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Article ; Online: Biological Hallmarks and Emerging Strategies to Target STAT3 Signaling in Multiple Myeloma

Jianbiao Zhou / Wee-Joo Chng

Cells, Vol 11, Iss 941, p

2022 Volume 941

Abstract: Multiple myeloma (MM) is the second most common hematological malignancy, characterized by an abnormal accumulation of plasma cells in the bone marrow. Signal transducer and activator of transcription 3 (STAT3) is a cytoplasmic transcription factor that ... ...

Abstract	Multiple myeloma (MM) is the second most common hematological malignancy, characterized by an abnormal accumulation of plasma cells in the bone marrow. Signal transducer and activator of transcription 3 (STAT3) is a cytoplasmic transcription factor that modulates the transcription of multiple genes to regulate various principal biological functions, for example, cell proliferation and survival, stemness, inflammation and immune responses. Aberrant STAT3 activation has been identified as a key driver of tumorigenesis in many types of cancers, including MM. Herein, we summarize the current evidence for the role of STAT3 in affecting cancer hallmark traits by: (1) sustaining MM cell survival and proliferation, (2) regulating tumor microenvironment, (3) inducing immunosuppression. We also provide an update of different strategies for targeting STAT3 in MM with special emphasis on JAK inhibitors that are currently undergoing clinical trials. Finally, we discuss the challenges and future direction of understanding STAT3 signaling in MM biology and the clinical development of STAT3 inhibitors.
Keywords	multiple myeloma ; signal transducer and activator of transcription 3 (STAT3) ; hallmarks of cancer ; targeted therapy ; JAK inhibitor ; Biology (General) ; QH301-705.5
Subject code	610 ; 570
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Biological Hallmarks and Emerging Strategies to Target STAT3 Signaling in Multiple Myeloma.

Zhou, Jianbiao / Chng, Wee-Joo

Cells

2022 Volume 11, Issue 6

Abstract	Multiple myeloma (MM) is the second most common hematological malignancy, characterized by an abnormal accumulation of plasma cells in the bone marrow. Signal transducer and activator of transcription 3 (STAT3) is a cytoplasmic transcription factor that modulates the transcription of multiple genes to regulate various principal biological functions, for example, cell proliferation and survival, stemness, inflammation and immune responses. Aberrant STAT3 activation has been identified as a key driver of tumorigenesis in many types of cancers, including MM. Herein, we summarize the current evidence for the role of STAT3 in affecting cancer hallmark traits by: (1) sustaining MM cell survival and proliferation, (2) regulating tumor microenvironment, (3) inducing immunosuppression. We also provide an update of different strategies for targeting STAT3 in MM with special emphasis on JAK inhibitors that are currently undergoing clinical trials. Finally, we discuss the challenges and future direction of understanding STAT3 signaling in MM biology and the clinical development of STAT3 inhibitors.
MeSH term(s)	Antineoplastic Agents/pharmacology ; Humans ; Multiple Myeloma/drug therapy ; Multiple Myeloma/pathology ; STAT3 Transcription Factor/metabolism ; Signal Transduction ; Tumor Microenvironment
Chemical Substances	Antineoplastic Agents ; STAT3 Transcription Factor ; STAT3 protein, human
Language	English
Publishing date	2022-03-10
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells11060941
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Article ; Online: [Corrigendum] PRIMA‑1

Li, Xiao-Lan / Zhou, Jianbiao / Xia, Chen-Jing / Min, Han / Lu, Zhong-Kai / Chen, Zhi-Rong

Oncology reports

2024 Volume 51, Issue 3

Abstract: Following the publication of the above article, the authors contacted the Editorial Office to explain that the strips of β‑actin, LC3 and p62 proteins of the RKO cell line shown in Fig. 2A and B, and those of the SW620 cell line shown in Fig. 3A and B, ... ...

Abstract	Following the publication of the above article, the authors contacted the Editorial Office to explain that the strips of β‑actin, LC3 and p62 proteins of the RKO cell line shown in Fig. 2A and B, and those of the SW620 cell line shown in Fig. 3A and B, were assembled in these figures incorrectly. To rectify the presentation of these two figures, the authors proposed that they replace the strips of β‑actin and p62 proteins in the original Figs. 2B and 3B with the β‑actin bands from one of the repeated western blotting experiments. The revised and corrected versions of Figs. 2 and 3 are shown on the next page. The authors wish to emphasize that these corrections do not grossly affect either the results or the conclusions reported in this work. The authors all agree to the publication of this Corrigendum, and are grateful to the Editor of
Language	English
Publishing date	2024-01-19
Publishing country	Greece
Document type	Published Erratum
ZDB-ID	1222484-4
ISSN	1791-2431 ; 1021-335X
ISSN (online)	1791-2431
ISSN	1021-335X
DOI	10.3892/or.2024.8703
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Article: First report of zucchini tigre mosaic virus infecting four cucurbit crops in China.

Zhou, Cuiji / Liang, Zirong / Zhang, Jianbiao / Huang, Bing / He, Gongzhe / Zhong, Chuangnan / Ouyang, Tianxi

Plant disease

2022

Abstract: Cucurbits including ridge ... ...

Abstract	Cucurbits including ridge gourd
Language	English
Publishing date	2022-09-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	754182-x
ISSN	0191-2917
ISSN	0191-2917
DOI	10.1094/PDIS-03-22-0454-PDN
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Article ; Online: BSN-ESC: A Big-Small Network-Based Environmental Sound Classification Method for AIoT Applications.

Peng, Lujie / Yang, Junyu / Yan, Longke / Chen, Zhiyi / Xiao, Jianbiao / Zhou, Liang / Zhou, Jun

Sensors (Basel, Switzerland)

2023 Volume 23, Issue 15

Abstract: In recent years, environmental sound classification (ESC) has prevailed in many artificial intelligence Internet of Things (AIoT) applications, as environmental sound contains a wealth of information that can be used to detect particular events. However, ...

Abstract	In recent years, environmental sound classification (ESC) has prevailed in many artificial intelligence Internet of Things (AIoT) applications, as environmental sound contains a wealth of information that can be used to detect particular events. However, existing ESC methods have high computational complexity and are not suitable for deployment on AIoT devices with constrained computing resources. Therefore, it is of great importance to propose a model with both high classification accuracy and low computational complexity. In this work, a new ESC method named BSN-ESC is proposed, including a big-small network-based ESC model that can assess the classification difficulty level and adaptively activate a big or small network for classification as well as a pre-classification processing technique with logmel spectrogram refining, which prevents distortion in the frequency-domain characteristics of the sound clip at the joint part of two adjacent sound clips. With the proposed methods, the computational complexity is significantly reduced, while the classification accuracy is still high. The proposed BSN-ESC model is implemented on both CPU and FPGA to evaluate its performance on both PC and embedded systems with the dataset ESC-50, which is the most commonly used dataset. The proposed BSN-ESC model achieves the lowest computational complexity with the number of floating-point operations (FLOPs) of only 0.123G, which represents a reduction of up to 2309 times in computational complexity compared with state-of-the-art methods while delivering a high classification accuracy of 89.25%. This work can achieve the realization of ESC being applied to AIoT devices with constrained computational resources.
Language	English
Publishing date	2023-07-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2052857-7
ISSN	1424-8220 ; 1424-8220
ISSN (online)	1424-8220
ISSN	1424-8220
DOI	10.3390/s23156767
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Article: The safety and efficacy of delayed surgery by simulating clinical progression of observable papillary thyroid microcarcinoma: a retrospective analysis of 524 patients from a single medical center.

Shi, Liuhong / Le, Kehao / Qi, Haiou / Feng, Yibing / Zhou, Liang / Wang, Jianbiao / Xie, Lei

Frontiers in oncology

2023 Volume 13, Page(s) 1046014

Abstract: Objective: When active surveillance (AS) is developed in the patients with low-risk papillary thyroid microcarcinoma (PTMC), a medical center needs to ensure the delayed operation that is caused by PTMC clinical progression to have the same prognosis as ...

Abstract	Objective: When active surveillance (AS) is developed in the patients with low-risk papillary thyroid microcarcinoma (PTMC), a medical center needs to ensure the delayed operation that is caused by PTMC clinical progression to have the same prognosis as that of immediate operation. The objective of this study was to investigate the efficacy of delayed surgery by simulating clinical progression (tumor size enlargement and appearance of lymph node metastasis) of PTMCs with AS in a single medical center. Methods: We retrospectively analyzed the response to therapy in 317 papillary thyroid carcinoma patients treated with total thyroidectomy and post-operative radioactive iodine ablation. They were classified into three groups according to tumor size (group A ≤0.5 cm; group B >0.5 cm and ≤1 cm; group C >1 cm and ≤1.5 cm) or two groups according to the presence (cN1) or absence (cN0) of the clinical lymph node (LN) metastasis. Groups C and cN1 were regarded as simulated clinical progression of observational PTMC and the operation for them was assumed to be "delayed surgery". However, Groups A, B and cN0 were regarded as no clinical progression and the operation for them was considered as immediate surgery. Results: There were no significantly differences in excellent response to therapy and recurrence-free survival not only among the group A, B and C, but also between the group cN0 and cN1. In other words, these insignificant differences were found between immediate and simulated "delayed" surgeries. Conclusion: For the PTMC patients suitable for AS, the oncological outcomes were also excellent even if surgery was delayed until after the presence of clinical progression, according to our clinical simulation. Furthermore, we consider that it was feasible for medical centers to assess the ability to implement AS for PTMC patients by retrospectively analyzing their own previous clinical data using the described simulation.
Language	English
Publishing date	2023-10-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2023.1046014
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Article: Novel mechanism of drug resistance to proteasome inhibitors in multiple myeloma.

Zhou, Jianbiao / Chng, Wee-Joo

World journal of clinical oncology

2019 Volume 10, Issue 9, Page(s) 303–306

Abstract: Multiple myeloma (MM) is a cancer caused by uncontrolled proliferation of antibody-secreting plasma cells in bone marrow, which represents the second most common hematological malignancy. MM is a highly heterogeneous disease and can be classified into a ... ...

Abstract	Multiple myeloma (MM) is a cancer caused by uncontrolled proliferation of antibody-secreting plasma cells in bone marrow, which represents the second most common hematological malignancy. MM is a highly heterogeneous disease and can be classified into a spectrum of subgroups based on their molecular and cytogenetic abnormalities. In the past decade, novel therapies, especially, the first-in-class proteasome inhibitor bortezomib, have been revolutionary for the treatment of MM patients. Despite these remarkable achievements, myeloma remains incurable with a high frequency of patients suffering from a relapse, due to drug resistance. Mutation in the proteasome β5-subunit (PSMB5) was found in a bortezomib-resistant cell line generated
Language	English
Publishing date	2019-09-12
Publishing country	United States
Document type	Editorial
ZDB-ID	2587357-X
ISSN	2218-4333
ISSN	2218-4333
DOI	10.5306/wjco.v10.i9.303
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Article ; Online: Crosstalk between endoplasmic reticulum stress and oxidative stress: a dynamic duo in multiple myeloma.

Xiong, Sinan / Chng, Wee-Joo / Zhou, Jianbiao

Cellular and molecular life sciences : CMLS

2021 Volume 78, Issue 8, Page(s) 3883–3906

Abstract: Under physiological and pathological conditions, cells activate the unfolded protein response (UPR) to deal with the accumulation of unfolded or misfolded proteins in the endoplasmic reticulum. Multiple myeloma (MM) is a hematological malignancy arising ... ...

Abstract	Under physiological and pathological conditions, cells activate the unfolded protein response (UPR) to deal with the accumulation of unfolded or misfolded proteins in the endoplasmic reticulum. Multiple myeloma (MM) is a hematological malignancy arising from immunoglobulin-secreting plasma cells. MM cells are subject to continual ER stress and highly dependent on the UPR signaling activation due to overproduction of paraproteins. Mounting evidence suggests the close linkage between ER stress and oxidative stress, demonstrated by overlapping signaling pathways and inter-organelle communication pivotal to cell fate decision. Imbalance of intracellular homeostasis can lead to deranged control of cellular functions and engage apoptosis due to mutual activation between ER stress and reactive oxygen species generation through a self-perpetuating cycle. Here, we present accumulating evidence showing the interactive roles of redox homeostasis and proteostasis in MM pathogenesis and drug resistance, which would be helpful in elucidating the still underdefined molecular pathways linking ER stress and oxidative stress in MM. Lastly, we highlight future research directions in the development of anti-myeloma therapy, focusing particularly on targeting redox signaling and ER stress responses.
MeSH term(s)	Animals ; Endoplasmic Reticulum Stress ; Humans ; Multiple Myeloma/metabolism ; Multiple Myeloma/pathology ; Oxidative Stress ; Signal Transduction
Language	English
Publishing date	2021-02-18
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	1358415-7
ISSN	1420-9071 ; 1420-682X
ISSN (online)	1420-9071
ISSN	1420-682X
DOI	10.1007/s00018-021-03756-3
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Article ; Online: First Report of Zucchini Tigre Mosaic Virus Infecting Four Cucurbit Crops in China

Zhou, Cuiji / Liang, Zirong / Zhang, Jianbiao / Huang, Bing / He, Gongzhe / Zhong, Chuangnan / Ouyang, Tianxi

Plant Disease. 2023 Apr. 03, v. 107, no. 4 p.1247-

2023

Abstract: Cucurbits, including ridge gourd (Luffa acutangula), Chieh-qua (Benincasa hispida Cogn. var. chieh-qua How), Trichosanthes anguina, and sponge gourd (L. cylindrica), are important vegetables in most Asian countries. The 90 viruses known to infect ... ...

Abstract	Cucurbits, including ridge gourd (Luffa acutangula), Chieh-qua (Benincasa hispida Cogn. var. chieh-qua How), Trichosanthes anguina, and sponge gourd (L. cylindrica), are important vegetables in most Asian countries. The 90 viruses known to infect cucurbits include 15 species in genus Potyvirus. In October 2020, nine cucurbit samples with leaf distortion, blister, and mottle were collected from the same field of Foshan City, Guangdong Province, China. All samples were tested by western blot with a potyvirus-specific antibody (Agdia, Elkhart, IN) and RT-PCR with potyvirus degenerate primers Sprimer/M4T (Chen et al. 2001). Seven out of nine samples were positive for potyvirus in both tests, including one ridge gourd, one Chieh-qua, one sponge gourd, two bottle gourd (Lagenaria siceraria), and two T. anguina. All PCR products (∼700 bp) were cloned and sequenced. Sequences of seven amplicons (OM522614 to OM522618, OP090158 to OP090159) containing partial nib and cp genes shared 80.3 to 100% nucleotide (nt) identity among themselves, and 81.2 to 97.7% nt identity with zucchini tigre mosaic virus (ZTMV) isolates from China (MN267689, LC371337, and MK988416). Except for one Chieh-qua sample, papaya ringspot virus (PRSV) was detected in the same samples where ZTMV was found through sequencing of the amplicons mentioned above. The obtained sequences (OM808942 to OM808945, OP090170 to OP090171) were 95.4 to 100% identical with PRSV isolates from China. Further RT-PCR was conducted with ZTMV-specific primers ZTMVdF/ZTMVdR targeting partial P3 and 6K1 genes, and PRSV-specific primers PRSV3778F/PRSV4630R targeting partial P3, full-length 6K1, and partial CI genes for all nine samples. Consistently, seven samples were positive for ZTMV, among which one Chieh-qua sample was infected with only ZTMV and six samples were coinfected with ZTMV and PRSV. An interspecific recombination event has been reported for ZTMV (Peng et al. 2021); to detect the recombinants, RT-PCR was conducted for all nine samples with primers ZTMV600F/ZTMV2400R covering the interspecies recombination site (Peng et al. 2021). A fragment (∼1.8 kb) was amplified from one T. anguina sample and sequenced (OP090172); it had 97.0% nt identity with the reported recombinant ZTMV-KF17 (MK988415). To fulfill Koch’s postulates, a Chieh-qua sample with detected ZTMV but not PRSV was used for mechanical inoculation on Chieh-qua seedlings. Blister and leaf distortion similar to the field symptoms were observed 21 days postinoculation. ZTMV infection was verified by RT-PCR with primer pairs Sprimer/M4T and ZTMVdF/ZTMVdR, respectively, followed by sequencing. No amplicon was detected with primer pairs PRSV3778F/PRSV4630R and ZTMV600F/ZTM2400R. To study the incidence of ZTMV and PRSV, 33 samples, including T. anguina, ridge gourd, and Chieh-qua, were collected from three different fields in Foshan City in May 2022 and tested by RT-PCR with the ZTMV and PRSV primers aforementioned. Of the samples, 30.3% (10/33) were positive for ZTMV, 39.4% (13/33) were positive for PRSV, and 21.2% (7/33) were coinfected with the two viruses. Then, amplicons of ZTMV (600 bp) from all positive samples were sequenced (OP090160 to OP090169); they were 84.8 to 85.5% identical with ZTMV-TW (LC371337). The recombinant of ZTMV was detected in one T. anguina with primers mentioned above and was sequenced (OP090173); it had 96.2% nt identity with ZTMV-KF17 (MK988415). To our knowledge, this is the first report of ZTMV infecting ridge gourd, Chieh-qua, T. anguina, and sponge gourd. The results implied that ZTMV has a potential risk to more cucurbit crops in the field.
Keywords	Benincasa hispida ; Lagenaria siceraria ; Luffa acutangula ; Luffa aegyptiaca ; Papaya ringspot virus ; Trichosanthes cucumerina var. anguina ; Western blotting ; Zucchini tigre mosaic virus ; antibodies ; leaves ; mixed infection ; risk ; China ; cucurbit crop ; pathogen detection ; Potyvirus ; vegetables ; viruses and viroids
Language	English
Dates of publication	2023-0403
Publishing place	The American Phytopathological Society
Document type	Article ; Online
ZDB-ID	754182-x
ISSN	0191-2917
ISSN	0191-2917
DOI	10.1094/PDIS-03-22-0454-PDN
Database	NAL-Catalogue (AGRICOLA)

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Article: Resistance to FLT3 inhibitors in acute myeloid leukemia: Molecular mechanisms and resensitizing strategies.

Zhou, Jianbiao / Chng, Wee-Joo

World journal of clinical oncology

2018 Volume 9, Issue 5, Page(s) 90–97

Abstract: FMS-like tyrosine kinase 3 (FLT3) is classified as a type III receptor tyrosine kinase, which exerts a key role in regulation of normal hematopoiesis. ...

Abstract	FMS-like tyrosine kinase 3 (FLT3) is classified as a type III receptor tyrosine kinase, which exerts a key role in regulation of normal hematopoiesis.
Language	English
Publishing date	2018-08-23
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2587357-X
ISSN	2218-4333
ISSN	2218-4333
DOI	10.5306/wjco.v9.i5.90
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