Cervical cancer worry and screening among appalachian women.

Although many have sought to understand cervical cancer screening (CCS) behavior, little research has examined worry about cervical cancer and its relationship to CCS, particularly in the underserved, predominantly rural Appalachian region. Our mixed method investigation aimed to obtain a more complete and theoretically-informed understanding of the role of cancer worry in CCS among Appalachian women, using the Self-Regulation Model (SRM). Our quantitative analysis indicated that the perception of being at higher risk of cervical cancer and having greater distress about cancer were both associated with greater worry about cancer.

Carbon nanotubes induce apoptosis resistance of human lung epithelial cells through FLICE-inhibitory protein.

Chronic exposure to single-walled carbon nanotubes (SWCNT) has been reported to induce apoptosis resistance of human lung epithelial cells. As resistance to apoptosis is a foundation of neoplastic transformation and cancer development, we evaluated the apoptosis resistance characteristic of the exposed lung cells to understand the pathogenesis mechanism. Passage control and SWCNT-transformed human lung epithelial cells were treated with known inducers of apoptosis via the intrinsic (antimycin A and CDDP) or extrinsic (FasL and TNF-α) pathway and analyzed for apoptosis by DNA fragmentation, annexin-V expression, and caspase activation assays.

Survey of Patients Referred to a University Cancer Center for Benign Hematology: Quality Measures and Patient Understanding.

Objective: To investigate patients' knowledge and understanding of benign hematology and the potential psychological impact that is associated with referral to outpatient clinics.

Methods: At Mary Babb Randolph Cancer Center, an anonymous and voluntary survey including 28 questions was designed on the basis of information obtained from a single focus group. A participatory pilot survey was performed with 10 patients followed by a full-scale survey from May until November 2013.

Network-based identification of biomarkers coexpressed with multiple pathways.

Unraveling complex molecular interactions and networks and incorporating clinical information in modeling will present a paradigm shift in molecular medicine. Embedding biological relevance via modeling molecular networks and pathways has become increasingly important for biomarker identification in cancer susceptibility and metastasis studies. Here, we give a comprehensive overview of computational methods used for biomarker identification, and provide a performance comparison of several network models used in studies of cancer susceptibility, disease progression, and prognostication.

Integrated DNA Copy Number and Gene Expression Regulatory Network Analysis of Non-small Cell Lung Cancer Metastasis.

Integrative analysis of multi-level molecular profiles can distinguish interactions that cannot be revealed based on one kind of data in the analysis of cancer susceptibility and metastasis. DNA copy number variations (CNVs) are common in cancer cells, and their role in cell behaviors and relationship to gene expression (GE) is poorly understood. An integrative analysis of CNV and genome-wide mRNA expression can discover copy number alterations and their possible regulatory effects on GE.

Sorafenib and thyroid cancer.

The emergence of serine-threonine small molecule, multi-targeted kinase inhibitors over the past decade is greatly impacting the therapeutic armamentarium for numerous malignancies, especially thyroid carcinoma. Chief among them are a class of agents referred to as vascular endothelial growth factor signal pathway inhibitors. Sorafenib is a lead compound that has been recently approved by the US FDA for radioactive iodine-refractory differentiated thyroid cancer (DTC).

The utility of positron emission tomography in the treatment planning of image-guided radiotherapy for non-small cell lung cancer.

In the thorax, the extent of tumor may be more accurately defined with the addition of (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) to computed tomography (CT). This led to the increased utility of FDG-PET or PET/CT in the treatment planning of radiotherapy for non-small cell lung cancer (NSCLC). The inclusion of FDG-PET information in target volume delineation not only improves tumor localization but also decreases the amount of normal tissue included in the planning target volume (PTV) in selected patients.

NEDD9/Arf6-dependent endocytic trafficking of matrix metalloproteinase 14: a novel mechanism for blocking mesenchymal cell invasion and metastasis of breast cancer.

NEDD9 is an established marker of invasive and metastatic cancers. NEDD9 downregulation has been shown to dramatically reduce cell invasion and metastasis in multiple tumors. The mechanisms by which NEDD9 regulates invasion are largely unknown.

Cancer treatment-related cardiotoxicity: current state of knowledge and future research priorities.

Cardiotoxicity resulting from direct myocyte damage has been a known complication of cancer treatment for decades. More recently, the emergence of hypertension as a clinically significant side effect of several new agents has been recognized as adversely affecting cancer treatment outcomes. With cancer patients living longer, in part because of treatment advances, these adverse events have become increasingly important to address.

MicroRNAs 206 and 21 cooperate to promote RAS-extracellular signal-regulated kinase signaling by suppressing the translation of RASA1 and SPRED1.

Despite the low prevalence of activating point mutation of RAS or RAF genes, the RAS-extracellular signal-regulated kinase (ERK) pathway is implicated in breast cancer pathogenesis. Indeed, in triple-negative breast cancer (TNBC), there is recurrent genetic alteration of pathway components. Using short hairpin RNA (shRNA) methods, we observed that the zinc finger transcription factor Krüppel-like factor 4 (KLF4) can promote RAS-ERK signaling in TNBC cells.

PSP94, an upstream signaling mediator of prostasin found highly elevated in ovarian cancer.

Ovarian cancer is a leading cause of cancer death as diagnosis is frequently delayed to an advanced stage. Effective biomarkers and screening strategies for early detection are urgently needed. In the current study, we identify PSP94 as a key upstream factor in mediating prostasin (a protein previously reported to be overexpressed in ovarian cancer) signaling that regulates prostasin expression and action in ovarian cancer cells.

In silico model-based inference: a contemporary approach for hypothesis testing in network biology.

Inductive inference plays a central role in the study of biological systems where one aims to increase their understanding of the system by reasoning backwards from uncertain observations to identify causal relationships among components of the system. These causal relationships are postulated from prior knowledge as a hypothesis or simply a model. Experiments are designed to test the model.

4D PET/CT as a Strategy to Reduce Respiratory Motion Artifacts in FDG-PET/CT.

The improved accuracy in tumor identification with FDG-PET has led to its increased utilization in target volume delineation for radiotherapy treatment planning in the treatment of lung cancer. However, PET/CT has constantly been influenced by respiratory motion-related image degradation, which is especially prominent for small lung tumors in the peri-diaphragmatic regions of the thorax. Here, we describe the current findings on respiratory motion-related image degradation in PET/CT, which may bring uncertainties to target volume delineation for image guided radiotherapy (IGRT) for lung cancer.

An exploratory phase 2 study of investigational Aurora A kinase inhibitor alisertib (MLN8237) in acute myelogenous leukemia and myelodysplastic syndromes.

Alisertib (MLN8237) is an investigational, oral, selective, Aurora A kinase (AAK) inhibitor. In this phase 2 trial, 57 patients with acute myeloid leukemia (AML) or high-grade myelodysplastic syndrome received alisertib 50 mg BID for 7 days in 21-day cycles. Responses in 6/35 AML patients (17% response rate with an additional 49% stable disease, 34% transfusion independence) included 1 complete response lasting >1 year.

Phase II study of bortezomib in combination with rituximab, cyclophosphamide and prednisone with or without doxorubicin followed by rituximab maintenance in patients with relapsed or refractory follicular lymphoma.

This non-comparative phase II study (ClinicalTrials.gov: NCT00715208) evaluated bortezomib in place of vincristine in established rituximab-chemotherapy regimens in relapsed/refractory follicular (FL) or marginal zone lymphoma (MZL). Patients were allocated (physician/patient preference) to receive six 21-d cycles of: bortezomib 1·6 mg/m(2) (days 1, 8), rituximab 375 mg/m(2) (day 1), cyclophosphamide 1000 mg/m(2) (day 1) and prednisone 100 mg (days 1-5; VR-CP; 47 FL, 1 MZL patients); or bortezomib, rituximab, prednisone per VR-CP, cyclophosphamide 750 mg/m(2) and doxorubicin 50 mg/m(2) (day 1; VR-CAP; 4 FL, 2 MZL, 1 chronic lymphocytic leukaemia patients).

Aprepitant and fosaprepitant use in children and adolescents at an academic medical center.

Objective: To describe the use of aprepitant and fosaprepitant, a neurokinin 1 (NK-1) receptor inhibitor, in children and adolescents at a large academic medical center, for the prevention and management of chemotherapy-induced nausea and vomiting (CINV).

Methods: A retrospective chart review was conducted using an electronic medical record system to evaluate the use of aprepitant and fosaprepitant in all pediatric patients that were discharged from a single academic medical center between February 25, 2009 and May 25, 2012.

Results: Twenty-six patients were included in this review and received a total of 287 doses over the span of 114 cycles.

The potential role of respiratory motion management and image guidance in the reduction of severe toxicities following stereotactic ablative radiation therapy for patients with centrally located early stage non-small cell lung cancer or lung metastases.

Image guidance allows delivery of very high doses of radiation over a few fractions, known as stereotactic ablative radiotherapy (SABR). This treatment is associated with excellent outcome for early stage non-small cell lung cancer and metastases to the lungs. In the delivery of SABR, central location constantly poses a challenge due to the difficulty of adequately sparing critical thoracic structures that are immediately adjacent to the tumor if an ablative dose of radiation is to be delivered to the tumor target.

Strategies of dose escalation in the treatment of locally advanced non-small cell lung cancer: image guidance and beyond.

Radiation dose in the setting of chemo-radiation for locally advanced non-small cell lung cancer (NSCLC) has been historically limited by the risk of normal tissue toxicity and this has been hypothesized to correlate with the poor results in regard to local tumor recurrences. Dose escalation, as a means to improve local control, with concurrent chemotherapy has been shown to be feasible with three-dimensional conformal radiotherapy in early phase studies with good clinical outcome. However, the potential superiority of moderate dose escalation to 74 Gy has not been shown in phase III randomized studies.

Role of H-Ras/ERK signaling in carbon nanotube-induced neoplastic-like transformation of human mesothelial cells.

Rapid development and deployment of engineered nanomaterials such as carbon nanotubes (CNTs) in various commercial and biomedical applications have raised concerns about their potential adverse health effects, especially their long-term effects which have not been well addressed. We demonstrated here that prolonged exposure of human mesothelial cells to single-walled CNT (SWCNT) induced neoplastic-like transformation as indicated by anchorage-independent cell growth and increased cell invasiveness. Such transformation was associated with an up-regulation of H-Ras and activation of ERK1/2.

Combining COPD with clinical, pathological and demographic information refines prognosis and treatment response prediction of non-small cell lung cancer.

Background: Accurate assessment of a patient's risk of recurrence and treatment response is an important prerequisite of personalized therapy in lung cancer. This study extends a previously described non-small cell lung cancer prognostic model by the addition of chemotherapy and co-morbidities through the use of linked SEER-Medicare data.

Methodology/principal Findings: Data on 34,203 lung adenocarcinoma and 26,967 squamous cell lung carcinoma patients were used to determine the contribution of Chronic Obstructive Pulmonary Disease (COPD) to prognostication in 30 treatment combinations.

Use of high frequency ultrasound to monitor cervical lymph node alterations in mice.

Cervical lymph node evaluation by clinical ultrasound is a non-invasive procedure used in diagnosing nodal status, and when combined with fine-needle aspiration cytology (FNAC), provides an effective method to assess nodal pathologies. Development of high-frequency ultrasound (HF US) allows real-time monitoring of lymph node alterations in animal models. While HF US is frequently used in animal models of tumor biology, use of HF US for studying cervical lymph nodes alterations associated with murine models of head and neck cancer, or any other model of lymphadenopathy, is lacking.

Effects of detraining on the temporal expression of positive and negative angioregulatory proteins in skeletal muscle of mice.

Temporal expression of positive and negative angiogenic factors in response to detraining is poorly understood. We report the protein expression of anti-angiogenic peptides (thrombospondin-1, TSP-1; and endostatin) as well as pro-angiogenic factors (vascular endothelial growth factor, VEGF; matrix metalloproteinases-2 and -9), and nucleolin (a nuclear protein involved with synthesis and maturation of ribosomes) in response to detraining in triceps surae muscles of C57BL/6 mice. Male mice were allowed to exercise voluntarily for 21 days, and then basal and acute response to exercise were evaluated at 1, 7, 14 and 28 days detraining (D1, D7, D14, D28, respectively, n = 12/group).

Caveolin-1 regulates lung cancer stem-like cell induction and p53 inactivation in carbon nanotube-driven tumorigenesis.

Cancer stem cells (CSCs) may represent targets for carcinogenic initiation by chemical and environmental agents. Recent studies have raised a concern over the potential carcinogenicity of carbon nanotubes (CNTs), one of the most commonly used engineered nanomaterials with asbestos-like properties. Here, we show that chronic (6-month) exposure of human lung epithelial cells to single-walled (SW) CNTs at the workplace-relevant concentration induced an emergence of lung CSCs, as indicated by the induction of CSC tumor spheres and side population (SP).