Article
Oncology
Sivan Gershanov, Helen Toledano, Nomi Pernicone, Suzana Fichman, Shalom Michowiz, Albert Pinhasov, Nitza Goldenberg-Cohen, Tamar Listovsky, Mali Salmon-Divon
Summary: By comparing the gene and microRNA expression of SUFU and PTCH1 mutated SHH medulloblastomas, differences were detected, providing clues for new treatment directions.
CANCER GENOMICS & PROTEOMICS
(2021)
Article
Neurosciences
Fengjiao Liu, Jingyuan Shao, Haihong Yang, Guochao Yang, Qian Zhu, Yan Wu, Lingling Zhu, Haitao Wu
Summary: Our study found that Rack1 was significantly upregulated in the majority of human cerebellar MB tumors. Genetic ablation of Rack1 expression in SHH-MB tumor mice could significantly inhibit MB proliferation, reduce the tumor size, and prolong the survival of tumor rescue mice. Further studies showed that in rescue mice, while apoptosis and autophagy levels were unaffected, the expression of Gli1 and HDAC2 was significantly decreased suggesting the inactivation of the SHH signaling pathway.
CNS NEUROSCIENCE & THERAPEUTICS
(2021)
Article
Chemistry, Medicinal
Christopher Lawson, Thowaiba Babikr Ahmed Alta, Georgia Moschou, Vasiliki Skamnaki, Theodora G. A. Solovou, Caroline Topham, Joseph Hayes, Timothy J. Snape
Summary: Medulloblastoma is a highly aggressive and heterogeneous tumor that accounts for 15-20% of childhood brain tumors. In this study, potent in vitro anticancer activity against medulloblastoma cell lines was achieved using first-generation compounds, leading to the development of second-generation compounds with up to sixty times the activity, providing promising new leads for further research.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Cell & Tissue Engineering
Yekaterina Galat, Haigang Gu, Mariana Perepitchka, Robert Taylor, Joon Won Yoon, Xenia A. Glukhova, Xiao-Nan Li, Igor P. Beletsky, David O. Walterhouse, Vasiliy Galat, Philip M. Iannaccone
Summary: This study investigated the impact of editing GLI1 gene in human embryonic stem cells, revealing the critical role of GLI1 intronic region in the feedback loop and lineage-specific effects on stem cell differentiation. Editing this region resulted in delayed neural commitment, inhibition of endodermal and mesodermal differentiation, and altered expression of osteogenic markers and cancer-related genes. Inhibition of GLI1 had similar effects, indicating potential therapeutic implications.
Article
Neurosciences
Haritha Kunhiraman, Leon McSwain, Shubin W. Shahab, Timothy R. Gershon, Tobey J. MacDonald, Anna Marie Kenney
Summary: This study found that the Sonic Hedgehog (SHH) subtype of medulloblastoma (MB) has a unique tumor microenvironment compared to other subtypes. The SHH MB cells were found to produce elevated levels of IGFBP2, which is required for SHH MB cell proliferation, colony formation, and cell migration. These findings suggest that targeting the IGFBP2-STAT3 axis could be a novel therapeutic approach for SHH medulloblastoma.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Liam D. Hendrikse, Parthiv Haldipur, Olivier Saulnier, Jake Millman, Alexandria H. Sjoboen, Anders W. Erickson, Winnie Ong, Victor Gordon, Ludivine Coudiere-Morrison, Audrey L. Mercier, Mohammad Shokouhian, Raul A. Suarez, Michelle Ly, Stephanie Borlase, David S. Scott, Maria C. Vladoiu, Hamza Farooq, Olga Sirbu, Takuma Nakashima, Shohei Nambu, Yusuke Funakoshi, Alec Bahcheli, J. Javier Diaz-Mejia, Joseph Golser, Kathleen Bach, Tram Phuong-Bao, Patryk Skowron, Evan Y. Wang, Sachin A. Kumar, Polina Balin, Abhirami Visvanathan, John J. Y. Lee, Ramy Ayoub, Xin Chen, Xiaodi Chen, Karen L. Mungall, Betty Luu, Pierre Berube, Yu C. Wang, Stefan M. Pfister, Seung-Ki Kim, Olivier Delattre, Franck Bourdeaut, Francois Doz, Julien Masliah-Planchon, Wieslawa A. Grajkowska, James Loukides, Peter Dirks, Michelle Fevre-Montange, Anne Jouvet, Pim J. French, Johan M. Kros, Karel Zitterbart, Swneke D. Bailey, Charles G. Eberhart, Amulya A. N. Rao, Caterina Giannini, James M. Olson, Miklos Garami, Peter Hauser, Joanna J. Phillips, Young S. Ra, Carmen de Torres, Jaume Mora, Kay K. W. Li, Ho-Keung Ng, Wai S. Poon, Ian F. Pollack, Enrique Lopez-Aguilar, G. Yancey Gillespie, Timothy E. Van Meter, Tomoko Shofuda, Rajeev Vibhakar, Reid C. Thompson, Michael K. Cooper, Joshua B. Rubin, Toshihiro Kumabe, Shin Jung, Boleslaw Lach, Achille Lolascon, Veronica Ferrucci, Pasqualino de Antonellis, Massimo Zollo, Giuseppe Cinalli, Shenandoah Robinson, Duncan S. Stearns, Erwin G. Van Meir, Paola Porrati, Gaetano Finocchiaro, Maura Massimino, Carlos G. Carlotti, Claudia C. Faria, Martine F. Roussel, Frederick Boop, Jennifer A. Chan, Kimberly A. Aldinger, Ferechte Razavi, Evelina Silvestri, Roger E. McLendon, Eric M. Thompson, Marc Ansari, Maria L. Garre, Fernando Chico, Pilar Eguia, Mario Perezpena, A. Sorana Morrissy, Florence M. G. Cavalli, Xiaochong Wu, Craig Daniels, Jeremy N. Rich, Steven J. M. Jones, Richard A. Moore, Marco A. Marra, Xi Huang, Juri Reimand, Poul H. Sorensen, Robert J. Wechsler-Reya, William A. Weiss, Trevor J. Pugh, Livia Garzia, Claudia L. Kleinman, Lincoln D. Stein, Nada Jabado, David Malkin, Olivier Ayrault, Jeffrey A. Golden, David W. Ellison, Brad Doble, Vijay Ramaswamy, Tamra E. Werbowetski-Ogilvie, Hiromichi Suzuki, Kathleen J. Millen, Michael D. Taylor
Summary: Medulloblastoma (MB) is a pediatric embryonal neoplasm of the hindbrain with subtypes including Sonic hedgehog MB, WNT MB and G4 MB. Somatic mutations in G4 MB converge on the core binding factor alpha (CBFA) complex, and knocking down OTX2 can relieve differentiation blockage.
Article
Oncology
Jiaqing Yi, BongWoo Kim, Xuanming Shi, Xiaoming Zhan, Q. Richard Lu, Zhenyu Xuan, Jiang Wu
Summary: This study reveals that PRC2 heterogeneity plays an oncogenic role in SHH medulloblastoma, promoting tumor growth. Deletion of PRC2 core subunit EED inhibits tumor growth, while mosaic deletion of EED enhances tumor growth. The presence of EED is essential for maintaining cerebellum granule neuron precursors.
Article
Pharmacology & Pharmacy
Huangyi Fang, Lingfei Wang, Lisheng Yu, Fang Shen, Zelin Yang, Yue Yang, Shize Li, Haipeng Dai, Feng Tan, Jian Lin, Hansong Sheng
Summary: This study investigated the inhibitory effect of metformin on medulloblastoma and the underlying mechanism involving the Sonic hedgehog (Shh) signaling pathway. The results showed that metformin effectively inhibited proliferation and metastasis of medulloblastoma cells, and this effect was associated with apoptosis, cell cycle arrest, and inhibition of the Shh pathway. In addition, metformin demonstrated anticancer effects in vivo using a murine model. These findings highlight the potential of metformin as a therapeutic strategy for medulloblastoma.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Oncology
Liangping Yuan, Hongying Zhang, Jingbo Liu, Anshu Malhotra, Abhinav Dey, Bing Yu, Kishore Kumar Jella, Leon F. McSwain, Matthew J. Schniederjan, Tobey J. MacDonald
Summary: This study highlights the critical role of STAT3 in Shh MB cells, its essential role in Smo-dependent Shh signaling and drug resistance, and its potential as a therapeutic target to overcome anti-Smo drug resistance in treating Shh MB. Additionally, STAT3 inhibitor treatment significantly prevents tumor formation and synergistic effects with Smo inhibitors in vitro suggest a promising approach for Shh MB treatment.
MOLECULAR ONCOLOGY
(2022)
Article
Cell Biology
Davide Vecchiotti, Daniela Verzella, Mauro Di Vito Nolfi, Daniel D'Andrea, Irene Flati, Barbara Di Francesco, Jessica Cornice, Edoardo Alesse, Daria Capece, Francesca Zazzeroni
Summary: The NF-kappa B-SHh-GLI1 axis plays an important role in advanced prostate cancer and its elevation is associated with worse prognosis, suggesting it could be a target for treating aggressive prostate cancer.
Article
Cell Biology
Weiyi Gong, Wenxuan Zhao, Gang Liu, Lei Shi, Xia Zhao
Summary: BDDD-721, a curcumin analogue, exhibits stronger anti-tumor activity than curcumin on medulloblastoma. It effectively inhibits the proliferation, migration, invasion, and promotes apoptosis of medulloblastoma cells. The study also discovered that BDDD-721 targets the Shh/Gli1 signaling pathway to exert its anticancer effects.
Article
Oncology
Maximillian S. Westphal, Eunjee Lee, Eric E. Schadt, Giselle S. Sholler, Jun Zhu
Summary: This study categorized medulloblastoma into molecular subgroups and found different survival rates among them. By analyzing the expression of molecular markers MYCN and let-7, one subgroup was further divided and it was found that high MYCN expression and high let-7 activity are associated with worse overall survival. These findings provide critical information for personalized treatment options for medulloblastoma.
Article
Oncology
Catena Kresbach, Lea Holst, Melanie Schoof, Tara Leven, Carolin Goebel, Sina Neyazi, Jacqueline Tischendorf, Carolin Loose, Antonina Wrzeszcz, Timur Yorgan, Stefan Rutkowski, Ulrich Schueller
Summary: The study evaluated the use of intraventricular Vismodegib treatment for medulloblastoma in mice and found that this treatment method can rapidly induce complete or partial remission of tumors, and significantly improve symptom-free survival in a dose-dependent manner.
Article
Clinical Neurology
Turki Elarjani, Malak Altewerki, Abdullah Alsuwaidan, Meshari Alhuthayl, Maher Hassounah
Summary: This article reports a rare case of an adult patient with sarcoidosis developing medulloblastoma. The patient's symptoms worsened but stabilized after surgical treatment and craniospinal radiation and chemotherapy, with no recurrence on MRI brain imaging. Further genetic and molecular studies are needed to investigate the possible causal relationship between these two conditions.
WORLD NEUROSURGERY
(2021)
Article
Oncology
Anna Kotulak-Chrzaszcz, Jacek Kiezun, Mateusz Czajkowski, Marcin Matuszewski, Jakub Klacz, Bartlomiej E. Krazinski, Janusz Godlewski, Zbigniew Kmiec, Piotr M. Wierzbicki
Summary: This study assessed the prognostic significance of SHH, GLI1, and VEGFA immunoreactivity in KIRC tissues. The findings suggest that GLI1 is increased in early-stage tumors, while VEGFA is increased in high-grade KIRC samples. Additionally, there is a correlation between SHH and VEGFA immunoreactivity and shorter patient survival.
Article
Biology
Alejandro Urdiciain, Elena Erausquin, Maria V. Zelaya, Idoya Zazpe, Jose L. Lanciego, Barbara Melendez, Juan A. Rey, Miguel A. Idoate, Natalia A. Riobo-Del Galdo, Javier S. Castresana
Summary: Glioblastoma multiforme (GBM) is the most common and aggressive malignant brain tumor with poor prognosis. HDAC6 is overexpressed in GBM and its silencing inhibits proliferation, migration, and clonogenic potential in GBM cell lines, as well as reversing the mesenchymal phenotype, decreasing autophagy, inhibiting the Sonic Hedgehog pathway, and restoring primary cilia expression. These findings suggest HDAC6 may be a promising therapeutic target for GBM treatment.
Article
Virology
Urvashi B. Singh, Mercy Rophina, Rama Chaudhry, Vigneshwar Senthivel, Kiran Bala, Rahul C. Bhoyar, Bani Jolly, Nayer Jamshed, Mohamed Imran, Ritu Gupta, Praveen Aggarwal, Mohit K. Divakar, Subrata Sinha, V. R. Arvinden, Anjali Bajaj, Afra Shamnath, Abhinav Jain, Vinod Scaria, Sridhar Sivasubbu, Randeep Guleria
Summary: This study analyzed the genomic profiles of breakthrough infections following vaccination with different vaccines, and found that variants of concern B.1.617.2 and B.1.1.7 were the predominant lineages causing a surge in cases in Delhi, India during April-May 2021.
JOURNAL OF MEDICAL VIROLOGY
(2022)
Article
Medicine, General & Internal
Sumit Malhotra, Kalaivani Mani, Rakesh Lodha, Sameer Bakhshi, Vijay Prakash Mathur, Pooja Gupta, Saurabh Kedia, Jeeva Sankar, Parmeshwar Kumar, Arvind Kumar, Vineet Ahuja, Subrata Sinha, Randeep Guleria
Summary: The study suggests that the BBV152 vaccine is associated with protection against symptomatic and asymptomatic reinfection in HCWs after complete vaccination, with the predominant circulating variant being B.1.617.2.
Review
Pharmacology & Pharmacy
Waseem Chauhan, Shoaib Shoaib, Rafat Fatma, Zeeba Zaka-ur-Rab, Mohammad Afzal
Summary: Beta-thalassaemia, including sickle cell anaemia and thalassaemia E, is most common in developing countries. Traditional techniques for managing thalassaemia have drawbacks and limitations, but innovative treatment methods have been developed in recent years. Regulating gene expression and erythropoiesis, as well as adjusting iron metabolism, can be potential targets for managing thalassaemia.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2022)
Article
Immunology
Khushboo Irshad, Chitrangda Srivastava, Nargis Malik, Manvi Arora, Yakhlesh Gupta, Sanjeev Goswami, Chitra Sarkar, Vaishali Suri, Swati Mahajan, Deepak Kumar Gupta, Ashish Suri, Parthaprasad Chattopadhyay, Subrata Sinha, Kunzang Chosdol
Summary: FAT1 promotes tumor immune suppression by upregulating the expression and secretion of TGF-beta1/2 in tumor cells, leading to the formation of an immunosuppressive microenvironment. FAT1 expression is also positively correlated with the expression of markers associated with MDSCs.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Cell Biology
Swalih P. Ahmed, Javier S. Castresana, Mehdi H. Shahi
Summary: Central nervous system tumors, including medulloblastoma and glioblastoma, are a leading cause of cancer-related death. Cell heterogeneity and genetic mutations result in treatment resistance. Circular RNAs play a role in cancer development processes. This study aims to uncover the relationship between GBM pathogenesis and circRNAs.
Article
Biochemistry & Molecular Biology
Shirin Farheen, Swalih P. Ahmed, Mubeena P. M. Mariyath, Tasneem Kausar, Md. Fakhrul Hoda, Sayeedul H. Arif, Shahid M. Nayeem, Asif Ali, Kunzang Chosdol, Mehdi H. Shahi
Summary: This study explored the potential interaction and regulation of Sonic hedgehog (Shh)-Gli1 cell signaling with Pax6 and IDH2 in glioma. It was found that Gli1 had differential dynamic interactions with IDH2 and Pax6, and Gli1 knockdown resulted in downregulation of Pax6 and upregulation of IDH2 expression. Additionally, the knockdown of Pax6 gene in glioma cells downregulated the expression of Gli1 and IDH2 and promoted cell proliferation. The study also showed that the combination of Gli1 inhibitor and an anti-cancer drug had a higher efficacy in treating glioma cells.
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Shirin Farheen, Mubeena P. M. Mariyath, Suhailur Rehman, Md Fakhrul Hoda, Yakhlesh Gupta, Asif Ali, Kunzang Chosdol, Mehdi H. Shahi
Summary: This study investigated the regulation of the Sonic Hedgehog-Gli1 cell signaling pathway in meningioma samples and its potential downstream targets. Results revealed aberrant activation of this pathway in meningioma cells, leading to upregulation of transcription factors Pax6 and Nkx2.2.
INDIAN JOURNAL OF CLINICAL BIOCHEMISTRY
(2022)
Article
Microbiology
Hilal Ahmad Parray, Naveen Narayanan, Sonal Garg, Zaigham Abbas Rizvi, Tripti Shrivastava, Sachin Kushwaha, Janmejay Singh, Praveenkumar Murugavelu, Anbalagan Anantharaj, Farha Mehdi, Nisha Raj, Shivam Singh, Jyotsna Dandotiya, Asha Lukose, Deepti Jamwal, Sandeep Kumar, Adarsh K. Chiranjivi, Samridhi Dhyani, Nitesh Mishra, Sanjeev Kumar, Kamini Jakhar, Sudipta Sonar, Anil Kumar Panchal, Manas Ranjan Tripathy, Shirlie Roy Chowdhury, Shubbir Ahmed, Sweety Samal, Shailendra Mani, Sankar Bhattacharyya, Supratik Das, Subrata Sinha, Kalpana Luthra, Gaurav Batra, Devinder Sehgal, Guruprasad R. Medigeshi, Chandresh Sharma, Amit Awasthi, Pramod Kumar Garg, Deepak T. Nair, Rajesh Kumar
Summary: This study reports the discovery of a highly potent antibody, P4A2, that can neutralize all circulating variants of SARS-CoV-2, including Omicron. It demonstrates broad neutralizing efficacy and prophylactic and therapeutic effectiveness in mice models. Due to its overlap with the ACE2 binding site, P4A2 may also be highly effective against future variants.
Article
Biochemistry & Molecular Biology
Rafat Fatma, Waseem Chauhan, Mohammad Afzal
Summary: This study aimed to investigate and compare the level of homozygosity in the genomes of progeny from four subtypes of first cousin mating in humans, using both pedigree and genomic measures. The results showed differences in the degree of homozygosity among the different subtypes.
Review
Cell Biology
Hera Hasan, Mohammad Afzal, Javier S. Castresana, Mehdi H. Shahi
Summary: Glioblastoma, a highly aggressive brain tumor originating from glial cells, has a maximum life expectancy of 14.6 months. Despite multiple promising therapies, clinical outcomes for glioblastoma patients are poor due to drug resistance. Epigenetic modification, particularly DNA methylation, and miRNAs have been identified as major factors in glioblastoma progression and drug resistance. This review aims to explore the role of known miRNAs in glioblastoma, how epigenetic modification affects their expression, and their potential as predictors of treatment response.
Article
Genetics & Heredity
Rafat Fatma, Waseem Chauhan, Seema Riyaz, Khalid Rasheed, Mohammad Afzal
Summary: This study investigated the association of genetic variant rs662799 of the APOA5 gene with body mass index (BMI) and blood pressure (BP). The results showed a significant association between this variant and increased BMI and BP, specifically in individuals with the G allele. This study provides important clinical and research implications for the diagnostic and prognostic value of the gene in question.
EGYPTIAN JOURNAL OF MEDICAL HUMAN GENETICS
(2023)
Article
Genetics & Heredity
Samanwoy Mukhopadhyay, Subrata Sinha, Saroj Kant Mohapatra
Summary: The study found that the expression of NETosis functional genes in the blood of severe COVID-19 patients increased with disease severity, and showed a negative correlation with blood oxygen saturation. This was also validated in the lungs of non-survivors. Additionally, the early increase of IL-6 in severe COVID-19 disease was found to be associated with complement activation.