CAR's made it to the pancreas

Despite intensive treatment, pancreatic adenocarcinoma still has the worst prognosis among all malignancies. Using clinically relevant models, we demonstrated the therapeutic efficacy of adoptively transferred T cells engineered with a carcinoembryonic antigen (CEA) and ERBB2-specific chimeric antigen receptor against pancreatic carcinoma. Targeting CD24, a putative cancer stem cell antigen expressed by a minority of carcinoma cells, was likewise effective

Delayed recompression for decompression sickness: retrospective analysis.

Most cases of decompression sickness (DCS) occur soon after surfacing, with 98% within 24 hours. Recompression using hyperbaric chamber should be administrated as soon as feasible in order to decrease bubble size and avoid further tissue injury. Unfortunately, there may be a significant time delay from surfacing to recompression. The time beyond which hyperbaric treatment is non effective is unclear. The aims of the study were first to evaluate the effect of delayed hyperbaric treatment, initiated more than 48 h after surfacing for DCS and second, to evaluate the different treatment protocols.From January 2000 to February 2014, 76 divers had delayed hyperbaric treatment (≥48 h) for DCS in the Sagol center for Hyperbaric medicine and Research, Assaf-Harofeh Medical Center, Israel. Data were collected from their medical records and compared to data of 128 patients treated earlier than 48 h after surfacing at the same hyperbaric institute.There was no significant difference, as to any of the baseline characteristics, between the delayed and early treatment groups. With respect to treatment results, at the delayed treatment divers, complete recovery was achieved in 76% of the divers, partial recovery in 17.1% and no improvement in 6.6%. Similar results were achieved when treatment started early, where 78% of the divers had complete recovery, 15.6% partial recovery and 6.2% no recovery. Delayed hyperbaric treatment using US Navy Table 6 protocol trended toward a better clinical outcome yet not statistically significant (OR=2.786, CI95%[0.896-8.66], p=0.07) compared to standard hyperbaric oxygen therapy of 90 minutes at 2 ATA, irrespective of the symptoms severity at presentation.Late recompression for DCS, 48 hours or more after surfacing, has clinical value and when applied can achieve complete recovery in 76% of the divers. It seems that the preferred hyperbaric treatment protocol should be based on US Navy Table 6

Redirected T Cells That Target Pancreatic Adenocarcinoma Antigens Eliminate Tumors and Metastases in Mice

BACKGROUND & AIMS: Pancreatic adenocarcinoma (PAC) is often diagnosed at an advanced and inoperable stage, and standard systemic treatments are generally ineffective. We investigated the effects of adoptive transfer of tumor-specific T cells that express chimeric antibody-based receptors (CAR) to mice with primary and metastatic PAC xenografts. METHODS: Human effector T cells were genetically modified to express CAR against Her2/neu or CD24, a putative PAC stem cell antigen. The antitumor reactivity of the engineered T cells (T-bodies) was evaluated in SCID mice with different PAC xenografts. A total of 1 x 10(7) T-bodies were injected via the tail vein or directly administered to the subcutaneous tumor on 3 or 4 alternating days. Mice were then given twice-daily intraperitoneal injections of interleukin-2 for 10 days. RESULTS: Intratumor injection of human CD24 and Her2/neu-specific T-bodies completely eliminated the tumors from most animals. Intravenous injection of T-bodies reduced tumor size and prolonged survival of mice with orthotopically transplanted tumors; more than 50% of animals appeared to be disease-free more than 2 months later. Additional systemic administration of T-bodies 8 weeks after the initial injection eliminated primary tumors, along with liver and draining lymph node metastases. A single administration of the Her2/neuspecific T-bodies prolonged the survival of mice with tumors in which most of the cells expressed the target antigen. In contrast, the CD24-specific T-bodies prolonged survival of mice in which only a subpopulation of the tumor cells expressed the antigen. CONCLUSIONS: CAR-redirected T cells stop growth and metastasis of PAC xenografts in mice. T-bodies specific to CD24, a putative cancer stem cell antigen, were effective against PAC xenografts that had only a subset of antigen-expressing cells

Flow chart describing study groups.

<p><b>*</b> The divers were divided into early recompression group (<48 hours) and delayed recompression group (≥48 hours from surfacing). The delayed group was further divided by the time to symptoms onset.</p

Clinical outcome of the early and delayed groups.

<p>* Clinical outcome was not significantly different between the delayed and early groups (<i>χ</i>² = 0.093, p = 0.955). Clinical outcome was divided to an ordinal variable of 3 values as shown. Graph values shown in %.</p

Published studies in the last decades showing the association between clinical outcome and time to recompression.

<p>Notice time to recompression was calculated from symptoms onset in most cases.</p><p>Most studies reports include very small cohorts, only few divers treated later than 24 hours.</p><p>Published studies in the last decades showing the association between clinical outcome and time to recompression.</p

Clinical outcome by treatment table divided to severity subgroups.

<p>* Divers with moderate symptoms treated with US Navy Table 6 had 84.6% complete recovery compared to 71.4% in divers treated with 2 ATA table for 90 minutes (<i>χ</i>² = 6.26, df = 2, p = 0.04). Note US Navy Table 6 results in a trend to better outcome irrespective of severity of symptoms, yet in mild and moderate symptoms, it did not reach statistical significance.</p

Symptoms distribution: Early (<48 hours) and Delayed (≥48 hours) recompression groups’ symptoms distribution.

<p>Symptoms distribution: Early (<48 hours) and Delayed (≥48 hours) recompression groups’ symptoms distribution.</p