scholarly journals PARP1 as a biomarker for early detection and intraoperative tumor delineation in epithelial cancers – first-in-human results

2019 ◽  
Author(s):  
Susanne Kossatz ◽  
Giacomo Pirovano ◽  
Paula Demétrio De Souza França ◽  
Arianna L. Strome ◽  
Sumsum P. Sunny ◽  
...  

AbstractMajor determining factors for survival of patients with oral, oropharyngeal, and esophageal cancer are early detection, the quality of surgical margins, and the contemporaneous detection of residual tumor. Intuitively, the exposed location at the epithelial surface qualifies these tumor types for utilization of visual aids to assist in discriminating tumor from healthy surrounding tissue. Here, we explored the DNA repair enzyme PARP1 as imaging biomarker and conducted optical imaging in animal models, human tissues and as part of a first-in-human clinical trial. Our data suggests that PARP1 is a quantitative biomarker for oral, oropharyngeal, and esophageal cancer and can be visualized with PARPi-FL, a fluorescently labeled small molecule contrast agent for topical or intravenous delivery. We show feasibility of PARPi-FL-assisted tumor detection in esophageal cancer, oropharyngeal and oral cancer. We developed a contemporaneous PARPi-FL topical staining protocol for human biospecimens. Using fresh oral cancer tissues within 25 min of biopsy, tumor and margin samples were correctly identified with >95% sensitivity and specificity without terminal processing. PARPi-FL imaging can be integrated into clinical workflows, potentially providing instantaneous assessment of the presence or absence of microscopic disease at the surgical margin. Additionally, we showed first-in-human PARPi-FL imaging in oral cancer. In aggregate, our preclinical and clinical studies have the unifying goal of verifying the clinical value of PARPi-FL-based optical imaging for early detection and intraoperative margin assignment.

Author(s):  
Cory Olsovsky ◽  
Rodrigo Cuenca ◽  
Yi-Shing Lisa Cheng ◽  
John Wright ◽  
Javier Jo ◽  
...  

2016 ◽  
Vol 121 (3) ◽  
pp. 290-300.e2 ◽  
Author(s):  
Bilal H. Malik ◽  
Joey M. Jabbour ◽  
Shuna Cheng ◽  
Rodrigo Cuenca ◽  
Yi-Shing Lisa Cheng ◽  
...  

2021 ◽  
Vol 10 (1) ◽  
pp. 10-12
Author(s):  
Farooq Ahmed ◽  
Honieh Bolooki ◽  
Senathrajah Ariyaratnam ◽  
Michael N. Pemberton

Oral cancer is a significant cause of morbidity and mortality worldwide. In this article we present two cases of potentially innocuous looking lesions, initially thought to be traumatic in origin, but later diagnosed as cancer. The first patient presented with a persistent laceration thought to be caused by an accidental shaving injury, which was subsequently diagnosed as squamous cell carcinoma. The second patient presented with a hyperplastic mucosal lesion, suspected as forming due to denture-clasp irritation, which was subsequently diagnosed as proliferative verrucous carcinoma. The importance of early detection and palpation of suspicious lesions is emphasised in this article.


Esophagus ◽  
2021 ◽  
Author(s):  
Ryoya Mizumachi ◽  
Koichi Hayano ◽  
Atsushi Hirata ◽  
Gaku Ohira ◽  
Shunsuke Imanishi ◽  
...  

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1859.2-1859
Author(s):  
L. Zerweck ◽  
U. Henkemeier ◽  
P. H. Nguyen ◽  
T. Rossmanith ◽  
A. Pippow ◽  
...  

Background:Psoriasis (Pso) is one of the most common chronic inflammatory skin diseases in Europe. Psoriatic arthritis (PsA) is closely associated to Pso whereas the skin manifestation appears usually years before PsA-related symptoms emerge. Up to 30% of Pso patients develop PsA, biomarkers for its early detection are of major importance. In early PsA, changes in synovial vascularisation appear first. Imaging biomarkers for detection of changes in vascularisation might be useful for early detection of musculoskeletal disease. Fluorescence-optical imaging (FOI) is a new method to detect changes in microvascularisation of the hands. Each collected data set of the FOI system contains 360 images representing a time progression of the indocyanine green (ICG) distribution.Objectives:To evaluate a reader-independent assessment method for evaluation of FOI in patients with PsO and PsA.Methods:A prospective study including patients with dermatological confirmed skin PsO was performed. 411 patients were included from German dermatology units without PsA diagnosis but potential risk for its development. Clinical examination (CE) was performed by a qualified rheumatologist. For a reader independent evaluation of the FOI images an objective joint-based scoring method was developed. For this method, the joint areas are defined by image segmentation and scored based on generated heatmaps. To calculate a heatmap indicating conspicuous joints from a data set containing 360 images, each pixel is converted to a time series containing 360 values. From this time series, three independent values (features) are extracted: amplitude, average value and maximal slope. Thus, each pixel is reduced to three different feature values. After the three features are determined for each pixel, k-means clustering is performed on each feature. The numbers of centroids (k) are set to 3, 5, 7 and 9. 12 heatmaps (3 features à 4 ks) are calculated, which results in 12 scores for each joint as well. The clusters are then sorted dependent on their centroid value and coloured accordingly to a predefined heatmap colour palette. To finally score each joint, the pixels in the segmented joint area and their assigned cluster are summed and normalized by the area’s amount of pixels and k.Results:271 of the patients were investigated by the newly developed method and compared with the CE scoring. 6426 joints were labeled as healthy whereas 1162 joints were either labeled as swollen, tender or both. The result over all investigated patients for k = 9 is summed in table 1. It is observable that every average and median healthy value is lower than the corresponding affected value.Table 1.Resulting scores for k = 9 for all 271 patients.Feature Statistic valueAmplitudeMeanSlopeHealthyAffectedHealthyAffectedHealthyAffectedAverage0.5030.5280.4860.5090.3950.414Median0.4960.5320.4820.5050.3890.415Conclusion:FOI is an innovative method that detects early changes in vascularization of the hands. So, this method can be useful in early detection of arthritis especially in risk populations such as PsO patients. The results of the objective scoring method show that a clear distinction between healthy and affected joints is possible with the average scores as well as the median values. However, if the range of the scores is considered, the overlap between healthy and affected is not neglectable. Thus, the current scoring system can be used as an indicator but not as a single classification marker. Nevertheless, the research at hand has shown the expected outcome and motivates further development on the heatmap approach.Disclosure of Interests:Lukas Zerweck: None declared, Ulf Henkemeier: None declared, Phuong-Ha Nguyen: None declared, Tanja Rossmanith Grant/research support from: Janssen, BMS, LEO, Pfizer, Andreas Pippow: None declared, Harald Burkhardt Grant/research support from: Pfizer, Roche, Abbvie, Consultant of: Sanofi, Pfizer, Roche, Abbvie, Boehringer Ingelheim, UCB, Eli Lilly, Chugai, Bristol Myer Scripps, Janssen, and Novartis, Speakers bureau: Sanofi, Pfizer, Roche, Abbvie, Boehringer Ingelheim, UCB, Eli Lilly, Chugai, Bristol Myer Scripps, Janssen, and Novartis, Frank Behrens Grant/research support from: Pfizer, Janssen, Chugai, Celgene, Lilly and Roche, Consultant of: Pfizer, AbbVie, Sanofi, Lilly, Novartis, Genzyme, Boehringer, Janssen, MSD, Celgene, Roche and Chugai, Michaela Köhm Grant/research support from: Pfizer, Janssen, BMS, LEO, Consultant of: BMS, Pfizer, Speakers bureau: Pfizer, BMS, Janssen, Novartis


2021 ◽  
Vol 6 (4) ◽  
pp. 160-165
Author(s):  
  RM Vatchala Rani ◽  
BC Manjunath ◽  
Manas Bajpai ◽  
Pooja Gupta ◽  
Akshay Bhargava ◽  
...  

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