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A major cause of death in cancer patients is distant metastasis of tumors, in which circulating tumor cells (CTCs) are an important marker. Photoacoustic flow cytometry (PAFC) can monitor CTCs in real time, non‐invasively, and label‐free; we built a PAFC system and validated the feasibility of PAFC for monitoring CTCs using in vivo animal experiments. By cultivating heavily‐pigmented and moderately‐pigmented melanoma cells, more CTCs were detected in mice inoculated with moderately‐pigmented tumor cells, resulting in more distant metastases and poorer survival status. Tumor cells with lower melanin content may produce more CTCs, increasing the risk of metastasis. CTC melanin content may be down‐regulated during the metastatic which may be a potential indicator for assessing the risk of melanoma metastasis. In conclusion, PAFC can be used to assess the risk of melanoma metastasis by dynamically monitoring the number of CTCs and the CTC melanin content in future clinical diagnoses. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common cancer, and triple‐negative breast cancer (TNBC) has the highest metastasis and mortality rate among all breast cancer subtypes. Rujifang is a traditional Chinese medicine formula with many years of clinical application in breast cancer treatment. Here, we aim to investigate the effects of Rujifang on circulating tumor cell (CTC) dynamics and the tumor microenvironment in a ZsGreen/luciferase double‐labeled TNBC orthotopic model. We report that the number of CTCs monitored by in vivo flow cytometry (IVFC) strongly correlates with disease progression. Rujifang treatment decreased the number of CTCs and suppressed the distant metastasis of TNBC. Moreover, immunofluorescence analysis revealed that Rujifang treatment could affect the tumor microenvironment by downregulating Kindlin‐1, which has been reported to promote metastasis of TNBC. Our study provides evidence of the anti‐metastatic effect of Rujifang against TNBC in an animal model using fluorescent cell lines. The results suggest the potential therapeutic value of Rujifang as an anti‐metastatic drug, however, further clinical trials are needed to validate these findings in humans. [ABSTRACT FROM AUTHOR]

Platelets buoy up cancer metastasis via arresting cancer cells, enhancing their adhesion, and facilitating their extravasation through the vasculature. When deprived of intracellular and granular contents, platelet decoys could prevent metastatic tumor formation. Inspired by these, we developed nanoplatesomes by fusing platelet membranes with lipid membranes (P-Lipo) to restrain metastatic tumor formation more efficiently. It was shown nanoplateletsomes bound with circulating tumor cells (CTC) efficiently, interfered with CTC arrest by vessel endothelial cells, CTC extravasation through endothelial layers, and epithelial-mesenchymal transition of tumor cells as nanodecoys. More importantly, in the mouse breast tumor metastasis model, nanoplateletsomes could decrease CTC survival in the blood and counteract metastatic tumor growth efficiently by inhibiting the inflammation and suppressing CTC escape. Therefore, nanoplatelesomes might usher in a new avenue to suppress lung metastasis. Nanoplateletsomes were inaugurated to restrain metastatic tumor formation efficiently through decoy and active targeting, serving as a platform to orchestrate the inhibition of circulating tumor cell survival and metastasis. [Display omitted] [ABSTRACT FROM AUTHOR]

Circulating tumor cells (CTCs) play an essential role in metastasis and serve as an important prognostic biomarker. The technology of CTC labeling and detection in vivo can greatly improve the research of cancer metastasis and therapy. However, there is no in vivo technology to detect CTCs in clinic. In this study, we demonstrate that 2‐[N‐(7‐nitrobenz‐2‐oxa‐1,3‐diazol‐4‐yl) amino]‐2‐deoxy‐d‐glucose (2‐NBDG), a 2‐deoxy‐glucose analog, can work in vivo to indicate CTCs and metastases fluorescently by direct intravenous injection. During the development of an implanted tumor in mice, the spontaneous CTCs released from the primary tumor into blood vessels can be labeled by 2‐NBDG due to the abnormal metabolism of CTCs. The green fluorescence of 2‐NBDG from CTCs is then noninvasively detected by an in vivo flow cytometry system. Due to the high uptake of glucose by tumor cells, the CTCs in mice can maintain a high 2‐NBDG level and thus be distinguished by 2‐NBDG fluorescence in vivo efficiently, enabling tumor detection in vivo like positron emission tomography (PET) but at the single‐cell resolution. Our results suggest 2‐NBDG, a glucose analog with high biosafety, holds promising potential in clinical applications, similar to the widely‐used contrast medium 2‐F18‐fluorodeoxyglucose in PET. [ABSTRACT FROM AUTHOR]

We examined our hypothesis that high‐intensity focused ultrasound (HIFU) treatment of pancreatic ductal adenocarcinoma (PDAC) in nude mice models may lead to an increased occurrence of hematogenous metastasis. The human PDAC cell line BxPC‐3 transfected with mCherry was implanted into nude mice to establish orthotopic and subcutaneous xenograft (OX and SX) tumor models. Mice were exposed to HIFU when tumor sizes reached approximately 200–300 mm3. The OX and SX tumor models were monitored continuously for tumor growth characteristics and hematogenous metastasis using in vivo flow cytometric (IVFC) detection of circulating tumor cells (CTCs) from the pancreas. We chose an appropriate mouse model to further examine whether or not HIFU increases the potential risk of hematogenous metastasis, using IVFC detection. Our results showed that the CTC number was greater in the OX model than in the SX model. The CTC number in the OX model increased gradually over time, whereas the CTC number in the SX model remained low. Therefore, the OX model was better for studying tumor metastasis by IVFC detection. We found significantly decreased CTC numbers and tumor volume after HIFU ablation. Our results showed the applicability of the PDAC OX tumor model for studying the occurrence of tumor metastasis due to the generation of CTCs. HIFU ablation substantially restricted PDAC hematogenous metastasis and provided effective tumor control locally. © 2020 The Authors. Cytometry Part A published by Wiley Periodicals Inc., on behalf of International Society for Advancement of Cytometry. [ABSTRACT FROM AUTHOR]

Cancer is a big threat to human life. Asia has about 60% of the global population and accounts for half of global cancer incidence and mortality. Circulating tumor cells (CTCs) have been a good biomarker for cancer diagnosis, staging, and prognosis. Conventional detection methods of CTCs require drawing blood. It may disturb the biological environment and limited real‐time monitoring. in vivo flow cytometry (IVFC) is a burgeoning technique that allows noninvasive detection of CTCs in vivo. Here, we review the technical development of IVFC based on various contrast principles, including fluorescence IVFC, photoacoustic IVFC, imaging IVFC, and label‐free IVFC. This powerful tool has been applied widely in many areas of cancer‐related studies, especially the CTC studies. We review applications of IVFC in preclinical studies on prevalent cancers in Asia, including liver cancer, blood cancer, and so forth. Other cancer‐related studies in breast cancer, prostate cancer, cancer‐related stem cell research and drug studies are also reviewed. © 2019 International Society for Advancement of Cytometry [ABSTRACT FROM AUTHOR]

Circulating tumor cells (CTCs) play a key role in cancer metastasis but are very difficult to detect. in vivo monitoring CTCs has been recognized as an important technique for cancer research and clinical diagnosis. Recently, a noninvasive method, in vivo flow cytometry (IVFC) has been developed to enable continuous, real‐time, and long‐duration detection of CTCs in animal models by detecting CTC fluorescence in blood vessels excited by lasers. In this study, we present a simple optical scheme for direct noninvasive CTC detection using confocal microscopes. We demonstrate that line scanning of confocal microscopy can provide effective and quantitative CTC detection in live mice during cancer development. Rare CTC signals can be acquired at the early stage of the tumor development after implantation of subcutaneous tumor and monitored continuously to the end. Signals from CTC clusters can also be acquired and distinguished from single CTCs. Our results suggest confocal microscopy is a simple and reliable method for biologists and doctors to use for cancer research. © 2018 International Society for Advancement of Cytometry [ABSTRACT FROM AUTHOR]

Abstract: It remains controversial whether surgical castration prolongs survival rate and improves therapy prospects in patients suffering from prostate cancer. We used PC3 cell line to establish prostate tumor models. In vivo flow cytometry and ultrasonic imaging were used to monitor the process of prostate cancer growth, development and metastasis. We found out that the number of circulating tumor cells (CTCs) in orthotopic tumor model was higher than that in subcutaneous tumor model. The CTC number in orthotopic tumor model was due to burst growth, while CTC number in subcutaneous tumor model showed a gradual increase with tumor size. After androgen deprivation therapy (ADT) through testicular extraction, we constructed GFP‐PC3 subcutaneous tumor models and orthotopic tumor models. We found dramatically decreased CTC number, relieved symptoms caused by the tumor, and significantly prolonged survival time after testicular extraction in orthotopically transplanted prostate tumor model, while the carcinogenesis process and metastases were little influenced by ADT in subcutaneous tumor model. ADT treatment can restrict tumor growth, decrease the CTC number significantly and inhibit distant invasion through inhibition of tumor proliferation and tumor angiogenesis in orthotopical prostate tumor model. © 2018 International Society for Advancement of Cytometry [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a highly malignant tumor characterized by rapid progression, poor prognosis, and frequent hematogenous metastasis. A minimally invasive diagnostic biomarker that can predict disease progression and treatment response would be of extraordinary benefit. Therefore, we have investigated whether the number of circulating tumor cells (CTCs) is correlated with disease progression and treatment response in HCC. Here we report that the number of CTCs, monitored by in vivo flow cytometry (IVFC), is strongly correlated with disease progression and treatment response in a highly metastatic orthotopic nude mouse model of green fluorescent protein (GFP)-labeled HCC. Sorafenib treatment reduces the number of CTCs significantly. The decreased number of CTCs is consistent with low lung metastasis. This study has demonstrated a considerable clinical value of CTCs as a biomarker in predicting disease progression and monitoring therapeutic efficacy in patients with HCC. © 2015 International Society for Advancement of Cytometry [ABSTRACT FROM AUTHOR]

In article number 1806620, Chen Jiang and co‐workers, inspired by the ability of activated platelets to track tumor metastasis, develop a novel activated plateletstargeting micelle for efficient anticancer drug delivery to primary and metastatic tumors. After specifically binding to activated platelets in circulation, the micelles capture circulating tumor cells (CTCs) through the "platelet bridge" and eliminate CTCs to prevent metastasis. [ABSTRACT FROM AUTHOR]

The frequent relapse and metastasis characteristics of triple negative breast cancer (TNBC) make it a fraught issue with very poor prognosis in clinic. An effective treatment for TNBC should prevent and even eliminate metastasis as well as suppress primary lesion expansion. Recent progress reveals that platelets can be recruited and activated by tumor cells through intercellular adhesion molecules (ICAM), and help aggressive circulating tumor cells (CTCs) form metastasis. Therefore, activated platelets are considered with possession of tumor‐homing, CTC‐capturing, and metastasis‐targeting abilities. In this work, a P‐selectin (expressed on activated platelet surface) targeting peptide (PSN) is modified on a redox‐responsive paclitaxel‐loaded micelle (PSN‐PEG‐SS‐PTX4 micelle) to utilize activated platelets as a "bridge" for interaction with cancer cells. The PSN‐modified micelle can easily adhere to the surface of activated platelets and subsequently capture CTCs in blood circulation. Compared to Taxol and PEG‐SS‐PTX4 micelle, PSN‐PEG‐SS‐PTX4 micelle also exhibits enhanced primary TNBC/metastasis targeting and penetrating effect through binding with tumor infiltrating platelets and thus significantly improves treatment outcome. More importantly, PSN‐PEG‐SS‐PTX4 micelle potently suppressed lung metastasis of TNBC and reduced incidence of distant liver metastasis. The activated platelet‐targeting redox‐responsive micelle system provides a promising prospect for the omnidirectional treatment of metastatic cancer. A novel P‐selectin targeting micelle with controlled drug release is designed to utilize activated platelets as an endogenous device for efficient drug delivery to metastatic tumors. The micelle captures and eliminates circulating tumor cells via binding with activated platelets to prevent metastasis as well as penetrates and accumulates at primary tumors or metastasis via tumor‐infiltrating activated platelets. [ABSTRACT FROM AUTHOR]

Antiangiogenesis therapy has been served as a potent cancer treatment strategy for decades, yet disrupting neovasculature would provoke tumor cells into invasive growth and result in distal metastasis. The basic cause of cancer metastasis can be traced down to the presence of circulating tumor cells (CTCs) which detach from primary tumor site and act as ‘seeds’. Epithelial cell adhesion molecule (EpCAM) is a potential biomarker for selective capture of epithelium-derived CTCs. Here, we integrated tumor neovessles-targetable ligands K237 peptide with Ep23 aptamer against EpCAM into a single drug-loaded nanoplatform using paclitaxel (PTX) as the model drug, aiming at damaging the primary tumor and neutralizing CTCs simultaneously to achieve a synergistic anti-tumor therapeutic effect. Enhanced cellular uptake, cell apoptosis-induction and cell-viability inhibition efficiency of the peptide and aptamer dual-functionalized nanoparticles (dTNP) were observed in both human umbilical vein endothelial cells (HUVEC) and 4T1 cells in vitro . Using cone-and-plate viscometer to create venous flow velocity, dTNP was also found to be able to capture CTCs under shear stress. The CTC-targeting and neutralization effect of dTNP in bloodstream and 4T1-GFP cell-derived lung metastasis mice model was confirmed via in vivo flow cytometry (IVFC), intravital imaging and confocal microscopy analysis. As a result, the orthotropic breast tumor-bearing mice administrated with PTX-loaded dTNP exhibited the optimal therapeutic effect. Taken together, the findings here provided direct evidence that the tumor neovasculature and CTCs dual-targeting drug delivery system could provide a novel modality for the treatment of highly-invasive breast cancer. [ABSTRACT FROM AUTHOR]