Browsing by Subject "Neoplastic cell transformation"

Now showing 1 - 5 of 5
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    Adenosquamous carcinoma arising within a long‐standing intrapulmonary bronchogenic cyst in an adult presenting with hyponatraemia
    (Wiley, 2025) Akinsanya, Adeyinka; Segura, Sheila; Cramer, Harvey; Mesa, Hector; Pathology and Laboratory Medicine, School of Medicine
    A 74-year-old woman's persistent hyponatraemia led to the discovery of an adenosquamous carcinoma within an intrapulmonary bronchogenic cyst (IPBC), diagnosed 59 years prior. This is the first reported case of such a transformation in an IPBC. An adenosquamous carcinoma, originating from an intrapulmonary bronchogenic cyst identified 59 years prior, was discovered during the workup for a patient's unexplained, persistent hyponatraemia.
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    Bidirectional Regulatory Cross-Talk between Cell Context and Genomic Aberrations Shapes Breast Tumorigenesis
    (American Association for Cancer Research, 2021) Kumar, Brijesh; Bhat-Nakshatri, Poornima; Maguire, Calli; Jacobsen, Max; Temm, Constance J.; Sandusky, George; Nakshatri, Harikrishna; Surgery, School of Medicine
    Breast cancers are classified into five intrinsic subtypes and 10 integrative clusters based on gene expression patterns and genomic aberrations, respectively. Although the cell-of-origin, adaptive plasticity, and genomic aberrations shape dynamic transcriptomic landscape during cancer progression, how interplay between these three core elements governs obligatory steps for a productive cancer progression is unknown. Here, we used genetic ancestry-mapped immortalized breast epithelial cell lines generated from breast biopsies of healthy women that share gene expression profiles of luminal A, normal-like, and basal-like intrinsic subtypes of breast cancers and breast cancer relevant oncogenes to develop breast cancer progression model. Using flow cytometry, mammosphere growth, signaling pathway, DNA damage response, and in vivo tumorigenicity assays, we provide evidence that establishes cell context-dependent effects of oncogenes in conferring plasticity, self-renewal/differentiation, intratumor heterogeneity, and metastatic properties. In contrast, oncogenic aberrations, independent of cell context, shaped response to DNA damage-inducing agents. Collectively, this study reveals how the same set of genomic aberration can have distinct effects on tumor characteristics based on cell-of-origin of tumor and highlights the need to utilize multiple "normal" epithelial cell types to decipher oncogenic properties of a gene of interest. In addition, by creating multiple isogenic cell lines ranging from primary cells to metastatic variants, we provide resources to elucidate cell-intrinsic properties and cell-oncogene interactions at various stages of cancer progression. IMPLICATIONS: Our findings demonstrate that how an interplay between the normal cell type that encountered genomic aberrations and type of genomic aberration influences heterogeneity, self-renewal/differentiation, and tumor properties including propensity for metastasis.
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    Hepatocellular Carcinoma: Carcinogenesis, Establishment, Progression, and Therapies
    (Hindawi, 2014) Guan, Yong-Song; Ahmad Al-Shatouri, Mohammad; He, Qing; Liu, Wei Mike; Pediatrics, School of Medicine
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    HNRNPM Regulates HCC Tumorigenesis and Cancer Stemness: Identification of a Novel Therapeutic Target?
    (Elsevier, 2022) Kennedy, Lindsey; Medicine, School of Medicine
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    Pten loss induces autocrine FGF signaling to promote skin tumorigenesis
    (Elsevier, 2014) Hertzler-Schaefer, Kristina; Mathew, Grinu; Somani, Ally-Khan; Tholpady, Sunil; Kadakia, Madhavi P.; Chen, Yiping; Spandau, Dan F.; Zhang, Xin; Dermatology, School of Medicine
    Inactivation of the Pten tumor suppressor negatively regulates the PI3K-mTOR pathway. In a model of cutaneous squamous cell carcinoma (SCC), we demonstrate that deletion of Pten strongly elevates Fgf10 protein levels without increasing Fgf10 transcription in vitro and in vivo. The translational activation of Fgf10 by Pten deletion is reversed by genetic disruption of the mTORC1 complex, which also prevents skin tumorigenesis in Pten mutants. We further show that ectopic expression of Fgf10 causes skin papillomas, whereas Pten deletion-induced skin tumors are inhibited by epidermal deletion of Fgfr2. Collectively, our data identify autocrine activation of FGF signaling as an essential mechanism in promoting Pten-deficient skin tumors.