Publications by authors named "Xiaoxia Chen"

152 Publications

Cathepsin B-Activated Fluorescent and Photoacoustic Imaging of Tumor.

Anal Chem 2021 07 28;93(27):9304-9308. Epub 2021 Jun 28.

Key Laboratory of Structure and Functional Regulation of Hybrid Materials, Ministry of Education, Institutes of Physical Science and Information Technology, Anhui University, Hefei 230601, China.

Early diagnosis is crucial to the treatment of cancer. Cathepsin B (CTB) plays an important role in numerous cancers, which is a promising biomarker for early diagnosis of cancer. It is necessary to exploit new probes for visualization of CTB . Fluorescent/photoacoustic (FL/PA) imaging is a powerful tool for study which possesses both excellent sensitivity and spatial resolution. To our knowledge, there has been no FL/PA probe to image CTB or . Therefore, we developed two CTB-activated FL/PA probes and , which could successfully monitor CTB activity . Both two probes had excellent sensitivity and selectivity . Cell imaging showed that or could image endogenous CTB in lysosome with 6.8-fold or 5.1-fold enhancement of the FL signal and 5.8-fold or 3.4-fold enhancement of the PA signal compared to their inhibitor contrast groups. Tumor imaging further confirmed the good applicability of these two probes to monitor CTB activity with high sensitivity and spatial resolution. Moreover, the property of is superior to due to the higher catalytic efficiency of CTB toward than . We envision that our FL/PA probe will be suitable for clinical early diagnosis of CTB-related cancer in the near future.
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http://dx.doi.org/10.1021/acs.analchem.1c02145DOI Listing
July 2021

α-Chaconine Affects the Apoptosis, Mechanical Barrier Function, and Antioxidant Ability of Mouse Small Intestinal Epithelial Cells.

Front Plant Sci 2021 9;12:673774. Epub 2021 Jun 9.

College of Animal Science and Technology, Jilin Agricultural Science and Technology University, Jilin City, China.

α-Chaconine is the most abundant glycoalkaloid in potato and toxic to the animal digestive system, but the mechanisms underlying the toxicity are unclear. In this study, mouse small intestinal epithelial cells were incubated with α-chaconine at 0, 0.4, and 0.8 μg/mL for 24, 48, and 72 h to examine apoptosis, mechanical barrier function, and antioxidant ability of the cells using a cell metabolic activity assay, flow cytometry, Western blot, immunofluorescence, and fluorescence quantitative PCR. The results showed that α-chaconine significantly decreased cell proliferation rate, increased apoptosis rate, decreased transepithelial electrical resistance (TEER) value, and increased alkaline phosphatase (AKP) and lactate dehydrogenase (LDH) activities, and there were interactions between α-chaconine concentration and incubation time. α-Chaconine significantly reduced the relative and mRNA expressions of genes coding tight junction proteins zonula occludens-1 (ZO-1) and occludin, increased malondialdehyde (MDA) content, decreased total glutathione (T-GSH) content, reduced the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and γ-glutamylcysteine synthetase (γ-GCS) and the mRNA expressions of SOD, CAT, GSH-Px, and γ-GCS genes. In conclusion, α-chaconine disrupts the cell cycle, destroys the mechanical barrier and permeability of mucosal epithelium, inhibits cell proliferation, and accelerates cell apoptosis.
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http://dx.doi.org/10.3389/fpls.2021.673774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220139PMC
June 2021

Imatinib reduces the fertility of male mice by penetrating the blood-testis barrier and inducing spermatogonia apoptosis.

Reprod Biol 2021 Jun 16;21(3):100527. Epub 2021 Jun 16.

Department of Hematology, The 967th Hospital of Chinese People's Liberation Army, Liaoning, China. Electronic address:

Imatinib, the first generation of tyrosine kinase inhibitor, is used to treat and improve the prognosis of chronic myelogenous leukemia (CML). Clinical data suggest that imatinib could cross the blood-testis barrier and reduces the fertility of patients with CML-chronic phase. However, its exact molecular mechanism has not been fully elucidated. In this study, adult male Kunming mice were treated with different doses of imatinib for 8 weeks. The fertility was evaluated, and the sex hormone levels in the blood were detected by enzyme-linked immunosorbent assay. Histological changes were detected by hematoxylin and eosin staining. The concentration of imatinib in semen and blood was detected by liquid chromatography-mass spectrometry. The ultrastructure of blood-testis barrier and apoptotic bodies were observed by transmission electron microscope. The expression of blood-testis barrier function-regulating protein, Mfsd2a, and apoptosis-associated proteins in testis tissue was detected by immunohistochemistry and Western blot. The results indicated that the fertility of male mice was significantly decreased in a dose-dependent manner after imatinib treatment. Certain hormones in the serum were increased in imatinib treatment groups. Sperm morphology and testicular tissue showed various changes after imatinib treatment. The blood-testis barrier was destroyed and the concentration of imatinib in semen was similar to that in blood after imatinib treatment. Apoptosis was significantly increased in testis tissue after imatinib treatment. Collectively, these results suggest that imatinib can alter blood-testis barrier function, induce apoptosis of spermatogonia, and adversely affect fertility by reducing the number of spermatozoa, decreasing sperm motility and increasing the deformity rate.
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http://dx.doi.org/10.1016/j.repbio.2021.100527DOI Listing
June 2021

Self-Assembled Growing DNA Tree Mediated by Exosomes for Amplified Imaging of Messenger RNA in Living Cells.

Anal Chem 2021 06 11;93(24):8414-8422. Epub 2021 Jun 11.

Department of Clinical Laboratory Medicine, Shanghai Tenth People's Hospital of Tongji University, Shanghai 200072, P. R. China.

Sensitive, accurate, and nondestructive probing of endogenous messenger RNA (mRNA) in living cells places extremely high demands on nanocarriers and probes and is still a challenge. In the present study, we describe a target-triggered self-assembled DNA tree for amplified analysis of mRNA in intact living cells. The probes assembled into a DNA tree are transported into cells by exosomes, which is beneficial for reducing cell damage and realizing nondestructive analysis. The probes are l-configured single-stranded DNAs (LDNAs) that can resist the degradation of exonuclease and endonuclease, thus laying the foundation for accurate analysis. Under the induction of the target mRNA, the probes in the cells assemble into a small plantlet and eventually grow into a tree after a few rounds of self-cycling, achieving the exponential amplification of fluorescence signals. Compared with the signal amplification based on one-dimensional DNA trunk self-assembly, the three-dimensional DNA tree shows an excellent sensitivity both ex situ and in situ. In this way, favorable sensitivity, accuracy, and nondestructive analysis are integrated into one system. This DNA tree expands the analysis platform for analyzing more biomarkers on a genetic level in an intracellular, nondestructive, and hypersensitive manner and holds great potential in clinical diagnostic and research applications.
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http://dx.doi.org/10.1021/acs.analchem.1c00211DOI Listing
June 2021

Single-cell profiling of tumor heterogeneity and the microenvironment in advanced non-small cell lung cancer.

Nat Commun 2021 05 5;12(1):2540. Epub 2021 May 5.

Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.

Lung cancer is a highly heterogeneous disease. Cancer cells and cells within the tumor microenvironment together determine disease progression, as well as response to or escape from treatment. To map the cell type-specific transcriptome landscape of cancer cells and their tumor microenvironment in advanced non-small cell lung cancer (NSCLC), we analyze 42 tissue biopsy samples from stage III/IV NSCLC patients by single cell RNA sequencing and present the large scale, single cell resolution profiles of advanced NSCLCs. In addition to cell types described in previous single cell studies of early stage lung cancer, we are able to identify rare cell types in tumors such as follicular dendritic cells and T helper 17 cells. Tumors from different patients display large heterogeneity in cellular composition, chromosomal structure, developmental trajectory, intercellular signaling network and phenotype dominance. Our study also reveals a correlation of tumor heterogeneity with tumor associated neutrophils, which might help to shed light on their function in NSCLC.
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http://dx.doi.org/10.1038/s41467-021-22801-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100173PMC
May 2021

Immune Checkpoint Inhibitors in EGFR-Mutated NSCLC: Dusk or Dawn?

J Thorac Oncol 2021 Aug 26;16(8):1267-1288. Epub 2021 Apr 26.

Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China. Electronic address:

Although immune checkpoint inhibitors (ICIs) that target programmed cell death protein-1/programmed cell death ligand-1 axis have significantly shifted the treatment paradigm in advanced NSCLC, clinical benefits of these agents are limited in patients with EGFR-mutated NSCLC. Several predictive biomarkers (e.g., programmed cell death ligand-1 expression, tumor mutation burden), which have been validated in EGFR-wild type NSCLC, however, are not efficacious in EGFR-mutated tumors, suggesting the unique characteristics of tumor microenvironment of EGFR-mutated NSCLC. Here, we first summarized the clinical evidence on the efficacy of ICIs in patients with EGFR-mutated NSCLC. Then, the cancer immunogram features of EGFR-mutated NSCLC was depicted to visualize the state of cancer-immune system interactions, including tumor foreignness, tumor sensitivity to immune effectors, metabolism, general immune status, immune cell infiltration, cytokines, and soluble molecules. We further discussed the potential subpopulations with EGFR mutations that could benefit from ICI treatment. Lastly, we put forward future strategies to adequately maximize the efficacy of ICI treatment in patients with EGFR-mutated NSCLC in the upcoming era of combination immunotherapies.
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http://dx.doi.org/10.1016/j.jtho.2021.04.003DOI Listing
August 2021

Allogeneic hematopoietic cell transplant overcomes the poor prognostic value of CDKN2 deletion in adult B-lineage acute lymphoblastic leukemia.

Cancer Lett 2021 Jul 24;510:59-66. Epub 2021 Apr 24.

Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China. Electronic address:

Emerging evidence suggested that CDKN2 deletion was a poor prognosis predictor in adult B-lineage acute lymphoblastic leukemia (B-ALL). Here, we investigated the effect of allogeneic hematopoietic cell transplant (allo-HCT) on adult B-ALL with CDKN2 deletion. The patients with adult B-ALL underwent more than two courses of chemotherapy were enrolled in the multicenter retrospective study. Relapse and survival were analyzed. A total of 1336 adult B-ALL, including 295 patients with CDKN2 deletion and 1041 wild-type (WT), from five institutes were enrolled. The complete remission (CR) rates were 86.8% and 91.1% (P = 0.229) after two cycles of chemotherapy in patients with CDKN2 deletion and WT, respectively. The 5-year cumulative relapse post-CR were 56% (95% CI, 52-68) and 43% (95% CI, 40-51) (P < 0.001), 5-year disease-free survival (DFS) were 30% (95% CI, 24-36) and 41% (95% CI, 39-46) (P < 0.001), and 5-year overall survival (OS) were 35% (95% CI, 28-39) and 47% (95% CI, 44-49) (P < 0.001) in the two groups, respectively. Subgroup analysis revealed that the 5-year relapse were 89.3% (95% CI, 83.0-96.5) and 68.4% (95% CI, 60.2-72.5) (P < 0.001), 5-year DFS were 4.9% (95% CI, 1.8-10.4) and 22.7% (95% CI, 18.0-27.7) (P < 0.001), and 5-year OS were 6.9% (95% CI, 3.1-12.9) and 23.4% (95% CI, 18.7-28.6) (P < 0.001) in CDKN2 deletion and WT groups undergoing chemotherapy alone, respectively, while there were not different in terms of 5-year relapse (38.1% vs 34.3%, P = 0.211), DFS (48.4% vs 52.2%, P = 0.325) and OS (54.5% vs 56.3%, P = 0.483) between those with CDKN2 deletion and WT undergoing allo-HCT. Multivariate analysis showed that CDKN2 deletion and high-risk stratification both were the risk factors for relapse, DFS and OS, while allo-HCT was a protective factor. CDKN2 deletion might be a poor prognostic predictor of adult B-ALL. Adult B-ALL with CDKN2 deletion might benefit from allo-HCT.
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http://dx.doi.org/10.1016/j.canlet.2021.04.009DOI Listing
July 2021

Lenvatinib in combination with transarterial chemoembolization for treatment of unresectable hepatocellular carcinoma (uHCC): a retrospective controlled study.

Hepatol Int 2021 Jun 20;15(3):663-675. Epub 2021 Apr 20.

Department II of Interventional Radiology, Eastern Hepatobiliary Surgery Hospital, Shanghai, China.

Purpose: To compare the efficacy and safety of combined treatment with lenvatinib and transarterial chemoembolization (TACE) versus TACE only in patients with unresectable hepatocellular carcinoma (uHCC).

Methods: Of the 120 patients enrolled in this study, 60 patients received treatment with TACE only, and 60 patients received TACE plus lenvatinib. We retrospectively compared the clinical outcomes including overall survival (OS), progression-free survival (PFS), and tumor response between the two groups. Both PFS and tumor response were based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Adverse events were analyzed to assess the safety profiles.

Results: The 1-year and 2-year OS rates were significantly higher in the TACE + lenvatinib group (88.4% and 79.8%) than that in the TACE group (79.2% and 49.2%, p = 0.047). A similar PFS benefit was observed in the TACE + lenvatinib group (1-y PFS rate: 78.4% vs. 64.7%, 2-y PFS rate: 45.5% vs. 38.0%, p < 0.001). The best overall objective response rate (ORR) was also better with TACE + lenvatinib treatment (ORR: 68.3% vs. 31.7%, p < 0.001) and disease control rate (DCR) numerically increased in the TACE + lenvatinib treatment (93.3% vs. 86.7%, p = 0.224). Patients' liver function remained comparable to baseline in the TACE + lenvatinib group. The most common adverse events were decreased albumin (55.0%), hypertension (48.3%) and decreased platelet count (46.7%) in the TACE + lenvatinib group.

Conclusions: Combination treatment with TACE and lenvatinib may significantly improve clinical outcomes over TACE monotherapy with a manageable safety profile for unresectable HCC. The efficacy of the combination treatment should be validated in prospective studies with a large sample size.
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http://dx.doi.org/10.1007/s12072-021-10184-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286947PMC
June 2021

Transcriptome Analysis of Ovarian Follicles Reveals Potential Pivotal Genes Associated With Increased and Decreased Rates of Chicken Egg Production.

Front Genet 2021 10;12:622751. Epub 2021 Mar 10.

College of Agricultural & Environmental Sciences, University of Georgia, Athens, GA, United States.

Egg production is an important economic trait in the commercial poultry industry. Ovarian follicle development plays a pivotal role in regulation of laying hen performance and reproductive physiology. However, the key genes and signaling pathways involved in the various-stages of laying hen follicular development remain poorly understood. In this study, transcriptomes of ovarian follicles at three developmental stages, the large white follicle (LWF), small yellow follicle (SYF), and large yellow follicle (LYF), were comparatively analyzed in hens with high (HR) and low (LR) egg-laying rates by RNA-sequencing. Eighteen cDNA libraries were constructed and a total of 236, 544, and 386 unigenes were significantly differentially expressed in the LWF, SYF, and LYF follicles of HR and LR hens, respectively. Among them, 47 co-transcribed differentially expressed genes (DEGs) in LWF and SYF, 68 co-expressed DEGs in SYF and LYF, and 54 co-expressed DEGs in LWF and LYF were mined. Thirteen co-expressed DEGs were found in LWF, SYF, and LYF follicles. Eighteen candidate genes, including , , , , , , , , , , , , , , , , , and were identified to be potentially related to egg production. Furthermore, Kyoto Encyclopedia of Genes and Genomes analysis indicated neuroactive ligand-receptor interaction, cell adhesion molecules, peroxisome proliferator-activated receptor pathway, and cAMP signaling pathway might elicit an important role in formation of egg-laying traits by influencing ovarian follicle development. This study represents the first transcriptome analysis of various-sized follicles between HR and LR hens. These results provide useful molecular evidence for elucidating the genetic mechanism underlying ovarian follicle development associated with egg production in chicken.
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http://dx.doi.org/10.3389/fgene.2021.622751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987945PMC
March 2021

Effect of mobile health based peripartum management of gestational diabetes mellitus on postpartum diabetes: A randomized controlled trial.

Diabetes Res Clin Pract 2021 May 23;175:108775. Epub 2021 Mar 23.

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Obstetric & Gynecologic Diseases, Beijing 100730, China. Electronic address:

Aims: To investigate the effects of mobile health based peripartum management of gestational diabetes mellitus (GDM) on postpartum diabetes and factors associated with postpartum diabetes.

Methods: Women with GDM (n = 309) were randomly assigned to receive standard management (SM) or mobile management (MM). 75-g OGTT was performed at 6 weeks postpartum.

Results: The incidence of postpartum T2DM in the MM group was much higher than that in SM group (12.36% vs. 3.88%, P =  0.0291). The fasting, 1-h and 2 h OGTT at 24-28 weeks of gestation of T2DM women were higher than those women without T2DM (fasting, 6.08 vs. 4.90, P = 0.0052; 1-h, 13.20 vs. 10.00, P < 0.0001; 11.96 vs. 8.83, P = 0.0026) in MM group. The 1-h and 2 h OGTT at 24-28 weeks of gestation of T2DM women were higher than those women without T2DM (11.54 vs. 9.78, P = 0.0484; 10.68 vs. 8.68, P = 0.0108) in SM group. Higher OGTT values at 24-28 weeks of gestation were risk factors of postpartum T2DM.

Conclusions: Higher OGTT values at 24-28 weeks of gestation were risk factors to develop postpartum T2DM. Mobile health based peripartum management of GDM increased the risk of postpartum diabetes among women with GDM for lacking of postpartum management. Further studies of mobile health based postpartum management of GDM are needed. ClinicalTrials.gov registration number NCT03748576.
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http://dx.doi.org/10.1016/j.diabres.2021.108775DOI Listing
May 2021

An MRI study of the tibial nerve in the ankle canal and its branches: a method of multiplanar reformation with 3D-FIESTA-C sequences.

BMC Med Imaging 2021 Mar 17;21(1):51. Epub 2021 Mar 17.

Department of Radiology, Third Medical Centre of Chinese PLA General Hospital, Beijing, 100039, China.

Background: The visualization of the tibial nerve and its branches in the ankle canal is helpful for the diagnosis of local lesions and compression, and it is also useful for clinical observation and surgical planning. The aim of this study was to investigate the feasibility of three-dimensional dual-excitation balanced steady-state free precession sequence (3D-FIESTA-C) multiplanar reformation (MPR) display of the tibial nerve and its branches in the ankle canal.

Methods: The subjects were 20 healthy volunteers (40 ankles), aged 22-50 years, with no history of ankle joint disease. The 3D-FIESTA-C sequence was used in the 3.0 T magnetic resonance equipment for imaging. During scanning, each foot was at an angle of 90° to the tibia. The tibial nerve of the ankle canal and its branches were displayed and measured at the same level through MPR.

Results: Most of the tibial nerve bifurcation points were located in the ankle canal (57.5%), few bifurcation points (42.5%) were located at the proximal end of the ankle canal, and none of them were found away from the distal end. The bifurcation between the medial plantar nerve and the lateral plantar nerve was on the line between the tip of the medial malleolus and the calcaneus, and it's angle ranged between 6° and 35°. In MPR images, the display rates of both the medial calcaneal nerve and the subcalcaneal nerve were 100%, and the starting point of the subcalcaneal nerve was always at the distal end of the starting point of the medial calcaneal nerve. In 55% of cases, there were more than two medial calcaneal nerve innervations.

Conclusion: The 3D-FIESTA-C MPR can display the morphological features and positions of the tibial nerve and its branches and the bifurcation point's projection position can be marked on the body surface. This method not only benefited the imaging diagnosis of the tibial nerve and branch-related lesions in the ankle canal, but it also provided a good imaging basis to plan a clinical operation of the ankle canal and avoid surgical injury.
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http://dx.doi.org/10.1186/s12880-021-00582-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968234PMC
March 2021

Exon 20 YVMA insertion is associated with high incidence of brain metastasis and inferior outcome of chemotherapy in advanced non-small cell lung cancer patients with HER2 kinase domain mutations.

Transl Lung Cancer Res 2021 Feb;10(2):753-765

Department of Medical Oncology, Shanghai Pulmonary Hospital and Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China.

Background: Chemotherapy remains the standard care for mutated advanced non-small cell lung cancer (NSCLC) even though several targeted drugs showed promising results in preliminary stages. This study aimed to investigate the association of mutation variants with clinical features and the efficacy of chemotherapy in patients with mutated advanced NSCLC.

Methods: ARMS-PCR was used to identify HER2 mutation in patients without common oncogenic alterations. Patients with detailed information were further enrolled for analysis of clinical features and efficacy of first line chemotherapy. Survival data was analyzed by Kaplan-Meier method and compared by log-rank test. Brain metastasis incidence was analyzed and compared by Gray's test.

Results: YVMA insertion accounted for the majority (68.4%, 67/98) of HER2 mutation, and associated with significantly higher incidence of baseline extrathoracic metastasis (P=0.009), notably brain metastasis (P=0.004). Among 82 patients those received first line chemotherapy, YVMA insertion remarkably associated with inferior treatment outcomes, namely, a significantly shorter median progression free survival (PFS) and lower objective response rate (ORR) both in total patients (PFS: 5.2 7.7 m, P=0.038; ORR: 30.9% 51.9%, P=0.09) and pemetrexed subgroup (PFS: 5.2 6.5 m, P=0.022; ORR: 31.8% 60.0%, P=0.054). Multivariate analysis further established YVMA insertion as prognostic factor of worse PFS both for total patients (HR =1.578, 95% CI, 0.956-2.606) and patients received pemetrexed-based chemotherapy (HR =1.789, 95% CI, 1.013-3.160). In addition, YVMA insertion associated with higher incidence of lifetime brain metastasis (P=0.002) compared by Gray's test, with estimated 12-month brain metastasis incidence as 40.2% compared with 3.6% in the non-YVMA group.

Conclusions: YVMA insertion is associated with a higher incidence of brain metastasis, and inferior outcomes to chemotherapy than non-YVMA variants in patients with advanced NSCLC and HER2 kinase domain mutations, which emphasized the unmet need of more potent anti-cancer therapies with high blood-brain barrier (BBB) penetration capacity for patients with YVMA insertion.
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http://dx.doi.org/10.21037/tlcr-20-559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947396PMC
February 2021

Corrigendum to 'The antiinflammatory effects of Xuefu Zhuyu decoction on C3H/HeJ mice with alopecia areata' [Phytomedicine vol. 81 (2021), 1-14 / 153423].

Phytomedicine 2021 Mar 21;83:153510. Epub 2021 Feb 21.

Department of dermatology, Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital, Chengdu 610071, China. Electronic address:

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http://dx.doi.org/10.1016/j.phymed.2021.153510DOI Listing
March 2021

A commentary on "Impact of the coronavirus (COVID-19) pandemic on scientific research and implications for clinical academic training - A review".

Int J Surg 2021 03 19;87:105899. Epub 2021 Feb 19.

Department of Pediatrics, Affiliated Huzhou Hospital, Zhejiang University School of Medicine, Zhejiang, 313000, China. Electronic address:

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http://dx.doi.org/10.1016/j.ijsu.2021.105899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893310PMC
March 2021

The antiinflammatory effects of Xuefu Zhuyu decoction on C3H/HeJ mice with alopecia areata.

Phytomedicine 2021 Jan 22;81:153423. Epub 2020 Nov 22.

Department of dermatology, Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital, Chengdu 610071, China. Electronic address:

Background: As a traditional and typical prescription of prominently activating blood circulation to remove blood stasis, Xuefu Zhuyu decoction (XZD) consists of 15 kinds of herbal medicine. Clinical investigations have showed that XZD could significantly promote the new hair generation of alopecia areata (AA) patients characterized by Qi stagnation and blood stasis.

Purpose: The purpose of this study was executed to determine whether the mechanisms by which XZD stimulated newborn hair were related to its anti-inflammatory effects.

Methods: Clinical AA individuals were recruited to confirm the efficies of XZD. High performance liquid chromatography (HPLC) analysis was performed to qualitatively and quantitatively determine the contents of 15 compounds in XZD. Schrodinger molecular docking and in vivo surface plasmon resonance (SPR) techniques were used to evaluate the potential binding properties of compounds to target proteins. C3H/HeJ mice were randomly assigned to groups control, AA, and the XZD administration (6.5, 13.0 and 26.0 g/kg/d). Except for mice in control group, all the mice in the other groups were treated with a 21-day chronic unpredictable mild stress (CUMS) induced AA. Hematoxylin-eosin (H&E) staining was performed to determine the degree of pathological damage to the skin. Enzyme-linked immunosorbent assay (ELISA) was performed to detect levels of interleukin-6 (IL-6), interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) and in serum and skin tissues. Western blot, immunohistochemistry and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) were used to examine the expression levels of IL-6, IL-1β, TNF-α and osteopontin proteins and genes in skin tissues.

Results: XZD could visibly promote hair regeneration of AA patients. The potential active ingredients in XZD prescription included at least amygdalin, hydroxysafflor yellow A, kaempferide, ferulic acid, catalpol, verbascoside, β-ecdysone, platycodin D, paeoniflorin, naringin, neohesperidin, liquiritin, glycyrrhizic acid, saikosaponin A and saikosaponin D. The results of molecular docking and SPR analysis showed that verbascoside, liquiritin, kaempferide and amygdalin showed the best potential binding properties with IL-6, IL-1β, TNF-α and osteopontin, respectively. Pathological evaluation showed that compared with the CUMS group, the administration of XZD significantly promoted hair regeneration, evidenced by increased number of skin hair follicles in C3H/HeJ AA mice. Compared with control group, ELISA data showed that the levels of IL-6, IL-1β and TNF-α in serum and skin tissues of CUMS induced AA mice were significantly increased, while XZD administration dramatically restrained the contents of the three pro-inflammatory factors. Western blot, immunohistochemistry, and qRT-PCR results further demonstrated that XZD administration notably down-regulated the protein and gene expression levels of osteopontin, IL-6, IL-1β and TNF-α in comparation with CUMS group.

Conclusion: XZD could dramatically ameliorate CUMS-induced AA damage in the skin of C3H/HeJ mice, possibly by suppressing the levels of IL-6, IL-1β, TNF-α and osteopontin.
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http://dx.doi.org/10.1016/j.phymed.2020.153423DOI Listing
January 2021

The value of coronary computed tomography angiography in assessing the cardiac circulation of an outpatient-based population.

Medicine (Baltimore) 2020 Nov;99(46):e23148

Department of Radiology, the Third Medical Centre, Chinese People's Liberation Army General Hospital, Beijing, China PR.

To evaluate the perfusion of coronary circulation and its related factors and the difference in the peak filling times in aortic sinus and coronary sinus by coronary computed tomography angiography (CCTA).From January 1 to August 1, 2018, 61 outpatients with angina pectoris were recruited, completed a questionnaire about risk factors and underwent CCTA, which was also used to assess the stenosis of different coronary artery segments.The duration of circulation was 9.50 ± 2.43 seconds in patients with flat T wave, which was shorter than the duration in normal subjects (P = .021). However, other cardiovascular risk factors showed no effect on the duration of circulation. In addition, the duration of circulation was closely related to the peak filling time of coronary sinus [r(s) = 0.681]. We further divided the circulation time difference (delta) values into 3 levels (<6, 6-12, and ≥12 seconds).It showed that the circulation duration (Y) was associated with:Therefore, the cardiac circulation duration was negatively related to the degree of stenosis in the 1 diagonal and proximal LCA.It compensates for the inability of CCTA to assess circulation at rest simply by determining the peak filling time in the aortic sinus and the coronary sinus. Moderate cardiac microcirculation duration was related to a low incidence of clinical symptoms and electrocardiogram disorders, which was determined mainly by the diagonal and left circumflex branch 1 of LCA.
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http://dx.doi.org/10.1097/MD.0000000000023148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7668512PMC
November 2020

EGFR-mutant NSCLC: emerging novel drugs.

Curr Opin Oncol 2021 01;33(1):87-94

Department of Medical Oncology, Shanghai Pulmonary Hospital, Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China.

Purpose Of Review: Despite the significant advances in EGFR-mutant nonsmall cell lung cancer (NSCLC), some challenges remain. One of the permanent and inevitable issues is the emergence of acquired resistance. Therefore, blocking the activation of EGFR pathway and overcoming drug resistance with novel agents are still in high demand. Here, we review the development of novel drugs in EGFR-mutant, advanced NSCLC, including targeting EGFR exon 20 insertion (EGFR20ins), and novel role of epidermal growth factor receptor, tyrosine kinase inhibitor (EGFR-TKIs) in early-stage NSCLC.

Recent Findings: EGFR-TKIs as adjuvant therapy or neoadjuvant therapy in patients with early-stage NSCLC with EGFR-sensitizing mutations have shown promising efficacy. The resistance mechanisms of third-generation EGFR-TKIs can be divided into two types: EGFR dependent and EGFR independent. Several clinical trials have demonstrated that the addition of MET inhibitors to EGFR-TKIs was an effective option for patients who had acquired resistance to EGFR-TKIs caused by hepatocyte growth factor receptor gene (MET) amplification or overexpression. Novel compounds that selectively and potently inhibit EGFR20ins are being investigated in phase III studies.

Summary: A better characterization and understanding of resistance mechanisms to first-line osimertinib and adjuvant osimertinib is helpful to guide further treatment.
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http://dx.doi.org/10.1097/CCO.0000000000000701DOI Listing
January 2021

Glycemic qualification rate and frequency of self-monitoring blood glucose glycemic qualification rate and frequency of self-monitoring blood glucose (SMBG) in women with gestational diabetes mellitus (GDM).

Diabetes Res Clin Pract 2020 Dec 28;170:108482. Epub 2020 Sep 28.

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing, 100730, China. Electronic address:

Aims: To explore the relationship between blood glucose (BG) control rate and self-monitoring blood glucose (SMBG) compliance of women with gestational diabetes mellitus (GDM).

Methods: Women with GDM (n = 309) were randomized to receive routine clinical prenatal care or additional online management. Follow-up visits were conducted every two weeks (noted here as T) from enrollment to delivery. SMBG records were used for the analysis.

Results: Both the intervention group and the control group had an increasing BG control rate and decreasing SMBG compliance during the whole follow-up period. Detailed data analysis on separate follow-up periods showed that the SMBG frequency was negatively correlated with the BG control rate in most Ts and that the BG control rate of T was negatively correlated with the SMBG frequency of T in the adjacent T. Only in the intervention group was T SMBG compliance not under the influence of the T BG control rate.

Conclusions: Our data suggested that regardless of management approach, the BG control rate increased, and the SMBG frequency decreased as gestational weeks increased in women with GDM. Even in separate follow-up periods, the SMBG frequency was negatively correlated with the BG control rate both within one follow-up period and between two adjacent follow-up periods.
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http://dx.doi.org/10.1016/j.diabres.2020.108482DOI Listing
December 2020

Mitochondria-Targeted Fluorescent and Photoacoustic Imaging of Hydrogen Peroxide in Inflammation.

Anal Chem 2020 10 28;92(20):14244-14250. Epub 2020 Sep 28.

Key Laboratory of Structure and Functional Regulation of Hybrid Materials, Ministry of Education, Institutes of Physical Science and Information Technology, Anhui University, Hefei, Anhui 230601, China.

Hydrogen peroxide (HO) is a prominent reactive oxygen species with relative stability, which makes it a potential diagnostic marker for pathological states. Excessive HO in mitochondria leads to oxidative stress and inflammation. However, precisely monitoring the level of HO at specific organelles (, mitochondria) is still of urgent necessity. Therefore, we rationally designed a mitochondria-targeted near-infrared probe for fluorescent/photoacoustic (FL/PA) dual-modal imaging of overproduced HO in an inflamed mouse model. had a low LOD (0.348 μM), which is comparable to those of recently reported probes for HO detection. The high kinetic rate constant ( = 4.72 × 10 s) of toward HO is superior to recently reported HO probes. Compared to control probe without the mitochondrial targeting moiety, successfully images exogenous or endogenous HO in mitochondria with an additional 2.4-fold FL increase and 4.7-fold PA increase in HeLa cells or additional 2.1-fold FL increase and 3.3-fold PA increase in RAW 264.7 cells. In LPS-induced acute inflammation , is more competent to image overproduced HO with additional 1.6-fold higher sensitivity of FL in abdomen and 2.0-fold higher sensitivity of PA in liver and longer retention time of 0.5 h than . We anticipate that could be employed for the FL/PA dual-modal diagnosis of pathological inflammation in clinic in near future.
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http://dx.doi.org/10.1021/acs.analchem.0c03506DOI Listing
October 2020

Interaction design for multi-user virtual reality systems: An automotive case study.

Procedia CIRP 2020 22;93:1259-1264. Epub 2020 Sep 22.

Chalmers University of Technology, Gothenburg 41296, Sweden.

Virtual reality (VR) technology have become ever matured today. Various research and practice have demonstrated the potential benefits of using VR in different application area of manufacturing, such as in factory layout planning, product design, training, etc. However, along with the new possibilities brought by VR, comes with the new ways for users to communicate with the computer system. The human computer interaction design for these VR systems becomes pivotal to the smooth integration. In this paper, it reports the study that investigates interaction design strategies for the multi-user VR system used in manufacturing context though an automotive case study.
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http://dx.doi.org/10.1016/j.procir.2020.04.036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7508012PMC
September 2020

Impact of ALK variants on brain metastasis and treatment response in advanced NSCLC patients with oncogenic ALK fusion.

Transl Lung Cancer Res 2020 Aug;9(4):1452-1463

Division of Hematology, Oncology and Blood & Marrow Transplantation, Department of Internal Medicine, Holden Comprehensive Cancer Center, University of Iowa Carver College of Medicine, Iowa City, IA, USA.

Background: To investigate the impact of ALK variants on the features of brain metastases (BM), the outcome of chemotherapy and targeted therapy using crizotinib, as well as the progression pattern in patients with ALK fusion.

Methods: Patients with ALK fusion were retrospectively collected from January 2013 to July 2017 in Shanghai Pulmonary Hospital. ALK rearrangements were identified via ARMS-PCR. ALK variants were identified via Sanger Sequencing.

Results: A total of 135 patients and 41 with brain metastasis were identified. Radiological features showed that the patients with ALK variant 1 had a larger BM size compared with patients with ALK non-variant 1 (median tumor size: 16.89 11.01 mm, P=0.031). Similar time to treatment failure (TTF) was observed in patients with ALK variant 1 and non-variant 1 who received first-line crizotinib (median TTF: 15.7 13.8 months, HR =0.75, P=0.34). Patients with ALK variant 1 who had baseline BM had significantly shorter TTF than non-variant 1 with baseline BM when treated with first-line crizotinib (median TTF: 9.1 14.9 months, HR =2.68, P=0.037). In patients treated with chemotherapy, ALK variant 1 was associated with inferior TTF (median TTF: 5.6 8.1 months, HR =1.66, P=0.039). Progression pattern was similar between ALK variant 1 and non-variant 1.

Conclusions: Patients with ALK variant 1 and baseline BM had inferior TTF on first-line crizotinib treatment and presented with more aggressive radiological features. Patients with ALK non-variant 1 had better clinical outcome on first-line chemotherapy.
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http://dx.doi.org/10.21037/tlcr-19-346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7481619PMC
August 2020

The impact of exon 19 deletion subtypes on clinical outcomes in non-small cell lung cancer.

Transl Lung Cancer Res 2020 Aug;9(4):1149-1158

Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China.

Background: The study investigated the resistant pattern and clinical outcomes of epidermal growth factor receptor () exon 19 deletion (19del) subtypes to tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC).

Methods: Two hundred eight treatment naive NSCLC patients detected as 19del using amplification-refractory mutation system (ARMS) were included. DNA sequencing was used to detect the subtypes. Clinicopathological features as well as patients' outcomes treated with first-line EGFR-TKIs were analyzed.

Results: Thirteen 19del subtypes were confirmed in 181 samples (87.0%). Among these, delE746_A750 was the most frequent subtype (130/181, 71.8%). delE746_A750 and deletions starting from E746 were frequently found in female (P=0.003 and P=0.013, respectively) and never smokers (P=0.002 and P=0.014, respectively) than non-delE746_A750 and deletions starting from L747 patients, respectively. T790M was more frequently occurred in delE746_A750 than non-delE746_A750 (P=0.001) and deletions starting from E746 than L747 patients (P=0.006) after first-line EGFR-TKIs resistance. Patients harboring deletions starting from L747 with insertions had significantly shorter progression-free survival (PFS) than deletions starting from L747 without insertion (8.3 15.0 m, P=0.017), or all other patients (8.3 12.6 m, P=0.027). Different 19del subtypes with T790M mutation had similar PFS when treated with osimertinib (P=0.102).

Conclusions: Patients with 19del subtypes had different clinicopathological features, and resistant pattern when treated with first-line TKIs. Patients harboring deletions starting from L747 with insertions had inferior outcomes than other subtypes.
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http://dx.doi.org/10.21037/tlcr-19-359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7481579PMC
August 2020

Distribution of pathogenic bacteria in lower respiratory tract infection in lung cancer patients after chemotherapy and analysis of integron resistance genes in respiratory tract isolates of uninfected patients.

J Thorac Dis 2020 Aug;12(8):4216-4223

Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, Shanghai, China.

Background: We studied the distribution of pathogenic bacteria in lower respiratory tract infection in lung cancer patients after chemotherapy and analyzed the integron resistance genes in respiratory tract isolates of uninfected patients.

Methods: Retrospective analysis was used to select sputum samples from 400 lung cancer patients after chemotherapy admitted in Fuyang People's Hospital from July 2017 to July 2019. Culture, isolation and identification of strains were conducted in accordance with the national clinical examination operating procedures.

Results: A total of 134 strains were identified. In 120 patients with pulmonary infection, 114 strains were cultured. Twenty strains of klebsiella pneumoniae were cultured in 280 patients without pulmonary infection. Among the 134 strains, the detection rate of gram-negative bacteria was 79.10%. The first four strains were , , , and . The gram-positive bacteria detection rate was 4.47%, mainly and . The fungus detection rate was 16.42%. The drug sensitivity results showed that the resistance rate of gram-negative bacillus to penicillin and cephalosporin was higher, and were more sensitive to carbapenem, piperacillin tazobactam and cefoperazone sulbactam. Gram-positive cocci were resistant to penicillin, macrolide and clindamycin, and sensitive to linezolid, vancomycin and rifampicin. All strains of fungal culture were candida albicans, which were sensitive to common antifungal drugs. Among the 20 strains of klebsiella pneumoniae cultured in sputum specimens of non-infected patients with lung cancer undergoing chemotherapy, 2 strains were integron-positive strains, and all of them were class I integrons.

Conclusions: Lung cancer patients after chemotherapy have a high resistance to commonly used antimicrobial drugs, so it is necessary to detect the resistance of pathogenic microorganisms in clinical practice. The strains carried by patients with lung cancer without pulmonary infection during chemotherapy can isolate type I integrons, suggesting that the spread of drug resistance at gene level should be closely detected.
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http://dx.doi.org/10.21037/jtd-20-928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7475539PMC
August 2020

Correction: Upregulation of SNX5 predicts poor prognosis and promotes hepatocellular carcinoma progression by modulating the EGFR-ERK1/2 signaling pathway.

Oncogene 2020 Oct;39(41):6511

State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41388-020-01440-7DOI Listing
October 2020

Cyclodextrin-mediated formation of porous RNA nanospheres and their application in synergistic targeted therapeutics of hepatocellular carcinoma.

Biomaterials 2020 12 7;261:120304. Epub 2020 Aug 7.

State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200032, PR China. Electronic address:

Spherical and porous nanoparticles are ideal nanostructures for drug delivery. But currently they are mainly composed of non-degradable inorganic materials, which hinder clinical applications. Here, biological porous nanospheres using RNA as the building blocks and cyclodextrin as the adhesive were synthesized. The RNA contained the aptamer of EpCAM for targeting delivery and siRNA for gene silencing of EpCAM, while cyclodextrin could load insoluble sorafenib, the core drug of targeted therapy for hepatocellular carcinoma (HCC), through its hydrophobic cavity. After being internalized into targeted HCC cells under the assistance of the aptamer, the porous nanospheres could be degraded by the cytoplasmic Dicer enzymes, releasing siRNA and sorafenib for synergistic therapy. The synergistic efficacy of the porous RNA nanospheres has been validated at in vitro function assay, subcutaneous tumor bearing mice, and orthotopic tumor bearing mice in vivo models. In view of the broad prospects of synergy of gene therapy with chemotherapy, and the fact that RNA and cyclodextrin of the porous nanospheres can be extended to load various types of siRNA and small molecule drugs, respectively, this form of biological porous nanospheres offers opportunities for targeted delivery of suitable drugs for treatment of specific tumors.
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http://dx.doi.org/10.1016/j.biomaterials.2020.120304DOI Listing
December 2020

Hypoproteinemia being a manifestation of immunotherapy-related liver dysfunction.

Ann Transl Med 2020 Jul;8(14):889

Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, Shanghai, China.

Immunotherapy has changed the pattern of treatment in cancer. The interaction between programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibits the activation of T cells, and PD-1/PD-L1 inhibitors can increase the immune response to cancer cells by inducing the immune cells, which has become an important clinical method to treat cancer. However, the alteration in the activation of T cells might lead to misidentification between the body's own cells and tumor cells and induce immune-related adverse events (IRAEs), such as pneumonitis, liver dysfunction, rash, colitis, nephritis, and endocrinopathies. And the IRAEs might lead to serious consequences. Studies have reported that PD-1/PD-L1 inhibitor-related hepatotoxicity is one of these adverse events. Most of the studies reported that hepatitis resulting from PD-1 inhibitor was manifested as elevated liver enzymes and bilirubin. Quite a few patients experienced lower degree of hepatotoxicity treated with checkpoint inhibitors, which indicated that it was necessary to focus on immunotherapy-related liver dysfunction. Here, we report a case of immunotherapy-related liver dysfunction with hypoproteinemia as the first manifestation under the treatment of PD-1 inhibitors combined with chemotherapy. This case suggests that hypoproteinemia was one of the manifestations of immunotherapy-related liver dysfunction, which helps us better understand the immunotherapy-related disease.
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http://dx.doi.org/10.21037/atm-20-4980DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396795PMC
July 2020

Folate receptor-positive circulating tumor cells as a predictive biomarker for the efficacy of first-line pemetrexed-based chemotherapy in patients with non-squamous non-small cell lung cancer.

Ann Transl Med 2020 May;8(10):631

Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China.

Background: There is a lack of well-established biomarkers to predict the efficacy of pemetrexed-based chemotherapy. In this prospective phase II study, we investigated the correlation of folate receptor (FR)-positive circulating tumor cell (CTC) level with the clinical outcomes of patients with advanced non-squamous non-small cell lung cancer (nsNSCLC) when treated with pemetrexed-based chemotherapy.

Methods: A total of 98 nsNSCLC patients were enrolled. Peripheral blood was collected from each patient prior to initiation of treatment. FR-positive CTCs were enriched by immunomagnetic leukocyte depletion and quantified using ligand-targeted polymerase chain reaction (LT-PCR) method.

Results: Patients with relatively low CTC level (11-16 FU/3 mL, n=32) showed a significantly shorter progression-free survival (PFS) and overall survival (OS) compared with those in the "high CTC level group" (>16 FU/3mL, n=28; median PFS, 133 versus 320 days, P<0.001; median OS, 632 days versus "not reached", P=0.003). Patients in the "high CTC level group" also achieved superior objective response rate (ORR) and disease control rate (DCR) over those in the "low CTC level group" (ORR, 40.9% versus 9.5%, P=0.0339; DCR, 100% versus 81.0%, P=0.0485). The clinical outcomes of pemetrexed in the "negative-CTC group" (<11 FU/3mL, n=38) fell between the "high CTC level group" and the "low CTC level group" (median PFS, 290 days; median OS, 1,122 days; ORR: 21.2%, DCR: 93.9%). Further multivariate Cox proportional hazards regression analysis demonstrated that "high CTC level" was an independent factor that was significantly associated with better PFS [hazard ratio (HR) =0.26, 95% confidence interval (CI), 0.12-0.58, P=0.001] and OS (HR =0.23, 95% CI, 0.06-0.92, P=0.037).

Conclusions: Our results implied that FR-positive CTC is a promising biomarker to predict the clinical outcome of pemetrexed-based chemotherapy in patients with advanced nsNSCLC.
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http://dx.doi.org/10.21037/atm-19-4680DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290650PMC
May 2020

Pan-cancer analysis identifies TERT alterations as predictive biomarkers for immune checkpoint inhibitors treatment.

Clin Transl Med 2020 Jun 20;10(2):e109. Epub 2020 Jun 20.

Department of Medical Oncology, Shanghai Pulmonary Hospital & Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China.

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http://dx.doi.org/10.1002/ctm2.109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403829PMC
June 2020

Challenges and countermeasures of thoracic oncology in the epidemic of COVID-19.

Transl Lung Cancer Res 2020 Apr;9(2):337-347

Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, Shanghai 200433, China.

Since December, 2019, a 2019 novel coronavirus disease (COVID-19) infected by the severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) emerged in Wuhan, Hubei province, and the epidemic situation has continued to spread globally. The epidemic spread of COVID-19 has brought great challenges to the clinical practice of thoracic oncology. Outpatient clinics need to strengthen the differential diagnosis of initial symptoms, pulmonary ground-glass opacity (GGO), consolidation, interstitial and/or interlobular septal thickening, and crazy paving appearance. In the routine of oncology, the differential diagnosis of adverse events from COVID-19 is also significant, including radiation pneumonitis, checkpoint inhibitor pneumonitis (CIP), neutropenic fever, and so on. During the epidemic, indications of transbronchial biopsy (TBB) and CT-guided percutaneous thoracic biopsy are strictly controlled. For patients who are planning to undergo biopsy operation, screening to exclude the possibility of COVID-19 should be carried out. For confirmed or suspected patients, three-level protection should be performed during the operation. Disinfection and isolation measures should be strictly carried out during the operation. At last, more attention to the protection of cancer patients and give priority to the treatment of infected cancer patients.
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http://dx.doi.org/10.21037/tlcr.2020.02.10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225133PMC
April 2020

ZNF143-Mediated H3K9 Trimethylation Upregulates CDC6 by Activating MDIG in Hepatocellular Carcinoma.

Cancer Res 2020 06 20;80(12):2599-2611. Epub 2020 Apr 20.

State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Zinc finger protein 143 (ZNF143) belongs to the zinc finger protein family and possesses transcription factor activity by binding sequence-specific DNA. The exact biological role of ZNF143 in hepatocellular carcinoma (HCC) has not been investigated. Here we report that ZNF143 is overexpressed in HCC tissues and its overexpression correlates with poor prognosis. Gain- and loss-of-function experiments showed that ZNF143 promoted HCC cell proliferation, colony formation, and tumor growth and . ZNF143 accelerated HCC cell-cycle progression by activating cell division cycle 6 (CDC6). Mechanistically, ZNF143 promoted expression of CDC6 by directly activating transcription of histone demethylase mineral dust-induced gene (MDIG), which in turn reduced H3K9me3 enrichment in the CDC6 promoter region. Consistently, ZNF143 expression correlated significantly with MDIG and CDC6 expression in HCC. Collectively, we propose a model for a ZNF143-MDIG-CDC6 oncoprotein axis that provides novel insight into ZNF143, which may serve as a therapeutic target in HCC. SIGNIFICANCE: These findings describe the mechanism by which ZNF143 promotes HCC proliferation and provide important clues for exploring new targets and strategies for clinical treatment of human liver cancer.
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http://dx.doi.org/10.1158/0008-5472.CAN-19-3226DOI Listing
June 2020
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