Publications by authors named "Juemin Fang"

16 Publications

  • Page 1 of 1

Immune checkpoint inhibitor combined with anti-angiogenesis agent inhibits metastasis of advanced adenoid cystic carcinoma of the tongue base to the lung: a case report.

Ann Transl Med 2021 Aug;9(16):1353

Department of Oncology, Shanghai Tenth People's Hospital, TongJi Cancer Center, School of Medicine, Tongji University, Shanghai, China.

Patients diagnosed with advanced adenoid cystic carcinoma (ACC) with metastasis to the lung generally have poor prognosis when they exhibit resistance to conventional therapies. Programmed cell-death protein 1 (PD-1) inhibitors, a type of Immune checkpoint inhibitors (ICI), have shown good response in the treatment of various types of malignant tumors; however, objective response rates of monotherapy for advanced ACC are low. Anlotinib, a novel, orally managed tyrosine kinase inhibitor, that targets vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptor (PDGFR), and c-kit, has appeared great adequacy in treating numerous sorts of malignant tumors, particularly tumors with lung metastases. Here, we have presented a case of refractory ACC with lung metastases that was reduced after combinatorial treatment using the immune checkpoint inhibitor (ICI) toripalimab and anti-angiogenesis agent anlotinib. The patient achieved a reduction in lung metastases by chest computed tomography (CT) examination, with an outcome of stable disease (SD) of 5 months, a significant decrease in the levels of peripheral blood cytokines interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α), as well as good tolerance without noteworthy unfavorable reactions, indicating that the combined therapy of toripalimab and anlotinib may be utilized in the management of advanced ACC.
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http://dx.doi.org/10.21037/atm-21-3426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8422104PMC
August 2021

The upregulation of PYCR2 is associated with aggressive colon cancer progression and a poor prognosis.

Biochem Biophys Res Commun 2021 Oct 28;572:20-26. Epub 2021 Jul 28.

Department of Oncology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China; Tongji University Cancer Center, Shanghai, China. Electronic address:

PYCR2 has previously been shown to be related to a range of malignancies including hepatocellular carcinoma and melanoma, but its mechanistic functions and prognostic relevance in colon cancer patients remain to be defined. Herein, we used the Oncomine, Human Protein Atlas, The Cancer Genome Atlas (TCGA), and UALCAN databases to explore the expression of this gene in different human cancer, after which the relationship between PYCR2 expression and patient clinicopathologic characteristics was evaluated. We utilized an in vitro approach to evaluate the association between PYCR2 expression and colon cancer cell proliferation, migration, invasion, and tumor microsphere formation. The cell apoptosis was analyzed by flow cytometry. Gene set enrichment analysis (GSEA) approaches were additionally used to probe signaling pathways related to PYCR2. These analyses confirmed that PYCR2 was upregulated in several cancer types including colon cancer, with such upregulation correlating with a poor patient prognosis and with malignant clinicopathological characteristics. PYCR2 expression was identified as an independent predictor of colon cancer patients' survival, and in vitro analyses suggested that knocking down this gene was sufficient to disrupt the proliferative, migratory, invasive, and microsphere formation activities of colon cancer cells. Moreover, shPYCR2 transfection induced colon cancer cell apoptosis. GSEA suggested that high PYCR2 expression correlates with the differential enrichment of the Wnt β-catenin signaling, MYC targets, RNA polymerase, and Notch signaling pathways. Overall, these data indicate that PYCR2 is an important mediator of tumor progression and metastasis, and suggest that it may be a valuable prognostic indicator for colon cancer patient evaluation.
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http://dx.doi.org/10.1016/j.bbrc.2021.07.084DOI Listing
October 2021

Targeted genomic profiling revealed a unique clinical phenotype in intrahepatic cholangiocarcinoma with fibroblast growth factor receptor rearrangement.

Transl Oncol 2021 Oct 9;14(10):101168. Epub 2021 Jul 9.

Department of Oncology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Middle Yanchang Road, Shanghai 200072, P.R. China. Electronic address:

Genomic aberrations (GAs) in fibroblast growth factor receptors (FGFRs) are involved in the pathogenesis of intrahepatic cholangiocarcinoma (ICC), and clinical trials have shown efficacy of FGFR inhibitors in treating ICC patients with FGFR GAs such as FGFR2 rearrangement. To clarify the FGFRs GA profile and corresponding clinicopathological features in Chinese patients with ICC, a total of 257 cases were identified. Fourteen cases (5.45%) were positive for FGFR2 rearrangement. Further analysis on the 110 FGFR2 rearrangement negative cases showed that 13 patients present additional FGFRs GAs, including FGFR3 rearrangement (2.73%), and FGFRs mutations. When compared with patients without FGFRs GAs, those with FGFR2 or FGFR3 rearrangement presented more under the age of 58 years, female sex, HBsAb positivity, CD10 expression, and PD-L1 expression. The clinical characteristics between patients with FGFRs mutation and those without FGFRs GAs were similar, with the exception that cases with FGFRs mutation have more hepatolithiasis. We concluded that FGFR rearrangement is associated with unique clinical phenotypes in ICC.
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http://dx.doi.org/10.1016/j.tranon.2021.101168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283138PMC
October 2021

Targeting STAT3 Abrogates Tim-3 Upregulation of Adaptive Resistance to PD-1 Blockade on Regulatory T Cells of Melanoma.

Front Immunol 2021 15;12:654749. Epub 2021 Apr 15.

Department of Oncology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.

Background: Less than 20% of melanoma patients respond to programmed cell death-1 (PD-1) blockade immunotherapies. Thus, it is crucial to understand the dynamic changes in the tumor microenvironment (TME) after PD-1 blockade, for developing immunotherapy efficacy.

Methods: A genomic analysis was conducted by The Cancer Genome Atlas (TCGA) datasets and web platform TIMER2.0 datasets. Pathway enrichment analysis was performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Peripheral blood mononuclear cells (PBMCs), regulatory T (Treg) cells, and B16-F10 melanoma mice were used as models. The cellular and molecular characteristics and mechanisms of Treg cells in melanoma were assessed by performing gene expression studies, immunohistochemistry, RNA sequencing, and flow cytometry.

Results: Here, we evaluate the countenance of T cell immunoglobulin and mucin-domain containing-3 (Tim-3), and various immunosuppressive factors within tumor-infiltrated Treg cells after treatment with anti-PD-1 or the indicator transduction and activator of transcription 3 (STAT3) inhibitors. Increased expression of Tim-3 is markedly observed within the tissues of the PD-1 blockade resistance of melanoma patients. Targeting STAT3 significantly boosts the response of resistant-PD-1 therapy within the melanoma mouse model. Mechanistically, the manifestation of STAT3 decreases the expression of Tim-3 and various cytokines in the purified Treg cells from individual PBMCs and the murine melanoma model, limiting the immunosuppression of Treg cells.

Conclusions: Our findings indicate that Tim-3 expression on Treg cells within the TME is STAT3-dependent, providing support to STAT3 as a target and enhancing the immunotherapy for patients suffering from melanoma.
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http://dx.doi.org/10.3389/fimmu.2021.654749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082190PMC
April 2021

αPD-1-mesoCAR-T cells partially inhibit the growth of advanced/refractory ovarian cancer in a patient along with daily apatinib.

J Immunother Cancer 2021 02;9(2)

Department of Medical Oncology, Shanghai Tenth People's Hospital, Tongji University Cancer Center, School of Medicine, Tongji University, Shanghai 200072, China

Epithelial ovarian cancer (EOC) is the leading cause of death among gynecological malignancies in China. In particular, advanced/refractory ovarian cancer lacks effective targeted therapies due to the immunosuppressive and proangiogenic tumor microenvironment. Mesothelin (MSLN) has been found to be highly expressive in most EOC. Targeting MSLN by antibodies or chimeric antigen receptor-modified T (CAR-T) cells and immune checkpoint blockades as well as apatinib, an anti-angiogenic drug, have been used in patients with refractory ovarian cancer. Apatinib was reported to promote the infiltration of CD8 T cells in lung cancer. However, the combination therapy of CAR-T secreting anti-PD-1 antibody with apatinib in EOC has not been reported.

Case Presentation: Here we report a case of refractory EOC in a patient who had relapsed after multiline chemotherapy. The patient received autologous T cells that contained sequences encoding single-chain variable fragments specific for MSLN and full-length antibody for PD-1 (αPD-1). The modified T cells were called αPD-1-mesoCAR-T cells. After infusion, the copy number and PD-1 antibody secretion of the CAR-T cells were increased in the blood. By application of multimodality tumor tracking, MRI of the liver showed shrinkage of metastatic nodules from average diameter of 71.3-39.1 mm at month 2. The patient achieved partial response and survived more than 17 months. IL-6 levels in the patient fluctuated from the baseline to 2-4-folds after treatment, but side effects were mild with only grade 1 hypertension and fatigue.

Conclusion: αPD-1-mesoCAR-T cell therapy combined with apatinib demonstrates a potential therapeutic effect on advanced refractory ovarian cancer.

Trial Registration Number: NCT03615313.
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http://dx.doi.org/10.1136/jitc-2020-001162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887368PMC
February 2021

Personalized neoantigen pulsed dendritic cell vaccine for advanced lung cancer.

Signal Transduct Target Ther 2021 Jan 20;6(1):26. Epub 2021 Jan 20.

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China.

Neoantigens are considered to be ultimate target of tumor immunotherapy due to their high tumor specificity and immunogenicity. Dendritic cell (DCs) vaccines based on neoantigens have exciting effects in treatment of some malignant tumors and are a promising therapeutic modality. Lung cancer is a lethal disease with the highest morbidity and mortality rate in the world. Despite the rapid development of targeted therapy and immune checkpoint inhibitors for lung cancer in recent years, their efficacy is still unsatisfactory overall. Therefore, there is an urgent unmet clinical need for lung cancer treatment. Here, we attempted to treat lung cancer using a personalized neoantigen peptide-pulsed autologous DC vaccine and conducted a single-arm, 2 medical centers, pilot study initiated by the investigator (ChiCTR-ONC-16009100, NCT02956551). The patients enrolled were patients with heavily treated metastatic lung cancer. Candidate neoantigens were derived from whole-exome sequencing and RNA sequencing of fresh biopsy tissues as well as bioinformatics analysis. A total of 12 patients were enrolled in this study. A total of 85 vaccine treatments were administered with a median value of 5 doses/person (range: 3-14 doses/person). In total, 12-30 peptide-based neoantigens were selected for each patient. All treatment-related adverse events were grade 1-2 and there were no delays in dosing due to toxic effects. The objective effectiveness rate was 25%; the disease control rate was 75%; the median progression-free survival was 5.5 months and the median overall survival was 7.9 months. This study provides new evidence for neoantigen vaccine therapy and new therapeutic opportunities for lung cancer treatment.
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http://dx.doi.org/10.1038/s41392-020-00448-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817684PMC
January 2021

Liposomal doxorubicin-related palmar-plantar erythrodysesthesia (hand-foot syndrome): a case report.

J Int Med Res 2020 Dec;48(12):300060520974854

Department of Pharmacy, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.

Hand-foot syndrome (HFS) is a skin toxicity that occurs in areas of compressed skin. HFS manifests mainly in insensitive palms and the soles of the feet or in erythematous areas on the extremities caused by chemotherapy, which may be related to the dosage. This paper reports a case of HFS caused by liposomal doxorubicin. A 64-year-old Asian woman presented with severe erythema, ulceration, pruritus, and edema-related pain in her back, hands, and feet after receiving four cycles of liposomal doxorubicin. Clinicians and a pharmacist analyzed and evaluated the patient's adverse reactions. After symptomatic treatment and patient education, her HFS symptoms were significantly relieved. The purpose of this study was to raise clinical awareness regarding adverse events following liposomal doxorubicin injection, and to provide new ideas for the clinical treatment of these adverse events.
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http://dx.doi.org/10.1177/0300060520974854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770262PMC
December 2020

Targeting STAT3 enhances NDV-induced immunogenic cell death in prostate cancer cells.

J Cell Mol Med 2020 04 26;24(7):4286-4297. Epub 2020 Feb 26.

Department of Medical Oncology, Shanghai Tenths People's Hospital, School of Medicine, Tongji University, Shanghai, China.

Oncolytic Newcastle disease virus (NDV) induces immunogenic cell death (ICD), liberating danger-associated molecular patterns (DAMPs) that provokes defiance in neoplastic malignancy. The present study aims to investigate whether and how oncolytic NDV triggers ICD in prostate cancer cells. We show that NDV/FMW, an oncolytic NDV strain FMW, elicited the expression and release of several ICD markers, that is calreticulin (CRT), heat shock proteins (HSP70/90) and high-mobility group box 1 (HMGB1), in prostate cancer cells. Furthermore, pharmacological repression of apoptosis, necroptosis, autophagy or endoplasmic reticulum (ER) stress exerted diverse effects on the HMGB1 and HSP70/90 evacuation in NDV/FMW-infected prostate cancer cells. Moreover, ICD markers induced in prostate cancer cells upon NDV/FMW infection, were enhanced by either treatment with a STAT3 (signal transducer and activator of transcription 3) inhibitor or shRNA-mediated knockdown of STAT3. In nude mice bearing prostate cancer cell-derived tumours, the tumours injected with the supernatants of NDV/FMW-infected cells grew smaller than mock-treated tumours. These results indicate that oncolytic NDV provokes the expression of ICD makers in prostate cancer cells. Our data also suggest that a combination of inhibition of STAT3 with oncolytic NDV could boost NDV-based anti-tumour effects against prostate cancer.
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http://dx.doi.org/10.1111/jcmm.15089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7171322PMC
April 2020

STAT3 Contributes To Oncolytic Newcastle Disease Virus-Induced Immunogenic Cell Death in Melanoma Cells.

Front Oncol 2019 29;9:436. Epub 2019 May 29.

Department of Medical Oncology, School of Medicine, Shanghai Tenths People's Hospital, Tongji University, Shanghai, China.

Oncolytic viruses (OVs) are emerging as potent inducers of immunogenic cell death (ICD), releasing danger-associated molecular patterns (DAMPs) that induce potent anticancer immunity. Oncolytic Newcastle disease virus (NDV) has been shown to educe ICD in both glioma and lung cancer cells. The objective of this study is to investigate whether oncolytic NDV induces ICD in melanoma cells and how it is regulated. Various time points were actuated to check the expression and release of ICD markers induced by NDV strain, NDV/FMW in melanoma cell lines. The expression and release of ICD markers induced by oncolytic NDV strain, NDV/FMW, in melanoma cell lines at various time points were determined. Surface-exposed calreticulin (CRT) was inspected by confocal imaging. The supernatants of NDV/FMW infected cells were collected and concentrated for the determination of ATP secretion by ELISA, HMGB1, and HSP70/90 expression by immunoblot (IB) analysis. Pharmacological inhibition of apoptosis, autophagy, necroptosis, ER Stress, and STAT3 (signal transducer and activator of transcription 3) was achieved by treatment with small molecule inhibitors. Melanoma cell lines stably depleted of STAT3 were established with lentiviral constructs. Supernatants from NDV-infected cells were intratumorally injected to mice bearing melanoma cells-derived tumors. Oncolytic NDV induced CRT exposure, the release of HMGB1 and HSP70/90 as well as secretion of ATP in melanoma cells. Inhibition of apoptosis, autophagy, necroptosis or ER stress attenuated NDV/FMW-induced release of HMGB1 and HSP70/90. Moreover, NDV/FMW-induced ICD markers in melanoma cells were also suppressed by either treatment with a STAT3 inhibitor or shRNA-mediated depletion of STAT3. Of translational importance, treatment of mice bearing melanoma cells-derived tumors with supernatants from NDV/FMW-infected cells significantly inhibited tumor growth. Our data authenticate that oncolytic NDV/FMW might be a potent inducer of ICD in melanoma cells, which is amalgamated with several forms of cell death. We also show that STAT3 plays a role in NDV/FMW-induced ICD in melanoma cells. Together, our data highlight oncolytic NDV as propitious for cancer therapeutics by stimulatingan anti-melanoma immune response.
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http://dx.doi.org/10.3389/fonc.2019.00436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6548873PMC
May 2019

SHP2 negatively regulates HLA-ABC and PD-L1 expression via STAT1 phosphorylation in prostate cancer cells.

Oncotarget 2017 Aug 21;8(32):53518-53530. Epub 2017 Jun 21.

Department of Medical Oncology, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai 200072, China.

Src homology region 2-containing protein tyrosine phosphatase 2 (SHP2) is a ubiquitous protein tyrosine phosphatase that activates the signal transduction pathways of several growth factors and cytokines. In our study, SHP2 expression was very high in prostate cancer (PCa) cell lines, and the expression of phospho-signal transducer and activator of transcription 1 (p-STAT1) and STAT1 was very low. SHP2 knockdown upregulated the expression of p-STAT1 and downregulated phospho-extracellular signal regulated kinase (p-ERK). SHP2 depletion also increased the expression of human leukocyte antigen (HLA)-ABC and programmed death ligand 1 (PD-L1). When tumor cells were pretreated with Janus kinase 2 (JAK2) inhibitor, SHP2 depletion failed to induce HLA-ABC and PD-L1 expression. Furthermore, treating tumor cells with the mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK) inhibitor PD0325901 did not upregulate HLA-ABC and PD-L1. SHP2 depletion was associated with increased T-cell activation (CD25 MFI of CD8) by coculture of allogeneic healthy donor peripheral blood monocytes (PBMC) with SHP2 siRNA pretreated PCa cell lines. These results show that SHP2 targeting upregulates HLA-ABC and PD-L1 expression via STAT1 phosphorylation in PCa cells and SHP2 depletion could increase T-cell activation.
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http://dx.doi.org/10.18632/oncotarget.18591DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5581127PMC
August 2017

EGFR-induced phosphorylation of type Iγ phosphatidylinositol phosphate kinase promotes pancreatic cancer progression.

Oncotarget 2017 Jun;8(26):42621-42637

Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester MN, USA.

Pancreatic cancer is one of the deadliest malignancies and effective treatment has always been lacking. In current study, we investigated how the type Iγ phosphatidylinositol phosphate kinase (PIPKIγ) participates in the progression of pancreatic ductal adenocarcinoma (PDAC) for novel therapeutic potentials against this lethal disease. We found that PIPKIγ is up-regulated in all tested PDAC cell lines. The growth factor (including EGFR)-induced tyrosine phosphorylation of PIPKIγ is significantly elevated in in situ and metastatic PDAC tissues. Loss of PIPKIγ inhibits the aggressiveness of PDAC cells by restraining the activities of AKT and STAT3, as well as MT1-MMP expression. Therefore when planted into the pancreas of nude mice, PIPKIγ-depleted PDAC cells exhibits substantially repressed tumor growth and metastasis comparing to control PDAC cells. Results from further studies showed that the phosphorylation-deficient PIPKIγ mutant, unlike its wild-type counterpart, cannot rescue PDAC progression inhibited by PIPKIγ depletion. These findings indicate that PIPKIγ, functioning downstream of EGFR signaling, is critical to the progression of PDAC, and suggest that PIPKIγ is potentially a valuable therapeutic target for PDAC treatment.
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http://dx.doi.org/10.18632/oncotarget.16730DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5522093PMC
June 2017

Effect of Carotene and Lycopene on the Risk of Prostate Cancer: A Systematic Review and Dose-Response Meta-Analysis of Observational Studies.

PLoS One 2015 15;10(9):e0137427. Epub 2015 Sep 15.

Department of Oncology, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, No.301 Middle Yanchang Road, Zhabei District, Shanghai 200072, China.

Background: Many epidemiologic studies have investigated the association between carotenoids intake and risk of Prostate cancer (PCa). However, results have been inconclusive.

Methods: We conducted a systematic review and dose-response meta-analysis of dietary intake or blood concentrations of carotenoids in relation to PCa risk. We summarized the data from 34 eligible studies (10 cohort, 11 nested case-control and 13 case-control studies) and estimated summary Risk Ratios (RRs) and 95% confidence intervals (CIs) using random-effects models.

Results: Neither dietary β-carotene intake nor its blood levels was associated with reduced PCa risk. Dietary α-carotene intake and lycopene consumption (both dietary intake and its blood levels) were all associated with reduced risk of PCa (RR for dietary α-carotene intake: 0.87, 95%CI: 0.76-0.99; RR for dietary lycopene intake: 0.86, 95%CI: 0.75-0.98; RR for blood lycopene levels: 0.81, 95%CI: 0.69-0.96). However, neither blood α-carotene levels nor blood lycopene levels could reduce the risk of advanced PCa. Dose-response analysis indicated that risk of PCa was reduced by 2% per 0.2mg/day (95%CI: 0.96-0.99) increment of dietary α-carotene intake or 3% per 1mg/day (95%CI: 0.94-0.99) increment of dietary lycopene intake.

Conclusions: α-carotene and lycopene, but not β-carotene, were inversely associated with the risk of PCa. However, both α-carotene and lycopene could not lower the risk of advanced PCa.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0137427PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4570783PMC
May 2016

The traditional Chinese medicinal formula BDL301 suppresses tumor growth by inhibiting STAT3 pathway and inducing apoptosis in colorectal cancer cells.

DNA Cell Biol 2015 Mar 21;34(3):178-88. Epub 2015 Jan 21.

1 Department of Medical Oncology, Shanghai Tenth People's Hospital, Tongji University , School of Medicine, Shanghai, China .

The traditional Chinese medicinal formula BDL301 has been used to inhibit inflammation for hundreds of years. The development of colorectal cancer and chronic inflammation are closely related. In this study, we investigated whether BDL301 could inhibit tumor growth. We found that angiogenesis and tumor growth were both inhibited in vivo. In addition, apoptosis was induced and the signal transducer and activator of transcription-3 (STAT3) pathway were suppressed in the colorectal cancer cells in vitro and in vivo by BDL301. This study demonstrates that BDL301 exerted significant anticancer activity by inhibiting the STAT3 pathways and inducing apoptosis in colorectal cancer cells.
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http://dx.doi.org/10.1089/dna.2014.2532DOI Listing
March 2015

JAK2 inhibitor blocks the inflammation and growth of esophageal squamous cell carcinoma in vitro through the JAK/STAT3 pathway.

Oncol Rep 2015 Jan 14;33(1):494-502. Epub 2014 Nov 14.

Department of Medical Oncology, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai 200072, P.R. China.

Recent research indicates that the Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) pathway may play an important role in chronic inflammation which promotes cancer progression, yet the mechanism is not clear. The present study aimed to investigate the role of the JAK/STAT3 pathway in the growth and cancer-related inflammation (CRI) of esophageal squamous cell carcinoma (ESCC) by studying the crosstalk between the JAK/STAT3 pathway and nuclear factor-κB (NF-κB) and cyclooxygenase-2 (COX-2) which are important inflammatory factors associated with tumorigenesis. Cell growth and the cell cycle were assessed by CCK-8 assays and flow cytometry, respectively. The protein levels of STAT3, phosphorylated STAT3, VEGF, NF-κB p65, phosphorylated NF-κB p65 and COX-2 in ESCC cells following treatment with JAK2 inhibitor for 48 h or interleukin-6 (IL-6) for 24 h were detected. RT-PCR was performed to study the interaction among STAT3, NF-κB and COX-2 by transfection of siRNAs targeted at STAT3 and NF-κB. STAT3 was activated in 3 ESCC cell lines at different levels. Blocking the JAK/STAT3 pathway inhibited cancer growth through regulation of cell growth, cell cycle and angiogenesis. Likewise, abrogation of the JAK/STAT3 pathway decreased CRI by downregulating levels of NF-κB p65 phosphorylation, COX-2 and IL-6 concentration. In addition, CRI and cancer growth were accelerated by IL-6 through stimulation of the JAK/STAT3 and NF-κB p65 pathway. Moreover, STAT3 and NF-κB both regulated COX-2 as a downstream gene. The JAK/STAT3 pathway is an important pathway which links CRI and cancer growth through IL-6 and crosstalk with the NF-κB p65 subunit and COX-2. The STAT3 pathway could be a novel target both for cancer treatment and prevention in ESCC.
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http://dx.doi.org/10.3892/or.2014.3609DOI Listing
January 2015

Bevacizumab combined with low-dose S-1 as maintenance therapy with a long progression-free survival in an elderly patient with heavily pre-treated advanced gastric cancer: A case report.

Biomed Rep 2013 Mar 2;1(2):239-242. Epub 2012 Nov 2.

Department of Medical Oncology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China.

Gastric cancer is known to have a high incidence in several countries around the world, while the treatment of advanced gastric cancer remains a challenge. Recent studies have shown that the antibody bevacizumab, a monoclonal vascular endothelial growth factor antibody, is effective in several solid tumors, while experience regarding its effect on gastric cancer remains limited. An 84-year-old patient with advanced gastric remnant cancer with liver and retroperitoneal lymph node metastasis treated in our hospital benefitted from the use of bevacizumab. Since previous treatment with multiple chemotherapeutic agents resulted in progressive disease (PD), a combined treatment with bevacizumab (intravenously) and low-dose S-1 (orally) was administered. With this individualized treatment, the patient exhibited stable disease (SD) and therapy was maintained for a long period of time as maintenance therapy, with a progression-free survival of ∼25 months prior to PD. The serum tumor marker cancer antigen (CA) 199 decreased from 508.7 to 188.1 ng/ml. No severe side-effects of bevacizumab were observed, with the exception of controlled grade I bleeding gums due to the long-term use of bevacizumab. Although no large-scale clinical trials have been conducted to evaluate the role of bevacizumab in maintenance therapy and second- or even third-line treatment of advanced gastric cancer, we showed that bevacizumab combined with S-1 was effective and well-tolerated by this patient, suggesting that it be considered a viable option for elderly patients with advanced gastric cancer as maintenance therapy and that it provide a novel treatment for advanced gastric cancer. However, additional clinical trials are required to evaluate the exact effects of long-term bevacizumab treatment on patients with advanced gastric cancer.
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http://dx.doi.org/10.3892/br.2012.37DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3956215PMC
March 2013
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