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DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO
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Vitamin A could prevent the spread of prostate cancer
Scientists funded by Yorkshire Cancer Research at the University of York have discovered that retinoic acid – a chemical made from vitamin A which is supplied in our diet by carrots, green vegetables and liver – can turn specific genes within prostate cancerstem cells back on, reducing the ability of the cancer to invade surrounding tissue.
The findings suggest that Vitamin A related compounds could be used to enhance clinical treatments for prostate cancer.
Professor Norman Maitland, Director of the YCR Cancer Research Unit in the Department of Biology at York, said: “Cancer arises from healthy cells going wrong. Certain controls can be turned off which allows the cancer to progress. For example, normal cells gain the ability to grow and invade the surrounding tissues.
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سیاهدانه Nigella Sativa حبة البركة Kills 89% of Lung Cancer Cells in Vitro
Nigella Sativa Kills 89% of Lung Cancer Cells in Vitro: Researchers have just shown that nigella sativa (also known as black seed or black cumin) seed oil killsup to 89% of human lung cancer cells (A-549) after just 24 hours, while a non-oil extract from the seeds killed up to 77% of the cancer cells.
The extracts were prepared from seeds obtained at a local market. Nigella sativa is a powerful medicinal herb which has been used for thousands of years in traditional Chinese, Ayurvedic, Unani and Arabic medicine. It is best known for its potent anti-inflammatory and antioxidant properties, and has been used to suppress coughs, treat kidney stones, diarrhea and stomach pain. But modern science has now also uncovered nigella’s powerful anti-diabetes and anti-cancer effects.
This super herb has already shown potent activity against cancer of the breast, prostate, kidney, pancreas, liver, colon and cervix in previous lab studies, and this new study has shown new activity against lung cancer. Good health and cancer prevention should always start with a well-balanced diet focused on organic vegetables, fruit and whole foods (consuming at least half in the raw state). But nigella sativa may offer sizeable benefits for those wanting an extra measure of protection.
read at
http://www.ncbi.nlm.nih.gov/pubmed/24568529
Nigella sativa is an annual flowering plant, native to south and southwest Asia. It grows to 20–30 cm (7.9–11.8 in) tall, with finely divided, linear (but not thread-like) leaves. The flowers are delicate, and usually coloured pale blue and white, with five to ten petals. The fruit is a large and inflated capsule composed of three to seven united follicles, each containing numerous seeds. The seed is used as a spice.
Etymology
Nigella sativa seed
The scientific name is a derivative of Latin niger (black).[2]
Common names
In English, Nigella sativa seed is variously called fennel flower,[3] nutmeg flower,[3] black caraway,[3] Roman coriander,[3] and also called black cumin.[3] Other names used, sometimes misleadingly, are onion seed and black sesame, both of which are similar-looking, but unrelated.Blackseed and black caraway may also refer to Bunium persicum.[4]
The seeds are frequently referred to as black cumin (as in Assamese: kaljeera or kolajeera or Bengali kalo jeeray), But black cumin (kala Jeera)[clarification needed] is different than Nigella sativa (Kali Jeeri).[citation needed] In south Indian language Kannada it is called [ಕೃಷ್ಣ ಜೀರಿಗೆ] “Krishna Jeerige”, but this is also used for a different spice, Bunium persicum.
In English-speaking countries with large immigrant populations, it is also variously known as kaljeera (Assamese কালজীৰা kalzira or ক’লাজীৰাkolazira), kalo jira (Bengali: কালোজিরা kalojira, black cumin), karum cheerakam, habbat al-barakah (Arabic حبة البركة) Kurdish “reşke” (rashkeh) (Tamil கருஞ்சீரகம்), kalonji (Hindi कलौंजी kalauṃjī or कलोंजी kaloṃjī, Urdu كلونجى kaloṃjī) or mangrail (Hindi मंगरैल maṃgarail), “Kala Jira in Marathi” ketzakh (Hebrew קצח), chernushka (Russian), çörek otu (Turkish), garacocco (Cypriot Turkish), ḥebbit al-barakah, seed of blessing (Arabic), siyah daneh (Persian سیاهدانه siyâh dâne), jintan hitam (Indonesian), karim jeerakam (കരിംജീരകം) in Malayalamor කළු දුරු in Sinhala, Karto Jeera in Beary.
It is used as part of the spice mixture paanch phoran or panch phoron (meaning a mixture of five spices) and by itself in a great many recipes in Bengali cookery and most recognizably in naan bread.[5]
The Turkish name çörek otu literally means “bun’s herb” from its use in flavouring the çörek buns. Such braided-dough buns are widespread in the cuisines of Turkey and its neighbours (see Tsoureki τσουρέκι). In Bosnian, the Turkish name for Nigella sativa is respelled as čurekot. The seed is used in Bosnia, and particularly its capital Sarajevo, to flavour pastries (Bosnian: somun) often baked on Muslim religious holidays.
The Arabic approbation about Bunium bulbocastanum (Kaala Jeera) Hebbit il barakah, meaning the “seed of blessing” is also applied toNigella sativa (Kali Jeeri).
Characteristics
Nigella sativa has a pungent bitter taste and smell. It is used primarily in confectionery and liquors. Peshawari naan is, as a rule, topped with kalonji seeds. Nigella is also used in Armenian string cheese, a braided string cheese called Majdouleh or Majdouli in the Middle East.
History
According to Zohary and Hopf, archaeological evidence about the earliest cultivation of N. sativa “is still scanty”, but they report supposed N. sativa seeds have been found in several sites from ancient Egypt, including Tutankhamun‘s tomb.[6] Although its exact role in Egyptian culture is unknown, it is known that items entombed with a pharaoh were carefully selected to assist him in the afterlife.
The earliest written reference to N. sativa is thought to be in the book of Isaiah in the Old Testament, where the reaping of nigella and wheat is contrasted (Isaiah 28: 25, 27). Easton’s Bible dictionary states the Hebrew word ketsah refers to N. sativa without doubt (although not all translations are in agreement). According to Zohary and Hopf, N. sativawas another traditional condiment of the Old World during classical times; and its black seeds were extensively used to flavour food.[6]
Found in Hittite flask in Turkey from 2nd millennium BCE.[7]
History of medicineIn the Unani Tibb system of medicine, black cumin (Bunium bulbocastanum) is regarded as a valuable remedy for a number of diseases. Sayings of the Islamic prophet Muhammadunderline the significance of black cumin. According to a hadith narrated by Abu Hurairah, he says, “I heard Allah’s Apostle saying, ‘There is healing in black seed (haba sowda) for all diseases except death.'” [8] [9]
The black cumin (Bunium bulbocastanum) seeds have been traditionally used in the Middle East and Southeast Asian countries for a variety of ailments. Nigella seeds are sold as black cumin in small bundles to be rubbed until warm, when they emit an aroma similar to black cumin which opens clogged sinuses in the way that do eucalyptus or Vicks.
Nestlé has purportedly filed a patent application covering use of Nigella sativa as a food allergy treatment.[10] Yet the firm denies the claim of patenting the plant, stating that the patent would only cover “the specific way that thymoquinone – a compound that can be extracted from the seed of the fennel flower – interacts with opioid receptors in the body and helps to reduce allergic reactions to food”.[11]
Medical studies
Thymoquinone, found in the seed oil extract of N. sativa, has been shown to have anti-neoplastic effects in rats and mice and in cultured human cells from several types of cancer, including pancreatic ductal adenocarcinoma.[12] It has protective antioxidant and anti-inflammatory effects, and promotes apoptosis (cell death) of the cancer cells.[12]
Black cumin
Nigella sativa oil
Original black cumin (Bunium bulbocastanum) is rarely available, so N. sativa is widely used instead; in India, Carum carvi is the substitute. Cumins are from the Apiaceae (Umbelliferae) family, but N. sativa is from Ranunculaceae family. Black cumin (not N. sativa) seeds come as paired or separate carpels, and are 3–4 mm long. They have a striped pattern of nine ridges and oil canals, and are fragrant (Ayurveda says, “Kaala jaaji sugandhaa cha” (black cumin seed is fragrant itself)), blackish in colour, boat-shaped, and tapering at each extremity, with tiny stalks attached; it has been used for medicinal purposes for centuries, both as a herb and pressed into oil, in Asia, the Middle East, and Africa.
Chemistry
Nigella sativa oil contains an abundance of conjugated linoleic (18:2) acid, thymoquinone, nigellone (dithymoquinone),[13] melanthin, nigilline,damascenine, and tannins. Melanthin is toxic in large doses and nigelline is paralytic, so this spice must be used in moderation.
References
- “The Plant List: A Working List of All Plant Species”.
- New International Encyclopedia
- “USDA GRIN Taxonomy”.
- Bunium persicum – (Boiss.) B.Fedtsch. Common Name Black Caraway
- Indian Naan with Nigella Seeds Recipe
- Zohary, Daniel; Hopf, Maria (2000). Domestication of plants in the Old World (3 ed.). Oxford University Press. p. 206. ISBN 0-19-850356-3.
- http://dx.doi.org/10.1016/j.jep.2009.05.039
- Sunan Ibn Majah.
- “71”. Sahih Bukhari 7. 592.
- Hammond, Edward (2012). “Food giant Nestlé claims to have invented stomach soothing use of habbat al-barakah (Nigella sativa)”. Briefing Paper. Third World Network. Retrieved 23 April 2013.
- “Is Nestlé trying to patent the fennel flower?”, http://www.nestle.com.
- Chehl, N.; Chipitsyna, G.; Gong, Q.; Yeo, C.J.; Arafat, H.A. (2009). “Anti-inflammatory effects of the Nigella sativa seed extract, thymoquinone, in pancreatic cancer cells”. HPB (Oxford) 11 (5): 373–381. doi:10.1111/j.1477-2574.2009.00059.x. PMID 19768141.
- Mohammad Hossein Boskabady, Batool Shirmohammadi (2002). “Effect of Nigella Sativa on Isolated Guinea Pig Trachea”. Arch Iranian Med 5 (2): 103–107.
Nigella sativa- Nigella from The Encyclopedia of Spices
- Ali BH, Blunden G (April 2003). “Pharmacological and toxicological properties of Nigella sativa”. Phytother Res 17 (4): 299–305.doi:10.1002/ptr.1309. PMID 12722128.
- Antimicrobial activity of Nigella sativa oil against Staphylococcus aureus and Pseudomonas aeruginosa obtained from clinical specimens.
- Effects of Black Seeds (Nigella Sativa) on Spermatogenesis and Fertility of Male Albino Rats
- Effects of oral administration of water extract of Nigella sativa on serum concentrations of insulin and testosterone in alloxan-induced diabetic rats
- Black Seed, Nigella Sativa, Deserves More Attention
- How to make a dessert pie from black cumin seeds
Apigenin: this chemical breaks the immortality of cancer cells
apigeninCuba may have found cure for cancer
Cuban doctors have filed Wednesday in Havana, the result of 14 years of research, a solution of antitumor peptides whose natural analogue is able to offer positive dynamics in cancer treatments
http://youthandeldersja.wordpress.com/2014/03/22/cuba-may-have-found-cure-for-cancer/
ELLAGIC ACID A CANCER FIGHTING WONDER
ELLAGIC ACID
2,3,7,8-Tetrahydroxy-chromeno[5,4,3-cde]chromene-5,10-dione
as a very potent CK2 inhibitor
Ellagic acid is a natural phenol antioxidant found in numerous fruits and vegetables. The antiproliferative and antioxidant properties of ellagic acid have spurred preliminary research into the potential health benefits of ellagic acid consumption.
Ellagic acid is the dilactone of hexahydroxydiphenic acid.
Ellagic acid is an antioxidant and an anti-proliferative compound present in fruits, nuts and vegetables. In spite of evidences for anticancer activity in various cancer cell-lines, human cancer cells, the mechanistic role of ellagic acid is not conclusive enough to be recommended for a clinical use. The present review provides information about the chemopreventive role of ellagic acid in oral cancer and proposes molecular basis for ellagic acid’s inhibitory activity against oral cancer. We show that ellagic acid modulates growth of tumor cells through regulation of multiple cell signaling pathways including cell proliferation pathway (cyclin dependent kinase 2, cyclin A2, cyclin B1, cyclin D1, c-myc, PKCα), cell survival/apoptosis pathway (Bcl-XL, Bax, Caspase 9/3, Akt), tumor suppressor pathway (p53, p21), inflaming Metastasis pathways (IL-1 beta, TNF-α, matrix metalloproteinases 9/3, COX-2), angiogenesis pathways (VEGF), cell immortalization (TERT), NF-κβ.
Moringa Oleifera Kills 97% of Pancreatic Cancer Cells in Vitro
Moringa Oleifera Kills 97% of Pancreatic Cancer Cells in Vitro:
A hot-water extract of moringa leaves was shown to kill up to 97% of human pancreatic cancer cells (Panc-1) after 72 hours in this study. Moringa, also called the “miracle tree,” has a long history of use in traditional and Ayurvedic medicine due to its many beneficial properties as an anti-fungal, anti-bacterial, antidepressant, anti-diabetes, pain and fever reducer and even relief from asthma. But it also contains numerous powerful anti-cancer compounds such as kaempferol, rhamnetin, isoquercetin and others.
Latest research is now proving out moringa’s anti-cancer potential with positive results so far against ovarian cancer, liver cancer, lung cancer, and melanoma. Moringa is now extensively cultivated throughout Southeast Asia, Oceania, the Caribbean and Central America, but the largest crop in the world is produced by India – where it grows natively.
That may be one reason why the death rate from pancreatic cancer in India is a stunning 84% lower than in the United States.
http://www.ncbi.nlm.nih.gov/pubmed/23957955
Carrots Cut Men’s Prostate Cancer Risk by 50%:
http://www.ncbi.nlm.nih.gov/pubmed/24519559
This Little Known Chinese Herb Kills 12,000 Cancer Cells For Every Healthy Cell
artemisininWormwood
Other common name(s): absinthium, absinth wormwood
Scientific/medical name(s): Artemisia absinthium
Description
Wormwood is a shrubby perennial plant whose upper shoots, flowers, and leaves are used in herbal remedies and as a bitter flavoring for alcoholic drinks. It is native to Europe, northern Africa, and western Asia, and now also grows in North America.
Overview
Available scientific evidence does not support claims that wormwood is effective in treating cancer, the side effects of cancer treatment, or any other conditions. The plant contains a volatile oil with a high level of thujone (see Thuja). There are reports that taking large doses of wormwood internally can cause serious problems with the liver and kidneys. It can also cause nausea, vomiting, stomach pain, headache, dizziness, seizures, numbness of the legs and arms, delirium, and paralysis.
Wormwood, or Artemisia absinthium, should not be confused with sweet wormwood, or Artemisia annua. Although wormwood is related to sweet wormwood, they are used in different ways. Extracts of sweet wormwood have been used in traditional herbal medicine, and an active ingredient, artemisinin, is now used in conventional medical treatment of malaria.
How is it promoted for use?
Wormwood is promoted as a sedative and anti-inflammatory. There are also claims that it can treat loss of appetite, stomach disorders, and liver and gallbladder complaints. In folk medicine it is used for a wide range of stomach disorders, fever, and irregular menstruation. It is also used to fight intestinal worms. Externally, it is applied to poorly healing wounds, ulcers, skin blotches, and insect bites. It is used in Moxibustion treatments for cancer (seeMoxibustion). Available scientific evidence does not support these claims.
What does it involve?
Wormwood is taken in small doses for a short period of time, usually a maximum of 4 weeks. It is available as a capsule and as a liquid that can be added to water to make a tincture. The whole herb is sometimes brewed as a tea. Wormwood oil, washes, or poultices can also be used on the skin. Although pure wormwood is not available, “thujone-free” wormwood extract has been approved by the US Food and Drug Administration (FDA) for use in foods and as a flavoring in alcoholic drinks such as vermouth.
What is the history behind it?
Artemisia absinthium was used by Hippocrates, and the earliest references to wormwood in Western civilization can be found in the Bible. Extract of wormwood was also used in ancient Egypt. The herb is mentioned often in first-century Greek and Roman writings and reportedly was placed in the sandals of Roman soldiers to help soothe their sore feet. It was taken as a treatment for tapeworms as far back as the Middle Ages.
In 1797, Henri Pernod developed absinthe, an alcoholic drink containing distilled spirits of wormwood, fennel, anise and sometimes other herbs. Absinthe became very popular in Europe and the United States in the nineteenth century. It was eventually banned in several countries in the early twentieth century due to its purported ill effects and addictive qualities. More recent analysis has suggested that, when properly prepared and distilled, the thujone content in these drinks was very low. It appears more likely that the addictiveness and other ill effects of absinthe were due to its alcohol content, which is around 60% to 85%. Varying additives or impurities from different distillers may have also produced some of these effects. Even though absinthe is illegal in some countries, various types can be found in some European countries. However, their thujone content is strictly limited. Wormwood is also an ingredient in vermouth and other drinks.
What is the evidence?
Available scientific studies do not support the use of wormwood for the treatment of cancer or the side effects of conventional cancer treatment. There is not enough evidence available to support its use for other conditions. Wormwood oil has been tested in laboratory studies and appears to inhibit the growth of some fungi. However, human tests have not been completed.
Some derivatives of Artemisia annua, or sweet wormwood, a relative of wormwood, have been shown to be effective in the treatment of malaria. In fact, the World Health Organization approved artemisinin for use against malaria in Africa in 2004. These extracts also show some promise in laboratory studies as cancer treatment drugs. Further studies are required to find out whether the anti-cancer results apply to people. It is important to remember that extracted compounds are not the same as the whole herb, and study results are not likely to show the same effects.
Are there any possible problems or complications?
Wormwood should be avoided, especially by women who are pregnant or breast-feeding, by people who have had seizures, and by those with ulcers or stomach irritation. Thujone, a component of wormwood, is known to cause muscle spasms, seizures, and hallucinations if taken internally. In high doses it is known to damage the liver and the kidneys.
Because of its thujone content, large doses of wormwood taken internally can lead to vomiting, stomach and intestinal cramps, headaches, dizziness, nervous system problems, and seizures. Wormwood can also lead to liver failure. The New England Journal of Medicine reported that a man who ordered essential oil of wormwood over the Internet, thinking he had purchased absinthe, suffered liver failure shortly after drinking the oil. Wormwood may also make seizures more likely and may interfere with the anti-convulsant effects of medicines such as phenobarbital.
The plant is a relative of ragweed and daisies. Those with allergies to these types of plants may also be allergic to wormwood. Contact with wormwood can cause rash in some people.
Relying on this type of treatment alone and avoiding or delaying conventional medical care for cancer may have serious health consequences.
Aldoxorubicin…….Treatment of cancer …HIV-derived Kaposi’s Sarcoma, pancreatic cancer and for the treatment of soft tissue sarcoma.
Aldoxorubicin
Click to access aldoxorubicin.pdf
in phase 3
(E)-N’-(1-((2S,4S)-4-(((2R,4S,5S,6S)-4-amino-5-hydroxy-6-methyltetrahydro-2H-pyran-2-yl)oxy)-2,5,12-trihydroxy-7-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydrotetracen-2-yl)-2-hydroxyethylidene)-6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanehydrazide hydrochloride
1H-Pyrrole-1-hexanoic acid, 2,5-dihydro-2,5-dioxo-, (2E)-2-[1-[(2S,4S)-4-[(3-amino-
2,3,6-trideoxy-α-L-lyxo-hexopyranosyl)oxy]-1,2,3,4,6,11-hexahydro-2,5,12-trihydroxy-
7-methoxy-6,11-dioxo-2-naphthacenyl]-2-hydroxyethylidene]hydrazide
N’-[(1E)-1-{(2S,4S)-4-[(3-amino-2,3,6-trideoxy-α-L-lyxo-hexopyranosyl)oxy]-2,5,12-
trihydroxy-7-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydrotetracen-2-yl}-2-
hydroxyethylidene]-6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanohydrazide
MOLECULAR FORMULA C37H42N4O13
MOLECULAR WEIGHT 750.7
SPONSOR CytRx Corp.
CODE DESIGNATION INNO-206
CAS REGISTRY NUMBER 1361644-26-9
CAS: 151038-96-9 (INNO-206); 480998-12-7 (INNO-206 HCl salt), 1361644-26-9
hydrochloride
CAS: 151038-96-9
Chemical Formula: C37H42N4O13
Exact Mass: 750.27484
Molecular Weight: 750.75
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Certificate of Analysis: |
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QC data: |
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Safety Data Sheet (MSDS): |
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In vitro protocol: |
Clin Cancer Res. 2012 Jul 15;18(14):3856-67 |
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In vivo protocol: |
Clin Cancer Res. 2012 Jul 15;18(14):3856-67. Invest New Drugs. 2010 Feb;28(1):14-9. Invest New Drugs. 2012 Aug;30(4):1743-9. Int J Cancer. 2007 Feb 15;120(4):927-34. |
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Clinical study: |
Expert Opin Investig Drugs. 2007 Jun;16(6):855-66. |
Aldoxorubicin (INNO-206): Aldoxorubicin, also known as INNO-206, is the 6-maleimidocaproyl hydrazone derivative prodrug of the anthracycline antibiotic doxorubicin (DOXO-EMCH) with antineoplastic activity. Following intravenous administration, doxorubicin prodrug INNO-206 binds selectively to the cysteine-34 position of albumin via its maleimide moiety. Doxorubicin is released from the albumin carrier after cleavage of the acid-sensitive hydrazone linker within the acidic environment of tumors and, once located intracellularly, intercalates DNA, inhibits DNA synthesis, and induces apoptosis. Albumin tends to accumulate in solid tumors as a result of high metabolic turnover, rapid angiogenesis, hyervasculature, and impaired lymphatic drainage. Because of passive accumulation within tumors, this agent may improve the therapeutic effects of doxorubicin while minimizing systemic toxicity.
“Aldoxorubicin has demonstrated effectiveness against a range of tumors in both human and animal studies, thus we are optimistic in regard to a potential treatment for Kaposi’s sarcoma. The current standard-of-care for severe dermatological and systemic KS is liposomal doxorubicin (Doxil®). However, many patients exhibit minimal to no clinical response to this agent, and that drug has significant toxicity and manufacturing issues,” said CytRx President and CEO Steven A. Kriegsman. “In addition to obtaining valuable information related to Kaposi’s sarcoma, this trial represents another opportunity to validate the value and viability of our linker technology platform.” The company expects to announce Phase-2 study results in the second quarter of 2015.
Kaposi’s sarcoma is an orphan indication, meaning that only a small portion of the population has been diagnosed with the disease (fewer than 200,000 individuals in the country), and in turn, little research and drug development is being conducted to treat and cure it. The FDA’s Orphan Drug Act may grant orphan drug designation to a drug such as aldoxorubicin that treats a rare disease like Kaposi’s sarcoma, offering market exclusivity for seven years, fast-track status in some cases, tax credits, and grant monies to accelerate research
INNO-206 is an anthracycline in early clinical trials at CytRx Oncology for the treatment of breast cancer, HIV-related Kaposi’s sarcoma, glioblastoma multiforme, stomach cancer and pancreatic cancer. In 2014, a pivotal global phase 3 clinical trial was initiated as second-line treatment in patients with metastatic, locally advanced or unresectable soft tissue sarcomas. The drug candidate was originally developed at Bristol-Myers Squibb, and was subsequently licensed to KTB Tumorforschungs. In August 2006, Innovive Pharmaceuticals (acquired by CytRx in 2008) licensed the patent rights from KTB for the worldwide development and commercialization of the drug candidate. No recent development has been reported for research that had been ongoing for the treatment of small cell lung cancer (SCLC).
INNO-206 is a doxorubicin prodrug. Specifically, it is the 6-maleimidocaproyl hydrazone of doxorubicin. After administration, the drug candidate rapidly binds endogenous circulating albumin through the acid sensitive EMCH linker. Circulating albumin preferentially accumulates in tumors, bypassing uptake by other non-specific sites including the heart, bone marrow and the gastrointestinal tract. Once inside the acidic environment of the tumor cell, the EMCH linker is cleaved and free doxorubicin is released at the tumor site. Like other anthracyclines, doxorubicin inhibits DNA and RNA synthesis by intercalating between base pairs of the DNA/RNA strand, thus preventing the replication of rapidly-growing cancer cells. It also creates iron-mediated free oxygen radicals that damage the DNA and cell membranes. In 2011, orphan drug designation was assigned in the U.S. for the treatment of pancreatic cancer and for the treatment of soft tissue sarcoma.
CytRx Corporation (NASDAQ:CYTR) has announced it has initiated a pivotal global Phase 3 clinical trial to evaluate the efficacy and safety of aldoxorubicin as a second-line treatment for patients with soft tissue sarcoma (STS) under a Special Protocol Assessment with the FDA. Aldoxorubicin combines the chemotherapeutic agent doxorubicin with a novel linker-molecule that binds specifically to albumin in the blood to allow for delivery of higher amounts of doxorubicin (3.5 to 4 times) without several of the major treatment-limiting toxicities seen with administration of doxorubicin alone.
According to a news from Medicalnewstoday.com; CytRx holds the exclusive worldwide rights to INNO-206. The Company has previously announced plans to initiate Phase 2 proof-of-concept clinical trials in patients with pancreatic cancer, gastric cancer and soft tissue sarcomas, upon the completion of optimizing the formulation of INNO-206. Based on the multiple myeloma interim results, the Company is exploring the possibility of rapidly including multiple myeloma in its INNO-206 clinical development plans.
According to CytRx’s website, In preclinical models, INNO-206 was superior to doxorubicin with regard to ability to increase dosing, antitumor efficacy and safety. A Phase I study of INNO-206 that demonstrated safety and objective clinical responses in a variety of tumor types was completed in the beginning of 2006 and presented at the March 2006 Krebskongress meeting in Berlin. In this study, doses were administered at up to 4 times the standard dosing of doxorubicin without an increase in observed side effects over historically seen levels. Objective clinical responses were seen in patients with sarcoma, breast, and lung cancers.
INNO-206 – Mechanism of action:
According to CytRx’s website, the proposed mechanism of action is as the follow steps: (1) after administration, INNO-206 rapidly binds endogenous circulating albumin through the EMCH linker. (2) circulating albumin preferentially accumulates in tumors, bypassing uptake by other non-specific sites including heart, bone marrow and gastrointestinal tract; (3) once albumin-bound INNO-206 reaches the tumor, the acidic environment of the tumor causes cleavage of the acid sensitive linker; (4) free doxorubicin is released at the site of the tumor.
INNO-206 – status of clinical trials:
CytRx has announced that, in December 2011, CytRx initiated its international Phase 2b clinical trial to evaluate the preliminary efficacy and safety of INNO-206 as a first-line therapy in patients with soft tissue sarcoma who are ineligible for surgery. The Phase 2b clinical trial will provide the first direct clinical trial comparison of INNO-206 with native doxorubicin, which is dose-limited due to toxicity, as a first-line therapy. (source:http://cytrx.com/inno_206, accessed date: 02/01/2012).
Results of Phase I study:
In a phase I study a starting dose of 20 mg/m2 doxorubicin equivalents was chosen and 41 patients with advanced cancer disease were treated at dose levels of 20–340 mg/m2 doxorubicin equivalents . Treatment with INNO-206 was well tolerated up to 200 mg/m2 without manifestation of drug-related side effects which is a ~3-fold increase over the standard dose for doxorubicin (60 mg/kg). Myelosuppression and mucositis were the predominant adverse effects at dose levels of 260 mg/m2 and became dose-limiting at 340 mg/m2. 30 of 41 patients were assessable for analysis of response. Partial responses were observed in 3 patients (10%, small cell lung cancer, liposacoma and breast carcinoma). 15 patients (50%) showed a stable disease at different dose levels and 12 patients (40%) had evidence of tumor progression. (source: Invest New Drugs (2010) 28:14–19)
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References |
1: Kratz F, Azab S, Zeisig R, Fichtner I, Warnecke A. Evaluation of combination therapy schedules of doxorubicin and an acid-sensitive albumin-binding prodrug of doxorubicin in the MIA PaCa-2 pancreatic xenograft model. Int J Pharm. 2013 Jan 30;441(1-2):499-506. doi: 10.1016/j.ijpharm.2012.11.003. Epub 2012 Nov 10. PubMed PMID: 23149257.
2: Walker L, Perkins E, Kratz F, Raucher D. Cell penetrating peptides fused to a thermally targeted biopolymer drug carrier improve the delivery and antitumor efficacy of an acid-sensitive doxorubicin derivative. Int J Pharm. 2012 Oct 15;436(1-2):825-32. doi: 10.1016/j.ijpharm.2012.07.043. Epub 2012 Jul 28. PubMed PMID: 22850291; PubMed Central PMCID: PMC3465682.
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Replacing insulin though stem cell-derived pancreatic cells under the skin
Microscopic view of Islet of Langerhans in the pancreas. Beta cells in the Islets are responsible for producing insulin
Sanford-Burnham and UC San Diego School of Medicine scientists have shown that by encapsulating immature pancreatic cells derived from human embryonic stem cells (hESC), and implanting them under the skin in animal models of diabetes, sufficient insulin is produced to maintain glucose levels without unwanted potential trade-offs of the technology. The research suggests that encapsulated hESC-derived insulin-producing cells hold great promise as an effective and safe cell-replacement therapy for insulin-dependent diabetes. “Our study critically evaluates some of the potential pitfalls of using stem cells to treat insulin-dependent diabetes,” said Pamela Itkin-Ansari, Ph.D., adjunct assistant professor in the Development, Aging, and Regenerative Program at Sanford-Burnham, with a joint appointment at UC San Diego. – See more at: http://beaker.sanfordburnham.org/2014/03/replacing-insulin-though-stem-cell-derived-pancreatic-cells-under-the-skin/#sthash.GDnpkm3h.dpuf
See more at: http://beaker.sanfordburnham.org/2014/03/replacing-insulin-though-stem-cell-derived-pancreatic-cells-under-the-skin/
New Drug Approvals 