Mechanism of metformin-dependent inhibition of mammalian target of rapamycin (mTOR) and Ras activity in pancreatic cancer: role of specificity protein (Sp) transcription factors.

The antidiabetic drug metformin exhibits both chemopreventive and chemotherapeutic activity for multiple cancers including pancreatic cancer; however, the underlying mechanism of action of metformin is unclear. A recent study showed that metformin down-regulated specificity protein (Sp) transcription factors (TFs) Sp1, Sp3, and Sp4 in pancreatic cancer cells and tumors, and this was accompanied by down-regulation of several pro-oncogenic Sp-regulated genes. Treatment with metformin or down-regulation of Sp TFs by RNAi also inhibits two major pro-oncogenic pathways in pancreatic cancer cells, namely mammalian target of rapamycin (mTOR) signaling and epidermal growth factor (EGFR)-dependent activation of Ras.

A candidate molecular biomarker panel for the detection of bladder cancer.

Background: Bladder cancer is among the five most common malignancies worldwide, and due to high rates of recurrence, one of the most prevalent. Improvements in noninvasive urine-based assays to detect bladder cancer would benefit both patients and health care systems. In this study, the goal was to identify urothelial cell transcriptomic signatures associated with bladder cancer.

A multi-analyte assay for the non-invasive detection of bladder cancer.

Accurate urinary assays for bladder cancer (BCa) detection would benefit both patients and healthcare systems. Through genomic and proteomic profiling of urine components, we have previously identified a panel of biomarkers that can outperform current urine-based biomarkers for the non-invasive detection of BCa. Herein, we report the diagnostic utility of various multivariate combinations of these biomarkers.

Neoadjuvant hormonal therapy use and the risk of death in men with prostate cancer treated with brachytherapy who have no or at least a single risk factor for coronary artery disease.

Background: Neoadjuvant hormone therapy (NHT) use is associated with an increased risk of all-cause mortality (ACM) in men with a history of coronary artery disease (CAD)-induced congestive heart failure (CHF) or myocardial infarction (MI). However, its effect in men with no or at least a single risk factor for CAD stratified by prostate cancer (PCa) aggressiveness is unknown.

Objective: To assess whether NHT use affects the risk of ACM in men with low-, intermediate-, and high-risk PCa treated with brachytherapy who have no or at least a single risk factor for CAD.

CCL18 in a multiplex urine-based assay for the detection of bladder cancer.

The early detection of bladder cancer (BCa) is pivotal for successful patient treatment and management. Through genomic and proteomic studies, we have identified a number of bladder cancer-associated biomarkers that have potential clinical utility. In a case-control study, we examined voided urines from 127 subjects: 64 tumor-bearing subjects and 63 controls.

The effect of temporal HU variations on the uncertainty of dose recalculations performed on MVCT images.

Over the course of radiation therapy, a patient's anatomy may change substantially. The relatively recent addition of frequent in-room imaging to assist with patient localization has provided a database of images that may be used to recalculate dose distributions for adaptive radiotherapy purposes. The TomoTherapy Hi-Art II unit (Accuray Inc.

A spatial resolution study of a new optical tomography-based polymer gel dosimetry system.

A spatial resolution investigation of the OCTOPUSTM-IQ scanner in combination with the new BANG3-Pro2(r) polymer gel was performed by scanning a high-contrast needle phantom. The phantom contained five thin needles (0.3_mm diameter) embedded in gel positioned in different patterns: needles were inserted (a) at 45° angle from the center of the gel container, and (b) vertically along the gel axis.

Phase III trial of induction gemcitabine or paclitaxel plus carboplatin followed by paclitaxel consolidation in ovarian cancer.

Objective: The safety and efficacy of gemcitabine plus carboplatin (GC) or paclitaxel plus carboplatin (TC) induction regimens with or without paclitaxel consolidation therapy were assessed in ovarian cancer (OC).

Methods: Patients with stage IC-IV OC were randomized to either GC (gemcitabine 1,000 mg/m(2), days 1 and 8, plus carboplatin area under the curve [AUC] 5, day 1) or TC (paclitaxel 175 mg/m(2) plus carboplatin AUC 6, day 1) every 21 days for up to six cycles. Patients with complete response (CR) were allowed optional consolidation with paclitaxel 135 mg/m(2) every 28 days for ≤ 12 months.

Analyzing the impact of intrafraction motion: correlation of different dose metrics with changes in target D95%.

Purpose: A number of techniques are available to determine the dosimetric impact of intrafraction motion during intensity modulated radiation therapy (IMRT). Motion-induced dose perturbations can be determined both computationally and experimentally using a number of different dosimetric metrics. However, these measures may lead to different conclusions regarding the clinical impact of motion.

The safety of rhytidectomy in the elderly.

Background: The purpose of this study was to evaluate the safety of face-lift surgery in an elderly population. Specifically, is chronologic age an independent risk factor leading to a higher complication rate in the elderly patient undergoing rhytidectomy surgery?

Methods: The authors retrospectively reviewed consecutive face lifts (216 patients) performed by a single surgeon over a 3-year period. Patients were divided into two groups, younger than 65 years (148 patients) and 65 years and older (68 patients).

An evaluation of intrafraction motion of the prostate in the prone and supine positions using electromagnetic tracking.

Purpose: To evaluate differences in target motion during prostate irradiation in the prone versus supine position using electromagnetic tracking to measure prostate mobility.

Materials/methods: Twenty patients received prostate radiotherapy in the supine position utilizing the Calypso Localization System® for prostate positioning and monitoring. For each patient, 10 treatment fractions were followed by a session in which the patient was repositioned prone, and prostate mobility was tracked.

Image-guided bolus electron conformal therapy - a case study.

We report on our initial experience with daily image guidance for the treatment of a patient with a basal cell carcinoma of the nasal dorsum using bolus electron conformal therapy. We describe our approach to daily alignment using treatment machine-integrated megavoltage (MV) planar imaging in conjunction with cone beam CT (CBCT) volumetric imaging to ensure the best possible setup reproducibility. Based on MV imaging, beam aperture misalignment with the intended treatment region was as large as 0.

Chemopreventive effects of tolfenamic acid against esophageal tumorigenesis in rats.

The primary objective of this study is to identify small molecules that target critical transcription factors for potential application in the chemoprevention of esophageal cancer. Specificity proteins (Sp) play a critical role in the growth and metastasis of several malignancies including esophageal cancer. Researchers at the M.

Therapeutic applications of NSAIDS in cancer: special emphasis on tolfenamic acid.

Non-steroidal anti-inflammatory drugs (NSAIDs) are primarily used for the treatment of acute or chronic conditions with pain and inflammation. Evidence from a wide range of sources suggested that chronic administration of NSAIDs reduced the risk of cancer incidences. Both the epidemiological and animal studies showed an inverse association between the incidence of various cancers and the use of aspirin or other NSAIDs.

Radiosurgery technology development and use.

Radiosurgery first became a clinical option in the 1960's because of the Gamma Knife, and the technology proliferated in the 1980's due to the availability of linear accelerator radiosurgery. The technology has continued to develop with both Gamma Knife and linac radiosurgery due primarily to advances in computer technology and robotic automation. Many of these advances include planning systems that enhance the conformity of the dose distribution, and delivery systems that can more safely and efficiently delivery these more complex treatment plans.

Blockade of MUC1 expression by glycerol guaiacolate inhibits proliferation of human breast cancer cells.

We sought to determine whether administration of glycerol guaiacolate at an optimal biological dose inhibits human breast cancer cell growth. Human breast cancer MCF-7 and ZR-75-1 cells were treated with glycerol guaiacolate and the therapeutic efficacy and biological activity of this drug was investigated on breast cancer cell growth. MCF-7 cells were injected into the mammary fat pad of overectamized female athymic nude mice.

Derivation of cancer diagnostic and prognostic signatures from gene expression data.

The ability to compare genome-wide expression profiles in human tissue samples has the potential to add an invaluable molecular pathology aspect to the detection and evaluation of multiple diseases. Applications include initial diagnosis, evaluation of disease subtype, monitoring of response to therapy and the prediction of disease recurrence. The derivation of molecular signatures that can predict tumor recurrence in breast cancer has been a particularly intense area of investigation and a number of studies have shown that molecular signatures can outperform currently used clinicopathologic factors in predicting relapse in this disease.

QA for helical tomotherapy: report of the AAPM Task Group 148.

Helical tomotherapy is a relatively new modality with integrated treatment planning and delivery hardware for radiation therapy treatments. In view of the uniqueness of the hardware design of the helical tomotherapy unit and its implications in routine quality assurance, the Therapy Physics Committee of the American Association of Physicists in Medicine commissioned Task Group 148 to review this modality and make recommendations for quality assurance related methodologies. The specific objectives of this Task Group are: (a) To discuss quality assurance techniques, frequencies, and tolerances and (b) discuss dosimetric verification techniques applicable to this unit.

Loss of tyrosine phosphatase-dependent inhibition promotes activation of tyrosine kinase c-Src in detached pancreatic cells.

Despite an intense focus on novel therapeutic strategies, pancreatic adenocarcinoma remains one of the deadliest human malignancies. The frequent and rapid mortality associated with pancreatic cancer may be attributed to several factors, including late diagnosis, rapid tumor invasion into surrounding tissues, and formation of distant metastases. Both local invasion and metastasis require disruption of tumor cell contacts with the extracellular matrix.

The combination of the novel glycolysis inhibitor 3-BrOP and rapamycin is effective against neuroblastoma.

Children with high-risk and recurrent neuroblastoma have poor survival rates, and novel therapies are needed. Many cancer cells have been found to preferentially employ the glycolytic pathway for energy generation, even in the presence of oxygen. 3-BrOP is a novel inhibitor of glycolysis, and has demonstrated efficacy against a wide range of tumor types.

Statewide cancer clinical trial navigation service.

Purpose: Realizing that education and awareness are paramount in making clinical trials available to improve overall accrual rates, we sought to create a clinical trial navigation service to improve the accessibility of cancer clinical trials in Florida for physicians and patients. This study was undertaken to evaluate this service. We hoped to identify characteristics of our service that were effective in promoting clinical trial enrollment and to better understand barriers that prevented enrollment.

Bioluminescence imaging correlates with tumor progression in an orthotopic mouse model of lung cancer.

Background And Objectives: To determine whether bioluminescence imaging of human lung cancer cells growing in an orthotopic murine model provides a sensitive tool for monitoring tumor progression in athymic nude mice.

Methods: Human lung cancer (A549) cells were stably transfected with the firefly luciferase gene and inoculated into the right lung of athymic nude mice. Seven days after inoculation tumor growth was evaluated using the Kodak in-vivo Imaging System FX and continued to be monitored on a weekly basis.