Browsing by Subject "prostate"

Now showing 1 - 6 of 6
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    Differentiation of Prostate Cancer from Normal Tissue in Radical Prostatectomy Specimens by Desorption Electrospray Ionization and Touch Spray Ionization Mass Spectrometry.
    (RSC, 2015-02-21) Kerian, K. S.; Jarmusch, A. K.; Pirro, V.; Koch, M. O.; Masterson, T. A.; Cheng, L.; Cooks, R. G.; Department of Urology, IU School of Medicine
    Radical prostatectomy is a common treatment option for prostate cancer before it has spread beyond the prostate. Examination for surgical margins is performed post-operatively with positive margins reported to occur in 6.5 – 32% of cases. Rapid identification of cancerous tissue during surgery could improve surgical resection. Desorption electrospray ionization (DESI) is an ambient ionization method which produces mass spectra dominated by lipid signals directly from prostate tissue. With the use of multivariate statistics, these mass spectra can be used to differentiate cancerous and normal tissue. The method was applied to 100 samples from 12 human patients to create a training set of MS data. The quality of the discrimination achieved was evaluated using principal component analysis - linear discriminant analysis (PCA-LDA) and confirmed by histopathology. Cross validation (PCA-LDA) showed >95% accuracy. An even faster and more convenient method, touch spray (TS) mass spectrometry, not previously tested to differentiate diseased tissue, was also evaluated by building a similar MS data base characteristic of tumor and normal tissue. An independent set of 70 non-targeted biopsies from six patients was then used to record lipid profile data resulting in 110 data points for an evaluation dataset for TS-MS. This method gave prediction success rates measured against histopathology of 93%. These results suggest that DESI and TS could be useful in differentiating tumor and normal prostate tissue at surgical margins and that these methods should be evaluated intra-operatively.
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    Metastatic small cell carcinoma of the prostate in an octogenarian with significant response to first-line chemotherapy
    (OAT, 2017-03) Wood, Anthony; Adra, Nabil; Cheng, Liang; Pili, Roberto; Department of Pathology and Laboratory Medicine, IU School of Medicine
    Patients with small cell carcinoma of the prostate generally present with metastatic disease and have an estimated life expectancy measured in months. In this brief report, we present a case of rapidly progressive metastatic small cell carcinoma of the prostate in an octogenarian with significant response to split-dosed cisplatin and etoposide. This case report shows that cautious treatment with platinum-based regimens should still be considered in elderly patients given the potential for improvement in performance status and quality of life with chemotherapy. Additionally, this case highlights that platinum-based regimens are still considered the therapeutic backbone of prostate cancers with a mixed small cell carcinoma and adenocarcinoma phenotype.
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    Novel Prostate-Specific Promoter Derived from PSA and PSMA Enhancers
    (Elsevier, 2002-09) Lee, Sang-Jin; Kim, Hong-Sup; Yu, Rong; Lee, KangRyul; Gardner, Thomas A.; Jung, Chaeyong; Jeng, Meei-Huey; Yeung, Fan; Cheng, Liang; Kao, Chinghai; Pathology and Laboratory Medicine, School of Medicine
    The expression of prostate-specific membrane antigen (PSMA) and prostate-specific antigen (PSA), two well characterized marker proteins, remains highly active in the hormone refractory stage of prostate cancer. In this study, an artificial chimeric enhancer (PSES) composed of two modified regulatory elements controlling the expression of PSA and PSMA genes was tested for its promoter activity and tissue specificity using the reporter system. As a result, this novel PSES promoter remained silent in PSA- and PSMA-negative prostate and non-prostate cancer cell lines, but mediated high levels of luciferase in PSA- and PSMA-expressing prostate cancer cell lines in the presence and absence of androgen. To determine whether PSES could be used for in vivo gene therapy of prostate cancer, a recombinant adenovirus, Ad-PSES-luc, was constructed. Luciferase activity in prostate cancer cell lines mediated by Ad-PSES-luc was 400- to 1000-fold higher than in several other non-prostate cell lines, suggesting the high tissue-specificity of the PSES promoter in an adenoviral vector. Finally, recombinant virus Ad-PSES-luc was injected into mice to evaluate the tissue-discriminatory promoter activity in an experimental animal. Unlike Ad-CMV-luc, the luciferase activity from systemic injection of Ad-PSES-luc was fairly low in all major organs. However, when injected into prostate, Ad-PSES-luc drove high luciferase activity almost exclusively in prostate and not in other tissues. Our results demonstrated the potential use of PSES for the treatment of androgen-independent prostate cancer patients.
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    Optimization of Survivin Dimerization Inhibitors for the Treatment of Docetaxel-Resistant Prostate Cancer
    (2020-01) Peery, Robert Craig; Jerde, Travis; Zhang, Jian-Ting; Pili, Roberto; Safa, Ahmad; Sullivan, William J., Jr.
    Despite therapeutic advancements, prostate cancer remains the second most common cause of cancer-related mortality in men. Docetaxel is the first cytotoxic agent to show modest improvements in overall survival rate in patients with metastatic prostate cancer. Unfortunately, over half of these patients do not respond to treatment and ultimately all develop resistance. The mechanism mediating docetaxel resistance remains unknown. Survivin has a classical biological role in cancer, in fact survivin has been shown to be overexpressed in almost every solid tumor and is associated with drug resistance and clinically aggressive disease. In these studies I demonstrate that docetaxel resistant cells have overexpression of survivin compared to sensitive parental cells, knockdown of survivin decreases docetaxel resistance, and stable overexpression of survivin increases resistance to docetaxel. The data in these studies suggest that survivin is likely implicated in docetaxel resistance and treatment with a direct survivin inhibitor may sensitize resistant cells to docetaxel. To this end the evaluation and optimization of two different backbones of survivin inhibitors was performed. One such inhibitor identified is LQZ-7-3 which decreases survivin level via proteasome degradation, leads to apoptosis of cells, and showed efficacy in a prostate cancer xenograft model in vivo when given in an oral formulation. LQZ- 7-3 showed strong specificity to survivin versus other IAP family members at the protein level. Another inhibitor, LQZ-7F-1, demonstrated nanomolar inhibition of cancer cell growth and similar effects on survivin. Both compounds synergized with docetaxel in vitro warranting future in vivo efficacy studies as a combinatorial therapy. Overall, our findings indicate survivin is a significant contributor to docetaxel resistance in metastatic prostate cancer at the molecular level and survivin inhibitors may prove efficacious as a new therapy to sensitize cancer cells to chemotherapies.
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    Outcomes of Holmium Laser Enucleation of the Prostate in the Re-Treatment Setting
    (Elsevier, 2017-06) Marien, Tracy; Kadihasanoglu, Mustafa; Tangpaitoon, Teerayut; York, Nadya; Blackburne, Andrew T.; Abdul-Muhsin, Haidar; Borofsky, Michael S.; Krambeck, Amy E.; Humphreys, Mitchell R.; Lingeman, James E.; Miller, Nicole L.; Department of Urology, IU School of Medicine
    Purpose Holmium laser enucleation of the prostate can also be applied in the re-treatment setting when other benign prostatic hyperplasia therapies fail. We compared outcomes in men who underwent holmium laser enucleation of the prostate in the primary vs the re-treatment setting. Materials and Methods We retrospectively reviewed the records of 2,242 patients who underwent holmium laser enucleation of the prostate at a total of 4 academic hospitals between 2003 and 2015. Patient demographics, and operative and perioperative outcomes were compared between re-treatment and primary holmium laser enucleation of the prostate. Results Of the 360 of 2,242 men (16%) who underwent re-treatment holmium laser enucleation of the prostate the procedure was done for residual urinary symptoms in 71%. The most common primary procedure was transurethral resection of the prostate in 42% of cases. Mean time between prior benign prostatic hyperplasia surgery and re-treatment was 68 months (range 1 to 444). There were no significant differences in age, prostate size, AUA (American Urological Association) symptom score or average flow rate between the cohorts. Perioperatively, re-treatment holmium laser enucleation of the prostate was associated with significantly shorter operative time, reduced blood loss, lower specimen weight and shorter length of stay. The AUA symptom score improved in both groups, although it remained higher in men who underwent re-treatment (6.5 vs 5.0, p <0.001). The likelihood of clot retention (4.7% vs 1.8%, p = 0.01) and urethral stricture (3.3% vs 1.5%, p = 0.043) was slightly higher in the re-treatment group. Conclusions Immediate perioperative outcomes of holmium laser enucleation of the prostate performed in the re-treatment setting were no different from those in the primary setting. While re-treatment was associated with an increased likelihood of clot retention, urethral stricture and higher AUA symptom score, these minimal differences must be considered against the overall favorable symptom improvement across both cohorts.
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    TMPRSS2-ERG gene fusion is rare compared to PTEN deletions in stage T1a prostate cancer
    (Wiley, 2016-03) Fisher, Kurt W.; Zhang, Shaobo; Wang, Mingsheng; Montironi, Rodolfo; Wang, Lisha; Baldridge, Lee Ann; Wang, Jonas Y.; MacLennan, Gregory T.; Williamson, Sean R.; Lopez-Beltran, Antonio; Cheng, Liang; Department of Pathology and Laboratory Medicine, IU School of Medicine
    T1a prostate cancers (cancer found incidentally in transurethral resection, <5% of the tissue) are indolent tumors of the transition zone. The overexpression of ERG and the inactivation of PTEN have been shown to be important drivers of carcinogenesis in large series of prostate cancer, but the genetics of transition zone tumors have not been well characterized. We evaluated the status of ERG and PTEN in formalin-fixed paraffin-embedded tissue using immunohistochemical and FISH analysis in 54 T1a transition zone tumors. The protein expression of ERG was determined using a rabbit monoclonal antibody and nuclear staining was scored as positive or negative. The genomic status of ERG was determined using three colored FISH using an ERG-TMPRSS2 tri-color probe set. The protein expression of PTEN was determined using a rabbit monoclonal antibody and cytoplasmic, and nuclear staining was scored as positive or negative. The genomic status of PTEN was determined using dual color FISH with a PTEN probe and a CEP10 probe. We found ERG rearrangement in 2 of 54 tumors (4%), one with protein overexpression by immunohistochemistry. PTEN inactivation was seen in 13 of 54 tumors (24%). Nine of the 13 PTEN alleles were inactivated by hemizygous deletion. No homozygous PTEN deletion was observed. PTEN deletion and ERG rearrangement were mutually exclusive. ERG rearrangement was rare compared to peripheral zone tumors and to PTEN inactivation in T1a transition zone tumors.