HuR Plays a Role in Double-Strand Break Repair in Pancreatic Cancer Cells and Regulates Functional BRCA1-Associated-Ring-Domain-1(BARD1) Isoforms.

Human Antigen R (HuR/ELAVL1) is known to regulate stability of mRNAs involved in pancreatic ductal adenocarcinoma (PDAC) cell survival. Although several HuR targets are established, it is likely that many remain currently unknown. Here, we identified BARD1 mRNA as a novel target of HuR.

Cancer Modeling as Learning Experience.

Cancer modeling has become an accepted method for generating evidence about comparative effectiveness and cost-effectiveness of candidate cancer control policies across the continuum of care. Models of early detection policies require inputs concerning disease natural history and screening test performance, which are often subject to considerable uncertainty. Model validation against an external data source can increase confidence in the reliability of assumed or calibrated inputs.

Single-cell spatial architectures associated with clinical outcome in head and neck squamous cell carcinoma.

There is increasing evidence that the spatial organization of cells within the tumor-immune microenvironment (TiME) of solid tumors influences survival and response to therapy in numerous cancer types. Here, we report results and demonstrate the applicability of quantitative single-cell spatial proteomics analyses in the TiME of primary and recurrent human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) tumors. Single-cell compositions of a nine patient, primary and recurrent (n = 18), HNSCC cohort is presented, followed by deeper investigation into the spatial architecture of the TiME and its relationship with clinical variables and progression free survival (PFS).

Molecular and Clinical Characterization of Postpartum-Associated Breast Cancer in the Carolina Breast Cancer Study Phase I-III, 1993-2013.

Background: Breast cancers in recently postpartum women may have worse outcomes, but studies examining tumor molecular features by pregnancy recency have shown conflicting results.

Methods: This analysis used Carolina Breast Cancer Study data to examine clinical and molecular tumor features among women less than 50 years of age who were recently (≤10 years prior) or remotely (>10 years prior) postpartum, or nulliparous. Prevalence odds ratios (POR) and 95% confidence intervals (CI) were estimated using multivariable models.

Label-free enrichment of rare unconventional circulating neoplastic cells using a microfluidic dielectrophoretic sorting device.

Cellular circulating biomarkers from the primary tumor such as circulating tumor cells (CTCs) and circulating hybrid cells (CHCs) have been described to harbor tumor-like phenotype and genotype. CHCs are present in higher numbers than CTCs supporting their translational potential. Methods for isolation of CHCs do not exist and are restricted to low-throughput, time consuming, and biased methodologies.

Geographic Disparities in Referral Rates and Oncologic Outcomes of Intrahepatic Cholangiocarcinoma: A Population-Based Study.

Background: Intrahepatic cholangiocarcinoma (ICC) is a rare cancer. Patients in rural areas may face reduced access to advanced treatments often only available at referral centers. We evaluated the association of referral center treatment with treatment patterns, outcomes, and geography in patients with ICC.

Relevance of circulating hybrid cells as a non-invasive biomarker for myriad solid tumors.

Metastatic progression defines the final stages of tumor evolution and underlies the majority of cancer-related deaths. The heterogeneity in disseminated tumor cell populations capable of seeding and growing in distant organ sites contributes to the development of treatment resistant disease. We recently reported the identification of a novel tumor-derived cell population, circulating hybrid cells (CHCs), harboring attributes from both macrophages and neoplastic cells, including functional characteristics important to metastatic spread.

Degree of biliary tract violation during treatment of gallbladder adenocarcinoma is independently associated with development of peritoneal carcinomatosis.

Background: Gallbladder cancer (GBC) is often incidentally diagnosed after cholecystectomy. Intra-operative biliary tract violations (BTV) have been recently associated with development of peritoneal disease (PD). The degree of BTV may be associated with PD risk, but has not been previously investigated.

Imatinib-resistant gastrointestinal stromal tumors in the era of second- and third-line tyrosine kinase inhibitors: Does surgical resection have a role?

Background: Imatinib resistance is associated with a poor prognosis in patients with gastrointestinal stromal tumors. Although novel tyrosine kinase inhibitors have improved outcomes in imatinib-resistant gastrointestinal stromal tumors, the role of resection remains unclear. We sought to investigate factors predictive of overall and progression-free survival in patients with imatinib-resistant gastrointestinal stromal tumors.

Galaxy-ML: An accessible, reproducible, and scalable machine learning toolkit for biomedicine.

Supervised machine learning is an essential but difficult to use approach in biomedical data analysis. The Galaxy-ML toolkit (https://galaxyproject.org/community/machine-learning/) makes supervised machine learning more accessible to biomedical scientists by enabling them to perform end-to-end reproducible machine learning analyses at large scale using only a web browser.

Disease-free Interval Is Associated with Oncologic Outcomes in Patients with Recurrent Gastrointestinal Stromal Tumor.

Background: Gastrointestinal stromal tumors (GIST) commonly recur following curative-intent resection. Patients with recurrent GIST display heterogeneous outcomes with limited prognostic tools. We investigated factors associated with post-recurrence survival (PRS) and progression-free survival (PFS).

Oncologic outcomes in resected ampullary cancer: Relevance of histologic subtype and adjuvant chemotherapy.

Background: Outcomes in ampullary cancer (AC) may differ by pathologic subtype. No guidelines exist for the administration of adjuvant therapy (AT). We sought to evaluate the effect of subtype and AT on survival.

Maternal Prenatal Hair Cortisol Is Associated with Child Wheeze among Mothers and Infants with Tobacco Smoke Exposure and Who Face High Socioeconomic Adversity.

The association of co-occurring prenatal stress and tobacco exposures on childhood wheezing and asthma are not well established. In this study, we compared maternal prenatal hair cortisol concentration (HCC) to the maternal report of infant wheezing (y/n) in the first year of life among mother-infant dyads exposed to tobacco smoke and socioeconomic adversity. Data were obtained from the Vitamin C to Decrease Effects of Smoking in Pregnancy on Infant Lung Function study.

Surgical and oncologic outcomes following repeat hepatic resection of colorectal liver metastasis: Who benefits?

Background: Resected colorectal liver metastases (CRLM) frequently recur intrahepatically. Selection criteria for repeat hepatectomy of recurrent CRLM are ill-defined.

Methods: We performed an institutional review of patients with recurrent CRLM undergoing repeat hepatectomy from 2003 to 19.

Neoadjuvant chemotherapy is associated with improved survival in patients undergoing hepatic resection for intrahepatic cholangiocarcinoma.

Background: The impact of neoadjuvant chemotherapy (NAC) on overall and recurrence-free survival (OS, RFS) in resectable intrahepatic cholangiocarcinoma (ICC) is poorly characterized. We sought to investigate the association of NAC with oncologic outcomes in ICC.

Methods: We identified n = 52 patients with ICC undergoing hepatectomy from 2004 to 2017.

Conventional hepatic arterial anatomy? Novel findings and insights of a multi-disciplinary hepatic arterial infusion pump program.

Introduction: Variant hepatic arterial anatomy (vHAA) is thought to occur in 20-30% of patients. Hepatic arterial infusion (HAI) pump placement for liver cancers requires thorough hepatic artery dissection; we sought to compare vHAA identified during pump placement with established dogma.

Methods: Between 2016 and 2020, n = 30 patients received a HAI pump.

A Dermatologist's Guide to Implementation of Gene Expression Profiling in the Management of Melanoma.

With the advent of effective therapeutics, melanoma mortality rates have decreased, yet incidence rates are continuing to rise, making accurate prognostication for risk of recurrence increasingly important. Gene expression profiling (GEP) is a clinically available, objective metric that can be used in conjunction with traditional clinicopathological staging to help physicians stratify risk in melanoma patients. There is a gap in guidance from the American Joint Committee on Cancer (AJCC) and the National Comprehensive Cancer Network (NCCN) regarding how to utilize GEP in melanoma care.

Dielectrophoresis: Developments and applications from 2010 to 2020.

The 20th century has seen tremendous innovation of dielectrophoresis (DEP) technologies, with applications being developed in areas ranging from industrial processing to micro- and nanoscale biotechnology. From 2010 to present day, there have been 981 publications about DEP. Of over 2600 DEP patents held by the United States Patent and Trademark Office, 106 were filed in 2019 alone.

Lamellipodia-like protrusions and focal adhesions contribute to collective cell migration in zebrafish.

Collective cell migration is a process where cohorts of cells exhibit coordinated migratory behavior. During individual and collective cellular migration, cells must extend protrusions to interact with the extracellular environment, sense chemotactic cues, and act as points of attachment. The mechanisms and regulators of protrusive behavior have been widely studied in individually migrating cells; however, how this behavior is regulated throughout collectives is not well understood.

Tricalcium phosphate cement supplemented with boron nitride nanotubes with enhanced biological properties.

A self-setting bone cement containing β-tricalcium phosphate (TCP) supplemented with boron nitride nanotubes (BNNTs, 1 wt%) was synthesized and analyzed in situ for its kinetics of hardening and selected physicochemical and biological properties. Moderately delayed due to the presence of BNNTs, the hardening reaction involved the transformation of the TCP precursor to the dicalcium phosphate (DCPD) product. In spite of the short-lived chemical transformations in the cement upon its hardening, the structural changes in it were extended.

Targeting Extracellular Matrix Remodeling Restores BRAF Inhibitor Sensitivity in BRAFi-resistant Melanoma.

Purpose: The extracellular matrix (ECM) is an intriguing, yet understudied component of therapy resistance. Here, we investigated the role of ECM remodeling by the collagenase, MT1-MMP, in conferring resistance of v-Raf murine sarcoma viral oncogene homolog B1 (BRAF)-mutant melanoma to BRAF inhibitor (BRAFi) therapy.

Experimental Design: Publicly available RNA-sequencing data and reverse phase protein array were used to determine the relevance of MT1-MMP upregulation in BRAFi-resistant melanoma in patients, patient-derived xenografts, and cell line-derived tumors.