Association of Mutation and Methylation in the Promoter Region of TIF1γ
with Non-small Cell Lung Cancer
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Background and objective TIF1γ (transcription intermediary factor 1 gamma), which belongs to transcription intermediary factor 1 family, is an inhibitor of the TGF-β/Smad signaling pathway and could inhibit the signal transduction mediated by TGF-β. The deficiency of TIF1γ expression in a variety of tumor cells suggests that TIF1γ may play as a tumor suppressor gene in cancer development. The aim of this study is to confirm the relationship between TIF1γ and non-small cell lung cancer (NSCLC) through exploring the expression of TIF1γ in NSCLC cells and tissues, and investigate the regulation mechanism of TIF1γ expression in NSCLC cells. Methods Thirteen NSCLC and the paired corresponding para-cancerous lung tissue samples and three cell lines (a normal bronchial epithelial cell lin...
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Preliminary Study of MALDI-TOF Mass Spectrometry-based Screening of Patients with the NSCLC Serum-Specific Peptides
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Background and objective The improved survival of patients with lung cancer depends on early diagnosis of lung cancer. However, the traditional diagnostic techniques have several limitations. Mass spectrometry (MS) has been applied as a core technology for cancer diagnosis in preliminary proteomic studies. The aim of this study is to explore the differences in the serum peptide levels of patients with non-small cell lung cancer (NSCLC) and healthy individuals using matrix-assisted laser desorption/ionization (MALDI)-time-of-flight (TOF)-MS. A NSCLC serum classification model was then established. Methods One hundred and thirty three cases of patients with NSCLC serum specimens and 132 cases of healthy human serum specimens were randomly divided into two groups in accordance with the ratio ...
Clinical Effects for Patients with Recurrent Advanced Non-small Cell Lung Cancer Treated with Icotinib Hydrochloride
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Background and objective Icotinib hydrochloride is the third single target EGFR-TKI used in clinical treatment of advanced non-small cell lung cancer (NSCLC). Clinical research reports on its efficacy and survival in patients with Recurrent Advanced NSCLC are still little.The aim of this study is to evaluate the efficacy and survival of Icotinib hydrochloride for patients with advanced non-small cell lung cancer who failed to previous chemotherapy and explore the association of clinical features with the efficacy and survival. Methods The clinical data of 60 NSCLC patients referred to the Beijing Chest Hospital, Capital Medical University from March 2009 to July 2012 were retrospectively analyzed. Results The overall response rate (ORR) was 45.0% and the disease control rate (DCR) was 80.0...
Pathological Characteristic and Clinical Management of Pulmonary Carcinoid
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Conclusion Pathological diagnosis of pulmonary carcinoid must combine morphology with immunohistochemistry. Early-stage patients can also achieve good effect after surgery. DOI: 10.3779/j.issn.1009-3419.2013.05.06 (Source: Chinese Journal of Lung Cancer)
Dosimetric Comparing between Protons Beam and Photons Beam
for Lung Cancer Radiotherapy: A Meta-analysis
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Background and objective The clinical evidences are not sufficient on the proton beam therapy of lung cancer for lacking of the RCTs on the comparing the proton with the photon beam in lung cancer radiotherapy. The aim of this study is to evaluate the dosimetry superiority of the proton beam and provide more valuable evidences to the clinical researches. Methods Clinical trails of dosimetric comparing between protons beam and photons beam for lung cancer radiotherapy were obtained from the Cochrane library, Pubmed, EMbase, CBM, CNKI, VIP, and Wan Fang databases. The data included in the study were evaluated and analyzed using the Cochrane Collaboration's RevMan 5.2 software. Results Six trails were included. Compared to photon therapy (three-dimensional conformal photon radiotherapy, 3D-CR...
Research Progress of Treatment Strategy for Pulmonary Nodule
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DOI: 10.3779/j.issn.1009-3419.2013.05.08 (Source: Chinese Journal of Lung Cancer)
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Interstitial Lung Disease Associated with Lung Cancer Treatment
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Interstitial lung disease is one of the most serious side effects caused by lung cancer treatment. Due to the complexity diagnosis and variability of the disease, it is often not diagnosied and treated in time, even endanger the patient's life and affect the patient's prognosis. The mechanism of interstitial pneumonia caused by radiotherapy, chemotherapy and targeted therapy is still not fully known. Therefore, it become a problem that how to early detection, diagnosis and treat the interstitial lung disease caused by lung cancer treatment and it should not be ignored in the future. DOI: 10.3779/j.issn.1009-3419.2013.05.09 (Source: Chinese Journal of Lung Cancer)
Giant Primitive Nuroectodermal Tumor of Mediastinum:
A Case Report with Literature Review
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DOI: 10.3779/j.issn.1009-3419.2013.05.10 (Source: Chinese Journal of Lung Cancer)
Using microRNA profiling in urine samples to develop a non‐invasive test for bladder cancer
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This study aimed to examine the microRNA (miRNA) expression profiles in urines of UCC patients in order to develop a non‐invasive accurate and reliable tool to diagnose and provide information on the aggressiveness of the tumour. We performed a global miRNA expression profiling analysis of the urinary cells from 40 UCC patients and controls using TaqMan® Human MicroRNA Array followed by validation of 22 selected potentially diagnostic and prognostic miRNAs in a separate cohort of 277 samples using a miRCURY LNATM qPCR system. miRNA‐based signatures were developed by multivariate logistic regression analysis and internally cross‐validated. In the initial cohort of patients, we identified 40 and 30 aberrantly expressed miRNA in UCC compared to control urines and in high compared to lo...
Abstract
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(Source: Pediatric Blood and Cancer)
Ultrasound Probe and Needle-Guide Calibration for Robotic Ultrasound Scanning and Needle Targeting
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We report a calibration method for 2-D ultrasound probes using robotic manipulation and a planar calibration rig. Moreover, a needle guide that is attached to the probe is also calibrated for ultrasound-guided needle targeting. The method is applied to a transrectal ultrasound (TRUS) probe for robot-assisted prostate biopsy. Validation experiments include TRUS-guided needle targeting accuracy tests. This paper outlines the entire process from the calibration to image-guided targeting. Freehand TRUS-guided prostate biopsy is the primary method of diagnosing prostate cancer, with over 1.2 million procedures performed annually in the U.S. alone. However, freehand biopsy is a highly challenging procedure with subjective quality control. As such, biopsy devices are emerging to assist the physic...
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Debye Parameter Extraction for Characterizing Interaction of Terahertz Radiation With Human Skin Tissue
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This paper is concerned with parameter extraction for the double Debye model, which is used for analytically determining human skin permittivity. These parameters are thought to be the origin of contrast in terahertz (THz) images of skin cancer. The existing extraction methods could generate Debye models, which track their measurements accurately at frequencies higher than 1 THz but poorly at lower frequencies, where the majority of permittivity contrast between healthy and diseased skin tissues is actually observed. We propose a global optimization-based parameter extraction, which results in globally accurate tracking and thus supports the full validity of the Debye model for simulating human skin permittivity in the whole usable THz frequencies. Numerical results confirm viability of ou...
THE GooseMan: A simulator for transhiatal esophagectomy
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Esophageal cancer is the fastest growing cancer in the United States and the seventh leading cause of cancer-related death worldwide. The gold standard therapy is surgical resection commonly performed as a transhiatal esophagectomy (THE), which involves blindly dissecting the esophagus in the mediastinum through abdominal and cervical neck incisions. Compared with transthoracic esophagectomy, which requires creating a direct thoracic incision, THE has similar long-term survival but is less invasive and has fewer complications, a shorter recovery time, and decreased in-hospital mortality. Yet, morbidity and mortality from THE remain high compared with other thoracic procedures, largely a result of complications that arise during the blind mobilization process, such as injury to blood vessel...
Novel mouse model for Gardner syndrome generated by a large‐scale N‐ethyl‐N‐nitrosourea mutagenesis program
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Mutant mouse models are indispensable tools for clarifying the functions of genes and elucidating the underlying pathogenic mechanisms of human diseases. We carried out large‐scale mutagenesis using the chemical mutagen N‐ethyl‐N‐nitrosourea. One specific aim of our mutagenesis project was to generate novel cancer models. We screened 7012 animals for dominant traits using a necropsy test and thereby established 17 mutant lines predisposed to cancer. Here, we report on a novel cancer model line that developed osteoma, trichogenic tumor, and breast cancer. Using fine mapping and genomic sequencing, we identified a point mutation in the adenomatous polyposis coli (Apc) gene. The Apc1576 mutants bear a nonsense mutation at codon 1576 in the Apc gene. Although most Apc mutant mice estab...
M.D. Anderson saw $330M increase in operating expenses
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Though the president of The University of Texas M.D. Anderson Cancer Center told employees this week the institution would make budget cuts in several areas, The University of Texas health care system's 2012 annual report foreshadowed the moves. The report, released in December, shows the cancer center's total operating revenue from August 2011 to August 2012 increased to $3.39 billion, compared to $3.16 billion a year earlier. But a sharp increased in total operating expenses to $278 million left… (Source: bizjournals.com Health Care:Hospitals headlines)
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PrePrint: Novel Multi-Sample Scheme for Inferring Phylogenetic Markers from Whole Genome Tumor Profiles
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Computational cancer phylogenetics seeks to enumerate the temporal sequence of aberrations in tumor evolution, thereby delineating the evolution of possible tumor progression pathways, molecular subtypes and mechanisms of action. We previously developed a pipeline for constructing phylogenies describing evolution between major recurring cell types computationally inferred from whole-genome tumor profiles. The accuracy and detail of the phylogenies, however, depends on the identification of accurate, high-resolution molecular markers of progression, i.e., reproducible regions of aberration that robustly differentiate different subtypes and stages of progression. Here we present a novel hidden Markov model (HMM) scheme for the problem of inferring such phylogenetically significant markers th...
Mammographical mass detection and classification using Local Seed Region Growing–Spherical Wavelet Transform (LSRG–SWT) hybrid scheme
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Abstract: The purpose of this study is to implement accurate methods of detection and classification of benign and malignant breast masses in mammograms. Our new proposed method, which can be used as a diagnostic tool, is denoted Local Seed Region Growing–Spherical Wavelet Transform (LSRG–SWT), and consists of four steps. The first step is homomorphic filtering for enhancement, and the second is detection of the region of interests (ROIs) using a Local Seed Region Growing (LSRG) algorithm, which we developed. The third step incoporates Spherical Wavelet Transform (SWT) and feature extraction. Finally the fourth step is classification, which consists of two sequential components: the 1st classification distinguishes the ROIs as either mass or non-mass and the 2nd classification distingu...
Computer-aided identification of EGFR tyrosine kinase inhibitors using ginsenosides from Panax ginseng
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Abstract: Natural products have served as structural resources in the history of drug discovery for cancer therapy. Among these natural products, Korean Panax ginseng serves as a potential anti-cancer medicinal plant. To determine the anti-cancer activities of Korean P. ginseng active compounds, we performed pharmacophore-based virtual screening and molecular docking studies on EGFR (epidermal growth factor receptor) tyrosine kinase domain. The EGFR family tyrosine kinase receptor is a cell surface receptor that regulates diverse biological processes including cell proliferation, differentiation, survival, and apoptosis. Over expression of EGFR tyrosine kinase domain associated with the development and progression of numerous human cancers. In our study, we developed the best pharmacophore...
Structural modeling and simulation studies of human cyclooxygenase (COX) isozymes with selected terpenes: Implications in drug designing and development
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Abstract: In view of recently implicated role of COX-1 in human health and diseases, including cancer, development of safe and selective drugs, as COX-1 inhibitor is desirable. Human COX-1 and COX-2 isozymes have been modeled using in silico tools and relative efficacies of terpenoids as their inhibitors have been investigated by docking. The docking analyses of 10 selected terpenoids along with drugs revealed that all of the terpenoids were more potent inhibitors of COX-1 rather than COX-2 with the oleanolic acid as the most potent inhibitor of COX in general (binding energy [−18.68Kcal/mol and −18.25Kcal/mol] and estimated Ki [5.57×10−8µM and 11.4×10−8µM] for COX-1 and COX-2, respectively) and β-carotene as most selective inhibitor of COX-1. Furthermore, ibuprofen and aspiri...
Correcting for rater bias in scores on a continuous scale, with application to breast density
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Existing literature on inter‐rater reliability focuses on quantifying the disagreement between raters. In this paper, we introduce a method to correct for inter‐rater disagreement (or observer bias), where raters are assigning scores on a continuous scale. To do this, we propose a two‐stage approach. In the first stage, we standardise the distributions of rater scores to account for each rater's subjective interpretation of the continuous scale. In the second stage, we correct for case‐mix differences between raters by exploiting pairwise information where two raters have read the same entity on a case. We illustrate the use of our procedure on clinicians’ visual assessments of breast density (a risk factor for breast cancer). After applying our procedure, 229 out of 1398 women w...
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Heme‐related gene expression signatures of meat intakes in lung cancer tissues
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Abstract Lung cancer causes more deaths worldwide than any other cancer. In addition to cigarette smoking, dietary factors may contribute to lung carcinogenesis. Epidemiologic studies, including the environment and genetics in lung cancer etiology (EAGLE), have reported increased consumption of red/processed meats to be associated with higher risk of lung cancer. Heme–iron toxicity may link meat intake with cancer. We investigated this hypothesis in meat‐related lung carcinogenesis using whole genome expression. We measured genome‐wide expression (HG‐U133A) in 49 tumor and 42 non‐involved fresh frozen lung tissues of 64 adenocarcinoma EAGLE patients. We studied gene expression profiles by high‐versus‐low meat consumption, with and without adjustment by sex, age, and smoking. ...
Best Doctors — Matthew Arneson
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Wichita Surgical Specialists Education: MD, University of Washington Medical School, Seattle, Wash. Employment History: Wichita Surgical Specialists 2006-current. WHY DID YOU BECOME A DOCTOR? I was first introduced to the medical community at age 12 when my father was diagnosed with terminal lung cancer. The way physicians can influence patients and their families lives was profound. HOW DID YOU CHOOSE YOUR AREA OF PRACTICE? Cardiothoracic surgery is one of a few fields in medicine that requires… (Source: bizjournals.com Health Care:Biotechnology headlines)
Clinical evidence of the efficacy of everolimus and its potential in the treatment of breast cancer
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Saksena R, Wong ST (Source: Vascular Health and Risk Management)
The role of indoleamine 2,3-dioxygenase in LP-BPM5 murine retroviral disease progression
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Conclusions: Collectively, these results demonstrate IDO neither plays an essential role, nor is required, in LP-BM5-induced disease progression or LP-BM5 viral load. (Source: Virology Journal)
Knowledge of human papillomavirus and cervical cancer among young women recruited using a social networking site
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Conclusions HPV and cervical cancer knowledge among participants were relatively high compared with other studies conducted both worldwide and in Australia. However, deficits in knowledge exist and warrant address in educational initiatives. (Source: Sexually Transmitted Infections)
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Primary Pulmonary Adenocarcinoma Mimicking Papillary Thyroid Carcinoma
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We herein reported a primary pulmonary papillary carcinoma with colloid-like luminal content in the glandular cavity and classic nuclear features such as pseudo-inclusions, intranuclear grooves in the tumor cell nuclei and ground glass nuclei which closely mimics papillary thyroid carcinoma. Meanwhile, lymph node in the left pulmonary hilum was involved and showed similar features to the primary pulmonary papillary carcinoma. This specific histopathological presentation caused a diagnostic dilemma.The patient didn't show previous concomitant or subsequent evidence of a thyroid tumor. Immunohistochemistry further confirmed pulmonary origin and excluded a metastasis from the thyroid, as it was thyroglobulin negative, thyroid transcription factor 1 and surfactant apoprotein A positive, which ...
Serum Thymidine Kinase 1 Activity in Solid Tumor (Breast and Colorectal Cancer) Patients Treated With Adjuvant Chemotherapy
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ConclusionOur results showed that serum TK1 activity in patients with breast and colorectal cancer was significantly higher than that of the healthy controls. Moreover, after the completion of chemotherapy the values were lower than baseline. Pretreatment TK1 activity should be considered as a useful marker for assessment tumor cell proliferation in breast and colorectal cancer. Further work is needed to understand TK1 activity better in large populations of patients with solid tumor. (Source: Journal of Clinical Laboratory Analysis)
Interaction between the TP63 and SHH pathways is an important determinant of epidermal homeostasis
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Authors: N S Chari, R A Romano, M I Koster, V Jaks, D Roop, E R Flores, S Teglund, S Sinha, W Gruber, F Aberger, L J Medeiros, R Toftgard & T J McDonnell (Source: Cell Death and Differentiation)
Danger signalling during cancer cell death: origins, plasticity and regulation
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Authors: A D Garg, S Martin, J Golab & P Agostinis (Source: Cell Death and Differentiation)
Impact of hepatitis C virus co-infection on HIV patients before and after highly active antiretroviral therapy: an immunological and clinical chemistry observation, Addis Ababa, Ethiopia
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Conclusion: We found that CD4+ T-cell recovery was negatively affected by the presence of ongoing HCV replication in under HAART co-infected individuals and fast decline of CD4+ T-cells in pre-ART patients. It was also associated with increased ALT and AST enzyme levels in both HAART initiated and treatment naive co-infected patients. (Source: BMC Immunology)
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Mutational analysis of BRCA1 and BRCA2 in hereditary breast and ovarian cancer families from Asturias (Northern Spain)
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Conclusions: In this study we report the BRCA1 and BRCA2 spectrum of mutations and their geographical distribution in Asturias, which largely differ from other areas of Spain. Our findings may help design a first step recurrent mutation panel for screening high-risk breast and/or ovarian cancer families from this specific area. (Source: BMC Cancer)
Histological and prognostic importance of CD44+/CD24+/EpCAM+ expression in clinical pancreatic cancer
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In conclusion, CD44+/CD24+/EpCAM+ expression overlapped with poorly differentiated cells and possessed high proliferative potential in clinical pancreatic cancer. In particular, the presence of double‐positive CD44+/CD24+ expression seemed to have clinical relevance, associating with poor prognosis. This article is protected by copyright. All rights reserved. (Source: Cancer Science)
Precision Oncology: An Overview [SPECIAL SERIES OVERVIEW]
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(Source: Journal of Clinical Oncology)
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Genomics-Driven Oncology: Framework for an Emerging Paradigm [REVIEW ARTICLES]
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A majority of cancers are driven by genomic alterations that dysregulate key oncogenic pathways influencing cell growth and survival. However, the ability to harness tumor genetic information for its full clinical potential has only recently become manifest. Over the past several years, the convergence of discovery, technology, and therapeutic development has created an unparalleled opportunity to test the hypothesis that systematic knowledge of genomic information from individual tumors can improve clinical outcomes for many patients with cancer. Rigorous evaluation of this genomics-driven cancer medicine hypothesis will require many logistic innovations that are guided by overarching conceptual advances in tumor genomic profiling, data interpretation, clinical trial design, and the ethic...
Existing and Emerging Technologies for Tumor Genomic Profiling [REVIEW ARTICLES]
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Ongoing global genome characterization efforts are revolutionizing our knowledge of cancer genomics and tumor biology. In parallel, information gleaned from these studies on driver cancer gene alterations—mutations, copy number alterations, translocations, and/or chromosomal rearrangements—can be leveraged, in principle, to develop a cohesive framework for individualized cancer treatment. These possibilities have been enabled, to a large degree, by revolutionary advances in genomic technologies that facilitate systematic profiling for hallmark cancer genetic alterations at increasingly fine resolutions. Ongoing innovations in existing genomics technologies, as well as the many emerging technologies, will likely continue to advance translational cancer genomics and precision can...
Clinical Analysis and Interpretation of Cancer Genome Data [REVIEW ARTICLES]
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We describe existing knowledge bases, databases, algorithms, and tools for identification and visualization of tumor variants and their actionable subsets. With the decreasing cost of tumor gene mutation testing and the increasing number of actionable therapeutics, we expect the methods for analysis and interpretation of cancer genomes to continue to evolve to meet the needs of patient-centered clinical decision making. The science of computational cancer medicine is still in its infancy; however, there is a clear need to continue the development of knowledge bases, best practices, tools, and validation experiments for successful clinical implementation in oncology. (Source: Journal of Clinical Oncology)
Designing Transformative Clinical Trials in the Cancer Genome Era [REVIEW ARTICLES]
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This article provides an overview of the emerging methodologic challenges in the cancer genome era and offers some potential solutions for transforming clinical trial designs so they can identify new active anticancer regimens in molecularly defined subgroups as efficiently as possible. (Source: Journal of Clinical Oncology)
Ethical, Legal, and Counseling Challenges Surrounding the Return of Genetic Results in Oncology [REVIEW ARTICLES]
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In the last decade, an overwhelming number of genetic aberrations have been discovered and linked to the development of treatment for cancer. With the rapid advancement of next-generation sequencing (NGS) techniques, it is expected that large-scale DNA analyses will increasingly be used to select patients for treatment with specific anticancer agents. Personalizing cancer treatment has many advantages, but sequencing germline DNA as reference material for interpreting cancer genetics may have consequences that extend beyond providing cancer care for an individual patient. In sequencing germline DNA, mutations may be encountered that are associated with increased susceptibility not only to hereditary cancer syndromes but also to other diseases; in those cases, disclosing germline data could...
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Building a Personalized Medicine Infrastructure at a Major Cancer Center [REVIEW ARTICLES]
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This article will focus on the challenges and opportunities that accompany the building of infrastructure for personalized cancer therapy. (Source: Journal of Clinical Oncology)
Lessons Learned From Lung Cancer Genomics: The Emerging Concept of Individualized Diagnostics and Treatment [REVIEW ARTICLES]
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The advent of novel therapeutics that specifically target signaling pathways activated by genetic alterations has revolutionized the way patients with lung cancer are treated. Although only few and largely ineffective chemotherapeutic regimens were available 10 years ago, a lung tumor diagnosed today requires extensive pathologic subtyping and diagnosis of genome alterations to afford more effective treatment (eg, in EGFR-mutant adenocarcinoma). This change of paradigm has several profound implications, ranging from preclinical work on the mechanism of action to a novel, more biologically oriented taxonomy and from genome diagnostics to trial design. Here, we have summarized these developments into six conceptual paradigms that illustrate the transition from empirical cancer medicine to me...
Advancing Precision Medicine for Prostate Cancer Through Genomics [REVIEW ARTICLES]
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Prostate cancer is the most common type of cancer in men and the second leading cause of cancer death in men in the United States. The recent surge of high-throughput sequencing of cancer genomes has supported an expanding molecular classification of prostate cancer. Translation of these basic science studies into clinically valuable biomarkers for diagnosis and prognosis and biomarkers that are predictive for therapy is critical to the development of precision medicine in prostate cancer. We review potential applications aimed at improving screening specificity in prostate cancer and differentiating aggressive versus indolent prostate cancers. Furthermore, we review predictive biomarker candidates involving ETS gene rearrangements, PTEN inactivation, and androgen receptor signaling. These...
Genomic Medicine Frontier in Human Solid Tumors: Prospects and Challenges [REVIEW ARTICLES]
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Recent discoveries of genomic alterations that underlie and promote the malignant phenotype, together with an expanded repertoire of targeted agents, have provided many opportunities to conduct hypothesis-driven clinical trials. The ability to profile each unique cancer for actionable aberrations by using high-throughput technologies in a cost-effective way provides unprecedented opportunities for using matched therapies in a selected patient population. The major challenges are to integrate and make biologic sense of the substantial genomic data derived from multiple platforms. We define two different approaches for the analysis, interpretation, and clinical applicability of genomic data: (1) the genomically stratified model originates from the "one test-one drug" paradigm and is currentl...
Leveraging Cancer Genome Information in Hematologic Malignancies [REVIEW ARTICLES]
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The use of candidate gene and genome-wide discovery studies in the last several years has led to an expansion of our knowledge of the spectrum of recurrent, somatic disease alleles, which contribute to the pathogenesis of hematologic malignancies. Notably, these studies have also begun to fundamentally change our ability to develop informative prognostic schema that inform outcome and therapeutic response, yielding substantive insights into mechanisms of hematopoietic transformation in different tissue compartments. Although these studies have already had important biologic and translational impact, significant challenges remain in systematically applying these findings to clinical decision making and in implementing new technologies for genetic analysis into clinical practice to inform re...
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Future of Clinical Genomics in Pediatric Oncology [REVIEW ARTICLES]
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The somatic genomic alterations in pediatric cancers to some extent overlap with those seen in adult cancers, but the exact distribution throughout the genome and the types and frequency of alterations differ. The ultimate goal of genomic research in children, as with adults, is translation to the clinic to achieve more accurate diagnosis, more precise risk stratification, and more effective, less toxic therapy. The genomic features of pediatric malignancies and pediatric-specific issues in clinical investigation may make translating genomic discoveries to the clinic more difficult. However, through large-scale molecular profiling of pediatric tumors, continued coordinated efforts to evaluate novel therapies in the pediatric population, thoughtful phase II and III trial design, and continu...
Personalizing Oncology: Perspectives and Prospects [REVIEW ARTICLES]
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This article provides an overview of the research, beginning a century ago, that has led to the current use of genomically informed methods for selection of targeted therapies to treat individual patients with cancer—so-called precision cancer medicine. Until 1980, most research on cancer therapy was not targeted in the sense we use the word today. Since then, there has been an acceleration in research identifying genetic and molecular targets and in clinical trials using biomarkers that identify the presence of genetic or molecular markers in a patient's cancer to select appropriate targeted therapy. This approach has been made possible by increased knowledge of the genetic pathogenesis of cancer and by increased capacity to sequence genes and genomes in clinically useful timeframes...
An HDAC inhibitor enhances cancer therapeutic efficiency of RNA polymerase III promoter-driven IDO shRNA
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Authors: M-C Yen, T-Y Weng, Y-L Chen, C-C Lin, C-Y Chen, C-Y Wang, H-L Chao, C-S Chen & M-D Lai (Source: Cancer Gene Therapy)
Differences in risk factors between patterns of recurrence in patients after curative resection for advanced gastric carcinoma
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Conclusions: This study clarified differences in risk factors between various patterns of recurrence. Careful examination of risk factors could help prevent oversight of recurrences and improve detection of recurrences during follow-up. The number of lymph node metastases represents an independent risk factor for all three patterns of recurrence; thus, patients with multiple lymph node metastases warrant particular attention. (Source: World Journal of Surgical Oncology)
p14ARF induces apoptosis via an entirely caspase‐3 dependent mitochondrial amplification loop
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Abstract The p14ARF tumor suppressor triggers cell death or cell cycle arrest upon oncogenic stress. In MCF‐7 breast carcinoma cells, expression of the tumor suppressor gene p14ARF fails to trigger apoptosis but induces an arrest in the G1 and, to a lesser extent, in the G2 phase in the cell division cycle. Here, inhibition of cell cycle arrest resulted in apoptosis induction in caspase‐3 proficient MCF‐7 cells upon expression of p14ARF. This occurred in the absence of S‐phase progression or mitotic entry. In contrast, syngeneic, caspase‐3 deficient MCF‐7 cells remained entirely resistant to p14ARF induced apoptosis. Thus, cell cycle checkpoint abrogation overcomes resistance to p14ARF induced cell death and promotes cell death via a caspase‐3 dependent pathway. Cell death co...
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Unbalanced estrogen metabolism in thyroid cancer
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Abstract Well‐differentiated thyroid cancer most frequently occurs in premenopausal women. Greater exposure to estrogens may be a risk factor for thyroid cancer. To investigate the role of estrogens in thyroid cancer, a spot urine sample was obtained from 40 women with thyroid cancer and 40 age‐matched controls. Thirty‐eight estrogen metabolites, conjugates and DNA adducts were analyzed by using ultraperformance liquid chromatography/tandem mass spectrometry, and the ratio of adducts to metabolites and conjugates was calculated for each sample. The ratio of depurinating estrogen‐DNA adducts to estrogen metabolites and conjugates significantly differed between cases and controls (p<0.0001), demonstrating high specificity and sensitivity. These findings indicate that estrogen meta...
Silencing the mannose 6‐phosphate/IGF‐II receptor differentially affects tumorigenic properties of normal breast epithelial cells
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ABSTRACT Although loss of the mannose 6‐phosphate/insulin‐like growth factor–II receptor (M6P/IGF‐IIR) in breast cancer is believed to play a role in tumorigenesis, it has not been demonstrated that M6P/IGF‐IIR loss is sufficient to confer a malignant phenotype in an untransformed cell. We investigated the impact of M6P/IGF‐IIR silencing using phenotypically normal (MCF‐10A) and oncogenically transformed (MCF‐10T, the c‐Ha‐ras transformed derivative of MCF‐10A) human breast epithelial cell lines as model systems. In both cell lines, silencing of M6P/IGF‐IIR increased cell proliferation and motility, with the effects being more pronounced in MCF‐10A cells. While anchorage independent growth was increased by M6P/IGF‐IIR silencing in MCF‐10T cells, MCF‐10A cell...