Browsing by Author "Colter, Austyn"

Now showing 1 - 4 of 4
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    Pharmacological inhibition of Carbonic Anhydrase IX and XII to enhance targeting of acute myeloid leukaemia cells under hypoxic conditions
    (Wiley, 2021-12) Chen, Fangli; Licarete, Emilia; Wu, Xue; Petrusca, Daniela; Maguire, Callista; Jacobsen, Max; Colter, Austyn; Sandusky, George E.; Czader, Magdalena; Capitano, Maegan L.; Ropa, James P.; Boswell, H. Scott; Carta, Fabrizio; Supuran, Claudiu T.; Parkin, Brian; Fishel, Melissa L.; Konig, Heiko; Pathology and Laboratory Medicine, School of Medicine
    Acute myeloid leukaemia (AML) is an aggressive form of blood cancer that carries a dismal prognosis. Several studies suggest that the poor outcome is due to a small fraction of leukaemic cells that elude treatment and survive in specialised, oxygen (O2 )-deprived niches of the bone marrow. Although several AML drug targets such as FLT3, IDH1/2 and CD33 have been established in recent years, survival rates remain unsatisfactory, which indicates that other, yet unrecognized, mechanisms influence the ability of AML cells to escape cell death and to proliferate in hypoxic environments. Our data illustrates that Carbonic Anhydrases IX and XII (CA IX/XII) are critical for leukaemic cell survival in the O2 -deprived milieu. CA IX and XII function as transmembrane proteins that mediate intracellular pH under low O2 conditions. Because maintaining a neutral pH represents a key survival mechanism for tumour cells in O2 -deprived settings, we sought to elucidate the role of dual CA IX/XII inhibition as a novel strategy to eliminate AML cells under hypoxic conditions. Our findings demonstrate that the dual CA IX/XII inhibitor FC531 may prove to be of value as an adjunct to chemotherapy for the treatment of AML.
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    Pituitary Adenoma and Social Determinants of Health: Tracing PAths to Better Outcomes
    (2024-09-28) Virtanen , Piiamaria S.; Obeng-Gyasi, Barnabas; Brown, Ethan D. L.; Colter, Austyn; Koenig, Jenna; Burket, Noah; Szilagyi, Halie; Williams, Greer; Halalmeh, Dia; Wang, Hannah S.; Tinkham, Shawn A.; Vetter, Cecelia J.; Richardson, Angela M.
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    A Post-Mortem Examination of COVID-19 Pulmonary Pathology in 9 Cases
    (Peertechz Publications, 2020-06-10) Bloom, Alexis; Colter, Austyn; Jacobsen, Max; Battles, Domnique; Albertson, Tamara; Sandusky, George; Pathology and Laboratory Medicine, School of Medicine
    A new novel virus called SARS-CoV-2 has expanded into a pandemic in the past several months. The virus is an acute respiratory RNA virus that has symptoms in three clinical groups: asymptomatic, suspicious, and COVID-19 positive. The clinical lab tests used for diagnosis are Nasalpharyngeal swabs, with further testing done with sputum or BAL samples. Serological samples are collected for diagnosis in deceased patients using RT-PCR. The clinical symptoms usually occur 2 to 14 days after exposure and include fever, dry cough, and fatigue. In some cases, symptoms can progress and cause multiple organ failure due to adult respiratory distress syndrome (ARDS). The virus is in the family of coronaviruses and has also been identified in lung tissue using transmission electron microscopy. Gross and microscopic lung pathology was examined in five positive cases and four negative cases by hematoxylin and eosin (H&E) and Masson’s Trichrome stains. Of the collected, the age range was 28 to 76. The ethnicities were six Caucasians and three minorities, with a male to female ratio of 7:2. The salient histology features seen in the study were multifocal to diffuse alveolar necrosis, bronchiolar epithelial necrosis, and interstitial mononuclear lymphocytic infiltrates. Other features were perivascular and peribronchiolar lymphoid infiltrates and marked congestion. Scattered fibroplasia was found in the damaged alveoli and the alveolar septae in the more severe cases. These pathologic features are similar to other coronaviruses.
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    A single-cell atlas of the healthy breast tissues reveals clinically relevant clusters of breast epithelial cells
    (Elsevier, 2021-03-16) Bhat-Nakshatri, Poornima; Gao, Hongyu; Sheng, Liu; McGuire, Patrick C.; Xuei, Xiaoling; Wan, Jun; Liu, Yunlong; Althouse, Sandra K.; Colter, Austyn; Sandusky, George; Storniolo, Anna Maria; Nakshatri, Harikrishna; Surgery, School of Medicine
    Single-cell RNA sequencing (scRNA-seq) is an evolving technology used to elucidate the cellular architecture of adult organs. Previous scRNA-seq on breast tissue utilized reduction mammoplasty samples, which are often histologically abnormal. We report a rapid tissue collection/processing protocol to perform scRNA-seq of breast biopsies of healthy women and identify 23 breast epithelial cell clusters. Putative cell-of-origin signatures derived from these clusters are applied to analyze transcriptomes of ~3,000 breast cancers. Gene signatures derived from mature luminal cell clusters are enriched in ~68% of breast cancers, whereas a signature from a luminal progenitor cluster is enriched in ~20% of breast cancers. Overexpression of luminal progenitor cluster-derived signatures in HER2+, but not in other subtypes, is associated with unfavorable outcome. We identify TBX3 and PDK4 as genes co-expressed with estrogen receptor (ER) in the normal breasts, and their expression analyses in >550 breast cancers enable prognostically relevant subclassification of ER+ breast cancers.