Spontaneous tumorigenesis in mice overexpressing the p53-negative regulator Mdm4.

High levels of the critical p53 inhibitor Mdm4 is common in tumors that retain a wild-type p53 allele, suggesting that Mdm4 overexpression is an important mechanism for p53 inactivation during tumorigenesis. To test this hypothesis in vivo, we generated transgenic mice with widespread expression of Mdm4. Two independent lines of transgenic mice, Mdm4(Tg1) and Mdm4(Tg15), developed spontaneous tumors, the most prevalent of which were sarcomas.

A randomized trial of rocking-chair motion on the effect of postoperative ileus duration in patients with cancer recovering from abdominal surgery.

Patients who undergo abdominal surgery experience a phenomenon commonly called postoperative ileus (POI). Standard of care requires patients to get out of bed, sit in a chair, and begin ambulating the first postoperative day. No evidence supports standard care activities reduce POI duration.

Nutrition during and after cancer therapy.

Diet and nutritional factors play a large role in influencing both the quality and quantity of life after the diagnosis of cancer. The oncology nurse is well-positioned to: 1) help ensure that nutritional needs are met for patients who are newly diagnosed, undergoing active treatment, or have advanced disease; 2) facilitate referral of patients with more intensive nutritional needs to registered dietitians; and 3) promote the importance of weight management and a healthful plant-based diet, low in saturated fat and simple sugars, and high in fruits and vegetables and unrefined whole grains, to patients likely to join the ranks of an ever-expanding population of cancer survivors--who now constitute roughly 4% of the US population and number more than 11 million.

Bendamustine in the treatment of non-Hodgkin's lymphomas.

Purpose: To review available data using bendamustine alone and in combination with other chemotherapeutic agents in treatment of patients with non-Hodgkin's lymphomas.

Methods: Internet database searches and literature review.

Results: Bendamustine was approved in March 2008 by the United States Food and Drug Administration for the treatment of patients with chronic lymphocytic leukemia.

Alpha-methylacyl-CoA racemase expression is upregulated in gastric adenocarcinoma: a study of 249 cases.

Alpha-methylacyl-CoA racemase (AMACR [P504S]) is a mitochondrial and peroxisomal enzyme involved in beta-oxidation of dietary branched-chain fatty acids and their derivatives. Recent studies showed that AMACR is expressed in several neoplasms, including prostate and colon cancer. However, AMACR expression in gastric neoplasms has yet to be thoroughly investigated.

Tissue transglutaminase regulates focal adhesion kinase/AKT activation by modulating PTEN expression in pancreatic cancer cells.

Purpose: Pancreatic ductal adenocarcinoma (PDAC) progresses rapidly and exhibits profound resistance to treatment. We recently reported that a great majority of PDAC tumors and tumor cell lines express elevated levels of tissue transglutaminase (TG2). Here, we provide first evidence that TG2 expression in PDAC cells results in constitutive activation of focal adhesion kinase/AKT by modulating the expression of the tumor suppressor phosphatase PTEN.

Granulocytic sarcoma involving the uterus and right fallopian tube with negative endometrial biopsy.

Granulocytic sarcoma is an extramedullary tumor associated with acute myelogenous leukemia (AML) and it is rarely seen in the female genital tract. We report an unusual case of granulocytic sarcoma of the uterus and fallopian tube in an AML patient who presented with vaginal bleeding and persistent abdominal pain. She was under chemotherapy.

Simultaneous inhibition of COX-2 and 5-LOX activities augments growth arrest and death of premalignant and malignant human lung cell lines.

The arachidonic acid-metabolizing enzymes cyclooxygenase-2 (COX-2) or 5-lipoxygenase (5-LOX) are overexpressed during lung carcinogenesis and their end products (e.g.; PGE2, 5-HETE, and LTB4) have been implicated in tumor development.

Hodgkin's lymphoma in younger patients: lessons learned on the road to success.

Despite significant improvements in the treatment of Hodgkin's lymphoma over the past 2 decades, physicians continue to face dilemmas in therapy for the disease, and many cured patients live with complications of treatment. Newer therapeutic options are still needed for the disease, to minimize complications and to improve the treatment of patients in relapse. This review considers the treatment of Hodgkin's lymphoma in younger patients, addressing such issues as which patients with early-stage disease may require radiotherapy, what prognostic factors provide information that can affect treatment choices in patients with advanced disease, and what we have learned about treatment complications in this setting.

A pilot study of imatinib, low-dose cytarabine and idarubicin for patients with chronic myeloid leukemia in myeloid blast phase.

Imatinib is the single most effective agent in chronic myelogenous leukemia (CML) in blast phase (BP), inducing hematologic responses in 30 - 50% of patients. However, only a few of these are complete (CHR) and durable. Imatinib is synergistic with idarubicin and cytarabine.

Subdivision approach to target-constrained conformational searching.

Conformational searching is common in many applications and algorithmic improvements on either speed or the quality would have a profound impact. In this paper, we address a target-constrained conformational searching problem and show two subdivision methods approximating the solutions rather than solving for the exact solutions. The performance of the methods is presented.

Using a priori structural information from magnetic resonance imaging to investigate the feasibility of prostate diffuse optical tomography and spectroscopy: a simulation study.

Implementation of diffuse optical tomography (DOT) for prostate cancer is challenging because the prostate is a deep-seated organ. We investigated whether diffuse optical tomography (DOT) and spectroscopy could be applied to monitor the physiology of prostate cancer using a small probe that could be placed endorectally. We manually segmented the prostate, the intraprostatic tumor, and the rectum using data from endorectal magnetic resonance imaging.

Polymorphisms of STK15 (Aurora-A) gene and lung cancer risk in Caucasians.

STK15/Aurora-A is a centrosome-localized serine/threonine kinase that functions primarily in centrosome maturation and mitotic spindle assembly. In a large lung cancer case-control study of 1401 cases and 1397 controls including three ethnic groups, we examined the associations between two non-synonymous SNPs (Phe31Ile and Val57Ile) of the STK15 gene and lung cancer risk. There were statistically significant differences in the distribution of the genotypes (P<0.

Polymorphisms and haplotypes of the NBS1 gene are associated with risk of sporadic breast cancer in non-Hispanic white women

DNA double-strand breaks (DSBs) may lead to genomic instability and cancer if unrepaired. Nijmegen breakage syndrome 1 (NBS1) protein is one of the key proteins that participates in recognition and repair of DSBs in humans. We hypothesized that polymorphisms of NBS1 are associated with breast cancer risk.

MDM2 gene promoter polymorphisms and risk of lung cancer: a case-control analysis.

The MDM2 protein negatively regulates p53 expression level in modulating DNA repair, cell-cycle control, cell growth and apoptosis. Polymorphisms in the promoter region of the MDM2 gene have been shown to alter protein expression and may, thus, play a role in carcinogenesis. To test our hypothesis that the MDM2 promoter polymorphisms are associated with risk of lung cancer, we conducted a hospital-based, case-control study of 1026 non-Hispanic white patients newly diagnosed with lung cancer and 1145 cancer-free controls who were frequency-matched by age (+/-5 years), sex, ethnicity and smoking status.

Canine transmissible venereal tumor: a large-animal transplantable tumor model.

The canine transplantable venereal tumor is a naturally occurring transplantable round-cell tumor in dogs. Although experimental transplantable tumor models in rodents and rabbits are readily available, a reliable transplantable tumor model in a large animal that more closely resembles the physical dimensions of humans has not been available. A tumor model in a large animal would have a wide range of biomedical research applications, including the study of various interventional imaging techniques.

Cancer-specific gene therapy.

Cancer cells transcriptionally activate many genes that are important for uncontrolled proliferation and cell death. Deregulated transcriptional machinery in tumor cells usually consists of increased expression/activity of transcription factors. Ideally, cancer-specific killing can be achieved by delivering a therapeutic gene under the control of the DNA elements that can be activated by transcription factors that are overexpressed and/or constitutively activated in cancer cells.

Assessing a conceptual framework of health-related quality of life in a HIV/AIDS population.

With the recognition of health-related quality of life (HRQOL) as an important outcome in the course of HIV-disease, it is important to gain a better understanding of the complex relationships among the various factors that influence it. This study assesses a conceptual framework of HRQOL, consisting of disease status, socio-economic status (SES), behavioral variables, symptom status, role-specific functional status and HRQOL, among a multiethnic, economically disadvantaged population of individuals living with HIV/AIDS. Self-report data were collected from 348 patients receiving care at a large HIV/AIDS care center, serving residents of a large metropolitan area.

Respiration-correlated treatment delivery using feedback-guided breath hold: a technical study.

Respiratory motion causes movement of internal structures in the thorax and abdomen, making accurate delivery of radiation therapy to tumors in those areas a challenge. To reduce the uncertainties caused by this motion, we have developed feedback-guided breath hold (FGBH), a novel delivery technique in which radiation is delivered only during a voluntary breath hold that is sustained for as long as the patient feels comfortable. Here we present the technical aspects of FGBH, which involve (1) fabricating the hardware so the respiratory trace can be displayed to the patient, (2) assembling a delay box to be used as a breath-hold detector, and (3) performing quality control tests to ensure that FGBH can be delivered accurately and safely.

Evolving role of skullbase surgery for patients with low and high grade malignancies.

Malignancy involving the skull base remains a formidable management challenge. Advances and refinements in diagnostic imaging, instrumentation, microvascular reconstruction, and an improved overall appreciation of the anatomy of the skullbase have extended the boundaries of tumor resectability and in some cases, obviated the need for adjuvant therapies. Successful management of high-grade malignancy however, requires a carefully constructed multi-modal treatment plan to maximize patient outcome.

A novel means of using gene clusters in a two-step empirical Bayes method for predicting classes of samples.

Motivation: The classification of samples using gene expression profiles is an important application in areas such as cancer research and environmental health studies. However, the classification is usually based on a small number of samples, and each sample is a long vector of thousands of gene expression levels. An important issue in parametric modeling for so many gene expression levels is the control of the number of nuisance parameters in the model.

Improving conformational searches by geometric screening.

Motivation: Conformational searches in molecular docking are a time-consuming process with wide range of applications. Favorable conformations of the ligands that successfully bind with receptors are sought to form stable ligand-receptor complexes. Usually a large number of conformations are generated and their binding energies are examined.

A deformable-model approach to semi-automatic segmentation of CT images demonstrated by application to the spinal canal.

Because of the importance of accurately defining the target in radiation treatment planning, we have developed a deformable-template algorithm for the semi-automatic delineation of normal tissue structures on computed tomography (CT) images. We illustrate the method by applying it to the spinal canal. Segmentation is performed in three steps: (a) partial delineation of the anatomic structure is obtained by wavelet-based edge detection; (b) a deformable-model template is fitted to the edge set by chamfer matching; and (c) the template is relaxed away from its original shape into its final position.