Abstract 1234: Somatic mutations of FAT1 in oral cancer are associated with tumor progression and survival

2018 ◽  
Author(s):  
Chung Ji Liu ◽  
Shu-Chun Lin ◽  
Li-Han Lin
Keyword(s):  
Oral Cancer ◽  
Tumor Progression ◽  
Somatic Mutations

scholarly journals The stress hormone norepinephrine promotes tumor progression through β2-adrenoreceptors in oral cancer

2020 ◽  
Vol 113 ◽  
pp. 104712 ◽  
Author(s):  
Bowen Zhang ◽  
Chenzhou Wu ◽  
Wen Chen ◽  
Ling Qiu ◽  
Shensui Li ◽  
...  
Keyword(s):  
Oral Cancer ◽  
Tumor Progression ◽  
Stress Hormone ◽  
Β2 Adrenoreceptors

Porphyromonas gingivalis Promotes Oral Squamous Cell Carcinoma Progression in an Immune Microenvironment

2020 ◽  
Vol 99 (6) ◽  
pp. 666-675 ◽  
Author(s):  
L. Wen ◽  
W. Mu ◽  
H. Lu ◽  
X. Wang ◽  
J. Fang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Cancer ◽  
Oral Squamous Cell Carcinoma ◽  
Tumor Progression ◽  
Cell Carcinoma ◽  
Porphyromonas Gingivalis ◽  
Squamous Cell ◽  
Oral Lesions ◽  
Potential Candidate

Increasing evidence has revealed a significant association between microorganisms and oral squamous cell carcinoma (OSCC). Porphyromonas gingivalis, the keystone pathogen in chronic periodontitis, is considered an important potential etiologic agent of OSCC, but the underlying immune mechanisms through which P. gingivalis mediates tumor progression of the oral cancer remain poorly understood. Our cohort study showed that the localization of P. gingivalis in tumor tissues was related to poor survival of patients with OSCC. Moreover, P. gingivalis infection increased oral lesion multiplicity and size and promoted tumor progression in a 4-nitroquinoline-1 oxide (4NQO)–induced carcinogenesis mouse model by invading the oral lesions. In addition, CD11b+ myeloid cells and myeloid-derived suppressor cells (MDSCs) showed increased infiltration of oral lesions. Furthermore, in vitro observations showed that MDSCs accumulated when human-derived dysplastic oral keratinocytes (DOKs) were exposed to P. gingivalis, and CXCL2, CCL2, interleukin (IL)–6, and IL-8 may be potential candidate genes that facilitate the recruitment of MDSCs. Taken together, our findings suggest that P. gingivalis promotes tumor progression by generating a cancer-promoting microenvironment, indicating a close relationship among P. gingivalis, tumor progression of the oral cancer, and immune responses.

scholarly journals Activation of iCaspase-9 in Neovessels Inhibits Oral Tumor Progression

2006 ◽  
Vol 85 (5) ◽  
pp. 436-441 ◽  
Author(s):  
M.S. Pinsky ◽  
W. Song ◽  
Z. Dong ◽  
K. Warner ◽  
B. Zeitlin ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Oral Cancer ◽  
Tumor Progression ◽  
Cancer Cells ◽  
Immunodeficient Mice ◽  
Oral Tumor ◽  
Biodegradable Scaffolds ◽  
Oral Tumors ◽  
Oral Cancer Cells

Tumors of the oral cavity are highly vascularized malignancies. Disruption of neovascular networks was shown to limit the access of nutrients and oxygen to tumor cells and inhibit tumor progression. Here, we evaluated the effect of the activation of an artificial death switch (iCaspase-9) expressed in neovascular endothelial cells on the progression of oral tumors. We used biodegradable scaffolds to co-implant human dermal microvascular endothelial cells stably expressing iCaspase-9 (HDMEC-iCasp9) with oral cancer cells expressing luciferase (OSCC3-luc or UM-SCC-17B-luc) in immunodeficient mice. Alternatively, untransduced HDMEC were co-implanted with oral cancer cells, and a transcriptionaly targeted adenovirus (Ad-VEGFR2-iCasp-9) was injected locally to deliver iCaspase-9 to neovascular endothelial cells. In vivo bioluminescence demonstrated that tumor progression was inhibited, and immunohistochemistry showed that microvessel density was decreased, when iCaspase-9 was activated in tumor-associated microvessels. We conclude that activation of iCaspase-9 in neovascular endothelial cells is sufficient to inhibit the progression of xenografted oral tumors.

scholarly journals TMOD-03. SOMATIC MUTATIONS OF CHROMATIN REGULATOR Kmt2d IN CEREBELLAR PRECURSORS INFLUENCES SHH-MEDULLOBLASTOMA TUMORIGENESIS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi263-vi263
Author(s):  
Reeti Sanghrajka ◽  
I-li Tan ◽  
Alexandre Wojcinski ◽  
Harikrishna Rallapalli ◽  
Daniel Turnbull ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Mouse Models ◽  
Somatic Mutations ◽  
Early Stage ◽  
Pediatric Brain Tumor ◽  
Gene Encoding ◽  
Positive Correlation ◽  
Activating Mutations ◽  
Shh Pathway ◽  
Chromatin Regulator

Abstract Medulloblastoma (MB), the most common malignant pediatric brain tumor, is a classic example of dysregulation of developmental pathways leading to tumorogenesis. Despite advancements in multi-modal therapies, most patients suffer from long-term neurocognitive and neuroendocrine disabilities. The Sonic Hedgehog subgroup of MB (SHH-MB) accounts for ~30% of all cases and originates from ATOH1+ cerebellar granule cell precursors (GCPs). Experimental data in mice has shown that activating mutations in the SHH pathway induce tumors only in rare GCPs, suggesting that additional mutations and epigenetic changes are required to influence tumor progression. The KMT2D gene, encoding the histone-lysine N-methyltransferase 2D, is amongst the ten most frequently mutated genes in MB, with somatic mutations seen in ~15% of all SHH-MB patients. We developed sporadic mouse models of SHH-MB with a low penetrance to enable studies of secondary mutations (Tan, PNAS, 2018). Immunofluorescence staining for KMT2D on early-stage SHH-MB lesions, mid-stage and late-stage tumors revealed that a subset of lesions/tumors (16/98) do not express KMT2D and are negative for H3K4me3. Interestingly, P53 and KMT2D expression showed a positive correlation in ~94% of tumors/lesions and NeuN and KMT2D showed a positive correlation in ~92% of tumors/lesions. In order to determine the roles for KMT2D in GCP proliferation and differentiation, and uncover whether and how KMT2D promotes SHH-MB tumorigenesis, we are using genetic mouse-models whereby Kmt2d is heterozygously or homozygously deleted alone, or in conjunction with activation of the SHH pathway. Mice with SHH-MB tumors expressing SmoM2 and a loss of Kmt2d develop aggressive tumors at high penetrance, with metastatic leptomeningeal spread in the brain stem and spinal cord. Thus, loss of Kmt2d increases SHH-MB tumor progression and leads to malignancy. Ongoing studies are determining how the chromatin landscape and gene expression are changed when Kmt2d is deleted in GCPs.

Oncogene protein co-expression in oral cancer and its possible association with tumor progression

1997 ◽  
Vol 26 ◽  
pp. 177
Author(s):  
M. Shiraki ◽  
T. Odajima ◽  
N. Tanaka ◽  
I. Nagai ◽  
T. Yamashita ◽  
...  
Keyword(s):  
Oral Cancer ◽  
Tumor Progression ◽  
Oncogene Protein

The importance of melanoma inhibitory activity gene family in the tumor progression of oral cancer

2018 ◽  
Vol 68 (5) ◽  
pp. 278-286 ◽  
Author(s):  
Tomonori Sasahira ◽  
Anja Katrin Bosserhoff ◽  
Tadaaki Kirita
Keyword(s):  
Oral Cancer ◽  
Gene Family ◽  
Tumor Progression ◽  
Inhibitory Activity ◽  
Melanoma Inhibitory Activity

scholarly journals Somatic USP8 mutations are frequent events in corticotroph tumor progression causing Nelson’s tumor

2018 ◽  
Vol 178 (1) ◽  
pp. 57-63 ◽  
Author(s):  
Luis G Pérez-Rivas ◽  
Marily Theodoropoulou ◽  
Troy H Puar ◽  
Julia Fazel ◽  
Mareike R Stieg ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Somatic Mutations ◽  
Visual Field Defects ◽  
Tumor Control ◽  
Specific Protease ◽  
Life Threatening ◽  
Ubiquitin Specific Protease ◽  
Acth Secreting ◽  
Design And Methods ◽  
Retrospective Multicenter Study

Objective Somatic mutations in the ubiquitin-specific protease 8 (USP8) gene are frequent in corticotroph tumors causing Cushing’s disease (CD). Corticotroph tumor progression, the so-called Nelson’s syndrome (NS), is a potentially life-threatening complication of bilateral adrenalectomy in patients with refractory CD that is caused by the development of an ACTH-secreting tumor of the pituitary gland. Whether USP8 alterations are also present in progressive Nelson’s tumors has not been studied in detail so far. Design and Methods Retrospective, multicenter study involving tumors from 33 patients with progressive corticotroph tumors (29 females) and screening for somatic mutations on the mutational hotspot of the USP8 gene in the exon 14 with Sanger sequencing. Results Fifteen out of 33 tumors (45%) presented with a mutation in the exon 14 of USP8, with c.2159C>A (p.Pro720Gln) being the most frequent (9/33), followed by c.2155_2157delTCC (p.Ser718del, 4/33) and c.2152T>C (p.Ser718Pro, 2/33). This prevalence is similar to that previously reported for CD. Mutations were found exclusively in females. Other variables, such as age at diagnosis with NS, body mass index, hyperpigmentation, visual field defects, adenoma size or mortality, did not significantly differ between patients with wild-type and mutant tumors. Patients with USP8 mutant tumors exhibited higher levels of plasma ACTH after surgery (median: 640 vs 112 pg/mL, P = 0.03). No differences were observed in ACTH normalization (<50 pg/mL) and tumor control after surgery for Nelson’s tumor. Conclusion Somatic mutations in USP8 are common in Nelson’s tumors, indicating that they do not drive the corticotroph tumor progression that leads to NS, and may be associated with a less favorable biochemical outcome after surgery for Nelson’s tumor.

scholarly journals Targeting all transforming growth factor-β isoforms with an Fc chimeric receptor impairs tumor growth and angiogenesis of oral squamous cell cancer

2020 ◽  
Vol 295 (36) ◽  
pp. 12559-12572
Author(s):  
Kazuki Takahashi ◽  
Yuichi Akatsu ◽  
Katarzyna A. Podyma-Inoue ◽  
Takehisa Matsumoto ◽  
Hitomi Takahashi ◽  
...  
Keyword(s):  
Growth Factor ◽  
Oral Cancer ◽  
Tumor Growth ◽  
Tumor Progression ◽  
Cancer Cells ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Type I ◽  
Oral Cancer Cells ◽  
Tgf Β1

Tumor progression is governed by various growth factors and cytokines in the tumor microenvironment (TME). Among these, transforming growth factor-β (TGF-β) is secreted by various cell types residing in the TME and promotes tumor progression by inducing the epithelial-to-mesenchymal transition (EMT) of cancer cells and tumor angiogenesis. TGF-β comprises three isoforms, TGF-β1, -β2, and -β3, and transduces intracellular signals via TGF-β type I receptor (TβRI) and TGF-β type II receptor (TβRII). For the purpose of designing ligand traps that reduce oncogenic signaling in the TME, chimeric proteins comprising the ligand-interacting ectodomains of receptors fused with the Fc portion of immunoglobulin are often used. For example, chimeric soluble TβRII (TβRII-Fc) has been developed as an effective therapeutic strategy for targeting TGF-β ligands, but several lines of evidence indicate that TβRII-Fc more effectively traps TGF-β1 and TGF-β3 than TGF-β2, whose expression is elevated in multiple cancer types. In the present study, we developed a chimeric TGF-β receptor containing both TβRI and TβRII (TβRI-TβRII-Fc) and found that TβRI-TβRII-Fc trapped all TGF-β isoforms, leading to inhibition of both the TGF-β signal and TGF-β–induced EMT of oral cancer cells, whereas TβRII-Fc failed to trap TGF-β2. Furthermore, we found that TβRI-TβRII-Fc suppresses tumor growth and angiogenesis more effectively than TβRII-Fc in a subcutaneous xenograft model of oral cancer cells with high TGF-β expression. These results suggest that TβRI-TβRII-Fc may be a promising tool for targeting all TGF-β isoforms in the TME.

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