This study aims to find a novel biomarker for early detection of pancreatic cancer through non-invasive means. Researchers are using a mouse model to induce pancreatic cancer and analyzing samples of blood, feces, and urine using NMR spectroscopy. Histological analysis of mouse pancreatic tissues will also be performed to determine levels of pancreatic intraepithelial neoplasia (PanIN) development. The goal is to correlate metabonomic data from NMR with known PanIN levels to identify a biomarker that could enable pre-cancerous detection of pancreatic cancer in patients through clinical trials.
ROI of Colorectal Cancer Screening - Colorado Cancer Coalition - Colorado Bus...Ryan Kerr
The Colorado Cancer Coalition presented to the Colorado Business Group on Health.
The aim of the presentation was to inform Colorado Businesses of the clinical and financial improvement opportunity that exists within the Colorectal Cancer space.
Dr. Talita Resende - Organoids as an invitro model for enteric diseasesJohn Blue
Organoids as an invitro model for enteric diseases - Dr. Talita Resende, from the 2018 Allen D. Leman Swine Conference, September 15-18, 2018, St. Paul, Minnesota, USA.
More presentations at http://www.swinecast.com/2018-leman-swine-conference-material
Assessment of Prostate Cancer Aggressiveness: A Metabolomics Evaluation of Ur...ChristianeProllMBA
Prostate cancer (PCa) is the most common non-skin cancer type among men and one of the leading
causes of cancer deaths worldwide [1]. The current diagnostic options of biopsy in combination with
PSA-based tests are not conclusive to the aggressiveness of the disease. Novel diagnostic tests for a
reliable non-invasive identification of aggressive PCa with high sensitivity and specificity are urgently
needed and would be a great advance in clinical routine. At the moment, no single biomarker could be
identified to be specific to prostate cancer. In this project, we attempt the identification and validation
of urinary metabolite biomarkers and biomarker networks, i.e. high-dimensional classifiers, associated
with aggressive prostate cancer.
The most complete map of oncogenes to date a summary of 568 oncogenes in 66 c...DoriaFang
By analyzing the genomes of 28,076 tumor samples from 66 types of cancer, 568 cancer driver genes were identified. This is the most complete map of cancer driver genes to date. The research data has been updated on the IntOGen platform.
HUMAN PAPILLOMAVIRUS IS A NECESSARY CAUSE OF INVASIVE CERVICAL CANCER WORLD-WIDEAlberto Cuadrado
Infection with oncogenic human papillomavirus (HPV) is the major risk factor in the aetiology of cervical cancer. In a
previous study of invasive cervical cancers collected from 22 countries (the International Biological Study on Cervical
Cancer, IBSCC), however, the PCR assay used failed to detect HPV DNA in 7% of samples. The current study
re-examined these so-called HPV-negative samples, as well as a proportion of the originally positive samples, using a
more stringent procedure to ensure the presence of carcinoma cells within the material used for PCR. In addition,
three different PCR assays targeting different open reading frames were used, to avoid misclassifying as negative
samples in which integration of HPV DNA had led to disruption of the PCR primer sequences or loss of the HPV L1
open reading frame, the target of the PCR assay used in the original study. Furthermore, sera from the patients
originally classified as HPV-negative were assayed for antibodies against viral-like particles (VLPs) and E6 and E7
proteins of HPV 16, which accounts for about 50% of HPV-positive cervical cancers world-wide.
Of those serum samples tested, antibodies to at least one HPV 16 protein were detected in a similar proportion of
those originally classified as HPV-negative or -positive: 56% and 67%, respectively. There was no significant difference
between the two groups in the proportion of antibodies reactive to VLPs, E6 or E7. After excluding histologically
inadequate samples (87%), only 6% of those initially classified as HPV-negative remained negative to all the PCR
assays used for retesting. Thus the true incidence of HPV-positive samples in the IBSCC is 99.7%.
Most of the HPV-negative samples in the earlier study proved to have been misclassified since a more stringent
testing procedure revealed them to be HPV-positive. The similarity of the serum antibody profiles from patients with
cancers originally classified as HPV-positive and –negative indicates that a significant proportion of the latter were in
fact HPV 16- associated. The extreme rarity of HPV-negative cancers reinforces the rationale for HPV testing in
addition to, or even instead of, cervical cytology in routine cervical screening.
The KRAS-Variant and miRNA Expression in RTOG Endometrial Cancer Clinical Tri...UCLA
The KRAS-variant may be a genetic marker of risk for type 2 endometrial cancers. In addition, tumor miRNA expression appears to be associated with patient age, lymphovascular invasion and the KRAS-variant, supporting the hypothesis that altered tumor biology can be measured by miRNA expression, and that the KRAS-variant likely impacts endometrial tumor biology.
Diagnosis of endometriosis in the 21 st centuryArunSharma10
Diagnosis of endometriosis is a challenge
Unmet needs in diagnosis of endometriosis
Non-invasive diagnosis of endometriosis
Urinary biomarkers
Peripheral biomarkers
Genetic predisposition in endometriosis
Genetic tests in endometriosis
Tissue biomarkers
miRNAs in the diagnosis of endometriosis
Endometriosis diagnosis
ROI of Colorectal Cancer Screening - Colorado Cancer Coalition - Colorado Bus...Ryan Kerr
The Colorado Cancer Coalition presented to the Colorado Business Group on Health.
The aim of the presentation was to inform Colorado Businesses of the clinical and financial improvement opportunity that exists within the Colorectal Cancer space.
Dr. Talita Resende - Organoids as an invitro model for enteric diseasesJohn Blue
Organoids as an invitro model for enteric diseases - Dr. Talita Resende, from the 2018 Allen D. Leman Swine Conference, September 15-18, 2018, St. Paul, Minnesota, USA.
More presentations at http://www.swinecast.com/2018-leman-swine-conference-material
Assessment of Prostate Cancer Aggressiveness: A Metabolomics Evaluation of Ur...ChristianeProllMBA
Prostate cancer (PCa) is the most common non-skin cancer type among men and one of the leading
causes of cancer deaths worldwide [1]. The current diagnostic options of biopsy in combination with
PSA-based tests are not conclusive to the aggressiveness of the disease. Novel diagnostic tests for a
reliable non-invasive identification of aggressive PCa with high sensitivity and specificity are urgently
needed and would be a great advance in clinical routine. At the moment, no single biomarker could be
identified to be specific to prostate cancer. In this project, we attempt the identification and validation
of urinary metabolite biomarkers and biomarker networks, i.e. high-dimensional classifiers, associated
with aggressive prostate cancer.
The most complete map of oncogenes to date a summary of 568 oncogenes in 66 c...DoriaFang
By analyzing the genomes of 28,076 tumor samples from 66 types of cancer, 568 cancer driver genes were identified. This is the most complete map of cancer driver genes to date. The research data has been updated on the IntOGen platform.
HUMAN PAPILLOMAVIRUS IS A NECESSARY CAUSE OF INVASIVE CERVICAL CANCER WORLD-WIDEAlberto Cuadrado
Infection with oncogenic human papillomavirus (HPV) is the major risk factor in the aetiology of cervical cancer. In a
previous study of invasive cervical cancers collected from 22 countries (the International Biological Study on Cervical
Cancer, IBSCC), however, the PCR assay used failed to detect HPV DNA in 7% of samples. The current study
re-examined these so-called HPV-negative samples, as well as a proportion of the originally positive samples, using a
more stringent procedure to ensure the presence of carcinoma cells within the material used for PCR. In addition,
three different PCR assays targeting different open reading frames were used, to avoid misclassifying as negative
samples in which integration of HPV DNA had led to disruption of the PCR primer sequences or loss of the HPV L1
open reading frame, the target of the PCR assay used in the original study. Furthermore, sera from the patients
originally classified as HPV-negative were assayed for antibodies against viral-like particles (VLPs) and E6 and E7
proteins of HPV 16, which accounts for about 50% of HPV-positive cervical cancers world-wide.
Of those serum samples tested, antibodies to at least one HPV 16 protein were detected in a similar proportion of
those originally classified as HPV-negative or -positive: 56% and 67%, respectively. There was no significant difference
between the two groups in the proportion of antibodies reactive to VLPs, E6 or E7. After excluding histologically
inadequate samples (87%), only 6% of those initially classified as HPV-negative remained negative to all the PCR
assays used for retesting. Thus the true incidence of HPV-positive samples in the IBSCC is 99.7%.
Most of the HPV-negative samples in the earlier study proved to have been misclassified since a more stringent
testing procedure revealed them to be HPV-positive. The similarity of the serum antibody profiles from patients with
cancers originally classified as HPV-positive and –negative indicates that a significant proportion of the latter were in
fact HPV 16- associated. The extreme rarity of HPV-negative cancers reinforces the rationale for HPV testing in
addition to, or even instead of, cervical cytology in routine cervical screening.
The KRAS-Variant and miRNA Expression in RTOG Endometrial Cancer Clinical Tri...UCLA
The KRAS-variant may be a genetic marker of risk for type 2 endometrial cancers. In addition, tumor miRNA expression appears to be associated with patient age, lymphovascular invasion and the KRAS-variant, supporting the hypothesis that altered tumor biology can be measured by miRNA expression, and that the KRAS-variant likely impacts endometrial tumor biology.
Diagnosis of endometriosis in the 21 st centuryArunSharma10
Diagnosis of endometriosis is a challenge
Unmet needs in diagnosis of endometriosis
Non-invasive diagnosis of endometriosis
Urinary biomarkers
Peripheral biomarkers
Genetic predisposition in endometriosis
Genetic tests in endometriosis
Tissue biomarkers
miRNAs in the diagnosis of endometriosis
Endometriosis diagnosis
Feature story from the Garvan Institute of Medical Research's April 2013 issue of Breakthrough newsletter. More at https://www.garvan.org.au/news-events/newsletters
26 ASBMB TODAY FEBRUARY 2021Discovering an old DoGs’ neMargaritoWhitt221
26 ASBMB TODAY FEBRUARY 2021
Discovering an old DoGs’
new trick
Heterotrimeric G proteins regulate
a variety of signaling pathways that
control cell development and influ-
ence cell morphology via actin/cyto-
skeleton remodeling. There are four
main families of G proteins: Gi/Go,
Gq, Gs and G12/13. Researchers long
have thought that Gs, unlike its family
members, is coupled specifically and
exclusively to adenylyl cyclases.
In a new study published in the
Journal of Biological Chemistry,
Alejandro Castillo–Kauil of the
Center for Research and Advanced
Studies of the National Polytechnic
Institute and collaborators challenge
this dogmatic view by identifying a
new Gs target. Using biochemical,
molecular biological and chemo-
genetic approaches, the researchers
demonstrated that the Gαs subfamily
of G proteins can regulate the activity
of Rho GTPases such as Rho guanine
nucleotide exchange factor, or Rho-
GEF. The interaction identified by the
group activates the small G protein
Cdc42 by Gs-coupled GPCRs, stimu-
lating a rearrangement of the cyto-
skeleton and inducing formation of
fingerlike protrusions called filopodia.
These results provide new insight
into G protein activity and define a
new role for RhoGEF coupling in G
protein function.
DOI: 10.1074/jbc.AC120.015204
A pathogen’s proteins target
mitochondria
The tick-borne pathogen Coxiella
burnetii causes Q fever, or query fever,
a rare flulike disease that can spread
to humans who inhale dust particles
contaminated by infected farm or
CONTINUED FROM PAGE 25
Noninvasive tool provides oral cancer prognosis
Oral squamous cell carcinoma, which affects about 34,000 people
in the U.S. each year, is found in the cells lining the lips and mouth.
Metastasis to the lymph nodes is a sign of disease progression and may
be accompanied by changes in proteolytic activity. During proteolysis,
enzymes cut up proteins into short fragments called peptides. Recent
work suggests that characterizing the sequence and abundance of these
molecules — a method dubbed peptidomics — might provide new in-
sight on cancer biology and in the clinic. In a recent paper in the journal
Molecular & Cellular Proteomics, Leandro Xavier Neves of the Brazil-
ian Biosciences National Laboratory and a team of Brazilian clinicians
and scientists describe their analysis of oral squamous cell carcinoma
patient saliva using peptidomics.
After extracting peptides from saliva samples, the research team ana-
lyzed and compared the peptide content in samples from patients with
and without metastasis to the lymph nodes. They found more than 1,000
uniquely expressed peptides in each group and an additional 1,628 pep-
tides expressed by both groups. A series of statistical analyses identified
77 peptides of particular interest; all of these peptides are overexpressed
in samples from patients with lymph node metastasis, which supports the
hypothesis that proteolytic activity increases ...
The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
All manuscripts are subject to rapid peer review. Those of high quality (not previously published and not under consideration for publication in another journal) will be published without delay.
Journal of the Formosan Medical Association (2011) 110, 695e70.docxcroysierkathey
Journal of the Formosan Medical Association (2011) 110, 695e700
Available online at www.sciencedirect.com
journal homepage: www.jfma-online.com
ORIGINAL ARTICLE
A multivariable logistic regression equation to
evaluate prostate cancer
Jhih-Cheng Wang a, Steven K. Huan a, Jinn-Rung Kuo b, Chin-Li Lu c,
Hung Lin a, Kun-Hung Shen a,*
a Division of Urology, Departments of Surgery, Chi-Mei Medical Center, Tainan, Taiwan
b Division of Neurosurgery, Department of Surgery, Chi-Mei Medical Center, Tainan, Taiwan
c Department of Medical Research, Chi-Mei Medical Center, Tainan, Taiwan
Received 29 January 2010; received in revised form 14 May 2010; accepted 9 August 2010
KEYWORDS
Logistic regression;
men’s health;
probability;
prostate cancer;
risk factor;
score
* Corresponding author. Division of U
Taiwan 710.
E-mail address: [email protected]
0929-6646/$ - see front matter Copyr
doi:10.1016/j.jfma.2011.09.005
Background/Purpose: A possible means of decreasing prostate cancer mortality is through
improved early detection. We attempted to create an equation to predict the likelihood of
having prostate cancer.
Methods: Between January 2005 and May 2008, patients who received prostate biopsies were
retrospective evaluated. The relationship between the possibility of prostate cancer and the
following variables were evaluated: age; serum prostate specific antigen (PSA) level, prostate
volume, numbers of prostatic biopsies, digital rectal examination (DRE) findings, and the pres-
ence of hypoechoic nodule under transrectal ultrasonography.
Results: A multivariate regression model was created to predict the possibility of having pros-
tate cancer, and a receiver-operating characteristic (ROC) curve was drawn based on the
predictive scoring equation. Using a predictive equation, P Z 1/(1 � e�x), where X Z
�4.88, þ 1.11 (if DRE positive), þ 0.75 (if hypoechoic nodule of prostate present), þ 1.27
(when 7 < PSA � 10), þ 2.02 (when 10 < PSA � 24), þ 2.28 (when 24 < PSA � 50), þ 3.93 (when
50 < PSA), þ 1.23 (when 65 < age � 75), þ 1.66 (when 75 < age), followed by ROC curve
analysis, we showed that the sensitivity was 88.5% and specificity was 79.1% in predicting
the possibility of prostate cancer.
Conclusion: Clinicians can tailor each patient’s follow-up according to the nomogram based on
this equation to increase the efficacy of evaluating for prostate cancer.
Copyright ª 2011, Elsevier Taiwan LLC & Formosan Medical Association. All rights reserved.
rology, Department of Surgery, Chi-Mei Medical Center, 901 Chung Hwa Road, Yung Kang City, Tainan,
il.com (K.-H. Shen).
ight ª 2011, Elsevier Taiwan LLC & Formosan Medical Association. All rights reserved.
mailto:[email protected]
http://dx.doi.org/10.1016/j.jfma.2011.09.005
www.sciencedirect.com/science/journal/09296646
http://www.jfma-online.com
http://dx.doi.org/10.1016/j.jfma.2011.09.005
http://dx.doi.org/10.1016/j.jfma.2011.09.005
696 J.-C. Wang et al.
Prostate cancer is the most common solid malignancy ...
Flavin-Containing Dimethylaniline Monooxygenase 5 Drives Malignancies in Hepa...semualkaira
Hepatic microsomes play an important role in drug metabolism,
but the potential biological functions of hepatic microsome-containing proteins in Hepatocellular Carcinoma (HCC) remain unclear. Here, we used HCC and corresponding adjacent Non-Tumor
(NT) tissues to isolate hepatic microsomes and then performed
RNA high-throughput sequencing
Flavin-Containing Dimethylaniline Monooxygenase 5 Drives Malignancies in Hepa...semualkaira
Hepatic microsomes play an important role in drug metabolism, but the potential biological functions of hepatic microsome-con- taining proteins in Hepatocellular Carcinoma (HCC) remain un- clear. Here, we used HCC and corresponding adjacent Non-Tumor (NT) tissues to isolate hepatic microsomes and then performed RNA high-throughput sequencing. After screening, flavin-con- taining dimethylaniline monooxygenase (FMO5) showed a significantly high expression level and was associated with poor prognosis in patients with HCC.
1. Novel Biomarker for Early Detection of Pancreatic Cancer
Daniel P. Regan, Michelle J. Veite, Michael A. Kennedy, Ph.D.
Department of Chemistry and Biochemistry, Miami University, Oxford, Ohio.
regandp@miamioh.edu, http://chemistry.muohio.edu/kennedy/
Over the course of the past fifteen years, pancreatic cancer has risen to be the
fourth leading cause of cancer-related deaths. With no accurate clinical
screenings available, the late detection of pancreatic cancer has contributed to
the 95% fatality rate after five years of prognosis[1]. The objective of this study is
to find a novel biomarker that will allow for a non-invasive diagnostic test to
identify precancerous lesions known as pancreatic intraepithelial neoplasia. By
utilizing a mouse model, PDAC (pancreatic ductal adenocarcinoma) will be
induced by activating the Kras oncogene, which is the same mutation that occurs
in human oncolytic pathways. The tissues of this sample will be put through
histological analysis for PanIN development and tissue activity. Samples from the
blood, fecal matter, and urine will then be analyzed with NMR spectroscopy. The
aim of this project is to combine the metabonomic data from the NMR and the
PanIN development from the histology to form a statistically specific and
sensitive correlation between a biomarker and known levels of PanIN
development[2]. This biomarker can then be used to perform clinical trials,
allowing for pre-cancerous detection of pancreatic cancer in patients. The
methodology of this project may also give rise to future investigations of
biomarker detection in many other diseases.
Abstract
Methodology
This study was conducted by using a mouse model. In order for the
development of pancreatic cancer, Ptf1a-Cre and Kras G12D mouse lines were
bred to form the study sample. After being genotyped by southern blot,
tissue collection was set up to be completed from a range of 5-16 months of
age. Sample size included 24 study mice per sex, as well as per age.
Within 24 hours of the mouse’s sac date, the mouse was transferred to a
metabolite cage for fecal and urine samples. Upon dissection, a serum
sample, collection of the vital organs and GI tract, and collection of the
pancreas and spleen are performed. Metabolic samples are stored a -80
freezer and organs are transferred to 70% EtOH solution an placed in cold
storage.
Pancreatic tissues are then processed and embedded into wax cassettes.
Protocol for H&E staining is conducted and histological analysis is then
conducted. Tissues are graded based on PanIN development. Remaining
tissue is saved for IHC analysis, targeting p53 among other metabolic activity.
NMR Spectroscopy is then conducted on the fecal, serum, and urine samples.
Samples will be prepared in 1 mL tubes for the 600 MHz Bruker Spectrometer.
Extensive metabonomic activity will be conducted at this level.
All data compiled into the projects database will be analyzed for a novel
biomarker to pancreatic cancer. This will be conducted by analyzing the
metabonomic data and comparing it against the PanIN development. Trends
in age, PanIN thresholds, and sex will be sought out.
The findings of our data will be published and give suggestion to conduct a
clinical experiment in which our biomarker is sought out using our non-
invasive methodology.
This project is made possible by the financial support of the National Institutes of Health, the First Year Research
Experience, Undergraduate Research Award, and Undergraduate Summer Scholars. Collaboration with Dr. David
Klimstra, Director of Pathology at Memorial Sloan Kettering Cancer Center, provides for expert analysis of the
histology. For information and publications related to this research and The HFMR Laboratory visit our website:
http://chemistry.muohio.edu/kennedy/
Acknowledgements
Discussion
The lab is currently in its fourth year of research on this study. At this point in the
study, the lab is collecting the NMR-Spectra and analyzing the histology of the
pancreata. Once all of the bio-fluids and tissues have been analyzed, our lab will have
compiled one of the most extensive molecular study of pancreatic cancer in terms of
sample size and correlation factors. Reviewing previous works and the data that has
been collected thus far, we have reason to believe that there will be a significant
biomarker that correlates to PanIN-2 and PanIN-3 Development[3]. Further
correlations to age, gender, and protein expression will also be analyzed. The goal of
this study is not only to introduce a novel biomarker for pancreatic cancer, but to
open up the door for others to use metabonomic research to find other biomarkers in
the developmental stages of other cancerous models.
Objectives
Create a database with all of the H&E and IHC slides, including notations
Discover trends in age, gender, or protein expression from histology
Understand the mutations caused by pancreatic cancer on a molecular level
Find dissimilarities in the NMR Spectra between control and study mice
Establish a biomarker that correlates to specific PanIN development
Suggest methodology for non-invasive screening for development of
pancreatic cancer in a clinical trial
Provide methodology of metabolomics research of biomarkers for other
cancer models
Results
Figure 1: The photos above are histology slides of the pancreatic tissue from the study exhibiting
varying PanIN development. Normal pancreas, Figure 1A. PanIN 1, Figure 1B. PanIN 2 &3,
Figure 1C. PanIN 3 & PDAC, Figure 1D.
Figure 2: This NMR-Sectra is from a urine sample of an 11 month study mouse. These spectra
will be analyzed against the control samples for variance in peak intensities and up-regulation or
down-regulation of specific metabonomics.
References
[1] Hidalgo, M. (2010). Pancreatic cancer. The New England Journal of Medicine, 362(17), 1605–17.
doi:10.1056/NEJMra0901557
[2]Goodpaster, A. M., Romick-Rosendale, L. E., & Kennedy, M. a. (2010). Statistical significance analysis of nuclear
magnetic resonance- based metabonomics data. Analytical Biochemistry, 401(1), 134–43.
doi:10.1016/j.ab.2010.02.005
[3]Hruban, R. H., Maitra, A., & Goggins, M. (2008). Update on pancreatic intraepithelial neoplasia. International
Journal of Clinical and Experimental Pathology, 1, 306–316.
A B
C D