Publications by authors named "Shuanglin Liu"

12 Publications

  • Page 1 of 1

Cancer/testis antigens: from serology to mRNA cancer vaccine.

Semin Cancer Biol 2021 Apr 25. Epub 2021 Apr 25.

Section of Epidemiology and Population Science, Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, United States. Electronic address:

Cancer/testis antigens (CTAs) are a group of tumor antigens expressed in numerous cancer tissues, as well as in the testis and placental tissues. There are over 200 CTAs supported by serology and expression data. The expression patterns of CTAs reflect the similarities between the processes of gametogenesis and tumorigenesis. It is notable that CTAs are highly expressed in three types of cancers (lung cancer, bladder cancer, and skin cancer), all of which have a metal etiology. Here, we review the expression, regulation, and function of CTAs and their translational prospects as cancer biomarkers and treatment targets. Many CTAs are highly immunogenic, tissue-specific, and frequently expressed in cancer tissues but not under physiological conditions, rendering them promising candidates for cancer detection. Some CTAs are associated with clinical outcomes, so they may serve as prognostic biomarkers. A small number of CTAs are membrane-bound, making them ideal targets for chimeric antigen receptor (CAR) T cells. Mounting evidence suggests that CTAs induce humoral or cellular immune responses, providing cancer immunotherapeutic opportunities for T-cell receptors (TCRs), CAR T cell, antibody-based therapy and peptide- or mRNA-based vaccines. Indeed, CTAs are the dominating non-mutated targets in mRNA cancer vaccine development. Clinical trials on CTA TCR and vaccines have shown effectiveness, safety, and tolerance, but these successes are limited to a small number of patients. In-depth studies on CTA expression and function are needed to improve CTA-based immunotherapy.
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http://dx.doi.org/10.1016/j.semcancer.2021.04.016DOI Listing
April 2021

Design, microwave synthesis, and molecular docking studies of catalpol crotonates as potential neuroprotective agent of diabetic encephalopathy.

Sci Rep 2020 11 23;10(1):20415. Epub 2020 Nov 23.

Department of Applied Chemistry, Zhengzhou University of Light Industry, Zhengzhou, 450002, Henan, China.

Catalpol has gained increasing attention for its potential contributions in controlling glycolipid metabolism and diabetic complications, which makes used as a very promising scaffold for seeking new anti-diabetic drug candidates. Acylation derivatives of catalpol crotonate (CCs) were designed as drug ligands of glutathione peroxidase (GSH-Px) based on molecular docking (MD) using Surfex-Docking method. Catalpol hexacrotonate (CC-6) was synthesized using microwave assisted method and characterized by FT-IR, NMR, HPLC and HRMS. The MD results indicate that with the increasing of esterification degree of hydroxyl, the C log P of CCs increased significantly, and the calculated total scores (Total_score) of CCs are all higher than that of catalpol. It shows that CCs maybe served as potential lead compounds for neuroprotective agents. It was found that the maximum Total_score of isomers in one group CCs is often not that the molecule with minimum energy. MD calculations show that there are five hydrogen bonds formed between CC-6 and the surrounding amino acid residues. Molecular dynamics simulation results show that the binding of CC-6 with GSH-Px is stable. CC-6 was screened for SH-SY5Y cells viability by MTT (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) assay, the result indicates CC-6 can effectively reverse SZT induced cells apoptosis with dose-dependent manner, which can indirectly show that CC-6 is a potential neuroprotective agent.
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http://dx.doi.org/10.1038/s41598-020-77399-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7684281PMC
November 2020

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 decreased number and function of lymphocytes is associated with Penicillium marneffei infection in HIV-negative patients.

J Microbiol Immunol Infect 2021 Jun 21;54(3):457-465. Epub 2020 Feb 21.

Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address:

Background/purpose: Penicillium marneffei (P. marneffei) infection, which has been traditionally considered as an indicator of immunosuppression, is one of the most common systemic opportunistic infections in patients with AIDS. Recently, more and more P. marneffei infections have been documented in HIV-negative patients without underlying diseases, which challenges the traditional view that P. marneffei infection is an indicator of immunosuppression. We aimed to evaluate the number and function of lymphocytes in HIV-negative patients with P. marneffei infection.

Methods: 15 HIV-negative P. marneffei-infected patients and 18 healthy controls were recruited and investigated. The number and function of lymphocytes were analyzed by flow cytometry.

Results: Most laboratory tests were within the reference ranges, except for a significant increase in total IgE in P. marneffei-infected patients. Lymphocyte subset analysis showed that the number of CD4 T cells and NK cells was significantly decreased in HIV-negative marneffei-infected patients compared with healthy controls. However, almost half of the marneffei-infected patients still had normal levels of lymphocytes. A further analysis of cell function showed that the activation and proliferation of CD4 T cells, the cytotoxicity of CD8 T cells and NK cells, and the cytokine secretion potential of CD4 T cells and NK cells were all impaired, in comparison with healthy controls.

Conclusions: P. marneffei infection has to be regarded as an indicator of immunosuppression. A further investigation of cell function is required in patients with opportunistic infection, as the cell function may be impaired in this condition.
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http://dx.doi.org/10.1016/j.jmii.2020.02.007DOI Listing
June 2021

Tissue-specific microRNA expression alters cancer susceptibility conferred by a TP53 noncoding variant.

Nat Commun 2019 11 7;10(1):5061. Epub 2019 Nov 7.

Department of Medicine, Section of Epidemiology and Population Sciences, Baylor College of Medicine, Houston, TX, USA.

A noncoding polymorphism (rs78378222) in TP53, carried by scores of millions of people, was previously associated with moderate risk of brain tumors and other neoplasms. We find a positive association between this variant and soft tissue sarcoma. In sharp contrast, it is protective against breast cancer. We generated a mouse line carrying this variant and found that it accelerates spontaneous tumorigenesis and glioma development, but strikingly, delays mammary tumorigenesis. The variant creates a miR-382-5p targeting site and compromises a miR-325-3p site. Their differential expression results in p53 downregulation in the brain, but p53 upregulation in the mammary gland of polymorphic mice compared to that of wild-type littermates. Thus, this variant is at odds with Li-Fraumeni Syndrome mutants in breast cancer predisposition yet consistent in glioma predisposition. Our findings elucidate an underlying mechanism of cancer susceptibility that is conferred by genetic variation and yet altered by microRNA expression.
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http://dx.doi.org/10.1038/s41467-019-13002-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6838078PMC
November 2019

Design, synthesis, and preliminary biological evaluation of catalpol propionates as antiaging drugs.

BMC Chem 2019 Dec 21;13(1):109. Epub 2019 Aug 21.

2Department of Applied Chemistry, Zhengzhou University of Light Industry, Zhengzhou, 450002 Henan China.

In this paper, catalpol propionylated analogs (CPs) were designed as drug ligands of glutathione peroxidase (GSH-Px) based on molecular docking (MD) using Surflex-Docking method. The calculated total scores (Total_score) and C log of CPs are higher than that of catalpol, which show that the CPs maybe served as potential lead compounds as new antiaging drugs. Furthermore, the maximum Total_score of isomers in one group CPs is often not that the molecule with minimum energy structure. These show that the CPs docking with GSH-Px maybe not only affected by the molecular energy, but also affected by their conformations. The CPs were synthesized by esterification of catalpol with propionic anhydride using pyridine as solvent and acid banding agent, DMAP as catalyst, reaction at specific temperature. The synthesized perpropionylated catalpol analog (CP-6) was determined by NMR, FT-IR, HRMS, and HPLC, and the synthesis process was optimized by means of orthogonal experimental design. Subsequently, CP-6 was screened for cells viability by MTT assay, the results show that the CP-6 can effectively reversed STZ-induced reduction of cells viability, and CP-6 has potential antiaging activity.
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http://dx.doi.org/10.1186/s13065-019-0626-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6702743PMC
December 2019

Notch-1 regulates proliferation and differentiation of human bladder cancer cell lines by inhibiting expression of Krüppel-like factor 4.

Oncol Rep 2014 Oct 23;32(4):1459-64. Epub 2014 Jul 23.

Department of Urology, Chinese PLA General Hospital, Beijing 100853, P.R. China.

Inhibition of Notch signaling pathways, consisting of 4 highly conserved receptors (Notch 1-4), induces expression of Krüppel-like transcription factors (KLFs) linked to bladder cancer tumorigenesis and metastasis. Effects of Notch-1 knockdown on cell proliferation, differentiation and KLF4 levels in bladder cancer cell lines were investigated. PsiRNA1‑mediated Notch-1 and KLF4 knockdown models and control model without the psiRNA1 vector were constructed using bladder cancer cell lines T24 and BIU87. Cell proliferation, apoptosis and expression of Notch-1 and KLF4 were assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry assay with Annexin V-FITC/PI staining, and reverse transcriptase polymerase chain reaction (RT-PCR) and western blot analysis, respectively. Proliferation was assessed in Notch-1 and/or KLF4 knockdown. The results showed that Notch-1 mRNA and protein expression levels were significantly lower following psiRNA1 vector transfection in both cell lines (P<0.05). Growth and proliferation of both cell lines were significantly inhibited by Notch-1 knockdown (P<0.05), and more G0/G1 arrest and apoptosis were observed compared to those in the control groups (P<0.05). The effects were time-dependent, peaking between 24-48 h and declining by 72 h. KLF4 expression was significantly higher in the Notch-1 knockdown group than in control cells (P<0.05). Notch-1 knockdown cell proliferation was significantly lower than that of Notch-1 and KLF4 knockdown (P<0.05). In conclusion, Notch-1 may act as an oncogene, regulating the proliferation and differentiation of bladder cancer cells by inhibiting KLF4. Pending further exploration of pathway variations and crosstalk, these pathways may be useful targets for bladder cancer therapy.
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http://dx.doi.org/10.3892/or.2014.3350DOI Listing
October 2014

Identification of a known GJB6 mutation in an autosomal dominant inherited Chinese family with hidrotic ectodermal dysplasia.

Zhong Nan Da Xue Xue Bao Yi Xue Ban 2013 Aug;38(8):761-5

State Key Laboratory of Medical Genetics, Central South University, Changsha 410078,China.

Objective: Mutation in the gap junction beta 6 (GJB6) gene has been reported to be associated with an autosomal dominant disorder hidrotic ectodermal dysplasia (HED), characterized by congenital nail clubbing, alopecia and palmoplantar keratoderma. The aim of this study is to investigate relationship between genetic mutation in GJB6 and HED in an affected Chinese family.

Methods: We selected a Chinese HED family consisting of a total of 17 individuals including 8 HED patients (5 males and 3 females). The whole coding region of GJB6 was amplified by polymerase chain reaction and sequenced.

Results: Sequence analysis identified a heterozygous missense mutation c.31G>A (p.G11R) in GJB6 gene of affected individuals, but not in healthy individuals.

Conclusion: A c.31G>A (p.G11R) missense mutation in GJB6 gene is the genotypic characteristic for HED in Chinese population.
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http://dx.doi.org/10.3969/j.issn.1672-7347.2013.08.001DOI Listing
August 2013

Berberine attenuates cigarette smoke-induced acute lung inflammation.

Inflammation 2013 Oct;36(5):1079-86

Institute of Respiratory Diseases, the Second Affiliated Hospital of the Third Military Medical University, 183 Xinqiao Street, Shapingba District, Chongqing, 400037, China.

Berberine (Ber), the major constituent of Coptidis Rhizoma, possesses anti-inflammatory properties. In this study, we investigated the effects of Ber on cigarette smoke (CS)-mediated acute lung inflammation. C57BL/6 mice (6-8 weeks) were exposed to CS to induce acute lung injury. Ber was used to pretreat CS-exposed mice (50 mg/kg, intragastrically). Lung tissues were collected for histological examination, myeloperoxidase (MPO) activity assay, Western blot analysis, and electrophoretic mobility shift assay. Bronchoalveolar lavage fluid (BALF) was measured for cell counts and cytokine analysis. Histological examination showed that CS exposure caused infiltration of inflammatory cells into alveolar spaces and interstitial edema. Pretreatment with Ber significantly attenuated CS-induced lung inflammation. The numbers of total cells, macrophages, and neutrophils in BALF were decreased by 43, 40, and 53 %, respectively, by Ber pretreatment in CS-exposed mice, accompanied by decreased MPO activity, a marker of neutrophil accumulation. Ber pretreatment also profoundly diminished CS-induced secretions of macrophage inflammatory protein 2, tumor necrosis factor alpha, interleukin-6, and monocyte chemotactic protein-1 in BALF, along with less nuclear translocation of the pro-inflammatory transcription factor nuclear factor-kappa B (NF-κB) p65 subunit and lower NF-κB DNA-binding activity (P < 0.01). Thus, our results indicated that Ber ameliorates CS-induced acute lung injury through its anti-inflammatory activity.
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http://dx.doi.org/10.1007/s10753-013-9640-0DOI Listing
October 2013

Blocking TREM-1 signaling prolongs survival of mice with Pseudomonas aeruginosa induced sepsis.

Cell Immunol 2012 15;272(2):251-8. Epub 2011 Oct 15.

Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

TREM-1 is a recently discovered receptor expressed on neutrophils and macrophages. Blocking of TREM-1 signaling improves the survival of mice with bacterial sepsis. However, the precise mechanism by which TREM-1 modulates the inflammatory responses is poorly defined. In this study, we investigated the role of TREM-1 in Pseudomonas aeruginosa-induced peritonitis. Our results showed that TREM-1 was not expressed on lymphocytes but emerged on the cell surface of neutrophils and peritoneal macrophages. Blockade of TREM-1 signaling significantly prolonged survival of mice with P. aeruginosa-induced peritonitis. However, blocking TREM-1 signaling had no effect on macrophage phagocytosis in vitro. Interestingly, the expression of the costimulatory molecules CD40 and CD86 on macrophages was significantly decreased after blocking TREM-1 signaling. Furthermore, interfering with TREM-1 engagement led to significant reduction of pro-inflammatory mediators such as IL-1, TNF-α, MCP-1 and IFN-γ. Therefore, our results showed that TREM-1 could be a potential therapeutic target for bacterial sepsis.
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http://dx.doi.org/10.1016/j.cellimm.2011.10.006DOI Listing
April 2012

Anti-tumor activity of curcumin against androgen-independent prostate cancer cells via inhibition of NF-κB and AP-1 pathway in vitro.

J Huazhong Univ Sci Technolog Med Sci 2011 Aug 7;31(4):530. Epub 2011 Aug 7.

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

The anti-tumor activity of curcumin against androgen-independent prostate cancer cells in vitro and the possible mechanism were investigated. After curcumin treatment, the effect of curcumin on the proliferation of prostate cancer PC-3 cells was assessed by CFSE staining. Flow cytometery (FCM) was performed to analyze the cell cycle and the induction of apoptosis of tumor cells. A luciferase reporter gene assay was used to determine the effects of curcumin on the activities of intracellular NF-κB and AP-1 signaling pathways. The results showed curcumin could effectively inhibit the proliferation of PC-3 cells in vitro (P<0.05). Cells were arrested at G(2)/M phase. After curcumin treatment, the percentage of apoptotic cells was significantly higher than in control group (P<0.05). The results of the luciferase assay revealed that curcumin selectively inhibited the activities of the NF-κB and AP-1 signaling pathways in PC-3 cells significantly. It was suggested that curcumin could exert anti-tumor activity against androgen-independent prostate cancer cells in vitro by inhibiting cellular proliferation and inducing apoptosis, which was probably contributed to the inhibition of transcription factors NF-κB and AP-1.
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http://dx.doi.org/10.1007/s11596-011-0485-1DOI Listing
August 2011

Association of DNA polymorphisms within the CYP11B2/CYP11B1 locus and postoperative hypertension risk in the patients with aldosterone-producing adenomas.

Urology 2010 Oct 13;76(4):1018.e1-7. Epub 2010 Aug 13.

Department of Urology, China PLA General Hospital, Beijing, People's Republic of China.

Objectives: Hypertension often persists after adrenalectomy for primary aldosteronism. Traditional factors associated with postoperative hypertension were evaluated, but whether genetic determinants were involved remains poorly understood. The aim of this study was to investigate the association of DNA polymorphisms within steroid synthesis genes (CYP11B2, CYP11B1) and the postoperative resolution of hypertension in Chinese patients undergoing adrenalectomy for aldosterone-producing adenomas (APA).

Methods: Ninety-three patients with APA were assessed for postoperative resolution of hypertension. All patients were genotyped for rs1799998 (C-344 T), intron 2 conversion, rs4539 (A2718G) within CYP11B2 and rs6410 (G22 5A), rs6387 (A2803G) within CYP11B1. The associations between CYPB11B2/CYP11B1 polymorphisms and persistent postoperative hypertension were assessed by multivariate analysis.

Results: CYP11B2-CYP11B1 haplotype was associated with persistent postoperative hypertension in Chinese patients undergoing adrenalectomy with APA (P = .006). Specifically, the rs4539 (AA) polymorphism was associated with persistent postoperative hypertension (P = .002). Multivariate logistic regression revealed the common haplotypes H1 (AGACT), H2 (AGAWT), and H3 (AGAWC) were associated with the persistent postoperative hypertension (P = .01, 0.03, 0.005 after Bonferroni correction). Additional predictors of persistent postoperative hypertension included duration of hypertension (P <.0005), family history of hypertension (P = .001), and elevated systolic blood pressure (P = .015).

Conclusions: The rs4539 (AA), H1, H2, and H3 are genetic predictors for postoperative persistence of hypertension for Chinese patients treated by adrenalectomy with APA. DNA polymorphisms at CYP11B2/B1 locus may confer susceptibility to postoperative hypertension of patients with APA.
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http://dx.doi.org/10.1016/j.urology.2010.03.019DOI Listing
October 2010