Review
Cell Biology
Deborah A. M. Joye, Jennifer A. Evans
Summary: The circadian system plays a crucial role in regulating behavior and physiology, and is influenced by biological sex and gonadal hormones. Studies have shown sex differences in daily rhythms in humans, and further research on this topic is needed to understand the underlying mechanisms.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2022)
Review
Pediatrics
Sukanya Priyadarshini, Rajni Sharma
Summary: Disorders of sex development (DSD) refers to congenital conditions where there is a difference in chromosomal, gonadal, or anatomical sex. Pediatricians often encounter the challenge of managing newborns/infants with atypical genitalia or older children with disordered puberty, which fall under the category of DSD. This article provides an updated comprehensive approach to managing DSD, with a focus on atypical genitalia.
INDIAN JOURNAL OF PEDIATRICS
(2023)
Article
Endocrinology & Metabolism
Anela Blazevic, Anand M. Iyer, Marie-Louise F. Van Velthuysen, Johannes Hofland, Lindsey Oudijk, Wouter W. de Herder, Leo J. Hofland, Richard A. Feelders
Summary: Small-intestinal neuroendocrine tumors (SI-NETs) have a higher prevalence and worse prognosis in male patients. This study found that mesenteric metastasis and fibrosis were more common in men than women. The risk of mesenteric metastasis in women increased around menopause. The expression of estrogen receptor alpha and androgen receptor was observed in primary tumors and mesenteric metastases.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Genetics & Heredity
Kheloud M. Alhamoudi, Balgees Alghamdi, Abeer Aljomaiah, Meshael Alswailem, Hindi Al-Hindi, Ali S. Alzahrani
Summary: A young girl with 46,XY DSD was found to have a unique novel mutation in the NR5A1 gene, resulting in severe gonadal dysgenesis and deficiency of testosterone and anti-Mullerian hormone secretion. Despite the atrophied testes and lack of breast development, the patient identified as female and responded well to estrogen/progesterone therapy, showing excellent breast development and normal cyclical menses. This case demonstrates the importance of a genetic mutation in explaining the clinical phenotype of DSD.
FRONTIERS IN GENETICS
(2022)
Article
Obstetrics & Gynecology
Duoduo Zhang, Fengxia Yao, Tiffany Tian, Shan Deng, Min Luo, Qinjie Tian
Summary: This study investigated the clinical and genetic characteristics of complete androgen insensitivity syndrome (CAIS) in patients from China, finding that the majority of patients had mutations in the androgen receptor (AR) gene and some had mutations in the steroid 5 alpha-reductase type 2 gene (SRD5A2). The study identified novel mutations in the AR gene, expanding the knowledge of genetic causes of CAIS.
FERTILITY AND STERILITY
(2021)
Article
Endocrinology & Metabolism
Aisha L. Siebert, Veronica Gomez-Lobo, Emilie K. Johnson, Leena Nahata, Kyle E. Orwig, Louise C. Pyle, Selma F. Witchel, Courtney Finlayson, Monica M. Laronda
Summary: Gonadal tissue cryopreservation (GTC) is offered at around 50% of the institutions surveyed in the US for patients with differences of sex development (DSD), but only a minority are preserving tissue for research purposes. GTC is offered for various DSD conditions. Future research will focus on examining the presence and quality of germ cells to support clinical decision making related to fertility preservation for patients with DSD.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Neharika Bhadouria, Alycia G. Berman, Joseph M. Wallace, Nilsson Holguin
Summary: Raloxifene, an estrogen agonist, protects intervertebral discs in mice from degeneration and pain-related substance P expression induced by aging and biological sex.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Ophthalmology
Abdullah Agin, Sibel Kocabeyoglu, Aysun Yucel Gencoglu, Sercan Aksoy, Jale Karakaya, Murat Irkec
Summary: This study using in vivo confocal microscopy found deteriorations in ocular surface parameters and corneal structural changes in breast cancer patients receiving aromatase inhibitor therapy, highlighting the importance of monitoring for ocular surface side effects during treatment.
Review
Clinical Neurology
Hayley A. Wilson, Carolyn Creighton, Helen Scharfman, Elena Choleris, Neil J. MacLusky
Summary: Autism spectrum disorder (ASD) is a class of neurodevelopmental disorders that affects males more frequently than females. Genetic and environmental risk factors may contribute to its development, with hormones like gonadal, thyroid, and glucocorticoids potentially playing a role. Environmental factors may influence ASD etiology by affecting neuroendocrine and neuroimmune system development, with the placenta likely serving as a key mediator of these effects on the developing brain, particularly in males. Understanding how various risk factors interact to impact neural development could lead to a better understanding of the causes of ASD.
Review
Biochemistry & Molecular Biology
Nina Tyutyusheva, Ilaria Mancini, Giampiero Igli Baroncelli, Sofia D'Elios, Diego Peroni, Maria Cristina Meriggiola, Silvano Bertelloni
Summary: Complete Androgen Insensitivity Syndrome (CAIS) is a rare condition caused by complete resistance to androgens, resulting in a female phenotype in individuals with a 46,XY karyotype. Proper management and treatment are crucial for improving the long-term quality of life for these patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Genetics & Heredity
Hui Zhu, Haijun Yao, Yue Xu, Yan Chen, Bing Han, Nan Wang, Hao Wang, Qiang Zhang, Wenjiao Zhu, Yuanping Shi, Hua Sun, Shuangxia Zhao, Huaidong Song, Yang Liu, Jie Qiao
Summary: This study aimed to describe the clinical features and molecular defects of 36 Chinese patients with AR variants, identifying eight novel and fifteen reported AR variants. Functional assays reclassified the novel AR variants and revealed that mutations in the Arg841 residue were recurrent in Chinese AIS patients. Postpubertal CAIS patients had higher gonadotropin levels compared to PAIS patients.
ORPHANET JOURNAL OF RARE DISEASES
(2021)
Article
Oncology
Malgorzata Lysiak, Malgorzata Trybula, Munila Mudaisi, Charlotte Bratthall, Michael Strandeus, Peter Milos, Martin Hallbeck, Annika Malmstrom
Summary: We analyzed the role of androgen receptor (AR) in glioblastoma (GBM) and found that high AR gene expression had sex-dependent effects on patient survival, being associated with DNA repair response in males and shorter survival in females.
MOLECULAR ONCOLOGY
(2022)
Article
Pediatrics
Aikaterini Kapama, Dimitrios T. T. Papadimitriou, George Mastorakos, Nikolaos F. F. Vlahos, Maria Papagianni
Summary: Complete Androgen Insensitivity Syndrome (CAIS) is a rare genetic condition characterized by mutations in the androgen receptor (AR) gene, resulting in resistance to androgens and a female phenotype in genetically male individuals. This study reports a case of CAIS in a 16-year-old patient, diagnosed through clinical evaluation, hormonal assessment, imaging studies, and genetic testing, highlighting the importance of prompt diagnosis and proper management.
Article
Psychology, Multidisciplinary
Cesar Augusto Bridi Filho, Saulo Batinga Cardoso, Bianca Machado Borba Soll, Marcelo Froeelich Noal, Karine Schwarz, Tiago Elias Rosito, Nicolino Cesar Rosito, Maria Ines Rodrigues Lobato
Summary: Research data on the consequences of Disorders of Sex Development (DSD) on sex life show that individuals with DSD tend to have atypical sexual experiences, such as delayed sexual debut, limited sexual relationships, and occurrence of Gender Dysphoria.
FRONTIERS IN PSYCHOLOGY
(2022)
Review
Endocrinology & Metabolism
Rafael Loch Batista, Flora Ladeira Craveiro, Raquel Martinez Ramos, Berenice Bilharinho Mendonca
Summary: This study aimed to explore the various aspects, clinical features, and molecular mechanisms of Mild Androgen Insensitivity Syndrome (MAIS). By collecting reported MAIS cases and comparing them with other AIS phenotypes, the study identified 49 different androgen receptor (AR) mutations among 69 individuals. Furthermore, it was found that most MAIS patients present with male factor infertility, suggesting that AR gene sequencing should be considered in male factor infertility investigations.
ENDOCRINE PRACTICE
(2022)
Article
Anatomy & Morphology
Jennie N. Jeyapalan, Victoria. James, David S. Gardner, Jennifer H. Lothion-Roy, Nigel P. Mongan, Catrin Sian Rutland
Summary: Research is an essential part of veterinary medicine degrees, and remote learning during the COVID-19 pandemic has affected the performance and experience of students. This study analyzed the outcomes and feedback of students who completed independent research projects, showing that the pandemic cohorts achieved higher grades with increased access to resources while facing challenges in workload management and conceptual exploration.
ANATOMIA HISTOLOGIA EMBRYOLOGIA
(2023)
Article
Cell Biology
Ayat Lashen, Michael S. Toss, Andrew R. Green, Nigel P. Mongan, Emad Rakha
Summary: This study compared several methods for scoring Ki67 in breast cancer, and found that quantifying Ki67-positive cells among 1000 tumor cells had the highest consistency between observers and was the most predictive of patient outcomes. The granular pattern of Ki67 expression was associated with poorer outcomes compared to other patterns.
Review
Pathology
Suzan F. Ghannam, Catrin Sian Rutland, Cinzia Allegrucci, Nigel P. Mongan, Emad Rakha
Summary: Basement membrane (BM) is an important structure separating the epithelium from the stroma, and its composition varies during different stages of breast development. In pathological conditions, the presence or absence of BM plays a crucial role in distinguishing in situ from invasive lesions. Although diagnostic techniques are evolving, BM is still considered a useful marker in ambiguous cases. This review discusses the structure, function, and clinical significance of BM in relation to breast lesions, with a focus on differentiating it from alternative pathological tissue.
JOURNAL OF CLINICAL PATHOLOGY
(2023)
Article
Oncology
Jaclyn M. Kubala, Kristian B. Laursen, Ryan Schreiner, Ryan M. Williams, Johannes C. van der Mijn, Michael J. Crowley, Nigel P. Mongan, David M. Nanus, Daniel A. Heller, Lorraine J. Gudas
Summary: In clear cell renal cell carcinoma (ccRCC), overexpression of NDUFA4L2 contributes to ccRCC proliferation and survival. NDUFA4L2 enhances glycolysis and regulates mitochondrial-lysosomal associations in ccRCC. Knocking out NDUFA4L2 decreases lysosomal size and abundance in ccRCC cells.
CANCER BIOLOGY & THERAPY
(2023)
Article
Genetics & Heredity
Jennifer Lothion-Roy, Daisy B. Haigh, Anna E. Harris, Veronika M. Metzler, Mansour Alsaleem, Michael S. Toss, Yousif Kariri, Atara Ntekim, Brian D. Robinson, Francesca Khani, Lorraine J. Gudas, Cinzia Allegrucci, Victoria H. James, Srinivasan Madhusudan, Melissa Mather, Richard D. Emes, Nathan Archer, Rupert G. Fray, Emad Rakha, Jennie N. Jeyapalan, Catrin S. Rutland, Nigel P. Mongan, Corinne L. Woodcock
Summary: N-6-methyladenosine (m(6)A) is the most abundant internal mRNA modification and plays crucial roles in gene expression, RNA stability, splicing and translation. The components of the m(6)A modification have been implicated in diseases, including prostate cancer (PCa). This study investigated the expression and clinical significance of METTL3, METTL14, WTAP, and CBLL1 in PCa specimens and cell lines, and found that METTL3 and CBLL1 expression were associated with poorer PCa patient outcomes. Functional analysis revealed the roles of METTL3 in androgen receptor regulation and gene expression in PCa cells.
FRONTIERS IN GENETICS
(2023)
Review
Pharmacology & Pharmacy
Juliette Brownlie, Sanat Kulkarni, Mashael Algethami, Jennie N. Jeyapalan, Nigel P. Mongan, Emad A. Rakha, Srinivasan Madhusudan
Summary: DNA repair targeted therapeutics, such as PARP inhibitors, have shown promising results in the treatment of BRCA germline deficient breast and ovarian cancer. However, not all patients respond to this treatment due to intrinsic or acquired resistance. Therefore, the exploration of other synthetic lethality approaches, including ATM, ATR, and WEE1 inhibitors, is currently an active area in cancer research.
CURRENT OPINION IN PHARMACOLOGY
(2023)
Article
Cell Biology
Suzan F. Ghannam, Catrin S. Rutland, Cinzia Allegrucci, Nigel P. Mongan, Emad Rakha
Summary: This study describes the geometric characteristics of the EPC capsule and provides evidence that it is a reactive process rather than a thickened native BM characteristic of normal and in situ lesions. The study supports the understanding that EPC is an indolent invasive carcinoma based on capsule characteristics.
Article
Cell Biology
Ayat G. Lashen, Michael S. Toss, Louisa Wootton, Andrew R. R. Green, Nigel P. Mongan, Srinivasan Madhusudan, Emad Rakha
Summary: This study aimed to evaluate the prognostic and predictive role of PLK1 in breast cancer (BC) and its molecular subtypes. The results showed that high PLK1 expression was significantly associated with better outcome in the whole cohort and luminal BC, but with poorer outcome in triple-negative breast cancer (TNBC).
Review
Pathology
Ayat Gamal Lashen, Michael S. Toss, Suzan Fathy Ghannam, Shorouk Makhlouf, Andrew Green, Nigel P. Mongan, Emad Rakha
Summary: Ki67 expression is an important and cost-effective surrogate marker for assessing tumour cell proliferation in breast cancer. It has prognostic and predictive value, especially in hormone receptor-positive, HER2-negative tumours. However, challenges exist in its routine clinical use and there is increasing criticism of its clinical utility. Overcoming these challenges and weighing the benefits against weaknesses are necessary to maximize its performance in breast cancer.
JOURNAL OF CLINICAL PATHOLOGY
(2023)
Article
Immunology
Shahd Talhouni, Wakkas Fadhil, Nigel P. Mongan, Lara Field, Kelly Hunter, Sogand Makhsous, Alexandre Maciel-Guerra, Nayandeep Kaur, Ausrine Nestarenkaite, Arvydas Laurinavicius, Benjamin E. Willcox, Tania Dottorini, Ian Spendlove, Andrew M. Jackson, Mohammad Ilyas, Judith M. Ramage
Summary: The characterization of the tumour immune infiltrate, specifically CD8+ T-cells, has a strong predictive survival value for cancer patients. A study found that the abundance and localization of activated tumour-specific tissue resident memory CD8 T-cells (T-RM) can provide a higher-resolution route to patient stratification.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Cell Biology
Veronika M. Metzler, Simone de Brot, Daisy B. Haigh, Corinne L. Woodcock, Jennifer Lothion-Roy, Anna E. Harris, Emeli M. Nilsson, Atara Ntekim, Jenny L. Persson, Brian D. Robinson, Francesca Khani, Kristian B. Laursen, Lorraine J. Gudas, Michael S. Toss, Srinivasan Madhusudan, Emad Rakha, David M. Heery, Catrin S. Rutland, Nigel P. Mongan, Jennie N. Jeyapalan
Summary: KDM1A and KDM5B play crucial roles in prostate cancer by promoting androgen regulated gene expression through interaction with AR. Developing therapies targeting KDM1A and KDM5B is of great importance due to the ineffectiveness of conventional androgen deprivation therapies and androgen receptor signalling inhibitors in castrate resistant prostate cancer (CRPC).
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Oncology
Mashael Algethami, Michael S. S. Toss, Corinne L. L. Woodcock, Chandar Jaipal, Juliette Brownlie, Ahmed Shoqafi, Adel Alblihy, Katia A. A. Mesquita, Andrew R. R. Green, Nigel P. P. Mongan, Jennie N. N. Jeyapalan, Emad A. A. Rakha, Srinivasan Madhusudan
Summary: This study found that Replication Protein A (RPA) plays a critical role in breast cancer, being involved in cell DNA replication, checkpoint regulation and DNA repair. Low levels of RPA are associated with aggressive breast cancer and shorter survival outcomes. The study suggests that a precision oncology strategy targeting RPA is feasible in breast cancer patients.
Article
Oncology
Shorouk Makhlouf, Noorul Wahab, Michael Toss, Asmaa Ibrahim, Ayat G. Lashen, Nehal M. Atallah, Suzan Ghannam, Mostafa Jahanifar, Wenqi Lu, Simon Graham, Nigel P. Mongan, Mohsin Bilal, Abhir Bhalerao, David Snead, Fayyaz Minhas, Shan E. Ahmed Raza, Nasir Rajpoot, Emad Rakha
Summary: In this study, artificial intelligence (AI) was used to assess the prognostic significance of tumour infiltrating lymphocytes (TILs) in a large cohort of luminal breast cancer patients. The results showed that TILs counts and their spatial distribution had predictive value for the prognosis of early-stage breast cancer patients.
BRITISH JOURNAL OF CANCER
(2023)
Article
Oncology
N. M. Atallah, M. Alsaleem, M. S. Toss, N. P. Mongan, E. Rakha
Summary: HER2-positive breast cancer subtypes exhibit differential responses to targeted anti-HER2 therapy. Patients with IHC 2+/Amplified subtype have lower pathological complete response rates and shorter survival. ER positivity significantly decreases response to anti-HER2 therapy in IHC 2+/Amplified patients.
BRITISH JOURNAL OF CANCER
(2023)
Review
Oncology
Mosebo Armstrong Manabile, Rodney Hull, Richard Khanyile, Thulo Molefi, Botle Precious Damane, Nigel Patrick Mongan, David Owen Bates, Zodwa Dlamini
Summary: Colorectal cancer is a leading cause of cancer-related deaths globally, with increasing incidence in developing countries. Dysregulated alternative splicing processes in colorectal cancer can promote its development and progression by producing proteins that activate cancer-promoting genes or deactivate cancer-inhibiting genes. It is important to identify these dysregulated alternative splicing genes in order to develop targeted treatments and diagnostics to stop cancer development and progression.
