8 research outputs found
Nullomer Derived Anticancer Peptides (NulloPs): Differential Lethal Effects on Normal and Cancer Cells \u3cem\u3ein vitro\u3c/em\u3e
We demonstrate the first use of the nullomer (absent sequences) approach to drug discovery and development. Nullomers are the shortest absent sequences determined in a species, or group of species. By identifying the shortest absent peptide sequences from the NCBI databases, we screened several potential anti-cancer peptides. In order to improve cell penetration and solubility we added short poly arginine tails (5Rs), and initially solubilized the peptides in1M trehalose. The results for one of the absent sequences 9R (RRRRRNWMWC), and its scrambled version 9S1R (RRRRRWCMNW) are reported here. We refer to these peptides derived from nullomers as PolyArgNulloPs. A control PolyArgNulloP, 124R (RRRRRWFMHW), was also included. The lethal effects of 9R and 9S1R are mediated by mitochondrial impairment as demonstrated by increased ROS production, ATP depletion, cell growth inhibition, and ultimately cell death. These effects increase over time for cancer cells with a concomitant drop in IC-50 for breast and prostate cancer cells. This is in sharp contrast to the effects in normal cells, which show a decreased sensitivity to the NulloPs over time
Safeguarding Forensic DNA Reference Samples with Nullomer Barcodes
Unintended transfer of biological material containing DNA is a concern to all laboratories conducting PCR analysis. While forensic laboratories have protocols in place to reduce the possibility of contaminating casework samples, there is no way to detect when a reference sample is mislabeled as evidence, or contaminates a forensic sample. Thus there is public concern regarding the safeguarding of DNA submitted to crime labs. We demonstrate a method of introducing an internal amplification control to reference samples, in the form of a nullomer barcode which is based upon sequences absent or rare from publically accessible DNA databases. The detection of this barcode would indicate that the source of analyzed DNA was from a reference sample provided by an individual, and not from an evidence sample. We demonstrate that the nullomers can be added directly to collection devices (FTA paper) to allow tagging during the process of sample collection. We show that such nullomer oligonucleotides can be added to existing forensic typing and quantification kits, without affecting genotyping or quantification results. Finally, we show that even when diluted a million-fold and spilled on a knife, the nullomer tags can be clearly detected. These tags support the National Research Council of the National Academy recommendation that “Quality control procedures should be designed to identify mistakes, fraud, and bias” in forensic science (National Academy of Sciences, 2009)
Structure, process, and impact of a staff support group in an oncology setting in a developing country
Background: Health-care staff working in oncology setting experience excessive stress, which if unrelieved can lead to burnout. Staff support groups have been found beneficial. Aims: This study aims to evaluate the structure, process, and impact of a staff support group conducted for field workers involved in cancer screening in an urban tertiary cancer center in a developing country. Settings and Design: Retrospective analysis of staff support group conducted in a tertiary care cancer center. Methodology: Prospectively maintained data with structured notes for documenting the process of the support group sessions for the field workers was analyzed. Impact was analyzed through a feedback questionnaire designed for the purpose completed by participants at 4 months, 1, and 2 years following session completion. Statistical Analysis: Descriptive statistics for reporting the overall structure and participants' profile and content analysis for identifying the support group process and themes expressed by the participants were used. Results: Eleven participants attended the support group consisting of 8 structured sessions. The processes identified were planning, implementation, and supervision of the lead therapist conducting the group. Work overload, target completion, feeling demoralized, interpersonal conflicts, and importance of team support were the main issues identified. Cognitive behavioral approaches were learnt for stress management. Eight, nine, and all 11 participants found the support group moderately to very useful at 4 months, 1 year, and 2 years, respectively. Conclusions: The support group followed a planned structure, with good implementation, recording of content and supervision, with both short-term and sustained positive impact
MB-54HYPERFRACTIONATED RADIATION THERAPY (HFRT) WITHOUT UPFRONT CHEMOTHERAPY IN CHILDREN WITH AVERAGE-RISK MEDULLOBLASTOMA: MATURE FUNCTIONAL OUTCOMES AND LONG-TERM SURVIVAL
Prospective assessment of neurocognitive outcomes in children and young adults with progressive/residual benign and low-grade brain tumors treated with high-precision conformal or conventional radiotherapy: Results of a randomized clinical trial.
Distress Management in Patients With Head and Neck Cancer Before Start of Palliative Chemotherapy: A Practical Approach
Purpose: This study reports the incidence of distress, the factors associated with distress, and a practical strategy to resolve distress in patients with head and neck cancer who are starting palliative chemotherapy. Methods: Adult patients with head and neck cancer planned for palliative chemotherapy underwent distress screening before the start of treatment as part of this single-arm prospective study. Patients who had a distress score > 3 on the National Comprehensive Cancer Network (NCCN) distress thermometer were counseled initially by the clinician. Those who continued to have high distress after the clinician-led counseling were referred to a clinical psychologist and were started on palliative chemotherapy. After counseling, distress was measured again. The relation between baseline distress and compliance was tested using Fisher's exact test. Results: Two hundred patients were enrolled, and the number of patients with high distress was 89 (44.5% [95% CI, 37.8% to 51.4%]). The number of patients who had a decrease in distress after clinician-led counseling (n = 88) was 52 (59.1% [95% CI, 48.6% to 68.8%]) and after psychologist-led counseling (n = 32) was 24 (75.0% [95% CI, 57.6% to 72.2%]; P = .136). Compliance rates did not differ between the patients with or without a high level of distress at baseline (74.2% v 77.4%, P = .620). Conclusion: The incidence of baseline distress is high in patients awaiting the start of palliative chemotherapy. It can be resolved in a substantial number of patients using the strategy of clinician-led counseling, with additional referral to a clinical psychologist as required. Patients with a greater number of emotional problems usually require psychologist-led counseling