Is participation in a clinical trial associated with a survival benefit in patients with bladder cancer?

Bladder cancer that is unresponsive to intravesical therapies is difficult to treat. Patients with this disease usually have to try salvage therapies, partial cystectomy, or radical cystectomy. Unfortunately, the population afflicted by bladder cancer is older and frailer than those afflicted by other cancers with mortality approaching 1.5% and readmission rates approaching 64%. These patients are left with no other options aside from participating in a clinical trial to delay or avoid surgery. We hypothesized that participation in a clinical trial provides survival benefits when controlling for tumor stage and pathology in the case of non-muscle invasive bladder cancer that is refractory to intravesical Bacillus Calmette-Guérin (BCG). Using our Institutional Review Board (IRB) approved Columbia Urologic Oncology Database, 55 patients with BCG-refractory NMIBC (29 clinical trial patients, 26 non-clinical trial patients) were identified between 2008 and 2012. Clinical characteristics, demographics, and outcomes were obtained from the medical records. Non-clinical trial patients had fewer mean BCG instillations than their clinical trial counterparts (7.8 versus 11.5 doses, p < .01). Kaplan Meier (KP) curves for Overall Survival (OS) and Cancer Specific Survival (CSS) indicate an increased survival benefit for patients enrolled in a clinical trial (OS: χ2 = 8.802, p< 0.01, median of 6.68 years versus 3.15 years; CSS: χ2 = 10.205, p < 0.01, mean 5.6 years versus 2.65 years). The data support the notion that there may be an inherent survival benefit gained by virtue of being included in a clinical trial. The drivers of this survival benefit may include more interactions with the hospitals and clinics, greater patient involvement in their health care, and increased surveillance by clinicians

Prognostic importance of lymphovascular invasion in urothelial carcinoma of the renal pelvis

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144274/1/cncr31372_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144274/2/cncr31372.pd

Peptide Library Approach to Uncover Phosphomimetic Inhibitors of the BRCA1 C‑Terminal Domain

Many intracellular protein–protein interactions are mediated by the phosphorylation of serine, and phosphoserine-containing peptides can inhibit these interactions. However, hydrolysis of the phosphate by phosphatases, and the poor cell permeability associated with phosphorylated peptides has limited their utility in cellular and <i>in vivo</i> contexts. Compounding the problem, strategies to replace phosphoserine in peptide inhibitors with easily accessible mimetics (such as Glu or Asp) routinely fail. Here, we present an <i>in vitro </i>selection strategy for replacement of phosphoserine. Using mRNA display, we created a 10 trillion member structurally diverse unnatural peptide library. From this library, we found a peptide that specifically binds to the C-terminal domain (BRCT)₂ of breast cancer associated protein 1 (BRCA1) with an affinity comparable to phosphorylated peptides. A crystal structure of the peptide bound reveals that the pSer-x-x-Phe motif normally found in BRCA1 (BRCT)₂ binding partners is replaced by a Glu-x-x-4-fluoroPhe and that the peptide picks up additional contacts on the protein surface not observed in cognate phosphopeptide binding. Expression of the peptide in human cells led to defects in DNA repair by homologous recombination, a process BRCA1 is known to coordinate. Overall, this work validates a new <i>in vitro</i> selection approach for the development of inhibitors of protein–protein interactions mediated by serine phosphorylation