Retroperitoneal Transdiaphragmatic Robotic-Assisted Laparoscopic Resection of a Left Thoracolumbar Neurofibroma

ObjectiveRobotic technology has been used in a variety of surgical procedures for its 3D magnification and precision. Minimally invasive techniques have already become common in neurosurgery; however, robotic-assisted procedures in neurosurgery are still a relatively new frontier. This report describes the first use of robotic technology to resect a left thoracolumbar neurofibroma.Case reportA 19-year-old male with a family history of neurofibromatosis was diagnosed with a suspected 3-cm x 4-cm neurofibroma in the T12-L1 left paraspinal area. His only complaint was back pain requiring narcotic analgesics. He had no other findings on physical examination or laboratory/radiologic workup.MethodsAfter consulting urologic robotic surgeons, it was agreed to use the da Vinci robot (Intuitive Surgical, Sunnyvale, CA) for the resection of this mass. Following retroperitoneal laparoscopic access, the urologic surgeons opened the diaphragm and began the initial mobilization of the mass laparoscopically. The robot was docked, and the neurosurgeon operated the robot at the console to resect the mass from its nerve origin. There were no complications, and the mass, a confirmed neurofibroma, was completely removed. The patient was discharged on postoperative day 2; his back pain resolved, requiring no analgesia by the end of the first postoperative week.ConclusionThis case provides early evidence that robotic assistance can be successfully used for the resection of a paraspinal neurofibroma

Masses, radii, and orbits of small Kepler planets : The transition from gaseous to rocky planets

We report on the masses, sizes, and orbits of the planets orbiting 22 Kepler stars. There are 49 planet candidates around these stars, including 42 detected through transits and 7 revealed by precise Doppler measurements of the host stars. Based on an analysis of the Kepler brightness measurements, along with high-resolution imaging and spectroscopy, Doppler spectroscopy, and (for 11 stars) asteroseismology, we establish low false-positive probabilities (FPPs) for all of the transiting planets (41 of 42 have an FPP under 1%), and we constrain their sizes and masses. Most of the transiting planets are smaller than three times the size of Earth. For 16 planets, the Doppler signal was securely detected, providing a direct measurement of the planet's mass. For the other 26 planets we provide either marginal mass measurements or upper limits to their masses and densities; in many cases we can rule out a rocky composition. We identify six planets with densities above 5 g cm-3, suggesting a mostly rocky interior for them. Indeed, the only planets that are compatible with a purely rocky composition are smaller than 2 R ⊕. Larger planets evidently contain a larger fraction of low-density material (H, He, and H2O).Peer reviewedFinal Accepted Versio

Quercetin abrogates chemoresistance in melanoma cells by modulating ΔNp73

<p>Abstract</p> <p>Background</p> <p>The alkylating agent Dacarbazine (DTIC) has been used in the treatment of melanoma for decades, but when used as a monotherapy for cancer only moderate response rates are achieved. Recently, the clinical use of Temozolomide (TMZ) has become the more commonly used analog of DTIC-related oral agents because of its greater bioavailability and ability to cross the blood brain barrier. The response rates achieved by TMZ are also unsatisfactory, so there is great interest in identifying compounds that could be used in combination therapy. We have previously demonstrated that the bioflavonoid quercetin (Qct) promoted a p53-mediated response and sensitized melanoma to DTIC. Here we demonstrate that Qct also sensitizes cells to TMZ and propose a mechanism that involves the modulation of a truncated p53 family member, ΔNp73.</p> <p>Methods</p> <p>DB-1 melanoma (p53 wildtype), and SK Mel 28 (p53 mutant) cell lines were treated with TMZ (400 μM) for 48 hrs followed by Qct (75 μM) for 24 hrs. Cell death was determined by Annexin V-FITC staining and immunocytochemical analysis was carried out to determine protein translocation.</p> <p>Results</p> <p>After treatment with TMZ, DB-1 cells demonstrated increased phosphorylation of Ataxia telangiectasia mutated (ATM) and p53. However, the cells were resistant to TMZ-induced apoptosis and the resistance was associated with an increase in nuclear localization of ΔNp73. Qct treatment in combination with TMZ abolished drug insensitivity and caused a more than additive induction of apoptosis compared to either treatment alone. Treatment with Qct, caused redistribution of ΔNp73 into the cytoplasm and nucleus, which has been associated with increased p53 transcriptional activity. Knockdown of ΔNp73 restored PARP cleavage in the TMZ treated cells, confirming its anti-apoptotic role. The response to treatment was predominantly p53 mediated as the p53 mutant SK Mel 28 cells showed no significant enhancement of apoptosis.</p> <p>Conclusion</p> <p>This study demonstrates that Qct can sensitize cells to TMZ and that the mechanisms of sensitization involve modulation of p53 family members.</p

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

A sub-Mercury-sized exoplanet

Since the discovery of the first exoplanet we have known that other planetary systems can look quite unlike our own. However, until recently we have only been able to probe the upper range of the planet size distribution. The high precision of the Kepler space telescope has allowed us to detect planets that are the size of Earth and somewhat smaller, but no previous planets have been found that are smaller than those we see in our own Solar System. Here we report the discovery of a planet significantly smaller than Mercury. This tiny planet is the innermost of three planets that orbit the Sun-like host star, which we have designated Kepler-37. Owing to its extremely small size, similar to that of Earth's Moon, and highly irradiated surface, Kepler-37b is probably a rocky planet with no atmosphere or water, similar to Mercury.Comment: Accepted and published in Nature (2013 Feb 28). This is the submitted version of paper, merged with the Supplementary Informatio

Masses, radii, and orbits of small Kepler planets: the transition from gaseous to rocky planets

We report on the masses, sizes, and orbits of the planets orbiting 22 Kepler stars. There are 49 planet candidates around these stars, including 42 detected through transits and 7 revealed by precise Doppler measurements of the host stars. Based on an analysis of the Kepler brightness measurements, along with high-resolution imaging and spectroscopy, Doppler spectroscopy, and (for 11 stars) asteroseismology, we establish low false-positive probabilities (FPPs) for all of the transiting planets (41 of 42 have an FPP under 1%), and we constrain their sizes and masses. Most of the transiting planets are smaller than three times the size of Earth. For 16 planets, the Doppler signal was securely detected, providing a direct measurement of the planet's mass. For the other 26 planets we provide either marginal mass measurements or upper limits to their masses and densities; in many cases we can rule out a rocky composition. We identify six planets with densities above 5 g cm-3, suggesting a mostly rocky interior for them. Indeed, the only planets that are compatible with a purely rocky composition are smaller than 2 R ⊕. Larger planets evidently contain a larger fraction of low-density material (H, He, and H2O)

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Retroperitoneal transdiaphragmatic robotic-assisted laparoscopic resection of a left thoracolumbar neurofibroma.

ObjectiveRobotic technology has been used in a variety of surgical procedures for its 3D magnification and precision. Minimally invasive techniques have already become common in neurosurgery; however, robotic-assisted procedures in neurosurgery are still a relatively new frontier. This report describes the first use of robotic technology to resect a left thoracolumbar neurofibroma.Case reportA 19-year-old male with a family history of neurofibromatosis was diagnosed with a suspected 3-cm x 4-cm neurofibroma in the T12-L1 left paraspinal area. His only complaint was back pain requiring narcotic analgesics. He had no other findings on physical examination or laboratory/radiologic workup.MethodsAfter consulting urologic robotic surgeons, it was agreed to use the da Vinci robot (Intuitive Surgical, Sunnyvale, CA) for the resection of this mass. Following retroperitoneal laparoscopic access, the urologic surgeons opened the diaphragm and began the initial mobilization of the mass laparoscopically. The robot was docked, and the neurosurgeon operated the robot at the console to resect the mass from its nerve origin. There were no complications, and the mass, a confirmed neurofibroma, was completely removed. The patient was discharged on postoperative day 2; his back pain resolved, requiring no analgesia by the end of the first postoperative week.ConclusionThis case provides early evidence that robotic assistance can be successfully used for the resection of a paraspinal neurofibroma