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Plants Used In Cancer Treatment - PowerPoint

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					Plants Used In Cancer Treatment


            Part - I
Cancer
   What is cancer?
   US cancer statistics
   Cancer costs
   Most frequent cancers by organ effected
Major types of cancers
   Over 200 types of cancer are known
    grouped into major categories
     Carcinomas
     Sarcomas
     Melanomas
     Teratomas
     Leukemias   and Lymphomas
History of Cancer Therapy
 Folk remedies
 NCI – 1955
 NCI-USDA – late 1950s
 NCI – 1985
 21st century
Current Plant Based Therapies
 Periwinkle
 Mayapple
 Yew
 Camptotheca
 Lapachol
Madagascar Periwinkle – Vinca alkaloids

                       Catharanthus roseus is
                        known as the common or
                        Madagascar periwinkle,
                       Formerly classified as
                        Vinca rosea
                       Perennial evergreen herb
                        in Apocynaceae
                       Originally native to island
                        of Madagascar
Traditional uses of periwinkle
   Used to treat a wide assortment of diseases
       In Europe, folk remedy for diabetes for centuries
       In India, juice from the leaves to treat wasp stings.
       In Hawaii, boiled to make a poultice to stop bleeding.
       In China, an astringent, diuretic and cough remedy.
       In Central and South America, homemade cold remedy
        to ease lung congestion and inflammation and sore
        throats
       Throughout the Caribbean, an flower extract to treat
        eye irritation and infections
Interest in Periwinkle
   Two groups began independently working on
    periwinkle in 1950s when they learned of a tea
    Jamaicans were drinking to treat diabetes
       Univ of Western Ontario - Beer and Noble -interested
        in plant as a possible “oral insulin” - they isolated
        alkalod - vinblastin
       Eli Lilly Pharmaceuticals - Svoboda
Lilly Pharmaceuticals
   Svoboda injected a crude extract of the whole
    periwinkle plant into mice that were infected with
    P-1534 leukemia
   60-80% of the mice experienced prolonged life
   Lilly produced vinblastin as the drug Velban
   Also synthesized another alkaloid, vincristine
    (VCR), as the drug Oncovin
   First human tests in 1960 - 49 yr old man dying of
    Hodgkin’s disease - within one week man was
    walking - 4 months later the tumor gone
More alkaloids in periwinkle
 Overall 70 alkaloids have been identified in
  periwinkle
 Some have anticancer properties
 Some lower blood sugar levels
 Some act as hemostatics (arrest bleeding)
 Periwinkles also contain the alkaloids
  reserpine and serpentine, which are
  powerful tranquilizer
Vincristine and vinblastine
   Major chemotherapeutic agents
   Vincristine has been especially effective for
    treating acute childhood leukemia, often with 99%
    remission rates
   Vinblastine has been especially effective for
    treating Hodgkin's disease - which had been
    considered a fatal up to that point
   Gave researchers hope that some cancers can be
    overcome by simple chemotherapy
   Today used for other types of cancers
Mode of action of vinca alkaloids
    Vinblastine, vincristine, and two semi-synthetic
     derivatives (vindesine and vinorelbine) all have
     the same mode of action
    Inhibit mitosis in metaphase by binding tubulin
Potent Drugs
 They are all administered intravenously
  once a week
 Cmpds are fatal if they're administered any
  other way, and can cause a lot of tissue
  irritation if they leak out of the vein.
 Compounds are very similar in structure
  and have the same basic action, they have
  distinctly different effects on the body.
Vinblastine
 Marketed as Velban
 Half-life in the bloodstream of 24 hours
 Vinblastine is mainly useful for treating
  Hodgkin's disease, lymphocytic lymphoma,
  histiocytic lymphoma, advanced testicular
  cancer, advanced breast cancer, Kaposi's
  sarcoma
 It also seems to fight cancer by interfering
  with glutamic acid metabolism
Side effects of vinblastine
 Side effects include hair loss, nausea,
  lowered blood cell counts, headache,
  stomach pain, numbness, constipation and
  mouth sores
 Bone marrow damage is the typical dose-
  limiting factor
 Caused severe birth defects in lab animals
  so not used on pregnant patients
Vincristine
   Marketed as Oncovin
   Serum half-life of about 85 hours.
   Used mainly to treat acute leukemia,
    rhabdomyosarcoma, neuroblastoma, Hodgkin's
    disease and other lymphomas
   Also Wilms' tumor (80%) and Burkitt's lymphoma
    (50%), when used in combination with other drugs
   Neurotoxicity is the dose limiting factor (it can
    cause damage to the peripheral nervous system)
Side effects of vincristine
   Same as those found with vinblastine
   Nervous system problems such as sensory
    impairment
   Breathing problems or lung spasms shortly after
    the drug is administered
   Secondary cancers if they receive the drug along
    with other anticancer drugs that are known to be
    carcinogens
   Severe birth defects in animal tests
Vindesine -semi synthetic
 Marketed as Eldisine and Fildesin
 Serum half-life of about 24 hours
 Mainly to treat melanoma and lung cancers
  (carcinomas) and, with other drugs, to treat
  uterine cancers
 Toxicity and side effects are similar to those
  of vinblastine
Vinorelbine - semi-synthetic
   Marketed as Navelbine
   Approved for non-small cell lung cancer and
    breast cancer – usually in combination with other
    drugs
   Clinical trials on-going as a treatment for ovarian,
    cervical, prostrate and other cancers
   Seems to have a wider range of antitumor activity
    than the other vinca alkaloids
   Side effects include diarrhea, nausea, hair loss,
    leukopenia

				
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