Effector T cell subclasses associate with tumor burden in neurofibromatosis type 1 patients

Abstract

Neurofibromatosis type 1 (NF1) is a hereditary tumor syndrome caused by mutations of the NF1 gene and resulting dysregulation of the Ras-pathway. In addition to peripheral nerve tumors, affected tissues include the musculoskeletal and cardiovascular system. The immune system has recently been suggested as a possible modulator NF1-related phenotypes. Therefore, we determined the immune phenotype in NF1 patients and investigated its relationship with the phenotypic severity of NF1-related tumor manifestations. We quantified global leukocytes and lymphocyte subpopulations of peripheral blood from 37 NF1 patients and 21 healthy controls by flow cytometry. To associate immune phenotype with tumor phenotype, all NF1 patients underwent whole-body magnetic resonance imaging and total internal tumor volume was calculated. The immunophenotypes were compared among four NF1 groups with different total internal tumor burdens and between NF1 patients and non-NF1 subjects. We found that NF1 patients show a generalized lymphopenia. Closer analysis revealed that the CD8⁺/CD27⁻ and CD8⁺/CD57⁺ effector T cell fractions strongly increase in NF1 patients with low tumor load and decrease to levels below control in patients with high tumor load. Moreover, increased production of IL2, IFN-γ and TNF-α was found in T cells of NF1 patients upon phorbol-12-myristate acetate (PMA) stimulation compared to healthy controls. The data indicate that decreasing CD8⁺/CD57⁺ and CD27⁻ T cell fractions correspond to increasing tumor load in NF1 patients, potentially making these populations useful marker for internal tumor burden.

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Downregulation of proinflammatory cytokines in HTLV-1-infected T cells by Resveratrol

Human T-cell leukemia virus (HTLV-1) is a lymphotropic retrovirus associated to adult T cell leukemia (ATL) and to non-neoplastic inflammatory conditions affecting the central nervous system, lung or skin. The...

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A phase 1 dose-escalation study of NEO-102 in patients with refractory colon and pancreatic cancer

Abstract

Purpose

NEO-102 is a novel chimeric IgG1 monoclonal antibody which recognizes a variant form of MUC5AC expressed specifically by human pancreatic and colorectal tumors. Preclinical models have demonstrated encouraging signs of anti-tumor activity through antibody-dependent cell-mediated cytotoxicity.

Methods

This is a phase 1, dose-escalation trial of NEO-102 (Ensituximab) for patients with refractory pancreatic and colorectal cancer. The primary objective was to determine safety and tolerability of escalating doses of NEO-102. Secondary objectives were to assess pharmacokinetics, anti-tumor activity and biologic correlates. Patients whose tumors express NPC-1 antigen were eligible. Dose-escalation was performed in a 3 + 3 design at doses of 1.5, 2, 3 and 4 mg/kg.

Results

A total of 19 patients (4 pancreatic and 15 colon cancer) were enrolled at participating institutions in the treatment phase. Most common treatment-related adverse events included anemia, fatigue, fevers, chills and flushing. There was no detectable hemolysis. Of twelve patients evaluable for disease response, the response rate at week 8 included 5 patients with stable disease and 8 patients with progressive disease (PD). Treatment-related grade 3/4 hyperbilirubinemia and anemia were observed at 4 mg/m2. Reversible hypoxia at 3 mg/kg was a dose-limiting toxicity. The maximum tolerated dose was established at 3 mg/kg. Of 74 patients who underwent tissue screening, positive NPC-1 expression was 47 % in colon and 59 % in pancreatic cancer.

Conclusions

Treatment with the NEO-102, in this first-in-human study, is well tolerated with a manageable safety profile. A maximum tolerated dose of 3 mg/kg has been established. Toxicity profile is typical for this therapeutic class and allows for combination with conventional cytotoxic therapies.

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Cancer Screening Perception Scale: Development and Construct Validation

Abstract

The aim of this study was to demonstrate the construct validity of a newly developed cancer screening perception scale as a measure of the perception of cancer screening in general among high-risk but healthy asymptomatic groups.

The cancer screening perception scale (CSPS) was developed based on extensive literature reviews guided by The Health Belief Model. Fifty-five written items were initially pooled, reviewed by experts for face validity, pretested by 25 healthcare workers and translated into Malay using simple back translation. The scale was then distributed to 300 respondents from two health clinics for construct validation purposes. The obtained data were analyzed using the varimax rotation method for exploratory factor analysis (EFA). The data was submitted for further confirmatory factor analysis using AMOS software.

Based on EFA, the results produced five constructs as predicted: perceived severity, perceived susceptibility, perceived benefits, perceived barriers, and cues for action. Two items with low factor loading and unrelated to the recovered domains were removed. Perceived barriers and cues for action had three and two sub-domains respectively which were further confirmed to fit the measurement and structural models. CFA demonstrated the scale fitted GFI = 0.936, CFI = 0.935, RMSEA = 0.076, NORMEDCHISQ = 2.162. The scale discriminated between the domains. Cronbach's alpha for perceived severity, perceived susceptibility, perceived benefits, perceived barrier, and cues for action were 0.907, 0.877, 0.940, 0.864 and 0.938, respectively.

The cancer screening perception scale with its promising psychometric properties is now available to measure risks to high-risk but healthy, asymptomatic groups aged 18 and above and can also be used for larger scale study purposes.

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Readability and Coherence of Department/Ministry of Health HPV Information

Abstract

Background

Human papilloma virus (HPV) is a prime factor in the development of many cancers and genital warts in Canada. A majority of sexually active Canadians are likely to have an HPV infection during their lifetime. Information provided online by each specific provincial department/ministry of health in regard to HPV and vaccination may not be at an ideal standard for the lay population to understand and should be evaluated.

Purpose

The purpose of this study is to assess the readability and coherence of provincial department/ministry of health HPV information to determine if it is adequate for the Canadian lay population to understand.

Methods and Results

Seven of ten Canadian provincial department/ministry of health's HPV information websites were evaluated for readability and coherence. The readability tools Gunning-Fog index and Simple Measure of Gobbledygook (SMOG) both found that approximately 60 % of the population for each of the provinces evaluated may be able to understand the information. The coherence measures of latent semantic analysis (LSA) and computerized propositional idea density rater (CPIDR) both concluded that relative to the benchmark that represents the lay population, the coherence level is not appropriate (LSA, p < 0.001and CPIDR, p < 0.001).

Interpretation

HPV information provided by the Canadian provincial department/ministry of health websites may not be adequate for the lay population to understand. Readability and coherence are important factors that should be considered to improve the quality and adequacy of the information provided so the message reaches the Canadian population.

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Orthopedic Oncology Caseload Among Orthopedic Surgery Residents

Abstract

Despite educational focus regarding orthopedic oncology during residency, assessment of resident orthopedic oncology caseload has not been performed. The purpose of this study was to evaluate orthopedic oncology caseload trends and variation among residents. The Accreditation Council for Graduate Medical Education case log reports for orthopedic surgery residents were reviewed for graduating years 2007 to 2013. Trends in orthopedic oncology cases and variation in the median number of cases performed by residents in the 90th, 50th, and 10th percentiles of caseload were evaluated. The proportion of orthopedic oncology caseload among all cases performed by residents increased significantly (P = 0.005) from 2007 to 2013. Likewise, the mean number of adult (P = 0.002), pediatric (P = 0.003), and total orthopedic oncology cases increased significantly (P = 0.002). On average, residents in the 90th, 50th, and 10th percentiles performed 83, 28, and 3 cases, respectively. The current study demonstrates a significant increase in adult, pediatric, and total orthopedic oncology caseload. There is also evidence of substantial caseload variation among residents. Caseload variation may influence the education and technical proficiency of orthopedic residents.

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Knowledgeability, Attitude and Behavior of Primary Care Providers Towards Oral Cancer: a Pilot Study

Abstract

The objective of this study was to assess current knowledgeability, attitudes, and practice behaviors of primary care providers (PCPs) towards oral cancer screening. Applying a cross-sectional design, a 14-question survey was emailed to 307 PCPs practicing at a large, multi-specialty, rurally based healthcare system. Survey data were collected and managed using REDCap and analyzed applying descriptive statistics. A 20 % response rate (n = 61/307) was achieved for survey completion. Approximately 70 % of respondents were physicians, 16 % were nurse practitioners, and 13 % were physician assistants. Nearly 60 % of respondents were family medicine practitioners. Limited training surrounding oral cancer screening during medical training was reported by 64 %. Although 78 % of respondents reported never performing oral cancer screening on patients in their practice, >90 % answered knowledge-based questions correctly. Frequency rate for specialist referral for suspicious lesions by PCPs was 56 % "frequently". Optimal periodicity for oral cancer screening on all patients selected by respondents was 61 % "annually", 3 % "every 6 months", 3 % "every visit", 2 % "not at all", and 31 % "unsure". This study established a baseline surrounding current knowledgeability, practice patterns, and opinions of PCPs towards oral cancer screening at a single, large, regional healthcare system. In the absence of evidence-based support for population-based cancer screening, this study result suggests a need for better integration of oral cancer surveillance into the medical setting, supplemented by education and training with emphasis on assessment of high-risk patients to achieve early detection. Prospectively, larger studies are needed to validate these findings.

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