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4,247 results on '"Wong, Kwok"'

1. Author Correction: Mechanisms and clinical activity of an EGFR and HER2 exon 20–selective kinase inhibitor in non–small cell lung cancer

Author

Robichaux, Jacqulyne P., Elamin, Yasir Y., Tan, Zhi, Carter, Brett W., Zhang, Shuxing, Liu, Shengwu, Li, Shuai, Chen, Ting, Poteete, Alissa, Estrada-Bernal, Adriana, Le, Anh T., Truini, Anna, Nilsson, Monique B., Sun, Huiying, Roarty, Emily, Goldberg, Sarah B., Brahmer, Julie R., Altan, Mehmet, Lu, Charles, Papadimitrakopoulou, Vassiliki, Politi, Katerina, Doebele, Robert C., Wong, Kwok-Kin, and Heymach, John V.

Published
2024
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3. Inequality and Nyman-Beurling-Baez-Duarte criteria

Author

Wong, Kwok Kwan

Subjects
Mathematics - General Mathematics, 11Mxx, 46Cxx
Abstract

We proposed a proof of the Riemann hypothesis. The proof is based on the Nyman-Beurling-Baez-Duarte condition. By proving existence of the solution for a system of inequalities, we can show that there is a sequence, which act as the coefficient of Beurling's sequence, can approximate the constant vector in a weighted Hilbert space., Comment: 9 pages, version 1 is wrong. Version 2 fixed an argument in the proof. This is version 4

Published
2023

4. TIP60 is required for tumorigenesis in non‐small cell lung cancer

Author

Shibahara, Daisuke, Akanuma, Naoki, Kobayashi, Ikei S, Heo, Eunyoung, Ando, Mariko, Fujii, Masanori, Jiang, Feng, Prin, P Nicholas, Pan, Gilbert, Wong, Kwok‐Kin, Costa, Daniel B, Bararia, Deepak, Tenen, Daniel G, Watanabe, Hideo, and Kobayashi, Susumu S

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Biotechnology, Cancer, Lung Cancer, Genetics, Lung, 2.1 Biological and endogenous factors, Aetiology, Animals, Mice, Carcinogenesis, Carcinoma, Non-Small-Cell Lung, Cell Transformation, Neoplastic, Histone Acetyltransferases, Lung Neoplasms, Humans, artemisinin, KAT5, lung cancer, TGM5, TIP60, Pharmacology and Pharmaceutical Sciences, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

Histone modifications play crucial roles in transcriptional activation, and aberrant epigenetic changes are associated with oncogenesis. Lysine (K) acetyltransferases 5 (TIP60, also known as KAT5) is reportedly implicated in cancer development and maintenance, although its function in lung cancer remains controversial. Here we demonstrate that TIP60 knockdown in non-small cell lung cancer cell lines decreased tumor cell growth, migration, and invasion. Furthermore, analysis of a mouse lung cancer model with lung-specific conditional Tip60 knockout revealed suppressed tumor formation relative to controls, but no apparent effects on normal lung homeostasis. RNA-seq and ChIP-seq analyses of inducible TIP60 knockdown H1975 cells relative to controls revealed transglutaminase enzyme (TGM5) as downstream of TIP60. Investigation of a connectivity map database identified several candidate compounds that decrease TIP60 mRNA, one that suppressed tumor growth in cell culture and in vivo. In addition, TH1834, a TIP60 acetyltransferase inhibitor, showed comparable antitumor effects in cell culture and in vivo. Taken together, suppression of TIP60 activity shows tumor-specific efficacy against lung cancer, with no overt effect on normal tissues. Our work suggests that targeting TIP60 could be a promising approach to treating lung cancer.

Published
2023

7. Kaplansky Unit conjecture for complex numbers

Author

Wong, Kwok Kwan

Subjects
Mathematics - Algebraic Geometry, 20C07, 16S34, 46L05
Abstract

We show that Kaplansky's unit conjecture is true, under the assumption that the underlying field is complex., Comment: The second lemma contains flaws

Published
2021

8. Inflammation in the tumor-adjacent lung as a predictor of clinical outcome in lung adenocarcinoma

Author

Dolgalev, Igor, Zhou, Hua, Murrell, Nina, Le, Hortense, Sakellaropoulos, Theodore, Coudray, Nicolas, Zhu, Kelsey, Vasudevaraja, Varshini, Yeaton, Anna, Goparaju, Chandra, Li, Yonghua, Sulaiman, Imran, Tsay, Jun-Chieh J., Meyn, Peter, Mohamed, Hussein, Sydney, Iris, Shiomi, Tomoe, Ramaswami, Sitharam, Narula, Navneet, Kulicke, Ruth, Davis, Fred P., Stransky, Nicolas, Smolen, Gromoslaw A., Cheng, Wei-Yi, Cai, James, Punekar, Salman, Velcheti, Vamsidhar, Sterman, Daniel H., Poirier, J. T., Neel, Ben, Wong, Kwok-Kin, Chiriboga, Luis, Heguy, Adriana, Papagiannakopoulos, Thales, Nadorp, Bettina, Snuderl, Matija, Segal, Leopoldo N., Moreira, Andre L., Pass, Harvey I., and Tsirigos, Aristotelis

Published
2023
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9. Mitochondrial diseases in Hong Kong: prevalence, clinical characteristics and genetic landscape

Author

Wong, Tsz-sum, Belaramani, Kiran M., Chan, Chun-kong, Chan, Wing-ki, Chan, Wai-lun Larry, Chang, Shek-kwan, Cheung, Sing-ngai, Cheung, Ka-yin, Cheung, Yuk-fai, Chong, Shuk-ching Josephine, Chow, Chi-kwan Jasmine, Chung, Hon-yin Brian, Fan, Sin-ying Florence, Fok, Wai-ming Joshua, Fong, Ka-wing, Fung, Tsui-hang Sharon, Hui, Kwok-fai, Hui, Ting-hin, Hui, Joannie, Ko, Chun-hung, Kwan, Min-chung, Kwok, Mei-kwan Anne, Kwok, Sung-shing Jeffrey, Lai, Moon-sing, Lam, Yau-on, Lam, Ching-wan, Lau, Ming-chung, Law, Chun-yiu Eric, Lee, Wing-cheong, Lee, Han-chih Hencher, Lee, Chin-nam, Leung, Kin-hang, Leung, Kit-yan, Li, Siu-hung, Ling, Tsz-ki Jacky, Liu, Kam-tim Timothy, Lo, Fai-man, Lui, Hiu-tung, Luk, Ching-on, Luk, Ho-ming, Ma, Che-kwan, Ma, Karen, Ma, Kam-hung, Mew, Yuen-ni, Mo, Alex, Ng, Sui-fun, Poon, Wing-kit Grace, Rodenburg, Richard, Sheng, Bun, Smeitink, Jan, Szeto, Cheuk-ling Charing, Tai, Shuk-mui, Tse, Choi-ting Alan, Tsung, Li-yan Lilian, Wong, Ho-ming June, Wong, Wing-yin Winnie, Wong, Kwok-kui, Wong, Suet-na Sheila, Wong, Chun-nei Virginia, Wong, Wai-shan Sammy, Wong, Chi-kin Felix, Wu, Shun-ping, Wu, Hiu-fung Jerome, Yau, Man-mut, Yau, Kin-cheong Eric, Yeung, Wai-lan, Yeung, Hon-ming Jonas, Yip, Kin-keung Edwin, Young, Pui-hong Terence, Yuan, Gao, Yuen, Yuet-ping Liz, Yuen, Chi-lap, and Fung, Cheuk-wing

Published
2023
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11. Adeno-to-squamous transition drives resistance to KRAS inhibition in LKB1 mutant lung cancer

Author

Tong, Xinyuan, Patel, Ayushi S., Kim, Eejung, Li, Hongjun, Chen, Yueqing, Li, Shuai, Liu, Shengwu, Dilly, Julien, Kapner, Kevin S., Zhang, Ningxia, Xue, Yun, Hover, Laura, Mukhopadhyay, Suman, Sherman, Fiona, Myndzar, Khrystyna, Sahu, Priyanka, Gao, Yijun, Li, Fei, Li, Fuming, Fang, Zhaoyuan, Jin, Yujuan, Gao, Juntao, Shi, Minglei, Sinha, Satrajit, Chen, Luonan, Chen, Yang, Kheoh, Thian, Yang, Wenjing, Yanai, Itai, Moreira, Andre L., Velcheti, Vamsidhar, Neel, Benjamin G., Hu, Liang, Christensen, James G., Olson, Peter, Gao, Dong, Zhang, Michael Q., Aguirre, Andrew J., Wong, Kwok-Kin, and Ji, Hongbin

Published
2024
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24. FGFR inhibition augments anti-PD-1 efficacy in murine FGFR3-mutant bladder cancer by abrogating immunosuppression

Author

Okato, Atsushi, Utsumi, Takanobu, Ranieri, Michela, Zheng, Xingnan, Zhou, Mi, Pereira, Luiza D., Chen, Ting, Kita, Yuki, Wu, Di, Hyun, Hyesun, Lee, Hyojin, Gdowski, Andrew S., Raupp, John D., Clark- Garvey, Sean, Manocha, Ujjawal, Chafitz, Alison, Sherman, Fiona, Stephens, Janaye, Rose, Tracy L., Milowsky, Matthew I., Wobker, Sara E., Serody, Jonathan S., Damrauer, Jeffrey S., Wong, Kwok-Kin, and Kim, William Y.

Subjects
Bladder cancer -- Drug therapy -- Models, Fibroblast growth factor receptors -- Health aspects, Monoclonal antibodies -- Dosage and administration -- Testing, Immunosuppression -- Methods, Health care industry
Abstract

The combination of targeted therapy with immune checkpoint inhibition (ICI) is an area of intense interest. We studied the interaction of fibroblast growth factor receptor (FGFR) inhibition with ICI in urothelial carcinoma (UC) of the bladder, in which FGFR3 is altered in 50% of cases. Using an FGFR3-driven, Trp53-mutant genetically engineered murine model (UPFL), we demonstrate that UPFL tumors recapitulate the histology and molecular subtype of their FGFR3-altered human counterparts. Additionally, UPFL1 allografts exhibit hyperprogression to ICI associated with an expansion of T regulatory cells (Tregs). Erdafitinib blocked Treg proliferation in vitro, while in vivo ICI-induced Treg expansion was fully abrogated by FGFR inhibition. Combined erdafitinib and ICI resulted in high therapeutic efficacy. In aggregate, our work establishes that, in mice, co-alteration of FGFR3 and Trp53 results in high-grade, non- muscle-invasive UC and presents a previously underappreciated role for FGFR inhibition in blocking ICI-induced Treg expansion., Introduction Bladder cancer is the sixth most common cancer in the United States, with an estimated 82,290 new cases and an estimated 16,710 deaths in 2023 (1). At diagnosis, approximately [...]

Published
2024
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25. KEAP1 mutation in lung adenocarcinoma promotes immune evasion and immunotherapy resistance

Author

Zavitsanou, Anastasia-Maria, Pillai, Ray, Hao, Yuan, Wu, Warren L., Bartnicki, Eric, Karakousi, Triantafyllia, Rajalingam, Sahith, Herrera, Alberto, Karatza, Angeliki, Rashidfarrokhi, Ali, Solis, Sabrina, Ciampricotti, Metamia, Yeaton, Anna H., Ivanova, Ellie, Wohlhieter, Corrin A., Buus, Terkild B., Hayashi, Makiko, Karadal-Ferrena, Burcu, Pass, Harvey I., Poirier, John T., Rudin, Charles M., Wong, Kwok-Kin, Moreira, Andre L., Khanna, Kamal M., Tsirigos, Aristotelis, Papagiannakopoulos, Thales, and Koralov, Sergei B.

Published
2023
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28. MCT4-dependent lactate secretion suppresses antitumor immunity in LKB1-deficient lung adenocarcinoma

Author

Qian, Yu, Galan-Cobo, Ana, Guijarro, Irene, Dang, Minghao, Molkentine, David, Poteete, Alissa, Zhang, Fahao, Wang, Qi, Wang, Jing, Parra, Edwin, Panda, Apekshya, Fang, Jacy, Skoulidis, Ferdinandos, Wistuba, Ignacio I., Verma, Svena, Merghoub, Taha, Wolchok, Jedd D., Wong, Kwok-Kin, DeBerardinis, Ralph J., Minna, John D., Vokes, Natalie I., Meador, Catherine B., Gainor, Justin F., Wang, Linghua, Reuben, Alexandre, and Heymach, John V.

Published
2023
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30. Histone Deacetylase 6 Inhibition Exploits Selective Metabolic Vulnerabilities in LKB1 Mutant, KRAS Driven NSCLC

Author

Zhang, Hua, Nabel, Christopher S., Li, Dezhi, O’Connor, Ruth Í., Crosby, Caroline R., Chang, Sarah M., Hao, Yuan, Stanley, Robyn, Sahu, Soumyadip, Levin, Daniel S., Chen, Ting, Tang, Sittinon, Huang, Hsin-Yi, Meynardie, Mary, Stephens, Janaye, Sherman, Fiona, Chafitz, Alison, Costelloe, Naoise, Rodrigues, Daniel A., Fogarty, Hilda, Kiernan, Miranda G., Cronin, Fiona, Papadopoulos, Eleni, Ploszaj, Magdalena, Weerasekara, Vajira, Deng, Jiehui, Kiely, Patrick, Bardeesy, Nabeel, Vander Heiden, Matthew G., Chonghaile, Triona Ni, Dowling, Catríona M., and Wong, Kwok-Kin

Published
2023
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33. Gain-of-Function RHOA Mutations Promote Focal Adhesion Kinase Activation and Dependency in Diffuse Gastric Cancer

Author

Zhang, Haisheng, Schaefer, Antje, Wang, Yichen, Hodge, Richard G, Blake, Devon R, Diehl, J Nathaniel, Papageorge, Alex G, Stachler, Matthew D, Liao, Jennifer, Zhou, Jin, Wu, Zhong, Akarca, Fahire G, de Klerk, Leonie K, Derks, Sarah, Pierobon, Mariaelena, Hoadley, Katherine A, Wang, Timothy C, Church, George, Wong, Kwok-Kin, Petricoin, Emanuel F, Cox, Adrienne D, Lowy, Douglas R, Der, Channing J, and Bass, Adam J

Subjects
Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Biological Sciences, Digestive Diseases, Cancer, Rare Diseases, Aetiology, 2.1 Biological and endogenous factors, 3T3 Cells, Animals, Antigens, CD, COS Cells, Cadherins, Chlorocebus aethiops, Focal Adhesion Kinase 1, Gain of Function Mutation, Gastric Mucosa, HEK293 Cells, Humans, Mice, Protein Kinase Inhibitors, Quinolones, Signal Transduction, Stomach Neoplasms, Sulfones, Xenograft Model Antitumor Assays, rhoA GTP-Binding Protein, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

Diffuse gastric cancer (DGC) is a lethal malignancy lacking effective systemic therapy. Among the most provocative recent results in DGC has been that of highly recurrent missense mutations in the GTPase RHOA. The function of these mutations has remained unresolved. We demonstrate that RHOAY42C, the most common RHOA mutation in DGC, is a gain-of-function oncogenic mutant, and that expression of RHOAY42C with inactivation of the canonical tumor suppressor Cdh1 induces metastatic DGC in a mouse model. Biochemically, RHOAY42C exhibits impaired GTP hydrolysis and enhances interaction with its effector ROCK. RHOA Y42C mutation and Cdh1 loss induce actin/cytoskeletal rearrangements and activity of focal adhesion kinase (FAK), which activates YAP-TAZ, PI3K-AKT, and β-catenin. RHOAY42C murine models were sensitive to FAK inhibition and to combined YAP and PI3K pathway blockade. These results, coupled with sensitivity to FAK inhibition in patient-derived DGC cell lines, nominate FAK as a novel target for these cancers. SIGNIFICANCE: The functional significance of recurrent RHOA mutations in DGC has remained unresolved. Through biochemical studies and mouse modeling of the hotspot RHOAY42C mutation, we establish that these mutations are activating, detail their effects upon cell signaling, and define how RHOA-mediated FAK activation imparts sensitivity to pharmacologic FAK inhibitors.See related commentary by Benton and Chernoff, p. 182.This article is highlighted in the In This Issue feature, p. 161.

Published
2020

34. Toward a comprehensive view of cancer immune responsiveness: a synopsis from the SITC workshop

Author

Bedognetti, Davide, Ceccarelli, Michele, Galluzzi, Lorenzo, Lu, Rongze, Palucka, Karolina, Samayoa, Josue, Spranger, Stefani, Warren, Sarah, Wong, Kwok-Kin, Ziv, Elad, Chowell, Diego, Coussens, Lisa M, De Carvalho, Daniel D, DeNardo, David G, Galon, Jérôme, Kaufman, Howard L, Kirchhoff, Tomas, Lotze, Michael T, Luke, Jason J, Minn, Andy J, Politi, Katerina, Shultz, Leonard D, Simon, Richard, Thórsson, Vésteinn, Weidhaas, Joanne B, Ascierto, Maria Libera, Ascierto, Paolo Antonio, Barnes, James M, Barsan, Valentin, Bommareddy, Praveen K, Bot, Adrian, Church, Sarah E, Ciliberto, Gennaro, De Maria, Andrea, Draganov, Dobrin, Ho, Winson S, McGee, Heather M, Monette, Anne, Murphy, Joseph F, Nisticò, Paola, Park, Wungki, Patel, Maulik, Quigley, Michael, Radvanyi, Laszlo, Raftopoulos, Harry, Rudqvist, Nils-Petter, Snyder, Alexandra, Sweis, Randy F, Valpione, Sara, Zappasodi, Roberta, Butterfield, Lisa H, Disis, Mary L, Fox, Bernard A, Cesano, Alessandra, and Marincola, Francesco M

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Women's Health, Genetics, Cancer, Human Genome, Underpinning research, 1.1 Normal biological development and functioning, Aetiology, 2.1 Biological and endogenous factors, Good Health and Well Being, Advisory Committees, Animals, Biomarkers, Tumor, Congresses as Topic, Disease Models, Animal, Humans, Immunotherapy, Medical Oncology, Neoplasms, Societies, Medical, Treatment Outcome, Tumor Microenvironment, Cancer immune responsiveness, Immune checkpoint inhibitor, Immune oncology, Tumor microenvironment, Tumor mutational burden, Immunogenic cell death, Biomarker, Germline molecular alterations, Somatic molecular alterations, Cancer immune phenotype, Society for Immunotherapy of Cancer (SITC) Cancer Immune Responsiveness Task Force and Working Groups, Oncology and carcinogenesis
Abstract

Tumor immunology has changed the landscape of cancer treatment. Yet, not all patients benefit as cancer immune responsiveness (CIR) remains a limitation in a considerable proportion of cases. The multifactorial determinants of CIR include the genetic makeup of the patient, the genomic instability central to cancer development, the evolutionary emergence of cancer phenotypes under the influence of immune editing, and external modifiers such as demographics, environment, treatment potency, co-morbidities and cancer-independent alterations including immune homeostasis and polymorphisms in the major and minor histocompatibility molecules, cytokines, and chemokines. Based on the premise that cancer is fundamentally a disorder of the genes arising within a cell biologic process, whose deviations from normality determine the rules of engagement with the host's response, the Society for Immunotherapy of Cancer (SITC) convened a task force of experts from various disciplines including, immunology, oncology, biophysics, structural biology, molecular and cellular biology, genetics, and bioinformatics to address the complexity of CIR from a holistic view. The task force was launched by a workshop held in San Francisco on May 14-15, 2018 aimed at two preeminent goals: 1) to identify the fundamental questions related to CIR and 2) to create an interactive community of experts that could guide scientific and research priorities by forming a logical progression supported by multiple perspectives to uncover mechanisms of CIR. This workshop was a first step toward a second meeting where the focus would be to address the actionability of some of the questions identified by working groups. In this event, five working groups aimed at defining a path to test hypotheses according to their relevance to human cancer and identifying experimental models closest to human biology, which include: 1) Germline-Genetic, 2) Somatic-Genetic and 3) Genomic-Transcriptional contributions to CIR, 4) Determinant(s) of Immunogenic Cell Death that modulate CIR, and 5) Experimental Models that best represent CIR and its conversion to an immune responsive state. This manuscript summarizes the contributions from each group and should be considered as a first milestone in the path toward a more contemporary understanding of CIR. We appreciate that this effort is far from comprehensive and that other relevant aspects related to CIR such as the microbiome, the individual's recombined T cell and B cell receptors, and the metabolic status of cancer and immune cells were not fully included. These and other important factors will be included in future activities of the taskforce. The taskforce will focus on prioritization and specific actionable approach to answer the identified questions and implementing the collaborations in the follow-up workshop, which will be held in Houston on September 4-5, 2019.

Published
2019

35. Correction to: Toward a comprehensive view of cancer immune responsiveness: a synopsis from the SITC workshop

Author

Bedognetti, Davide, Ceccarelli, Michele, Galluzzi, Lorenzo, Lu, Rongze, Palucka, Karolina, Samayoa, Josue, Spranger, Stefani, Warren, Sarah, Wong, Kwok-Kin, Ziv, Elad, Chowell, Diego, Coussens, Lisa M, De Carvalho, Daniel D, DeNardo, David G, Galon, Jérôme, Kaufman, Howard L, Kirchhoff, Tomas, Lotze, Michael T, Luke, Jason J, Minn, Andy J, Politi, Katerina, Shultz, Leonard D, Simon, Richard, Thórsson, Vésteinn, Weidhaas, Joanne B, Ascierto, Maria Libera, Ascierto, Paolo Antonio, Barnes, James M, Barsan, Valentin, Bommareddy, Praveen K, Bot, Adrian, Church, Sarah E, Ciliberto, Gennaro, De Maria, Andrea, Draganov, Dobrin, Ho, Winson S, McGee, Heather M, Monette, Anne, Murphy, Joseph F, Nisticò, Paola, Park, Wungki, Patel, Maulik, Quigley, Michael, Radvanyi, Laszlo, Raftopoulos, Harry, Rudqvist, Nils-Petter, Snyder, Alexandra, Sweis, Randy F, Valpione, Sara, Zappasodi, Roberta, Butterfield, Lisa H, Disis, Mary L, Fox, Bernard A, Cesano, Alessandra, and Marincola, Francesco M

Subjects
Biomedical and Clinical Sciences, Immunology, Cancer, Society for Immunotherapy of Cancer (SITC) Cancer Immune Responsiveness Task Force and Working Groups, Oncology and carcinogenesis
Abstract

Following publication of the original article [1], the author reported that an author name, Roberta Zappasodi, was missed in the authorship list.

Published
2019

43. Bi-steric mTORC1 inhibitors induce apoptotic cell death in tumor models with hyperactivated mTORC1

Author

Du, Heng, Yang, Yu Chi, Liu, Heng-Jia, Yuan, Min, Asara, John M., Wong, Kwok- Kin, Henske, Elizabeth P., Singh, Mallika, and Kwiatkowski, David J.

Subjects
Thermo Fisher Scientific Inc., Biochemistry -- Models, Cancer -- Models, Apoptosis -- Models, Health care industry
Abstract

The PI3K/AKT/mTOR pathway is commonly dysregulated in cancer. Rapalogs exhibit modest clinical benefit, likely owing to their lack of effects on 4EBP1. We hypothesized that bi-steric mTORC1-selective inhibitors would have greater potential for clinical benefit than rapalogs in tumors with mTORC1 dysfunction. We assessed this hypothesis in tumor models with high mTORC1 activity both in vitro and in vivo. Bi-steric inhibitors had strong growth inhibition, eliminated phosphorylated 4EBP1, and induced more apoptosis than rapamycin or MLN0128. Multiomics analysis showed extensive effects of the bi-steric inhibitors in comparison with rapamycin. De novo purine synthesis was selectively inhibited by bi-sterics through reduction in JUN and its downstream target PRPS1 and appeared to be the cause of apoptosis. Hence, bi-steric mTORC1-selective inhibitors are a therapeutic strategy to treat tumors driven by mTORC1 hyperactivation., Introduction The PI3K/AKT/mTOR network is a critical intracellular signaling pathway directing cell growth and metabolism in physiological and pathological conditions (1). The evolutionarily conserved mammalian target of rapamycin (mTOR) is [...]

Published
2023
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45. Utilization of circulating tumor DNA (ctDNA) testing by race and ethnicity in more than 135,000 patients.

Author

Davis, Andrew A., primary, Bucheit, Leslie A, additional, Zhang, Nicole, additional, Pretz, Christopher, additional, Strickler, John H, additional, Chachoua, Abraham, additional, Wise, David R, additional, Wong, Kwok-Kin, additional, Aviki, Emeline Mariam, additional, Zhang, Tian, additional, Qin, Qian, additional, and Clemens, Keelia M., additional

Published
2024
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47. On Effective Existence of Symmetric Differentials of Complex Hyperbolic Space Forms

Author

Wong, Kwok-Kin

Subjects
Mathematics - Complex Variables, 32Q20, 32Q40, 32J05, 32Q45
Abstract

For a noncompact complex hyperbolic space form of finite volume $X=\mathbb{B}^n/\Gamma$, we consider the problem of producing symmetric differentials vanishing at infinity on the Mumford compactification $\overline{X}$ of $X$ similar to the case of producing cusp forms on hyperbolic Riemann surfaces. We introduce a natural geometric measurement which measures the size of the infinity $\overline{X}-X$ called `canonical radius' of a cusp of $\Gamma$. The main result in the article is that there is a constant $r^*=r^*(n)$ depending only on the dimension, so that if the canonical radii of all cusps of $\Gamma$ are larger than $r^*$, then there exist symmetric differentials of $\overline{X}$ vanishing at infinity. As a corollary, we show that the cotangent bundle $T_{\overline{X}}$ is ample modulo the infinity if moreover the injectivity radius in the interior of $\overline{X}$ is larger than some constant $d^*=d^*(n)$ which depends only on the dimension., Comment: 30pages, may not be the same as published version

Published
2018
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49. CXCR7 Reactivates ERK Signaling to Promote Resistance to EGFR Kinase Inhibitors in NSCLC

Author

Becker, Jeffrey H, Gao, Yandi, Soucheray, Margaret, Pulido, Ines, Kikuchi, Eiki, Rodríguez, María L, Gandhi, Rutu, Lafuente-Sanchis, Aranzazu, Aupí, Miguel, Alcácer Fernández-Coronado, Javier, Martín-Martorell, Paloma, Cremades, Antonio, Galbis-Caravajal, José M, Alcácer, Javier, Christensen, Camilla L, Simms, Patricia, Hess, Ashley, Asahina, Hajime, Kahle, Michael P, Al-Shahrour, Fatima, Borgia, Jeffrey A, Lahoz, Agustín, Insa, Amelia, Juan, Oscar, Jänne, Pasi A, Wong, Kwok-Kin, Carretero, Julian, and Shimamura, Takeshi

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Lung Cancer, Cancer, Lung, Clinical Research, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Animals, Carcinoma, Non-Small-Cell Lung, Cell Line, Tumor, Drug Resistance, Neoplasm, Epithelial-Mesenchymal Transition, ErbB Receptors, Humans, Lung Neoplasms, MAP Kinase Signaling System, Mice, Transgenic, Mutation, Neoplasms, Experimental, Protein Kinase Inhibitors, Receptors, CXCR, beta-Arrestins, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

Although EGFR mutant-selective tyrosine kinase inhibitors (TKI) are clinically effective, acquired resistance can occur by reactivating ERK. We show using in vitro models of acquired EGFR TKI resistance with a mesenchymal phenotype that CXCR7, an atypical G protein-coupled receptor, activates the MAPK-ERK pathway via β-arrestin. Depletion of CXCR7 inhibited the MAPK pathway, significantly attenuated EGFR TKI resistance, and resulted in mesenchymal-to-epithelial transition. CXCR7 overexpression was essential in reactivation of ERK1/2 for the generation of EGFR TKI-resistant persister cells. Many patients with non-small cell lung cancer (NSCLC) harboring an EGFR kinase domain mutation, who progressed on EGFR inhibitors, demonstrated increased CXCR7 expression. These data suggest that CXCR7 inhibition could considerably delay and prevent the emergence of acquired EGFR TKI resistance in EGFR-mutant NSCLC. SIGNIFICANCE: Increased expression of the chemokine receptor CXCR7 constitutes a mechanism of resistance to EGFR TKI in patients with non-small cell lung cancer through reactivation of ERK signaling.

Published
2019

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