoluminescence (PL) dual-mode imaging efficiency and an excellent photothermal therapy (PTT) effect in vivo/in vitro.

Inhibition of HOXB7 suppresses p27-mediated acute lymphoblastic leukemia by regulating basic fibroblast growth factor and ERK1/2.

AIMS: Acute lymphoblastic leukemia (ALL) is characterized by abnormal proliferation of immature lymphocytes in the bone marrow, peripheral blood, and other tissues. HOXB7 is upregulated in tumors and is related to cell proliferation and cell cycle. However, the role of HOXB7 in ALL progression remains unclear. In this study, we explored the molecular mechanism of HOXB7 in cell viability and cell cycle in ALL cell lines. MATERIALS AND METHODS: Peripheral blood lymphocytes was isolated by Isopycnic Ficoll-Hypaque solution; Relative mRNA expression of HOXB7 was measured by RT-qPCR; Relative protein expressions of HOXB7, p27, bFGF, pERK1/2 were tested by Western blot assay; Cell viability was tested by MTT; Cell proliferation was detected by BrdU assay; 2.8. Cell cycle was analyzed by flow cytometry. KEY FINDINGS: HOXB7 was significantly elevated in peripheral blood lymphocytes of patients with ALL. HOXB7 was inhibited by HOXB7 siRNA transfection; cell viability decreased; and cell cycle was arrested in ALL cell lines. Meanwhile, HOXB7 suppression significantly induced the protein expression of p27 (cyclin-dependent kinase inhibitor). We also demonstrated the molecular mechanism of HOXB7 regulation on p27. HOXB7 suppression obviously inhibited the protein expressions of b basic fibroblast growth factor (bFGF) and p-ERK1/2. Also, the inhibitory effects of HOXB7 suppression on p-ERK1/2, cell viability, and cell cycle in ALL cell lines were markedly reversed after culturing with bFGF (9 ng/mL) for 24 h. After incubating with bFGF, cells with HOXB7 inhibition were treated with a specific ERK1/2 inhibitor, PD98095, after which the effects of bFGF on protein expression of p27, cell viability, and cell cycle were obviously reversed. SIGNIFICANCE: Our study suggests that inhibiting HOXB7 suppresses p27-mediated ALL progression by regulating bFGF/ERK1/2.

MoS2 quantum dots as a unique fluorescent "turn-off-on" probe for the simple and rapid determination of adenosine triphosphate.

We report a one-step hydrothermal method for the preparation of fluorescent molybdenum disulfide quantum dots (MoS2 QDs) and demonstrate the feasibility of fluorescent "turn-off-on" sensing of adenosine triphosphate (ATP) by using the MoS2 QDs. MoS2 QDs having strong blue-green fluorescence at 506 nm and good water-solubility were successfully synthesized by using ammonium tetrathiomolybdate as a single precursor. The fluorescence of MoS2 QDs was first quenched by Fe3+ through the formation of a MoS2 QDs/Fe3+ complex. ATP with the ability to coordinate with Fe3+ caused the dissociation of MoS2 QDs/Fe3+, resulting in the final release of MoS2 QDs and the recovery of fluorescence through a one-step competitive chelating process that took only 10 min to reach equilibrium at room temperature (RT). Facile and rapid sensing of Fe3+ and ATP could thus be achieved through the fluorescent "turn-off-on" strategy. Good linear relationships were obtained over the concentration ranges of 0-200 µM for Fe3+ and 0-140 µM for ATP with a lowest detectable concentration of 5 µM for ATP. Satisfactory results were obtained when the method was applied to a standard addition recovery trial of ATP in human serum samples. No complex surface modification during the preparation or detection process was needed based on the fluorescent "turn-off-on" method of the MoS2 QDs, which suggests its great potential in fluorescent sensing.

Water-soluble MoS2 quantum dots for facile and sensitive fluorescence sensing of alkaline phosphatase activity in serum and live cells based on the inner filter effect.

We report a facile and sensitive method for the detection of alkaline phosphatase (ALP) activity in serum and live cells using molybdenum disulfide quantum dots (MoS2 QDs) based on the Inner Filter Effect (IFE). In the present work, water soluble MoS2 QDs with bright green fluorescence were synthesized through direct ultrasonic exfoliation of MoS2 powder in 85 vol% aqueous ethanol solution. p-Nitrophenylphosphate (PNPP) was employed to act as an ALP substrate, and its enzyme catalytic product (p-nitrophenol (PNP)) functioned as a powerful absorber in the IFE to influence the excitation of MoS2 QDs. PNPP was transformed into PNP in the presence of ALP, leading to the transition of the absorption peak from 310 nm to 405 nm and therefore resulted in a complementary overlap between the absorption of PNP and the excitation of MoS2 QDs. The fluorescence of MoS2 QDs was quenched due to the significant weakening of the excitation of MoS2 QDs by competitive absorption between QDs and PNP. A good linear relationship was obtained from 0 to 5 U L-1 (R2 = 0.9919) using the present IFE based sensing strategy with the lowest detection activity of 0.1 U L-1. The proposed sensing approach was successfully applied to ALP sensing in serum samples and ALP inhibitor investigation, as well as in ALP cell imaging.

V8 induces apoptosis and the endoplasmic reticulum stress response in human multiple myeloma RPMI 8226 cells via the PERK-eIF2α-ATF4 signaling pathway.

Multiple myeloma (MM) is a fatal hematological cancer characterized by clonal plasma cell proliferation in the bone marrow. MM has an increasing global incidence and a poor prognosis. There are limited treatment options available for MM, and this is further compounded by the development of drug resistance. The present study demonstrated that 7-{4-[Bis-(2-hydroxyethyl)-amino]-butoxy}-5-hydroxy-8-methoxy-2-phenylchromen-4-one (V8), a novel synthetic flavonoid, induced apoptosis in human MM RPMI 8226 cells in a dose- and time-dependent manner, using cell viability assays and flow cytometry. Subsequently, V8-induced apoptosis in RPMI 8226 cells was revealed to occur via mitochondria-mediated pathways. The activity of caspase-3, -8 and -9, and the mRNA level of B-cell lymphoma 2 (Bcl-2) and B-cell lymphoma-extra large were greatly increased, while the expression of Bcl-2-like protein 4 and BH3 interacting domain death agonist was significantly decreased in RPMI 8226 cells following V8 treatment, as observed using quantitative polymerase chain reaction (qPCR). In addition, western blotting revealed that the release of mitochondrial cytochrome c into the cytosol was promoted by V8. Furthermore, a clear alteration in endoplasmic reticulum (ER) stress was observed in cells treated with V8; upregulation of glucose-regulated protein (GRP) 78, GRP94, C/EBP homologous protein, cleavage of caspase-12, phosphorylated protein kinase RNA-like endoplasmic reticulum kinase (p-PERK), phosphorylated eukaryotic initiation factor 2α (p-eIF2α) and activating transcription factor 4 (ATF4) was observed with qPCR and western blotting, suggesting that V8-induced apoptosis is involved in the ER stress response. Overall, the present results demonstrated that V8 induced apoptosis in human MM RPMI 8226 cells via the PERK-eIF2α-ATF4 ER stress response pathway, which may provide novel directions for exploiting this compound as a potential anti-neoplastic drug for MM therapy.

CSTMP induces apoptosis and mitochondrial dysfunction in human myeloma RPMI8226 cells via CHOP-dependent endoplasmic reticulum stress.

BACKGROUND: The natural product tetramethylpyrazine (TMP) and resveratrol have a variety of biologic activities, including anti-cancer effects. However the pharmacological function of CSTMP (a newly designed and synthesized TMP and resveratrol derivative) in cancer have not been elucidated. METHODS: In RPMI8226 cells, the cytotoxic effects and apoptosis were detected by MTT and Double staining for Annexin V-FITC and propidium iodide (PI). The protein and mRNA expression levels were detected by Real Time PCR and Western blot, respectively. The localization of cleaved caspase-12 was evaluated by immunofluorescent staining. The activation of caspase were measured by colorimetric assays and Western blot. RESULTS: CSTMP showed significantly cytotoxic effects and induced apoptosis in RPMI8226 cells. Caspase activation, Cytochrome c release and Bax, Bcl-2 and Bcl-XL levels analyses demonstrated that the anti-cancer effect of CSTMP in RPMI8226 cells was mediated by promoting caspase- and mitochondria-dependent apoptosis. In addition, CSTMP induced the increased expression of endoplasmic reticulum (ER) stress related proteins (CHOP, GRP78, GRP94 and cleaved caspase-12) and the activation of multiple branches of ER stress transducers (PERK-eIF2α, IRE1α and ATF6). Moreover, knockdown of CHOP by siRNA markedly inhibited CSTMP-induced cytotoxic effects, caspases activity and mitochondrial dysfunction in RPMI8226 cells. CONCLUSIONS: Our results indicated that CSTMP could induce apoptosis and mitochondrial dysfunction in RPMI8226 cells via CHOP-dependent ER stress.