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Artikel ; Online: Detection and genetic characterization of circulating canine parvovirus from stray dogs in Shanghai, China.

Pu, Junyi / Zhang, Yan / Zhong, Dengke / Chen, Qiusheng

2024 Band 595, Seite(n) 110041

Abstract: Canine parvovirus (CPV) is the main cause of viral diarrhea in dogs. CPV became a global disease in 1978 and was endemic all over the world. CPV-2 was the first strain to be identified, but with genetic mutations, new genotypes such as CPV-2a/2b/2c/new- ... ...

Abstract	Canine parvovirus (CPV) is the main cause of viral diarrhea in dogs. CPV became a global disease in 1978 and was endemic all over the world. CPV-2 was the first strain to be identified, but with genetic mutations, new genotypes such as CPV-2a/2b/2c/new-2a/new-2b have emerged. In this study, 128 fecal samples of stray dogs suspected of CPV-2 infection were collected from January to March 2021 in Shanghai, China. All samples were screened by PCR and further analyzed by VP2 gene. The positive rate of CPV-2 was 9.4% (12/128), of which 6 CPV-2 isolates were successfully isolated. Phylogenetic tree analysis showed that 4 isolates were CPV-2c genotype and 2 were new-CPV-2b genotype. VP-2 is a key protein that determines the antigenic properties, host range and receptor binding of cpv-2. The results of VP2 amino acid sequence analysis in this study showed that the CPV-2c isolated strain was the same as the previous strains reported in China, including F267Y, Y324I, Q370R and A5G mutations in addition to the typical N426E mutations. Similarly, in addition to the conventional N426D, S297A, F267Y and Y324I mutations, the new CPV-2b isolate also had a new mutation of T440A. This study further confirmed the prevalence of CPV-2c and new-CPV-2b in Shanghai, and also found a new mutation site of new-CPV-2c, which provided a theoretical basis for further enriching the epidemiological data of CPV-2 in Shanghai, as well as the development of vaccines and the prevention and control of the disease.
Mesh-Begriff(e)	Animals ; Parvovirus, Canine/genetics ; Parvovirus, Canine/isolation & purification ; Parvovirus, Canine/classification ; Dogs ; China/epidemiology ; Parvoviridae Infections/veterinary ; Parvoviridae Infections/virology ; Parvoviridae Infections/epidemiology ; Dog Diseases/virology ; Dog Diseases/epidemiology ; Phylogeny ; Feces/virology ; Genotype ; Capsid Proteins/genetics ; Mutation
Sprache	Englisch
Erscheinungsdatum	2024-03-23
Erscheinungsland	United States
Dokumenttyp	Journal Article
ZDB-ID	200425-2
ISSN	1096-0341 ; 0042-6822
ISSN (online)	1096-0341
ISSN	0042-6822
DOI	10.1016/j.virol.2024.110041
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: A Novel Strategy to Identify Prognosis-Relevant Gene Sets in Cancers.

Pu, Junyi / Yu, Hui / Guo, Yan

Genes

2022 Band 13, Heft 5

Abstract: Molecular prognosis markers hold promise for improved prediction of patient survival, and a pathway or gene set may add mechanistic interpretation to their prognostic prediction power. In this study, we demonstrated a novel strategy to identify prognosis- ...

Abstract	Molecular prognosis markers hold promise for improved prediction of patient survival, and a pathway or gene set may add mechanistic interpretation to their prognostic prediction power. In this study, we demonstrated a novel strategy to identify prognosis-relevant gene sets in cancers. Our study consists of a first round of gene-level analyses and a second round of gene-set-level analyses, in which the Composite Gene Expression Score critically summarizes a surrogate expression value at gene set level and a permutation procedure is exerted to assess prognostic significance of gene sets. An optional differential coexpression module is appended to the two phases of survival analyses to corroborate and refine prognostic gene sets. Our strategy was demonstrated in 33 cancer types across 32,234 gene sets. We found oncogenic gene sets accounted for an increased proportion among the final gene sets, and genes involved in DNA replication and DNA repair have ubiquitous prognositic value for multiple cancer types. In summary, we carried out the largest gene set based prognosis study to date. Compared to previous similar studies, our approach offered multiple improvements in design and methodology implementation. Functionally relevant gene sets of ubiquitous prognostic significance in multiple cancer types were identified.
Mesh-Begriff(e)	Biomarkers ; Humans ; Neoplasms/diagnosis ; Neoplasms/genetics ; Prognosis ; Survival Analysis
Chemische Substanzen	Biomarkers
Sprache	Englisch
Erscheinungsdatum	2022-05-12
Erscheinungsland	Switzerland
Dokumenttyp	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2527218-4
ISSN	2073-4425 ; 2073-4425
ISSN (online)	2073-4425
ISSN	2073-4425
DOI	10.3390/genes13050862
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: MTX-13, a Novel PTK7-Directed Antibody-Drug Conjugate with Widened Therapeutic Index Shows Sustained Tumor Regressions for a Broader Spectrum of PTK7-Positive Tumors.

Kong, Chao / Pu, Junyi / Zhao, Qianqian / Weng, Weining / Ma, Linjie / Qian, Yu / Hu, Wenhao / Meng, Xun / Meng, Tao

Molecular cancer therapeutics

2023 Band 22, Heft 10, Seite(n) 1128–1143

Abstract: Protein tyrosine kinase 7 (PTK7) is a Wnt signaling pathway protein implicated in cancer development and metastasis. When using a potent microtubule inhibitor (Aur0101), PTK7-targeting antibody-drug conjugate (ADC), h6M24-vc0101 (PF-06647020/cofetuzumab ... ...

Abstract	Protein tyrosine kinase 7 (PTK7) is a Wnt signaling pathway protein implicated in cancer development and metastasis. When using a potent microtubule inhibitor (Aur0101), PTK7-targeting antibody-drug conjugate (ADC), h6M24-vc0101 (PF-06647020/cofetuzumab pelidotin) is efficacious only in limited tumor types with low response rates in a phase I trial. To improve patient response and to expand responding tumor types, we designed MTX-13, a PTK7-targeting ADC consisting of a novel antibody (Ab13) conjugated to eight molecules of topoisomerase I inhibitor exatecan through T1000, a novel self-immolative moiety. MTX-13 exhibited PTK7-specific cell binding, efficient internalization, and exatecan release to cause cytotoxic activity through DNA damage and apoptosis induction, and a strong bystander killing. MTX-13 displayed potent antitumor activities on cell line-derived xenograft and patient-derived xenograft models from a wide range of solid tumors, significantly outperforming h6M24-vc0101. PTK7 was shown to be an actionable target in small cell lung cancer for which MTX-13 showed complete and durable responses. With a consistent overexpression of PTK7 in squamous cell carcinomas derived from diverse anatomic sites, strong potency of MTX-13 in this group of heterogenous tumors suggested a common treatment strategy. Finally, MTX-13 inhibited tumor growth and metastasis in an orthotopic colon cancer xenograft model. MTX-13 displayed a favorable pharmacokinetic and safety profile in monkeys with the highest non-severely toxic dose (HNSTD) of ≥30 mg/kg, significantly higher than 3-5 mg/kg of HNSTD for h6M24-vc0101. The higher therapeutic index of MTX-13 bodes well for its clinical translation with the potential to expand the responding patient population beyond that of current PTK7-targeting ADCs.
Mesh-Begriff(e)	Humans ; Immunoconjugates/pharmacology ; Immunoconjugates/therapeutic use ; Immunoconjugates/chemistry ; Receptor Protein-Tyrosine Kinases/metabolism ; Cell Line, Tumor ; Antibodies ; Cell Adhesion Molecules/genetics
Chemische Substanzen	Immunoconjugates ; cofetuzumab pelidotin ; Receptor Protein-Tyrosine Kinases (EC 2.7.10.1) ; Antibodies ; PTK7 protein, human (EC 2.7.10.1) ; Cell Adhesion Molecules
Sprache	Englisch
Erscheinungsdatum	2023-06-23
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2063563-1
ISSN	1538-8514 ; 1535-7163
ISSN (online)	1538-8514
ISSN	1535-7163
DOI	10.1158/1535-7163.MCT-23-0164
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: KANK1

Pu, Junyi / Shen, Jianfeng / Zhong, Zihua / Yanling, Ma / Gao, Jie

Artificial cells, nanomedicine, and biotechnology

2020 Band 48, Heft 1, Seite(n) 639–647

Abstract: Paclitaxel (PTX), a tubulin-binding agent, is widely used and has shown good efficacy in the initial period of treatment for non-small cell lung cancer (NSCLC). However, the relatively rapid acquisition of resistance to PTX treatments that is observed in ...

Abstract	Paclitaxel (PTX), a tubulin-binding agent, is widely used and has shown good efficacy in the initial period of treatment for non-small cell lung cancer (NSCLC). However, the relatively rapid acquisition of resistance to PTX treatments that is observed in virtually all cases significantly limits its utility and remains a substantial challenge to the clinical management of NSCLC. The aim of this study was to identify candidate genes and mechanisms that might mediate acquired paclitaxel resistance. In this work, we established paclitaxel-resistant cells (A549-T) from parental cell lines by step-dose selection
Mesh-Begriff(e)	A549 Cells ; Adaptor Proteins, Signal Transducing/genetics ; Adaptor Proteins, Signal Transducing/metabolism ; Adenocarcinoma of Lung/drug therapy ; Adenocarcinoma of Lung/genetics ; Adenocarcinoma of Lung/pathology ; Antineoplastic Agents, Phytogenic/pharmacology ; Antineoplastic Agents, Phytogenic/therapeutic use ; Apoptosis/genetics ; Cell Line, Tumor ; Cell Movement/genetics ; Cytoskeletal Proteins/genetics ; Cytoskeletal Proteins/metabolism ; DNA Methylation ; Disease-Free Survival ; Drug Resistance, Neoplasm/drug effects ; Drug Resistance, Neoplasm/genetics ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; Lung Neoplasms/pathology ; Paclitaxel/pharmacology ; Paclitaxel/therapeutic use ; Tumor Suppressor Proteins/genetics ; Tumor Suppressor Proteins/metabolism
Chemische Substanzen	Adaptor Proteins, Signal Transducing ; Antineoplastic Agents, Phytogenic ; Cytoskeletal Proteins ; KANK1 protein, human ; Tumor Suppressor Proteins ; Paclitaxel (P88XT4IS4D)
Sprache	Englisch
Erscheinungsdatum	2020-02-16
Erscheinungsland	England
Dokumenttyp	Journal Article
ZDB-ID	2723095-8
ISSN	2169-141X ; 2169-1401
ISSN (online)	2169-141X
ISSN	2169-1401
DOI	10.1080/21691401.2020.1728287
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: TJP1, a Membrane-Expressed Protein, is a Potential Therapeutic and Prognostic Target for Lung Cancer.

Pu, Junyi / Ai, Tao / Weng, Weining / Wang, Lijun / Yang, Yuan / Ma, Linjie / Hu, Zhiping / Meng, Xun

Technology in cancer research & treatment

2022 Band 21, Seite(n) 15330338221106855

Abstract: Objective: ...

Abstract	Objective:
Mesh-Begriff(e)	Humans ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; Lung Neoplasms/metabolism ; Molecular Targeted Therapy ; Pancreatic Neoplasms/genetics ; Prognosis ; Prospective Studies ; Zonula Occludens-1 Protein/genetics ; Zonula Occludens-1 Protein/metabolism
Chemische Substanzen	TJP1 protein, human ; Zonula Occludens-1 Protein
Sprache	Englisch
Erscheinungsdatum	2022-08-11
Erscheinungsland	United States
Dokumenttyp	Journal Article
ZDB-ID	2146365-7
ISSN	1533-0338 ; 1533-0346
ISSN (online)	1533-0338
ISSN	1533-0346
DOI	10.1177/15330338221106855
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: AMT-562, a Novel HER3-targeting Antibody-Drug Conjugate, Demonstrates a Potential to Broaden Therapeutic Opportunities for HER3-expressing Tumors.

Weng, Weining / Meng, Tao / Pu, Junyi / Ma, Linjie / Shen, Yi / Wang, Zhaohui / Pan, Rong / Wang, Mingqiao / Chen, Caiwei / Wang, Lijun / Zhang, Jianjian / Zhou, Biao / Shao, Siyuan / Qian, Yu / Liu, Shuhui / Hu, Wenhao / Meng, Xun

Molecular cancer therapeutics

2023 Band 22, Heft 9, Seite(n) 1013–1027

Abstract: HER3 is a unique member of the EGFR family of tyrosine kinases, which is broadly expressed in several cancers, including breast, lung, pancreatic, colorectal, gastric, prostate, and bladder cancers and is often associated with poor patient outcomes and ... ...

Abstract	HER3 is a unique member of the EGFR family of tyrosine kinases, which is broadly expressed in several cancers, including breast, lung, pancreatic, colorectal, gastric, prostate, and bladder cancers and is often associated with poor patient outcomes and therapeutic resistance. U3-1402/Patritumab-GGFG-DXd is the first successful HER3-targeting antibody-drug conjugate (ADC) with clinical efficacy in non-small cell lung cancer. However, over 60% of patients are nonresponsive to U3-1402 due to low target expression levels and responses tend to be in patients with higher target expression levels. U3-1402 is also ineffective in more challenging tumor types such as colorectal cancer. AMT-562 was generated by a novel anti-HER3 antibody Ab562 and a modified self-immolative PABC spacer (T800) to conjugate exatecan. Exatecan showed higher cytotoxic potency than its derivative DXd. Ab562 was selected because of its moderate affinity for minimizing potential toxicity and improving tumor penetration purposes. Both alone or in combination therapies, AMT-562 showed potent and durable antitumor response in low HER3 expression xenograft and heterogeneous patient-derived xenograft/organoid models, including digestive system and lung tumors representing of unmet needs. Combination therapies pairing AMT-562 with therapeutic antibodies, inhibitors of CHEK1, KRAS, and tyrosine kinase inhibitor showed higher synergistic efficacy than Patritumab-GGFG-DXd. Pharmacokinetic and safety profiles of AMT-562 were favorable and the highest dose lacking severe toxicity was 30 mg/kg in cynomolgus monkeys. AMT-562 has potential to be a superior HER3-targeting ADC with a higher therapeutic window that can overcome resistance to generate higher percentage and more durable responses in U3-1402-insensitive tumors.
Mesh-Begriff(e)	Male ; Humans ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Lung Neoplasms/drug therapy ; Immunoconjugates/pharmacology ; Immunoconjugates/therapeutic use ; Receptor, ErbB-3 ; ErbB Receptors ; Cell Line, Tumor
Chemische Substanzen	Immunoconjugates ; Receptor, ErbB-3 (EC 2.7.10.1) ; ErbB Receptors (EC 2.7.10.1)
Sprache	Englisch
Erscheinungsdatum	2023-06-09
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2063563-1
ISSN	1538-8514 ; 1535-7163
ISSN (online)	1538-8514
ISSN	1535-7163
DOI	10.1158/1535-7163.MCT-23-0198
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Antibody-Exatecan Conjugates with a Novel Self-immolative Moiety Overcome Resistance in Colon and Lung Cancer.

Weng, Weining / Meng, Tao / Zhao, Qianqian / Shen, Yi / Fu, Guoxiang / Shi, Jing / Zhang, Yue / Wang, Zhaohui / Wang, Mingqiao / Pan, Rong / Ma, Linjie / Chen, Caiwei / Wang, Lijun / Zhou, Biao / Zhang, Hui / Pu, Junyi / Zhang, Jianjian / Hu, Yi Peter / Hua, Guoqiang /

Qian, Yu / Liu, Shu-Hui / Hu, Wenhao / Meng, Xun

Cancer discovery

2023 Band 13, Heft 4, Seite(n) 950–973

Abstract: Antibody-drug conjugates (ADC) using DNA topoisomerase I inhibitor DXd/SN-38 have transformed cancer treatment, yet more effective ADCs are needed for overcoming resistance. We have designed an ADC class using a novel self-immolative T moiety for ... ...

Abstract	Antibody-drug conjugates (ADC) using DNA topoisomerase I inhibitor DXd/SN-38 have transformed cancer treatment, yet more effective ADCs are needed for overcoming resistance. We have designed an ADC class using a novel self-immolative T moiety for traceless conjugation and release of exatecan, a more potent topoisomerase I inhibitor with less sensitivity to multidrug resistance (MDR). Characterized by enhanced therapeutic indices, higher stability, and improved intratumoral pharmacodynamic response, antibody-T moiety-exatecan conjugates targeting HER2, HER3, and TROP2 overcome the intrinsic or treatment resistance of equivalent DXd/SN-38 ADCs in low-target-expression, large, and MDR+ tumors. T moiety-exatecan ADCs display durable antitumor activity in patient-derived xenograft and organoid models representative of unmet clinical needs, including EGFR ex19del/T790M/C797S triple-mutation lung cancer and BRAF/KRAS-TP53 double-mutant colon cancer, and show synergy with PARP/ATR inhibitor and anti-PD-1 treatment. High tolerability of the T moiety-exatecan ADC class in nonhuman primates supports its potential to expand the responding patient population and tumor types beyond current ADCs. Significance: ADCs combining a novel self-immolative moiety and topoisomerase I inhibitor exatecan as payload show deep and durable response in low-target-expressing and MDR+ tumors resistant to DXd/SN-38 ADCs without increasing toxicity. This new class of ADCs has the potential to benefit an additional patient population beyond current options. See related commentary by Gupta et al., p. 817. This article is highlighted in the In This Issue feature, p. 799.
Mesh-Begriff(e)	Animals ; Humans ; Topoisomerase I Inhibitors/pharmacology ; Topoisomerase I Inhibitors/therapeutic use ; Irinotecan ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; Cell Line, Tumor ; Mutation ; Protein Kinase Inhibitors ; Antineoplastic Agents/pharmacology ; Immunoconjugates/pharmacology ; Immunoconjugates/therapeutic use ; Receptor, ErbB-2 ; Colon
Chemische Substanzen	exatecan (OC71PP0F89) ; Topoisomerase I Inhibitors ; Irinotecan (7673326042) ; Protein Kinase Inhibitors ; Antineoplastic Agents ; Immunoconjugates ; Receptor, ErbB-2 (EC 2.7.10.1)
Sprache	Englisch
Erscheinungsdatum	2023-01-24
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2625242-9
ISSN	2159-8290 ; 2159-8274
ISSN (online)	2159-8290
ISSN	2159-8274
DOI	10.1158/2159-8290.CD-22-1368
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Transcriptome profiling identified differentially expressed genes and pathways associated with tamoxifen resistance in human breast cancer.

Men, Xin / Ma, Jun / Wu, Tong / Pu, Junyi / Wen, Shaojia / Shen, Jianfeng / Wang, Xun / Wang, Yamin / Chen, Chao / Dai, Penggao

Oncotarget

2018 Band 9, Heft 3, Seite(n) 4074–4089

Abstract: Tamoxifen (TAM) resistance is an important clinical problem in the treatment of breast cancer. In order to identify the mechanism of TAM resistance for estrogen receptor (ER)-positive breast cancer, we screened the transcriptome using RNA-seq and ... ...

Abstract	Tamoxifen (TAM) resistance is an important clinical problem in the treatment of breast cancer. In order to identify the mechanism of TAM resistance for estrogen receptor (ER)-positive breast cancer, we screened the transcriptome using RNA-seq and compared the gene expression profiles between the MCF-7 mamma carcinoma cell line and the TAM-resistant cell line TAMR/MCF-7, 52 significant differential expression genes (DEGs) were identified including
Sprache	Englisch
Erscheinungsdatum	2018-01-09
Erscheinungsland	United States
Dokumenttyp	Journal Article
ZDB-ID	2560162-3
ISSN	1949-2553 ; 1949-2553
ISSN (online)	1949-2553
ISSN	1949-2553
DOI	10.18632/oncotarget.23694
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Nucleoside diphosphate kinase 2 confers acquired 5-fluorouracil resistance in colorectal cancer cells.

Wen, Shaojia / Wang, Xun / Wang, Yamin / Shen, Jianfeng / Pu, Junyi / Liang, Hui / Chen, Chao / Liu, Linna / Dai, Penggao

Artificial cells, nanomedicine, and biotechnology

2018 Band 46, Heft sup1, Seite(n) 896–905

Abstract: Colorectal cancer (CRC) is the third leading cause of cancer-related deaths worldwide. 5-fluorouracil (5-FU)-based chemotherapeutic regimens are routinely used for the treatment of patients with CRC. However, recurrence and chemotherapeutic drug ... ...

Abstract	Colorectal cancer (CRC) is the third leading cause of cancer-related deaths worldwide. 5-fluorouracil (5-FU)-based chemotherapeutic regimens are routinely used for the treatment of patients with CRC. However, recurrence and chemotherapeutic drug resistance limit the survival rates of patients with CRC. DNA methylation participates in diverse cellular processes by regulating the transcription of a large number of genes expression, cell division, apoptosis, cell adhesion and differentiation, and metabolism, thus it might mediate chemoresistance. Using an Illumina Infinium HD Assay, DNA methylation levels in a human 5-FU-resistant HCT-8 CRC cell line (HCT-8/FU) and its progenitor cell line HCT-8 were analysed. A total of 16,580 differentially methylated genes were identified, of which 8885 were hypermethylated and 7695 were hypomethylated in resistant cells. Among these genes, NME2 (nucleoside diphosphate kinase 2) exhibited a significant difference in methylation between cell lines and has known roles in gastric cancer and breast cancer; accordingly, we hypothesized that it plays a role in acquired resistance in CRC. Knockdown of NME2 restored 5-FU sensitivity in 5-FU-resistant CRC cells, reduced cell survival and increased cell apoptosis; and overexpression of NME2 in HCT-8 cells results in the acquisition of resistance to 5-FU, this alteration enhanced HCT-8 cells growth abilities and reduced apoptosis. These findings suggest that NME2 mediates chemoresistance to 5-FU in CRC and that specific NME2 inhibition could optimize 5-FU-based chemotherapy of CRC.
Mesh-Begriff(e)	Apoptosis/drug effects ; Cell Line, Tumor ; Colorectal Neoplasms/pathology ; DNA Methylation/drug effects ; Drug Resistance, Neoplasm/genetics ; Fluorouracil/pharmacology ; Gene Expression Regulation, Neoplastic/drug effects ; Gene Silencing ; Humans ; Nucleoside-Diphosphate Kinase/deficiency ; Nucleoside-Diphosphate Kinase/genetics ; Nucleoside-Diphosphate Kinase/metabolism
Chemische Substanzen	nucleoside diphosphate kinase 2 (EC 2.7.4.-) ; Nucleoside-Diphosphate Kinase (EC 2.7.4.6) ; Fluorouracil (U3P01618RT)
Sprache	Englisch
Erscheinungsdatum	2018-02-23
Erscheinungsland	England
Dokumenttyp	Journal Article
ZDB-ID	2723095-8
ISSN	2169-141X ; 2169-1401
ISSN (online)	2169-141X
ISSN	2169-1401
DOI	10.1080/21691401.2018.1439835
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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