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| 1 | Albumin-linked prostate-specific antigen-activated thapsigargin- and niclosamide-based molecular grenades targeting the microenvironment in metastatic castration-resistant prostate cancer显示文摘Localized prostate cancer is curable via annihilation of the entire cancer neighborhood by surgery or local radiation.Unfortunately,once metastatic,no available therapy is curative.The vast majority will die despite aggressive systemic combinational androgenablation therapies.Thus,there is an urgent need for effective systemic therapeutics that sterilize the entire microenvironment in metastatic castration-resistant prostate cancer(mCRPC).To accomplish this goal,advantage can be taken of the unique biology of mCRPC cells.Like their normal cell of origin,mCRPCs retain expression of the prostate-specific differentiation protein,prostate-specific antigen(PSA),which they abundantly secrete into their extracellular fluid(ECF).This unique,and essentially universal,secretion of enzymatically active PSA into the ECF by mCRPCs creates an exploitable therapeutic index for activation of systemically delivered highly lipophilic toxins as“molecular grenades”covalently linked to cysteine-34 of human serum albumin(HSA)via a stable maleimide containing PSA cleavable peptide such that PSA-dependent hydrolysis(i.e.,“detonation”)releases the grenades restrictively within the ECF of mCRPC.This approach decreases dose-limiting host toxicity while enhancing plasma half-life from minutes to days(i.e.,pharmacokinetic effect)and increasing the tissue concentration of the maleimide coupled albumin delivery(MAD)in the ECF at sites of cancer due to the enhanced permeability of albumin at these sites(i.e.,enhanced permeability and retention effect).This allows the MAD-PSA detonated grenades to circulate throughout the body in a non-toxic form.Only within sites of mCRPC is there a sufficiently high level of enzymatically active PSA to efficiently“pull the pin”on the grenades releasing their lipophilic cellpenetrant toxins from HSA.Thus,if a sufficient level of“detonation”occurs,this will kill mCRPC cells,and sterilize the entire PSA-rich metastatic sites via a bystander effect.In this review,two examples of such MAD-PSA detonated molecular grenades are presenteddone based upon thapsigagin and the other on niclosamide. | Emmanuel S.Akinboye W.Nathaniel Brennen Samuel R.Denmeade John T.Isaacs | 2019 | Asian Journal of Urology2019，6，1： | 2 |
| 2 | A regional audit of hand and wrist injuries, a study of 4873 injuries显示文摘 | Hill C Mozzam A Brennen MD | 1998 | J Hand Surg ( Br )1998，23，： | 1 |
| 3 | Association with prior fluoroquinolone therapy of widespread ciprofloxacin resistance among gram-negative isolates in a veterans affairs medical center显示文摘 | MUDER R R BRENNEN C GOETZ M A | 1999 | Antimicrob Agents Chemother1999，35，： | 1 |
| 4 | Acoustic saturation in bubbly cavitating flow adjacent to an oscillating wail 显示文摘 | Colonius T d'Auria F Brennen C E | 2000 | Physics of Fluids2000，12，11： | 1 |
| 5 | Fluid-induced rotordynamic forces and instabilities显示文摘 | BRENNEN C E ACOSTA A J | 2006 | Structural Control and Health Monitoring2006，13，： | 1 |
| 6 | A numerical investigation of unsteady bubbly cavitating nozzle flows 显示文摘 | Preston A Colonius T Brennen C E | 2002 | Physics of Fluids2002，14，1： | 1 |
| 7 | Hydraulic analysis of a reversible fluid coupling 显示文摘 | Charles N Mckinnon Danamichele Brennen Christopher E Brennen | 2001 | ASAE Journal of Fluids Engineering2001，123，2： | 1 |
| 8 | Experimental Investi- gation of Rotor-Stator Interaction in a Centrifugal Pump With Several Vaned Diffusers 显示文摘 | Arndt N Acosta A J Brennen C E | 1990 | Journal of Turboma- chinery1990，112，： | 1 |
| 9 | Hydraulic jumps ingranular material flow显示文摘 | Brennen C E Sieck K Paslaski J | 1983 | Powder Technol1983，，35： | 1 |
| 10 | The second dorsal metacarpal artery neurovascular island flap 显示文摘 | Small JO Brennen MD | 1990 | Br J Plast Surg1990，43，1： | 1 |
| 11 | Rotor-stator interaction in a diffuser pump 显示文摘 | Arndt N Acosta A J Brennen C E | 1989 | ASME Journal of Turbomachinery1989，111，3： | 1 |
| 12 | Fibroblastactivation protein peptide substrates identified fromhuman collagenⅠderived gelatin cleavage sites显示文摘 | Aggarwal S Brennen WN Kole TP | 2008 | Biochemistry2008，47，3： | 1 |
| 13 | Emlyactivemobiliza-tion follow- ing flexor tendon repair in zone 显示文摘 | Small JG Brennen MD Coville J | 1989 | Hand Surg(Br)1989，14，： | 1 |
| 14 | Rotor-stator interaction in a centrifugal pump with several vaned diffusers显示文摘 | Arndt N Acosta A J Brennen C E | 1990 | ASME Journal of Turbomachinery1990，112，1： | 1 |
| 15 | One-dimensional bubbly cavitating flows through a converging-diverging nozzle 显示文摘 | Wang Y C Brennen C E | 1998 | Journal of Fluids Engineering1998，120，1： | 1 |
| 16 | The effects of inlet flow modification on cavitating inducer performance显示文摘 | VALLE J D BRAISTED D M BRENNEN C E | 1992 | Transactions of the ASME1992，14，： | 1 |
| 17 | Acoustic saturation in bubbly cavitating flow adjacent to an oscillating wall 显示文摘 | Colonius T d'Auria F Brennen C E | 2000 | Physics of Fluids2000，12，11： | 1 |
| 18 | Computer simulation of granular shear flows显示文摘 | CAMPBELL C S BRENNEN C E | 1985 | J Fluid Mech1985，151，： | 1 |
| 19 | A numerical investigation of unsteady bubbly cavitating nozzle flows 显示文摘 | Preston A Colonius T Brennen C E | 2002 | Physics of Fluids2002，14，1： | 1 |
| 20 | One-dimensional bubbly eavitating flows through a converging-diverging nozzle显示文摘 | Wang Y C Brennen C | 1998 | Journal of Fluids Engineering1998，120，1： | 1 |
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