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1.
Clin Nucl Med ; 47(2): e116-e117, 2022 Feb 01.
Article in English | MEDLINE | ID: mdl-35006112

ABSTRACT

ABSTRACT: Biochemical recurrence of prostate cancer, detected by a rising PSA, may reflect intraprostatic or extraprostatic recurrence. 18F-Fluciclovine (Axumin), a synthetic amino acid substrate in tumor metabolism, has frequently been used for to localize recurrent prostate cancers. We present a 71-year-old man with biochemical recurrence of prostate cancer but no convincing imaging findings on 18F-fluciclovine PET/CT. Of note, however, was an incidental uptake within the anterior mediastinum, which was found on biopsy to be a type AB thymoma. With this, we stress that awareness of false-positive uptake patterns is crucial for accurate diagnosis of recurrent prostate cancer.


Subject(s)
Cyclobutanes , Prostatic Neoplasms , Thymoma , Thymus Neoplasms , Aged , Carboxylic Acids , Humans , Male , Neoplasm Recurrence, Local , Positron Emission Tomography Computed Tomography
2.
Transl Oncol ; 14(8): 101140, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34107419

ABSTRACT

Disruptin is a cell-permeable decoy peptide designed to destabilize activated EGFR, both by inhibiting Hsp90 chaperoning and dissociating the active asymmetric EGFR dimer, which leads to an increase in engagement of activated EGFR with the proteolytic degradation machinery and subsequent loss from the cells. Disruptin is an N-terminally biotinylated nonadecapeptide, with 8 amino acids from the αC-helix-ß4 sheet loop of EGFR (S767-C774) fused to a TAT undecapeptide. The S767-R775 loop is at the interface with juxtamembrane domains in the active EGFR dimers and is a binding site for Hsp90. Cellular studies in EGFR-activated tumor cells demonstrated that Disruptin causes the disappearance of EGFR protein from cells over a few hours, a growth inhibitory effect, similar but more effective than the EGFR kinase inhibition. Interestingly, cells without activated EGFR remained unaffected. In vivo studies showed that Disruptin slowed the growth of small tumors. Larger tumors responded to intratumoral injections but did not respond to systemic administration at tolerated doses. Investigation of these results revealed that systemic administration of Disruptin has acute toxicities, mainly related to its TAT peptide moiety. Therefore, we conclude that although the efficacy of both in vitro and in vivo intratumoral injection of Disruptin supports the therapeutic strategy of blocking activated EGFR dimerization, Disruptin is not suitable for further development. These studies also highlight the importance of the chosen models and drug-delivery methods for such investigations.

3.
Cureus ; 12(10): e11023, 2020 Oct 18.
Article in English | MEDLINE | ID: mdl-33214951

ABSTRACT

Despite the well-established relationship between volume and outcomes, patients continue to have procedures performed at low-volume hospitals. The factors patients use to make the complex decision of where to have hepatopancreaticobiliary (HPB) surgery remain poorly characterized. A novel survey instrument was administered to all patients who had undergone HPB surgery at two university-affiliated community hospitals. 76 patients participated in the study (89% response rate). The majority of patients were unaware of the volume-outcome relationship (58.8%). No demographic factors differed between patients who were or were not aware except for patient research. Physician factors were the most important selection category (64.4%). Only 28.9% of patients were willing to travel more than two hours to have an operation performed at a hospital with a high volume/improved quality. Despite many voices calling for regionalization, patient decision-making factors should be considered before any realistic implementation.

4.
Acad Forensic Pathol ; 10(1): 56-61, 2020 Mar.
Article in English | MEDLINE | ID: mdl-32983294

ABSTRACT

Forensic DNA testing can play a critical role in homicide investigations. Selecting the appropriate evidence on which to perform DNA testing requires foresight and reasoning based on experience and science. Although successful DNA testing can occur using many substrates, including blood, hair, and sweat/epithelial cells, positive results can also result from testing various unorthodox samples. The authors report on a triple-murder investigation where DNA testing of dog feces at the crime scene matched DNA testing of feces found on the shoe of a suspect resulting in successful prosecution of the case.

5.
J Gastrointest Oncol ; 10(2): 339-347, 2019 Apr.
Article in English | MEDLINE | ID: mdl-31032103

ABSTRACT

BACKGROUND: Intrahepatic cholangiocarcinoma (IHC) is a malignancy with an increasing incidence. Surgery is the only treatment modality associated with long term survival. The objective of this study is to utilize a nationwide representative database to quantify the trends in incidence, and surgery for IHC in the United States from 2004-2014, as well as identify any disparities in the receipt of surgery. METHODS: All patients admitted with a diagnosis of IHC between 2005 and 2014 were identified from the Nationwide Inpatient Sample (NIS) database. Trends in the number of IHC admissions and surgery procedures as well as outcomes were examined, and a multivariate analysis was used to determine the effects of demographic and clinical co-variables on resection rates. RESULTS: An estimated total of 104,045 IHC related admissions occurred between 2005 and 2014. The hospitalization rate for IHC increased by nearly 2-fold in 2014 [38.9 per 100,000 (95% CI, 35.7-42.2)] from 18.1 per 100,000 (95% CI, 15.8-20.3) in 2005. Liver resections increased 248% (P<0.01) with an increasing majority being performed at teaching hospitals and 56% being minor resections. There was an increase in estimated hospital charges from $87,124 to $148,613 (P<0.001) and decrease in LOS from 12 days to 10 days (P<0.01). Inpatient mortality for IHC decreased significantly from 11% to 8.4% (P=0.004), from year 2005 to 2014 respectively. Age >80 years (OR =0.45; 95% CI, 0.33-0.60), Black race (OR =0.50; 95% CI, 0.39-063), Hispanic race (OR =0.59; 95% CI, 0.45-0.79), Medicaid insurance (OR =0.58; 95% CI, 0.42-0.79) and Elixhauser comorbidity score >3 (OR =0.58; 95% CI, 0.47-0.73) were associated with decreased rates of resection. CONCLUSIONS: Overall hospitalization and volume of surgery for IHC has increased dramatically over the past decade. There has been an increase in cost, decrease in LOS and inpatient mortality during the period. Socioeconomic and racial disparities were observed in the receipt of surgery for IHC. Additional work is needed to understand the complex interplay between socioeconomic status and race in in the treatment of IHC.

6.
Oncotarget ; 7(42): 68597-68613, 2016 Oct 18.
Article in English | MEDLINE | ID: mdl-27612423

ABSTRACT

Non-small cell lung cancer (NSCLC) patients carrying specific EGFR kinase activating mutations (L858R, delE746-A750) respond well to tyrosine kinase inhibitors (TKIs). However, drug resistance develops within a year. In about 50% of such patients, acquired drug resistance is attributed to the enrichment of a constitutively active point mutation within the EGFR kinase domain (T790M). To date, differential drug-binding and altered ATP affinities by EGFR mutants have been shown to be responsible for differential TKI response. As it has been reported that EGFR stability plays a role in the survival of EGFR driven cancers, we hypothesized that differential TKI-induced receptor degradation between the sensitive L858R and delE746-A750 and the resistant T790M may also play a role in drug responsiveness. To explore this, we have utilized an EGFR-null CHO overexpression system as well as NSCLC cell lines expressing various EGFR mutants and determined the effects of erlotinib treatment. We found that erlotinib inhibits EGFR phosphorylation in both TKI sensitive and resistant cells, but the protein half-lives of L858R and delE746-A750 were significantly shorter than L858R/T790M. Third generation EGFR kinase inhibitor (AZD9291) inhibits the growth of L858R/T790M-EGFR driven cells and also induces EGFR degradation. Erlotinib treatment induced polyubiquitination and proteasomal degradation, primarily in a c-CBL-independent manner, in TKI sensitive L858R and delE746-A750 mutants when compared to the L858R/T790M mutant, which correlated with drug sensitivity. These data suggest an additional mechanism of TKI resistance, and we postulate that agents that degrade L858R/T790M-EGFR protein may overcome TKI resistance.


Subject(s)
ErbB Receptors/genetics , Erlotinib Hydrochloride/pharmacology , Mutation , Protein Kinase Inhibitors/pharmacology , Animals , CHO Cells , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , Cell Line, Tumor , Cricetinae , Cricetulus , Drug Resistance, Neoplasm/drug effects , ErbB Receptors/metabolism , Humans , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Phosphorylation/drug effects , Polyubiquitin/metabolism , Protein Stability/drug effects , Proteolysis/drug effects , Ubiquitination/drug effects
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