Oxaliplatin - Essay Example

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This was ascribed to the pronounced activity of cisplatin, specifically in testicular and ovarian cancers1. Before going into the history of discovery…

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Subject: Miscellaneous
Type: Essay
Level: Undergraduate
Pages: 14 (3500 words)
Downloads: 1
Author: rudy19

Extract of sample "Oxaliplatin"

Download file to see previous pages This was developed following discovery of cisplatin in an attempt to reduce the problematic side effects of cisplatin. This is administered intravenously, and till date, no commercially viable orally active agent has been reported to be accepted for therapy3,4. Like cisplatin, oxaliplatin is also associated with quite a few dose-limiting adverse effects, which include myelosuppression along with others5. These are neurotoxic side effects that include sensory peripheral neuropathy which can be dose limiting. The other side effects include gastrointestinal disturbances and ototoxicity, while renal function may be normally monitored during therapy6. In this assignment contemporary literature will be reviewed to address the effects of oxaliplatin genotoxicity on human lymphocytes by using various cytogenetic techniques.
Oxaliplatin contains a cyclohexyl and a pentadilactone ring, which will be evident from its chemical structure in a later section7. This has been approved for treatment of metastatic colon cancer in combination with 5-fluorouracil and folinic acid8. Therefore, this is a diaminocyclohexane (DACH) platinum compound9. This was considered as a probable chemotherapeutic agent since it demonstrated preclinical activities in some cisplatin-resistant cell lines and xenografts10. Oxaliplatin is an important member of this DACH platinum group of compounds. Its preclinical activity against colorectal cancer has been studied in great detail. It has been suggested that oxaliplatin has a greater extent of cell kill in resistant cancers since therapy with this agent may result in greater resistance to repair mechanisms leading to affected recovery of cancer cells11. This has been attributed to the size of the DACH carrier ligands, resulting into a bulkier platinum-DNA adduct in comparison to that created by cisplatin12.
The inhibitory effects of platinum compounds have been ascribed to formation of inorganic platinum compounds in presence ...Download file to see next pagesRead More

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Lab Report

...novel biomarker for DNA double-strand breaks. The general practice has been to use alkaline comet assay to monitor patients undergoing chemotherapy. The gamma-H2AX assay has been reported to detect DNA damage as low as 100-fold below the detection limit of the alkaline comet assay (Ismail et al., 2007). Furthermore, Ismail et al. also observed induction of gamma-H2AX in response to DSBs in all nucleated blood cell types, including the short-lived neutrophils. The main aim of the present study was to investigate the induction of DNA double strand breaks in lymphocytes in response to oxaliplatin and satraplatin treatments, using gamma-H2AX phosphorylation, assayed by an immunofluorescence technique, as a biomarker of DNA double strand...

12 Pages(3000 words)Lab Report

Lap report

...–protein crosslinks (Woynarowski et al., 2000). According to Chiu et al. (2008), oxaliplatin induces persistent gamma-H2AX production, leading to apoptosis in colorectal cancer cells. Oxaliplatin is a potent inhibitor of survivin. Recently, Liu et al. (2010) showed that survivin protein expression is significantly reduced in human colon cancer cells exposed to oxaliplatin whereas the survivin gene expression changes slightly. However, the primary mechanism through which cell death occurs with oxaliplatin depends on the cell type (Ngan et al., 2007). Vinflunine is a second generation Vinca alkaloid showing anti-neoplastic activity in a wide spectrum of solid tumours. It acts by binding to tubulin and causing the subsequent cellular arrest...

10 Pages(2500 words)Lab Report

Lab report 3

...in oxaliplatin- or satraplatin-treated lymphocytes. In contrast to this, when used in the nanoparticle form both TF and EGCG caused a concentration-dependent increase in DNA damage in the lymphocytes. The maximum increase noted with TF was around 2.5-fold. The reverse activities exhibited by the two forms, namely bulk- and nanoparticle forms, of TF as well as EGCG support the notion that TF and EGCG act as both antioxidant and pro-oxidant, depending on the form in which they are administered. In the bulk form, the compounds likely act as antioxidants, which was observed as a decrease in the DNA damage measured as Olive Tail Moment in the comet assays. It is also our hypothesis that, changing their mode of action in the...

12 Pages(3000 words)Lab Report

Justification and future work

...., 2000), and the absence of resistance due to mismatch repair deficiency (Sergent et al., 2002). Oxaliplatin activity and mechanisms of action and resistance are quite different from those of other platinum-containing compounds such as cisplatin. Peripheral neuropathy is the main side effect of oxaliplatin treatment. Satraplatin [bisacetato-ammine-dichloro-cyclohexylamine-platinum(IV)] is an orally bioavailable platinum analogue having myelosuppression as the dose-limiting toxic side-effect. Adverse effects due to high toxicity have led to the abandonment of a majority of platinum compounds synthesised (Boulikas et al., 2007). The authors’ expert belief is that encapsulation into tumour targeted...

4 Pages(1000 words)Essay

The Use of 5 Fluorouracil Pumps in Gastro-Intestinal Patients

.... Comella, P., Massidda, B., Palmeri, S., Putzu, C., De Rosa, V., Izzo, F., Fiore, F., Casaretti, R. and Sandomenico, C., 2006. Biweekly oxaliplatin plus irinotecan and folinic acid- modulated 5-fluorouracil: a phase II study in pretreated patients with metastatic colorectal cancer. Anticancer Drugs, 17 (8), pp. 985-92. Cunningham, J., Bukowski, R., Budd, G., Weick, J. and Purvis, J., 1984. 5-Fluorouracil and folinic acid: a Phase I-II trial in gastrointestinal malignancy. Invest New Drugs, 2 (4), pp. 391-5. Falcone, A., Allegrini, G., Lencioni, M., Pfanner, E., Brunetti, I., Cianci, C., Galli, C., Masi, G., Antonuzzo, A. and Conte, P., 1998. Protracted continuous infusion of 5-fluorouracil and low-dose leucovorin in patients...

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Role Of Notch Signaling In Oncogenesis

.... and Karsan, A. (2006). Recent insights into the role of Notch signaling in tumorigenesis. Blood 107, 2223-33. Meng, R.D., Shelton, C.C., Li, Y.M. (2009). gamma-Secretase inhibitors abrogate oxaliplatin-induced activation of the Notch-1 signaling pathway in colon cancer cells resulting in enhanced chemosensitivity. Cancer Res. 69(2), 573-82. Murtaugh, L.C., Stanger, B.Z., Kwan, K.M., and Melton, D.A. (2003). Notch signaling controls multiple steps of pancreatic differentiation. Proc Natl Acad Sci, 100 (25), 14920–5. Real, P.J., Tosello, V., Palomero, T. (2009). Gamma-secretase inhibitors reverse glucocorticoid resistance in T cell acute lymphoblastic leukemia. Nat Med.15(1), 50-8. Rustiqhi, A., Tiberi, L., Soldano,...

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Death in the laboratory

...the nucleus. Cancer Focus. (http://cancerfocus.org/how _cisplatin_reaches_the_nucleus/653?s=fb25220c9360f5f4816660edbd4c92da&) Fischel, J. L., P. Formento, J. Ciccolini, P. Rostagno, M. C. Etienne, J. Catalin, and G. Milano. 8 April 2002. Impact of the oxaliplatin - 5 fluorouracil - folinic acid combination on respective intracellular determinants of drug activity. British Journal of Cancer. Vol. 86, pp. 1162-1168. Ganz, Patricia. 2007. Cancer survivorship: today and tomorrow. East Sussex: Routledge. International Symposium on Platinum Coodination Compounds in Cancer Chemotherapy, and Andrea Bonetti. 2009. Platinum and other heavy metal compounds in cancer chemotherapy: molecular mechanisms and clinical...

4 Pages(1000 words)Essay

Discussion part

...rough damage repair or apoptosis (Liu and Kulesz-Martin, 2001). The tumour-suppressor protein, p53, functions by binding DNA, and stimulating the synthesis of protein p21 which, following DNA damage, interacts with cdk2, a cell division-stimulating protein (Coqueret, 2003). Complexing of p21 with cdk2 inhibits cell division. Thus, cells that lack p53 divide uncontrollably, and form tumours. Kalimutho et al. (2010), working with colorectal cancer cells, observed that satraplatin was a stronger inducer of apoptosis compared to oxaliplatin. However, with both the Pt compounds, induction of apoptosis was associated with an increase in p53 protein levels. Yet satraplatin could induce apoptosis in a p53-dependent as well as p53-independent...

12 Pages(3000 words)Lab Report

Retroanalyses nonrandomized study over a X period of time for esophageal cancer patient which compares two treatment options: intra-luminal brachytherapy alone vs. intra-luminal brachytherapy treatment combined with chemotherapy

... Cunningham D, Allum W, Stenning SP, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355:11–20. Cunningham D, Rao S, Starling N, et al. Randomised multicenter phase III study comparing capecitabine with fluorouracil and oxaliplatin with cisplatin in patients with advanced oesophagogastric cancer: the REAL-2 trial. J Clin Oncol. 2006;24(18S):182s. Dank M, Zaluski J, Barone C, et al. Randomized phase 3 trial of irinotecan + 5FU/folinic acid vs CDDP + 5FU in first line advanced gastric cancer patients. Proc Am Soc Clin Oncol. 2005;23:308. De Besi P, Sileni VC, Salvagno L, et al. Phase II study of cisplatin, 5-FU, and allopurinol in advanced esophageal cancer. Cancer Treat Rep...

20 Pages(5000 words)Thesis

The role of controlled drug release in cancer therapeutics

...clusion complex. Adv Drug Deliv Rev 57(15):2203–2214 Petros, R. 2010. Strategies in the design of nanoparticles for therapeutic applications. Nat Rev Drug Discovery 9(8):615–627 Rothenfl uh, D. 2008, Biofunctional polymer nanoparticles for intra-articular targeting and retention in cartilage. Nat Mater 7(3):248–254 Salvador, M. 2009. Immunocompatibility properties of lipid-polymer hybrid nanoparticles with heterogeneous surface functional groups. Biomaterials 30(12):2231–2240 Sankhala, K. 2009. A phase I pharmacokinetic (PK) study of MBP-426, a novel liposome encapsulated oxaliplatin. J Clin Oncol 27(15S):2535 Schiffelers, R. 2003 Anti-tumor efficacy of tumor vasculature-targeted liposomal doxorubicin. J Control Release...

7 Pages(1750 words)Dissertation

Pharmacogenetics in Cancer

... in UGT1IA1, this polymorphism is associated with an elevated toxicity with irinotecan. The other pharmacogenetic knowledge of substances usually given to patients with colorectal cancer, include oxaliplatin and flouropyremidines. Second, acute lymphoblastic leukemia (ALL) can also be treated using pharmacogenetics. Physicians often utilize pharmacogenomic testing for children with severe lymphoblastic leukemia. This has led to ALL being a lethal disease about 40 years ago to the current cure rates of about 80 percent. The exemplary progress is attributed to the optimization of existing treatment modalities in contrast to the discovery of new antileukemic agents (Cheok, Pottier and Kager 39-41). The genetic variants affecting antileukemic...

5 Pages(1250 words)Essay

Cisplatin-Incorporated Polymeric Micelles (NC-6004)

... and CDDP in this study it compared with those that received the same doses of cisplatin. The indication of these results is the markedly less-extensive toxicity of NC-6004. The blood–cochlear barrier, which is similar to the blood–brain barrier, isolates the organ of Corti from the systemic circulation [32]. CDDP enters the perilymph of the inner ear after readily penetrating this barrier, where it reaches the hair cells and exerts its toxic action. The limited cochlear uptake of oxaliplatin is considered responsible for the lower ototoxicity of oxaliplatin than CDDP [33]. The size of NC-6004 particle is approximately 30 nm [11] and that of the intrastrial space is approximately 15 nm [33,34]; consequently, the decrease of the toxicity...

12 Pages(3000 words)Essay

Treatment of Colorectal Cancer

.... It is used in cases of tumor recurrence or spread after primary chemotherapy. Disadvantage of this drug: Diarrhoea and neutropenia, which can be life threatening if not treated promptly and aggressively. Oxaliplatin It is also used in treatment of colorectal cancer. It causes no renal toxicity and minimal hematological toxicity, but it is associated with reversible, acute, cold-related dysesthesia and a dose-limiting, cumulative, peripheral sensory neuropathy. [2] Combined Therapy Use of radiotherapy together with chemotherapy decreases the possibility of local or regional recurrences after complete resection of stage B or stage C rectal cancer and prolong survival. The chemotherapy causes radiosensetization so...

15 Pages(3750 words)Case Study

Oxaliplatin Genotoxicity on Human Lymphocytes

... loss of p53 dependent apoptosis. CBMN could detect micronuclei which are indicative of DNA damage. Detection of micronuclei through CBMN indicated chromosome loss, breakage, rearrangement, nondisjunction, and apoptosis. All of these could mean specific genotoxic effects. These all are chromosomal aberrations, which may be caused by oxaliplatin. Mitotic catastrophe was a plausible mechanism of DNA toxicity caused by oxaliplatin through endocycling indicated in this experiment. This has been described as a process of mitotic failure induced by DNA damage leading to cell death. The other plausible mechanism that has been suggested is through decreased expression of the antiapoptotic protein, survivin, leading to cell death. Conclusion Apart...

15 Pages(3750 words)Research Paper

Therapeutics of Colon Cancer

... used for Colon Cancer Colon Cancer is one of the most dangerous cancers which is cured through either a surgery or chemotherapy. Surgery at times does not prove to be beneficial in colon cancer as it has reached its late stages. And thus chemotherapy is considered to be the best option for individuals who are suffering from this kind of cancer. The chemotherapy drugs which are prescribed to patients suffering from this cancer are given in collaboration so that all of these drugs act together to produce the desired effect. The drugs which are widely used for the treatment are 5-Fluorouracil, Oxaliplatin, leucovorin, irinotecan, and capecitabine (Richard et al 2009; Rang et al 2007; Pratt et al 1990) 5-Fluorouracil Most... Colon...

6 Pages(1500 words)Coursework

Treatment of Cancer and Its Progress: Solving Cancer Problems

.... Therefore, future research should focus more on the long term effects of using thalidomine, bortezomib, lenalidomide, cetuximab and temozolomide. References Anmdre T, Boni C, Mounedji-Boudiaf L, Navarro M, Tabernero J, & Hickish T. 2004. Oxaliplatin, fluorouracil and leucovorin as adjuvant treatment of colon cancer. New England Journal of Medicine. (350):2343–2351 Bonner JA, Harari PM, Giralt J. 2006. Radiotherapy plus cetuximab for squamous cell carcinoma of the head and neck. N Engl J Med. 354:567–578. Bonner JA, Harari PM, Giralt J, Baselga D, Shin R, Cohen J. 2005. Improved preservation of larynx with the addition of cetuximab to radiation for cancers of the larynx and hypopharynx. J Clin Oncol....

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Oxaliplatin - Essay Example

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