1. Derya Yenigun, Rebecca Jones, Amber Rauch
Vincristine
Derya Yenigun, Rebecca Jones, Amber Rauch

2. Importance of Vincristine
Vincristine is an extremely wide spread drug that is included on the World Health Organization's List of Essential Medicines for the treatment of cancers.

3. Introduction Vincristine was approved by the FDA in 1963.
Vincristine specifically targets cell replication and helps prevent cells from replicating to stop metastasizing of cancers.

4. Introduction
Vincristine is also known as Leurocristine, Oncovin, Vincasar, and Vincrex.
Vincristine is an extremely effective chemotherapy drug that is used to combat cancer cells in humans, cats, and dogs.
Vincristine is used to treat many different types of cancers including leukemia, Hodgkin’s lymphoma, lung cancer, breast cancer and more! 

5. Origin
Vincristine was originally derived from the mildly toxic plant Catharanthus roseus.
Today, the drug is synthetically created due to the small yield (0.0003%) and high cost of the medicine extracted from the plant.

6. Catharanthus roseus Otherwise known as the Madagascar Periwinkle
 Vincristine is a naturally occurring alkaloid isolated from the leaves of the plant Catharanthus roseus. 
It has a wide range of clinical applications to treat infection, high blood pressure, and diabetes.

7. Structure
Vincristine is formed via the coupling of the alkaloids vindoline and catharanthine in the vinca plant.

8. Approval
Many studies were performed and published leading up to the approval of Vincristine.
Several studies were published in 1963 to determine the toxicity, tolerated dose,  effect of dose schedule on toxicity, and the antitumor properties of vincristine in patients with malignant disease. 
Amongst these studies was one performed by Paul Carbone and his colleagues.  They treated the patients at a point of toxicity and adjusted the dose accordingly.  The tolerated dose for the weekly schedule was determined to be 0.05 mg. per Kg in most subjects.

9. Mechanism
Vincristine and other vinca alkaloids destabilize microtubules by induction of microtubule depolymerization and mitotic spindle destruction.
This prevents metaphase and cells remain in senescent-like G1 state until cell death is triggered.

10. Mechanism
The effectiveness of vincristine in chemotherapy may also be associated with their influence on other mechanisms including inhibition of several protein kinase cascades and upregulation of p53. 
The modulation of p53 and p21 pathway is involved in apoptosis and regulation of several protein kinase phosphorylation cascades. 
      

11. Pharmacokinetics
Plasma membrane transporter such as P-gp were found to be upregulated in several cell lines treated by vincristine.
Cellular metabolism of vincristine seems to be related to high expression of CYP3A5.
However, low expression of CYP3A5 is also associated with a higher risk of vincristine neurotoxicity.

12. Clinical Use
Vincristine has been indicated in the management of pediatric and adult malignancies, mostly in combination therapy in the first or second-line settings.
Clinically, vincristine is administered intravenously by a trained professional, typically once a week.

13. Clinical use
New clinical research efforts to maximize the therapeutic effects.
Liposomal vincristine formulation is being explored.
It seems to be clinically effective and less toxic. 

14. Side Effects Vincristine has several side effects including: Hair loss
Change in blood pressure
Dizziness
Nausea
Peripheral neuropathy
Paralysis
Injection into the spine can cause death

15. Toxicology
The dose-limiting toxicities of vincristine are conformed to the peripheral nervous system such as symmetric mixed sensory-motor, and autonomic polyneuropathy on a weekly treatment schedule.
Central nervous system toxicity is not observed due to poor penetration of the blood brain barrier.
Catastrophic neurotoxicity has been associated with the administration of it directly into the cerebrospinal fluid.

16. Toxicology
Cytochrome P450 enzymes and other drugs such as corticosteroids and other drugs effect the vincristine pharmacokinetics.
-Drugs such as itraconazole that alter the metabolism of vincristine should be used with caution if at all.
-Drugs with antineoplastic agents that have platinum such as cisplatin could cause hearing impairment
-Phenytoin when mixed with Vincristine can cause seizures.

17. Conclusion
Despite the long list of side effects caused by Vincristine, it remains one of the safest and most effective cancer drugs on the market.
Research on the drug has been continued over the years in order to find the safest, most effective form.  Some studies performed on the drug have occurred as recently as 2019.
Because of these things, Vincristine remains incredibly wide-spread and important in the world of cancer treatment for humans and animals alike.

18. Future Research
Several more recent studies have also shown that vincristine's effectiveness can be improved with compounded drugs. Compounded treatments can potentially be much safer and more effective and require less dosage. 
One research group found that using calcium channel blockers with vincristine actually significantly increase the effectiveness of the drugs ability to stop cancer cells and increase vincristine resistance.
Another research group used a drug called Clotam along with vincristine and found that it also greatly increased the effectiveness of the drug.

19. Future Research
Drug interactions can have very negative effects but also positive effects! If we could increase the effectiveness of safer drugs like vincristine by combining two known treatments, we could save a lot of money and possibly reduce the LD50  and survival rate of certain cancers without having to develop new treatments! 
Further Research possibilities on vincristine compounds should be explored and have many exciting possibilities on the toxicology! 

20. Sources
Carbone, Paul P, et al. Clinical Studies With Vincristine. Blood Journal. American Society of Hematology, “Catharanthus Roseus.” Catharanthus Roseus - an Overview | ScienceDirect Topics, ScienceDirect, “Catharanthus Roseus.” Catharanthus Roseus - an Overview | ScienceDirect Topics, ScienceDirect, Sabres, Yolanda D., and Juan M. Coello. Vincristine : Clinical Uses, Pharmacokinetics and Impacts on Health. Nova Science Publishers, Inc, EBSCOhost, search.ebscohost.com/login.aspx?direct=true&db=nlebk&AN=650691&site=eds- live&scope=site.\ Shelake, S., Sankpal, U. T., Eslin, D., Bowman, W. P., Simecka, J. W., Raut, S., Basha, R. (2019). Clotam enhances anti-proliferative effect of vincristine in Ewing sarcoma cells. Apoptosis, 24(1-2), doi: /s

21. Sources
Taghizadehghalehjoughi, A., Sezen, S., Hacimuftuoglu, A., & Güllüce, M. (2019). Vincristine combination with Ca 2 channel blocker increase antitumor effects. Molecular Biology Reports,46(2), doi: /s w
"Vincristine.". “Vincristine.” Gale Encyclopedia of Cancer, Encyclopedia.com, 2019,
Vutukuri, Venkateswar Rao, et al. “Evaluation of Acute Oral Toxicity of Ethanol Leaves Extract of Catharanthus Roseusin Wistar Albino Rats.” Journal of Clinical and Diagnostic Research : JCDR, JCDR Research and Publications (P) Limited, Mar. 2017, 
Yin, Loh Keng. “Know the Medicinal Herb: Catharanthus Roseus (Vinca Rosea).” Malaysian Family Physician : the Official Journal of the Academy of Family Physicians of Malaysia, Academy of Family Physician of Malaysia, 31 Aug. 2008,