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Skrypnyk M, Yatsenko T, Riabets O, Salama Y, Skikevych M, Osada T, Tobita M, Takahashi S, Hattori K, Heissig B. Interleukin-10 induces TNF-driven apoptosis and ROS production in salivary gland cancer cells. Heliyon 2024; 10:e31777. [PMID: 38882335 PMCID: PMC11176751 DOI: 10.1016/j.heliyon.2024.e31777] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Revised: 05/21/2024] [Accepted: 05/21/2024] [Indexed: 06/18/2024] Open
Abstract
Treatment resistance after chemo-/immunotherapy occurs in patients with head and neck squamous cell cancers (HNSCs), including salivary gland cancers (SGCs). Interleukin-10 (IL-10), a cytokine with pro- and anti-cancer effects, has an unclear impact on HNSC/SGC cells. We show that HNSC patients exhibiting high expression of IL-10 and its receptor IL-10Rα experience have prolonged overall survival. Immunoreactive IL-10 was low in ductal cells of human SGC biopsies. Human (A253) and murine WR21-SGC cells expressed IL-10Rβ, but only A253 cells expressed IL-10 and IL-10Rα. The addition of recombinant IL-10 impaired SGC cell proliferation and induced apoptosis in vitro. N-acetylcysteine restored IL-10-induced reactive oxygen species (ROS) production but did not prevent IL-10-mediated viability loss. Mechanistically, recIL-10 delayed cell cycle progression from G0/G1 to the S phase with cyclin D downregulation and upregulation of NF-kB. IL-10 increased tumor necrosis factor-α (TNF-α) in A253 and WR21 and FasL in WR21 cells. Neutralizing antibodies against TNF-α and NF-kB inhibition restored SGC proliferation after IL-10 treatment, emphasizing the critical role of TNF-α and NF-kB in IL-10-mediated anti-tumor effects. These findings underscore the potential of IL-10 to impede SGC cell growth through apoptosis induction, unraveling potential therapeutic targets for intervention in salivary gland carcinomas.
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Affiliation(s)
- Maksym Skrypnyk
- Department of Research Support Utilizing Bioresource Bank, Graduate School of Medicine, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan
| | - Tetiana Yatsenko
- Department of Research Support Utilizing Bioresource Bank, Graduate School of Medicine, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan
| | - Oleksandra Riabets
- Department of Research Support Utilizing Bioresource Bank, Graduate School of Medicine, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan
| | - Yousef Salama
- An-Najah Center for Cancer and Stem Cell Research, Faculty of Medicine and Health Sciences, An-Najah National University, P.O. Box 7, Nablus 99900800, Palestine
| | - Margarita Skikevych
- Department of Surgical Dentistry and Maxillofacial Surgery with Plastic and Reconstructive Surgery of Head and Neck, Poltava State Medical University, 23 Shevchenko Street. Poltava, Ukraine
| | - Taro Osada
- Department of Gastroenterology Juntendo University Urayasu Hospital, Japan
| | - Morikuni Tobita
- Department of Oral and Maxillofacial Surgery, Juntendo University School of Medicine, Japan
| | - Satoshi Takahashi
- Division of Clinical Precision Research Platform, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
| | - Koichi Hattori
- Center for Genome and Regenerative Medicine, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan
| | - Beate Heissig
- Department of Research Support Utilizing Bioresource Bank, Graduate School of Medicine, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan
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Shu L, Dai Q, Zhu P, Wu T. Mechanism of Survivin-mediated neovascularization in ischemic stroke. Asian J Surg 2024:S1015-9584(24)00746-2. [PMID: 38653701 DOI: 10.1016/j.asjsur.2024.04.085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Accepted: 04/12/2024] [Indexed: 04/25/2024] Open
Affiliation(s)
- Lingfeng Shu
- Encephalopathy Hospital, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Henan, Zhengzhou, 450099, China; The First Clinical Medical College of Henan University of Chinese Medicine, Henan, Zhengzhou, 450046, China.
| | - Qinghai Dai
- The First Clinical Medical College of Henan University of Chinese Medicine, Henan, Zhengzhou, 450046, China.
| | - Pengcheng Zhu
- The First Clinical Medical College of Henan University of Chinese Medicine, Henan, Zhengzhou, 450046, China.
| | - Tao Wu
- Encephalopathy Hospital, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Henan, Zhengzhou, 450099, China; The First Clinical Medical College of Henan University of Chinese Medicine, Henan, Zhengzhou, 450046, China.
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Amano S, Hirashita T, Kawano Y, Nishida H, Orimoto H, Kawamura M, Kawasaki T, Masuda T, Endo Y, Ohta M, Daa T, Inomata M. Apoptosis-related factors are relevant to progression of pancreatic neuroendocrine tumors. World J Surg Oncol 2023; 21:381. [PMID: 38082268 PMCID: PMC10714622 DOI: 10.1186/s12957-023-03267-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Accepted: 12/05/2023] [Indexed: 12/18/2023] Open
Abstract
BACKGROUND Multidisciplinary therapy centered on antitumor drugs is indicated in patients with unresectable pancreatic neuroendocrine tumors (PanNET). However, the criteria for selection of optimal therapeutic agents is controversial. The aim of this study was to assess the malignancy of PanNET for optimal therapeutic drug selection. METHODS Forty-seven patients with PanNET who underwent surgery were reviewed retrospectively, and immunohistochemical characteristics, including expression of GLUT1, SSTR2a, SSTR5, Survivin, X-chromosome-linked inhibitor of apoptosis protein (XIAP), and Caspase3 in the resected specimens, were investigated. Relapse-free survival (RFS) and overall survival (OS) were evaluated with regard to the characteristics using the Kaplan-Meier method and compared with the log-rank test. RESULTS GLUT1 expression showed significant correlation with sex (p = 0.036) and mitotic rate (p = 0.048). Survivin and XIAP expression showed significant correlation with T-stage (p = 0.014 and 0.009), p-Stage (p = 0.028 and 0.045), and mitotic rate (p = 0.023 and 0.007). XIAP expression also significantly influenced OS (p = 0.044). CONCLUSIONS Survivin and XIAP correlated with grade of malignancy, and expression of XIAP in particular was associated with a poor prognosis. Expression of these proteins may be a useful indicator to select optimal therapeutic agents in PanNET.
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Affiliation(s)
- Shota Amano
- Department of Gastroenterological and Pediatric Surgery, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-Machi, Yufu, Oita, 879-5593, Japan.
- Department of Diagnostic Pathology, Oita University Faculty of Medicine, Oita, Japan.
| | - Teijiro Hirashita
- Department of Gastroenterological and Pediatric Surgery, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-Machi, Yufu, Oita, 879-5593, Japan
| | - Yoko Kawano
- Department of Gastroenterological and Pediatric Surgery, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-Machi, Yufu, Oita, 879-5593, Japan
| | - Haruto Nishida
- Department of Diagnostic Pathology, Oita University Faculty of Medicine, Oita, Japan
| | - Hiroki Orimoto
- Department of Gastroenterological and Pediatric Surgery, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-Machi, Yufu, Oita, 879-5593, Japan
| | - Masahiro Kawamura
- Department of Gastroenterological and Pediatric Surgery, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-Machi, Yufu, Oita, 879-5593, Japan
| | - Takahide Kawasaki
- Department of Gastroenterological and Pediatric Surgery, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-Machi, Yufu, Oita, 879-5593, Japan
- Department of Comprehensive Surgery for Community Medicine, Oita University Faculty of Medicine, Oita, Japan
| | - Takashi Masuda
- Department of Gastroenterological and Pediatric Surgery, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-Machi, Yufu, Oita, 879-5593, Japan
| | - Yuichi Endo
- Department of Gastroenterological and Pediatric Surgery, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-Machi, Yufu, Oita, 879-5593, Japan
| | - Masayuki Ohta
- Department of Gastroenterological and Pediatric Surgery, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-Machi, Yufu, Oita, 879-5593, Japan
- Global Oita Medical Advanced Research Center for Health, Oita University, Oita, Japan
| | - Tsutomu Daa
- Department of Diagnostic Pathology, Oita University Faculty of Medicine, Oita, Japan
| | - Masafumi Inomata
- Department of Gastroenterological and Pediatric Surgery, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-Machi, Yufu, Oita, 879-5593, Japan
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Eskandari F, Razavian A, Zare R, Ejlali S, Razmahang A, Zanjani M, Aghili SS, Mahdiyar MA, Mofidi H, Abbasi K, Badkoobeh A, Shamloo N, Hakim LK, Hussain A, Tebyaniyan H. Evaluation of BIRC6 Expression in Oral Squamous Cell Carcinoma, Epithelial Dysplasia, Lichen Planus with and without Dysplasia, and Hyperkeratosis. Diagnostics (Basel) 2023; 13:3560. [PMID: 38066801 PMCID: PMC10706016 DOI: 10.3390/diagnostics13233560] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Revised: 11/22/2023] [Accepted: 11/23/2023] [Indexed: 01/01/2025] Open
Abstract
BACKGROUND BIRC6, regarded as the pivotal member of the inhibitor of the apoptosis (IAP) family, has been linked to the development of different types of cancer in humans. The objective of this study was to examine the expression of BIRC6 in various oral conditions, including OLP with dysplasia (OLPD), hyperkeratosis (HK), OLP, epithelial dysplasia (ED), and oral squamous cell carcinoma (OSCC), to investigate its potential involvement in the development of OSCC and the pathogenesis and malignant transformation of OLP, which is known as a precancerous condition. METHODS In this retrospective cross-sectional study, 99 cases, consisting of 19 cases of OSCC, 21 cases of ED, 23 cases of OLP, 20 cases of OLPD, and 16 cases of HK as the control group, were investigated regarding BIRC6 expression by immunohistochemical staining. After that, the immunohistochemical expression of BIRC6 in the epithelial compartment was analyzed. Statistical analysis was performed to investigate the relationship between the expression of BIRC6 and clinicopathological variables. The statistical analysis of the data involved the use of one-way ANOVA, post hoc Tukey, Kruskal-Wallis, Chi-square, Spearman's correlation, and Mann-Whitney tests. The significance level was set at p < 0.05. RESULTS Positive BIRC6 staining was found in 91.7% of the subjects of OLP, 88.1% of HK, 86.1% of ED, 93% of OLPD, and 94.7% of OSCC. OSCC showed the highest BIRC6 expression (p = 0.00). The average total staining score was remarkably greater in OSCC and dysplastic lesions compared with HK (p = 0.00, p = 0.00). CONCLUSIONS While the current study suggested that BIRC6 may play a role in the tumorigenesis of OSCC, its role in the malignant transformation of OLP has yet to be definitively established.
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Affiliation(s)
- Fateme Eskandari
- School of Dentistry, Shiraz University of Medical Sciences, Shiraz 71348-14336, Iran; (F.E.); (S.S.A.)
| | - Alireza Razavian
- Department of Endodontics, Semnan Dental School, Semnan University of Medical Sciences, Semnan 35147-99442, Iran
| | - Razieh Zare
- Oral and Maxillofacial Research Center, Department of Oral and Maxillofacial Pathology, School of Dentistry, Shiraz University of Medical Sciences, Shiraz 71348-14336, Iran
| | - Shayan Ejlali
- School of Dentistry, Borujerd Branch, Islamic Azad University, Borujerd 69151-36335, Iran;
| | - Alireza Razmahang
- Molecular Pathology Research Center, Shiraz University of Medical Sciences, Shiraz 71348-14336, Iran;
| | - Milad Zanjani
- Department of Oral and Maxillofacial Surgery, School of Dentistry, Shiraz University of Medical Sciences, Shiraz 71348-14336, Iran;
| | - Seyedeh Sara Aghili
- School of Dentistry, Shiraz University of Medical Sciences, Shiraz 71348-14336, Iran; (F.E.); (S.S.A.)
| | - Mohammad Amin Mahdiyar
- Department of Orthopedics, School of Medicine, Shiraz University of Medical Sciences, Shiraz 71348-14336, Iran
| | - Hossein Mofidi
- Department of Endodontics, School of Dentistry, Shiraz University of Medical Sciences, Shiraz 71348-14336, Iran
| | - Kamyar Abbasi
- Department of Prosthodontics, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran 19839-69411, Iran
| | - Ashkan Badkoobeh
- Department of Oral and Maxillofacial Surgery, School of Dentistry, Qom University of Medical Sciences, Qom 37136-49373, Iran
| | - Nafiseh Shamloo
- Department of Oral and Maxillofacial Pathology, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran 19839-69411, Iran
| | | | - Ahmed Hussain
- School of Dentistry, Edmonton Clinic Health Academy, University of Alberta, Edmonton, AB T6G 1C9, Canada
| | - Hamid Tebyaniyan
- Department of Science and Research, Islimic Azade University, Tehran 15847-15414, Iran
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Saleh E, Ukwas A. Adenoid Cystic Carcinoma of Salivary Glands: A Ten-Year Review and an Assessment of the Current Management, Surgery, Radiotherapy, and Chemotherapy. Int J Otolaryngol 2023; 2023:7401458. [PMID: 37159817 PMCID: PMC10163974 DOI: 10.1155/2023/7401458] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2023] [Revised: 02/14/2023] [Accepted: 02/18/2023] [Indexed: 05/11/2023] Open
Abstract
Adenoid cystic carcinoma (ACC) is a rare cancer that arises from the salivary glands and other sites in the body, such as the lung and breast. Although the tumor accounts for 10% of all salivary gland malignancies, it only accounts for 1% of head and neck malignancies. It can affect both major and minor salivary glands; here, it is called salivary gland adenoid cystic carcinoma or SACC, with a slight predilection to the latter, and commonly manifests between the 6th and 7th decades of life. The disease also shows a slight female predilection, with a reported female to male ratio of 3 : 2. Lesions of SACC are often insidious and slow-growing, and symptoms such as pain and altered sensation are frequently associated with advanced stages of the disease. Salivary adenoid cystic carcinoma is characterized by perineural invasion (PNI), a distinctive feature that potentially plays a significant role in the tumor's relapse and recurrence, which is approximately 50%. The disease is not prevalent, and its etiopathogenesis is poorly understood, although several genetic patterns and biomarkers have been linked to its initiation and/or progression. The discovery of these mutations and biomarkers has encouraged several clinical studies to use therapeutic agents to target the specific receptors on the cancer cells to potentially prevent further proliferation of the tumor cells and metastasis of the disease. Diagnosis of SACC is often challenging and frequently requires a combination of clinical examination, imaging, and histopathology. Management of SACC is primarily surgical excision, while radiotherapy has shown to be effective in improving local control in cases with microscopic residual disease. However, treatment of recurrent or metastatic tumors by radiotherapy with or without chemotherapy has so far shown limited success. The aim of this thesis is to provide an update of literature on SACC with a particular focus on the latest management approaches and future trends.
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Affiliation(s)
- Eyad Saleh
- Eastman Dental Institute, University College London, London, UK
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Schnoell J, Kotowski U, Jank BJ, Stoiber S, Gurnhofer E, Schlederer M, Heiduschka G, Kenner L, Kadletz-Wanke L. Prognostic Relevance of Thyroid-Hormone-Associated Proteins in Adenoid Cystic Carcinoma of the Head and Neck. J Pers Med 2021; 11:jpm11121352. [PMID: 34945824 PMCID: PMC8703850 DOI: 10.3390/jpm11121352] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Revised: 12/06/2021] [Accepted: 12/08/2021] [Indexed: 12/14/2022] Open
Abstract
The proteins sodium iodide symporter (NIS), μ-crystallin (CRYM), and thyroid hormone receptor beta (THRB) have been associated with prognosis in various cancer entities. While NIS and THRB may serve as possible therapeutic targets, the role of CRYM in cancer is still unclear. Protein levels of 44 patients with adenoid cystic carcinoma of the head and neck were analyzed using immunohistochemistry and correlated with clinicopathological data and outcome. NIS was positive in 72%, CRYM was positive in 55%, and THRB was positive in 39% of the patients. CRYM-positive adenoid cystic carcinomas were associated with a better cause-specific survival. Thus, our data indicate that CRYM might be a suitable positive prognostic marker in adenoid cystic carcinoma of the head and neck. Furthermore, expression of NIS was present in most patients and therefore evaluation of the use of radioiodine treatment is recommended.
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Affiliation(s)
- Julia Schnoell
- Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Vienna, 1090 Vienna, Austria; (J.S.); (U.K.); (B.J.J.); (L.K.-W.)
| | - Ulana Kotowski
- Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Vienna, 1090 Vienna, Austria; (J.S.); (U.K.); (B.J.J.); (L.K.-W.)
| | - Bernhard J. Jank
- Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Vienna, 1090 Vienna, Austria; (J.S.); (U.K.); (B.J.J.); (L.K.-W.)
| | - Stefan Stoiber
- Department of Pathology, Comprehensive Cancer Center, Institute of Cancer Research, Medical University of Vienna, 1090 Vienna, Austria; (S.S.); (E.G.); (M.S.)
- Christian Doppler Laboratory for Applied Metabolomics, 1090 Vienna, Austria
| | - Elisabeth Gurnhofer
- Department of Pathology, Comprehensive Cancer Center, Institute of Cancer Research, Medical University of Vienna, 1090 Vienna, Austria; (S.S.); (E.G.); (M.S.)
| | - Michaela Schlederer
- Department of Pathology, Comprehensive Cancer Center, Institute of Cancer Research, Medical University of Vienna, 1090 Vienna, Austria; (S.S.); (E.G.); (M.S.)
| | - Gregor Heiduschka
- Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Vienna, 1090 Vienna, Austria; (J.S.); (U.K.); (B.J.J.); (L.K.-W.)
- Correspondence: (G.H.); (L.K.)
| | - Lukas Kenner
- Department of Pathology, Comprehensive Cancer Center, Institute of Cancer Research, Medical University of Vienna, 1090 Vienna, Austria; (S.S.); (E.G.); (M.S.)
- Christian Doppler Laboratory for Applied Metabolomics, 1090 Vienna, Austria
- Unit of Laboratory Animal Pathology, University of Veterinary Medicine, 1210 Vienna, Austria
- CBmed GmbH-Center for Biomarker Research in Medicine, 8010 Graz, Austria
- Correspondence: (G.H.); (L.K.)
| | - Lorenz Kadletz-Wanke
- Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Vienna, 1090 Vienna, Austria; (J.S.); (U.K.); (B.J.J.); (L.K.-W.)
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Schnoell J, Kadletz L, Jank BJ, Oberndorfer F, Brkic FF, Gurnhofer E, Cede J, Seemann R, Kenner L, Heiduschka G. Expression of inhibitors of apoptosis proteins in salivary gland adenoid cystic carcinoma: XIAP is an independent marker of impaired cause-specific survival. Clin Otolaryngol 2020; 45:364-369. [PMID: 31984681 PMCID: PMC7317768 DOI: 10.1111/coa.13509] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2018] [Revised: 12/28/2019] [Accepted: 01/15/2020] [Indexed: 01/17/2023]
Abstract
Objectives Inhibitors of apoptosis proteins are crucial to carcinogenesis since their expression results in evasion of apoptosis. Overexpression of inhibitors of apoptosis has repeatedly been associated with resistance to treatment and poor prognosis in various cancers. The role of inhibitors of apoptosis in adenoid cystic carcinoma of the salivary gland is still unclear. The aim of this study was to investigate the expression of inhibitors of apoptosis and their potential prognostic value in adenoid cystic carcinoma. Design, setting and participants Forty‐nine patients, diagnosed with adenoid cystic carcinoma of the salivary gland between 1996 and 2016, were retrospectively included in this study. The expression of cIAP1, cIAP2, XIAP, Birc6, Livin and Survivin was assessed using immunohistochemistry, and their association of survival and prognosis was evaluated during a median follow‐up of 6.4 years. Main outcome measure Cause‐specific survival and recurrence‐free survival rates. Results XIAP, cIAP2, Livin and nuclear Survivin showed high expression levels in adenoid cystic carcinoma in most patients. There was no significant association of cIAP1, cIAP2, Livin, Birc6 and Survivin with outcome. However, high XIAP expression was associated with worse cause‐specific survival and worse response to radiotherapy and proved to be an independent marker in multivariable analysis. Conclusion Our data indicate that high expression of XIAP may be used as a prognosticator for poor survival and poor response to radiotherapy in adenoid cystic carcinoma patients.
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Affiliation(s)
- Julia Schnoell
- Department of Otorhinolaryngology, Head and Neck Surgery, Medical University Vienna, Vienna, Austria
| | - Lorenz Kadletz
- Department of Otorhinolaryngology, Head and Neck Surgery, Medical University Vienna, Vienna, Austria
| | - Bernhard J Jank
- Department of Otorhinolaryngology, Head and Neck Surgery, Medical University Vienna, Vienna, Austria
| | | | - Faris F Brkic
- Department of Otorhinolaryngology, Head and Neck Surgery, Medical University Vienna, Vienna, Austria
| | | | - Julia Cede
- Department of Oral and Maxillofacial Surgery, Medical University of Vienna, Vienna, Austria
| | - Rudolf Seemann
- Department of Oral and Maxillofacial Surgery, Medical University of Vienna, Vienna, Austria
| | - Lukas Kenner
- Department of Pathology, Medical University of Vienna, Vienna, Austria.,Ludwig Boltzmann Institute for Cancer Research, Vienna, Austria.,Unit of Laboratory Animal Pathology, University of Veterinary Medicine Vienna, Vienna, Austria
| | - Gregor Heiduschka
- Department of Otorhinolaryngology, Head and Neck Surgery, Medical University Vienna, Vienna, Austria
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