Inhibitory effects of megakaryocytic cells in prostate cancer skeletal metastasis

Prostate cancer cells commonly spread through the circulation, but few successfully generate metastatic foci in bone. Osteoclastic cellular activity has been proposed as an initiating event for skeletal metastasis. Megakaryocytes (MKs) inhibit osteoclastogenesis, which could have an impact on tumor establishment in bone. Given the location of mature MKs at vascular sinusoids, they may be the first cells to physically encounter cancer cells as they enter the bone marrow. Identification of the interaction between MKs and prostate cancer cells was the focus of this study. K562 (human MK precursors) and primary MKs derived from mouse bone marrow hematopoietic precursor cells potently suppressed prostate carcinoma PC-3 cells in coculture. The inhibitory effects were specific to prostate carcinoma cells and were enhanced by direct cell-cell contact. Flow cytometry for propidium iodide (PI) and annexin V supported a proapoptotic role for K562 cells in limiting PC-3 cells. Gene expression analysis revealed reduced mRNA levels for cyclin D1, whereas mRNA levels of apoptosis-associated specklike protein containing a CARD (ASC) and death-associated protein kinase 1 (DAPK1) were increased in PC-3 cells after coculture with K562 cells. Recombinant thrombopoietin (TPO) was used to expand MKs in the marrow and resulted in decreased skeletal lesion development after intracardiac tumor inoculation. These novel findings suggest a potent inhibitory role of MKs in prostate carcinoma cell growth in vitro and in vivo. This new finding, of an interaction of metastatic tumors and hematopoietic cells during tumor colonization in bone, ultimately will lead to improved therapeutic interventions for prostate cancer patients. © 2011 American Society for Bone and Mineral Research.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78486/1/204_ftp.pd

Beyond the androgen receptor II: New approaches to understanding and treating metastatic prostate cancer; Report from the 2017 Coffey‐Holden Prostate Cancer Academy Meeting

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138883/1/pros23424.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138883/2/pros23424_am.pd

Macroscopic transport by synthetic molecular machines

Nature uses molecular motors and machines in virtually every significant biological process, but demonstrating that simpler artificial structures operating through the same gross mechanisms can be interfaced with—and perform physical tasks in—the macroscopic world represents a significant hurdle for molecular nanotechnology. Here we describe a wholly synthetic molecular system that converts an external energy source (light) into biased brownian motion to transport a macroscopic cargo and do measurable work. The millimetre-scale directional transport of a liquid on a surface is achieved by using the biased brownian motion of stimuli-responsive rotaxanes (‘molecular shuttles’) to expose or conceal fluoroalkane residues and thereby modify surface tension. The collective operation of a monolayer of the molecular shuttles is sufficient to power the movement of a microlitre droplet of diiodomethane up a twelve-degree incline.

Tumor cell heterogeneity and resistance; report from the 2018 Coffey‐Holden Prostate Cancer Academy Meeting

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147081/1/pros23729.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147081/2/pros23729_am.pd

Validating Chemistry Faculty Members’ Self-Reported Familiarity with Assessment Terminology

With the increasing emphasis placed upon chemistry instructors and departments to assess and evaluate their courses and curricula, understanding the structure of chemistry faculty members’ knowledge and use of assessment terms and concepts can shed light on potential areas for targeted professional development. Survey research that might accomplish this objective often relies on self-reported responses from the target audience, and such information is sometimes difficult to assess in terms of validity. As an example of an internal mechanism to help establish validity, it is possible to include an “internal standard” item early in the survey. For the sake of understanding faculty members’ familiarity with assessment terminology, an item that asked participants to identify analogous pairs of terms comparing assessment measures (assessment validity and assessment reliability) to laboratory measures (accuracy and precision) served this purpose. Using ordered logistic regression, participants who answered the analogy question completely correctly were more likely to report higher levels of familiarity with the assessment terms. Because the self-reported data appears to be valid, these data can be further used in subsequent analyses in order to determine the general familiarity trends among chemistry faculty regarding assessment terminology

Prostate Carcinoma Skeletal Metastases: Cross-talk between Tumor and Bone

The majority of men with progressive prostate cancer develop metastases with the skeleton being the most prevalent metastatic site. Unlike many other tumors that metastasize to bone and form osteolytic lesions, prostate carcinomas form osteoblastic lesions. However, histological evaluation of these lesions reveals the presence of underlying osteoclastic activity. These lesions are painful, resulting in diminished quality of life of the patient. There is emerging evidence that prostate carcinomas establish and thrive in the skeleton due to cross-talk between the bone microenvironment and tumor cells. Bone provides chemotactic factors, adhesion factors, and growth factors that allow the prostate carcinoma cells to target and proliferate in the skeleton. The prostate carcinoma cells reciprocate through production of osteoblastic and osteolytic factors that modulate bone remodeling. The prostate carcinoma-induced osteolysis promotes release of the many growth factors within the bone extracellular matrix thus further enhancing the progression of the metastases. This review focuses on the interaction between the bone and the prostate carcinoma cells that allow for development and progression of prostate carcinoma skeletal metastases.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44522/1/10555_2004_Article_402865.pd

Novel therapeutic approach: organic arsenical (melarsoprol) alone or with all-trans -retinoic acid markedly inhibit growth of human breast and prostate cancer cells in vitro and in vivo

The organic arsenical known as melarsoprol (Mel-B) is used to treat African trypanosomiasis. Recently, another arsenical, As2O3was shown to be effective in treatment of acute promyelocytic leukaemia. We have investigated the anti-tumour activities of Mel-B either with or without all-trans -retinoic acid (ATRA) using the MCF-7 human breast cancer cells, as well as the PC-3 and DU 145 human prostate cancer cells both in vitro and in vivo. The antiproliferative effects of Mel-B and/or ATRA against breast and prostate cancer were tested in vitro using clonogenic assays and in vivo in triple immunodeficient mice. Furthermore, the mechanism of action of these compounds was studied by examining the cell cycle, levels of bcl-2, apoptosis and antiproliferative potency using a pulse-exposure assay. Clonogenic assays showed that the cancer cell lines were sensitive to the inhibitory effect of Mel-B (effective dose that inhibited 50% clonal growth [ED50]: 7 × 10−9M for MCF-7, 2 × 10−7M for PC-3, 3 × 10−7M for DU145 cells. Remarkably, the combination of Mel-B and ATRA had an enhanced antiproliferative activity against all three cancer cell lines. Furthermore, the combination of Mel-B and ATRA induced a high level of apoptosis in all three cell lines. Treatment of PC-3 and MCF-7 tumours growing in triple immunodeficient mice with Mel-B and ATRA either alone or in combination markedly retarded tumour size and weight of the tumours without major side-effects. In conclusion, our results suggest that either Mel-B alone or with ATRA may be a useful, novel therapy for breast and prostate cancers. © 2000 Cancer Research Campaig

Somatostatin in human pancreatic and gastric juice

Considerable amounts of IRS are secreted after secretin injection in human pancreatic juice collected during endoscopic retrograde cholangiopancreatography. The mean IRS levels in the pancreatic juice of non-diabetic patients were 79+/-10 (SE) pg/ml. The IRS levels in NIDDM were considerably higher, the mean value being 1635+/-313 (SE) pg/ml. The mean IRS level in IDDM were 312+/-151 (SE) pg/ml. In IDDM, those patients whose blood glucose levels were well controlled by insulin showed low pancreatic juice IRS ranging from non-detectable to 46 pg/ml. On the other hand, those with uncontrolled hyperglycemia showed IRS levels ranging from 452 to 1047 pg/ml. Gel-filtration profiles of IRS in pancreatic juice extracts were not consistent in all cases. Some showed IRS peaks eluting with SS14 and SS28, while others contained IRS species that were eluted in more retarded fractions. The retarded IRS fraction exhibited biological activity indistinguishable from that of SS14 as indexed using a quantitative cytochemical method.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24539/1/0000818.pd

Test-retest repeatability of organ uptake on PSMA‐targeted 18F‐DCFPyL PET/CT in patients with prostate cancer

Objectives We evaluated 18F-DCFPyL test–retest repeatability of uptake in normal organs. Methods Twenty-two prostate cancer (PC) patients underwent two 18F-DCFPyL PET scans within 7 days within a prospective clinical trial (NCT03793543). In both PET scans, uptake in normal organs (kidneys, spleen, liver, and salivary and lacrimal glands) was quantified. Repeatability was determined by using within-subject coefficient of variation (wCOV), with lower values indicating improved repeatability. Results For SUVmean, repeatability was high for kidneys, spleen, liver, and parotid glands (wCOV, range: 9.0%–14.3%) and lower for lacrimal (23.9%) and submandibular glands (12.4%). For SUVmax, however, the lacrimal (14.4%) and submandibular glands (6.9%) achieved higher repeatability, while for large organs (kidneys, liver, spleen, and parotid glands), repeatability was low (range: 14.1%–45.2%). Conclusion We found acceptable repeatability of uptake on 18F-DCFPyL PET for normal organs, in particular for SUVmean in the liver or parotid glands. This may have implications for both PSMA-targeted imaging and treatment, as patient selection for radioligand therapy and standardized frameworks for scan interpretation (PROMISE, E-PSMA) rely on uptake in those reference organs