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Recent News and Articles on the Keywords: retinoblastoma + combination + topotecan  Related to the article below (Last Update: 12/1/2008)

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Recent News and Articles on the Keywords: retinoblastoma + combination + topotecan  Related to the article below (Last Update: 8/7/2008)

Benign Tumors and Tumorlike Conditions of the Lung
RedOrbit, TX - Jul 16, 2008
Gupta D, Holden J, Layfield L. Topoisomerase alpha II, retinoblastoma gene product, and p53: potential relationships with aggressive behavior and malignant ...
Lung Tumors With Neuroendocrine Morphology: Essential Radiologic ... RedOrbit
all 5 news articles »
Source: Google News

Topotecan Combination Chemotherapy in Two New Rodent Models of Retinoblastoma -
NA Laurie, JK Gray, J Zhang, M Leggas, M Relling, … - Clinical Cancer Research, 2005 - AACR
... The combination of topotecan and carboplatin most effectively halted retinoblastoma
progression in our rodent models and was superior to the current triple ...

Phase I trial of UCN-01 in combination with topotecan in patients with advanced solid cancers: a … -
SJ Hotte, A Oza, EW Winquist, M Moore, EX Chen, S … - Annals of Oncology, 2006 - Eur Soc Med Oncology
... combination of UCN-01 and topotecan at clinically ... to better evaluate this combination
in women ... the phosphorylation of the retinoblastoma susceptibility gene ...

Sodium phenylbutyrate induces apoptosis in human retinoblastoma Y79 cells: the effect of combined … -
G Calvaruso, M Carabillo, M Giuliano, M Lauricella … - Int J Oncol, 2001 - ncbi.nlm.nih.gov
Sodium phenylbutyrate induces apoptosis in human retinoblastoma Y79 cells: the effect
of combined treatment with the topoisomerase I-inhibitor topotecan. ...

… Cytotoxic Interactions between Sodium Butyrate, MG132 and Camptothecin in Human Retinoblastoma Y79 … -
T Biol - Logo, 2000 - content.karger.com
... Table 1. CI values for treatments of human retinoblastoma Y79 cells with combinations
of camptothecin (or topotecan), sodium butyrate and MG132 ...

Topotecan in Pediatric Patients With Recurrent and Progressive Solid Tumors: A Pediatric Oncology … -
R Nitschke, J Parkhurst, J Sullivan, MB Harris, M … - Journal of Pediatric Hematology Oncology, 1998 - jpho-online.com
... retinoblastoma, and possibly in hepatoblastoma, rhab- domyosarcoma, and in ... comparing
topotecan alone to the combination of topotecan with cyclophosphamide ...

Activity of topotecan in retinoblastoma -
GL Chantada, AC Fandi?, SJ Casak, G Mato, J … - Ophthalmic Genetics, 2004 - ingentaconnect.com
... five-day intravenous infusion of topotecan was encouraging. ... the activity of the
combination carboplatin and ... the treatment of extraocu- lar retinoblastoma in 20 ...

Use of preclinical models to improve treatment of retinoblastoma -
MA Dyer, C Rodriguez-Galindo, MW Wilson - PLoS Med, 2005 - medicine.plosjournals.org
... Relling M, et al. (2005) Topotecan combination chemotherapy in two new
rodent models of retinoblastoma. Clin Cancer Res In press. ...

… Levels after Periocular or Intravenous Delivery in Rabbits: An Alternative for Retinoblastoma … -
AM Carcaboso, GF Bramuglia, GL Chantada, AC … - Investigative Ophthalmology & Visual Science, 2007 - ARVO
... al. Topotecan combination chemotherapy in two new rodent models of
retinoblastoma. Clin Cancer Res. 2005;11:7569?7578. [Abstract ...

Retinoblastoma: From the Two-Hit Hypothesis to Targeted Chemotherapy -
D MacPherson, MA Dyer - Cancer Research, 2007 - AACR
... Topotecan combination chemotherapy in two new rodent models of retinoblastoma.
Clin Cancer Res 2005;11:7569?78. [Abstract/Free Full Text]. ...

Phase II Window of Idarubicin in Children With Extraocular Retinoblastoma -
GL Chantada, A Fandino, G Mato, S Casak - Journal of Clinical Oncology, 1999 - jcojournal.org
... with Taxol (txl) and Topotecan (topo) in ... regimen using idarubicin in combination
with cytarabine and ... White L: Chemotherapy in retinoblastoma: Current status ...

Source: Google Scholar
 
 

Retinoblastoma: combination therapy with Topotecan and Carboplatin

Researchers at St. Jude Children's Research Hospital have demonstrated in laboratory studies a new treatment for the pediatric eye cancer, retinoblastoma, that appears to be more effective than the current standard therapy, and more likely to prevent the recurrence of this cancer.

The study is published in the Clinical Cancer Research.

Retinoblastoma is a tumor that arises in the cells of the retina, following mutation of the gene RB1.
It is the third most common form of cancer in infants. Left untreated, the cancer spreads and is fatal.
Retinoblastoma strikes about 250-350 infants and young children each year in the United States.
 
The St. Jude study suggests a new approach to treatment that could save both lives and vision, according to Michael A. Dyer, the senior author of the report.
The new treatment might also prevent recurrence of retinoblastoma in children whose cancer is very advanced, he noted.

The study showed that combination therapy with Topotecan and Carboplatin is superior to the standard triple-drug therapy using Vincristine, Carboplatin and Etoposide.
The new combination eliminates the use of Etoposide, which is known to increase the risk of the children getting a form of leukemia called acute myeloblastic leukemia.
 
The findings also suggest that Vincristine, which is used in the standard combination therapy, contributes little to the treatment of retinoblastoma, and therefore can be eliminated from therapy.

Dyer's group was prompted to look for new treatments because of the difficulty in managing this cancer. Patients with retinoblastoma usually undergo enucleation; and children with retinoblastoma in both eyes often must undergo anticancer therapy in order to avoid the loss of both eyes and blindness.
 
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But despite the critical need for new treatments that are more effective and have less severe side effects, researchers have been limited in their ability to identify new drugs and drug combinations that will improve the outcome of retinoblastoma.
One reason for this problem is that there are not enough patients for researchers to enroll in large clinical trials designed to investigate new treatments, Dyer said.

Until last year when researchers at St. Jude developed the first "knockout" model of retinoblastoma and the two other models presented in this work, there were few options for preclinical studies on retinoblastoma. A knockout model is one that lacks one or more specific genes; knockout models are developed in order to study specific human diseases caused by gene defects.

The researchers made their findings during a sequence of experiments.
First, they tested the ability of drugs and drug combinations to kill retinoblastoma tumors removed from patients and grown in tissue cultures.
Then the team determined how much drug to use, and how often to use it, by doing pharmacokinetic studies.
Finally, the team tested the drugs in laboratory models of the cancer they had developed for this purpose.

" Our models of retinoblastoma behave very much like the tumors that occur in children, so our investigation of potential new treatments for this cancer gave us very relevant and useful information, said Nikia Laurie, the paper's first author.

The two retinoblastoma models the St. Jude team developed were a xenograft model of retinoblastoma, in which a cell line from a tumor removed from a child grew naturally and was available for testing new drug combinations; and a genetic model, in which the team injected a virus carrying a gene that induced from one to five individual tumors in the retina. Importantly, these tumors spread through the blood vessels of the retina, which is particularly important for future studies that could test cancer drugs that work by blocking formation of blood vessels, according to Dyer.

The St. Jude team plans to use their two new models as a "high-throughput" screen to test many new drugs and drug combinations rapidly after determining what doses to use based on culture and pharmacokinetic studies. Treatments that appear to be effective will then be tested in a previously developed "knock-out" laboratory model. This model lacks three critical genes, which causes retinoblastoma. "The knock-out model closely mimics the course of the disease in children, Dyer said.

Source: St. Jude Children's Research Hospital, 2005

 

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