Endoplasmic reticulum aminopeptidase 2 involvement in metastasis of oral cavity squamous cell carcinoma discovered by proteome profiling of primary cancer cells

Oral cancer account for 30% of all malignant tumors in the head and neck, more than 90% of these cancers are squamous cell carcinoma. The p53 tumor suppressor gene known as "the guardian of the genome" has a major function in cell cycle control and act as a main defense against cancer, the occurrence of genomic instability causes inactivation and mutation of p53, which related to the progression of cancer cells and poor prognosis for patients. Human telomerase reverse transcriptase (hTERT), a catalytic protein subunit of the complex telomerase enzyme, prevents telomere erosion during DNA replication, thus allowing cells to escape the aging cell step. The relationship between hTERT and malignant transformation is around 90%, the detection of hTERT is associated with malignancy that leads to a worse prognosis which increases immortality or continuous growth in cancer cells. This study was conducted with retrospective cross sectional using immunohistochemical p53 and hTERT smear in 30 paraffin blocks of squamous cell carcinoma of the oral cavity, held at the Anatomical Pathology Department of Hasan Sadikin Hospital Bandung. P53 and hTERT immunoexpression were correlated with histopathological grading of squamous cell carcinoma of oral cavity (SCC) and statistically analyzed with Rank Spearman correlation with significance of p<0.05 (95%) and Kendall Coefficient of Concordance with significance of p <0.05% (95%). The results showed a significant positive correlation between p53 immunoexpression with histopathological grading (rs=0.497, p-value = 0.005), between hTERT immunoexpression and histopathological grading (rs=0.441, p-value=0.015), and between p53 and immunoexpression hTERT with histopathological grading (W=0.568, p-value=3.99E-08) Conclusion: the higher p53 and/or hTERT immunoexpression, the higher or worse the level of histopathological grading of oral cavity squamous cell carcinoma (poorly differentiated).

Download Full-text

Apatinib induces endoplasmic reticulum stress-mediated apoptosis and autophagy and potentiates cell sensitivity to paclitaxel via the IRE-1α–AKT–mTOR pathway in esophageal squamous cell carcinoma

Cell & Bioscience ◽

10.1186/s13578-021-00640-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yu-Ming Wang ◽

Xin Xu ◽

Jian Tang ◽

Zhi-Yong Sun ◽

Yu-Jie Fu ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Endoplasmic Reticulum ◽

Esophageal Squamous Cell Carcinoma ◽

Er Stress ◽

Cell Carcinoma ◽

Cancer Cells ◽

Squamous Cell ◽

Molecular Mechanisms ◽

Mtor Pathway ◽

Induced Apoptosis

Abstract Background Apatinib, a novel vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor, has been approved for the treatment of metastatic gastric cancer and other tumors. Apatinib exerts antiproliferative and proapoptotic effects in different kinds of cancer cells. However, the molecular mechanisms by which apatinib effective against esophageal squamous cell carcinoma (ESCC) have only been partially researched and whether it has a sensitizing effect on paclitaxel remains unclear. Materials and methods The effects of apatinib or paclitaxel on endoplasmic reticulum (ER) stress, autophagy, apoptosis and proliferation of ESCC cell lines were evaluated. Western blot and immunohistochemistry analyses were performed to detect the expression of related genes. The weight and volume of xenograft tumors in mice were measured. Results In the current study, we elucidated the antiproliferative and ER-stress-mediated autophagy-inducing effects of apatinib on ECA-109 and KYSE-150 esophageal squamous cancer cells and identified the underlying mechanisms of its action. We demonstrated that apatinib not only inhibited the proliferation and induced the apoptosis of ESCC cells, but also activated ER stress and triggered protective autophagy. Moreover, inhibiting autophagy by chloroquine (CQ) enhanced the apatinib-induced apoptosis of ESCC cells through the IRE-1α–AKT–mTOR pathway. In addition, we showed, for the first time, the paclitaxel combined with apatinib and CQ exhibited the best antitumor effect on ESCC both in vivo and in vitro via the IRE-1α–AKT–mTOR pathway. Conclusions Our data showed that apatinib induced ER stress, autophagy and apoptosis in ESCC. Inhibiting autophagy by CQ enhanced apatinib-induced apoptosis. The combination of apatinib and CQ sensitized ESCC cells to paclitaxel to induce apoptosis through the IRE-1α–AKT–mTOR signaling pathway, thus providing the basis for its use in innovative anticancer therapeutic strategies. Graphic abstract

Download Full-text

Multiple primary cancer risk in patients with squamous cell carcinoma of the oral cavity

Plastic & Reconstructive Surgery ◽

10.1097/00006534-198811000-00093 ◽

1988 ◽

Vol 82 (5) ◽

pp. 931

Author(s):

H. Shibuya ◽

Hal G. Bingham

Keyword(s):

Squamous Cell Carcinoma ◽

Cancer Risk ◽

Oral Cavity ◽

Cell Carcinoma ◽

Squamous Cell ◽

Multiple Primary Cancer ◽

Primary Cancer ◽

Multiple Primary

Download Full-text

Multiple primary cancer risk in patients with squamous cell carcinoma of the oral cavity

Cancer ◽

10.1002/1097-0142(19871215)60:12<3083::aid-cncr2820601237>3.0.co;2-l ◽

1987 ◽

Vol 60 (12) ◽

pp. 3083-3086 ◽

Cited By ~ 42

Author(s):

Hitoshi Shibuya ◽

Shigemasa Hisamitsu ◽

Shigeaki Shioiri ◽

Junichi Horiuchi ◽

Soji Suzuki

Keyword(s):

Squamous Cell Carcinoma ◽

Cancer Risk ◽

Oral Cavity ◽

Cell Carcinoma ◽

Squamous Cell ◽

Multiple Primary Cancer ◽

Primary Cancer ◽

Multiple Primary

Download Full-text

Saliva proteome profiling reveals potential salivary biomarkers for detection of oral cavity squamous cell carcinoma

PROTEOMICS ◽

10.1002/pmic.201500157 ◽

2015 ◽

Vol 15 (19) ◽

pp. 3394-3404 ◽

Cited By ~ 53

Author(s):

Chih-Ching Wu ◽

Hao-Wei Chu ◽

Chia-Wei Hsu ◽

Kai-Ping Chang ◽

Hao-Ping Liu

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Cavity ◽

Cell Carcinoma ◽

Squamous Cell ◽

Proteome Profiling ◽

Salivary Biomarkers

Download Full-text

Abstract #906: Squamous Cell Carcinoma of the Pituitary Stalk, A Primary Cancer

Endocrine Practice ◽

10.1016/s1530-891x(20)45196-1 ◽

2016 ◽

Vol 22 ◽

pp. 196

Author(s):

Viviana Ortiz-Santiago ◽

Oscar Ruiz ◽

Milliette Alvarado Santiago ◽

Loida Gonzalez-Rodriguez ◽

Margarita Ramirez-Vick

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Pituitary Stalk ◽

Primary Cancer

Download Full-text

Spindle Cell Carcinoma of the Tongue: Fallacies in Its Diagnosis

International Journal of Innovative Research in Medical Science ◽

10.23958/ijirms/vol03-i02/14 ◽

2018 ◽

Vol 3 (02) ◽

Author(s):

Amrit Kaur Kaler, Shweta C, Smitha Chandra B.C, Rajeev Naik

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Cavity ◽

Cell Carcinoma ◽

Cell Population ◽

Squamous Cell ◽

Spindle Cell ◽

Spindle Cell Carcinoma ◽

Biphasic Tumor ◽

Carcinoma Of The Tongue ◽

Ihc Markers

Spindle cell carcinoma is a rare aggressive biphasic tumor, composed of neoplastic proliferation of both epithelial (squamous) and spindle cell population. It constitutes about 1% of all oral cavity tumors 2a and is almost rare on the tongue; only few cases have been reported so far. This variant of squamous cell carcinoma, comprises major diagnostic problems due to its varied histomorphology and resemblance to sarcomatous lesion; hence diligent screening and IHC markers are mandatory for its diagnosis.

Download Full-text

PD-L1 and survival in oral cavity squamous cell carcinoma

Periodontology ◽

10.33925/1683-3759-2020-25-4-287-294 ◽

2020 ◽

Vol 25 (4) ◽

pp. 287-294

Author(s):

S. I. Kutukova ◽

N. P. Beliak ◽

G. A. Raskin ◽

M. S. Mukhina ◽

Yu. V. Ivaskova ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Cavity ◽

Cell Carcinoma ◽

Tumor Cells ◽

Squamous Cell ◽

Immune Cells ◽

Negative Impact ◽

Progression Free Survival ◽

Negative Effect ◽

Effect Of Pd

Relevance. Prognostic value of PD-L1 expression in oral cavity squamous cell carcinoma (OCSCC) and its effect on survival is still controversial. It should be to determine the prognostic role of PD-L1 expression on tumor and immune cells of OCSCC and assess their effect on overall survival (OS) and progression-free survival (PFS).Materials and methods. A prospective study included 145 patients, first diagnosed with OCSCC. PD-L1 expression on tumor and immune cells, infiltrating tumor and its microenvironment, was assessed in all tumor samples by IHC, CPS was calculated. Cut-off values were determined by ROC analysis for identification of PD-L1 expression effect on OS and PFS.Results. Most patients with oral mucosa squamous cell carcinoma showed positive expression of PD-L1 on tumor (77.2%) and immune cells (92.4%). The median PD-L1 expression on tumor cells was 13.5% [1.0-40.0], the median PD-L1 expression on immune cells was 5.0% [1.0-11.0], and the median CPS – 18.0 [3.0-7.8]. Univariate and multivariate analyses revealed a significant negative effect of PD-L1 expression on immune cells ≤ 7% on OS (HR 0.66; 95% CI 0.45-0.93; p = 0.0498); PD-L1 expression in tumor cells ≤ 15% (HR 0.65; 95% CI 0.43-0.98; p = 0.0416) and CPS ≤ 21 (HR 0.62; 95% CI 0.44-0.92; p = 0.0183) for PFS. PD-L1 expression in tumor cells ≤ 6% (HR 0.71; 95% CI 0.47-1.08; p = 0.1096) and CPS ≤ 7 (RR 0.67; 95% CI 0.44-1.01; p = 0.0575) had a confident tendency to negative impact on OS.Conclusion. Positive PD-L1 expression in tumor and immune cells as well as CPS are effective additional factors in the prognosis of the disease course, OS and PFS in patients with OCSCC.

Download Full-text

The Length of Peri-Neural Spreading in Clinically Mandibular Invaded Oral Cavity Squamous Cell Carcinoma

Journal of the Medical Association of Thailand ◽

10.35755/jmedassocthai.2020.05. ◽

2020 ◽

pp. 459-464

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Cavity ◽

Cell Carcinoma ◽

Squamous Cell ◽

Lymphovascular Invasion ◽

Perineural Invasion ◽

Inferior Alveolar Nerve ◽

Surgical Margin ◽

Neural Invasion ◽

Resected Margin

Background: The objective of surgical management of oral squamous cell carcinoma (OSCC) is adequate resection with a clear margin. However, there is still a debate as to the optimal length for a mandibular resected margin. Objective: To examine the length of peri-neural spreading in T4 mandibular invaded oral cavity squamous cell carcinoma. Materials and Methods: Twenty-eight T4 pathological OSCC specimens that involved mandible and serial slices were studied and the length of tumor spreading along the inferior alveolar nerve (IAN) was determined. Tumor characteristics, risk factors, and survival were analyzed. Results: The incidence of peri-neural invasion was 11.11%, and IAN invasion was found in 14.29% of the tumor-invaded mandibular marrow. The length of tumor spreading along IAN was 3 to 12 mm. Poor prognostic factors of T4 OSCC were it being located on the tongue (HR 14.16), was pathological N2-3 (HR 31.05), and had high-risk features such as peri-neural invasion, lymphovascular invasion, and extra-nodal extension. Conclusion: A mandibular resected margin of at least 18 mm is recommended as a clear surgical margin in cases of T4 mandibular invasion OSCC. Keywords: Oral cancer, Perineural invasion, Inferior alveolar nerve, Squamous cell carcinoma, Mandibulectomy

Download Full-text