Lauren+Reuther+Log

Created Wiki page and started a research log for independent research paper. Began thinking of ideas on what to research. Decided to write research paper pertaining to previous Co-op.
 * September 24, 2009**

Registered for SciFinder. Began searching SciFinder and PubMed to look for information on synthesis, reactions, and use of Ubiquitin and its derivatives with degredation of specific proteins.
 * September 30, 2009**

Researched more possible topics:
 * October 6, 2009**
 * Renewable Hydrogen Production
 * Manipulation of Serotonin Levels to help in Depression Disorders. Possibly targeting chemicals that regulate serotonin levels, serotonin effects on the nervous system, or ways in which serotonin affect mood.**[Very good starting point - see if you can identify a key review paper JCB]**
 * Pharmacological manipulation of serotonin levels in the nervous system of the opisthobranch mollusc Tritonia diomedea. By: Fickbohm, David J.; Spitzer, Nadja; Katz, Paul S.
 * Serotonin regulation of the human stress response. By: Hood, Sean D.; Hince, Dana A.; Robinson, Hayley; Cirillo, Melita; Christmas, David; Kaye, Joey M.
 * Association of serotonin transporter gene polymorphism and emotion By: Murakami, Hiroki; Matsunaga, Masahiro; Ohira, Hideki
 * Substituted 2, 3, 4, 5- tetrahydro- 1H- pyrido[4, 3- b] indoles as selective antagonists of 5- HT6 serotonin regulators of neuron calcium metabolism for treatment of neurodegenerative disorders receptors and By: Ivashchenko, A. V.; Tkachenko, S. E.; Frolov, E. B.; Mit'kin, O. D.; Kravchenko, D. V.; Okun, I. M.; Savchuk, N. F.; Ivashchenko, A. A.

Continued research on Serotonin including SSRI using Web of Science because SciFinder will not work from home? **[you need to install VPN from resource page JCB]** Also, may narrow research to side-effects of serotonin on body or serotonin receptor activation?
 * October 7, 2009**
 * Effects of selective serotonin reuptake inhibitors on platelet serotonin parameters in major depressive disorder Authors: Bakish, Cavazzoni, Chudzik, Ravindran, Hrdina
 * Characterization of serotonin 5-hydroxytryptamine-1A receptor activation using a phospho-extracellular-signal regulated kinase 2 sensor Authors: Huwiler, Kristin G., Machleidt, Thomas, Chase, Lucas, Hanson, Bonnie, Robers, Matthew B.
 * Serotonin 5-HT1A receptor-mediated Erk activation requires calcium/calmodulin-dependent receptor endocytosis Authors: Della Rocca GJ, Mukhin YV, Garnovskaya MN, Daaka Y, Clark GJ, Luttrell LM, Lefkowitz RJ, Raymond JR
 * Serotonin and Norepinephrine Inhibitors as a dual drug target:
 * Inhibition of serotonin and norepinephrine reuptake and inhibition of phosphodiesterase by multi-target inhibitors as potential agents for depression Authors: Cashman JR (Cashman, John R.)1, Ghirmai S (Ghirmai, Senait)1
 * Antidepressants Targeting the Serotonin Reuptake Transporter Act via a Competitive Mechanism Authors: Apparsundaram S (Apparsundaram, Subbu)1, Stockdale DJ (Stockdale, Daniel J.)1, Henningsen RA (Henningsen, Robert A.)1, Milla ME (Milla, Marcos E.)1, Martin RS (Martin, Renee S.)1
 * Clinical evidence for serotonin and norepinephrine reuptake inhibition of duloxetine Authors:Trivedi MH (Trivedi, Madhukar H.)1, Desaiah D (Desaiah, Durisala)2, Ossanna MJ (Ossanna, Melissa J.)2, Pritchett YL (Pritchett, Yili L.)3, Brannan SK (Brannan, Stephen K.)4, Detke MJ (Detke, Michael J.)2,5,6

Created Second Life account with username Laur Roddenham **[great - if you can bring your laptop at next class we can discuss JCB]

October 15, 2009** The synthesis of Serotonin from L-Tryptophan, with two enzymes tryptophan hydroxylase (THP) and amino acid decarboxylase (AAD), can be found on the Serotonin Wikipedia page.

Found one article outlining how serotonin and its receptors regulate various organ systems and disease processes. Could not figure out how to use the DOI: The Expanded Biology of SerotoninMiles Berger, John A. Gray, Bryan L. Roth Annual Review of Medicine 2009 60355-366
 * [Always create the link to the article on the publisher's site - never from the database. Look for the DOI. I can show you at next class or you can see Peggy in the meantime JCB]**

May try using KEGG to find the enzymes serotonin acts upon.

Because I haven't been finding very interesting information relating to the chemical and reactivity aspects of Serotonin and SSRI's, I decided to possibly change my topic. **[That's fine - we can discuss either JCB]** Looking for current Chemistry news topics online, I had found interesting information on new Metal ligands used in cancer treatment. A few of the interesting papers I had found are:
 * October 28, 2009**

Articles: Journal Articles (cannot change the format of these from Heading to normal?):
 * New trends for metal complexes with anticancer activity Pieter CA Bruijnincx and Peter J Sadler, [|DOI]
 * Mechanistic insight into the cellular uptake and processing of cisplatin 30 years after its approval by FDA Dedicated to the memory of Dr. Lloyd R. Kelland, a great advocate for platinum anticancer drugs. Fabio Arnesano and Giovanni Natile DOI
 * van Rijt et al. Amide Linkage Isomerism As an Activity Switch for Organometallic Osmium and Ruthenium Anticancer Complexes. //Journal of Medicinal Chemistry//, 2009; 090930083513062 DOI
 * Encapsulation of platinum anticancer drugs by apoferritin. Zhen Yang, Xiaoyong Wang, Huajia Diao, Junfeng Zhang, Hongyan Li, Hongzhe Sun and Zijian Guo [|DOI]

The Review Paper talked much about the platinum-based chemotherapy drug which is currently in clinical trials and seems to be a very good treatment for early-detected cancer, Cisplatin. Cisplatin targets cancer cells and causes apoptosis, or triggered cell death. Also, this article describes the way in which platinum toxicity is being addressed. The Wikipedia page for Cisplatin is very informative.


 * Assignment #1**
 * Encapsulation of platinum anticancer drugs by apoferritin** [|DOI]
 * [Full Marks JCB]**
 * Inorganic chemotherapeutic drugs cisplatin (CDDP) and carboplatin (CBDCA) are used for the treatment of cancer, but of which use is restricted due to toxicity and tumor resistance. Targeting these drugs specifically to cancer cells would greatly reduce the toxicity of these drugs, and ligand-receptor-mediated delivery systems are believed to be the best way in which to target these drugs.
 * The iron storage protein ferritin is taken in by cancer cells by membrane-specific receptors. Ferritin-binding sites and the intake of ferritin has been shown in both neoplastic and brain tumor cells. Ferritin contains 24 subunits which naturally form a protein cage with a hollow center and also contains eight hydrophilic channels that lead through the protein shell to the center. Various inorganic nonaparticles have been incorporated into the center of the cage previously.
 * Two methods of inserting cisplatin and carboplatin into the hollow center of apoferritin, which is a derivative of ferritin, are described and believed to reduce the toxic side effects of cisplatin and carboplatin.
 * Apoferritin is dissociated at pH 2.0 into its subunits and then reformed at pH 7.5 trapping both CDDP and CBDCA into its hollow core, forming Aft-CDDP and Aft-CBDCA. Then, Aft-CDDP and Aft-CBDCA were separated from the remaining CDDA and CBDCA by exhaustive dialysis.
 * By ICP-AES, it was found that 2 CDDP and 5 CBDCA could be trapped in each AFt. 15N-labelled drugs were then used in the NMR to confirm that the CDDP and CBDCA existed in the AFt core as active species. CBDCA was confirmed by NMR, but no signal was detected by CDDP.
 * Aft-CDDP prepared in-situ was confirmed to be entrapped as [PtCl4]2- by TEM and spherical particles of Pt were observed. Also, the UV-Vis spectrum of Aft-Pt confirmed the encapsulation of Pt particles formed by the reduction of [PtCl4]2-. A mixture of Aft-CDDP and Aft-TDDP (Ft-transplatin, no anticancer activity) resulted, but seems to be more efficient of producing Aft-CDDP than the unfolding-refolding process used to generate Aft-CBDCA.
 * To confirm that the protein cage is stable, both PAGE and SDS gels were run, which showed bands around 440kDa. This shows that the cage remains stable after the drug is put into the center.
 * The cytotoxicity was tested in the rat pheochromocytoma cell through MTT assay using AFt as a control. AFt-CDDP produced through the in-situ procedure showed cell death at a much lower concentration of AFt-CDDP than AFt alone. AFt-CBDCA produced through the dissociation-association method showed very little death.
 * C DDA and CBDCA have been encapsulated by AFt and do shows signs of cytotoxicity on cancer cells. AFt is already known to be specific to tumor cells, so AFt-CDDP and AFt-CBDCA are believed to be specific to tumor cells that express ferritin receptors. The protein shell remains intact after the insertion of the CDDP and CBDCA, which furthers strengthens the idea of tumor cell specifity.

I believe the main topic of my research paper will be the encapsulation of Cisplatin and possibly other inorganic-based anti-cancer drugs. **[great topic JCB]**
 * October 29, 2009**

Articles: = =
 * Reversible Cell- Specific Drug Delivery with Aptamer- Functionalized Liposomes By: Cao, Zehui; Tong, Rong; Mishra, Abhijit; Xu, Weichen; Wong, Gerard C. L.; Cheng, Jianjun; Lu, Yi [|DOI]
 * Simultaneous optimization of cisplatin - loaded PLGA- mPEG nanoparticles with regard to their size and drug encapsulation By: Beletsi, A.; Klepetsanis, P.; Ithakissios, D. S.; Kounias, S.; Stavropoulos, A.; Avgoustakis, K.[|DOI] **I was unable to get free access to this article. I will possibly try to see if there is another way to get access.**
 * Nanocapsules: a novel formulation technology for platinum-based anticancer drugs . Irene HL Hamelers  & Anton IPM de Kroon.  [|DOI] **Also having trouble finding this article for free online through the Drexel library, but from the abstract seems to be very relevant to my topic**.
 * Cisplatin encapsulated in phosphatidylethanolamine liposomes enhances the in vitro cytotoxicity and in vivo intratumor drug accumulation against melanomas By: Hwang, Tsong-Long; Lee, Woan-Ruoh; Hua, Shu-Chiou; Fang, Jia-You. DOI
 * Cisplatin Nanoliposomes for Cancer Therapy: AFM and Fluorescence Imaging of Cisplatin Encapsulation, Stability, Cellular Uptake, and Toxicity. Srinivasan Ramachandran, Arjan P. Quist, Sashi Kumar, and Ratnesh Lal. [|DOI]
 * Peptide Targeting of Platinum Anti-Cancer Drugs. [|DOI]
 * Carboplatin nanocapsules: a highly cytotoxic, phospholipid-based formulation of carboplatin. [|DOI]

Important Wikipedia Sources:
 * Cisplatin - []
 * Apatmer - []

Decided to work on the layout of this page. Removed spans and any hyperlinks that were not wanted. Tried to edit and fix the DOI's for each paper that I will be using. **[Thanks - that is helpful JCB]**
 * November 10, 2009**

Articles:


 * Nanocapsules of Platinum-Based Anti-Cancer Drugs.
 * Evaluation of a nanotechnology based carrier for delivery of curcumin in prostate cancer cells. Authors: Thangapazham, Rajesh L.; Puri, Anu; Tele, Shrikant; Blumenthal, Robert; Maheshwari, Radha K. in International Journal of Oncology **Cannot Find Full Article or DOI**
 * Transport of liposomal and albumin loaded curcumin to living cells: an absorption and fluorescence spectroscopic study. [|DOI]
 * Liposome-encapsulated curcumin: in vitro and in vivo effects on proliferation, apoptosis, signaling, and angiogenesis. [|DOI]

Assignment #3
 * November 11, 2009**


 * November 12, 2009**
 * Important Wikipedia Articles:**
 * [|Curcumin]


 * Articles:**
 * Developing new metal-based therapeutics: challenges and opportunities. [|DOI]
 * This paper describes some of the difficulties with inorganic medications
 * Targeting platinum anti-tumour drugs: Overview of strategies employed to reduce systemic toxicity. [|DOI]
 * Basis for Design and Development of Platinum(IV) Anticancer Complexes. [|DOI]
 * Soluble Single-Walled Carbon Nanotubes as Longboat Delivery Systems for Platinum(IV) Anticancer Drug Design. [|DOI]
 * This is a different method of delivery that I had not found in other papers.
 * A Photoactivated trans-Diammine Platinum Complex as Cytotoxic as Cisplatin. [|DOI]
 * platinum(IV) complex trans,trans,trans-[Pt(N3)2(OH)2(NH3)2], transplatin, is the trans isomer of cisplatin and used as anti-cancer reagent. This is photoactivated to be used as anti-cancer reagent which is another method of activating these inorganic drugs
 * Transplatin Is Cytotoxic When Photoactivated: Enhanced Formation of DNA Cross-Links. [|DOI] Article that describes the above mentioned Transplatin.

There are three listings for **Cisplatin** on ChemSpider, but the one with most information is [|ChemSpider]. Image of Cisplatin found on ChemSpider follows: Cannot find **Transplatin** on ChemSpider, possibly because it is the same structure just different orientation as Cisplatin. I wanted to compare properties between Cis-and Trans-platin.
 * ChemSpider Listings for important molecules:**

Also, because **curcumin** is delivered to cells similarly as Cisplatin as an anticancer drug I found the ChemSpider site for it and is located at [|ChemSpider]. Image of Curcumin found on ChemSpider follows:

I was wondering about the way in which we should set-up the paper we are writing. Is it supposed to be more of an informative paper telling about what we had researched or a review paper where we talk about what we learned and then makes inferences from what we researched. Also, do we need to have sections (abstract, introduction containing background and information researched, and conclusions giving our take on the topic) in our final report? **[I am pretty flexible about the format - but it must be about a topic that is narrow enough to be covered completely JCB]**
 * November 19, 2009**


 * November 30, 2009**
 * [screenshot for Beilstein and Knovel don't match the values you report - also check your outlier point for errors - if bp is not at 1 atm you must convert the value JCB]**


 * || [|Beilstein] || [|Wikipedia] || [|ChemSpider] || [|WolframAlpha] || [|Knovel] || [|RSC] ||
 * **Density of Liquid (g/cm3)** || 1.2613 || 1.261 || 1.260 || 1.25 || 1.26557 || - ||
 * **Boiling Point (°C)** || 290 || 290 || 290 || - || 290 || 290 ||
 * **Melting Point (°C)** || 17.8 || 18 || 18 || - || 17.8 || 18.2 ||
 * **Surface Tension (mN/m)** || 66.39 || 64.00 || 61.9 || - || 63.4±0.3 || 64.00 ||
 * **Refractive Index** || 1.47063 || 1.4746 || 1.4740 || 1.474 || 1.4758 || - ||

Knovel** Do I have full marks yet for this assignment? [No you didn't address my comments JCB]**
 * Screen Shots:
 * Beilstein**
 * RSC