Cdk5 Loss Alters Mitochondrial Cristae Organization
DOI: 10.29245/2578-2967/2021/1.1189 View / Download PdfSaranya Navaneetha Krishnan1, Jesusa L. Rosales1, Ki-Young Lee1*
1Department of Cell Biology & Anatomy, Arnie Charbonneau Cancer and Alberta Children’s Hospital Research Institutes, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
AP-2 Family of Transcription Factors: Critical Regulators of Human Development and Cancer
Yi-Liu Yang1, Lin-Yong Zhao2*
1West China School of Medicine, West China Hospital, Sichuan University, Chengdu, China
2Department of Gastrointestinal Surgery and Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China
The AP-2 family of transcription factors consist of DNA-binding proteins: AP-2α to AP-2ε. Members and homologs of this family are also known in frogs, fish and invertebrates. These proteins have the same central basic region and a helix-span-helix dimerization motif, which is necessary for dimerization and DNA binding. This family have been found to influence facial, limbs and kidney development in embryogenesis while regulating differentiation and apoptosis. These proteins are also involved in regulation of endocrine processes. In addition to their influence on growth and development, this family have also been reported to correlate with tumorigenesis and development of cancer. At present, this family have been related to tumors of ovary, melanoma, lung, nasopharynx, breast, glioma, neuroblastoma, colon, etc. They regulate expression of many cancer-related genes and affect the occurrence, development, invasiveness and therapeutic response of cancers. Different expression levels of AP-2s are also related to different survival rate. These findings may bring new idea to the diagnosis, classification, treatment and prognosis of cancer.
DOI: 10.29245/2578-2967/2021/1.1187 View / Download Pdf Ex-Vivo Detection of Breast Cancer with a Bio-Impedance Sensor
Justina Ugwaha5, Niall Savage1, Walter Messina1, Yineng Wang5, Edel Whelton5, Ann-Marie O’Donovan3, Martin J.O’Sullivan2, Brian D.O. Donnell2,4, Eric J. Moore1,5*
1Life Sciences Interface, Tynadall National Institute, University College Cork, Ireland
2Department of Surgery, Cork University Hospital, Cork
3Department of Pathology, Cork university Hospital, Cork
4Department of Anaesthesia, Cork University Hospital, Cork
5School of Chemistry, University College Cork
Bioimpedance is the opposition to flow of an applied electrical current through biological tissues1. Our research group designed and fabricated bipolar micro-sensors on the tip of a silicone probe, capable of measuring biological tissue impedance. It is known that the bioimpedance of cultured cancer cells differs substantially from that of healthy cell lines. We hypothesised that the bioimpedance of cancer in surgically excised human tissue would be significantly different to surrounding healthy tissue. To test this hypothesis, we designed a study to evaluate the bioimpedance of healthy and diseased breast tissue in surgically excised breast specimens. This manuscript reports the outcome of this study.
DOI: 10.29245/2578-2967/2021/1.1193 View / Download Pdf Development of a Companion Diagnostic PD-L1 Immunohistochemistry Assay for Pembrolizumab Therapy in Head and Neck Squamous Cell Carcinoma
Christopher J. La Placa1*, Monika D. Vilardo1, Brittany M. Watts1, Monika D. Polewski1, Siena Tabuena-Frolli1, Malinka Jansson1, Kenneth Emancipator1, Fan Jin1, Burak Gumuscu1, Joy Y. Ge2, Michael DiMaio1, Karina Kulangara1*
1Agilent Technologies, Inc. 6392 Via Real, Carpinteria, California, United States
2Merck & Co., Inc. 2000 Galloping Hill Road, Kenilworth, New Jersey, United States
Objectives: FDA approval of PD-L1 IHC 22C3 pharmDx for use as an aid in identifying head and neck squamous cell carcinoma (HNSCC) patients for treatment with pembrolizumab was based on the results of rigorous analytical and clinical validation testing.
Methods: For the HNSCC indication, the device was validated at Agilent Technologies on the performance of sensitivity and precision using the Combined Positive Score (CPS) ≥ 1 and CPS ≥ 20 cutoffs; external validation studies were performed at three external laboratories. CPS ≥ 1 and CPS ≥ 20 cutoffs were evaluated in KEYNOTE-048, a phase 3 clinical trial.
Results: Analytical validation studies supporting the companion diagnostic indication (CPS ≥ 1) achieved point estimates of > 85% for negative, positive, and overall percent agreement. Clinical validation studies show that HNSCC patients treated with pembrolizumab as a single agent had an overall survival (OS) of 12.3 months at CPS ≥ 1 (95% CI, 10.8-14.9) compared with patients receiving cetuximab, platinum, and 5-fluorouracil (CPS ≥ 1 OS of 10.3 months (95% CI, 9.0-11.5)).
Conclusion: Analytical and clinical validation studies demonstrate that PD-L1 IHC 22C3 pharmDx is a precise companion diagnostic assay, allowing for selection of eligible HNSCC patients for treatment with pembrolizumab.
DOI: 10.29245/2578-2967/2021/1.1190 View / Download Pdf Outcome measures following Sono and Photodynamic Therapy – A Case Series
Julian N. Kenyon1*
1The Dove Clinic, Twyford, Winchester, Hampshire, SO21 1NT, England
Sono and Photodynamic Therapy (SPDT) is a novel therapeutic modality that utilises a non-toxic photosensitive agent with reported ultrasound-activated properties. SPDT has previously demonstrated significant tumour cell inhibition in animal studies. There has been much research into the efficacy of photodynamic therapy and development in understanding of the underlying mechanism of tumour cytotoxicity. Synergistic ultrasound activation represents a promising development to Photodynamic Therapy, as photo-activation is limited by access and penetrance issues. Ultrasound has been demonstrated to activate a number of sono-sensitive agents allowing the possibility of non-invasive targeted treatment of deeper tumour sites than is currently achievable with photodynamic therapy. This case series of 17 consecutive patients with a variety of cancer diagnoses outlines clinical outcomes over a four-year period of SPDT. The results have been encouraging in that all cases who carried our Circulating Tumour Cell Tests before and after SPDT showed a significant drop in tumour cells post-SPDT. SPDT is worthy of further investigation as an effective and well tolerated treatment for a wide variety of primary and metastatic tumours, including those refractory to Chemotherapy.
DOI: 10.29245/2578-2967/2021/1.1195 View / Download Pdf