Article
Biology
Gaia Bianco, Mairene Coto-Llerena, John Gallon, Venkatesh Kancherla, Stephanie Taha-Mehlitz, Mattia Marinucci, Martina Konantz, Sumana Srivatsa, Hesam Montazeri, Federica Panebianco, Vijaya G. Tirunagaru, Marta De Menna, Viola Paradiso, Caner Ercan, Ahmed Dahmani, Elodie Montaudon, Niko Beerenwinkel, Marianna Kruithof-de Julio, Luigi M. Terracciano, Claudia Lengerke, Rinath M. Jeselsohn, Robert C. Doebele, Francois-Clement Bidard, Elisabetta Marangoni, Charlotte K. Y. Ng, Salvatore Piscuoglio
Summary: This study reveals the synthetic lethal interaction between GATA3 and MDM2 in ER-positive breast cancer, suggesting MDM2 inhibition as a potential therapeutic target for this subgroup of patients.
COMMUNICATIONS BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Naoyuki Kataoka, Eri Matsumoto, So Masaki
Summary: Pre-mRNA splicing is a crucial process for gene expression in higher eukaryotes, and mutations in splicing factors can lead to various human diseases, including MDS. Recent studies have shown that mutations in splicing factors play a driver role in human cancers, affecting about 50% of MDS patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Oncology
Jacob J. Adashek, Aakash P. Desai, Alexander Y. Andreev-Drakhlin, Jason Roszik, Gilbert J. Cote, Vivek Subbiah
Summary: Activating receptor-tyrosine kinase rearranged during transfection (RET) mutations and fusions are potent drivers of oncogenesis. The recent FDA approvals of highly potent and selective RET inhibitors have changed therapeutic management of RET aberrant tumors. There is evidence of the important role of RET signaling in certain cancers, but with considerable phenotypic diversity, and emerging data suggests lack of responsiveness to immunotherapy in RET-altered cancers.
MOLECULAR CANCER THERAPEUTICS
(2021)
Article
Oncology
Oren Yakovian, Julia Sajman, Rand Arafeh, Yair Neve-Oz, Michal Alon, Yardena Samuels, Eilon Sherman
Summary: The study reveals the nanoscale organization and signal coupling of NRas and BRAF in melanoma cells, showing that mutant NRas exhibits more pronounced self-clustering and increased association with BRAF. The findings suggest a new regulatory mechanism for NRas signaling and potential therapeutic targets for MEK inhibitors in melanoma.
Article
Biochemistry & Molecular Biology
Timothy E. Hoffman, Varuna Nangia, C. Ryland III, Victor J. Passanisi, Claire Armstrong, Chen Yang, Sabrina L. Spencer
Summary: Many cancers with pro-proliferative mutations in the MAPK pathway can rapidly escape the effects of MAPK pathway inhibitors. Cancer cells driven by BRAF, EGFR, or KRAS mutations can adapt and resume slow proliferation after being treated with these inhibitors. The escape of cells is associated with DNA replication deficits, DNA lesions, and stress responses that rely on the ATR kinase. The recruitment of components from the FA DNA repair pathway enables the successful completion of cell division in escapee cells.
Article
Genetics & Heredity
I Dominguez, M. Cruz-Gamero, V Corasolla, N. Dacher, S. Rangasamy, A. Urbani, V Narayanan, H. Rebholz
Summary: The Okur-Chung neurodevelopmental syndrome, or OCNDS, is a rare neurodevelopmental disorder characterized by intellectual disability, language deficits, and behavioral abnormalities. Researchers found that mutations in the CK2α gene in OCNDS patients lead to reduced kinase activity and abnormal localization, suggesting a potential underlying cause for the syndrome.
Article
Biochemistry & Molecular Biology
Vidhi Malik, Vipul Kumar, Sunil C. Kaul, Renu Wadhwa, Durai Sundar
Summary: The study demonstrates that Wi-A and Wi-N have the potential to bind to multiple mutated EGFRs, while CAPE is limited to wildtype EGFR and exon 20 insertion mutants. The binding free energy of the natural compounds against EGFRs is comparable to positive controls, suggesting their potential as therapeutic agents against mutated EGFRs.
Article
Microbiology
Satoshi Imai, Takuya Ooki, Naoko Murata-Kamiya, Daisuke Komura, Kamrunnesa Tahmina, Weida Wu, Atsushi Takahashi-Kanemitsu, Christopher Takaya Knight, Akiko Kunita, Nobumi Suzuki, Adriana A. Del Valle, Mayo Tsuboi, Masahiro Hata, Yoku Hayakawa, Naomi Ohnishi, Koji Ueda, Masashi Fukayama, Tetsuo Ushiku, Shumpei Ishikawa, Masanori Hatakeyama
Summary: Infection with CagA-producing H. pylori leads to gastric cancer development through disrupting DNA repair mechanisms, inhibiting apoptosis of damaged cells, and promoting somatic mutation. This hit-and-run mechanism creates a favorable environment for the initiation and progression of gastric carcinogenesis.
CELL HOST & MICROBE
(2021)
Article
Multidisciplinary Sciences
Lorenzo Massimi, Tamara Suaris, Charlotte K. Hagen, Marco Endrizzi, Peter R. T. Munro, Glafkos Havariyoun, P. M. Sam Hawker, Bennie Smit, Alberto Astolfo, Oliver J. Larkin, Richard M. Waltham, Zoheb Shah, Stephen W. Duffy, Rachel L. Nelan, Anthony Peel, J. Louise Jones, Ian G. Haig, David Bate, Alessandro Olivo
Summary: X-ray phase contrast imaging (XPCI) shows higher sensitivity in detecting margin involvement during breast conserving surgery, potentially leading to a reduction in the number of re-operations.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
Mangesh A. Thorat, Pauline M. Levey, J. Louise Jones, Sarah E. Pinder, Nigel J. Bundred, Ian S. Fentiman, Jack Cuzick
Summary: The study found that ER expression is a strong predictor of ipsilateral recurrence risk in ductal carcinoma in situ. Patients with multi-clonal ER expression and patients with uni-clonal ER expression faced similarly higher risks of ipsilateral breast events.
CLINICAL CANCER RESEARCH
(2021)
Review
Endocrinology & Metabolism
Andrew Arnold, Elaine Dennison, Christopher S. Kovacs, Michael Mannstadt, Rene Rizzoli, Maria Luisa Brandi, Bart Clarke, Rajesh V. Thakker
Summary: This article discusses the physiological and pathological aspects of hormonal regulation of biomineralization, emphasizing the importance of mineral intake, serum concentrations of mineral, and hormonal regulators in this process. It also highlights the crucial role of biomineralization in providing rigidity and flexibility to the skeleton, and the balance required for proper skeletal metabolism.
NATURE REVIEWS ENDOCRINOLOGY
(2021)
Review
Endocrinology & Metabolism
Paul J. Newey, Fadil M. Hannan, Abbie Wilson, Rajesh Thakker
Summary: Disorders of calcium homeostasis are common metabolic bone diseases encountered by endocrinologists, with some cases having a monogenic etiology. Recognition and diagnosis of these disorders are important for patient management and identifying family members at risk of disease.
CLINICAL ENDOCRINOLOGY
(2022)
Article
Endocrinology & Metabolism
Michael Mannstadt, Luisella Cianferotti, Rachel Gafni, Francesca Giusti, Elizabeth Helen Kemp, Christian A. Koch, Kelly L. Roszko, Liam Yao, Gordon H. Guyatt, Rajesh Thakker, Weibo Xia, Maria-Luisa Brandi
Summary: This article summarizes the diagnostic criteria for hypoparathyroidism and discusses the clinical presentation and genetic causes of the nonsurgical forms. It provides an update on these topics and suggests a research agenda for improving diagnosis and prognosis. The article also discusses the characteristics of measuring calcium and PTH and the utility of these measurements in predicting long-term hypoparathyroidism. In addition, it addresses the genetic diagnosis of hypoparathyroidism and the associated phenotypic characteristics.
JOURNAL OF BONE AND MINERAL RESEARCH
(2022)
Review
Endocrinology & Metabolism
John P. Bilezikian, Aliya A. Khan, Shonni J. Silverberg, Ghada El-Hajj Fuleihan, Claudio Marcocci, Salvatore Minisola, Nancy Perrier, Antonio Sitges-Serra, Rajesh Thakker, Gordon Guyatt, Michael Mannstadt, John T. Potts, Bart L. Clarke, Maria Luisa Brandi
Summary: The last international guidelines on the evaluation and management of primary hyperparathyroidism (PHPT) were published in 2014. New research since then has led to new insights in epidemiology, pathophysiology, diagnosis, measurements, genetics, outcomes, presentations, new imaging modalities, target and other organ systems, pregnancy, evaluation, and management. An international group of experts reviewed these advances in knowledge and provided evidence-based recommendations and guidelines for the evaluation and management of PHPT.
JOURNAL OF BONE AND MINERAL RESEARCH
(2022)
Review
Endocrinology & Metabolism
Fadil M. Hannan, Taha Elajnaf, Laura N. Vandenberg, Stephen H. Kennedy, Rajesh V. Thakker
Summary: Lactation is crucial for the health of both infants and mothers, and is regulated by reproductive and metabolic hormones. The development of mammary glands and synthesis of milk are closely related to hormonal functions, which are stimulated by infant suckling. After weaning, there is a large-scale cell loss in the glands leading to involution. The hormonal composition of human milk also has effects on infant health and development. Additionally, endocrine and metabolic diseases, labor interventions, and exposure to endocrine-disrupting chemicals can cause lactation insufficiency.
NATURE REVIEWS ENDOCRINOLOGY
(2022)
Article
Oncology
Mary-Kate Hayward, Michael D. Allen, Jennifer J. Gomm, Iain Goulding, Clare L. Thompson, Martin M. Knight, John F. Marshall, J. Louise Jones
Summary: Women with DCIS have an increased risk of developing invasive breast cancer. A study found that the size of DCIS ducts is associated with the progression to invasion, and mechanical stimulation can alter the phenotype of myoepithelial cells in DCIS, affecting invasion.
Review
Endocrinology & Metabolism
Salvatore Minisola, Seiji Fukumoto, Weibo Xia, Alessandro Corsi, Luciano Colangelo, Alfredo Scillitani, Jessica Pepe, Cristiana Cipriani, Rajesh Thakker
Summary: Tumor-induced osteomalacia is a rare paraneoplastic syndrome characterized by bone softening and various symptoms. It is often underdiagnosed due to nonspecific symptoms. Biochemical features include hypophosphatemia, abnormal FGF23 levels, and abnormal vitamin D levels. The underlying tumors are usually phosphaturic mesenchymal tumors.
Editorial Material
Endocrinology & Metabolism
Rajesh V. Thakker
JOURNAL OF BONE AND MINERAL RESEARCH
(2023)
Article
Endocrinology & Metabolism
Caroline M. Gorvin, Paul J. Newey, Rajesh Thakker
Summary: By evaluating more than 300 uncharacterized variants, researchers found that 5 rare PRLR gene variants were associated with altered signaling pathways, including STAT5 signaling, Akt and FOXO1 activity, cell viability, and apoptosis. These findings provide further understanding of PRLR structure-function and suggest that rare PRLR gene variants may have diverse modulating effects on PRLR signaling, although the pathophysiological relevance of such alterations remains to be defined.
JOURNAL OF MOLECULAR ENDOCRINOLOGY
(2023)
Review
Oncology
Shayin V. Gibson, Reza M. Roozitalab, Michael D. Allen, J. Louise Jones, Edward P. Carter, Richard P. Grose
Summary: Ductal carcinoma in situ (DCIS) is a pre-invasive form of breast cancer characterized by neoplastic luminal cells confined to the ductal tree. While most cases will remain indolent, overtreatment is a concern and new methods are needed to stratify patients. Recent studies have focused on the complex microenvironment of DCIS, highlighting the role of different cell types in regulating tumor progression. Understanding these aspects may lead to more effective care for patients.
Review
Endocrinology & Metabolism
Katherine A. English, Kate E. Lines, Rajesh V. Thakker
Summary: Primary hyperparathyroidism (PHPT) can occur as part of a hereditary syndromic disorder or as a non-syndromic disease. Recognition of the hereditary forms is important for implementing screening protocols and investigating associated tumors. Most patients with syndromic PHPT require parathyroidectomy to limit end-organ damage. Non-syndromic PHPT may be associated with MEN1 gene or CASR mutations.
HORMONES-INTERNATIONAL JOURNAL OF ENDOCRINOLOGY AND METABOLISM
(2023)
Article
Endocrinology & Metabolism
Mark Stevenson, Alistair T. Pagnamenta, Heather G. Mack, Judith Savige, Edoardo Giacopuzzi, Kate E. Lines, Jenny C. Taylor, Rajesh Thakker
Summary: Bartter syndrome and Gitelman syndrome are renal tubular disorders that affect the reabsorption of sodium, potassium, and chloride ions. This study reports a case of GS and establishes a diagnosis of BS type-3 through whole-genome sequencing analysis. The results demonstrate the utility of whole-genome sequencing in diagnosing renal tubular disorders with overlapping phenotypes.
JOURNAL OF THE ENDOCRINE SOCIETY
(2022)
Article
Endocrinology & Metabolism
Marianne S. Elston, Taha Elajnaf, Fadil M. Hannan, Rajesh Thakker
Summary: This study reports a case of ADH1 patient with intracerebral calcifications who also experienced recurrent hypocalcemic and hypercalcemic episodes and myoclonic jerks. Treatment with medication relieved the myoclonus symptoms. Mutational analysis identified a reported CaSR gene mutation in the patient.
JOURNAL OF THE ENDOCRINE SOCIETY
(2022)