Pituitary metastasis: a rare condition

Tumor metastasis to the pituitary gland is a rare, not well-documented and life-threatening condition associated with a shortened life span. A better understanding of its clinical manifestations could lead to earlier diagnosis, appropriate therapy and potentially improving quality of life. Therefore, we retrospectively studied the charts of patients with pituitary metastases who were treated at the City of Hope National Medical Center (Duarte, CA) from 1984 to 2018. We reviewed and analyzed tumor origin, primary pituitary clinical manifestation, duration between primary tumor diagnosis and pituitary metastasis, type of treatment and patient survival. A total of 11 patients were identified with a mean age of 59.2 years and median survival following the diagnosis of metastasis of 10 months. Breast cancer and lymphoma were the most common primary origins in these cases, and diabetes insipidus and panhypopituitarism were the most common clinical manifestations of their metastasis. We also compared our results with reports in the literature published between 1957 and 2018. A total 289 patients with pituitary metastasis have been reported in the literature. Breast cancer was the most frequent primary origin of the metastasis, and visual symptoms were the most common primary manifestation. The posterior part of the pituitary is more susceptible than the anterior to metastasis. Pituitary metastasis may occur as a consequence of successful primary tumor treatment prolonging the chance of seeding. Future studies are needed to determine the molecular mechanism of metastasis to the pituitary

Early Changes in Tumor Perfusion from T1-Weighted Dynamic Contrast-Enhanced MRI following Neural Stem Cell-Mediated Therapy of Recurrent High-Grade Glioma Correlate with Overall Survival

Background. The aim of this study was to correlate T1-weighted dynamic contrast-enhanced MRI- (DCE-MRI-) derived perfusion parameters with overall survival of recurrent high-grade glioma patients who received neural stem cell- (NSC-) mediated enzyme/prodrug gene therapy. Methods. A total of 12 patients were included in this retrospective study. All patients were enrolled in a first-in-human study (NCT01172964) of NSC-mediated therapy for recurrent high-grade glioma. DCE-MRI data from all patients were collected and analyzed at three time points: MRI#1—day 1 postsurgery/treatment, MRI#2— day 7 ± 3 posttreatment, and MRI#3—one-month follow-up. Plasma volume (Vp), permeability (Ktr), and leakage (λtr) perfusion parameters were calculated by fitting a pharmacokinetic model to the DCE-MRI data. The contrast-enhancing (CE) volume was measured from the last dynamic phase acquired in the DCE sequence. Perfusion parameters and CE at each MRI time point were recorded along with their relative change between MRI#2 and MRI#3 (Δ32). Cox regression was used to analyze patient survival. Results. At MRI#1 and at MRI#3, none of the parameters showed a significant correlation with overall survival (OS). However, at MRI#2, CE and λtr were significantly associated with OS (p<0.05). The relative λtr and Vp from timepoint 2 to timepoint 3 (Δ32λtr and Δ32Vp) were each associated with a higher hazard ratio (p<0.05). All parameters were highly correlated, resulting in a multivariate model for OS including only CE at MRI#2 and Δ32Vp, with an R2 of 0.89. Conclusion. The change in perfusion parameter values from 1 week to 1 month following NSC-mediated therapy combined with contrast-enhancing volume may be a useful biomarker to predict overall survival in patients with recurrent high-grade glioma

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

Early Changes in Tumor Perfusion from T1-Weighted Dynamic Contrast-Enhanced MRI following Neural Stem Cell-Mediated Therapy of Recurrent High-Grade Glioma Correlate with Overall Survival

Background. The aim of this study was to correlate T1-weighted dynamic contrast-enhanced MRI- (DCE-MRI-) derived perfusion parameters with overall survival of recurrent high-grade glioma patients who received neural stem cell- (NSC-) mediated enzyme/prodrug gene therapy. Methods. A total of 12 patients were included in this retrospective study. All patients were enrolled in a first-in-human study (NCT01172964) of NSC-mediated therapy for recurrent high-grade glioma. DCE-MRI data from all patients were collected and analyzed at three time points: MRI#1—day 1 postsurgery/treatment, MRI#2— day 7 ± 3 posttreatment, and MRI#3—one-month follow-up. Plasma volume (Vp), permeability (Ktr), and leakage (λtr) perfusion parameters were calculated by fitting a pharmacokinetic model to the DCE-MRI data. The contrast-enhancing (CE) volume was measured from the last dynamic phase acquired in the DCE sequence. Perfusion parameters and CE at each MRI time point were recorded along with their relative change between MRI#2 and MRI#3 (Δ32). Cox regression was used to analyze patient survival. Results. At MRI#1 and at MRI#3, none of the parameters showed a significant correlation with overall survival (OS). However, at MRI#2, CE and λtr were significantly associated with OS (p<0.05). The relative λtr and Vp from timepoint 2 to timepoint 3 (Δ32λtr and Δ32Vp) were each associated with a higher hazard ratio (p<0.05). All parameters were highly correlated, resulting in a multivariate model for OS including only CE at MRI#2 and Δ32Vp, with an R2 of 0.89. Conclusion. The change in perfusion parameter values from 1 week to 1 month following NSC-mediated therapy combined with contrast-enhancing volume may be a useful biomarker to predict overall survival in patients with recurrent high-grade glioma

Mid-Infrared Plasmonic Excitation in Indium Tin Oxide Microhole Arrays

Transparent conducting oxides (TCOs) are emerging as possible alternative constituent materials to replace noble metals such as silver and gold for low-loss plasmonic applications in the near-infrared (NIR) and mid-infrared (MIR) regimes. In particular, TCO-based nanostructures are extensively investigated for biospectroscopy exploiting their surface-enhanced infrared absorption (SEIRA). The latter enhances the absorption from vibrational and rotational modes of nearby biomolecules, making TCO nanostructures a promising candidate for IR sensing applications. Nevertheless, in order to produce inexpensive devices for lab-on-a-chip diagnostics, it would be favorable to achieve surface-enhanced infrared absorption with very simple microstructures not requiring nanosize control. In this work, we attempt to demonstrate a SEIRA effect with the least challenging fabrication, μm-scale instead of nm-scale, by tailoring both device design and charge density of the indium tin oxide (ITO) film. We show that microperiodic hole arrays in a ITO film are able to produce SEIRA via grating coupling. Such a study opens the way for innovative and disrupting biosensing devices

Characterization of Arginase Expression in Glioma-Associated Microglia and Macrophages

<div><p>Microglia (MG) and macrophages (MPs) represent a significant component of the inflammatory response to gliomas. When activated, MG/MP release a variety of pro-inflammatory cytokines, however, they also secrete anti-inflammatory factors that limit their cytotoxic function. The balance between pro and anti-inflammatory functions dictates their antitumor activity. To evaluate potential variations in MG and MP function in gliomas, we isolated these cells (and other Gr1⁺ cells) from intracranial GL261 murine gliomas by FACS and evaluated their gene expression profiles by microarray analysis. As expected, arginase 1 (Arg1, M2 marker) was highly expressed by tumor-associated Gr1⁺, MG and MP. However, in contrast to MP and Gr1⁺ cells that expressed Arg1 shortly after tumor trafficking, Arg1 expression in MG was delayed and occurred in larger tumors. Interestingly, depletion of MPs in tumors did not prevent MG polarization, suggesting direct influence of tumor-specific factors on MG Arg1 upregulation. Finally, Arg1 expression was confirmed in human GBM samples, but most Arg1⁺ cells were neutrophils and not MPs. These findings confirm variations in tumor MG and MP polarization states and its dependency on tumor microenvironmental factors.</p></div