Activated lymphocyte recruitment into the tumor microenvironment following preoperative sipuleucel-T for localized prostate cancer.

BackgroundSipuleucel-T is a US Food and Drug Administration-approved immunotherapy for asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). Its mechanism of action is not fully understood. This prospective trial evaluated the direct immune effects of systemically administered sipuleucel-T on prostatic cancer tissue in the preoperative setting.MethodsPatients with untreated localized prostate cancer were treated on an open-label Phase II study of sipuleucel-T prior to planned radical prostatectomy (RP). Immune infiltrates in RP specimens (posttreatment) and in paired pretreatment biopsies were evaluated by immunohistochemistry (IHC). Correlations between circulating immune response and IHC were assessed using Spearman rank order.ResultsOf the 42 enrolled patients, 37 were evaluable. Adverse events were primarily transient, mild-to-moderate and infusion related. Patients developed T cell proliferation and interferon-γ responses detectable in the blood following treatment. Furthermore, a greater-than-three-fold increase in infiltrating CD3(+), CD4(+) FOXP3(-), and CD8(+) T cells was observed in the RP tissues compared with the pretreatment biopsy (binomial proportions: all P < .001). This level of T cell infiltration was observed at the tumor interface, and was not seen in a control group consisting of 12 concurrent patients who did not receive any neoadjuvant treatment prior to RP. The majority of infiltrating T cells were PD-1(+) and Ki-67(+), consistent with activated T cells. Importantly, the magnitude of the circulating immune response did not directly correlate with T cell infiltration within the prostate based upon Spearman's rank order correlation.ConclusionsThis study is the first to demonstrate a local immune effect from the administration of sipuleucel-T. Neoadjuvant sipuleucel-T elicits both a systemic antigen-specific T cell response and the recruitment of activated effector T cells into the prostate tumor microenvironment

The critically ill patient after hepatobiliary surgery

BACKGROUND: We analyzed the causes and results of utilization of critical care services in the special care unit in patients after surgical procedures performed by the hepatobiliary surgical service during a 23-month period. RESULTS: Thirty-two of 537 patients (6.0%) required postoperative admission to the special care unit. Twenty-one patients were admitted directly from operating room or from recovery room because of inability to wean from ventilator (n = 10), hypovolemic shock (n = 4), myocardial ischemia or infarction (n = 2), sepsis (n = 2), upper gastrointestinal bleeding (n = 2), and acute renal failure (n =1). Eleven postoperative patients were admitted from floor care for respiratory failure (n = 4), cardiac dysrhythmia or infarction (n = 4), sepsis (n = 2), and upper gastrointestinal bleeding (n = 1). Thirty-eight per cent of patients (n = 12) admitted to the special care unit after surgery died. By multivariate analysis, total postoperative stay in the special care unit that was greater than median total duration of stay of 4.5 days was the only independent predictor of mortality (P = 0.041). CONCLUSIONS: Respiratory failure was the predominant component of all complications after hepatobiliary surgery. No clinically useful predictors of eventual outcome could be identified

Direct-detection Free-space Laser Transceiver Test-bed

NASA Goddard Space Flight Center is developing a direct-detection free-space laser communications transceiver test bed. The laser transmitter is a master-oscillator power amplifier (MOPA) configuration using a 1060 nm wavelength laser-diode with a two-stage multi-watt Ytterbium fiber amplifier. Dual Mach-Zehnder electro-optic modulators provide an extinction ratio greater than 40 dB. The MOPA design delivered 10-W average power with low-duty-cycle PPM waveforms and achieved 1.7 kW peak power. We use pulse-position modulation format with a pseudo-noise code header to assist clock recovery and frame boundary identification. We are examining the use of low-density-parity-check (LDPC) codes for forward error correction. Our receiver uses an InGaAsP 1 mm diameter photocathode hybrid photomultiplier tube (HPMT) cooled with a thermo-electric cooler. The HPMT has 25% single-photon detection efficiency at 1064 nm wavelength with a dark count rate of 60,000/s at -22 degrees Celsius and a single-photon impulse response of 0.9 ns. We report on progress toward demonstrating a combined laser communications and ranging field experiment

Melanocortin receptors in GtoPdb v.2021.3

Melanocortin receptors (provisional nomenclature as recommended by NC-IUPHAR [41]) are activated by members of the melanocortin family (α-MSH, β-MSH and γ-MSH forms; δ form is not found in mammals) and adrenocorticotrophin (ACTH). Endogenous antagonists include agouti and agouti-related protein. ACTH(1-24) was approved by the US FDA as a diagnostic agent for adrenal function test, whilst NDP-MSH was approved by EMA for the treatment of erythropoietic protoporphyria. Several synthetic melanocortin receptor agonists are under clinical development

Recipient Morbidity After Living and Deceased Donor Liver Transplantation: Findings from the A2ALL Retrospective Cohort Study †

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72284/1/j.1600-6143.2008.02440.x.pd

Melanocortin receptors in GtoPdb v.2023.1

Melanocortin receptors (provisional nomenclature as recommended by NC-IUPHAR [41]) are activated by members of the melanocortin family (α-MSH, β-MSH and γ-MSH forms; δ form is not found in mammals) and adrenocorticotrophin (ACTH). Endogenous antagonists include agouti and agouti-related protein. ACTH(1-24) was approved by the US FDA as a diagnostic agent for adrenal function test. setmelanotide was approved by the US FDA for weight management in patients with POMC, PCSK1 or LEPR defiency, bremelanotide was approved by the US FDA for generalized hypoactive sexual desire disorder in premenopausal women, and NDP-MSH (afamelanotide) was approved by the EMA for the treatment of erythropoietic protoporphyria. Several synthetic melanocortin receptor agonists are under clinical development