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1.
Front Chem ; 8: 1, 2020.
Article in English | MEDLINE | ID: mdl-32117862

ABSTRACT

Supramolecular nanoparticles for photothermal therapy (PTT) have shown promising therapeutic efficacy in the primary tumor and great potential for turning the whole-body immune microenvironment from "cold" to "hot," which allows for the simultaneous treatment of the primary tumor and the metastatic site. In this work, we develop a liposome-based PTT nanoparticle through the self-assembly of FDA-approved intravenous injectable lipids and a photothermal agent, indocyanine green (ICG). The obtained ICG-liposome shows long-term storage stability, high ICG encapsulation efficiency (>95%), and enhanced near-infrared (NIR) light-triggered photothermal reaction both in vitro and in vivo. The ICG-liposome efficiently eradicated the primary tumor upon laser irradiation in two colon cancer animal models (CT26 and MC38) and promoted the infiltration of CD8 T cells to distant tumors. However, PTT from ICG-liposome shows only a minimal effect on the inhibition of distant tumor growth in long-term monitoring, predicting other immunosuppressive mechanisms that exist in the distant tumor. By immune-profiling of the tumor microenvironment, we find that the distant tumor growth after PTT highly correlates to compensatory upregulation of immune checkpoint biomarkers, including program death-1 (PD-1), T-cell immunoglobulin, and mucin domain-containing protein 3 (TIM-3), in tumor-infiltrating CD8 T cells. Based on this mechanism, we combine dual PD-1 and TIM-3 blockade with PTT in an MC38 tumor model. This combo successfully clears the primary tumor, generates a systemic immune response, and inhibits the growth of the distant tumor. The ICG-liposome-combined PD-1/TIM-3 blockade strategy sheds light on the future clinical use of supramolecular PTT for cancer immunotherapy.

2.
Acta Pharmacol Sin ; 36(12): 1514-9, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26592508

ABSTRACT

AIM: We have reported novel anticancer bioactive peptides (ACBPs) that show tumor-suppressive activities in human gastric cancer, leukemia, nasopharyngeal cancer, and gallbladder cancer. In this study, we investigated the effects of ACBPs on human colorectal cancer and the underlying mechanisms. METHODS: Cell growth and apoptosis of human colorectal tumor cell line HCT116 were measured using cell proliferation assay and flow cytometry, respectively. The expression levels of PARP, p53 and Mcl1A were assessed with Western blotting and immunohistochemistry. For evaluation of the in vivo antitumor activity of ACBPs, HCT116 xenograft nude mice were treated with ACBPs (35 µg/mL, ip) for 10 days. RESULTS: Treatment of HCT116 cells with ACBPs (35 µg/mL) for 4-6 days significantly inhibited the cell growth. Furthermore, treatment of HCT116 cells with ACBPs (35 µg/mL) for 6-12 h significantly enhanced UV-induced apoptosis, increased the expression of PARP and p53, and decreased the expression of Mcl-1. Administration of ACBPs did not change the body weight of HCT116 xenograft nude mice, but decreased the tumor growth by approximately 43%, and increased the expression of PARP and p53, and decreased the expression of Mcl-1 in xenograft mouse tumor tissues. CONCLUSION: Administration of ACBPs inhibits human colorectal tumor cell growth and induces apoptosis in vitro and in vivo through modulating the PARP-p53-Mcl-1 signaling pathway.


Subject(s)
Antineoplastic Agents/therapeutic use , Colorectal Neoplasms/drug therapy , Myeloid Cell Leukemia Sequence 1 Protein/metabolism , Peptides/therapeutic use , Poly(ADP-ribose) Polymerases/metabolism , Signal Transduction/drug effects , Tumor Suppressor Protein p53/metabolism , Animals , Apoptosis/drug effects , Cell Proliferation/drug effects , Colon/drug effects , Colon/metabolism , Colon/pathology , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , HCT116 Cells , Humans , Male , Mice, Nude , Rectum/drug effects , Rectum/metabolism , Rectum/pathology
3.
Curr Vasc Pharmacol ; 13(4): 492-503, 2015.
Article in English | MEDLINE | ID: mdl-25360840

ABSTRACT

OBJECTIVE: To reveal the cutoff point and influencing factors in the dynamic change in phenotypic group in patients with stable angina pectoris (SAP) after Xinxuekang capsule treatment. METHODS: Five hundred and seventy-six SAP patients were randomly assigned to receive Xinxuekang (XXK) capsules or Compound Danshen (CDS) tablets for 8 weeks. Global similarity degree analysis and nonlinear mixed effects modeling (NONMEM) were employed to reveal the cutoff points and influencing factors in dynamic changes in the SAP phenotypic group. The phenotypic group was defined as the six phenotypes in SAP, including angina, choking sensation in the chest, palpitations, dark purple lips, ecchymosis on the tongue, and fine-choppy pulse, which were quantitatively evaluated on Days 0, 14, 28, 42, and 56. RESULTS: Variation in the six individual phenotypes and distribution of the SAP phenotypic profile were similar between the two experimental groups, but cutoff points for changes in the SAP phenotypic group were 7.28 and 10.73 weeks in XXK and CDS groups, respectively. Degree of severity of SAP as well as study site significantly affected the tendency for change in the SAP Xueyu Zheng in both XXK and CDS treatment groups. Different Chinese patent drugs affected the tendency for change in phenotypic group in patients with SAP. XXK was superior to CDS in controlling a clinical phenotypic group. CONCLUSION: Based on global similarity degree analysis and NONMEM, the cutoff point and influencing factors in phenomic variation of SAP may be determined, to improve the development and modification of treatment regimens.


Subject(s)
Angina, Stable/diagnosis , Angina, Stable/drug therapy , Drugs, Chinese Herbal/therapeutic use , Medicine, Chinese Traditional/methods , Adult , Aged , Capsules , Data Interpretation, Statistical , Double-Blind Method , Drugs, Chinese Herbal/administration & dosage , Humans , Middle Aged , Salvia miltiorrhiza , Treatment Outcome
4.
Tumour Biol ; 35(10): 10051-6, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25015188

ABSTRACT

Recently, we reported that anticancer bioactive peptide (ACBP), purified from goat spleens immunized with human gastric cancer extracts, significantly inhibited gastric cancer cells in vitro and gastric tumors in vivo via repressing cell growth and promoting apoptosis, making it a promising potential biological anticancer drug. However, it is not known what genes are functionally required for the ACBP effects. Here, we first found that two tumor suppressor genes, cyclin-dependent kinase inhibitor 2B (CDKN2B) and growth arrest and DNA damage-inducible alpha (GADD45A), were upregulated significantly in the cells with ACBP treatment by microarray screening and the findings were validated by real-time RT-PCR. Next, GADD45A mRNA and protein expressions were downregulated in the gastric cancer cells by lentivirus-mediated RNAi; then, cell viability, cell cycle, and apoptosis were assayed by MTT and flow cytometry. Interestingly, our results indicated that cell viability was not dependent on GADD45A without ACBP treatment; however, cell sensitivity to ACBP was significantly decreased in ACBP-treated gastric cancer cells with GADD45A downregulation. Therefore, we demonstrate that GADD45A was functionally required for ACBP to inhibit gastric cancer cells, suggesting that GADD45A may become a biomarker for ACBP sensitivity. Our findings have significant implications on the molecular mechanism understanding, biomarker development, and anticancer drug development of ACBP.


Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Cell Cycle Checkpoints/drug effects , Cell Cycle Proteins/biosynthesis , Nuclear Proteins/biosynthesis , Stomach Neoplasms/metabolism , Blotting, Western , Cell Line, Tumor , Cyclin-Dependent Kinase Inhibitor p15/biosynthesis , Flow Cytometry , Humans , Oligonucleotide Array Sequence Analysis , Peptides/pharmacology , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Up-Regulation
5.
Zhonghua Bing Li Xue Za Zhi ; 42(9): 580-3, 2013 Sep.
Article in Chinese | MEDLINE | ID: mdl-24314241

ABSTRACT

OBJECTIVE: To use array-based comparative genomic hybridization (aCGH) technology to study the molecular cytogenetic abnormalities of anaplastic large cell lymphoma (ALCL) at genome level. METHODS: ALK protein expression and molecular genetic abnormalities were detected by immunohistochemistry and fluorescence in situ hybridization, respectively, in 25 cases of ALCL. Any chromosomal gains/losses were detected by aCGH and correlated with ALK status. RESULTS: aCGH showed that chromosomal alterations in all 25 ALCL cases, and the frequency of chromosomal gains was higher than that of the losses. Chromosomal gains at 5p13.2, 3q21.1, 2q21.3, 3p25.1, 14q32.33, and 17q21.2 regions were detected in more than 50% of the ALCL cases; gains at 4q27, 6p22.1, 20p11.21, 2q22.3, 4q35.1, 1p36.22, 8p23.1, 8p12, 11q14.1, 12q13.13, and 19p13.3 regions were detected in 30%-50% of the ALCL cases; chromosomal losses at 3q26.1 and 3q26.31 regions were detected in 36.0% (9/25) and 24.0% (6/25) of the ALCL cases, respectively. Chromosomal gains at 2q21.3, 6p22.1 and 3p25.1 regions showed significant differences between ALK (+) and ALK (-) ALCL groups (P < 0.05). CONCLUSIONS: aCGH demonstrates complex molecular genetic variations in all ALCL cases. Gains at 2q21.3, 6p22.1 and 3p25.1 regions are significantly different between ALK (+) and ALK (-) ALCL groups, suggesting that the pathogenesis of ALK (+) and ALK (-) ALCL may involve different signaling pathway.


Subject(s)
Chromosome Aberrations , Comparative Genomic Hybridization/methods , Lymphoma, Large-Cell, Anaplastic/enzymology , Lymphoma, Large-Cell, Anaplastic/genetics , Receptor Protein-Tyrosine Kinases/metabolism , Adolescent , Anaplastic Lymphoma Kinase , Female , Gene Expression Profiling , Humans , In Situ Hybridization, Fluorescence , Male , Paraffin Embedding , Receptor Protein-Tyrosine Kinases/genetics
6.
Chin Med J (Engl) ; 126(23): 4448-52, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24286405

ABSTRACT

BACKGROUND: Differential diagnosis of isolated calf muscle vein thrombosis (ICMVT) and gastrocnemius hematoma is essential for early identification of deep vein thrombosis (DVT). This study aimed to investigate the diagnostic value of high-frequency color Doppler ultrasound for differential diagnosis of ICMVT and gastrocnemius hematoma. METHODS: A retrospective case series of 35 ICMVT (M:F, 21:14; mean age (64.5 ± 10.6) years) and 23 gastrocnemius hematoma (M:F, 16:7; mean age (75.4 ± 11.8) years) patients with bilateral/unilateral lower limb pain was conducted between January 2006 and September 2012. Characteristics and the morphology of high-frequency color Doppler ultrasonography of the lower limb deep vein, great saphenous vein, calf muscles, skin, and soft tissue were examined. RESULTS: ICMVT hypoechoic signals were characterized by long, tube-like masses on longitudinal sections and oval masses on transverse sections, with apparent muscle thrombosis boundaries, distal and proximal venous connections, and, often, lower limb DVT. Gastrocnemius hematoma hypoechoic signals were characterized by large volumes, enhanced posterior hematoma echo, hyperechoic muscle boundaries, no hematoma blood flow, and no DVT, and clear differences in trauma/exercise- and oral anticoagulant-induced hematomas were readily apparent. According to the measurement, the ratio of long diameter/transverse diameter (D/T) in ICMVT patients was about less than 2.0, whereas in gastrocnemius hematoma patients the ratio was more than 2.0. Early stage isoechoic and hypoechoic signals were detected with gradually increasing ovular anechoic areas. Partial muscle fibers in the hematoma due to muscle fractures were apparent. CONCLUSION: High-frequency color Doppler ultrasound was found to be a sensitive and reliable method for differential diagnosis of ICMVT and gastrocnemius hematoma due to trauma and exercise or prolonged oral anticoagulant use.


Subject(s)
Leg/diagnostic imaging , Muscle, Skeletal/diagnostic imaging , Venous Thrombosis/diagnostic imaging , Aged , Diagnosis, Differential , Female , Humans , Male , Middle Aged , Retrospective Studies , Ultrasonography
7.
Zhonghua Yi Xue Za Zhi ; 92(37): 2649-51, 2012 Oct 09.
Article in Chinese | MEDLINE | ID: mdl-23290070

ABSTRACT

OBJECTIVE: To explore the sonographic characteristics of autoimmune pancreatitis (AIP). METHODS: The ultrasonographic features and clinical data of 8 AIP patients were analyzed retrospectively and compared with the findings of computed tomography and magnetic resonance imaging. RESULTS: Ultrasound images showed diffuse pancreatic swelling (n = 6), focal pancreatic head thickening (n = 1) and tail enlargement (n = 1). In 7 patients, pancreatic echogenicities were of Grade 1 or less while the other 1 patient Grade 2. Among them, 6 showed hyperechoic "pseudocapsule". And enlarged gallbladder, dilated biliary and pancreatic ducts were seen in 2 patients with jaundice. CONCLUSION: Ultrasonic features play an important role in an early diagnosis of AIP.


Subject(s)
Autoimmune Diseases/diagnostic imaging , Pancreatitis/diagnostic imaging , Aged , Female , Humans , Male , Middle Aged , Pancreatitis/etiology , Retrospective Studies , Ultrasonography
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