Impact of ultrasound probe pressure on uterine positional displacement in gynecologic cancer patients.

Aim: The aim of this study was to quantify the uterine positional displacement induced by ultrasound probe pressure on a phantom and address the daily uterine motion in a healthy volunteer.

Materials & Methods: The phantom mimics the female pelvic region. The incorporated organs were subjected to displacement.

No evidence for role of extracellular choline-acetyltransferase in generation of gamma oscillations in rat hippocampal slices in vitro.

Acetylcholine (ACh) is well known to induce persistent γ-oscillations in the hippocampus when applied together with physostigmine, an inhibitor of the ACh degrading enzyme acetylcholinesterase (AChE). Here we report that physostigmine alone can also dose-dependently induce γ-oscillations in rat hippocampal slices. We hypothesized that this effect was due to the presence of choline in the extracellular space and that this choline is taken up into cholinergic fibers where it is converted to ACh by the enzyme choline-acetyltransferase (ChAT).

The development of potential antibody-based therapies for myeloma.

With optimal target antigen selection antibody-based therapeutics can be very effective agents for hematologic malignancies, but none have yet been approved for myeloma. Rituximab and brentuximab vedotin are examples of success for the naked antibody and antibody-drug conjugate classes, respectively. Plasma cell myeloma is an attractive disease for antibody-based targeting due to target cell accessibility and the complementary mechanism of action with approved therapies.

ASCL1 is a lineage oncogene providing therapeutic targets for high-grade neuroendocrine lung cancers.

Aggressive neuroendocrine lung cancers, including small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), represent an understudied tumor subset that accounts for approximately 40,000 new lung cancer cases per year in the United States. No targeted therapy exists for these tumors. We determined that achaete-scute homolog 1 (ASCL1), a transcription factor required for proper development of pulmonary neuroendocrine cells, is essential for the survival of a majority of lung cancers (both SCLC and NSCLC) with neuroendocrine features.

Relevance of random biopsy at the transformation zone when colposcopy is negative.

Objective: A post hoc analysis to determine the diagnostic yield of random biopsy in detecting high-grade cervical disease in women with negative colposcopy.

Methods: The ATHENA (Addressing the Need for Advanced HPV Diagnostics) trial screened more than 47,000 women with cytology and high-risk human papillomavirus (HPV) DNA genotyping. Colposcopy was performed in all women with abnormal cytology or positive HPV results.

The low risk of precancer after a screening result of human papillomavirus-negative/atypical squamous cells of undetermined significance papanicolaou and implications for clinical management.

Background: Different US practice guidelines have conflicting recommendations for when women should return after a screening result of human papillomavirus (HPV)-negative with an equivocal Papanicolaou (Pap) result of atypical squamous cells of undetermined significance (ASC-US) (ie, return in either 3 or 5 years). One way to determine management is to compare the risk of precancer/cancer after an HPV-negative/ASC-US result with the risks after other negative screening results. For example, if the risk after an HPV-negative/ASC-US result was similar to the risk after a negative Pap test, a 3-year return would be preferred because guidelines agree that women with negative Pap test results should return in 3 years.

A search for novel cancer/testis antigens in lung cancer identifies VCX/Y genes, expanding the repertoire of potential immunotherapeutic targets.

Cancer/testis (CT) antigens are potential immunotherapeutic targets in cancer. However, the expression of particular antigens is limited to a subset of tumors of a given type. Thus, there is a need to identify antigens with complementary expression patterns for effective therapeutic intervention.

Dosimetric and geometric evaluation of the use of deformable image registration in adaptive intensity-modulated radiotherapy for head-and-neck cancer.

The aim of this study was to carry out geometric and dosimetric evaluation of the usefulness of a deformable image registration algorithm utilized for adaptive head-and-neck intensity-modulated radiotherapy. Data consisted of seven patients, each with a planning CT (pCT), a rescanning CT (ReCT) and a cone beam CT (CBCT). The CBCT was acquired on the same day (± 1 d) as the ReCT (i.

Essential role of aldehyde dehydrogenase 1A3 for the maintenance of non-small cell lung cancer stem cells is associated with the STAT3 pathway.

Purpose: Lung cancer stem cells (CSC) with elevated aldehyde dehydrogenase (ALDH) activity are self-renewing, clonogenic, and tumorigenic. The purpose of our study is to elucidate the mechanisms by which lung CSCs are regulated.

Experimental Design: A genome-wide gene expression analysis was performed to identify genes differentially expressed in the ALDH(+) versus ALDH -: cells.

VEGF/VEGFR-2 upregulates EZH2 expression in lung adenocarcinoma cells and EZH2 depletion enhances the response to platinum-based and VEGFR-2-targeted therapy.

Purpose: To investigate the mechanisms of regulation and role associated with enhancer of zeste homolog 2 (EZH2) expression in lung cancer cells.

Experimental Design: We investigated the mechanisms of EZH2 expression associated with the VEGF/VEGFR-2 pathway. Furthermore, we sought to determine the role of EZH2 in response of lung adenocarcinoma to platinum-based chemotherapy, as well as the effect of EZH2 depletion on VEGFR-2-targeted therapy in lung adenocarcinoma cell lines.

Few-femtosecond time-resolved measurements of X-ray free-electron lasers.

X-ray free-electron lasers, with pulse durations ranging from a few to several hundred femtoseconds, are uniquely suited for studying atomic, molecular, chemical and biological systems. Characterizing the temporal profiles of these femtosecond X-ray pulses that vary from shot to shot is not only challenging but also important for data interpretation. Here we report the time-resolved measurements of X-ray free-electron lasers by using an X-band radiofrequency transverse deflector at the Linac Coherent Light Source.

Expression profiling stratifies mesothelioma tumors and signifies deregulation of spindle checkpoint pathway and microtubule network with therapeutic implications.

Background: Malignant pleural mesothelioma (MPM) is a lethal neoplasm exhibiting resistance to most treatment regimens and requires effective therapeutic options. Though an effective strategy in many cancer, targeted therapy is relatively unexplored in MPM because the therapeutically important oncogenic pathways and networks in MPM are largely unknown.

Materials And Methods: We carried out gene expression microarray profiling of 53 surgically resected MPMs tumors along with paired normal tissue.

Membrane carbonic anhydrase IX expression and relapse risk in resected stage I-II non-small-cell lung cancer.

Background: Adjuvant chemotherapy reduces recurrences of non-small-cell lung cancer (NSCLC). To determine which patients need adjuvant chemotherapy, we assessed factors associated with time to relapse (TTR).

Methods: In 230 resected stage I-II NSCLCs, we correlated immunohistochemistry scores for factors associated with cell growth rate, growth regulation, hypoxia, cell survival, and cell death with TTR.

Combined glyco- and protein-Fc engineering simultaneously enhance cytotoxicity and half-life of a therapeutic antibody.

While glyco-engineered monoclonal antibodies (mAbs) with improved antibody-dependent cell-mediated cytotoxicity (ADCC) are reaching the market, extensive efforts have also been made to improve their pharmacokinetic properties to generate biologically superior molecules. Most therapeutic mAbs are human or humanized IgG molecules whose half-life is dependent on the neonatal Fc receptor FcRn. FcRn reduces IgG catabolism by binding to the Fc domain of endocytosed IgG in acidic lysosomal compartments, allowing them to be recycled into the blood.

Radiation-enhanced lung cancer progression in a transgenic mouse model of lung cancer is predictive of outcomes in human lung and breast cancer.

Purpose: Carcinogenesis is an adaptive process between nascent tumor cells and their microenvironment, including the modification of inflammatory responses from antitumorigenic to protumorigenic. Radiation exposure can stimulate inflammatory responses that inhibit or promote carcinogenesis. The purpose of this study is to determine the impact of radiation exposure on lung cancer progression in vivo and assess the relevance of this knowledge to human carcinogenesis.

Prognostic implications of tumoral expression of insulin like growth factors 1 and 2 in patients with non-small-cell lung cancer.

Introduction: The currently available systemic therapies for non-small-cell lung cancer (NSCLC) have limited efficacy. Previous studies indicated an association of elevated insulinlike growth factor (IGF)-1 receptor (IGF-1R) and insulin receptor expression levels with poor survival in patients with NSCLC. To better understand the molecular biomarkers involved in the IGF signaling pathway in NSCLC, the expression levels of IGF-1 and IGF-2 are characterized and evaluated for their association with IGF-1R and phosphorylated IGF-1R (pIGF-1R) expression in NSCLC.

TGFBI expression is an independent predictor of survival in adjuvant-treated lung squamous cell carcinoma patients.

Background: Transforming growth factor β-induced protein (TGFBI) is a secreted protein that mediates cell anchoring to the extracellular matrix. This protein is downregulated in lung cancer, and when overexpressed, contributes to apoptotic cell death. Using a small series of stage IV non-small cell lung cancer (NSCLC) patients, we previously suggested the usefulness of TGFBI as a prognostic and predictive factor in chemotherapy-treated late-stage NSCLC.

A reevaluation of CD22 expression in human lung cancer.

CD22 is a transmembrane glycoprotein expressed by mature B cells. It inhibits signal transduction by the B-cell receptor and its coreceptor CD19. Recent reports indicate that most human lung cancer cells and cell lines express CD22, making it an important new therapeutic target for lung cancer.

Prediction of survival in resected non-small cell lung cancer using a protein expression-based risk model: implications for personalized chemoprevention and therapy.

Purpose: Patients with resected non-small cell lung cancer (NSCLC) are at risk for recurrence of disease, but we do not have tools to predict which patients are at highest risk. We set out to create a risk model incorporating both clinical data and biomarkers.

Experimental Design: We assembled a comprehensive database with archival tissues and clinical follow-up from patients with NSCLC resected between 2002 and 2005.

Identification of a subset of human non-small cell lung cancer patients with high PI3Kβ and low PTEN expression, more prevalent in squamous cell carcinoma.

Purpose: The phosphoinositide 3-kinase (PI3K) pathway is a major oncogenic signaling pathway and an attractive target for therapeutic intervention. Signaling through the PI3K pathway is moderated by the tumor suppressor PTEN, which is deficient or mutated in many human cancers. Molecular characterization of the PI3K signaling network has not been well defined in lung cancer; in particular, the role of PI3Kβ and its relation to PTEN in non-small cell lung cancer NSCLC remain unclear.

Coherent-radiation spectroscopy of few-femtosecond electron bunches using a middle-infrared prism spectrometer.

Modern, high-brightness electron beams such as those from plasma wakefield accelerators and free-electron laser linacs continue the drive to ever-shorter bunch durations. In low-charge operation (~20 pC), bunches shorter than 10 fs are reported at the Linac Coherent Light Source (LCLS). Though suffering from a loss of phase information, spectral diagnostics remain appealing as compact, low-cost bunch duration monitors suitable for deployment in beam dynamics studies and operations instrumentation.

Methods for site-specific drug conjugation to antibodies.

Antibody drug conjugates (ADCs) are an emerging class of targeted therapeutics with the potential to improve therapeutic index over traditional chemotherapy. Drugs and linkers have been the current focus of ADC development, in addition to antibody and target selection. Recently, however,the importance of conjugate homogeneity has been realized.

Interlaboratory variation in the performance of liquid-based cytology: insights from the ATHENA trial.

Although it is recognized that cervical cytology is highly subjective, and that there is considerable interlaboratory variation in how slides are evaluated, little is known as to how this impacts the performance of cytology. In the ATHENA trial, liquid-based cytology specimens from 46,887 eligible women ≥21 years of age were evaluated at four large regional US laboratories, providing a unique opportunity to evaluate the impact of interlaboratory variations on the performance of cervical cytology. All women with abnormal cytology (atypical squamous cells of undetermined significance or higher) were referred to colposcopy, as were all high-risk human papillomavirus (hrHPV)-positive women ≥25 years of age and a random subset of those ≥25 years of age who were negative by both hrHPV testing and cytology.

EZH2 protein expression associates with the early pathogenesis, tumor progression, and prognosis of non-small cell lung carcinoma.

Purpose: Enhancer of zeste homolog 2 (EZH2) promotes carcinogenesis by epigenetically silencing tumor suppressor genes. We studied EZH2 expression by immunohistochemistry in a large series of non-small cell lung carcinomas (NSCLC) in association with tumor characteristics and patient outcomes.

Experimental Design: EZH2 immunohistochemistry expression was analyzed in 265 normal and premalignant bronchial epithelia, 541 primary NSCLCs [221 squamous cell carcinomas (SCC) and 320 adenocarcinomas] and 36 NSCLCs with paired brain metastases.