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VEGF
Mayo Clinic study shows Parkinson's disease drug might work in cancer patients
By admin at 2008-03-14 19:43
 

ROCHESTER, Minn. -- A study published in the March 13 online issue of The Journal of Clinical Investigation shows that dopamine, a drug currently used to treat Parkinson’s disease and other illnesses, also might work in cancer patients. The study, which was done in mouse and laboratory models, shows that dopamine could possibly prevent new blood vessels from growing and as a result, slow cancer progression.

Dopamine is a neurotransmitter in the brain that regulates movement and affects behavior. In its synthetic form, dopamine is used to treat heart attack victims, Parkinson’s disease and pituitary tumors. But it wasn’t known until now that dopamine worked by blocking the growth of new blood vessels (a process called angiogenesis).

read more | 1033 reads

Precancerous Stem Cells Can Form Tumor Blood Vessels
By Dross at 2008-02-19 04:48
 

COLUMBUS, Ohio – Tumors require a blood supply to grow, but how they acquire their network of blood vessels is poorly understood. A new study here shows that tumor blood vessels can develop from precancerous stem cells, a recently discovered type of cell that can either remain benign or become malignant.

            Researchers say the findings provide new information about how tumors develop blood vessels, and why new drugs designed to block tumor blood-vessel growth are often less effective than expected.

read more | 1774 reads

Lymphatic vessel and lymph node function are restored with growth factor treatment
By Dross at 2007-12-03 21:20
 

The frequent spread of certain cancers to lymph nodes often necessitates surgery or radiation therapy that damages the lymphatic system and can cause lymphedema, a condition of localized fluid retention that often increases susceptibility to infections.

The researchers of the University of Helsinki, Finland, and the Ludwig Institute of Cancer Research show that application of vascular endothelial growth factor-C (VEGFterm-C) to replace excised mouse lymph nodes and lymph vessels ensures formation of mature lymphatic vessels and incorporation of lymph node transplants into existing lymphatic vasculature. An improved outcome of lymph node transplantation is evidenced by improved lymphatic drainage and restoration of normal lymphatic vascular anatomy in VEGF-C-treated mice.

read more | 1425 reads

Study shows blood markers can help choose best dose for antiangiogenic drugs
By Dross at 2007-10-26 02:20
 

Scientists at Sunnybrook have new information that may help to improve the use of anti-cancer drugs designed to block the growth of new blood vessels in tumors, a process called angiogenesis that is critical to tumor growth. While these antiangiogenic drugs are effective, at present there are no reliable methods for determining whether they are working, if the right dose is used, or if a patient will benefit (or not) from treatment.

A team led by Dr. Robert Kerbel - a senior scientist in Molecular and Cellular Biology at Sunnybrook and Canada Research Chair - has just published a paper in the October issue of the Proceedings of the National Academy of Sciences which may help to answer these questions. “In the clinic, patients receiving these antiangiogenic drugs have a number of blood plasma proteins that rise and fall after treatment, so it is speculated that they could be used as surrogate biomarkers to tell us about drug activity and efficacy - our studies in mice show that this is correct”, says Dr. Kerbel. In the study, Kerbel’s team found that drug-induced molecular changes observed in mice occurred at the same doses that had the best anti-tumor effect, suggesting that monitoring these changes in patients could predict the optimal dose of drug.

read more | 1 comment | 1501 reads

Study finds blocking angiogenesis signaling from inside cell may lead to serious health problems
By Dross at 2007-08-26 01:14
 

'Extremely surprising' outcome may result in more caution in use of angiogenesis drugs

Angiogenesis inhibitors that block a tumor’s development of an independent blood supply have been touted as effective cancer fighters that result in fewer side effectsterm than traditional chemotherapyterm. However, a new study by researchers at UCLA’s Jonsson Cancer Center showed that one method of blocking blood supply development could result in serious and potentially deadly side effects.

Several newly developed angiogenesis inhibitors work by blocking vascular endothelial growth factor (VEGFterm), an important signaling protein that spurs growth of new blood vessels. Avastinterm, an approved angiogenesis inhibitor for colon and lung cancers, inhibits angiogenesis by blocking VEGF signaling from outside of the cell. UCLA researchers wanted to know what happened when VEGF signaling was blocked from within endothelial cells, a mechanism used by some small molecule drugs currently being tested in late phase clinical trials.

read more | 4 comments | 1287 reads

St. Jude study shows temporary improvement of tumor blood flow can improve chemotherapy
By Dross at 2007-07-12 19:17
 

A treatment for neuroblastoma that lands a one-two punch works best when the second punch is timed to take maximum advantage of the first one, according to results of studies at St. Jude Children’s Research Hospital. Neuroblastoma is a pediatric solid tumor that arises from cells in the peripheral nervous system.

The finding holds promise for improving neuroblastoma treatment by using the drug bevacizumabtermterm to block VEGFterm, a protein that stimulates blood vessel growth in tumors and then following with the chemotherapyterm drug topotecan, which depends on blood vessels to penetrate the tumor and kill the cancer cells. A report on this work appears in the current issue of “Clinical Cancer Research.”

read more | 1355 reads

Targeting sugar on blood vessels may inhibit cancer growth
By Dross at 2007-05-07 21:34
 

In a study that could point to novel therapies to prevent cancer spread, or metastasistermterm, researchers at the University of California, San Diego (UCSD) School of Medicine have targeted a sugar that supports blood vessel growth in the tumor. Their findings will be published in the May 7 on-line issue of Journal of Cell Biology.

Lung cancer is the most common cause of cancer death and an area where novel therapies to block metastasis are desperately needed, according to first author Mark M. Fuster, M.D., assistant professor in the Division of Pulmonary and Critical Care Medicine in UCSD’s Department of Medicine. Solid tumors need a network of blood vessels, or vasculature, in order to grow, and this vasculature drives metastasis. The research team, led by the paper’s principal investigator Jeffrey D. Esko, Ph.D., professor of Cellular and Molecular Medicine at UCSD, showed that modifying the action of heparan sulfate uniquely impacted the tumor vasculature, and in doing so, altered the growth rate of tumors prepared from lung carcinomaterm cells in the mice.

read more | 1543 reads

EntreMed Starts Phase II Clinical Trial of Panzem with Sutent for Kidney Cancer Patients
By HCat at 2007-03-13 03:58
 

    EntreMed, Inc has commenced a Phase 2 trial to evaluate the safety and efficacy of Panzem (2-methoxyestradiol; 2ME2) alone or in combination with Sutenttermterm (sunitinibterm) in patients with metastaticterm renal cell carcinomaterm. The University of Wisconsin, Paul P. Carbone Comprehensive Cancer Center will be the main center conducting the trial under the guidance of Dr. Glenn Liu. The trial will investigate Panzem’s potential to treat patients who are progressing on sunitinib.

     Panzem NCD uses Elan Drug Delivery's (Elan) NanoCrystal Colloidal Dispersion (NCD) technology, a technology that is being used in marketed pharmaceuticals. The NCD technology produces nanometer-sized particles, which are up to 500 times smaller than particles manufactured by conventional milling techniques. Panzem NCD works by blocking the VEGFterm receptor and by inhibiting HIF-1alpha. The theory behind Panzem’s anti-tumor effects is that renal cell cancers are frequently associated with VEGF and PDGF overexpression involving a HIF-1alpha mechanism. It is thought that patients who progress through the tyrosine kinase inhibitor response, such as those on the tyrosine kinase inhibitor sunitinib, have an increase in HIF-1alpha expression to compensate for the kinase inhibition in order to continue tumor growth. Dr. Liu has stated that this trial will test this hypothesis. Panzem NCD is also currently in Phase 2 clinical trials for brain, ovarian, carcinoid, and prostate cancers as well as in Phase 1 study in metastatic breast cancer.

read more | 5327 reads

Reasons Why Cancer Drug Discovery is so Difficult
By HCat at 2007-01-31 23:56
 

    In the perspective article in Nature Reviews Drug Discovery, the authors discuss the challenges facing drug discovery as intricate and numerous. They present a broad picture of drug discovery as three parts pertaining to targets, drugs, and patients. Targets for drug discovery are broken down into two classes, each of which is either essential or non-essential. Essential targets for drug discovery are targets that have essential function within all cells or a specific cell type. That means that the cell has to have this function operating or it will die. Non-essential targets are targets whose function can be lost and the cell will still survive. This concept can also be applied in terms of tissues as a target such as in breast tissue which is considered a non-essential tissue for life. Drugs that inhibit or block essential functions are likely to have narrow therapeutic windows. That is the drugs beneficial dose range is likely to be small before it becomes toxic such as 5-FUterm. 5-FU relies on the principle that cancer cells should be faster growing since they are growing out of control. 5-FU inhibits DNA synthesis, an essential function. Slow growing cells are not as affected as fast growing cells from 5-FU. This therapeutic windowterm is narrow and the consequences or side effectsterm of the narrow window is that 5-FU affects some of the naturally fast growing cells in the body, which is why hair loss is a common side-effect in 5-FU treatment.

read more | 3256 reads

Important mechanism identified in the formation of blood vessels
By Dross at 2007-01-29 21:43
 

Tumors cannot grow to more than 1-2mm without new blood vessels. Antibodies against VEGFterm such as Avastinterm have been shown to be effective in slowing the growth of tumors by inhibiting the proliferation of blood vessels. Now a new target has been found. By combining drugs such as Avastin with Erbituxterm or Vectibixterm with a drug against this target we will be closer to extending the lives of many.

 

All tissues, sick and healthy alike, need a blood supply to survive and grow. The key to many medical problems, like preventing tumour development, is therefore to obstruct the spread of the blood vessels. Research scientists at Karolinska Institutet have now discovered a heretofore unknown mechanism for how the body links together its blood vessels.

read more | 1 comment | 1616 reads

INGN 241 in Combination with Avastin Results in Complete Tumor Regression in Lung Cancer
By HCat at 2007-01-25 10:42
 

    AUSTIN, Texas--(BUSINESS WIRE)--Jan. 24, 2007--Introgen Therapeutics, Inc. (NASDAQ:INGN) announced today the publication of data in Molecular Therapy, the journal of the American Society of Gene Therapy, highlighting the results of a preclinical study with INGN 241 in combination with Avastinterm(R) (Bevacizumabtermterm). Synergistic activity resulting in a curative therapeutic effect was seen in the treatment of lung cancer following the combination of the two agents. In contrast, treatment with Avastin alone demonstrated only minor tumor regression and no animals were cured of their cancer. The study was conducted at The University of Texas M.D. Anderson Cancer Center by Introgen's collaborator Dr. Rajagopal Ramesh, associate professor, Department of Thoracic and Cardiovascular Surgery.

read more | 4214 reads

Colorectal Cancer Basics
By HCat at 2007-01-16 12:35

Colorectal Cancer Basics

 

Hereditary CRC

Colorectal cancer (CRC) can be divided into two basic types, hereditary or sporadic.

    Hereditary CRC are germlineterm (passed to offspring) mutations (a damaging change in DNA) with two well described forms. These hereditary mutations are thought to reduce the time it takes for the cells to turn cancerous. Mutations can be thought of in terms of “hits”. One hit is one mutation. It is thought that a normal cell needs 3 to 6 hits to become cancerous. With an inherited mutation, there is one fewer hit needed to reach the correct number to transform the cell to cancer. One odd aspect to CRC is that there is a relatively well defined set of events for the progression from adenomaterm to carcinomaterm.

read more | 26445 reads

AVEO Acquires Clinical Stage Anti-Cancer Compound From Kirin
By Dross at 2007-01-05 01:51
 

Although this information is very preliminary, 7 out of 7 success isn't bad. A VEGFterm inhibitor curtails the construction of new blood vessels to a solid tumour thereby "suffocating" it but does not address the cause of the cancer itself.

AVEO Pharmaceuticals, Inc., a biopharmaceutical company focused on the discovery and development of novel cancer medicines, today announced it has acquired from Kirin Brewery Co., Ltd. an exclusive license to develop and commercialize Kirin's highly potent and selective, once-a-day, oral VEGF receptor inhibitor, KRN951, in all territories outside of Asia. Financial terms of the agreement were not disclosed. KRN951 is currently completing a 30-patient Phase I clinical trial in patients with advanced solid tumors in which the maximum tolerated dose of KRN951 has been established. Results recently presented at the EORTC-NCI-AACR meeting in Prague by lead investigator Dr. Ferry Eskens of the Department of Medical Oncology, Erasmus Medical Center in Rotterdam, found that of seven patients with refractory renal cell carcinomaterm enrolled to date, all have achieved either a partial response or stable disease as defined by the trial protocol, with one patient exhibiting a response lasting more than 2.5 years. Treatment with KRN951 in the trial was well-tolerated. The most common side effect seen in the trial was hypertension -- an expected mechanism-based toxicity. Blood pressure was readily controlled by standard antihypertensive agents in all but one of the patients who developed hypertension during the trial. AVEO expects to commence Phase II clinical studies for KRN951 by mid-2007. Given the strong activity signal in the Phase I trial, AVEO initially plans to develop KRN951 for the treatment of renal cell carcinoma, but also intends to develop this well-tolerated VEGF receptor inhibitor as a combination treatment in multiple solid tumor types. AVEO will apply its unique Human Response Prediction(TM) Platform to identify optimal chemotherapyterm combinations, as well as additional patient populations likely to respond to KRN951 monotherapy and combination therapy.

read more | 1013 reads

Downregulation of VEGF-A, STAT5 and AKT in acute myeloid leukemia blasts of patients treated with SU5416.
By admin at 2006-12-20 03:55
 

[via Entrez PubMed]:

Interesting article re a tyrosine kinase inhibitor Sugen is developing. I love to see real translational research, using patients' cells in trials and doing molecular assays for effects. In this case the researchers are demonstrating down regulation of VEGFterm messenger RNA levels, which is an assumption of down regulation in the final protein product.

In acute myeloid leukemiaterm (AML), autocrine or paracrine activation of receptor tyrosine kinases such as c-kit and FLT3 contributes to proliferation and apoptosis resistance of leukemic blasts. This provided the rationale for a multicenter clinical trial in patients with refractory AML with SU5416, a small molecule kinase inhibitor which blocks phosphorylation of c-kit, FLT3, VEGFR-1, VEGFR-2 (KDR) and VEGFR-3. The levels of VEGF mRNA expression were investigated in peripheral blood leukemic blasts taken from AML patients before and during treatment with SU5416. Rapid down regulation of VEGF was observed in AML blasts from 72% (13 of 18) of patients analysed. Patients initially expressing high VEGF-levels had a stronger downregulation and a higher clinical response rate (mean 865-fold, n = 10, P = 0,01) than patients initially expressing low VEGF-levels (mean four-fold, n = 8). These results suggest that abnormal high VEGF expression is downregulated by SU5416 treatment, and furthermore that decreases in VEGF mRNA levels may provide an early marker of therapeutic response with anti-angiogenic therapy. Additionally, protein expression of STAT5 and AKT was assessed by western blotting in these patient samples, as well as in the leukemia cell line, M-07e, treated in vitro with SU5416 as a model system. In the AML patient samples, parallel downregulation of both STAT5 and AKT was observed in several cases (STAT5 in four of 15; AKT in three of six examined patients). These effects were confirmed with the cell line M-07e after incubation with SU5416 in vitro using concentrations that are achievable in patients. In summary, our data show suppression of the expression of VEGF and key signal transduction intermediates in AML blasts during treatment with SU5416.

read more | 2205 reads

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