Search

The risk of prostate cancer (PCa) is strongly influenced by race and ethnicity. The purpose of this study is to investigate differences in the diagnostic performance of multiparametric MRI (mpMRI) in African American (AA) and white (W) men. 111 patients (37 AA and 74 W men) were selected from the study's initial cohort of 885 patients after matching age, prostate-specific antigen, and prostate volume. The diagnostic performance of mpMRI was assessed using detection rates (DRs) and positive predictive values (PPVs) with/without combining Ktrans (volume transfer constant) stratified by prostate zones for AA and W sub-cohorts. The DRs of mpMRI for clinically significant PCa (csPCa) lesions in AA and W sub-cohort with PI-RADS scores ≥ 3 were 67.3% vs. 80.3% in the transition zone (TZ; p=0.026) and 81.2% vs. 76.1% in the peripheral zone (PZ; p>0.9). The Ktrans of csPCa in AA men was significantly higher than in W men (0.23±0.08 min-1 vs. 0.19±0.07 min-1 ; p=0.022). This emphasizes that there are race-related differences in the performance of mpMRI and quantitative MRI measures that are not reflected in age, PSA, and prostate volume.

The NCCN Guidelines for Prostate Cancer address staging and risk assessment after a prostate cancer diagnosis and include management options for localized, regional, recurrent, and metastatic disease. The NCCN Prostate Cancer Panel meets annually to reevaluate and update their recommendations based on new clinical data and input from within NCCN Member Institutions and from external entities. These NCCN Guidelines Insights summarizes much of the panel's discussions for the 4.2022 and 1.2023 updates to the guidelines regarding systemic therapy for metastatic prostate cancer.

Planning complex operations such as robotic-assisted radical prostatectomy requires surgeons to review 2-dimensional magnetic resonance imaging (MRI) cross-sectional images to understand 3-dimensional (3D), patient-specific anatomy. We sought to determine surgical outcomes for robotic-assisted radical prostatectomy when surgeons reviewed 3D, virtual reality (VR) models for operative planning.A multicenter, randomized, single-blind clinical trial was conducted from January 2019 to December 2020. Patients undergoing robotic-assisted laparoscopic radical prostatectomy were prospectively enrolled and randomized to either a control group undergoing usual preoperative planning with prostate biopsy results and MRI only or to an intervention group where MRI and biopsy results were supplemented with a 3D VR model. The primary outcome measure was margin status, and secondary outcomes were oncologic control, sexual function and urinary function.Ninety-two patients were analyzed, with trends toward lower positive margin rates (33% vs 25%) in the intervention group, no significant difference in functional outcomes and no difference in traditional operative metrics (p0.05). Detectable postoperative prostate specific antigen was significantly lower in the intervention group (31% vs 9%, p=0.036). In 32% of intervention cases, the surgeons modified their operative plan based on the model. When this subset was compared to the control group, there was a strong trend toward increased bilateral nerve sparing (78% vs 92%), and a significantly lower rate of postoperative detectable prostate specific antigen in the intervention subset (31% vs 0%, p=0.038).This randomized clinical trial demonstrated patients whose surgical planning involved 3D VR models have better oncologic outcomes while maintaining functional outcomes.

The NCCN Guidelines for Prostate Cancer address staging and risk assessment after a prostate cancer diagnosis and include management options for localized, regional, and metastatic disease. Recommendations for disease monitoring and treatment of recurrent disease are also included. The NCCN Prostate Cancer Panel meets annually to reevaluate and update their recommendations based on new clinical data and input from within NCCN Member Institutions and from external entities. This article summarizes the panel's discussions for the 2021 update of the guidelines with regard to systemic therapy for metastatic castration-resistant prostate cancer.

Patient-specific 3D-printed molds and ex vivo MRI of the resected prostate have been two important strategies to align MRI with whole-mount histopathology (WMHP) for prostate cancer (PCa) research, but the combination of these two strategies has not been systematically evaluated.To develop and evaluate a system that combines patient-specific 3D-printed molds with ex vivo MRI (ExV) to spatially align in vivo MRI (InV), ExV, and WMHP in PCa patients.Prospective cohort study.Seventeen PCa patients who underwent 3T MRI and robotic-assisted laparoscopic radical prostatectomy (RALP).TImmediately after RALP, the fresh whole prostate specimens were imaged in patient-specific 3D-printed molds by 3T MRI and then sectioned to create WMHP slides. The time required for ExV was measured to assess impact on workflow. InV, ExV, and WMHP images were registered. Spatial alignment was evaluated using: slide offset (mm) between ExV slice locations and WMHP slides; overlap of the 3D prostate contour on InV versus ExV using Dice's coefficient (0 to 1); and 2D target registration error (TRE, mm) between corresponding landmarks on InV, ExV, and WMHP. Data are reported as mean ± standard deviation (SD).Differences in 2D TRE before versus after registration were compared using the Wilcoxon signed-rank test (P 0.05 considered significant).ExV (duration 115 ± 15 min) was successfully incorporated into the workflow for all cases. Absolute slide offset was 1.58 ± 1.57 mm. Dice's coefficient was 0.865 ± 0.035. 2D TRE was significantly reduced after registration (P 0.01) with mean (±SD of per patient means) of 1.9 ± 0.6 mm for InV versus ExV, 1.4 ± 0.5 mm for WMHP versus ExV, and 2.0 ± 0.5 mm for WMHP versus InV.The proposed system combines patient-specific 3D-printed molds with ExV to achieve spatial alignment between InV, ExV, and WMHP with mean 2D TRE of 1-2 mm.2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:270-279.

Kurzfassung Durch eine möglichst frühzeitige Abbildung der Produktionsanlagen in digitalen (virtuellen) Modellen können diese Anlagen lange vor der realen Inbetriebnahme „im Rechner“ getestet und hinsichtlich ihrer Funktionsfähigkeit abgesichert werden, wodurch erhebliche Kosten- und Zeiteinsparungen erzielt werden. Für viele Unternehmen – nicht nur aus der Automobilbranche – ist die Digitale Fabrik deshalb heute ein hochaktuelles strategisches Thema. Seit etwa 2005 ist die Digitale Fabrik in der Realität der Automobilindustrie angekommen und wird produktiv eingesetzt. Dieser Artikel stellt sich der Frage, ob und besonders wie sich die Digitale Fabrik heute schon in mittelständischen Unternehmen anwenden lässt.

CO 2 exchange and water relations of selected lichen species were investigated in the field and also in the laboratory, at a height of 3106 m above sea level in the Austrian Alps, during the short snowless summer period from middle of July to the end of August. In the course of the field investigations, clear summer days were quite rare. Altogether 14 diurnal courses of CO 2 exchange were measured spanning a time of 255 h of measurements. The air temperatures measured close to the ground ranged between −0.7 and 17.1 °C and their daily fluctuation was lower than 10.7 °C. Fog was present for more than one-third of the measuring period and relative humidity (RH) exceeded 90% in almost half of the time. Temperature optimum of net photosynthesis (NP) of Xanthoria elegans and Brodoa atrofusca determined in the laboratory increased with increasing photosynthetic photon flux density (PPFD) from 1.5 to 11.3 °C and the maximal CO 2 uptake was found to be at 10 °C. In the field the lichens were metabolically active at air temperatures between −0.7 and 12.8 °C. The light compensation points (LCP) of both lichen species ranged in the laboratory between 50 and 200 μmol m −2 s −1 PPFD (0–20 °C) and in the field between 22 and 56 μmol m −2 s −1 PPFD (3–8 °C). At 30 °C the NP of X. elegans surpassed the LCP, whereas B. atrofusca remained below the LCP. NP in X. elegans did not reach light saturation at 1500 μmol m −2 s −1 PPFD. NP in B. atrofusca reached light saturation at low temperatures (−5 to +5 °C). At higher temperatures light saturation was almost detectable. On sunny days the lichens in the field were metabolically active only for 3 h during the early morning. In this time they reached the maximal values or values close to their maximal CO 2 uptake in situ . Under dry weather conditions the lichens dried out to a minimal water content (WC) of 5–12% which is below the moisture compensation point (MCP) of 34–25%. The optimal WC was between 90% and 120% dry weight (DW) in B. atrofusca and Umbilicaria cylindrica , in X. elegans between 140% and 180% DW. Species specific differences in water-holding capacity, desiccation intensity and in the compensation points of temperature, light and moisture are responsible for differences in metabolic activity. The lichens were active during less than half of the observation time. Total time of NP of X. elegans was 24% of the measuring period, for U. cylindrica 22% and for B. atrofusca 16%.

Objective: There are fundamental differences between the administration of medications and the application of manual procedures, such as those used by chiropractors. The objective of this study was to gather preliminary information on how to address these differences in the design of a multisite, randomized placebo-controlled trial of chiropractic care for women with chronic pelvic pain (CPP). Design: Pilot study for a multisite, randomized, placebo-controlled clinical trial. Setting: Three chiropractic research clinics in the midwest United States. Subjects: Thirty-nine (39) women with CPP of at least 6 months' duration, diagnosed by board-certified gynecologists. Interventions: The active intervention consisted of the chiropractic technique, lumbar spine flexion-distraction, combined with manual Trigger Point Therapy. The placebo intervention consisted of a sham chiropractic procedure performed with an instrument combined with effleurage (light massage). Outcome measures: The primary outcome measure was...

The von Hippel-Lindau syndrome is the most well known cause of familial renal cancer. Because affected individuals with renal lesions can have complex, multisystem manifestations of von Hippel-Lindau disease, our renal management strategy has included parenchymal sparing surgery whenever possible. From May 1988 to January 1993,20 patients with hereditary renal cell carcinoma (19 with von Hippel-Lindau disease and 1 with hereditary papillary renal cancer) underwent renal exploration with the intent of performing parenchymal sparing surgery. A total of 7 nephrectomies and 27 parenchymal sparing procedures was performed. Additional procedures performed included 2 bilateral adrenalectomies for pheochromocytomas, 1 resection of a renal vein thrombus and 1 resection of a pancreatic islet cell tumor. Renal atrophy occurred in 3 of 27 kidneys (11%) treated by parenchymal sparing surgery. In 8 kidneys of 7 patients new solid lesions developed and in 14 kidneys of 12 patients no new solid lesions developed during a mean followup of 26 months (range 6 to 60 months). The use of parenchymal sparing surgery in patients with familial forms of kidney cancer is based on a desire to maintain renal function as long as possible while reducing the risk of metastases. The potential advantages and disadvantages of more ablative surgical treatment requiring subsequent dialysis or transplantation in patients with existing or potential central nervous system, eye, pancreas and/or adrenal tumors must be weighed against the possibility of renal cancer metastases or recurrence when deciding on the use of parenchymal sparing surgery. von Hippel-Lindau disease is an autosomal dominant hereditary disorder characterized by hemangioblastomas of the central nervous system, retinal angiomas, pheochromocytomas, epididymal cystadenomas, pancreatic cysts and tumors, and renal cysts and carcinomas.’.2 The von Hippel-Lindau gene has recently been identified on chromosome and is associated with the formation of clear cell renal carcinoma~.~,~ Before the widespread use of noninvasive imaging 23 to 45% of patients with von Hippel-Lindau disease were reported to have renal cell carcinoma and about a third died of metastatic renal cell carcinoma.1.2*6.7 Because von HippelLindau disease is genetic in origin, multiple, bilateral cysts and tumors can develop in young patients and patients are at risk of new tumors developing throughout life?ss*9 Treatment strategies for renal tumors in patients with von Hippel-Lindau disease have included bilateral nephrectomy with subsequent dialysis andor transplantation or renal sparing operation^.'^-'^ Removal of both kidneys, while eliminating the risk of metastatic renal cell carcinoma, impacts greatly on quality of life, especially since many patients are already afflicted with other manifestations of von HippelLindau disease. We have chosen a parenchymal sparing surgical approach in select patients with von Hippel-Lindau disease and renal tumors in an attempt to control local tumor growth, prevent metastases and maintain a higher quality of life than is possible for those undergoing renal transplantation or dialysis.

Current literature suggests that the activation of the androgen receptor (AR) pathway in metastatic castrate resistant prostate cancer (CRPC), to be a driving force for resistance, yet AR is not ubiquitously expressed in cancer cells, suggesting there are alternate mechanisms for independence of AR. Overexpression of N-cadherin caused invasion, metastasis and castrate resistance in multiple models of CRPC and in clinical samples. It has been shown that N-cadherin is a possible marker of epithelial mesenchymal transition (EMT). We looked at the N-cadherin driven signaling events in CRPC cells that can induce aggressive biologic effects, as well as the requirement of N-cadherin domains for these effects. We reported that N-cadherin overexpression activated NF-kappa B pathway, of which blockade inhibited invasion. N-cadherin overexpression also caused increased PI3K/AKT activity which further mediated NF-kB activation. The combination of N-cadherin antibody and PI3K inhibitor showed in vitro synergistic effect in blocking invasion but not growth. The extracellular N-cadherin domain is critical for cell migration and invasion while the cytoplasmic domain is dispensable. Full length intact N-cadherin is required for in vitro castrate resistant growth of prostate cancer cells. In vivo studies were conducted to confirm these findings. We have tried to build our understanding of the signaling events that occur as a result of N-cadherin expression to identify biochemical targets that can be used therapeutically in combination with our N-cadherin antibody to achieve additive or synergistic anti-tumor activity.

The humanized antibody to prostate stem cell antigen (PSCA), a cell surface marker on prostate cancer cells, combined with PET scanning was developed to image prostate tumor. The antibody was successful in preclinical model, although humanization caused a loss of affinity relative to the parental monoclonal antibody. To improve the imaging agent, multiple versions of humanized PSCA antibody fragments were created and subsequently tested for their abilities to image in vivo using micro-PET, with the goal to eventually detect distant metastases. Both the engineered minibodies and diabodies were able to successfully detect tumor, and the affinity that was decreased upon humanization was improved. Experiments are ongoing to characterize the affinity matured variant of the minibodies, therefore a lead agent has not been chosen, but this is expected to happen in the next year. On the other hand, a human PSCA knockin mouse model was generated, verified and maintained. This genetically engineered murine line is being expanded and will be used to cross to a known model of mouse prostate cancer in the next year.

We have recently demonstrated that a monoclonal antibody against prostate stem cell antigen (PSCA) can exert anti-tumor activity in a xenograft animal model suggesting oncogenic activity of PSCA in prostate cancer. Therefore the our goal is to elucidate the role of PSCA in the development of prostate cancer. A better understanding of PSCA function and its antibody activity will enable rational patient selection and trial design all of which are particularly relevant to subsequent clinical trials of PSCA antibody. There were difficulties in using the LAPC9 xenograft cells to study the effect of suppressing PSCA but we have since moved ahead to perform an in vivo experiment to study the effect of knocking down PSCA in LAPC9 tumor cells. While the results showed no difference in tumor size we will repeat this experiment this time making sure that PSCA is greatly attenuated before innoculating the tumor cells back into mice. The exciting new data came from the in vitro study of overexpressing PSCA in cell lines. We showed that PSCA promote cell growth in prostate cancer cell line 22RV1 but not in normal cells PZ-HPV7. This results agree with previous data that PSCA is upregulated in prostate cancer. We have also engineered the gene targeting construct to make the human PSCA knockin mice and expect to generate this line in the next 6 month.

The molecular and cellular origins of prostate cancer are poorly understood. Recent evidence from our laboratory suggests that prostate cancer may arise from a basal/luminal precursor cell marked by cell surface expression of PSCA. The evidence supporting this hypothesis is that (I) PSCA marks an intermediate cell population that coexpresses basal and luminal cell cytokeratins (2) this cell population is does not express p63 and is androgen receptor positive, all hallmarks of prostate cancer, and (3) PSCA is highly expressed in HGPIN and prostate cancer and in all animal models of prostate cancer. To test this hypothesis and to develop new models of prostate, we propose to determine whether delivery of oncogenes specifically to the PSCA positive cells of mouse prostate is sufficient to cause cancer. To accomplish this, we will develop a transgenic mouse model in which the retroviral receptor gene tva is expressed in the prostate under control of the PSCA promoter. Virus containing one or more oncogenes will be delivered to the prostate and the resulting phenotype characterized.

Die Planung der Pkw-Endmontage im BMW-Werk Dingolfing wird bereits mit Hilfe von CAx-Methoden durchgefuhrt. Dazu zahlt auch die Ablaufsimulation, allerdings bisher erst ab einer relativ spaten Planungsphase. Fur kurzere Planungszeiten und eine hohere Planungsqualitat ist sie datentechnisch und methodisch durchgangig einzubinden.

There has been a continual evolution in methods used to determine the genetic makeup of individuals. The complete genetic makeup or genotype of an individual is represented by its entire DNA sequence; however, until entire genomes can be sequenced with little effort, geneticists will continue to rely on genetic markers as a means of characterising the genotypic variation of individuals.

In the 1980s, DNA-based molecular markers were identified as having the potential to enhance corn (Zea mays L.) breeding. Research has demonstrated the advantage of using molecular markers for selection of simply inherited traits, however only a few studies have evaluated the potential to enhance genetic gain for quantitative traits. In the late 1990s, Monsanto decided to implement marker assisted selection for quantitative traits in our global plant breeding programs. We built genotyping systems and information tools and developed marker assisted methodologies that increased the mean performance in elite breeding populations.