Comparison of efficacy and toxicity of chemoradiation regimens for head and neck squamous cell carcinoma primary treatment.

Background: The best chemoradiation regimen to treat locally and regionally advanced head and neck squamous cell carcinoma (HNSCC) is yet to be established.

Methods: We compared overall survival (OS) and adverse events following chemoradiation regimens (high-dose [HDC] or low-dose [LDC] cisplatin, or carboplatin [CB]) in HNSCC cases selected from SEER-Medicare linked database.

Results: Of the 1335 cases who underwent radiotherapy, 264 received HDC, 259 received LDC, and 353 received CB, concurrently.

Adherence to Guideline-Concordant Care and Its Effect on Survival in Black Patients with Head and Neck Cancers: A SEER-Medicare Analysis.

Background: In head and neck squamous cell carcinoma (HNSCC), Black patients continue to have worse survival when compared with White patients. The cause of this disparity is multifaceted and cannot be explained by one etiology alone. To investigate this disparity, we used the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database to examine adherence to guideline-concordant care (GCC) as defined by the National Comprehensive Cancer Network.

Draft Genome Sequence of Pseudomonas aeruginosa Strain PA14-UM.

is a Gram-negative nosocomial pathogen that is a leading cause of morbidity and mortality in cystic fibrosis patients and immunocompromised individuals worldwide. The isolate examined in this study, PA14-UM, is a well-characterized isolate utilized in studies from the University of Maryland.

Decreased nonspecific adhesivity, receptor-targeted therapeutic nanoparticles for primary and metastatic breast cancer.

Development of effective tumor cell-targeted nanodrug formulations has been quite challenging, as many nanocarriers and targeting moieties exhibit nonspecific binding to cellular, extracellular, and intravascular components. We have developed a therapeutic nanoparticle formulation approach that balances cell surface receptor-specific binding affinity while maintaining minimal interactions with blood and tumor tissue components (termed "DART" nanoparticles), thereby improving blood circulation time, biodistribution, and tumor cell-specific uptake. Here, we report that paclitaxel (PTX)-DART nanoparticles directed to the cell surface receptor fibroblast growth factor-inducible 14 (Fn14) outperformed both the corresponding PTX-loaded, nontargeted nanoparticles and Abraxane, an FDA-approved PTX nanoformulation, in both a primary triple-negative breast cancer (TNBC) model and an intracranial model reflecting TNBC growth following metastatic dissemination to the brain.

Definitive radiation with concurrent cetuximab vs. radiation with or without concurrent cytotoxic chemotherapy in older patients with squamous cell carcinoma of the head and neck: Analysis of the SEER-medicare linked database.

Objective: To evaluate OS and toxicity after definitive radiation with concurrent cetuximab (CTX-RT) compared to radiation with concurrent cytotoxic chemotherapy (CRT) in older HNSCC patients via the SEER-Medicare linked database.

Materials And Methods: We used the SEER-Medicare linked database to evaluate OS in HNSCC patients (Oropharynx, Larynx, Hypopharynx, Nasopharynx) diagnosed over 2005-2011, following FDA approval of cetuximab in combination with radiation therapy (RT) in March 2006.

Results: 2135 beneficiaries were identified.

Ultrasound use during cardiopulmonary resuscitation is associated with delays in chest compressions.

Aim: High-quality chest compressions are a critical component of the resuscitation of patients in cardiopulmonary arrest. Point-of-care ultrasound (POCUS) is used frequently during emergency department (ED) resuscitations, but there has been limited research assessing its benefits and harms during the delivery of cardiopulmonary resuscitation (CPR). We hypothesized that use of POCUS during cardiac arrest resuscitation adversely affects high-quality CPR by lengthening the duration of pulse checks beyond the current cardiopulmonary resuscitation guidelines recommendation of 10s.

Non-specific binding and steric hindrance thresholds for penetration of particulate drug carriers within tumor tissue.

Therapeutic nanoparticles (NPs) approved for clinical use in solid tumor therapy provide only modest improvements in patient survival, in part due to physiological barriers that limit delivery of the particles throughout the entire tumor. Here, we explore the thresholds for NP size and surface poly(ethylene glycol) (PEG) density for penetration within tumor tissue extracellular matrix (ECM). We found that NPs as large as 62nm, but less than 110nm in diameter, diffused rapidly within a tumor ECM preparation (Matrigel) and breast tumor xenograft slices ex vivo.

Patient-reported Adherence to Adjuvant Aromatase Inhibitor Therapy Using the Morisky Medication Adherence Scale: An Evaluation of Predictors.

Objectives: Endocrine therapy is part of standard adjuvant therapy for patients with hormone receptor-positive breast cancer and has been shown to improve recurrence-free and overall survival. However, adherence to endocrine therapy is suboptimal and is difficult to measure. In this study we evaluate the feasibility of using the Morisky Medication Adherence Scale (MMAS) to assess patient adherence to aromatase inhibitor (AI) therapy.

Upregulation of Cyclooxygenase-2/Prostaglandin E2 (COX-2/PGE2) Pathway Member Multiple Drug Resistance-Associated Protein 4 (MRP4) and Downregulation of Prostaglandin Transporter (PGT) and 15-Prostaglandin Dehydrogenase (15-PGDH) in Triple-Negative Breast Cancer.

Elevated levels of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) are indicators of a poor prognosis in breast cancer. Using several independent publicly available breast cancer gene expression databases, we investigated other members of the PGE2 pathway. PGE2 is produced by COX-2 and actively exported by multiple drug resistance-associated protein 4 (MRP4) into the extracellular microenvironment, where PGE2 can bind four cognate EP receptors (EP1-EP4) and initiate diverse biological signaling pathways.

The RUNX2 Transcription Factor Negatively Regulates SIRT6 Expression to Alter Glucose Metabolism in Breast Cancer Cells.

Activation of genes promoting aerobic glycolysis and suppression of mitochondrial oxidative phosphorylation is one of the hallmarks of cancer. The RUNX2 transcription factor mediates breast cancer (BC) metastasis to bone and is regulated by glucose availability. But, the mechanisms by which it regulates glucose metabolism and promotes an oncogenic phenotype are not known.

α-Tubulin acetylation elevated in metastatic and basal-like breast cancer cells promotes microtentacle formation, adhesion, and invasive migration.

Metastatic cases of breast cancer pose the primary challenge in clinical management of this disease, demanding the identification of effective therapeutic strategies that remain wanting. In this study, we report that elevated levels of α-tubulin acetylation are a sufficient cause of metastatic potential in breast cancer. In suspended cell culture conditions, metastatic breast cancer cells exhibited high α-tubulin acetylation levels that extended along microtentacle (McTN) protrusions.

Disparities in black and white patients with multiple myeloma referred for autologous hematopoietic transplantation: a single center study.

Background: Racial disparity in the incidence of multiple myeloma is well established; however, to the authors' knowledge, little is known regarding the impact of racial differences on disease characteristics, response to therapy, and clinical outcome.

Methods: The authors studied 453 patients (174 of whom were black and 279 of whom were white) who underwent transplant between 2000 and 2013. The median follow-up was 4.

Emergence of HPV16-positive oropharyngeal cancer in Black patients over time: University of Maryland 1992-2007.

While we previously reported a striking racial difference in the prevalence of human papilloma virus (HPV)-positive squamous cell carcinoma of the oropharynx (OPSCC), less is known about differences in outcomes and trends over time in OPSCC by HPV status and race. We conducted a retrospective analysis of 467 patients with OPSCC treated at the University of Maryland Greenebaum Cancer Center (Baltimore, MD) between 1992 and 2007, of which 200 had tissue available for HPV16 testing. HPV16-positive patients were significantly more likely to be white, with 45.

HDAC inhibitor entinostat restores responsiveness of letrozole-resistant MCF-7Ca xenografts to aromatase inhibitors through modulation of Her-2.

We previously showed that in innately resistant tumors, silencing of the estrogen receptor (ER) could be reversed by treatment with a histone deacetylase (HDAC) inhibitor, entinostat. Tumors were then responsive to aromatase inhibitor (AI) letrozole. Here, we investigated whether ER in the acquired letrozole-resistant tumors could be restored with entinostat.

Metformin prevents liver tumorigenesis by inhibiting pathways driving hepatic lipogenesis.

A number of factors have been identified that increase the risk of hepatocellular carcinoma (HCC). Recently it has become appreciated that type II diabetes increases the risk of developing HCC. This represents a patient population that can be identified and targeted for cancer prevention.

Computer assisted quantitative immunofluorescence of tumor tissue marker expression and clinical outcome to chemotherapy in advanced breast cancer patients.

Chemotherapy is frequently used in the treatment of advanced breast cancer. The identification of patient-specific tumor characteristics that can improve the ability to predict response to chemotherapy would help optimize advanced breast cancer treatment approaches. Quantitative immunofluorescence (QIF) may be applied to the standardization of protein analysis, resulting in increased sensitivity and reproducibility.

Combination of anastrozole with fulvestrant in the intratumoral aromatase xenograft model.

Although the aromatase inhibitor anastrozole has been shown to be very effective in the treatment of hormone-dependent postmenopausal breast cancer, some patients with advanced disease will develop resistance to treatment. To investigate therapeutic strategies to overcome resistance to anastrozole treatment, we have used an intratumoral aromatase model that simulates postmenopausal breast cancer patients with estrogen-dependent tumors. Growth of the tumors in the mice was inhibited by both anastrozole and fulvestrant compared with the control tumors.

Germinal center function in the spleen during simian HIV infection in rhesus monkeys.

Infection with HIV-1, SIV, or simian HIV is associated with abnormalities in the number, size, and structure of germinal centers (GCs). To determine whether these histopathologic abnormalities are associated with abnormalities in Ab development, we analyzed nucleotide sequences of Igs from splenic GCs of simian HIV-infected macaques. Virus-specific GCs were identified in frozen splenic tissue sections by inverse immunohistochemistry using rHIV-1 gp120 as a probe.

Mitochondrial DNA content increase in response to cigarette smoking.

An increase in mitochondrial DNA (mtDNA) content and decline in mitochondrial function occurs with aging and in response to DNA-damaging agents, including tobacco smoke. We did a cross-sectional study and quantified changes in mtDNA content in a population of individuals with varied smoking and alcohol exposure. Age, smoking history, ethanol intake, and other demographic data were characterized for 604 individuals participating in a screening study for smoking-related upper aerodigestive malignancy.

Additive antitumor effect of aromatase inhibitor letrozole and antiestrogen fulvestrant in a postmenopausal breast cancer model.

Blocking estrogen receptors with antiestrogens and blocking estrogen synthesis with aromatase inhibitors are two strategies currently being used for reducing the effect of estrogen in postmenopausal estrogen receptor-positive breast cancer patients. To optimize these treatment strategies, we have investigated whether tumor progression can be delayed by combining the pure antiestrogen fulvestrant with the nonsteroidal aromatase inhibitor letrozole. These studies were done in ovariectomized, athymic mice bearing tumors of estrogen receptor-positive human breast cancer cells stably transfected with the aromatase gene (MCF-7Ca).

Activation of mitogen-activated protein kinase in xenografts and cells during prolonged treatment with aromatase inhibitor letrozole.

Ovariectomized mice bearing tumor xenografts grown from aromatase-transfected estrogen receptor (ER)-positive human breast cancer cells (MCF-7Ca) were injected s.c. with 10 microg/d letrozole for up to 56 weeks.

Phase I clinical trial of the inosine monophosphate dehydrogenase inhibitor mycophenolate mofetil (cellcept) in advanced multiple myeloma patients.

Purpose: Inosine monophosphate dehydrogenase (IMPDH) inhibitors have been used to induce leukemia blast cell differentiation but have not been tested in multiple myeloma for activity. Currently, available IMPDH inhibitor, mycophenolate mofetil (MMF), which is known as an immunosuppressant, was shown to induce apoptosis in myeloma cell lines. On the basis of our preclinical studies, we designed a clinical study to test our hypothesis that MMF has antimyeloma activity.