Search

Hematologic malignancies (HMs) mainly include acute and chronic leukemia, lymphoma, myeloma and other heterogeneous tumors that seriously threaten human life and health. The common effective treatments are radiotherapy, chemotherapy and hematopoietic stem cell transplantation (HSCT), which have limited options and are prone to tumor recurrence and (or) drug resistance. Metformin is the first-line drug for the treatment of type 2 diabetes (T2DM). Recently, studies identified the potential anti-cancer ability of metformin in both T2DM patients and patients that are non-diabetic. The latest epidemiological and preclinical studies suggested a potential benefit of metformin in the prevention and treatment of patients with HM. The mechanism may involve the activation of the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway by metformin as well as other AMPK-independent pathways to exert anti-cancer properties. In addition, combining current conventional anti-cancer drugs with metformin may improve the efficacy and reduce adverse drug reactions. Therefore, metformin can also be used as an adjuvant therapeutic agent for HM. This paper highlights the anti-hyperglycemic effects and potential anti-cancer effects of metformin, and also compiles the in vitro and clinical trials of metformin as an anti-cancer and chemosensitizing agent for the treatment of HM. The need for future research on the use of metformin in the treatment of HM is indicated.

Background: Glucose oxidase (GOx)-based starvation therapy is a new cancer treatment strategy. However, the characteristics such as limited curative effect and hypoxic tumor environment hinder its further application seriously., Methods: Herein, doxorubicin (DOX) loaded in hollow mesoporous copper sulfide (HMCuS) nanoparticles assembled with manganese dioxide (HMMD) as nanoshell was prepared. We developed a targeted enhanced cancer treatment method to camouflage HMMD by GOx-functionalized platelet (PLT) membranes (HMMD@PG)., Results: GOx can be specially transported to the tumor site with PLT membrane for effective starvation treatment. Glucose and oxygen (O 2 ) in the tumor were converted to H 2 O 2 under the catalysis of GOx. HMMD can catalyze H 2 O 2 to produce O 2 and consume glutathione (GSH) in time, which regulates the tumor microenvironment (TME) and improves the adverse conditions of anti-tumor. In addition, DOX encapsulated in HMCuS-MnO 2 release was accelerated from the nanoparticles after the "gatekeeper" MnO 2 is consumed. The study of anti-tumor mechanism shows that the remarkable tumor suppressive ability of HMMD@PG comes from the three peaks synergy of starvation treatment, photothermal treatment (PTT), and chemotherapy. This nanoplatform disguised by PLT membrane has significant tumor inhibition ability, good biocompatibility and almost has no side effects in main organs., Conclusion: This work broadens the application mode of GOx and shows the new development of a multi-mode collaborative processing system of nanoplatforms based on cell membrane camouflage., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 Du et al.)

Background: The death of a child is a traumatic life event that may influence mortality in patients with cancer. Only a few studies investigated this association and their findings have been mixed. We analyzed whether the death of a child is associated with mortality in patients with cancer., Methods: We conducted a cohort study of 371,673 parents who were diagnosed with cancer in Sweden during 1973 to 2014 by linking several population-based registers. We analyzed the association between the death of a child after the diagnosis of cancer and mortality using Cox proportional hazards models with time-varying exposure., Results: The death of a child was associated with an increased risk of mortality [HR, 1.27; 95% confidence intervals (CI), 1.17-1.39]. The association was present not only in case of children's death due to cancer or other natural deaths, but also in case of unnatural deaths. Mortality was increased only in the long-term follow-up period (HR, 1.42; 95% CI, 1.29-1.56), but not in the short-term (HR, 0.95; 95% CI, 0.78-1.15). The association was most pronounced following loss of an adult child and for patients with reproductive cancers., Conclusions: Death of a child is associated with increased risks of overall and long-term mortality in patients with cancer. The findings that the association was present not only in case of natural but also in case of unnatural deaths suggests that stress-related mechanisms may also operate., Impact: Our findings highlight the importance of psychosocial support for patients with cancer experiencing severe stress., (©2020 American Association for Cancer Research.)

Cancers have always been an intractable problem because of recurrence and drug resistance. In the past few decades, nanoparticles have been explored intensely to diagnose, prevent and treat malignancy due to their good penetrability and better targeting. However, most nanocarriers have poor biodegradation and can be discharged out of the body quickly or cleared by immune cells while failing to obtain effective drug concentration at the specific sites. The emergence of biological membrane encapsulation technology relieves the fast clearance of antitumor drugs and reduces toxicity in vivo. This review will discuss the advantages and disadvantages of several blood cell membrane-coated nanoparticles and further introduce exosome-carried drugs to evidence the promising prospect of biomimetic nanoparticle drug delivery systems., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Zhang et al.)

Human mucin-1 (MUC1) has attracted considerable attention owing to its overexpression in diverse malignancies. Here, for the rapid and efficient detection of MUC1, we present a SERS-colorimetric dual-mode aptasensor, by integrating SERS probes with magnetic separation, which has several distinctive advantages. Using such a dual-mode aptasensor, the colorimetric functionality is distinguishable by the naked eye, providing a fast and straightforward screening ability for the detection of MUC1. Moreover, SERS-based detection greatly improves the detection sensitivity, reaching a limit of detection of 0.1 U/mL. In addition, the combination of SERS and colorimetric method holds the advantages of these two techniques and thereby increases the reliability and efficiency of MUC1 detection. On the one hand, the magnetic nanobeads functionalized with MUC1-specific aptamer were utilized as an efficient capturing substrate for separating MUC1 from biological complex medium. On the other hand, the gold-silver core-shell nanoparticles modified with Raman reporters and the complementary sequences of MUC1 were used as the signal indicator, which could simultaneously report the SERS signal and colorimetric change. This strategy can achieve a good detection range and realize MUC1 analysis in real patients' samples. Thus, we anticipate that this kind of aptasensor would provide promising potential applications in the diagnosis and prognosis of cancers. Graphical abstract.

Exosomes are endosome-derived vesicles enriched in body fluids such as urine, blood, and saliva. So far, they have been recognized as potential biomarkers for cancer diagnostics. However, the present single-variate analysis of exosomes has greatly limited the accuracy and specificity of diagnoses. Besides, most diagnostic approaches focus on bulk analysis using lots of exosomes and tend to be less accurate because they are vulnerable to impure extraction and concentration differences of exosomes. To address these challenges, a quantitative analysis platform is developed to implement a sequential quantification analysis of multiple exosomal surface biomarkers at the single-exosome level, which utilizes DNA-PAINT and a machine learning algorithm to automatically analyze the results. As a proof of concept, the profiling of four exosomal surface biomarkers (HER2, GPC-1, EpCAM, EGFR) is developed to identify exosomes from cancer-derived blood samples. Then, this technique is further applied to detect pancreatic cancer and breast cancer from unknown samples with 100% accuracy., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Multidrug resistance is one of the leading causes of chemotherapy failure in cancer patients. Early detection and capture of drug-resistant tumor cells can facilitate the monitoring of the therapy process and improve the prognosis of patients. In this study, novel P-glycoprotein (P-gp) antibody modified porous hydrogel particles are proposed for drug-resistant tumor cells capture. The hydrogel particles employ a highly biocompatible hydrogel, methacrylate gelatin (GelMA), as the carrier and replicate from the silica colloidal crystal beads. By the modification of P-gp antibody probes on their surfaces, the hydrogel particles are endowed with the ability to capture drug-resistant tumor cells, which overexpress specific components of P-gp on their membranes. Additionally, the acquired ordered porous nanostructure of the particles can provide not only more surface area for antibody immobilization but also a nanopatterned platform for highly efficient target cell capture. The above advantages make the porous hydrogel particles ideal for efficient capture and detection of the drug-resistant tumor cells, which can be expected to facilitate the point-of-care pharmacotherapy and promisingly improve the patient outcomes., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Minimal residual disease (MRD) measurement is important for the diagnosis and prognosis of B cell hematological malignancies in the clinic. Thus, a sensitive and accurate method for monitoring the corresponding surface markers is in high demand for early diagnosis and treatment instruction. Herein, we developed a surface enhanced Raman scattering (SERS)-based sandwich-type immunoassay for the simultaneous detection of two surface markers (i.e., CD19 and CD20) in Raji cell lines as well as in clinical blood samples. First, to compare with the results obtained by flow cytometry, we evaluated the sensitivity and reproducibility of the SERS immunoassay for real-time detection of CD19 and CD20 expressions in Raji cells and blood samples. Then, we conducted follow-up tests on 13 B cell hematological malignancy patients for one month and dynamically monitored their CD19 and CD20 expressions by the SERS immunoassay. In addition to the improved sensitivity of the SERS method, good linear correlations between the SERS intensities and flow cytometry results were also observed for both CD19 and CD20, which indicated the accuracy of this SERS-based strategy. Therefore, this SERS-based simultaneous detection approach shows great potential for accurate and early diagnosis of MRD in B cell hematological malignancies.

As a kind of most important cancer biomarker, exosomes are getting more frequently investigated in cancer diagnosis. In this study, we proposed an SERS-based method for the screening and simultaneous multiple detection of exosomes using magnetic substrates and SERS probes. Specifically, the capturing substrates are achieved using gold shell magnetic nanobeads modified by aptamers, which can capture most kinds of exosomes by recognizing the generic surface protein CD63. Moreover, the SERS probes are made of gold nanoparticles decorated with a Raman reporter and a specific aptamer for targeting exosomes. Further, for the simultaneous detection of multiple kinds of exosomes, three kinds of SERS probes were designed using different SERS reporters. While detecting specific kinds of exosomes, the capturing substrates were mixed with these three kinds of SERS probes. When the target exosome is present, an apta-immunocomplex can be formed among the target exosomes, the substrate, and the corresponding kind of SERS probes, and the other non-specific SERS probes remain in the suspension. Hence, an SERS signal with a decreased intensity will be detected in the supernatant, indicating the presence of the target exosomes. Finally, this detection method has also been successfully employed for the detection of exosomes in real blood samples; this proves that the proposed SERS-based method is a promising tool for clinical cancer screening based on exosomes.

Autophagy is a normal physiological process necessary for cellular homeostasis to maintain adequate levels of cellular components. It is essential to stabilize the source of energy during development and nutritional stress and plays the dual role of survival or cell killing in various diseases including cancer. The selectivity of the response to removal of selected organelles may vary according to the each type. Macroautophagy forms a double-membraned autophagosome around the organelle destined for processing. Microautophagy involves direct engulfment of the cellular components by lysosomal invagination. Chaperone mediated autophagy (CMA) is highly selective and is dependent on the chaperone hsc70 for its activity. The effects of all these types are implemented by autophagy related genes. In this review, the markers, activators, inhibitors biological effects and roles of the three classes of autophagy in cancer and obesity are discussed., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose: Develop and evaluate an electrochemical method to identify healthy individuals, malignant hematopathic patients and solid tumor patients by detecting the leukocytes in whole-blood., Methods: A total of 114 individual blood samples obtained from our affiliated hospital in China (June 2015- August 2015) were divided into three groups: healthy individuals (n = 35), hematologic malignancies (n = 41) and solid tumors (n = 38). An electrochemical workstation system was used to measure differential pulse voltammetry due to the different electrochemical behaviors of leukocytes in blood samples. Then, one-way analysis of variance (ANOVA) was applied to analyze the scanning curves and to compare the peak potential and peak current., Results: The scanning curve demonstrated the specific electrochemical behaviors of the blank potassium ferricyanide solution and that mixed with blood samples in different groups. Significant differences in mean peak potentials of mixture and shifts (ΔEp (mV)) were observed of the three groups (P< = 0.001). 106.00±9.00 and 3.14±7.48 for Group healthy individuals, 120.90±11.18 and 18.10±8.81 for Group hematologic malignancies, 136.84±11.53 and 32.89±10.50 for Group solid tumors, respectively. In contrast, there were no significant differences in the peak currents and shifts., Conclusions: The newly developed method to apply the electrochemical workstation system to identify hematologic malignancies and solid tumors with good sensitivity and specificity might be effective, suggesting a potential utility in clinical application.

Siltuximab (CNTO 328) is a promising antibody-drug conjugate targeting cytokine interleukin-6 (IL-6). It is highly binding to IL-6 and thus neutralizing IL-6 bioactivity and promoting death of tumor cell. In this review, we mainly focus on the mechanisms, clinical studies, and adverse effect of siltuximab in the treatment of human malignancies. We also provide our recommendations for siltuximab treatment in the future.

Objective: MicroRNA-182 (miR-182) exhibits altered expression in various cancers. The aim of this study was to investigate the predictive value of miR-182 expression for cancer patient survival., Methods: Eligible studies were identified through multiple search strategies, and the hazard ratios (HRs) for patient outcomes were extracted and estimated. A meta-analysis was performed to evaluate the prognostic value of miR-182., Results: In total, 14 studies were included. A high miR-182 expression level predicted a worse outcome with a pooled HR of 2.18 (95% CI: 1.53-3.11) in ten studies related to overall survival (OS), especially in Chinese populations. The results of seven studies evaluating disease-free survival/relapse-free survival/recurrence-free interval/disease-specific survival (DFS/RFS/RFI/DSS) produced a pooled HR of 1.77 (95% CI: 0.91-3.43), which was not statistically significant; however, the trend was positive. When disregarding the DSS from one study, the expression of miR-182 was significantly correlated with DFS/RFS/RFI (pooled HR = 2.52, 95% CI: 1.67-3.79)., Conclusions: High miR-182 expression is associated with poor OS and DFS/RFS/RFI in some types of cancers, and miR-182 may be a useful prognostic biomarker for predicting cancer prognosis. However, given the current insufficient relevant data, further clinical studies are needed.

Magnetic nanoparticles have been intensively investigated due to their magnetic characteristics, quantum dot effects, as well as their potential applications in the area of bioscience and medicine. Very promising nanoparticles are magnetic iron oxide nanoparticles with appropriate surface modification which have been widely used experimentally for masses of in vivo applications such as magnetic resonance imaging contrast enhancement, drug delivery, and hyperthermia, etc.. All these biomedical applications require that these nanoparticles have effective magnetic values and suitable sizes. On the other hand, these applications need special surface modification of these particles, which not only have to be non-toxic and biocompatible, but also allow a targetable drug delivery in a specific area. This review summarizes the current research situation and development of magnetic iron oxide nanoparticles, and the biomedical applications ranging from drug delivery to hyperthermia for tumor-targeted therapy.

In this review we have focused on the utilization of the biocompatible nanomaterials to reverse multidrug resistance (MDR), a major clinical obstacle in cancer therapeutics. Based on the comprehension of the mechanism of MDR and common reversal methods, the strategies and key properties of anti-MDR nanomaterials are explored and described to show how these features could provide the potential therapeutic effects that are not achievable with other modalities. The use of biocompatible nanoparticles with different designs and therapeutic approaches to reverse the MDR of cancer chemotherapeutics offers promising opportunities to benefit patients in the future.

Porous nanostructure with its unique properties is found to be able to hold promise in drug delivery. We fabricated the one-dimensional titanium dioxide whiskers (TiO2 Ws) and designed a strategy to explore their drug delivery application and anti-tumor function combined with daunorubicin (DNR). We observed good biocompatibility of TiO2 Ws and noted better photocatalytic activity. In human hepatocarcinoma cells (SMMC-7721 cells), TiO2 Ws can obviously increase the intracellular concentration of DNR and enhance its potential anti-tumor efficiency, indicating TiO2 Ws could produce an efficient drug delivery carrier effect importing DNR into target cells. Furthermore, its photocatalysis further led to the enhanced mortality of cancer cells under UV irradiation. These findings reveal that TiO2 Ws-based delivery of anticancer drugs represents a promising approach in cancer therapy.

In this study, we have proposed a novel strategy for the rapid identification and high sensitive detection of different kinds of cancer cells by means of electrochemical and contact angle measurements. A simple, unlabeled method based on the functionalized Au nanoparticles (GNPs) modified interface has been utilized to distinguish the different cancer cells, including lung cancer cells, liver cancer cells, drug sensitive leukemia K562/B.W cells and drug resistant leukemia K562/ADM cells. The relevant results indicate that under optimal conditions, this method can provide the quantitative determination of cancer cells, with a detection limit of approximately 10(3)cells mL(-1). Our observations demonstrate that the difference in the hydrophilic properties for target cellular surfaces and in the uptake efficiency of the anticancer drug daunorubicin for different cancer cells could be readily chosen as the elements of cancer identification and sensitive detection. This raises the possibility to advance the promising clinic diagnosis and monitoring of tumors with the aim of successful chemotherapy of human cancers.

In this report, we have explored the possibility to facilitate the drug delivery efficiency for cancer cells through the surface chemistry modification of gold nanoparticles (AuNPs), where the functional AuNPs were synthesized by the ligand exchange reaction between triphenyl phosphide-stabilized precursor nanoparticles and mercaptopropionic acid. Our observations demonstrate that the combination of the anticancer drug daunorubicin with relevant AuNPs could be used as an efficient way to mark the cancer cells, which may afford the potential application for the early diagnosis of the respective cancers. Besides, the synergistic enhanced effect of the relevant gold nanoparticles on the drug uptake of target cancer cells could provide a new strategy to inhibit the multidrug resistance of the respective cancers.