MedInsight Research Institute

Hampshire, United Kingdom

MedInsight Research Institute

Hampshire, United Kingdom
SEARCH FILTERS
Time filter
Source Type

Rogosnitzky M.,MedInsight Research Institute | Finegold M.J.,Texas College | McLaughlin P.J.,Pennsylvania State University | Zagon I.S.,Pennsylvania State University
Investigational New Drugs | Year: 2013

Summary: Hepatoblastoma is the most common liver malignancy in children, typically diagnosed before age 2. The survival rate for hepatoblastoma has increased dramatically in the last 30 years, but the typical chemotherapeutic agents used for treatment are associated with significant toxicity. In this report, the authors present two cases of hepatoblastoma treated with surgical resection and a novel biotherapeutic regimen that included opioid growth factor (OGF). Case #1 is an infant diagnosed with a large mass on prenatal ultrasound. After subsequent diagnosis of hepatoblastoma, she was treated with one course of neoadjuvant chemotherapy at approximately 1 week of age. Following significant complications from the chemotherapy (neutropenic fever, pneumonia and sepsis), the patient's parents declined further chemotherapy, and the infant was treated with surgical resection and opioid growth factor (OGF)/low dose naltrexone (LDN). She is currently at close to 10 years disease-free survival. Case #2 is a child diagnosed with a liver mass on ultrasound at 20 months of age, later biopsy-proven to represent hepatoblastoma. Due to existing co-morbidities including autosomal recessive polycystic kidney disease and hypertension, and indications from the biopsy that the tumor might be insensitive to chemotherapy, the parents elected not to proceed with neoadjuvant chemotherapy. The patient was treated with surgical resection and OGF/LDN, and is currently at more than 5 years disease-free survival. This case series highlights the need for less toxic treatment options than conventional chemotherapy. Modulation of the OGF-OGF receptor axis represents a promising safe and therapeutic avenue for effective treatment of hepatoblastoma. © 2012 Springer Science+Business Media New York.


Carlock B.H.,Vision Works | Bienstock C.A.,MedInsight Research Institute | Rogosnitzky M.,MedInsight Research Institute
Case Reports in Ophthalmology | Year: 2014

Purpose: We report a case of a symptomatic, inflamed pterygium treated nonsurgically with topical dipyridamole and followed for 12 months. Case Report: A 35-year-old woman presented with a stage II to III, V3, C3, K2, P1 (using Johnston, Williams & Sheppard's classification) pterygium in her right eye. She complained of a foreign body sensation, dryness, burning, and persistent uncontrolled blinking. A raised lesion was observed on the nasal conjunctiva that was 1.5 mm in size. It extended slightly onto the nasal cornea. There was moderate vascularity of the lesion that obscured the underlying scleral vessels. Moderate conjunctival hyperemia was detected at and medial to the pterygium. The cornea, anterior chamber, and external anatomy were otherwise unremarkable. The eye was initially treated twice daily with a topical application of dipyridamole in a normal saline solution, which was later reduced to once daily. Results: There was a marked improvement in both the pterygium and the patient's symptoms. The tissue regressed from the limbal region of the cornea, had decreased in length from 1.5 to 1.0 mm, and decreased in height from approximately 1.0 to approximately 0.3 mm. Conjunctival hyperemia and vascularization resolved completely, and the underlying scleral vessels could once again be visualized. At 12 months, the pterygium was graded as stage 0 to I, V0, C2, K0, P0. Conclusions: To our knowledge, this is the first case of successful management of a pterygium and associated symptoms using topical dipyridamole. Further investigation is required to clarify the potential role of dipyridamole in the treatment of pterygia and pingueculae. © 2014 S. Karger AG, Basel.


Barken I.,Prostate Cancer Research and Education Foundation | Geller J.,Anticancer, Inc. | Geller J.,University of California at San Diego | Rogosnitzky M.,MedInsight Research Institute
Anticancer Research | Year: 2010

Background: Noscapine has demonstrated potent antitumour activity and minimum toxicity in cancer models. Recently, noscapine has been shown to limit tumour growth and lymphatic metastasis of PC3 human prostate cancer mice. The prophylactic effects of noscapine are not known. Materials and Methods: Nude mice received oral noscapine (300 mg/kg per day; 'treatment'; n=10) or diluent ('control'; n=10) for 56 days, beginning 7 days after inoculation with PC3 human prostate cancer cells; or noscapine for 70 days, beginning 7 days before inoculation ('pretreatment'; n=10). Results: Mean total tumour volumes were 1731.6±602.0 mm3 in the control group, 644.3±545.1 mm3 in the noscapine pretreatment group and 910.9±501.1 mm3 in the noscapine treatment group (p<0.001 pretreatment vs. control, p<0.05 pretreatment vs. control, p<0.001 pretreatment vs. treatment group), with no evidence of toxicity. Noscapine pretreatment and treatment also reduced tumour weight, the incidence of metastasis and primary tumour inhibition rate. Conclusion: Pretreatment with oral noscapine limited tumour growth and lymphatic metastasis of PC3 human prostate cancer in this mouse model and conferred a significant additional benefit over noscapine treatment in final tumour volume.


Rogosnitzky M.,MedInsight Research Institute | Danks R.,MedInsight Research Institute
Pharmacological Reports | Year: 2011

Cepharanthine (CEP) is a naturally occurring alkaloid extracted from the plant Stephania cepharantha Hayata. It has been widely used in Japan for more than 40 years to treat a wide variety of acute and chronic diseases. CEP inhibits tumor necrosis factor (TNF)-α-mediated NFκB stimulation, plasma membrane lipid peroxidation and platelet aggregation and suppresses cytokine production. It has also been shown to scavenge free radicals and to have a protective effect against some of the responses mediated by pro-inflammatory cytokines such as TNF-α, interleukin (IL)-1β and IL6. CEP has successfully been used to treat a diverse range of medical conditions, including radiation-induced leukopenia, idiopathic thrombocytopenic purpura, alopecia areata, alopecia pityrodes, venomous snakebites, xerostomia, sarcoidosis, refractory anemia and various cancer-related conditions. No safety issues have been observed with CEP, and side effects are very rarely reported. Copyright © 2011 by Institute of Pharmacology Polish Academy of Sciences.


Dalgleish A.,St George's, University of London | Featherstone P.,Queen Alexandra Hospital | Vlassov V.,MedInsight Research Institute | Rogosnitzky M.,MedInsight Research Institute
Investigational New Drugs | Year: 2014

Summary A role for CD20 antibodies in treating prostate cancer has not yet been established. We report a case of advanced prostate cancer presenting with generalized lymphadenopathy that expressed CCR7 and CD20. CCR7 expression in prostate cancer has been previously reported only once; the expression of CD20 has not been reported before. Rituximab therapy was initiated in this case and resulted in a significant biochemical response. This unique metastatic and biochemical pattern may signify a distinct subtype of prostate cancer that may be amenable to treatment with anti-CD20 antibodies. © 2014 Springer Science+Business Media New York.


Rogosnitzky M.,MedInsight Research Institute | Danks R.,MedInsight Research Institute | Kardash E.,MedInsight Research Institute
Anticancer Research | Year: 2012

Tranilast (N-[3,4-dimethoxycinnamoyl]-anthranilic acid; Rizaben®) is an anti-allergy drug approved for use in Japan and South Korea, also used against asthma, autoimmune diseases, and atopic and fibrotic pathologies. The antitumor potential of tranilast is attracting considerable interest. This review summarizes recent evidence concerning the effect of tranilast on different tumor types and discusses the drug's possible mode of action in this area. In vivo and in vitro studies are covered, as well as evidence from clinical trials, in which tranilast was evaluated in various models of proliferative disorders. The findings presented in this report, demonstrate the excellent potential of tranilast in the management of certain types of tumor, and provide a strong rationale for the initiation of controlled clinical trials in this area.


Rogosnitzky M.,MedInsight Research Institute | Danks R.,MedInsight Research Institute | Holt D.,MedInsight Research Institute
Autoimmunity Reviews | Year: 2012

Crohn's disease (CD) is a debilitating condition which still requires improvement in its management. There is a need for alternatives to anti-tumour necrosis factor drugs which are costly and beneficial in less than 50% of patients. Intravenous immunoglobulin (IVIG) has been used in the management of aminosalicylate- and steroid-resistant CD for more than 20. years, although the published literature available is limited. A literature search identified 17 relevant publications since 1969, including five case reports of single patients, two abstracts, three conference papers, one review paper and six book or journal articles. No randomised controlled trials of IVIG in CD have been published. A review of the evidence identified indicates that IVIG can induce a rapid and significant improvement in aminosalicylate- and steroid-resistant CD, often within days of the initial administration. Data from longer-term studies show that maintenance of remission over the medium term is also possible. These encouraging findings provide a rationale for the initiation of larger randomised controlled trials of IVIG in CD with the aim of providing further treatment options for this difficult-to-manage condition. © 2012 Elsevier B.V.


Rogosnitzky M.,MedInsight Research Institute | Rogosnitzky M.,Ariel University | Branch S.,MedInsight Research Institute
BioMetals | Year: 2016

Gadolinium chelates are widely used as contrast media for magnetic resonance imaging. The approved gadolinium-based contrast agents (GBCAs) have historically been considered safe and well tolerated when used at recommended dosing levels. However, for nearly a decade, an association between GBCA administration and the development of nephrogenic systemic fibrosis (NSF) has been recognized in patients with severe renal impairment. This has led to modifications in clinical practices aimed at reducing the potential and incidence of NSF development. Newer reports have emerged regarding the accumulation of gadolinium in various tissues of patients who do not have renal impairment, including bone, brain, and kidneys. Despite the observations of gadolinium accumulation in tissues regardless of renal function, very limited clinical data regarding the potential for and mechanisms of toxicity is available. This significant gap in knowledge warrants retrospective cohort study efforts, as well as prospective studies that involve gadolinium ion (Gd3+) testing in patients exposed to GBCA. This review examines the potential biochemical and molecular basis of gadolinium toxicity, possible clinical significance of gadolinium tissue retention and accumulation, and methods that can limit gadolinium body burden. © 2016 The Author(s)


PubMed | MedInsight Research Institute and VisionWorks
Type: Journal Article | Journal: Case reports in ophthalmology | Year: 2014

We report a case of a symptomatic, inflamed pterygium treated nonsurgically with topical dipyridamole and followed for 12 months.A 35-year-old woman presented with a stage II to III, V3, C3, K2, P1 (using Johnston, Williams & Sheppards classification) pterygium in her right eye. She complained of a foreign body sensation, dryness, burning, and persistent uncontrolled blinking. A raised lesion was observed on the nasal conjunctiva that was 1.5 mm in size. It extended slightly onto the nasal cornea. There was moderate vascularity of the lesion that obscured the underlying scleral vessels. Moderate conjunctival hyperemia was detected at and medial to the pterygium. The cornea, anterior chamber, and external anatomy were otherwise unremarkable. The eye was initially treated twice daily with a topical application of dipyridamole in a normal saline solution, which was later reduced to once daily.There was a marked improvement in both the pterygium and the patients symptoms. The tissue regressed from the limbal region of the cornea, had decreased in length from 1.5 to 1.0 mm, and decreased in height from approximately 1.0 to approximately 0.3 mm. Conjunctival hyperemia and vascularization resolved completely, and the underlying scleral vessels could once again be visualized. At 12 months, the pterygium was graded as stage 0 to I, V0, C2, K0, P0.To our knowledge, this is the first case of successful management of a pterygium and associated symptoms using topical dipyridamole. Further investigation is required to clarify the potential role of dipyridamole in the treatment of pterygia and pingueculae.


PubMed | MedInsight Research Institute and Ariel University
Type: Journal Article | Journal: Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics | Year: 2016

Dipyridamole was introduced decades ago as a treatment for angina, subsequently found to inhibit platelet aggregation. It is most commonly used, and approved for use in thromboembolism prevention, following surgery. Some of its recognized effects such as adenosine uptake inhibition, elevation of cAMP and cGMP levels, vasodilation, and tissue perfusion are important in various ocular disorders. For this reason, dipyridamole represents an interesting candidate as a therapeutic target for the treatment of eye disorders affecting different ocular structures. The aim of this article is to review the evidence and current understanding of the mechanisms by which dipyridamole exerts its effects on different ocular tissues, discuss the role of dipyridamole in clinical practice, and highlight areas of use and routes of administration.

Loading MedInsight Research Institute collaborators
Loading MedInsight Research Institute collaborators