Articles

Circular RNA MAPK4 (circ-MAPK4) inhibits cell apoptosis via MAPK signaling pathway by sponging miR-125a-3p in gliomas

Recent evidences have shown that circular RNAs (circRNAs) are frequently dysregulated and play paramount roles in various cancers. circRNAs are abundant in central nervous system (CNS); however, few studies de...

Authors: Jiehua He, Zuoyu Huang, Mingliang He, Jianyou Liao, Qianqian Zhang, Shengwen Wang, Lin Xie, Leping Ouyang, H. Phillip Koeffler, Dong Yin and Anmin Liu

Correction to: Vascular endothelial growth factor is an autocrine growth factor, signaling through neuropilin-1 in non-small cell lung cancer

Since the publication of this work [1] and in response to a recent query that was brought to our attention in relation to the Western Blot in Figure 1(C) for NP2, protein lysates prepared around the same time ...

Authors: Martin P. Barr, Steven G. Gray, Kathy Gately, Emily Hams, Padraic G. Fallon, Anthony Mitchell Davies, Derek J. Richard, Graham P. Pidgeon and Kenneth J. O’Byrne

Circulating tumor cells in cancer patients: developments and clinical applications for immunotherapy

Cancer metastasis is the leading cause of cancer-related death. Circulating tumor cells (CTCs) are shed into the bloodstream from either primary or metastatic tumors during an intermediate stage of metastasis....

Authors: Xiaoming Zhong, Hangtian Zhang, Ying Zhu, Yuqing Liang, Zhuolin Yuan, Jiachen Li, Jing Li, Xin Li, Yifan Jia, Tian He, Jiangyuan Zhu, Yu Sun, Wengting Jiang, Hui Zhang, Cheng Wang and Zunfu Ke

Roles of circRNAs in the tumour microenvironment

The tumour microenvironment (TME) constitutes the area surrounding the tumour during its development and has been demonstrated to play roles in cancer-related diseases through crosstalk with tumour cells. Circ...

Authors: Qiuge Zhang, Weiwei Wang, Quanbo Zhou, Chen Chen, Weitang Yuan, Jinbo Liu, Xiaoli Li and Zhenqiang Sun

CircPTK2 (hsa_circ_0005273) as a novel therapeutic target for metastatic colorectal cancer

As a novel class of noncoding RNAs, circRNAs have been recently identified to regulate tumorigenesis and aggressiveness. However, the function of circRNAs in colorectal cancer (CRC) metastasis remains unclear....

Authors: Hongbao Yang, Xiaobo Li, Qingtao Meng, Hao Sun, Shenshen Wu, Weiwei Hu, Guilai Liu, Xianjing Li, Yong Yang and Rui Chen

Autophagy and autophagy-related proteins in cancer

Autophagy, as a type II programmed cell death, plays crucial roles with autophagy-related (ATG) proteins in cancer. Up to now, the dual role of autophagy both in cancer progression and inhibition remains contr...

Authors: Xiaohua Li, Shikun He and Binyun Ma

Hypoxia induced LUCAT1/PTBP1 axis modulates cancer cell viability and chemotherapy response

Hypoxic tumors are refractory to DNA damage drugs. However, the underlying mechanism has yet to be elucidated. We aimed to identify lncRNAs that upregulated under hypoxia and their effects on colorectal cancer...

Authors: Lin Huan, Tianan Guo, Yangjun Wu, Linguo Xu, Shenglin Huang, Ye Xu, Linhui Liang and Xianghuo He

The PI3K subunits, P110α and P110β are potential targets for overcoming P-gp and BCRP-mediated MDR in cancer

PI3K/AKT is a vital signaling pathway in humans. Recently, several PI3K/AKT inhibitors were reported to have the ability to reverse cancer multidrug resistance (MDR); however, specific targets in the PI3K/AKT ...

Authors: Lei Zhang, Yidong Li, Qianchao Wang, Zhuo Chen, Xiaoyun Li, Zhuoxun Wu, Chaohua Hu, Dan Liao, Wei Zhang and Zhe-Sheng Chen

lncRNA JPX/miR-33a-5p/Twist1 axis regulates tumorigenesis and metastasis of lung cancer by activating Wnt/β-catenin signaling

MicroRNAs (miRNAs) and Twist1-induced epithelial-mesenchymal transition (EMT) in cancer cell dissemination are well established, but the involvement of long noncoding RNAs (lncRNAs) in Twist1-mediated signalin...

Authors: Jinchang Pan, Shuai Fang, Haihua Tian, Chengwei Zhou, Xiaodong Zhao, Hui Tian, Jinxian He, Weiyu Shen, Xiaodan Meng, Xiaofeng Jin and Zhaohui Gong

Circular RNAs in the tumour microenvironment

Circular RNAs (circRNAs) are a new class of endogenous non-coding RNAs (ncRNAs) widely expressed in eukaryotic cells. Mounting evidence has highlighted circRNAs as critical regulators of various tumours. More ...

Authors: Zhonghua Ma, You Shuai, Xiangyu Gao, Xianzi Wen and Jiafu Ji

Downregulation of MYPT1 increases tumor resistance in ovarian cancer by targeting the Hippo pathway and increasing the stemness

Ovarian cancer is one of the most common and malignant cancers, partly due to its late diagnosis and high recurrence. Chemotherapy resistance has been linked to poor prognosis and is believed to be linked to t...

Authors: Sandra Muñoz-Galván, Blanca Felipe-Abrio, Eva M. Verdugo-Sivianes, Marco Perez, Manuel P. Jiménez-García, Elisa Suarez-Martinez, Purificacion Estevez-Garcia and Amancio Carnero

TEAD4 modulated LncRNA MNX1-AS1 contributes to gastric cancer progression partly through suppressing BTG2 and activating BCL2

Gastric cancer (GC) is the third leading cause of cancer-related mortality globally. Long noncoding RNAs (lncRNAs) are dysregulated in obvious malignancies including GC and exploring the regulatory mechanisms ...

Authors: You Shuai, Zhonghua Ma, Weitao Liu, Tao Yu, Changsheng Yan, Hua Jiang, Shengwang Tian, Tongpeng Xu and Yongqian Shu

Role of HDACs in normal and malignant hematopoiesis

Normal hematopoiesis requires the accurate orchestration of lineage-specific patterns of gene expression at each stage of development, and epigenetic regulators play a vital role. Disordered epigenetic regulat...

Authors: Pan Wang, Zi Wang and Jing Liu

A novel IFNα-induced long noncoding RNA negatively regulates immunosuppression by interrupting H3K27 acetylation in head and neck squamous cell carcinoma

Interferon alpha (IFNα) is a well-established regulator of immunosuppression in head and neck squamous cell carcinoma (HNSCC), while the role of long noncoding RNAs (lncRNAs) in immunosuppression remains large...

Authors: Hailong Ma, Hanyue Chang, Wenyi Yang, Yusheng Lu, Jingzhou Hu and Shufang Jin

m⁶A demethylase ALKBH5 inhibits pancreatic cancer tumorigenesis by decreasing WIF-1 RNA methylation and mediating Wnt signaling

Pancreatic cancer is one of the most lethal types of cancer with extremely poor diagnosis and prognosis, and chemo-resistance remains a major challenge. The dynamic and reversible N⁶-methyladenosine (m⁶A) RNA mod...

Authors: Bo Tang, Yihua Yang, Min Kang, Yunshan Wang, Yan Wang, Yin Bi, Songqing He and Fumio Shimamoto

The emerging role of SPOP protein in tumorigenesis and cancer therapy

The nuclear speckle-type pox virus and zinc finger (POZ) protein (SPOP), a representative substrate-recognition subunit of the cullin-RING E3 ligase, has been characterized to play a dual role in tumorigenesis...

Authors: Yizuo Song, Yichi Xu, Chunyu Pan, Linzhi Yan, Zhi-wei Wang and Xueqiong Zhu

The significance of exosomes in the development and treatment of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the most commonmalignancy. Exsome plays a significant role in the elucidation of signal transduction pathways between hepatoma cells, angiogenesis and early diagnosis of HCC. ...

Authors: Xin Li, Chuanyun Li, Liping Zhang, Min Wu, Ke Cao, Feifei Jiang, Dexi Chen, Ning Li and Weihua Li

m⁶A mRNA methylation regulates CTNNB1 to promote the proliferation of hepatoblastoma

N⁶-Methyladenosine (m⁶A) modification has been implicated in many biological processes. It is important for the regulation of messenger RNA (mRNA) stability, splicing, and translation. However, its role in cancer...

Authors: Li Liu, Jing Wang, Guifeng Sun, Qiong Wu, Ji Ma, Xin Zhang, Nan Huang, Zhixuan Bian, Song Gu, Min Xu, Minzhi Yin, Fenyong Sun and Qiuhui Pan

LINC02273 drives breast cancer metastasis by epigenetically increasing AGR2 transcription

The majority of breast cancer patients die of metastasis rather than primary tumors, whereas the molecular mechanisms orchestrating cancer metastasis remains poorly understood. Long noncoding RNAs (lncRNA) hav...

Authors: Bingqiu Xiu, Yayun Chi, Lei Liu, Weiru Chi, Qi Zhang, Jiajian Chen, Rong Guo, Jing Si, Lun Li, Jingyan Xue, Zhi-Ming Shao, Zhao-Hui Wu, Shenglin Huang and Jiong Wu

KIAA1429 contributes to liver cancer progression through N6-methyladenosine-dependent post-transcriptional modification of GATA3

N6-methyladenosine (m6A) modification, the most abundant internal methylation of eukaryotic RNA transcripts, is critically implicated in RNA processing. As the largest known component in the m6A methyltransfer...

Authors: Tian Lan, Hui Li, Delin Zhang, Lin Xu, Hailing Liu, Xiangyong Hao, Xiaokai Yan, Haotian Liao, Xiangzheng Chen, Kunlin Xie, Jiaxin Li, Mingheng Liao, Jiwei Huang, Kefei Yuan, Yong Zeng and Hong Wu

m⁶A modification-mediated CBX8 induction regulates stemness and chemosensitivity of colon cancer via upregulation of LGR5

Colon cancer (CC) cells can exhibit stemness and expansion capabilities, which contribute to resistance to conventional chemotherapies. Aberrant expression of CBX8 has been identified in many types of cancer, ...

Authors: Yi Zhang, Min Kang, Bin Zhang, Fanchao Meng, Jun Song, Hiroshi Kaneko, Fumio Shimamoto and Bo Tang

The reciprocal regulation between host tissue and immune cells in pancreatic ductal adenocarcinoma: new insights and therapeutic implications

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death and is one of the most difficult-to-treat cancers. Surgical resection and adjuvant therapy have limited effects on th...

Authors: Xiaomeng Liu, Jin Xu, Bo Zhang, Jiang Liu, Chen Liang, Qingcai Meng, Jie Hua, Xianjun Yu and Si Shi

RNA-Seq reveal the circular RNAs landscape of lung cancer

Authors: Christophe Nicot

Chemotherapeutic drugs stimulate the release and recycling of extracellular vesicles to assist cancer cells in developing an urgent chemoresistance

Chemotherapy is a widely used treatment for cancer. However, the development of acquired multidrug resistance (MDR) is a serious issue. Emerging evidence has shown that the extracellular vesicles (EVs) mediate...

Authors: Xiaokun Wang, Dongjuan Qiao, Likun Chen, Meng Xu, Shupeng Chen, Liyan Huang, Fang Wang, Zhen Chen, Jiye Cai and Liwu Fu

N6-methyladenosine induced miR-143-3p promotes the brain metastasis of lung cancer via regulation of VASH1

Brain metastasis (BM) is one of the principal causes of mortality for lung cancer patients. While the molecular events that govern BM of lung cancer remain frustrating cloudy.

Authors: Hongsheng Wang, Qianqian Deng, Ziyan Lv, Yuyi Ling, Xue Hou, Zhuojia Chen, Xiaoxiao Dinglin, Shuxiang Ma, Delan Li, Yingmin Wu, Yanxi Peng, Hongbing Huang and Likun Chen

Molecular networks of FOXP family: dual biologic functions, interplay with other molecules and clinical implications in cancer progression

Though Forkhead box P (FOXP) transcription factors comprising of FOXP1, FOXP2, FOXP3 and FOXP4 are involved in the embryonic development, immune disorders and cancer progression, the underlying function of FOX...

Authors: Ju-Ha Kim, Jisung Hwang, Ji Hoon Jung, Hyo-Jung Lee, Dae Young Lee and Sung-Hoon Kim

Circular RNA circFGFR1 promotes progression and anti-PD-1 resistance by sponging miR-381-3p in non-small cell lung cancer cells

Immune system evasion, distance tumor metastases, and increased cell proliferation are the main reasons for the progression of non-small cell lung cancer (NSCLC) and the death of NSCLC patients. Dysregulation ...

Authors: Peng-Fei Zhang, Xu Pei, Ke-Sang Li, Li-Na Jin, Fei Wang, Jing Wu and Xue-Mei Zhang

N⁶-methyladenosine (m⁶A) RNA modification in gastrointestinal tract cancers: roles, mechanisms, and applications

Analogous to DNA methylation and histone modification, RNA modification, as another epigenetic layer, plays an important role in many diseases, especially in tumours. As the most common form of RNA modificatio...

Authors: Bin-bin Hu, Xiao-yan Wang, Xu-Yu Gu, Chen Zou, Zhen-jun Gao, Heng Zhang and Yu Fan

Harnessing tumor-associated macrophages as aids for cancer immunotherapy

Cancer immunotherapies that engage immune cells to fight against tumors are proving to be powerful weapons in combating cancer and are becoming increasingly utilized in the clinics. However, for the majority o...

Authors: Xiaolei Li, Rui Liu, Xiao Su, Yongsha Pan, Xiaofeng Han, Changshun Shao and Yufang Shi

Functions of N6-methyladenosine and its role in cancer

N6-methyladenosine (m6A) is methylation that occurs in the N6-position of adenosine, which is the most prevalent internal modification on eukaryotic mRNA. Accumulating evidence suggests that m6A modulates gene...

Authors: Liuer He, Huiyu Li, Anqi Wu, Yulong Peng, Guang Shu and Gang Yin

Extracellular vesicles of carcinoma-associated fibroblasts creates a pre-metastatic niche in the lung through activating fibroblasts

Carcinoma-associated fibroblasts (CAFs) have been known to promote cancer progression by modifying the primary tumor microenvironment. We aimed to elucidate the intercellular communication between CAFs and sec...

Authors: Jing Kong, Hongzhu Tian, Fuyin Zhang, Zebing Zhang, Jiao Li, Xue Liu, Xiancheng Li, Jing Liu, Xiaojie Li, Dong Jin, Xuesong Yang, Bo Sun, Tao Guo, Yong Luo, Yao Lu, Bingcheng Lin…

LncRNA LINRIS stabilizes IGF2BP2 and promotes the aerobic glycolysis in colorectal cancer

Long noncoding RNAs (lncRNAs) play nonnegligible roles in the epigenetic regulation of cancer cells. This study aimed to identify a specific lncRNA that promotes the colorectal cancer (CRC) progression and cou...

Authors: Yun Wang, Jia-Huan Lu, Qi-Nian Wu, Ying Jin, De-Shen Wang, Yan-Xing Chen, Jia Liu, Xiao-Jing Luo, Qi Meng, Heng-Ying Pu, Ying-Nan Wang, Pei-Shan Hu, Ze-Xian Liu, Zhao-Lei Zeng, Qi Zhao, Rong Deng…

Role of the microbiome in occurrence, development and treatment of pancreatic cancer

Pancreatic cancer is one of the most lethal malignancies. Recent studies indicated that development of pancreatic cancer may be intimately connected with the microbiome. In this review, we discuss the mechanis...

Authors: Yicheng Wang, Gang Yang, Lei You, Jinshou Yang, Mengyu Feng, Jiangdong Qiu, Fangyu Zhao, Yueze Liu, Zhe Cao, Lianfang Zheng, Taiping Zhang and Yupei Zhao

Correction to: c-Src confers resistance to mitotic stress through inhibition of DMAP1/Bub3 complex formation in pancreatic cancer

Following publication of the work [1], authors reported the “flow cytometery plots” panel in Fig. 4e contained an inter-duplication in error.

Authors: Jingjie Li, Bin Hu, Ting Wang, Wenhua Huang, Chunmin Ma, Qin Zhao, Lingang Zhuo, Tao Zhang and Yuhui Jiang

Long noncoding RNA LCAT1 functions as a ceRNA to regulate RAC1 function by sponging miR-4715-5p in lung cancer

Long noncoding RNAs (lncRNAs) are emerging as key players in the development and progression of cancer. However, the biological role and clinical significance of most lncRNAs in lung carcinogenesis remain uncl...

Authors: Juze Yang, Qiongzi Qiu, Xinyi Qian, Jiani Yi, Yiling Jiao, Mengqian Yu, Xufan Li, Jia Li, Chunyi Mi, Jisong Zhang, Bingjian Lu, Enguo Chen, Pengyuan Liu and Yan Lu

Prostate Cancer-associated SPOP mutations enhance cancer cell survival and docetaxel resistance by upregulating Caprin1-dependent stress granule assembly

The gene encoding the E3 ubiquitin ligase substrate-binding adaptor SPOP is frequently mutated in primary prostate cancer, but how SPOP mutations contribute to prostate cancer pathogenesis remains poorly under...

Authors: Qing Shi, Yasheng Zhu, Jian Ma, Kun Chang, Dongling Ding, Yang Bai, Kun Gao, Pingzhao Zhang, Ren Mo, Kai Feng, Xiaying Zhao, Liang Zhang, Huiru Sun, Dongyue Jiao, Yingji Chen, Yinghao Sun…

MRE11-RAD50-NBS1 complex alterations and DNA damage response: implications for cancer treatment

Genome instability is a hallmark of cancer cells and can be accelerated by defects in cellular responses to DNA damage. This feature of malignant cells opens new avenues for tumor targeted therapy. MRE11-RAD50...

Authors: Lei Bian, Yiling Meng, Meichao Zhang and Dong Li

Mettl14 inhibits bladder TIC self-renewal and bladder tumorigenesis through N⁶-methyladenosine of Notch1

N⁶-methyladenosine (m⁶A) emerges as one of the most important modification of RNA. Bladder cancer is a common cancer type in developed countries, and hundreds of thousands of bladder cancer patients die every yea...

Authors: Chaohui Gu, Zhiyu Wang, Naichun Zhou, Guanru Li, Yiping Kou, Yang Luo, Yidi Wang, Jinjian Yang and Fengyan Tian

LncRNA-HGBC stabilized by HuR promotes gallbladder cancer progression by regulating miR-502-3p/SET/AKT axis

Long non-coding RNAs (lncRNAs) are essential factors that regulate tumor development and metastasis via diverse molecular mechanisms in a broad type of cancers. However, the pathological roles of lncRNAs in ga...

Authors: Yun-ping Hu, Yun-peng Jin, Xiang-song Wu, Yang Yang, Yong-sheng Li, Huai-feng Li, Shan-shan Xiang, Xiao-ling Song, Lin Jiang, Yi-jian Zhang, Wen Huang, Shi-li Chen, Fa-tao Liu, Chen Chen, Qin Zhu, Hong-zhuan Chen…

Circular RNA circERBB2 promotes gallbladder cancer progression by regulating PA2G4-dependent rDNA transcription

CircRNAs are found to affect initiation and progression of several cancer types. However, whether circRNAs are implicated in gallbladder cancer (GBC) progression remains obscure.

Authors: Xince Huang, Ming He, Shuai Huang, Ruirong Lin, Ming Zhan, Dong Yang, Hui Shen, Sunwang Xu, Wei Cheng, Jianxiu Yu, Zilong Qiu and Jian Wang

EGFR-TKI resistance promotes immune escape in lung cancer via increased PD-L1 expression

The ATLANTIC trial reported that higher PD-L1 expression in tumors was involved in a higher objective response in patients with EGFR⁺/ALK⁺ non-small cell lung cancer (NSCLC), indicating the possibility of anti-PD...

Authors: Shunli Peng, Rong Wang, Xiaojuan Zhang, Yueyun Ma, Longhui Zhong, Ke Li, Akihiro Nishiyama, Sachiko Arai, Seiji Yano and Wei Wang

Correction to: KIF5B-RET fusion kinase promotes cell growth by multilevel activation of STAT3 in lung cancer

After the publication of this work [1],

Authors: Yingying Qian, Shoujie Chai, Zuyu Liang, Yongfang Wang, You Zhou, Xia Xu, Chenchen Zhang, Min Zhang, Jingxing Si, Feiteng Huang, Zhangdan Huang, Wei Hong and Kai Wang

YTHDF2 reduction fuels inflammation and vascular abnormalization in hepatocellular carcinoma

Dynamic N⁶-methyladenosine (m⁶A) modification was previously identified as a ubiquitous post-transcriptional regulation that affected mRNA homeostasis. However, the m⁶A-related epitranscriptomic alterations and f...

Authors: Jiajie Hou, He Zhang, Jun Liu, Zhenjun Zhao, Jianye Wang, Zhike Lu, Bian Hu, Jiankui Zhou, Zhicong Zhao, Mingxuan Feng, Haiyan Zhang, Bin Shen, Xingxu Huang, Beicheng Sun, Chuan He and Qiang Xia

circLMTK2 acts as a sponge of miR-150-5p and promotes proliferation and metastasis in gastric cancer

As a novel class of non-coding RNAs, circular RNAs (circRNAs) are key regulators of the development and progression of different cancers. However, little is known about the function and biological mechanism of...

Authors: Sen Wang, Dong Tang, Wei Wang, Yining Yang, Xiaoqing Wu, Liuhua Wang and Daorong Wang

m⁶A modification suppresses ocular melanoma through modulating HINT2 mRNA translation

Dynamic N⁶-methyladenosine (m⁶A) RNA modification generated and erased by N⁶-methyltransferases and demethylases regulates gene expression, alternative splicing and cell fate. Ocular melanoma, comprising uveal me...

Authors: Ruobing Jia, Peiwei Chai, Shanzheng Wang, Baofa Sun, Yangfan Xu, Ying Yang, Shengfang Ge, Renbing Jia, Yun-Gui Yang and Xianqun Fan

circGSK3β promotes metastasis in esophageal squamous cell carcinoma by augmenting β-catenin signaling

Circular RNAs (circRNAs), a novel class of noncoding RNAs, have recently drawn much attention in the pathogenesis of human cancers. However, the role of circRNAs in esophageal squamous cell carcinoma (ESCC) re...

Authors: Xueting Hu, Duoguang Wu, Xiaotian He, Huiying Zhao, Zhanghai He, Jiatong Lin, Kefeng Wang, Wenjian Wang, Zihao Pan, Huayue Lin and Minghui Wang

Salinomycin effectively eliminates cancer stem-like cells and obviates hepatic metastasis in uveal melanoma

Uveal melanoma (UM) is the most common primary intraocular tumor. Hepatic metastasis is the major and direct death-related reason in UM patients. Given that cancer stem-like cells (CSCs) are roots of metastasi...

Authors: Jingfeng Zhou, Shenglan Liu, Yun Wang, Wei Dai, Hailin Zou, Shubo Wang, Jing Zhang and Jingxuan Pan

Circ-HuR suppresses HuR expression and gastric cancer progression by inhibiting CNBP transactivation

Circular RNAs (circRNAs), a subclass of non-coding RNAs, play essential roles in tumorigenesis and aggressiveness. Our previous study has identified that circAGO2 drives gastric cancer progression through activat...

Authors: Feng Yang, Anpei Hu, Dan Li, Jianqun Wang, Yanhua Guo, Yang Liu, Hongjun Li, Yajun Chen, Xiaojing Wang, Kai Huang, Liduan Zheng and Qiangsong Tong

Role of hypoxia in cancer therapy by regulating the tumor microenvironment

Clinical resistance is a complex phenomenon in major human cancers involving multifactorial mechanisms, and hypoxia is one of the key components that affect the cellular expression program and lead to therapy ...

Authors: Xinming Jing, Fengming Yang, Chuchu Shao, Ke Wei, Mengyan Xie, Hua Shen and Yongqian Shu

ASPH-notch Axis guided Exosomal delivery of Prometastatic Secretome renders breast Cancer multi-organ metastasis

Aspartate β-hydroxylase (ASPH) is silent in normal adult tissues only to re-emerge during oncogenesis where its function is required for generation and maintenance of malignant phenotypes. Exosomes enable proo...

Authors: Qiushi Lin, Xuesong Chen, Fanzheng Meng, Kosuke Ogawa, Min Li, Ruipeng Song, Shugeng Zhang, Ziran Zhang, Xianglu Kong, Qinggang Xu, Fuliang He, Xuewei Bai, Bei Sun, Mien-Chie Hung, Lianxin Liu, Jack Wands…