scholarly journals CD44, γ-H2AX, and p-ATM Expressions in Short-Term Ex Vivo Culture of Tumour Slices Predict the Treatment Response in Patients with Oral Squamous Cell Carcinoma

2022 ◽  
Vol 23 (2) ◽  
pp. 877
Author(s):  
Pierre Philouze ◽  
Arnaud Gauthier ◽  
Alexandra Lauret ◽  
Céline Malesys ◽  
Giovanna Muggiolu ◽  
...  

Squamous cell carcinoma is the most common type of head and neck cancer (HNSCC) with a disease-free survival at 3 years that does not exceed 30%. Biomarkers able to predict clinical outcomes are clearly needed. The purpose of this study was to investigate whether a short-term culture of tumour fragments irradiated ex vivo could anticipate patient responses to chemo- and/or radiotherapies. Biopsies were collected prior to treatment from a cohort of 28 patients with non-operable tumours of the oral cavity or oropharynx, and then cultured ex vivo. Short-term biopsy slice culture is a robust method that keeps cells viable for 7 days. Different biomarkers involved in the stemness status (CD44) or the DNA damage response (pATM and γ-H2AX) were investigated for their potential to predict the treatment response. A higher expression of all these markers was predictive of a poor response to treatment. This allowed the stratification of responder or non-responder patients to treatment. Moreover, the ratio for the expression of the three markers 24 h after 4 Gy irradiation versus 0 Gy was higher in responder than in non-responder patients. Finally, combining these biomarkers greatly improved their predictive potential, especially when the γ-H2AX ratio was associated with the CD44 ratio or the pATM ratio. These results encourage further evaluation of these biomarkers in a larger cohort of patients.

2014 ◽  
Vol 395 (9) ◽  
pp. 1051-1062 ◽  
Author(s):  
Emmanouela Foteinou ◽  
Christos K. Kontos ◽  
Aris I. Giotakis ◽  
Andreas Scorilas

Abstract Several members of the family of tissue kallikrein and kallikrein-related peptidases have been suggested as promising tumor biomarkers with important prognostic significance. However, only one (KLK11) has already been studied in laryngeal squamous cell carcinoma (LSCC) as a potential biomarker for LSCC diagnosis and/or prognosis. Our study investigated the prognostic value of kallikrein-related peptidase-4 (KLK4) mRNA expression as a molecular tissue biomarker in LSCC. For this purpose, KLK4 mRNA expression analysis was performed in 116 cancerous and 74 paired non-cancerous laryngeal tissue specimens obtained from patients that had undergone surgical treatment for primary LSCC. A remarkable downregulation of KLK4 mRNA expression was discovered in laryngeal tumors, compared to non-cancerous laryngeal tissue specimens. KLK4 mRNA expression was also shown to distinguish LSCC from non-cancerous laryngeal tissues. Furthermore, low KLK4 mRNA expression was shown to predict poor disease-free survival, independently of the histological grade and size of the malignant tumor as well as patient TNM stage. According to Kaplan-Meier survival analysis, low KLK4 mRNA expression predicts short-term relapse even among patients with well-differentiated tumors or those at an early TNM stage. Thus, KLK4 mRNA positivity could be regarded as a novel independent indicator of favorable prognosis for the disease-free survival of LSCC patients.


Oral Oncology ◽  
2021 ◽  
Vol 118 ◽  
pp. 4-5
Author(s):  
M.E. Capala ◽  
G.M. Verduijn ◽  
S.F. Petit ◽  
M.A. de Korte ◽  
J.A. Hardillo ◽  
...  

Author(s):  
Roberto Milazzotto ◽  
Rocco Luca Emanuele Liardo ◽  
Giuseppe Privitera ◽  
Luigi Raffaele ◽  
Vincenzo Salamone ◽  
...  

Abstract Aim: Conjunctival squamous cell carcinoma (SCC) is a rare tumour of the ocular region and microscopic radical surgical is difficult. There are no single guidelines for therapeutic management and the role of radiation therapy is not clearly defined although conventionally photon or electron beams are used. Proton beam radiotherapy (PBRT) is a new option for a conservative approach and allows good sparing of the organs at risk. Materials and methods: After surgical resection, we collected 15 cases treated at our institution with PBRT. The dose delivered was between 48 and 60 Gy relative biological effectiveness (RBE), with fractions of 12–15 Gy RBE. Results: After an average period of 48 months, the patients achieved excellent disease control (overall survival and disease-free survival: 86·6%), with minimal acute and late toxicity. Findings: In this work, we present our experience on the use of PBRT technique in SCC treatment. A larger sample of patients is needed to draw conclusions about the impact of this treatment on disease recurrence and overall survival.


2021 ◽  
Vol 28 (4) ◽  
pp. 2409-2419
Author(s):  
Arslan Babar ◽  
Neil M. Woody ◽  
Ahmed I. Ghanem ◽  
Jillian Tsai ◽  
Neal E. Dunlap ◽  
...  

Adjuvant chemoradiation (CRT), with high-dose cisplatin remains standard treatment for oral cavity squamous cell carcinoma (OCSCC) with high-risk pathologic features. We evaluated outcomes associated with different cisplatin dosing and schedules, concurrent with radiation (RT), and the effect of cumulative dosing of cisplatin. An IRB-approved collaborative database of patients (pts) with primary OCSCC (Stage I–IVB AJCC 7th edition) treated with primary surgical resection between January 2005 and January 2015, with or without adjuvant therapy, was established from six academic institutions. Patients were categorized by cisplatin dose and schedule, and resultant groups compared for demographic data, pathologic features, and outcomes by statistical analysis to determine disease free survival (DFS) and freedom from metastatic disease (DM). From a total sample size of 1282 pts, 196 pts were identified with high-risk features who were treated with adjuvant CRT. Administration schedule of cisplatin was not significantly associated with DFS. On multivariate (MVA), DFS was significantly better in patients without perineural invasion (PNI) and in those receiving ≥200 mg/m2 cisplatin dose (p < 0.001 and 0.007). Median DFS, by cisplatin dose, was 10.5 (<200 mg/m2) vs. 20.8 months (≥200 mg/m2). Our analysis demonstrated cumulative cisplatin dose ≥200 mg/m2 was associated with improved DFS in high-risk resected OCSCC pts.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Danielle R. L. Brogden ◽  
Christopher C. Khoo ◽  
Christos Kontovounisios ◽  
Gianluca Pellino ◽  
Irene Chong ◽  
...  

AbstractAnal Squamous Cell Carcinoma (ASCC) is a rare cancer that has a rapidly increasing incidence in areas with highly developed economies. ASCC is strongly associated with HIV and there appears to be increasing numbers of younger male persons living with HIV (PLWH) diagnosed with ASCC. This is a retrospective cohort study of HIV positive and HIV negative patients diagnosed with primary ASCC between January 2000 and January 2020 in a demographic group with high prevalence rates of HIV. One Hundred and seventy six patients were included, and clinical data was retrieved from multiple, prospective databases. A clinical subgroup was identified in this cohort of younger HIV positive males who were more likely to have had a prior diagnosis of Anal Intraepithelial Neoplasia (AIN). Gender and HIV status had no effect on staging or disease-free survival. PLWH were more likely to develop a recurrence (p < 0.000) but had a longer time to recurrence than HIV negative patients, however this was not statistically significant (46.1 months vs. 17.5 months; p = 0.077). Patients known to have a previous diagnosis of AIN were more likely to have earlier staging and local tumour excision. Five-year Disease-Free Survival was associated with tumour size and the absence of nodal or metastatic disease (p < 0.000).


Author(s):  
Veronika Shavlokhova ◽  
Christa Flechtenmacher ◽  
Sameena Sandhu ◽  
Michael Vollmer ◽  
Jürgen Hoffmann ◽  
...  

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