Pan-tissue mitochondrial phenotyping reveals lower OXPHOS expression and function across cancer types.

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.

The North Carolina Tissue Consortium: Ensuring Equitable Representation and Accessibility to Cancer Specimens from Eastern North Carolina.

The 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.

Bioenergetic Phenotyping of DEN-Induced Hepatocellular Carcinoma Reveals a Link Between Adenylate Kinase Isoform Expression and Reduced Complex I-Supported Respiration.

Hepatocellular 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.

Protein expression of the gp78 E3 ligase predicts poor breast cancer outcome based on race.

Women of African ancestry suffer higher rates of breast cancer mortality compared with all other groups in the United States. Though the precise reasons for these disparities remain unclear, many recent studies have implicated a role for differences in tumor biology. Using an epitope-validated antibody against the endoplasmic reticulum-associated E3 ligase, gp78, we show that elevated levels of gp78 in patient breast cancer cells predict poor survival.

Pathobiologic Stratification of Oncotype DX Recurrence Scores and Comparative Validation of 3 Surrogate Models.

Context.—: The Oncotype DX Recurrence Score (RS) predicts recurrence and chemotherapy benefit in early-stage estrogen receptor-positive breast cancer patients. Cost and unavailability are 2 major disadvantages of the assay.

Racial Disparity in the Surgical Management of Diverticular Disease.

Introduction: Although minimally invasive surgery (MIS) has clearly been associated with improved colorectal surgery outcomes, not all populations benefit from this approach. Using a national database, we analyzed both, the trend in the utilization of MIS for diverticulitis and differences in utilization by race.

Methods: Colon-targeted participant user files (PUFs) from 2012 to 18 were linked to respective PUFs in National Surgical Quality Improvement Project.

Improvement in Surgical Quality Following Pancreaticoduodenectomy With Increasing Case Volume in a Rural Hospital.

Background: 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.

Refining breast cancer prognosis by incorporating age at diagnosis into clinical prognostic staging: introduction of a novel online calculator.

Purpose: 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.

Kaiso (ZBTB33) subcellular partitioning functionally links LC3A/B, the tumor microenvironment, and breast cancer survival.

The use of digital pathology for the histomorphologic profiling of pathological specimens is expanding the precision and specificity of quantitative tissue analysis at an unprecedented scale; thus, enabling the discovery of new and functionally relevant histological features of both predictive and prognostic significance. In this study, we apply quantitative automated image processing and computational methods to profile the subcellular distribution of the multi-functional transcriptional regulator, Kaiso (ZBTB33), in the tumors of a large racially diverse breast cancer cohort from a designated health disparities region in the United States. Multiplex multivariate analysis of the association of Kaiso's subcellular distribution with other breast cancer biomarkers reveals novel functional and predictive linkages between Kaiso and the autophagy-related proteins, LC3A/B, that are associated with features of the tumor immune microenvironment, survival, and race.

A case of the world's largest renal cell carcinoma.

Introduction: Renal cell carcinoma is often discovered at an early stage due to the increased use of imaging studies in the current era; therefore, its presentation as a gigantic renal cell carcinoma is rarely encountered.

Case Presentation: A 59-year-old male presented to our hospital due to dizziness, fatigue, and increasing abdominal distension. A computed tomography scan showed an extremely large mass occupying most of the abdomen and pelvis.

Development and Assessment of a Systematic Approach for Detecting Disparities in Surgical Access.

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.

Proteomic identification of tumor- and metastasis-associated galectin-1 in claudin-low breast cancer.

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.

Race May Not Impact Endocrine Therapy-Related Changes in Breast Density.

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.

Racial Differences in the Association Between Luminal Master Regulator Gene Expression Levels and Breast Cancer Survival.

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.

Epigenetic re-wiring of breast cancer by pharmacological targeting of C-terminal binding protein.

The C-terminal binding protein (CtBP) is an NADH-dependent dimeric family of nuclear proteins that scaffold interactions between transcriptional regulators and chromatin-modifying complexes. Its association with poor survival in several cancers implicates CtBP as a promising target for pharmacological intervention. We employed computer-assisted drug design to search for CtBP inhibitors, using quantitative structure-activity relationship (QSAR) modeling and docking.

Quantifying the relationship between age at diagnosis and breast cancer-specific mortality.

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.

The effect of local therapy on breast cancer-specific mortality of women with occult breast cancer and advanced nodal disease (N2/N3): a population analysis.

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.

Post-Treatment Symptoms of Pain, Anxiety, Sleep Disturbance, and Fatigue in Breast Cancer Survivors.

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.

The Impact of Locoregional Therapy in Nonmetastatic Inflammatory Breast Cancer: A Population-Based Study.

Background: 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 in metastatic breast cancer: A propensity-matched analysis, 1988-2011 SEER data base.

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.

An Evaluation of a Rural Community-Based Breast Education and Navigation Program: Highlights and Lessons Learned.

Cancer has become the leading cause of death in North Carolina (NC) (North Carolina DHHS, State Center for Health Statistics 2015) and the eastern region of North Carolina (ENC) has experienced greater cancer mortality than the remainder of the state. The Pitt County Breast Wellness Initiative-Education (PCBWI-E) provides culturally tailored breast cancer education and navigation to screening services for uninsured/underinsured women in Pitt and Edgecombe Counties in ENC. PCBWI-E created a network of 23 lay breast health educators, and has educated 735 women on breast health and breast cancer screening guidelines.