Effect of metastatic site biopsy on circulating tumor cell (CTC) count in castrate resistant prostate cancer (CRPC) stage.
Manish KohliPatrick W. EikenBrendan P. McMenomyThomas D. AtwellWinston TanRui QinRachel E. CarlsonMichael B. CampionLiewei WangBrian A. CostelloHenry C. PitotFernando QuevedoElizabeth A ScheelThai H. HoAlan H. BryceRicardo Paz‐FumagalliTimothy J. MoynihanRoxana DroncaMinetta C. Liu
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190 Background: It is not known if biopsy of CRPC stage metastases alters CTC results. We evaluated pre & post biopsy CTC counts in a prospective cohort undergoing pre-chemotherapy abiraterone acetate/prednisone (AA/P). Methods: CTC enumeration was performed on 7.5mL blood using the FDA cleared immunomagnetic/immunofluorescence assay (CellSearch). Time of blood draw for CTC counts pre/post biopsy was recorded for each biopsy. Biopsies were performed using 11/13 gauge core biopsy device for bone lesions and 18 gauge core needle biopsy device for soft tissue/nodal metastases. All patients (pts) underwent two serial biopsies 3 months apart. Change in CTC counts pre/post biopsy for visits 1 and 2 were evaluated using Wilcoxon signed rank test (significance at p<0.05). Differences in CTC count change (visit1) pre/post biopsy based on metastatic site (skeletal vs. non-skeletal) was compared using Wilcoxon rank-sum test. Results: Median age of the cohort was 74 years (IQR: 68-78); median PSA at V1 was 16.4 ng/ml (IQR: 6.4-87.6); at V2 was 11.5 ng/ml (IQR: 1.8-23.7). Of 59 pts undergoing biopsies 42 were in bone and 17 in nodal/soft tissue masses. At V1, pre/post biopsy CTC counts were measured on 50 and 49 pts, respectively; at V2, pre/post CTC counts were measured on 43 and 36 pts. High volume metastatic disease at V1 was observed in 67.8 % of all pts. Table lists CTC counts and time of collection pre/post biopsy for both visits. Mean change in pre/post biopsy CTC counts for skeletal sites was 0.7 (range: -12 to 64) compared to 12.1 (range: -21 to 13) for non-skeletal sites (p=0.23). Conclusions: An increase in mean CTC counts after biopsy of CRPC metastases was observed. No significant differences in change of CTC counts based on site biopsied (skeletal versus non-skeletal) was noted. Correlation with clinical outcomes is on-going. Clinical trial information: NCT# 01953640. [Table: see text]Enzalutamide
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Prostate cancer is a malignancy commonly occuring in male genitourinary system.Androgen receptor promotes gene transcription in prostate cell growth and carcinogenesis of prostate cancer,which makes it to become an important target in prostate cancer treatment possibly.Prostate cancer may be deteriorated into be castration-resistant prostate cancer easily after androgen deprivation therapy,so it is popular to seek the effective androgen receptor antagonists for treating of castration-resistant prostate cancer.This review focuses on the action mechanism and the development of androgen receptor antagonists for the treatment of prostate cancer.
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Androgen deprivation therapy has been the standard treatment for the patients with advanced prostate cancer. Androgen deprivation therapy initially suppresses the growth of prostate cancer. However, most patients eventually progress to castration-resistant prostate cancer. Novel drugs, including enzalutamide and abiraterone acetate, are recently able to be used for the patients with castration-resistant prostate cancer. Even so, the therapeutic options for castration-resistant prostate cancer are not enough. Interestingly, androgen receptor degradation enhancer ASC-J9 is reported to degrade the androgen receptor, resulting in the suppression of the growth in castration-resistant prostate cancer cells. In this chapter, ASC-J9 for prostate cancer is reviewed.
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Prostate cancer is one of the most common and socially significant cancers among men. The aim of this study was to identify significant changes in the expression of exosomal miRNAs associated with an increase in the level of prostate specific antigen in castration-resistant prostate cancer during therapy and to evaluate them as potential prognostic markers for this category of disease. High-throughput miRNA sequencing was performed on 49 blood plasma samples taken from 11 Russian patients with castration-resistant cancer during therapy. Bioinformatic analysis of the obtained miRNA-seq data was carried out. Additionally, miRNA-seq data from the PRJNA562276 project were analyzed to identify exosomal miRNAs associated with castration-resistant prostate cancer. We found 34 differentially expressed miRNAs associated with the progression of castration-resistant prostate cancer during therapy in Russian patients. It was also shown that hsa-miRNA-148a-3p expression can serve as a potential prognostic marker. We found the exosomal miRNA expression signature associated with castration-resistant prostate cancer progression, in particular on the Russian patient cohort. Many of these miRNAs are well-known players in either oncogenic transformation or tumor suppression. Further experimental studies with extended sampling are required to validate these results.
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Abstract : Prostate cancer cells have a remarkable affinity to develop metastases in bone. Clinical data and laboratory observations both suggest that bone-malignant epithelium interactions play a central role in prostate cancer progression. We have developed an in vitro model system that reflects the most common cellular features of prostate cancer bone metastases. The model consists of the prostate cancer cell lines: MDA PCa 2a or MDA PCa 2b (the TabBO cells) co-cultured with primary mouse osteoblasts (PMO). The two cell types share medium but are not in physical contact because the prostate cancer cells are plated in cell-culture inserts. We have established the optimal conditions for growing prostate cancer cells in co-culture with PMO. Using those conditions, we defined the effect that prostate cancer cells have in PMO in our model system. This effect reflects the interaction between prostate cancer cells and osteoblasts in prostate cancer bone metastases. Therefore we conclude that our model system may be suitable to study the molecular and cellular events involved in the new bone formation observed in prostate cancer bone metastases.
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Recurrence of localized prostate cancer following treatment can lead to lethal metastatic castration-resistant prostate cancer. Although numerous studies aimed at developing biomarkers for predicting recurrence of localized prostate cancer are promising, they have not yet led to useful applications. Dysregulation of exportins (XPOs, nucleocytoplasmic transporters) associated with subcellular mislocalization of proteins has been reported for various human cancers. However, most of the XPOs have not been studied in prostate cancer. In this study, we are the first to examine whether changes in expression of XPOs could be used as potential biomarkers for recurrence of localized prostate cancer. Using the oncomine database, gene expressions of 7 known XPOs by 1128 patient samples, obtained from 16 independent prostate cancer patient cohorts, were analyzed. Relatively highly elevated expression of XPO6 (compared to prostate cancer tissue) was found to be significantly associated with poor patient prognosis, in particular, with rapid recurrence in a clinical low risk group. As such, expression of XPO6 may be a potential prognostic biomarker for predicting prostate cancer recurrence.
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地方性甲状腺腫は臨床, 病理学的に複雑な経過を示し, 疫学的, 病理学的発生論や治療の選択に多くの難題が残されている. 著者は本症の病期検討および妥当な病期分類がこれらの検索, 解明にきわめて有用であると着目し, 甲状腺剔出を行なった地方性甲状腺腫336例を臨床, 病理学的に精査し下記の結果をえた. 1) 地方性甲状腺腫は臨床的, 病理学的経過からStage 1;過形成期, Stage 2;腫大期, Stage 3;結節形成期と分類できた. 2) 本症は病期の進行に伴い病悩期間は長くなり, 甲状腺腫は増大し種々の局所圧迫症状をみるが, 合併症がなければ全身的, 臨床生化学的所見はほぼ正常である. 3) 臨床, 病理学的に本症はStage 1からStage 2さらにStage 3に進行し, Stage 3は終末期である. 4) 病変の占居部位はStage 1では両葉性, Stage 2では両葉性と単葉性がほぼ等しく, Stage 3では単葉性が多い点からもStageの進行度を裏付けられる. 5) 336例のうち男性39例, 女性297例, 男女比1:7.6で, 発生のピークは女性では20才から30才代, 男性は30才から40才代であった. 6) 手術適応例は若年者より成人に多く, 女性は男性より著しく多い. ヨード治療の効果が若年者ほど良好で, 男性は女性よりもヨード感受性が高いためである. 7) Stage 3の9.4%に甲状腺機能亢進症 (4.03%), 腺腫 (1.34%), 甲状腺癌 (4.03%) などの共存疾患がみられた. 8) ヨード治療はStage 1では効果的であるがStage 2では無効でStage 3に進行し, 種々の合併症を起こすこともあり, Stage 2における手術が望ましい.
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