Immune Reactivity and Pseudoprogression or Tumor Flare in a Serially Biopsied Neuroendocrine Patient Treated with the Epigenetic Agent RRx-001.

Neuroendocrine tumors (NETs) are grouped together as a single class on the basis of histologic appearance, immunoreactivity for the neuroendocrine markers chromogranin A and synaptophysin, and potential secretion of hormones, neurotransmitters, neuromodulators and neuropeptides. Nevertheless, despite these common characteristics, NETs differ widely in terms of their natural histories: high-grade NETs are clinically aggressive and, like small cell lung cancer, which they most closely resemble, tend to respond to cisplatin and etoposide. In contrast, low-grade NETs, which as a rule progress and behave indolently, do not. In either case, the treatment strategy, apart from potentially curative surgical resection, is very poorly defined. This report describes the case of a 28-year-old white male with a diagnosis of high-grade NET of undetermined primary site metastatic to the lymph nodes, skin and paraspinal soft tissues, treated with the experimental anticancer agent RRx-001, in the context of a phase II clinical trial called TRIPLE THREAT (NCT02489903); serial sampling of tumor material through repeat biopsies demonstrated an intratumoral inflammatory response, including the amplification of infiltrating T cells, which correlated with clinical and symptomatic benefit. This case suggests that pseudoprogression or RRx-001-induced enlargement of tumor lesions, which has been previously described for several RRx-001-treated patients, is the result of tumoral lymphocyte infiltration

Probable Gravitational Microlensing towards the Galatic Bulge

The MACHO project carries out regular photometric monitoring of millions of stars in the Magellanic Clouds and Galactic Bulge, to search for very rare gravitational microlensing events due to compact objects in the galactic halo and disk. A preliminary analysis of one field in the Galactic Bulge, containing {$\sim430,000$} stars observed for 190 days, reveals four stars which show clear evidence for brightenings which are time-symmetric, achromatic in our two passbands, and have shapes consistent with gravitational microlensing. This is significantly higher than the $\sim 1$ event expected from microlensing by known stars in the disk. If all four events are due to microlensing, a 95\% confidence lower limit on the optical depth towards our bulge field is $1.3 \times 10^{-6}$, and a ``best fit" value is $\tau \approx 1.6 \times 10^{-6}/\epsilon$,where $\epsilon$ is the detection efficiency of the experiment, and $\epsilon < 0.4$. If the true optical depth is close to the ``best fit" value, possible explanations include a ``maximal" disk which accounts for most of the galactic circular velocity at the solar radius, a halo which is centrally concentrated, or bulge-bulge microlensing.Comment: submitted to Astrophysical Journal Letters, 10 pages text as uuencoded compressed PostScript, 5 figures and paper also available via anonymous ftp from merlin.anu.edu.au in /pub/kcf/mach

Searching for periodicities in the MACHO light curve of LMC X-2

Using the exceptional long-term monitoring capabilities of the MACHO project, we present here the optical history of LMC X-2 for a continuous 6-yr period. These data were used to investigate the previously claimed periodicities for this source of 8.15 h and 12.54 d : we find upper amplitude limits of 0.10 mag and 0.09 mag, respectively.Comment: 4 pages, 4 figures. Minor changes, including title. MNRAS, in pres