Effects of Progressive Additional Lenses on Binocular Vision in Children with Pseudophakia

Binocular vision may be compromised in children after unilateral cataract surgery because the distances at which clear vision is present are different for the two eyes. We believe that wearing progressive additional lenses can be effective in improving the binocular vision in children with pseudophakia.
Case Rep Ophthalmol 2018;9:304–309

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Establishment of adoptive cell therapy with tumor infiltrating lymphocytes for non-small cell lung cancer patients

Abstract

Adoptive cell therapy (ACT) of tumor infiltration lymphocytes (TIL) yields promising clinical results in metastatic melanoma patients, who failed standard treatments. Due to the fact that metastatic lung cancer has proven to be susceptible to immunotherapy and possesses a high mutation burden, which makes it responsive to T cell attack, we explored the feasibility of TIL ACT in non-small cell lung cancer (NSCLC) patients. Multiple TIL cultures were isolated from tumor specimens of five NSCLC patients undergoing thoracic surgery. We were able to successfully establish TIL cultures by various methods from all patients within an average of 14 days. Fifteen lung TIL cultures were further expanded to treatment levels under good manufacturing practice conditions and functionally and phenotypically characterized. Lung TIL expanded equally well as 103 melanoma TIL obtained from melanoma patients previously treated at our center, and had a similar phenotype regarding PD1, CD28, and 4-1BB expressions, but contained a higher percent of CD4 T cells. Lung carcinoma cell lines were established from three patients of which two possessed TIL cultures with specific in vitro anti-tumor reactivity. Here, we report the successful pre-clinical production of TIL for immunotherapy in the lung cancer setting, which may provide a new treatment modality for patients with metastatic NSCLC. The initiation of a clinical trial is planned for the near future.

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Comparison of Duke Activity Status Index with cardiopulmonary exercise testing in cancer patients

Abstract

Purpose

The Duke Activity Status Index (DASI), a patient-administered questionnaire, is used to quantify functional capacity in patients undergoing cancer surgery.

Methods

This retrospective cohort study assessed whether the DASI was accurate in predicting peak oxygen consumption (pVO₂) that was objectively measured using cardiopulmonary exercise testing (CPET) in 43 consecutive patients scheduled for elective major cancer surgery at a tertiary cancer centre. The primary outcome measured the limits of agreement between DASI-predicted pVO₂ and actual measured pVO₂.

Results

The study population was elderly (median 63 years, interquartile range 18), 58% were male, with the majority having intraabdominal cancer surgery. Although the DASI scores were statistically related to the measured pVO₂ (N = 43, adjusted R² = 0.20, p = 0.002), both the bias (8 ml kg^− 1 min^− 1) and 95% limits of agreement (19.5 to − 3.4 ml kg^− 1 min^− 1) between the predicted and measured pVO₂ were large. Using some of the individual components, recalibrating the intercept and regression coefficient of the total DASI score did not substantially improve its ability to predict the measured pVO₂.

Conclusion

In summary, both the limits of agreement and bias between the measured and DASI-predicted pVO₂ were substantial. The DASI-predicted pVO₂ based on patient's assessment of their functional status could not be considered a reliable surrogate of measured pVO₂ during CPET for the population of patients pending major cancer surgery and cannot, therefore, be used as a triage tool for referral to CPET centres for objective risk assessment.

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AJCC-8ed nodal staging does not predict outcomes in surgically managed HPV-associated oropharyngeal cancer

Publication date: July 2018
Source:Oral Oncology, Volume 82
Author(s): Kealan C. Hobelmann, Michael C. Topf, Voichita Bar-Ad, Adam J. Luginbuhl, William M. Keane, Joseph M. Curry, David M. Cognetti
ObjectiveTo assess the pathological outcomes of surgically-managed human papillomavirus (HPV) positive oropharyngeal squamous cell carcinoma (OPSCC) using the 8th Edition of the American Joint Committee on Cancer Staging Manual (AJCC-8ed).Materials and methodsA retrospective review was conducted of 156 patients with previously untreated OPSCC who underwent primary TORS between March 2010 and February 2015 to evaluate the impact of the new AJCC-8ed pathologic staging system. Only patients who had complete pathologic staging with neck dissection and at least 2 years of follow-up records or disease recurrence within 2 years were included for analysis.Results and conclusionsOf the 156 patients, 116 patients had neck dissections and adequate follow-up data. There were 10 total recurrences, including 2 regional recurrences and 1 local recurrence. Lymph node size, number of positive lymph nodes, and presence of any positive nodes were not associated with recurrence for HPV-positive patients. The presence of extranodal extension approached significance. Pathologic N-stage was not predictive of recurrence under the AJCC-7ed or the AJCC-8ed systems. Cancer staging under the AJCC-8ed, but not the AJCC-7ed system was significantly associated with recurrence. In conclusion, pathologic node status as defined in the AJCC-8ed pathologic staging system does not appear to drive prognosis for surgically managed patients. While the new AJCC-8ed staging is an improvement in prognostication, the use of T-stage alone is still a better predictor of recurrence. TORS with adjuvant therapy determined by pathologic findings provides excellent locoregional control for HPV-positive OPSCC.



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Gene signatures and expression of miRNAs associated with efficacy of panitumumab in a head and neck cancer phase II trial

Publication date: July 2018
Source:Oral Oncology, Volume 82
Author(s): Marco Siano, Vittoria Espeli, Nicolas Mach, Paolo Bossi, Lisa Licitra, Michele Ghielmini, Milo Frattini, Silvana Canevari, Loris De Cecco
ObjectivePlatinum-based chemotherapy plus the anti-EGFR monoclonal antibody (mAb) cetuximab is used to treat recurrent/metastatic (RM) head-neck squamous cell carcinoma (HNSCC). Recently, we defined Cluster3 gene-expression signature as a potential predictor of favorable progression-free survival (PFS) in cetuximab-treated RM-HNSCC patients and predictor of partial metabolic FDG-PET response in an afatinib window-of-opportunity trial. Another anti-EGFR-mAb (panitumumab) was used as the treatment agent in RM-HNSCC patients in the phase II PANI01trial. PANI01 tumor samples were analyzed using functional genomics to explore response predictors to anti-EGFR therapy.Materials and methodsWhole-gene expression and real-time PCR analyses were applied to pre-treatment samples from 25 PANI01 patients. Three gene signatures (Cluster3 score, RAS onco-signature, microenvironment score) and seven selected miRNAs were separately analyzed for association with panitumumab efficacy.ResultsCluster3 expression levels had a profile with a significant bimodal separation of samples (P =  3.08 E−13). Higher RAS activation, microenvironment score, and miRNA expression were associated with low-Cluster3 patients. The same biomarkers were separately associated with PFS. Patients with high-Cluster3 had significantly longer PFS than patients with low-Cluster3 (median PFS: 174 versus 51 days; log-rank P = 0.0021). ROC analysis demonstrated accuracy in predicting PFS (AUC = 0.877).ConclusionsDespite differences in clinical settings and anti-EGFR inhibitors used for treatment, response prediction by the Cluster3 signature and selected miRNAs was essentially the same. Translation into a useful clinical assay requires validation in a broader setting.



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Modular MLV-VLPs co-displaying ovalbumin peptides and GM-CSF effectively induce expansion of CD11b+ APC and antigen-specific T cell responses in vitro

Publication date: September 2018
Source:Molecular Immunology, Volume 101
Author(s): Patricia Gogesch, Stefan Schülke, Stephan Scheurer, Michael D. Mühlebach, Zoe Waibler
The development of novel vaccination strategies is a persistent challenge to provide effective prophylactic treatments to encounter viral infections. In general, the physical conjugation of selected vaccine components, e.g. antigen and adjuvant, has been shown to enhance the immunogenicity and hence, can increase effectiveness of the vaccine. In our proof-of-concept study, we generated non-infectious, replication deficient Murine Leukemia Virus (MLV)-derived virus-like particles (VLPs) that physically link antigen and adjuvant in a modular fashion by co-displaying them on their surface. For this purpose, we selected the immunodominant peptides of the model antigen ovalbumin (OVA) and the cytokine granulocyte macrophage-colony stimulating factor (GM-CSF) as non-classical adjuvant. Our results show that murine GM-CSF displayed on MLV-VLPs mediates expansion and proliferation of CD11b⁺ cells within murine bone marrow and total spleen cells. Moreover, we show increased immunogenicity of modular VLPs co-displaying OVA peptides and GM-CSF by their elevated capacity to induce OVA-specific T cell-activation and -proliferation within OT-I and OT-II splenocyte cultures. These enhanced effects were not achieved by using an equimolar mixture of VLPs displaying either OVA or GM-CSF. Taken together, OVA and GM-CSF co-displaying MLV-VLPs are able to target and expand antigen presenting cells which in turn results in enhanced antigen-specific T cell activation and proliferation in vitro. These data suggest MLV-VLPs to be an attractive platform to flexibly combine antigen and adjuvant for novel modular vaccination approaches.

Graphical abstract

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Dendritic cells with increased expression of suppressor of cytokine signaling 1(SOCS1) gene ameliorate lipopolysaccharide/d-galactosamine-induced acute liver failure

Publication date: September 2018
Source:Molecular Immunology, Volume 101
Author(s): Shan-Shan Li, Min Yang, Yong-Ping Chen, Xin-Yue Tang, Sheng-Guo Zhang, Shun-Lan Ni, Nai-Bin Yang, Ming-Qin Lu
Acute liver failure is a devastating clinical syndrome with extremely terrible inflammation reaction, which is still lack of effective treatment in clinic. Suppressor of Cytokine Signaling 1 protein is inducible intracellular negative regulator of Janus kinases (JAK)/signal transducers and activators of transcription (STAT) pathway that plays essential role in inhibiting excessive intracellular signaling cascade and preventing autoimmune reaction. In this paper, we want to explore whether dendritic cells (DCs) with overexpression of SOCS1 have a therapeutic effect on experimental acute liver failure. Bone marrow derived dendritic cells were transfected with lentivirus encoding SOCS1 and negative control lentivirus, thereafter collected for costimulatory molecules analysis, allogeneic Mixed Lymphocyte Reaction and Western blot test of JAK/STAT pathway. C57BL/6 mice were randomly separated into normal control and treatment groups which respectively received tail vein injection of modified DCs, negative control DCs and normal saline 12 h earlier than acute liver failure induction. Our results indicated that DCs with overexpression of SOCS1 exhibited like regulatory DCs (DCregs) with low level of costimulatory molecules and poor allostimulatory ability in vitro, which was supposed to correlate with block of JAK2/STAT1 signaling. In vivo tests, we found that infusion of modified DCs increased survival rate of acute liver failure mice and alleviate liver injury via inhibition of TLR4/HMGB1 pathway. We concluded that DCs transduced with SOCS1 gene exhibit as DCregs through negative regulation of JAK2/STAT1 pathway and ameliorated lipopolysaccharide/d-galactosamine induced acute liver failure via inhibition of TLR4 pathway.



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