Advertisement

Topics

Study to Investigate the Therapeutic Role of RNA Fragments in Platelet Production During Chemotherapy

2014-08-27 03:12:11 | BioPortfolio

Summary

The purpose of this study is to measure the therapeutic potential of Escherichia coli (E. coli) and yeast ribosomal Ribonucleic acid (RNA) fragments to maintain the production of platelets in patients undergoing cytotoxic therapy for cancer.

Description

Myelosuppressive chemotherapy has the potential to produce life threatening neutropenia, anemia, and thrombocytopenia. All of these conditions compromise therapeutic dosing which impacts survival as well as quality of life. The introduction of recombinant growth factors has enabled oncologists to minimize or prevent the development of treatment-induced anemia and neutropenia, but the management of chemotherapy-induced thrombocytopenia (CIT) remains a major challenge. American Society of Clinical Oncology (ASCO) guidelines recommend dose reduction in chemotherapy following onset of thrombocytopenia despite data showing full dose, on time, chemotherapy leads to reduced tumor burden and better overall survival [1-3]. Patients with CIT experience potentially life threatening complications, delay in treatment, poorer outcomes, and consume inordinate amounts of health care resources for supportive care [4]. Development of an agent that ameliorates CIT would represent a major breakthrough in cancer treatment.

Platelets are anuclear cell particles that are released into the bloodstream by megakaryocytes located in the bone marrow. The differentiation of megakaryocytes is regulated by an intricate interaction of specific cytokines and growth factors [5]. Bone marrow stromal elements are also critical to the differentiation and release of platelets. Cancer chemotherapy often depletes the stem and progenitor cells involved in platelet proliferation, which leads to a diminution of platelets and temporary interruption of platelet production lasting until stromal elements and megakaryocytes regenerate.

There are several experimental agents targeted to prevent thrombocytopenia. These investigational agents are cytokines involved in the differentiation and production of platelets [6]. Currently, the only agent commercially available for prevention of thrombocytopenia is Neumega, a derivative of IL-11. Data on Neumega (Oprelekin) indicates a shorter duration of chemotherapy-induced thrombocytopenia, but the toxicity profile has prevented its widespread introduction into the clinical setting. Overall, the absence of agents that minimize or reverse CIT continues to severely limit many patients' ability to complete the full schedule of chemotherapy at the doses originally prescribed by treating oncologists [1].

This study is a dose escalation trial investigating the anti-thrombocytopenic benefits and safety of single stranded RNA fragments. The short chain RNA fragments are obtained by controlled degradation of prokaryotic RNA with ribonuclease. Beljanski showed that these RNA fragments act as primers for DNA synthesis in vitro and found that variations in the method of degradation yielded different preparations that prime deoxyribonucleic acid (DNA) synthesis with distinct tissue specificity. The RNA fragments used in this study, when administered orally, localize in the bone marrow where they appear to prime DNA replication in stem cells resulting in proliferation of white blood cells and platelets. Beljanski et al. reported that these specific RNA fragments were effective in restoring normal levels of circulating platelets following drug induced thrombocytopenia [7;8]. Demonstrating the utility of these specific RNA fragments for prevention and treatment of thrombocytopenia among cancer patients undergoing chemotherapy is especially attractive given the absence of the side effects associated with growth factors and hormones.

This trial investigated the efficacy of two RNA preparations—extracted, purified and fragmented according Beljanski's procedure—to ameliorate CIT: one derived from E. coli and the second from yeast (a eukaryote). RNA molecules are present in any diet and can be considered conditional essential nutrients under conditions of physiological stress [9]. Purified RNA prepared by various methods can be found in nutritional products for hospitalized patients and infant formula [9-11]. This clinical trial evaluated the biologic effects of various doses of these specially prepared 'primer' RNA fragments on platelet numbers in cancer patients who have already developed thrombocytopenia while undergoing chemotherapy.

Study Design

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Conditions

Thrombocytopenia

Intervention

E. coli RNA fragments

Location

Midwestern Regional Medical Center
Zion
Illinois
United States
60099

Status

Completed

Source

Cancer Treatment Centers of America

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-08-27T03:12:11-0400

Clinical Trials [269 Associated Clinical Trials listed on BioPortfolio]

The Protective Immune Response to Attenuated Enterotoxigenic Escherichia Coli Infection

The existing diarrhoeagenic Escherichia coli (E. coli) challenge model is already suitable for dietary interventions in its current form, targeted to impact on the immediate clinical sympt...

Characterization of Resistance Against Live-attenuated Diarrhoeagenic E. Coli

Although the existing diarrhoeagenic Escherichia coli (E. coli) challenge model is already suitable for dietary interventions in its current form, further characterization of the working-...

Management of Fragments During Ureteroscopy

The purpose of this study is to study the outcome of patients after ureteroscopy in which all fragments remaining after holmium laser lithotripsy were retrieved compared to those where sma...

Mortality Due to Septic Shock Associated With Thrombocytopenia

A prospective longitudinal study similar to the one performed by Claushuis and colleagues (2016) will be performed in order to further understand the epidemiology and clinical relationship...

Epidemiology of ST131 in Besançon University Hospital

The sequence type 131 (ST131) is a predominant lineage among extraintestinal pathogenic Escherichia coli. It plays a major role in the worldwide dissemination of E. coli that produce exten...

PubMed Articles [2554 Associated PubMed Articles listed on BioPortfolio]

Rapid detection of Escherichia coli based on 16S rDNA nanogap network electrochemical biosensor.

Simple, fast and effective detection methods of Escherichia coli (E. coli) are essential for human life and health. This article proposes a sensitive and rapid detection method of E. coli based on ele...

CRISPR-Cas adaptation in Escherichia coli requires RecBCD helicase but not nuclease activity, is independent of homologous recombination, and is antagonized by 5' ssDNA exonucleases.

Prokaryotic adaptive immunity is established against mobile genetic elements (MGEs) by 'naïve adaptation' when DNA fragments from a newly encountered MGE are integrated into CRISPR-Cas systems. In Es...

Designing and Assembling Plasmids for the Construction of Escherichia coli Biosensor for Vibrio cholerae Detection.

In the process of constructing and characterizing the whole cell biosensor for Vibrio cholerae detection, two main techniques have been employed-DNA assembly using the Gibson isothermal assembly react...

Retrospective analysis of the risk of hemorrhage associated with moderate and severe thrombocytopenia of 173 patients with systemic lupus erythematosus.

The aim of the study was to observe the risk of hemorrhage from moderate and severe thrombocytopenia in systemic lupus erythematosus (SLE).A retrospective analysis was undertaken of cases admitted to ...

Rapid onset severe thrombocytopenia following reexposure to piperacillin-tazobactam: report of two cases and review of the literature.

Pipercillin-tazobactam is a frequently used antibiotic that has a broad spectrum of antibacterial activity. The development of severe thrombocytopenia following the use of piperacillin-tazobactam is u...

Medical and Biotech [MESH] Definitions

Strains of ESCHERICHIA COLI that are a subgroup of SHIGA-TOXIGENIC ESCHERICHIA COLI. They cause non-bloody and bloody DIARRHEA; HEMOLYTIC UREMIC SYNDROME; and hemorrhagic COLITIS. An important member of this subgroup is ESCHERICHIA COLI O157-H7.

Strains of Escherichia coli that possess virulence traits which allow them to invade, colonize, and induce disease in tissues outside of the GASTROINTESTINAL TRACT. They are a cause of URINARY TRACT INFECTIONS (UROPATHOGENIC ESCHERICHIA COLI); neonatal MENINGITIS; SEPSIS; PNEUMONIA; and SURGICAL WOUND INFECTION.

An enterohemorrhagic Escherichia coli of the O subfamily that can cause severe FOODBORNE DISEASE. The H4 serotype strain produces SHIGA TOXINS and has been linked to human disease outbreaks, including some cases of HEMOLYTIC-UREMIC SYNDROME, resulting from contamination of foods by feces containing E. coli O104.

Variation in a population's DNA sequence that is detected by determining alterations in the conformation of denatured DNA fragments. Denatured DNA fragments are allowed to renature under conditions that prevent the formation of double-stranded DNA and allow secondary structure to form in single stranded fragments. These fragments are then run through polyacrylamide gels to detect variations in the secondary structure that is manifested as an alteration in migration through the gels.

A verocytotoxin-producing serogroup belonging to the O subfamily of Escherichia coli which has been shown to cause severe food-borne disease. A strain from this serogroup, serotype H7, which produces SHIGA TOXINS, has been linked to human disease outbreaks resulting from contamination of foods by E. coli O157 from bovine origin.

More From BioPortfolio on "Study to Investigate the Therapeutic Role of RNA Fragments in Platelet Production During Chemotherapy"

Advertisement
Quick Search
Advertisement
Advertisement

 

Relevant Topics

Blood
Blood is a specialized bodily fluid that delivers necessary substances to the body's cells (in animals) – such as nutrients and oxygen – and transports waste products away from those same cells.  In vertebrates, it is composed of blo...

Cancer Disease
Cancer is not just one disease but many diseases. There are more than 100 different types of cancer. Most cancers are named for the organ or type of cell in which they start - for example, cancer that begins in the colon is called colon cancer; cancer th...


Searches Linking to this Trial