Article
Biochemistry & Molecular Biology
Kota Sato, Hironori Yoshino, Yoshiaki Sato, Manabu Nakano, Eichi Tsuruga
Summary: This study demonstrates that Delta Np63, a KPNB1-carrying nucleoprotein, is involved in radioresistance of HNSCC cells. Knockdown of Delta Np63 decreases cell survival, increases apoptosis, and is associated with decreased nuclear expression of Delta Np63. KPNA1 is implicated in nuclear expression of Delta Np63.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2023)
Article
Oncology
Xiang Wu, Jin Li, Tingyuan Yan, Xueping Ke, Xin Li, Yumin Zhu, Jianrong Yang, Zhongwu Li
Summary: HOXB7 is overexpressed in HNSCC and associated with tumor aggressiveness and poor prognosis, serving as a potential therapeutic target in HNSCC.
CANCER CELL INTERNATIONAL
(2021)
Article
Oncology
Jonathan E. E. Bard, Norma J. Nowak, Michael J. Buck, Satrajit Sinha
Summary: This study utilizes computational strategies and multimodal integration techniques to analyze tumor data, identifying new cancer subtypes and offering insights into carcinogenesis and targeted therapy.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Alexandra Ruth Glathar, Akinsola Oyelakin, Christian Gluck, Jonathan Bard, Satrajit Sinha
Summary: The heterogeneity of head and neck squamous cell carcinoma (HNSCC) is reflected in its diverse etiology, including Human Papillomavirus-positive (HPV+) HNSCC subtypes. One aggressive subtype of HPV+ HNSCC is characterized by elevated expression of genes involved in keratinization, which is regulated by the oncogenic transcription factor Delta Np63. The TP63 gene locus is frequently targeted by HPV integration, and HPV oncoproteins drive Delta Np63 expression, suggesting a functional link between Delta Np63 and HPV+ HNSCC that has not been explored. This study demonstrates that HPV+ HNSCCs can be classified based on Delta Np63 expression levels, and an associated gene signature profile is derived. The study also identifies crucial Delta Np63-bound super-enhancers that likely mediate subtype-specific gene expression in HPV+ HNSCC, anchored by the PI3K-mTOR pathway. These findings highlight the importance of Delta Np63 as a key regulator of oncogenic pathways in a specific subtype of HPV+ HNSCC, and suggest its potential as a biomarker for patient stratification and treatment choices.
FRONTIERS IN ONCOLOGY
(2022)
Article
Multidisciplinary Sciences
U. Sangeetha Shenoy, Richard Morgan, Keith Hunter, Shama Prasada Kabekkodu, Raghu Radhakrishnan
Summary: This study investigates the importance of altered HOX gene expression in HNSCC and identifies 16 DEHGs that play a role in stage stratification and HPV infection. The study also identifies 55 HNSCC driver genes that are targeted by DEHGs. Additionally, the study demonstrates that the oncogenic nature of DEHGs can be targeted by novel and approved anti-neoplastic drugs. The regulatory network constructed provides insights into the interaction between DEHGs, DEHMs, and their target genes in HNSCC.
SCIENTIFIC REPORTS
(2022)
Letter
Oncology
Chao Jiang, Xuanchen Zhou, Jie Han, Zhiyong Yue, Butuo Li
Summary: The study examines the prognostic value of circulating tumor DNA sequencing in head and neck squamous cell carcinoma, highlighting TP53 as a central gene of interest and its potential role in predicting immunotherapy outcomes in HNSCC.
Review
Oncology
Martine Froukje van der Kamp, Gyorgy Bela Halmos, Victor Guryev, Peter Laszlo Horvatovich, Ed Schuuring, Bernardus Franciscus Augustinus Maria van der Laan, Bert van der Vegt, Boudewijn Evert Christiaan Plaat, Cornelia Johanna Verhoeven
Summary: In recent clinical practice, an increasing number of elderly patients with head and neck squamous cell carcinoma (HNSCC) of unknown pathophysiology is observed. HNSCC patients can be divided into three subcategories: young patients with genomic aberrations and inheritable diseases, HPV-related HNSCCs with a more favorable prognosis, and HPV-negative tumors involving lifestyle factors. The proposed fourth subcategory is elderly (HPV-negative) HNSCC patients without a history of tobacco and alcohol consumption, which may have different pathophysiological mechanisms. Future research is needed to fill the knowledge gap.
Article
Biochemistry & Molecular Biology
Jiang Li, Tan Wu, Kai Song, Lina Zhu, Yijuan Wang, Tingting Chen, Xin Wang
Summary: Head and neck squamous cell carcinoma (HNSC) is a common malignancy with high mortality worldwide. Recent studies have identified multiple molecular subtypes of HNSC, and in this study, a network-based bioinformatics framework was used to investigate the subtype-specific regulatory mechanisms. A key regulator called LNCOG was identified, which is associated with the mesenchymal subtype of HNSC and plays a role in promoting cancer progression. The findings provide potential biomarkers for optimized treatment of HNSC.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Article
Medicine, Research & Experimental
Rocio Granda-Diaz, Lorea Manterola, Francisco Hermida-Prado, Rene Rodriguez, Laura Santos, Vanessa Garcia-de-la-Fuente, Maria Teresa Fernandez, M. Daniela Corte-Torres, Juan P. Rodrigo, Saul Alvarez-Teijeiro, Charles H. Lawrie, Juana M. Garcia-Pedrero
Summary: Treatment of head and neck squamous cell carcinomas (HNSCC) remains challenging. Dysregulation of miRNA is closely linked to tumorigenesis and tumor progression, making it a suitable target for cancer treatment. In this study, miR-301a was found to be overexpressed in HNSCC tumors and was shown to play a role in promoting tumor growth and invasion. The PI3K/PTEN/AKT and MEK/ERK pathways were identified as central signaling nodes responsible for mediating the oncogenic activity of miR-301a.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Review
Oncology
Dominic H. Moon, David J. Sher
Summary: Up to 40% of patients with metastatic head and neck squamous cell carcinoma have oligometastatic disease, which is associated with improved overall survival. Local ablative therapy and radiation therapy have shown promise in improving outcomes. Stereotactic ablative radiotherapy is a less invasive alternative to surgical resection, but more research is needed to determine its role.
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
(2022)
Article
Genetics & Heredity
Lian Zheng, Zhenjie Guan, Miaomiao Xue
Summary: The study established a gene signature model based on the TGF-beta pathway, which has good predictive efficiency for predicting the prognosis of HNSCC patients and guiding the selection of immunotherapy. This model can help identify high-risk and low-risk patients and provide a new direction for research in individualized immuno-oncology.
FRONTIERS IN GENETICS
(2022)
Review
Biochemistry & Molecular Biology
Sindhu Nair, James A. Bonner, Markus Bredel
Summary: EGFR is overexpressed in head and neck squamous cell carcinoma and anti-EGFR strategies have shown some clinical benefit but often lead to resistance. Mutations in various domains of the EGFR gene can impact drug binding, radiation response, and overall survival in HNSCC patients. Understanding the EGFR mutational landscape and its effects on treatment resistance can help stratify patients for targeted therapies and maximize therapeutic benefits.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Verena Boschert, Jonas Teusch, Urs D. A. Mueller-Richter, Roman C. Brands, Stefan Hartmann
Summary: PKM2 is commonly phosphorylated at Tyr105 in HNSCC, and its levels depend on tyrosine kinase activity. It is also correlated with the expression of CD44 and has an impact on the metabolism of HNSCC cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Oncology
Patricia Chaves, Maria Garrido, Javier Oliver, Elisabeth Perez-Ruiz, Isabel Barragan, Antonio Rueda-Dominguez
Summary: Head and neck cancer is the sixth most frequent cancer type, and the existing therapies face challenges of drug resistance and toxicity. Reliable preclinical models are crucial for studying molecular mechanisms and improving clinical outcomes. The most frequently used preclinical models for head and neck squamous cell carcinoma, including cell lines and animal models, are discussed in this review. Their efficiency in mimicking the complexity of the disease is evaluated, and the potential of the models for developing personalized therapies is explored.
BRITISH JOURNAL OF CANCER
(2023)
Article
Biochemistry & Molecular Biology
Ayaka Koma, Shunichi Asai, Chikashi Minemura, Sachi Oshima, Takashi Kinoshita, Naoko Kikkawa, Keiichi Koshizuka, Shogo Moriya, Atsushi Kasamatsu, Toyoyuki Hanazawa, Katsuhiro Uzawa, Naohiko Seki
Summary: The study identified downregulated miR-139 in head and neck squamous cell carcinoma and demonstrated its role in attenuating cancer cell aggressiveness by regulating GNA12 and OLR1 expression, which are associated with patient survival.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Firli Rahmah Primula Dewi, Shabierjiang Jiapaer, Akiko Kobayashi, Masaharu Hazawa, Dini Kurnia Ikliptikawati, Hartono, Hemragul Sabit, Mitsutoshi Nakada, Richard W. Wong
Summary: Children with ependymoma face high mortality rates due to resistance to conventional therapy. Targeting the oncogenic role of TPR in regulating HSF1 and MTOR signaling pathways may serve as a potential therapeutic approach for ependymoma treatment. TPR expression levels could potentially act as a biomarker for ependymoma, with pharmacological interventions showing promise in reducing tumor size in vivo.
Article
Biochemistry & Molecular Biology
Koki Kato, Dini Kurnia Ikliptikawati, Akiko Kobayashi, Hiroya Kondo, Keesiang Lim, Masaharu Hazawa, Richard W. Wong
Summary: Studies have shown that the ORF6 protein of SARS-CoV-2 can manipulate the localization and functions of nucleoporins, leading to abnormal nucleocytoplasmic trafficking and ultimately reducing the size of host cell nucleus and halting cell growth.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Chemistry, Physical
Goro Nishide, Keesiang Lim, Mahmoud Shaaban Mohamed, Akiko Kobayashi, Masaharu Hazawa, Takahiro Watanabe-Nakayama, Noriyuki Kodera, Toshio Ando, Richard W. Wong
Summary: The study utilized high-speed atomic force microscopy to observe dynamic DNA-histone H2A interactions, revealing different conformations on different substrates and observing reversible liquid-liquid phase separation of DNA-H2A aggregates.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2021)
Article
Biochemistry & Molecular Biology
Kei Makiyama, Masaharu Hazawa, Akiko Kobayashi, Keesiang Lim, Dominic C. Voon, Richard W. Wong
Summary: The study unveils the impact of SARS-CoV-2 NSP9 on host cell's nuclear pore complex formation through interaction with nucleoporin 62, consequently inhibiting the nuclear transport of NF-kappa B subunit p65.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Naoyuki Sano, Hironori Yoshino, Yoshiaki Sato, Hideo Honma, Christopher E. J. Cordonier, Ikuo Kashiwakura
Summary: The importance of NF-kappa B in cancer and metastasis is highlighted, and inhibiting its action is considered a potential cancer treatment strategy. A new gold complex was synthesized, and its effects on THP1 cells were evaluated.
CURRENT MEDICINAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Yasuto Takeuchi, Natsuko Kimura, Takahiko Murayama, Yukino Machida, Daisuke Iejima, Tatsunori Nishimura, Minoru Terashima, Yuming Wang, Mengjiao Li, Reiko Sakamoto, Mizuki Yamamoto, Naoki Itano, Yusuke Inoue, Masataka Ito, Nobuaki Yoshida, Jun-ichiro Inoue, Koichi Akashi, Hideyuki Saya, Koji Fujita, Masahiko Kuroda, Issay Kitabayashi, Dominic Voon, Takeshi Suzuki, Arinobu Tojo, Noriko Gotoh
Summary: Adaptor protein FRS20 induces proinflammatory changes in premalignant mammary tissues and is responsible for disease onset, while the FRS2 beta-NF-kappa B axis reveals the molecular link between inflammation changes and tumorigenesis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Cell Biology
Taichi Nyui, Hironori Yoshino, Tetsuya Nunota, Yoshiaki Sato, Eichi Tsuruga
Summary: cGAS has a role in promoting radioresistance in HNSCC cells, as its knockdown enhances radiosensitivity and increases radiation-induced cell death and senescence.
Article
Chemistry, Medicinal
Yoshiaki Sato, Ikuo Kashiwakura, Masaru Yamaguchi, Hironori Yoshino, Takeshi Tanaka, Ken Ikeda, Zhengmao Ye, Hirotsugu Komatsu, Takao Matsuzaki, Masato Hosoda
Summary: This study evaluated the biological activities of a new small-molecule IL-6 inhibitor. The compounds showed inhibition of IL-6-dependent cell growth and suppressed IL-6-induced signaling pathway. These findings provide a basis for further development of small-molecule IL-6 inhibitors.
MEDICINAL CHEMISTRY
(2022)
Article
Oncology
Mijeong Kim, Manjot Singh, Bum-Kyu Lee, Moira Hibbs, Kirsty Richardson, Lesley Ellies, Larissa Wintle, Lisa M. Stuart, Jenny Y. Wang, Dominic C. Voon, Pilar Blancafort, Jianlong Wang, Jonghwan Kim, Peter J. Leedman, Andrew J. Woo
Summary: In this study, researchers identified ZNF148 as a direct target of MYC in breast cancer. ZNF148 suppressed cell proliferation and migration and was transcriptionally repressed by MYC. Depletion of ZNF148 increased triple-negative breast cancer (TNBC) cell proliferation and migration. Mechanistically, ZNF148 was found to transcriptionally repress ID1 and ID3 expression, resulting in inhibition of cancer stem cell traits and plasticity. These findings uncover a previously unknown tumor suppressor role for ZNF148 and reveal a transcriptional regulatory circuitry involving MYC, ZNF148, and ID1/3 in driving aggressive breast cancer.
Article
Genetics & Heredity
Cai Ping Koh, Avinash Govind Bahirvani, Chelsia Qiuxia Wang, Tomomasa Yokomizo, Cherry Ee Lin Ng, Linsen Du, Vinay Tergaonkar, Dominic Chih-Cheng Voon, Hiroaki Kitamura, Hiroki Hosoi, Takashi Sonoki, Mok Meng Huang Michelle, Lii Jye Tan, Akiko Niibori-Nambu, Yi Zhang, Archibald S. Perkins, Zakir Hossain, Daniel G. Tenen, Yoshiaki Ito, Byrappa Venkatesh, Motomi Osato
Summary: The generation of a tamoxifen-inducible CreERT2 transgenic mouse using a stem cell enhancer provides a powerful tool for labeling and studying normal and malignant hematopoietic stem cells at all developmental stages.
Article
Biochemistry & Molecular Biology
Jong-Wan Kwon, Sang-Hyuk Seok, Somi Kim, Hyeok-Won An, Anahita Dev Choudhury, Sang-Ho Woo, Jeong-Seop Oh, Jong Kyoung Kim, Dominic C. Voon, Dae-Yong Kim, Jun Won Park
Summary: The study reveals the important role of ST2 and IL-33 in gastric cancer progression, with their expression levels clinically correlated to cancer progression. The IL-33/ST2 axis enhances the self-renewal and survival of gastric cancer stem cells, and cooperates with the canonical Wnt pathway to promote cancer stem cell activity. Inhibiting Bcl-xL can suppress the activity of the IL-33/ST2 axis, offering a novel therapeutic strategy for gastric cancer.
Article
Cell Biology
Hyeok-Won An, Sang Hyeok Seok, Jong-Wan Kwon, Anahita Dev Choudhury, Jeong-Seop Oh, Dominic C. Voon, Dae-Yong Kim, Jun Won Park
Summary: This study reveals that Smad4 deficiency in human gastric cancer cells allows them to evade tumor immunity and form tumors. Smad4 deficiency leads to an increase in cancer stem-like cells, suppression of dendritic cell and cytotoxic T cell functions, and accumulation of granulocytic myeloid-derived suppressor cells through CXCL1 secretion. Moreover, Smad4 deficiency alters tumor immunogenicity. Combinatorial immune checkpoint blockade effectively treats Smad4-deficient tumors resistant to monotherapy.
Article
Engineering, Biomedical
Katsuya Sakai, Nozomi Sugano-Nakamura, Emiko Mihara, Nichole Marcela Rojas-Chaverra, Sayako Watanabe, Hiroki Sato, Ryu Imamura, Dominic Chih-Cheng Voon, Itsuki Sakai, Chihiro Yamasaki, Chise Tateno, Mikihiro Shibata, Hiroaki Suga, Junichi Takagi, Kunio Matsumoto
Summary: The study shows that genetically grafting macrocyclic peptide pharmacophores into the structural loops of the Fc region of a human immunoglobulin can generate surrogate receptor agonists with longer half-lives in circulation and enhanced transport rates across the blood-brain barrier. This lasso-grafting approach allows for the development of protein therapeutics with improved stability and pharmacokinetics.
NATURE BIOMEDICAL ENGINEERING
(2023)
Article
Biology
Yoshiaki Sato, Hironori Yoshino, Kota Sato, Ikuo Kashiwakura, Eichi Tsuruga
Summary: Mitochondria play important roles in the cellular response to ionizing radiation-induced stress. The mitochondrial ribosomal protein DAP3 has been found to regulate the radioresistance of lung adenocarcinoma cells, but the underlying mechanism is unclear. This study reveals that DAP3 knockdown attenuates the radiation-induced G2/M cell population increase and downregulates proteins related to G2/M arrest. Chk1 inhibitor enhances radiosensitivity in H1299 cells, while both chk1-mediated G2/M arrest and chk2-mediated events contribute to radioresistance in A549 cells.
JOURNAL OF RADIATION RESEARCH
(2023)
Article
Oncology
Ryo Saga, Yusuke Matsuya, Hikari Sato, Kazuki Hasegawa, Hideki Obara, Fumio Komai, Hironori Yoshino, Masahiko Aoki, Yoichiro Hosokawa
Summary: By modeling the cells and tumor, this study reveals the close relationship between the efficacy of radiotherapy for non-small cell lung cancer and cancer stem cells. Using the integrated microdosimetric-kinetic model, the survival rate in vitro and clinical outcomes were successfully predicted, providing a precise estimation model of radiotherapy worldwide.
RADIOTHERAPY AND ONCOLOGY
(2023)
