The well-known “penicillin of cancer drugs” is probably an appropriate nickname of cisplatin due to its world widely use as the first and one of the most effective treatment for numerous cancer diagnoses. One important thing that must be point out is that cisplatin is a very simple inorganic molecule comparing to other cancer drugs which generally are complex organic molecules. In order to design and develop new related cancer drugs, cisplatin has been used as a gold model by many scientists.
General information
Cisplatin is a metal-based anticancer chemotherapy drug which is a clear liquid and can be given directly into a vein by injection. It can target fast growing cancer cells to slow or stop the proliferation of the cancer cells and finally cause apoptosis. The systematic name of cisplatin is cis-diamminedichloroplatinum(II) and CDDP is the abbreviation. The trade name of cisplatin in the market is Platinol® (cisplatin for Injection) or Platinol®-AQ.
History
The reason why cisplatin is called the “penicillin of cancer” is that because of its widespread use and also it was the first big and strong chemotherapy drug in medication history. It was first synthesized in the 1845 by Michel Peyrone, and known as Peyrone's chloride as well. At the time that cisplatin was discovered, actually no one would think it can be used to against cancer at all, and it was just one of the inorganic compound that researchers used to prove one of their synthetic route could work. About 50 years later, it become a significant factor of establishing the theory of coordination chemistry by Alfred Werne, in the work he figured out the accurate square planar configuration of cisplatin and pointed out the difference between the cis and trans is...
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...d with surgery or radiation therapy for different types of cancers.
Conclusion
Since the discovery of cisplatin, thousands of platinum complexes were evaluated, but only five were approved. Consequently, more than 10000 compound need to be screened so as to get a novel and more effective anticancer drug than cisplatin with the aid of inorganic or coordination chemistry. Solubility, reactivity, electronic and steric effects, and the configuration of metal complexes can be controlled by modifying the metal to other transition metal such as Pd and Ni or the ligand around the metal atom which has been reported that both the metal and the ligand can determine the biological activity. Hopefully we can find more efficient drugs that may contain much less side effects than cisplatin, as well as solve the problem of overcoming drug resistance of some cancers to cisplatin.
The Factor of War in the Development of Penicillin The discovery, development and subsequent use of penicillin can be considered to be one of the most important breakthroughs in medical history. There were many factors, which were involved in the development of penicillin, and it could be argued that war was the most important, but other factors were also responsible. Alexander Fleming was working in London as a bacteriologist in 1928 when he noticed that a growth of a mould called penicillin produced a substance that actually killed the germs he was working on. He realised that this might be very important and a year later he wrote an article about his findings. However, Fleming did not have the facilities or the support to develop and test his idea that penicillin could fight infection, and he didn't develop it further.
Penicillin, derived from the mold Penicillium, is the first antibiotic to successfully treat bacterial infections on humans. It was accidentally discovered by scientist, Alexander Fleming. While Fleming was growing Staphylococcus, a serious and often deadly infection, in a dish, he noticed the bacteria had stopped growing after a mold found its way
Specifically “TP53, p16INK4A, and SMAD4. The p53 nuclear protein activates transcription of a cyclin kinase inhibitor p21WAF1/CIP1. Following genomic stress, inappropriate growth factor stimulation or expression of oncogenic ras increased expression of p53, and thus p21WAF1/CIP1 resulted in inactivation of specific CDK/cyclin complexes” (MedScape). If this transformed cell can escape internal and external fail-safe mechanisms, receive nutrients, and activate its proliferative program, it can form a mass of cancerous cells. Tumor growth can cause the loss of pancreatic functions. Another characteristic of pancreatic cancer is metastasis happens early in tumor growth, which is most likely responsible for pancreatic cancer’s aggressive
Years later other scientists were also intrigued by the possibilities of penicillin and produced enough penicillin to prove that it was a useable antibiotic. The scientists from Great Britain were developing all of this during World War II, and unfortunately funding for their drug was unavailable due to the war. They decided to bring their concepts to the United States, and once enough was made, it was eventually used, to treat wounded soldiers during World War I.
Altman, Lawrence K. ìShark Substance Found to Limit Tumor Growth.î New York Times 1 May 1996: A15.
Chemotherapy is the treatment of a tumor with chemical agents to reduce mass or eradicate a tumor completely. There are certain mechanisms by which chemotherapy inhibits cancer. The first mechanism is cell death by cytotoxicity. Some chemical agents in certain amounts are toxic to cells. The cells die due to the toxic...
The topic of this article is medication error related to chemotherapy drugs. Forty percent of medication errors have been related to chemotherapy drugs. It is imperative that the nurses are properly trained on these medications and fully understand what is being administered before giving it to the patient as well as know what the proper dose is before administering anything to the patient. More importantly the nurse must pay close attention to their patient’s response to the chemotherapy given to the patient or it could lead to a serious injury or death.
“When someone has cancer, the whole family and everyone who loves them does, too.” – Terri Clark
Chemotherapy is the use of chemicals to cure cancer. Chemotherapy is also known as “chemo”. The term for chemo came from the German bacteriologist Paul Ehrlich around the year 1900. He came up with the term when he was examining aniline dyes and arsenicals as possible treatments for diseases such as syphilis. He envisioned “magic bullets” that would be able to target invading organisms but still leave the host unscathed. This goal has been providing therapeutic benefits without many side effects in all areas of drug development. There has been a lot of success with compounds that modulate normal biochemistry within the body.
Different approaches have been tested to discover new biomarkers for the detection of prostate cancer, and there has been success in this field with specific markers found such as PCA3 (FDA approved) and TMPRSS2:ERG fusion gene which have a synergistic sensitivity when both are tested in combination for prostate cancer (Otero) (Dijkstra). Within the field of prostate cancer research, the drug Docetaxel is used effectively in the treatment of advanced prostate cancer known as castration-refractory prostate cancer (CRPC). However, patients eventually develop resistance, and the search for a biomarker of disease and drug resistance in prostate cancer is in demand (O’neill) (O’connell). A mass spectrometry (MS) analysis of drug resistant prostate cancer cell lines, parental and docetaxel-resistant, found that...
Almost everyone is touched by cancer in some way and the number of people living with and beyond cancer grows greater every year. Globally 14 million people are diagnosed with cancer each year and 8 million people will die from it annually. Half of all men and one-third of all women will develop cancer during their lifetime. (13) There are many treatments for cancer, mainly: surgery, radiation and chemotherapy. These traditional treatments have many negative side effects. Therefore, increasingly, other treatments, such as hormonal therapy and targeted therapy are being used for certain cancers. Nanotechnology is a form of targeted therapy that destroys cancer tumors with minimal damage to healthy tissues and organs. Scientists are already using nanotechnology in early detection of elimination of cancer cells before they form tumors. But the real game changer will be when nanotechnology targets cancer tumors in treatment (11,13).
Cancer is one of the leading causes of death worldwide as it can develop in almost any organ or tissue. Significant advances in understanding the cellular basis of cancer and the underlying biological mechanisms of tumour has been vastly improved in the recent years (Jiang et al. 1994). Cancer is a genetic disease which requires series of mutation during cell division to develop, it has characteristics which can be associated with their ability to grow and divide abnormal cells uncontrollable while in the mean time invade and cause nearby blood vessels to serve its need. Even though many people are affected by cancer today, the abilities which cancer cells own make it hard to find single effective treatment for cancer. The focus of research now lies on developing drugs which target cancer cells in the hope to cure cancer once and for all.
Cheever MA, Higano CS. PROVENGE (Sipuleucel-T) in prostate cancer: the first FDA-approved therapeutic cancer vaccine. Clinical cancer research: an official journal of the American Association for Cancer Research.
Both these cell lines are known to express endogenous transporters (39) and results from these studies should be interpreted with caution. When uptake studies were done in LLC-PK1 wild type cells, dasatinib intracellular concentrations were found to be significantly increased in the presence of 50μM pazopanib and regorafenib. LLC-PK1 cells express endogenous BCRP and pazopanib and regorafenib were found to be significant BCRP inhibitors in our earlier uptake study with MDCK-II-BCRP cells. Therefore, it is likely that these endogenous BCRP transporters maybe responsible for the uptake change observed. Further, dasatinib intracellular concentrations significantly decreased in the presence of afatinib, bosutinib, gefitinib, imatinib, lapatinib, ponatinib, sunitinib and vandetanib. LLC-PK1 cells do not express OATP-C uptake transporters.(40) Dasatinib uptake studies in MDCK-II wild type cells revealed a slightly different trend. Among the 14 ingredients screened, 6 of them, namely, axitinib, erlotinib, imatinib, lapatinib, nilotinib and pazopanib exhibited a significant increase in dasatinib intracellular concentrations. MDCK-II cells have very little BCRP expression but have endogenous Pgp expression. Since axitinib, imatinib, lapatinib, nilotinib and pazopanib showed potent Pgp inhibition in the uptake study conducted in LLC-PK1-Pgp cells, the increased dasatinib uptake in MDCK-II wild
Pre-discovery process is the first stage of drug discovery. During Pre-discovery stage chemists and pharmacologists endeavor to understand and identify the factors which can play a significant role in the particular disease. After revealing the cause of disease or understanding it a target molecule against which drug will act is being chosen. In order to understand the structure the target molecule is eliminated, isolated and its various interactions are inquired. Understanding interactions of the molecule can be helpful in finding treatment of a specific disease. Next stage includes the demonstration that the chosen molecule is relevant to the disease and proof that the drug target is associated with a desired change in the behavior of diseased cells (PPD, 2011).