On-Court Activity and Game-Related Statistics during Scoring Streaks in Basketball: Applied Use of Accelerometers.

The aim of this observational study was to determine if on-court activity and match statistics differed between periods of scoring streaks and regular play in basketball. Thirty-seven basketballers including professional women, semi-professional women and semi-professional men wore accelerometers during competitive matches throughout a season. Accelerometry-derived live-time individual on-court exercise intensity and team game-related statistics were compared between scoring streaks (periods of play where the teams participating in the study scored at least three times in a row), streaks against (periods of play where the opposition teams scored at least three times in a row) and regular play. Few differences existed in the average exercise intensity between streak types. During streaks against, there was a 5-15% lower proportion of 2-point attempts, 0.8-1.3 fewer defensive rebounds per minute and 0.3-1.6 fewer shot attempts per minute compared to regular play and scoring streaks, and there were 0.3 fewer offensive rebounds per minute compared to regular play. During scoring streaks, there were 0.5 more defensive rebounds per minute, 1.3 more shot attempts per minute, a 43% greater shooting percentage and a 10% lower proportion of 3-point attempts compared to regular play. To reduce the chances of streaks against, teams should focus on facilitating 2-point shot attempts and consider implementing a 3:1 ratio of 2-point to 3-point attempts to maximize scoring success, and they should focus on winning rebounds to facilitate more shot attempts.

Physical Demands of Elite Women's Ultimate Frisbee Between Halves and Across Matches in an International Tournament.

ABSTRACT: Palmer, JA, Landers, G, Buttfield, A, and Polglaze, T. Physical demands of elite women's Ultimate Frisbee between halves and across matches in an international tournament. J Strength Cond Res 36(3): 838-844, 2022-To quantify the physical match demands of elite women's Ultimate Frisbee across a tournament, elite female Ultimate players (N = 9) from the Australian Under 24 Women's team wore global positioning system units in all 12 matches of the 2018 Under 24 World Championship competition. Temporal, displacement, and energetic parameters were obtained. Distribution of activity above and below a generic speed threshold (12.42 km·h-1) and its equivalent metabolic power value (16.02 W·kg-1) were determined. Players spent 12:44 ± 6:41 min:s on the field, covered 1,559 ± 741 m and expended 8.95 ± 4.21 kJ·kg-1 during a match. The mean stint duration was 2:00 ± 0:48 min:s, mean bench duration was 13:25 ± 7:05 min:s, and work-to-recovery ratio was 0.22 ± 0.11. Players performed 57 ± 27 high-speed runs per match and 45 ± 20 high-accelerations. Mean match speed was 127 ± 18 m·min-1, mean metabolic power was 12.2 ± 1.7 W·kg-1, and mean intermittency index was 1.24 ± 0.04. No differences were found between halves for any parameters. Compared with the first 4 matches, the last 4 matches were shorter and more intense (p < 0.05). At the international level, Ultimate is an intense and highly intermittent sport, characterized by brief playing stints interspersed with long periods of recovery, which allow playing intensity to be maintained throughout a match and elevated in the latter stages of a tournament. The information gained from this research can be used to guide the creation of Ultimate-specific conditioning programs for elite female players.

A gut microbial signature for combination immune checkpoint blockade across cancer types.

Immune checkpoint blockade (ICB) targeting programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte protein 4 (CTLA-4) can induce remarkable, yet unpredictable, responses across a variety of cancers. Studies suggest that there is a relationship between a cancer patient's gut microbiota composition and clinical response to ICB; however, defining microbiome-based biomarkers that generalize across cohorts has been challenging. This may relate to previous efforts quantifying microbiota to species (or higher taxonomic rank) abundances, whereas microbial functions are often strain specific. Here, we performed deep shotgun metagenomic sequencing of baseline fecal samples from a unique, richly annotated phase 2 trial cohort of patients with diverse rare cancers treated with combination ICB (n = 106 discovery cohort). We demonstrate that strain-resolved microbial abundances improve machine learning predictions of ICB response and 12-month progression-free survival relative to models built using species-rank quantifications or comprehensive pretreatment clinical factors. Through a meta-analysis of gut metagenomes from a further six comparable studies (n = 364 validation cohort), we found cross-cancer (and cross-country) validity of strain-response signatures, but only when the training and test cohorts used concordant ICB regimens (anti-PD-1 monotherapy or combination anti-PD-1 plus anti-CTLA-4). This suggests that future development of gut microbiome diagnostics or therapeutics should be tailored according to ICB treatment regimen rather than according to cancer type.

Residual neuromuscular fatigue influences subsequent on-court activity in basketball.

The aim of this study was to determine if residual neuromuscular fatigue influenced subsequent match and training activity in professional women's basketball. Prior to matches and training sessions throughout a season, players performed countermovement jumps while wearing a magnetic, angular rate and gravity (acceleration) sensor on their upper back. Flight time to contraction time ratio was used to determine neuromuscular performance and to identify neuromuscular fatigue. Average session intensity and volume, the proportion of live time spent in different intensity bands (matches), and absolute and relative time spent in different intensity bands (training) were quantified using accelerometry. Residual neuromuscular fatigue was deemed to be present when the decrement in neuromuscular performance relative to pre-season baseline was greater than the smallest worthwhile change. Players displayed residual neuromuscular fatigue before 16% of matches and 33% of training sessions. When players were fatigued prior to matches, the proportion of live time undertaking supramaximal activity was 5.7% less (p = 0.02) and moderate-vigorous activity was 3.7% more than when not fatigued (p = 0.02). When fatigued prior to training, the players displayed a 2.6% decrement in average intensity (p = 0.02), 2.8% decrement in absolute (p = 0.01) and 5.0% decrement in relative (p = 0.01) maximal activity, as well as 13.3% decrement in absolute (p < 0.01) and 6.8% decrement in relative (p < 0.01) supramaximal activity when compared to not being fatigued. These findings suggest that residual neuromuscular fatigue influences players' ability to perform supramaximal activity, which highlights the importance of monitoring neuromuscular performance throughout a professional season.Highlights Residual neuromuscular fatigue can influence the amount of supramaximal activity players perform in a subsequent training session or match.Practices should be implemented to minimise residual neuromuscular fatigue carried into matches while maintaining a sufficient training volume to elicit physiological adaptations.MARG sensors can be used as an affordable and time-efficient tool for regularly monitoring countermovement jump-derived neuromuscular fatigue.

Training and match demands differ between the regular season and finals in semi-professional basketball.

Basketball competitions often include a scheduled regular season followed by knock-out finals. Understanding training and match demands through the season can help optimize performance and reduce injury risk. This study investigated whether training and/or match demands differed between the regular season and finals, and whether these differences were dependent on player role. Average session intensity and volume and durations of relative exercise intensities (inactive, light, moderate-vigorous, maximal, supramaximal) were quantified during training sessions and matches using accelerometry in two semi-professional basketball teams (n = 23; 10 women, 13 men). Training and match demands were compared between the regular season (training: 445 observations; matches: 387 observations) and finals (training: 113 observations, matches: 75 observations) with consideration of player role (starters, in-rotation bench, out-rotation bench). During finals matches, starters received 4.4 min more playing time (p = 0.03), performed 14% more absolute maximal activity (p < 0.01) and had 8% less relative inactive time (p = 0.02) when compared to the regular season. Out-rotation bench players received 2.1 min less playing time (p < 0.01), performed 33% less absolute maximal activity (p = 0.01) and 57% less absolute supramaximal activity (p < 0.01) in finals when compared to the regular season. During finals training sessions, average training intensity was 5% higher (p = 0.02), absolute moderate-vigorous activity was 3% higher (p = 0.04), relative maximal activity was 12% higher (p < 0.01), and relative inactive time was 5% lower (p = 0.03) when compared to the regular season. These findings suggest starters need to be physically prepared for greater match demands during finals, while out-rotation bench players should supplement their training during finals with extra supramaximal activity to maintain their conditioning levels for matches.

Criterion Validity of an Automated Method of Detecting Live Play Periods in Basketball.

This study aimed to develop an automated method to detect live play periods from accelerometry-derived relative exercise intensity in basketball, and to assess the criterion validity of this method. Relative exercise intensity (% oxygen uptake reserve) was quantified for two men's semi-professional basketball matches. Live play period durations were automatically determined using a moving average sample window and relative exercise intensity threshold, and manually determined using annotation of video footage. The sample window duration and intensity threshold were optimised to determine the input parameters for the automated method that would result in the most similarity to the manual method. These input parameters were used to compare the automated and manual active play period durations in another men's semi-professional match and a women's professional match to assess the criterion validity of the automated method. The optimal input parameters were a 9-s sample window and relative exercise intensity threshold of 31% oxygen uptake reserve. The automated method showed good relative (ρ = 0.95-0.96 and ICC = 0.96-0.98, p < 0.01) and absolute (median bias = 0 s) agreement with the manual method. These findings support the use of an automated method using accelerometry-derived relative exercise intensity and a moving average sample window to detect live play periods in basketball.

Effect of Player Role and Competition Level on Player Demands in Basketball.

This study compared basketball training and match demands between player roles (starters, in-rotation bench players, out-rotation bench players) and between competition levels (semi-professional, professional). Thirty-seven players from one professional women's team, one semi-professional women's team, and one semi-professional men's team wore accelerometers during training and matches throughout a competitive season. All teams were used for player role comparisons and the women's teams were used to compare competition levels. Match and training session average intensity and volume, and durations of relative exercise intensities (inactive, light, moderate-vigorous, maximal, supramaximal) were calculated. Compared to out-rotation bench players, starters experienced twice the average match intensity and volume, spent 50% less match time being inactive, and spent 1.7-4.2× more match time in all other activity categories (p < 0.01). Compared to in-rotation bench players, starters experienced 1.2× greater average match intensity and volume, spent 17% less match time being inactive, and spent 1.4-1.5× more match time performing moderate-vigorous and maximal activity (p < 0.01). No differences in match demands were found between women's competition levels, however the professional team experienced double the cumulative weekly training volume of the semi-professional team and spent 1.6-2.1× more cumulative weekly time in all activity categories (p < 0.01). To improve performance and reduce injury risk, players should prepare for the greatest match demands they could encounter during a season while considering potential changes to their role. Additionally, players might need their training volume managed when transitioning from a semi-professional to a professional season to reduce the injury risk from sharp increases in training demands.

Combination immunotherapy with nivolumab and ipilimumab in patients with rare gynecological malignancies: results of the CA209-538 clinical trial.

BACKGROUND: Patients with rare cancers represent 55% of all gynecological malignancies and have poor survival outcomes due to limited treatment options. Combination immunotherapy with the anti-programmed cell death protein 1 (anti-PD-1) antibody nivolumab and the anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) antibody ipilimumab has demonstrated significant clinical efficacy across a range of common malignancies, justifying evaluation of this combination in rare gynecological cancers. METHODS: This multicenter phase II study enrolled 43 patients with advanced rare gynecological cancers. Patients received induction treatment with nivolumab and ipilimumab at a dose of 3 mg/kg and 1 mg/kg, respectively, every 3 weeks for four doses. Treatment was continued with nivolumab monotherapy at 3 mg/kg every 2 weeks until disease progression or a maximum of 2 years. The primary endpoint was the proportion of patients with disease control at week 12 (complete response, partial response or stable disease (SD) by Response Evaluation Criteria In Solid Tumor V.1.1). Exploratory evaluations correlated clinical outcomes with tumor programmed death-ligand 1 (PD-L1) expression and tumor mutational burden (TMB). RESULTS: The objective response rate in the radiologically evaluable population was 36% (12/33 patients) and in the intention-to-treat population was 28% (12/43 patients), with additional 7 patients obtaining SD leading to a disease control rate of 58% and 44%, respectively. Durable responses were seen across a range of tumor histologies. Thirty-one (72%) patients experienced an immune-related adverse event (irAE) with a grade 3/4 irAE observed in seven (16%) patients. Response rate was higher among those patients with baseline PD-L1 expression (≥1% on tumor cells) but was independent of TMB. CONCLUSIONS: Ipilimumab and nivolumab combination treatment has significant clinical activity with a favorable safety profile across a range of advanced rare gynecological malignancies and warrants further investigation in these tumor types.

Combination immunotherapy with ipilimumab and nivolumab in patients with advanced adrenocortical carcinoma: a subgroup analysis of CA209-538.

Background: Adrenocortical carcinoma is a rare malignancy, with poor prognosis and limited treatment options for patients with advanced disease. Chemotherapy is the current standard first-line treatment, providing only a modest survival benefit. There is only limited treatment experience with immunotherapy using single-agent anti-PD-1/PD-L1 therapy. To date no clinical trials have been reported using combination immunotherapy with anti-CTLA-4 and anti-PD-1 blockade in this patient population. Methods: CA209-538 is a prospective multicentre clinical trial in patients with advanced rare cancers. Participants received the anti-PD-1 antibody nivolumab (3 mg/kg IV) and the anti-CTLA-4 antibody ipilimumab (1 mg/kg IV) every three weeks for four doses, followed by nivolumab (3 mg/kg IV) every two weeks and continued for up to 96 weeks, until disease progression or unacceptable toxicity. Response was assessed every 12 weeks by RECIST version 1.1. Primary endpoint was clinical benefit rate (complete response, partial response, stable disease at 12 weeks). Results: Six patients with adrenocortical carcinoma were enrolled and received treatment. Two patients (33%) have an ongoing partial response (10 and 25 months +) and two patients (33%) stable disease leading to a disease control rate of 66%. Both responders had tumors with a microsatellite instable phenotype. One patient rapidly progressed shortly after enrollment into the trial and did not undergo restaging. Immunotherapy-related toxicity was reported in all patients, with four patients (67%) experiencing grade 3/4 hepatitis leading to discontinuation of treatment. Conclusions: This is the first treatment experience using ipilimumab and nivolumab combination immunotherapy in patients with advanced adrenocortical carcinoma. Durable responses have been observed in a subset of patients suggesting that this treatment regimen should be further investigated in this patient population.

Evaluation of Combination Nivolumab and Ipilimumab Immunotherapy in Patients With Advanced Biliary Tract Cancers: Subgroup Analysis of a Phase 2 Nonrandomized Clinical Trial.

Importance: Biliary tract cancers represent a rare group of malignant conditions with very limited treatment options. Patients with advanced disease have a poor outcome with current therapies. Objective: To evaluate the efficacy and safety of combination immunotherapy with nivolumab and ipilimumab in patients with advanced biliary tract cancers. Design, Setting, and Participants: The CA209-538 prospective multicenter phase 2 nonrandomized clinical trial included patients with advanced rare cancers including patients with biliary tract cancers. This subgroup analysis evaluated 39 patients from CA209-538 with biliary tract cancers who were enrolled from December 2017 to December 2019. Most of the patients (n = 33) had experienced disease progression after 1 or more lines of therapy and had tumor tissue available for biomarker research. Interventions: Patients received treatment with nivolumab at a dose of 3 mg/kg and ipilimumab at 1 mg/kg every 3 weeks for 4 doses, followed by nivolumab 3 mg/kg every 2 weeks and continued for up to 96 weeks until disease progression or the development of unacceptable toxic events. Main Outcomes and Measures: The primary end point was disease control rate (complete remission, partial remission, or stable disease) as assessed by RECIST 1.1. Results: Among the 39 patients included in this subgroup analysis of a phase 2 clinical trial (20 men, 19 women; mean [range] age, 65 [37-81] years), the objective response rate was 23% (n = 9) with a disease control rate of 44% (n = 17); all responders had received prior chemotherapy, and none had a microsatellite unstable tumor. Responses were exclusively observed in patients with intrahepatic cholangiocarcinoma and gallbladder carcinoma. The median duration of response was not reached (range, 2.5 to ≥23 months). The median progression-free survival was 2.9 months (95% CI, 2.2-4.6 months), and overall survival was 5.7 months (95% CI, 2.7-11.9 months). Immune-related toxic events were reported in 49% of patients (n = 19), with 15% (n = 6) experiencing grade 3 or 4 events. Conclusions and Relevance: This subgroup analysis of a phase 2 clinical trial found that combination immunotherapy with nivolumab and ipilimumab was associated with substantial positive outcomes patients with advanced biliary tract cancers. This treatment compares favorably to single-agent anti-programmed cell death protein 1 (anti-PD-1) therapy and warrants further investigation. Ongoing translational research is focused on identifying biomarkers that can predict treatment response. Trial Registration: ClinicalTrials.gov Identifier: NCT02923934.

Immunotherapy of Ipilimumab and Nivolumab in Patients with Advanced Neuroendocrine Tumors: A Subgroup Analysis of the CA209-538 Clinical Trial for Rare Cancers.

PURPOSE: Combination immunotherapy with anti-CTLA-4 and anti-PD-1 blockade has demonstrated significant clinical activity across several tumor types. Neuroendocrine tumors (NET) are a heterogeneous group of rare tumors with limited treatment options. CA209-538 is a clinical trial of combination immunotherapy with ipilimumab and nivolumab in rare cancers, including advanced NETs. PATIENTS AND METHODS: CA209-538 is a prospective multicenter clinical trial in patients with advanced rare cancers. Patients received treatment with nivolumab at a dose of 3 mg/kg and ipilimumab at 1 mg/kg every three weeks for four doses, followed by nivolumab 3 mg/kg every two weeks and continued for up to 96 weeks, until disease progression or the development of unacceptable toxicity. Response was assessed every 12 weeks by RECIST 1.1. The primary endpoint was clinical benefit rate (CBR; complete remission + partial remission + stable disease). RESULTS: Twenty-nine patients with advanced NETs received treatment. Three (10%) patients had low-, 13 (45%) had intermediate-, and 13 (45%) had high-grade tumors; lung was the most common primary site (39%). The objective response rate was 24% with a CBR of 72%; 43% of patients with pancreatic neuroendocrine neoplasms (NEN), and 33% of patients with atypical bronchial carcinoid achieved an objective response. The median progression-free survival was 4.8 months [95% confidence interval (CI): 2.7-10.5] and overall survival was 14.8 months (95% CI: 4.1-21.3). Immune-related toxicity was reported in 66% of patients with 34% experiencing grade 3/4 events. CONCLUSIONS: Combination immunotherapy with ipilimumab and nivolumab demonstrated significant clinical activity in subgroups of patients with advanced NETs including patients with atypical bronchial carcinoid and high-grade pancreatic NENs.

Androgen-independent growth and tumorigenesis of prostate cancer cells are enhanced by the presence of PKA-differentiated neuroendocrine cells.

The neuroendocrine status of prostatic adenocarcinomas is considered a prognostic indicator for development of aggressive, androgen-independent disease. Neuroendocrine-like cells are thought to function by providing growth and survival signals to surrounding tumor cells, particularly following androgen ablation therapy. To test this hypothesis directly, LNCaP cells were engineered to inducibly express a constitutively activated form of the cyclic AMP-dependent protein kinase A catalytic subunit (caPKA), which was previously found upon transient transfection to be sufficient for acquisition of neuroendocrine-like characteristics and loss of mitotic activity. Clonal cells that inducibly expressed caPKA enhanced the growth of prostate tumor cells in anchorage-dependent and anchorage-independent in vitro assays as well as the growth of prostate tumor xenografts in vivo, with the greatest effects seen under conditions of androgen deprivation. These results suggest that neuroendocrine-like cells of prostatic tumors have the potential to enhance androgen-independent tumor growth in a paracrine manner, thereby contributing to progression of the disease.

A pilot study of intrahepatic yttrium-90 microsphere radioembolization in combination with intravenous cisplatin for uveal melanoma liver-only metastases.

BACKGROUND: Metastatic uveal melanoma is a highly aggressive disease with no standard of care treatment option. A large proportion of patients have liver-only metastatic disease which raises the question if liver-directed therapy can be efficacious in this subpopulation. AIMS: The study aims to evaluate the safety and efficacy of radiosensitizing chemotherapy in combination with yttrium-90 microspheres in patients with uveal melanoma with liver-only metastases. METHODS AND RESULTS: This single arm, open labeled, non-randomized study enrolled 10 patients with liver-only metastatic uveal melanoma between November 2012 and January 2018. Eligible patients received intrahepatic yttrium-90 microspheres followed by intravenous cisplatin (20 mg/m2) for 5 days. Ten patients were enrolled, but nine patients received treatment who were included in the final analysis with a median follow-up of 30 months (range 7 to 44). Five (50%) were female, five (50%) had an elevated lactate dehydrogenase (LDH), and one (10%) had prior anti-PD-1 therapy. The combination was well tolerated with no greater than or equal to grade 3 toxicity observed. The liver objective response rate (ORR) was 33% (3/9), the median progression-free survival (PFS) in the liver was 3 months (95% CI, 3-NA), and the extrahepatic PFS was 3 months (95% CI, 3-NA). Seventy-eight percent (7/9) received an immune checkpoint inhibitor on disease progression, with no responses seen. The median overall survival (OS) was 10 months (95% CI, 7-NA). CONCLUSION: The combination of cisplatin with yttrium-90 microspheres was well tolerated; however, it was associated with intrahepatic disease control of relatively short duration. No responses were seen in patients treated with immune checkpoint inhibitors post radioembolization.

Comprehensive expression analysis of L-dopa decarboxylase and established neuroendocrine markers in neoadjuvant hormone-treated versus varying Gleason grade prostate tumors.

Current hormone withdrawal therapies used for treatment of advanced prostate cancer lead to androgen-independent tumor growth. Increased prostatic neuroendocrine (NE) cell density has been implicated in promoting progression of prostate cancer, but the process by which this occurs remains unclear. The aim of this study was to determine whether there is an association of increased NE differentiation with neoadjuvant hormone therapy and Gleason grade. Using adjacently sectioned tissue microarrays, the expression profile of novel and known NE markers were monitored. L-Dopa decarboxylase (DDC), a catecholamine synthesis enzyme and androgen receptor (AR) coregulator protein, was identified as an additional NE marker of prostate cancer. Immunohistochemical analysis of DDC with the established NE markers, chromogranin A and bombesin, revealed a significant increase in NE differentiation after 6 months of hormone therapy and after progression to androgen independence but no apparent correlation with Gleason grade. In addition, dual immunofluorescence analysis revealed that approximately 55% of the mixed population of DDC- and chromogranin A-expressing NE cells continue to express AR. Taken together, these results suggest that the increase of NE differentiation in prostate cancers depends specifically on duration of hormone therapy. This increase may be due to the transdifferentiation of AR-expressing epithelial-derived adenocarcinoma cells into an NE cell phenotype.

Demonstration of upregulated H2 relaxin mRNA expression during neuroendocrine differentiation of LNCaP prostate cancer cells and production of biologically active mammalian recombinant 6 histidine-tagged H2 relaxin.

Relaxin was recently implicated as a regulator of breast and prostate cancer progression. We characterized upregulated H2 relaxin gene expression during neuroendocrine differentiation of the human prostate cancer model, LNCaP. To examine the impact of relaxin on host cells associated with prostatic adenocarcinomas, we generated recombinant 6 His-tagged relaxin (RLXH) in a mammalian expression system. This immunoreactive and biologically active relaxin preparation was used to screen a variety of cell types for cAMP responsiveness. Of the cell types screened, none was more responsive to RLXH than the well-characterized monocyte/macrophage cell line THP-1.

PTEN loss promotes mitochondrially dependent type II Fas-induced apoptosis via PEA-15.

Two distinct biochemical signals are delivered by the CD95/Fas death receptor. The molecular basis for the differential mitochondrially independent (type I) and mitochondrially dependent (type II) Fas apoptosis pathways is unknown. By analyzing 24 Fas-sensitive tumor lines, we now demonstrate that expression/activity of the PTEN tumor suppressor strongly correlates with the distinct Fas signals. PTEN loss-of-function and gain-of-function studies demonstrate the ability to interconvert between type I and type II Fas pathways. Importantly, from analyses of Bcl-2 transgenic Pten(+/-) mice, Pten haploinsufficiency converts Fas-induced apoptosis from a Bcl-2-independent to a Bcl-2-sensitive response in primary thymocytes and activated T lymphocytes. We further show that PTEN influences Fas signaling, at least in part, by regulating PEA-15 phosphorylation and activity that, in turn, regulate the ability of Bcl-2 to suppress Fas-induced apoptosis. Thus, PTEN is a key molecular rheostat that determines whether a cell dies by a mitochondrially independent type I versus a mitochondrially dependent type II apoptotic pathway upon Fas stimulation.

The impact of diet and micronutrient supplements on the expression of neuroendocrine markers in murine Lady transgenic prostate.

BACKGROUND: Neuroendocrine (NE) differentiation (NED) in prostate cancer (PCa) is associated with morbidity and death; however, the underlying cause(s) promoting NED in PCa have yet to be determined. In this study, we examined the effect of both diet and micronutrient supplementation on the expression of NE markers using the Lady (12T-10) transgenic model of PCa. Lady (12T-10) transgenic animals develop advanced adenocarcinoma with NE characteristics that exhibits metastases in approximately 80% of cases. In this model a high fat diet has been shown to increase the severity of disease, while the use of micronutrients can inhibit this progression. METHODS: In this study we used immunohistochemical analysis to determine expression of the NE markers: chromogranin A (CgA), neuron-specific enolase (NSE), bombesin, parathyroid hormone-related peptide (PTHrP), neurotensin and serotonin in prostates of PCa-bearing Lady (12T-10) mice. RESULTS: High fat diet was correlated with significantly elevated expression of CgA and serotonin in prostate tissue of Lady (12T-10) mice. Addition of micronutrients to the control and high fat diet reproducibly elevated PTHrP and bombesin expression and suppressed NSE expression, while prostate tissue from the control diet supplemented with micronutrients exhibited significantly lower numbers of calcitonin- and neurotensin-positive cells. CONCLUSIONS: These results highlight the importance of dietary control in management of disease and identify differential changes in NE marker expression, which may be diagnostically viable in monitoring the impact of therapies on disease status.