Publications by authors named "Jiquan Fan"

7 Publications

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Clinical characteristics and risk factors associated with COVID-19 disease severity in patients with cancer in Wuhan, China: a multicentre, retrospective, cohort study.

Lancet Oncol 2020 07 29;21(7):893-903. Epub 2020 May 29.

Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: COVID-19 has spread globally. Epidemiological susceptibility to COVID-19 has been reported in patients with cancer. We aimed to systematically characterise clinical features and determine risk factors of COVID-19 disease severity for patients with cancer and COVID-19.

Methods: In this multicentre, retrospective, cohort study, we included all adult patients (aged ≥18 years) with any type of malignant solid tumours and haematological malignancy who were admitted to nine hospitals in Wuhan, China, with laboratory-confirmed COVID-19 between Jan 13 and March 18, 2020. Enrolled patients were statistically matched (2:1) with patients admitted with COVID-19 who did not have cancer with propensity score on the basis of age, sex, and comorbidities. Demographic characteristics, laboratory examinations, illness severity, and clinical interventions were compared between patients with COVID-19 with or without cancer as well as between patients with cancer with non-severe or severe COVID-19. COVID-19 disease severity was defined on admission on the basis of the WHO guidelines. Univariable and multivariable logistic regression, adjusted for age, sex, comorbidities, cancer type, tumour stage, and antitumour treatments, were used to explore risk factors associated with COVID-19 disease severity. This study was registered in the Chinese Clinical Trial Register, ChiCTR2000030807.

Findings: Between Jan 13 and March 18, 2020, 13 077 patients with COVID-19 were admitted to the nine hospitals in Wuhan and 232 patients with cancer and 519 statistically matched patients without cancer were enrolled. Median follow-up was 29 days (IQR 22-38) in patients with cancer and 27 days (20-35) in patients without cancer. Patients with cancer were more likely to have severe COVID-19 than patients without cancer (148 [64%] of 232 vs 166 [32%] of 519; odds ratio [OR] 3·61 [95% CI 2·59-5·04]; p<0·0001). Risk factors previously reported in patients without cancer, such as older age; elevated interleukin 6, procalcitonin, and D-dimer; and reduced lymphocytes were validated in patients with cancer. We also identified advanced tumour stage (OR 2·60, 95% CI 1·05-6·43; p=0·039), elevated tumour necrosis factor α (1·22, 1·01-1·47; p=0·037), elevated N-terminal pro-B-type natriuretic peptide (1·65, 1·03-2·78; p=0·032), reduced CD4+ T cells (0·84, 0·71-0·98; p=0·031), and reduced albumin-globulin ratio (0·12, 0·02-0·77; p=0·024) as risk factors of COVID-19 severity in patients with cancer.

Interpretation: Patients with cancer and COVID-19 were more likely to deteriorate into severe illness than those without cancer. The risk factors identified here could be helpful for early clinical surveillance of disease progression in patients with cancer who present with COVID-19.

Funding: China National Natural Science Foundation.
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http://dx.doi.org/10.1016/S1470-2045(20)30309-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7259911PMC
July 2020

The aberrant expression of ADAR1 promotes resistance to BET inhibitors in pancreatic cancer by stabilizing c-Myc.

Am J Cancer Res 2020 1;10(1):148-163. Epub 2020 Jan 1.

Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430022, China.

Pancreatic cancer is a malignant tumor with the worst prognosis worldwide. This cancer type requires new insight to help with diagnosis and, eventually, treatment. Adenosine deaminases acting on RNA 1 (ADAR1) is reportedly overexpressed in many types of tumors, such as lung, liver, breast, and esophageal cancers. However, the biological significance and specific mechanism of ADAR1 in pancreatic cancer have not been explored. In this study, we reveal that the expression level of ADAR1 is significantly up-regulated in pancreatic cancer tissues. We also find that highly expressed ADAR1 is closely associated with poor prognosis in pancreatic cancer specimens. Overexpressed ADAR1 equally increased the growth activity of pancreatic cancer cells and . We further demonstrate that ADAR1 stabilizes c-Myc through AKT signaling, which contributes to cancer cell resistance to BET inhibitors in pancreatic cancer cells. Moreover, we reveal that EZH2 regulates ADAR1 expression, and EZH2 and BET inhibitors show synergistic inhibition in pancreatic cancer. Collectively, these findings suggest that ADAR1 could serve as a new diagnostic and prognostic marker for the treatment of pancreatic cancer.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7017738PMC
January 2020

RhoA/ROCK pathway inhibition by fasudil suppresses the vasculogenic mimicry of U2OS osteosarcoma cells in vitro.

Anticancer Drugs 2017 06;28(5):514-521

aCancer Center bDepartment of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

GTPase RhoA and its downstream Rho-associated coiled-coil-containing protein kinases (ROCKs) are frequently overexpressed in human cancers. Inhibition of the RhoA/ROCK pathway blocks angiogenesis mediated by the vascular endothelial growth factor, which led us to investigate the role of this pathway in vasculogenic mimicry (VM) - a process by which aggressive cancer cells form vessel-like structures that provide adequate blood supply for tumor growth. We showed that the expression of RhoA and its effector kinases ROCK1/2 was much higher in human osteosarcoma (OS) tissues and the human OS cell line U2OS than in nontumorous tissues and cell line hFOB 1.19 using western blot analysis and real-time PCR. Inhibition of the RhoA/ROCK signaling pathway by the pharmacological inhibitor fasudil reduced vascular-like channels of U2OS cells in Matrigel. Furthermore, we used rhodamine-phalloidin immunofluorescence, wound healing assay, and transwell migration assay to examine the effect of fasudil on tumor cell plasticity and motility, both of which play key roles in VM formation. Finally, we explored the underlying mechanisms of fasudil-induced VM destruction. In this context, we showed that the RhoA/ROCK signaling pathway is a novel regulator in VM of U2OS OS cells and suggest that fasudil in conjunction with established treatments may present a novel therapeutic strategy for OS.
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http://dx.doi.org/10.1097/CAD.0000000000000490DOI Listing
June 2017

Alternative splicing of S6K1 promotes non-small cell lung cancer survival.

Tumour Biol 2016 Oct 27;37(10):13369-13376. Epub 2016 Jul 27.

Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 JieFang Avenue, Wuhan, 430022, China.

Ribosomal S6 kinase 1 (S6K1) that acts downstream of the mammalian target of rapamycin (mTOR) plays an important role in cell proliferation, protein translation, and cell survival. The gene RPS6KB1 encoding for S6K1 had been found to be alternatively spliced to form different isoforms. In this study, we identified that short isoforms of S6K1 splice variant were overproduced in non-small cell lung cancer (NSCLC). Moreover, suppression of S6K1 short isoforms inhibited NSCLC cell growth and induced apoptosis via upregulation of the BH3-only protein Bim in vitro and in vivo. Additionally, short isoforms of S6K1 activated mTORC1, leading to increased 4E-BP1 phosphorylation. Taken together, our findings suggested that S6K1 short isoforms were deregulated in NSCLC and promoted cell survival. Altogether, our study opens possibilities of new therapeutic approaches for NSCLC that selectively downregulate S6K1 shorter isoforms.
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http://dx.doi.org/10.1007/s13277-016-5253-1DOI Listing
October 2016

Effect of the dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor NVP-BEZ235 against human Merkel cell carcinoma MKL-1 cells.

Oncol Lett 2015 Dec 12;10(6):3663-3667. Epub 2015 Oct 12.

Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.

Merkel cell carcinoma (MCC) is an aggressive skin cancer with an increasing incidence. Aberrant activation of the phosphatidylinositol-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway is common in human cancers and has been revealed to play an important function in cell proliferation, metabolism and tumorigenesis. In the present study, NVP-BEZ235, a dual PI3K/mTOR inhibitor, was revealed to be effective in inhibiting proliferation and inducing cell cycle arrest in MKL-1 cells. Additional investigations revealed that NVP-BEZ235 attenuated PI3K/Akt/mTOR signaling and upregulated the levels of the cell cycle inhibitors p21 and p27. Overall, the present results possess considerable implications for future development of dual PI3K/mTOR inhibitor as potential agents in the management of MCC.
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http://dx.doi.org/10.3892/ol.2015.3791DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4665364PMC
December 2015

Peripheral T-cell lymphoma complicated by immunoglobulin A pemphigus: A case report and literature review.

Oncol Lett 2014 Jul 25;8(1):62-66. Epub 2014 Apr 25.

Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.

Peripheral T-cell lymphomas (PTCLs) account for 12% of non-Hodgkin's lymphomas (NHLs). Immunoglobulin (Ig) A pemphigus is an autoimmune blistering disease characterized by tissue-bound and circulating IgA antibodies that target epidermal cell surface components. Malignant lymphomas are often linked with autoimmune disease and the autoimmune blistering disease, paraneoplastic pemphigus, has been associated with NHL. However, cases of PTCLs that are complicated by IgA pemphigus are particularly rare. The current study presents the first known case of PTCL complicated by IgA pemphigus. A 43-year-old male was admitted to the Union Hospital (Wuhan, China) in March 2012 with multiple swollen lymph nodes. Pathology examinations revealed PTCL. Immunohistochemical staining was positive for cluster of differentiation (CD)2, CD3, CD5, CD7 and CD47, and negative for CD20. Ki-67 was ~40% positive. The patient was treated with four cycles of cyclophosphamide, Adriamycin, vincristine and prednisone, and two cycles of gemcitabine, cisplatin and dexamethasone; in addition, the patient received radiation of the retroperitoneal region (total dose, 36 Gy). The patient underwent thalidomide maintenance therapy for 20 days before flaccid blisters appeared on the trunk and limbs. Histopathology and immunofluorescence indicated IgA pemphigus, and intravenous methylprednisolone was administered, followed by treatment with prednisone. Subsequently, no evidence of recurrent lymphoma or pemphigus has been observed.
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http://dx.doi.org/10.3892/ol.2014.2088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4063644PMC
July 2014

The invasive malignancy from peritoneal epithelial cell: a report of four cases and review of literature.

Med Oncol 2011 Jun 19;28(2):597-600. Epub 2010 Mar 19.

Cancer Center, Union Hospital, Huazhong University of Science and Technology, 430023, Wuhan, Hubei, China.

To analyze the clinical characteristics, diagnosis and treatment of primary peritoneal carcinoma (PPC) and to review the literature, so as to raise the awareness of the disease. Four cases of PPC diagnosed in our department from March 2005 to September 2007 were retrospectively analyzed. Four cases were all treated with platinum-based chemotherapy. They were treated with intraperitoneal chemohyperthermia (IPCH) with cisplatin, carboplatin or oxaliplatin with a closed sterile circuit of 1,000 ml physiologic saline and inflow temperature is 43°C, while they were receiving high-intensity focused microwave hyperthermia (HIFMH) concomitantly. Intravenous paclitaxel or docetaxel was used in three patients, while cyclophosphamide and adriamycin injection in another patient. After two cycles of chemotherapy, ascites decreased significantly or even disappeared. Up to 6 January 2010, the four cases had survived for 38, 51, 33 and 29 months, respectively. PPC is a group of invasive malignancy derived from the peritoneal epithelium, it is common in women and is homogeneous with ovarian cancer in pathology. Diagnosis relies mainly on postoperative pathologic diagnosis and cytology after ruling out ovarian cancer and gastrointestinal cancer. Platinum-containing chemotherapy, IPCH and the administration of taxanes can improve the overall response rate and long-term survival.
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http://dx.doi.org/10.1007/s12032-010-9471-xDOI Listing
June 2011
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