Digestive System Diseases

Symptoms and General Pathology

All Conditions

Neoplasms

Infections

Liver Cirrhosis

Carcinoma

Carcinoma, Hepatocellular

Hepatitis A

Hepatitis

Fibrosis

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Liver Diseases

Gastrointestinal Diseases

Adenocarcinoma

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Hematinics

All Drugs and Chemicals

Liver Extracts

Bilirubin

Normal volunteers without any history of liver disease and with normal liver functions test (LFT), including total protein/Albumin, LDH, ALT, AST, GGT, total bilirubin, direct and indirect bilirubin and do not belong to group B.

Volunteers will be screened using questionnaires. Those deemed suitable will then be asked to have the blood test done. All blood tests are done free of charge to subjects.

Liver cirrhosis, proven by liver biopsy or on clinical evidences, such as varices on CT scan indicative of portal hypertension.

HCC patients with active malignant disease and only palliative care are offered.

Alex Chang, MD

Hepatocellular carcinoma (HCC) is the fifth commonest cancer in the world with poor prognosis, as the annual mortality is almost equivalent to the incidence. This is mainly due to late diagnosis and co-morbid liver dysfunction. HCC is prevalent in our region than in the West due to prevalent Hepatitis B infection and carriers. At the time of diagnosis, only 10 - 20% of HCC patients are candidates for liver resection or transplantation. Almost 40-50% of patients have such poor liver function and co-morbid conditions that only supportive cares are offered. Thus the median survival time is 18-24 months for resectable disease, 6 months for unresectabe disease and 3 months for metastatic disease.

Current screening methods for HCC in high risk patients depend on alpha-fetoprotein (AFP) and ultrasound of the liver. Neither test is sensitive or specific enough for early detection. Therefore, early diagnosis with novel protein biomarkers is needed urgently and may provides hope to improve treatment outcome.

Our preliminary study in 49 HCC patients have identified several proteins such as truncated complement C3a, albumin, B2 microglobulin, may be potentially helpful in early diagnosis. We have started a large prospective and longitudinal study in July 2006, with nearly 100 patients accrued. This application is to extend and expand our current study. We aim to (i) identify and validate novel protein biomarkers for early diagnosis of HCC (ii) conduct longitudinal proteomics with most up-to-date methods to discover new biomarker for early detection and prognostication of HCC (iii) set up gene and plasma depository and clinical database for HCC in collaboration with Singapore Tissue Network.

Up to 40% of HCC patients have normal AFP. Moreover, AFP can also be elevated in patients with cirrhosis or exacerbation of chronic hepatitis. Prospective studies evaluating the value of AFP in HCC surveillance have reported sensitivities of 39-64%, specificity of 76-91% and positive predictive values of 9 -32% 9-11.

Recently, a small handful of biomarkers were identified in the blood of 49 HCC patients by SELDI / MS proteomic analysis of their blood with specificity and sensitivity both at 90% 12, 13. These were truncated complement C3a, albumin, B2 microglobulin, and histidine-rich glycoprotein. In addition, insulin growth factor (IGF) and its binding protein have been shown to be novel biomarkers of HCC 14-17. A larger prospective study is necessary to validate these findings.

Other investigators have also used Surface-enhanced laser desorption / ionization time-of-flight mass spectrometry (SELDI) to study proteomics in HCC. Most of the studies included small numbers of patients and did not include independent test set or report on reproducibility most of the time. Thus, controversies continue on both the technology of SELDI and validation of the findings. Nevertheless, Ward et al reported that Kappa and Lumda immunoglobulin light chains were elevated by an average pf 50% in the serum of HCC patients (p \< 0.001, sensitivity 94%, specificity 86%) with Hepatitis C related cirrhosis 18. Schwegler et al reported that SELDI-TOF MS profiling of serum can distinguish chronic Hepatitis C from HCV- related HCC with a sensitivity of 61% and a specificity of 76%. Sensitivity and specificity can be improved with the addition of AFP, des-gamma carboxyprothrombin, and GP73 19. Other reports also indicated potential marker of heat-shock protein 27 20 and complement C3a 21. However, all studies lack prospective and longitudinal follow-up with multiple serum samples from same patient. Our trial is designed to test the changes of proteomic overtime to identify the earliest possible biomarkers for HCC.

Protein Biomarker in Hepatocellular Carcinoma

Protein Biomarkers for Early Detection and Prognostication in Hepatocellular Carcinoma (HCC)

Number of participants with truncated complement C3a, albumin, B2-microglobulin and histidine-rich glycoprotein, IGF-I, and IGF-II on first blood sample.

To study the prospective and longitudinal value of these protein markers in detecting HCC by regular measurement of these proteins and follow up with routine clinical practice in high-risk patients.

Singapore Cancer Society

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Patients undergo DCE-MRI over approximately 30-60 minutes consisting of an anatomical scout image to localize the region of interest, a set of pre-injection scans to calibrate the dynamic image set, a dynamic image set during which contrast agent will be injected, and a set of post-injection scans to calibrate the DCE-MRI database.

Jinha Park, MD, Ph.D.

This pilot clinical trial studies dynamic contrast enhanced (DCE)-magnetic resonance imaging (MRI) in diagnosing cancer. New diagnostic procedures, such as DCE-MRI may help find and diagnose cancer

PRIMARY OBJECTIVES:

I. Optimize and develop functional DCE-MRI pulse sequences, which involve the injection of MRI-visible contrast agents, for imaging in the head/neck, abdominal and pelvic regions.

II. Determine the ideal radiofrequency (RF) coil setup to maximize signal to noise ratio of the optimized pulse sequences.

III. Distill the findings of specific aims 1 and 2 into streamlined protocols that can be used in subsequent studies for cancer phenotyping and treatment monitoring in a quantitative manner.

IV. To establish a virtual reference image repository for future studies.

OUTLINE: Patients undergo DCE-MRI over approximately 30-60 minutes consisting of an anatomical scout image to localize the region of interest, a set of pre-injection scans to calibrate the dynamic image set, a dynamic image set during which contrast agent will be injected, and a set of post-injection scans to calibrate the DCE-MRI database.

Optimization of Novel DCE-MRI Imaging Sequences for Cancer Therapy Monitoring

Analysis of DCE-MRI data will be by semi-quantitative metrics such as the area under the curve (AUC), the slopes of contrast agent uptake and washout curves as well as peak contrast agent uptake. Alternatively quantitative metrics based upon pharmacokinetic modeling will be derived. The model is the 2-compartment Kety model from which volume transfer constants between compartments and volume of the tissue compartments can be calculated.

City of Hope Medical Center

Skin and Connective Tissue Diseases

Rare Diseases

Skin Diseases

Carcinoma, Merkel Cell

Communicable Diseases

Polyomavirus Infections

Virus Diseases

DNA Virus Infections

Tumor Virus Infections

Carcinoma, Neuroendocrine

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Merkel Cell Carcinoma

Neuroendocrine Tumor

Neuroepithelioma

Subjects with a skin disease or at risk of developing a skin disease/ Family member of persons with a skin disease

Monica Taylor, R.N.

For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)

Heidi H Kong, M.D.

Background:

- Skin disease can have many causes. It can have widespread consequences, and in rare cases can lead to death. Researchers want to determine the causes of various types of skin diseases and find a way to treat them.

Objectives:

- To determine the causes of various skin diseases and find ways to treat them.

Eligibility:

* People ages 2 and older who have:

  * A skin disease or at risk of developing a skin disease OR
  * A family member of persons with a skin disease
* Healthy volunteers ages 2 and older

Design:

* Participants will be screened under a separate protocol.
* Participants may take a survey about how their skin condition affects their quality of life.
* Participants will have a medical history and a physical exam including a detailed skin exam. Pictures will be taken of their skin to document any skin disease.
* Participants will have specimens collected. This may include:

  * Several teaspoons of blood taken at each visit
  * Stool samples
  * Nail and body fluid (like saliva) samples
  * Cheek swabs. The inside of the cheek will be scraped for about a minute in each direction to collect cells.
  * Collection of skin samples with:

    * A swab (like a Q-tip)
    * Gently scraping skin to remove the outer layers of cells
    * Applying and removing 1-inch pieces of tape
* Participants may have up to 4 skin biopsies in 12 months, with 4 separate biopsies taken each time.

  * An area of skin will be numbed with an injection.
  * A piece of skin the size of a pencil eraser will be removed using a small instrument.
  * A flat scar usually develops at the biopsy site.

Background:

* Skin diseases represent one of the most common medical problems in the United States, affecting 1 in 3 people at any given time.
* Complex interactions between genetic background and the environment are relevant to understanding skin disease.
* By studying dermatoses, we may gain insight into the complex host-environment interactions that give rise to or exacerbate these skin conditions, and into links between inflammation and cancer.

Objective:

-To procure biologic samples for exploratory cellular, molecular, genetic and genomic biological studies from subjects with dermatologic conditions, subjects at risk for developing dermatologic conditions and healthy volunteers in the support of NIH biomedical studies

Eligibility:

-Subjects with or at risk of developing dermatologic diseases, family members of subjects with dermatologic diseases, or healthy volunteers, including adults and children.

Design:

* The purpose of this study is to examine, in an exploratory fashion, a variety of biologic assays relevant to the investigation of dermatologic diseases.
* Approximately 50 subjects are anticipated to consent to the study each year with an accrual ceiling of 500 consented subjects planned over 10 years.

Studies of Dermatologic Diseases Biospecimen Acquisition Protocol

Studies of Dermatologic Diseases-Biospecimen Acquisition Protocol

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Syndrome

Polycystic Ovary Syndrome

Cysts

Ovarian Cysts

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Gonadal Disorders

Endocrine System Diseases

Reproductive Control Agents

Ganirelix

Chorionic Gonadotropin

Menotropins

Women with infertility diagnosis of male factor only or women who are oocyte donors

Women with Polycystic Ovary Syndrome with a BMI between 30-35

Women with Polycustic Ovary Syndrom with a BMI between 20 \& 25

1. Ovulation Induction: Achieved with recombinant FSH (Follistim®) with or without HMG (Menopur®) at total doses of 75-450 IU/day subcutaneous (SC) for 9-14 days.
2. Ovulation Suppression: GnRH Antagonist (Ganirelix® - 250microgram 0.5ml) will be initiated following ovulation induction when lead follicle \>14mm diameter on ultrasound and continued through the day of hCG (Novirel® or Ovidrel ®) injection
3. hCG Injection: Once patient has met criteria for oocyte retrieval, she will inject either Novarel® (5,000-10,000 units Intramuscular) or Ovidrel® (250microgram - 500microgram SC) 35 hours prior to oocyte retrieval.

IVF Antagonist Protocol

Steven Lindheim, MD, MMM

Julie Sroga, MD

Steven Lindheim, MD,MMM

To the best of the investigators knowledge, exhaustive characterization of the low and high abundant proteins and glyco-proteins of the Follicular Fluid (FF) has not yet been achieved. Such an analysis may provide critical molecular data on the role of the FF in oocyte maturation and may identify specific changes in the FF proteome of patients with gynecologic problems, such as Polycystic Ovary Syndrome (PCOS).

Specific Aims

1. To perform a comprehensive analysis of normal human FF using sensitive mass spectrometry in combination with conventional approaches for proteomic evaluation and using HPLC and Western blot for glyco-proteomic analysis.
2. Characterize differential proteomic and glyco-proteomic patterns of the FF in normal women compared to lean and obese women with PCOS.
3. To supplement the differential proteomic and glyco-proteomic analysis with steroid hormone analysis in all FF samples.

In this study, we plan to utilize ultrasensitive mass spectrometry (MS) and other conventional proteomic approaches to identify the low and high abundant proteins present in human FF. Additionally, we plan to use high-performance liquid chromatography (HPLC) and Western blot techniques to evaluate the Neu5Gc and glycan array based ELISA techniques to detect anti-Neu5Gc antibody profile in human FF. This analysis will be performed on FF samples obtained from normal women undergoing In-Vitro Fertilization and Embryo Transfers (IVF-ET) for a male factor alone and oocyte donors from our 3rd Party Reproduction Program and from lean and obese women with PCOS. This study will provide information on protein, glycoprotein, and steroid hormone expression during normal folliculogenesis and during the pathologic condition of PCOS, which should also provide basic scientific information on normal and abnormal oocyte development.

Human FF bathes the developing oocyte. Previous studies indicate that the FF contains cytokines, steroidal and protein hormones, and growth factors. The presence of proteins with such significant biological properties implies a paracrine and autocrine role for the FF in promoting normal oocyte development. Furthermore, the presence of any antigenic sialic acid Neu5Gc and the presence of antibodies targeting these antigenic glycoconjugates (glycolipid and glycoproteins decorated with sialic acid) may interfere with oocyte development, hormonal expression, fertilization, and possibly implantation. Here we hypothesize that an exhaustive proteomic and glyco-proteomic characterization of human FF is essential for a thorough understanding of its biological significance. We also hypothesize that PCOS may have differential expression of the FF protein and glyco-protein milieu, and that the expression may differ further between lean and obese women with PCOS. PCOS represents a heterogeneous disorder. The severity of hyperandrogensim, metabolic and menstrual disturbance, and obesity is variable with up to 40% not clinically expressing signs of classic hyperandrogenism. On the other hand, these atypical, often lean, PCOS women can have impaired glucose tolerance and diabetes. Reports suggest that these lean PCOS women have altered serum IGFBP-1, a characteristic endocrine feature of patients with obese PCOS, and related to hyperinsulinemia and/or obesity. The lean phenotype of PCOS and its significance is unclear but may represent a cryptic or unexpressed form of PCOS or may be a prelude to individuals who will later manifest clinical signs of obese/overweight PCOS. Changes in expression may be expected because of the different amounts of steroidal hormones and inflammatory markers in the FF derived from women with PCOS.

Proteomics & Glyco-Proteomic Analysis of Follicular Fluid

Proteomics & Glyco-Proteomic Analysis of Follicular Fluid Derived From Health Patient/Donors and Polycystic Ovary Syndrome Patients

For proteomic analysis the follicular fluid samples will be either directly analyzed by MS or will be processed to deplete albumin which is likely to be present in very high abundance in the FF.

An aliquot of FF from each patient will be analyzed for the following steroid hormones: progesterone, 17-alpha-hydroxyprogesterone, androstenedione, testosterone, estradiol, and dihydrotestosterone.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Protein Biomarker in Hepatocellular Carcinoma	NCT00465842	Normal Voluntee... Hepatitis Liver Cirrhosis Hepatocellular ...		18 Years -	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Optimization of Novel DCE-MRI Imaging Sequences for Cancer Therapy Monitoring	NCT01752231	Normal Voluntee...		18 Years - 100 Years	City of Hope Medical Center
Protein Biomarker in Hepatocellular Carcinoma	NCT00465842	Normal Voluntee... Hepatitis Liver Cirrhosis Hepatocellular ...		18 Years -	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Studies of Dermatologic Diseases Biospecimen Acquisition Protocol	NCT02471352	Dermatologic Co... Healthy Volunte... Normal Voluntee... Carcinoma, Merk...		1 Day - 100 Years	National Institutes of Health Clinical Center (CC)
Proteomics & Glyco-Proteomic Analysis of Follicular Fluid	NCT01487486	Polycystic Ovar... Normal Voluntee...	IVF Antagonist ...	18 Years -	University of Cincinnati
Proteomics & Glyco-Proteomic Analysis of Follicular Fluid	NCT01487486	Polycystic Ovar... Normal Voluntee...	IVF Antagonist ...	18 Years -	University of Cincinnati

Spots Global Cancer Trial Database for normal volunteers