Targeting mitochondrial oxidative phosphorylation (OXPHOS) to treat cancer has been hampered due to serious side-effects potentially arising from the inability to discriminate between non-cancerous and cancerous mitochondria. Herein, comprehensive mitochondrial phenotyping was leveraged to define both the composition and function of OXPHOS across various murine cancers and compared to both matched normal tissues and other organs. When compared to both matched normal tissues, as well as high OXPHOS reliant organs like heart, intrinsic expression of the OXPHOS complexes, as well as OXPHOS flux were discovered to be consistently lower across distinct cancer types.
View Article and Find Full Text PDFThe objective of the North Carolina Tissue Consortium is to facilitate cancer-related research by providing a means through which normal and malignant tissue specimens are procured, processed, stored, and distributed to researchers while protecting the rights and confidentiality of participants.
View Article and Find Full Text PDFHepatocellular carcinoma (HCC) is the most common form of liver cancer worldwide. Increasing evidence suggests that mitochondria play a central role in malignant metabolic reprogramming in HCC, which may promote disease progression. To comprehensively evaluate the mitochondrial phenotype present in HCC, we applied a recently developed diagnostic workflow that combines high-resolution respirometry, fluorometry, and mitochondrial-targeted nLC-MS/MS proteomics to cell culture (AML12 and Hepa 1-6 cells) and diethylnitrosamine (DEN)-induced mouse models of HCC.
View Article and Find Full Text PDFBackground: The literature is replete with studies that define the nexus of quantity and quality in complex surgical operations. These observations have heralded a call for centralization of care to high-volume centers. The purpose of this study was to chronicle improvements in quality associated with pancreaticoduodenectomy (PD) as a rural hospital matures from a low- to very high-volume center.
View Article and Find Full Text PDFBackground: Phyllodes tumor (PT) is a rare fibroepithelial lesion of the breast with variable malignant potential. Black women have a higher incidence of a related benign tumor, fibroadenoma, but there are limited epidemiological data on PT. The aim of our study was to evaluate race-related differences in the clinicopathologic features and outcomes of PT.
View Article and Find Full Text PDFPurpose: American Joint Committee on Cancer (AJCC) clinical staging is used to estimate breast cancer prognosis, but individual patient survival within each stage varies considerably by age at diagnosis. We hypothesized that the addition of age at diagnosis to the staging schema will enable more refined risk stratification.
Methods: We performed a retrospective population analysis of adult women diagnosed with invasive breast cancer between 2010 and 2015 registered in SEER.
Importance: Although optimal access is accepted as the key to quality care, an accepted methodology to ascertain potential disparities in surgical access has not been defined.
Objective: To develop a systematic approach to detect surgical access disparities.
Design, Setting, And Participants: This cross-sectional study used publicly available data from the Health Cost and Utilization Project State Inpatient Database from 2016.
Biochim Biophys Acta Gen Subj
February 2021
Background: Metastasis and mortality remain high among breast cancer patients with the claudin-low subtype because these tumors are aggressive, chemoresistant, and lack targeted therapies. Our objective was to utilize discovery-based proteomics to identify proteins associated with claudin-low primary and metastatic tumors to gain insight into pathways and mechanisms of tumor progression.
Methods: We used nano-LC-MS/MS proteomics to analyze orthotopic and metastatic tumors from the syngeneic murine T11 tumor model, which displays gene expression profiles mirroring human claudin-low tumors.
Cancer Epidemiol Biomarkers Prev
May 2020
Background: Reduction in breast density may be a biomarker of endocrine therapy (ET) efficacy. Our objective was to assess the impact of race on ET-related changes in volumetric breast density (VBD).
Methods: This retrospective cohort study assessed longitudinal changes in VBD measures in women with estrogen receptor-positive invasive breast cancer treated with ET.
Purpose: Compared with their European American (EA) counterparts, African American (AA) women are more likely to die from breast cancer in the United States. This disparity is greatest in hormone receptor-positive subtypes. Here we uncover biological factors underlying this disparity by comparing functional expression and prognostic significance of master transcriptional regulators of luminal differentiation.
View Article and Find Full Text PDFBreast Cancer Res Treat
October 2019
Purpose: The relationship between age at diagnosis and breast cancer-specific mortality (BCSM) is unclear. The aim of this study was to examine the nature of this relationship using rigorous statistical methodology.
Methods: A historical cohort study of adult women with invasive breast cancer in the SEER database from 2000 to 2015 was conducted.
Purpose: Current NCCN guidelines for occult breast cancer (OBC) recommend modified radical mastectomy, with the option for breast preservation with radiation instead of mastectomy for N1 patients. Our aim was to compare the effect of local therapy-mastectomy versus breast radiation-on breast cancer-specific mortality (BCSM) in a contemporary cohort of OBC patients of all nodal stages.
Methods: Competing risk analyses were performed to evaluate the effect of local therapy, nodal stage, and other demographic and clinical prognostic variables on risk of BCSM for women registered in the SEER database with T0N+M0 breast cancer from 2004 to 2015.
Background: In part because of improvements in early detection and treatment, the number of breast cancer survivors is increasing. After treatment, however, breast cancer survivors often experience distressing symptoms, including pain, sleep disturbance, anxiety, and fatigue; at the same time, they have less frequent contact with health care providers. Pain commonly co-occurs with other symptoms and the combination of symptoms contribute to the amount of distress experienced by survivors.
View Article and Find Full Text PDFBackground: Inflammatory breast cancer (IBC) is a rare but most aggressive breast cancer subtype. The impact of locoregional therapy on survival in IBC is controversial.
Methods: Patients with nonmetastatic IBC between 1988 and 2013 were identified in the Surveillance, Epidemiology, and End Results (SEER) registry.
Primary tumor resection (PTR) in metastatic breast cancer is not a standard treatment modality, and its impact on survival is conflicting. The primary objective of this study was to analyze impact of PTR on survival in metastatic patients with breast cancer. A retrospective study of metastatic patients with breast cancer was conducted using the 1988-2011 Surveillance, Epidemiology, and End Results (SEER) data base.
View Article and Find Full Text PDFPurpose: Obesity and breast density are both associated with an increased risk of breast cancer and are potentially modifiable. Weight loss surgery (WLS) causes a significant reduction in the amount of body fat and a decrease in breast cancer risk. The effect of WLS on breast density and its components has not been documented.
View Article and Find Full Text PDFThe role of surgical resection in low-grade pancreatic neuroendocrine tumors (P-NET) is unclear. The patients diagnosed with low-grade P-NET from 1988 to 2012 were identified in SEER. Five hundred and sixty-one patients met the inclusion criteria.
View Article and Find Full Text PDFReadmission rates after pancreaticoduodenectomy (PD) are among the highest of any surgical procedure. The purpose of this study was to identify those factors present at discharge that may predict readmission after PD. All patients undergoing PD between 2010 and 2015 at a very high (>35 PD/year) volume center were entered into a prospective database.
View Article and Find Full Text PDFBenefits of ERAS protocol have been well documented; however, it is unclear whether the improvement stems from the protocol or shifts in expectations. Interdisciplinary educational seminars were conducted for all health professionals. However, one test surgeon adopted the protocol.
View Article and Find Full Text PDFBackground: The accurate diagnosis of malnutrition is imperative if we are to impact outcomes in the malnourished. The American Society of Parenteral and Enteral Nutrition (ASPEN) and Academy of Nutrition and Dietetics (AND), in an attempt to address this issue, have provided evidence-based criteria to diagnose malnutrition. The purpose of this study was to validate the ASPEN/AND criteria in a cohort of patients from a single high-volume surgical oncology unit.
View Article and Find Full Text PDFBackground: The impact of radiotherapy on local control in limb-preserving surgery for high-risk sarcoma has been well studied. However, the impact of the use and timing of radiation therapy on survival is unclear.
Methods: From 1988 to 2010, patients with Stage III extremity sarcoma were identified within the SEER registry and cohorts were created using propensity score matching between irradiated and non-irradiated groups.
Merkel cell carcinoma is a cutaneous neuroendocrine neoplasm that has been poorly studied in contemporary cohorts. Patients with Merkel cell carcinoma from 1986 to 2011 were identified in the Surveillance Epidemiology and End Results registry. A total of 5211 patients met the inclusion criteria.
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