VEGF-A and TGF-β in bioptates of oral squamous cell carcinoma reflect tumor response to chemotherapy and monoclonal antibodies (cetuximab).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e18563-e18563
Author(s):  
Liubov Yu Vladimirova ◽  
Elena M. Frantsiyants ◽  
Irina V. Neskubina ◽  
Aza A. Lyanova ◽  
Elena V. Shalashnaya ◽  
...  

e18563 Background: Cetuximab is a monoclonal antibody directed against the EGFR receptor, able to block the EGFR signaling pathway and also indirectly affect the secretion of some growth factors. The search for biomarkers responsible for cetuximab resistance is an urgent task. The purpose of the study was to analyze VEGF-A and TGF-β levels in tumor tissue bioptates in patients with squamous cell carcinoma of the oral cavity receiving chemotherapy (CT) and cetuximab. Methods: The study included 30 patients with HNSCC St III-IV, T3-4N0-1M0. All patients received 2 cycles: cisplatin 100 mg/m2, intravenously, day 1, 5-fluorouracil 1000 mg/m2/day, intravenously, 96-hour continuous infusion, in combination with targeted therapy cetuximab 400 mg/m2 on day 1 in a loading dose, then 250 mg/m2 on days 8 and 15). Patients were divided into two groups: with response to cetuximab and CT (partial regression and stabilization) n = 17 and progression considered (resistance to the treatment) n = 13. Levels of VEGF-A and TGF-β were determined in tumor tissue bioptates by ELISA using standard test systems (Bender Med System, Austria). Statistical processing of results was performed using the Statistica 6.0 program (Stat-Soft, 2001). Results: CT and cetuximab in patients with resistance did not result in statistically significant changes in levels of VEGF-A, TGF-β and the VEGF-A/TGF-β ratio in tumor tissue bioptates, compared to the initial values. The studied markers in tumor tissue bioptates in patients with response to CT were statistically significantly different from the initial values: VEGF-A was decreased by 1.46 times, TGF-β by 2.96 times, while the VEGF-A/TGF-β ratio was twice elevated (p < 0.05). Conclusions: The results on levels of VEGF-A and TGF-β and the VEGF-A/TGF-β ratio are of a prognostic value and can be used for evaluating the efficacy of cetuximab and CT in patients with HNSCC.

2019 ◽  
Vol 6 (3) ◽  
pp. 20-28 ◽  
Author(s):  
O. I. Kit ◽  
E. M. Frantsiyants ◽  
I. V. Neskubina ◽  
L. Yu. Vladimirova ◽  
A. A. Lyanova ◽  
...  

Aim. Study of VEGF-A and TGF-β growth factors in tumor tissue bioptates in patients with squamous cell carcinoma of the tongue and floor of the oral cavity depending on the effectiveness of polychemotherapy targeted therapy with cetuximab. Patients and methods. The study included 30 patients with squamous cell carcinoma of the tongue and mouth floor mucosa (T3-4N0-1M0). All patients received 2 cycles of therapy: cisplatin 100 mg/m2 , intravenously, day 1, 5-fluorouracil 1000 mg/m2 /day, intravenously, 96-hour continuous infusion in combination with targeted therapy (cetuximab 400 mg/ m2 on day 1 in a loading dose, then 250 mg/m2 on days 8 and 15). Patients were divided into two subgroups: target sensitivity of patients (partial regression and stabilization) n = 17 and target resistance (progression) n = 13. Levels of growth factors VEGF-A and TGF-β were determined in tumor tissue bioptates by ELISA using standard test systems (Bender Med System, Austria). Statistical processing of results was performed using the Statistica 6.0 program (Stat-Soft, 2001). Results. Polychemotherapy with cetuximab in some patients (n = 13), antitumor therapy with cetuximab did not result in statistically significant changes in levels of VEGF-A, TGF-β and the VEGF-A/TGF-β ratio compared to the initial values. In other patients (n = 17), the studied markers in tumor tissue bioptates were statistically significantly different from the initial values: VEGF-A was decreased by 1.46 times, TGF-β by 2.96 times, while the VEGF-A/TGF-β ratio was twice elevated. Conclusions. The results on levels of growth factors VEGF-A and TGF-β, as well as the VEGF-A/TGF-β ratio, are of a certain prognostic value and can be used as criteria for evaluating the efficacy of antitumor therapy in patients with squamous cell carcinoma of the tongue and mouth floor mucosa.


2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Chaokui Wang ◽  
Ning Gan ◽  
Ping Liu ◽  
Hongying Chen ◽  
Yong Li ◽  
...  

The aim of this study was to investigate the expression of the excision repair cross-complementation group 1 (ERCC1) in oral squamous cell carcinoma (OSCC) and the possible association of ERCC1 polymorphisms with susceptibility and response to chemotherapy of OSCC in a Chinese Han population. The expression of ERCC1 was determined by real-time PCR in eight patients. Four single-nucleotide polymorphisms (SNPs) rs11615, rs3212948, rs3212961, and rs735482 of ERCC1 were genotyped in 113 OSCC patients and 184 healthy controls using a PCR restriction matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) assay. We found that a higher gene expression of ERCC1 was observed in tumor tissue as compared to pericarcinomatous tissue in OSCC patients. All genotypic and allelic frequencies of the tested ERCC1 polymorphisms were in Hardy-Weinberg equilibrium. The genotypic and allelic frequencies of rs11615, rs3212948, rs3212961, and rs735482 of ERCC1 were not different between OSCC patients and controls. No correlation was observed between ERCC1 polymorphisms and the response to chemotherapy. Our results show that ERCC1 is increased in the tumor tissue of OSCC patients. The investigated ERCC1 gene polymorphisms (rs11615, rs3212948, rs3212961, and rs735482) are not associated with the susceptibility and response to chemotherapy of OSCC in our investigated Chinese Han population.


Cytokine ◽  
2015 ◽  
Vol 76 (2) ◽  
pp. 123-130 ◽  
Author(s):  
Anupam Dutta ◽  
Arunabha Banerjee ◽  
Nabajyoti Saikia ◽  
Jyotirmoy Phookan ◽  
Munindra Narayan Baruah ◽  
...  

2021 ◽  
Vol 49 ◽  
Author(s):  
Yasmin Najm Bortoletto ◽  
Júlia De Assis Arantes ◽  
Alessandra Mayer Coelho ◽  
Lais Maria Gomes ◽  
Manuela Cristine Camargo Lambert ◽  
...  

Background: Equines are routinely subjected to enucleation due to palpebral tumors. Blepharoplasties in horses, especially in the lower eyelid, are rarely performed due to the difficulty of sliding once the tissue around the eyes presents low mobility. Defects involving more than 50% of the lower eyelid is considered challenging after tumor removal. Squamous cell carcinoma (SCC) is the second most reported neoplasm in horses, being very common in regions of the lower eyelid, third eyelid, sclera and or cornea. The aim of this study is to present the Destro VY skin advancement flap as a blepharoplasty technique performed after surgical excision of a SCC, with total commitment of the lower eyelid, completely covering the right eye of a mare.Case: A 8-year-oldmarePaint Horse, weighing420 kg,was referred for evaluation of tumor tissue of 6.0 x 4.0 x 2.0 cm, with nodular and ulcerated appearance, involving the right lower eyelid, in its total extension and completely covering the eye, without adhering to it. Considering the initial suspicion of SCC, the treatment strategy performed was surgical eyelid excision and maintenance of the eye, followed by blepharoplasty as an attempt to reconstruct the eyelid. Under general inhalation anesthesia, the animal was placed in left lateral recumbency, when the surgical region was prepared and local anesthetic block was performed. After antisepsis, a skin incision was made circumscribing the tumor, respecting a margin of 10 mm apart and excision of all visible tumor tissue was performed followed by intralesional ozone therapy. Blepharoplasty was performed to cover the portions of the exposed lacrimal and zygomatic bones, as well as correction of the eyelid aesthetics. For this, Destro VY skin advancement flap was performed for reconstruction of the lower eyelid. An incision of approximately 7 cm in V-shaped skin was performed, and the subcutaneous tissue under the V was dissected, maintaining a central pedicle, responsible for the vascularization of the flap, which was slid, approximately 20 mm, towards the eye. After obtaining the desired skin approximation, Y-suture was performed, covering the exposed bone and reconstructing the lower eyelid. In the postoperative period, local instillation of mitomycin eye drops and systemic meloxicam administration were instituted. The mare had her vision restored, presenting satisfactory morpho functional and aesthetic results and no tumor recurrence during 1-year of follow-up. Discussion: The repair of lower eyelid imperfections is challenging, especially when they have large defects, and there are no reports of performing the Destro VY skin advancement flap technique in horses for lower eyelid reconstruction. In this case, the importance of the blepharoplasty technique is emphasized, avoiding enucleation, preserving horse’s vision and aesthetics. In addition, aiming to avoid tumor recurrence, especially if surgical safety margins can not be achieved, other complementary treatments should be associated, including intralesional ozone therapy, mitomycin, an antineoplastic chemotherapy drug, and meloxicam, a COX-2 selective, non-steroidal anti-inflammatory drug, as performed in this study. It is concluded that the use of the Destro VY skin advancement flap technique for reconstruction of the external lamella in cases of SCC in the lower eyelid of horses is a feasible technique, which preserves the animal's vision, as well as aesthetics. The safety margin in the surgical excision of the SCC and the association of complementary therapies in the resolution of the condition are important points also to be considered.Keywords: epidermoid carcinoma, equine, ophthalmology, plastic surgery, skin tumor. Título: Exérese tumoral seguida de blefaroplastia no tratamento de carcinoma de células escamosas em pálpebra inferior de equino 


2018 ◽  
Vol 13 (1) ◽  
pp. 527-532
Author(s):  
Qingyuan Lv ◽  
Weijuan Zhong ◽  
Xiabin Ye ◽  
Yang Lv ◽  
Haiying Liu ◽  
...  

AbstractObjectiveThe aim of this study was to evaluate the expression of Angiopoietin-1 (Ang-1), Angiopoietin-2 (Ang-2) and vascular endothelial growth factor (VEGF) in cervical cancer and its clinical significance.MethodsImmunohistochemical assay was used to examine the expression of Ang-1/2 and VEGF in tumor tissue from 56 cervical squamous cell carcinoma patients treated with operation only (SCC-O group), as well as 51 subjects with cervical squamous cell carcinoma treated with neoadjuvant radiotherapy (SCC-RCO group, n=28) or neoadjuvant chemotherapy (SCC-CO group, n=23). Both microvessel density (MVD) and lymphatic vessel density (LVD) were examined in the three groups through detection of CD34 and D2-40 expression in respective tissue samples.ResultsWith the progression of cervical cancer, the positive expression scores of Ang-2 and VEGF were significantly increased (p<0.05). Compared with surgical intervention, neoadjuvant chemoradiotherapy significantly reduced the positive expression scores of Ang-1, Ang-2, and VEGF in cervical cancer tissues (p<0.05). The MVD values of the SCC-CO and SCC-RO groups were significantly reduced as compared to the SCC-O group (p<0.05). Similarly, the LVD values of the SCC-CO and SCC-RO groups were also significantly reduced when compared to those of the SCC-O group (p<0.05). However, LVD values of the SCC-CO and SCC-RO groups were not statistical different (p>0.05).ConclusionAng-1, Ang-2 and VEGF may play an important role in the development of cervical cancer. Mutual synergism of Ang-2 and VEGF demonstrated a close relationship with the generation of cervical blood and lymphatic vessels. Cervical cancer radiotherapy and chemotherapy could significantly inhibit the formation of blood vessels and lymphatic vessels in tumor tissue.


2002 ◽  
Vol 112 (4) ◽  
pp. 638-644 ◽  
Author(s):  
Douglas K. Trask ◽  
Gregory T. Wolf ◽  
Carol R. Bradford ◽  
Susan G. Fisher ◽  
Kenneth Devaney ◽  
...  

2019 ◽  
Vol 8 (12) ◽  
pp. 2041 ◽  
Author(s):  
Irimie-Aghiorghiesei ◽  
Pop-Bica ◽  
Pintea ◽  
Braicu ◽  
Cojocneanu ◽  
...  

Head and neck squamous cell carcinoma (HNSCC) is a group of malignancies with serious impact on patient quality of life due to a reduced rate of response to chemotherapy or radiation therapy. MiR-21 has been identified as one of the most common proto-oncogenes. It is hypothesized that upregulated miR-21 could serve as a potential biomarker for human cancer diagnosis. Considering the target genes identified for miR-21 in HNSCC, this transcript is an important player in several cellular processes that control carcinogenesis. The abnormal expression of miR-21 in this group of pathologies has been assessed in several publications, but given the heterogeneity of the published results, a meta-analysis and proper bioinformatics analysis of expression databases are needed to correctly establish the prognostic potential of this molecule. The present meta-analysis comprises the published survival data on HNSCC patients, reported as HR and 95% CI, in association with the expression levels of miR-21. Our investigation revealed that miR-21 could be used successfully as a prognostic biomarker in HNSCC patients, confirming its oncogenic potential. Specifically, the upregulation of miR-21 in these patients predicts a worse outcome in terms of survival rate.


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