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1.
Cancer Immunol Res ; 9(4): 371-385, 2021 04.
Article in English | MEDLINE | ID: mdl-33608256

ABSTRACT

Immunologic checkpoint blockade has been proven effective in a variety of malignancies. However, high rates of resistance have substantially hindered its clinical use. Understanding the underlying mechanisms may lead to new strategies for improving therapeutic efficacy. Although a number of signaling pathways have been shown to be associated with tumor cell-mediated resistance to immunotherapy, T cell-intrinsic resistant mechanisms remain elusive. Here, we demonstrated that diacylglycerol kinase alpha (Dgka) mediated T-cell dysfunction during anti-PD-1 therapy by exacerbating the exhaustion of reinvigorated tumor-specific T cells. Pharmacologic ablation of Dgka postponed T-cell exhaustion and delayed development of resistance to PD-1 blockade. Dgka inhibition also enhanced the efficacy of anti-PD-1 therapy. We further found that the expression of DGKA in cancer cells promoted tumor growth via the AKT signaling pathway, suggesting that DGKA might be a target in tumor cells as well. Together, these findings unveiled a molecular pathway mediating resistance to PD-1 blockade and provide a potential therapeutic strategy with combination immunotherapy.


Subject(s)
Antineoplastic Agents, Immunological/therapeutic use , B7-H1 Antigen/antagonists & inhibitors , Diacylglycerol Kinase/metabolism , Neoplasms/pathology , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Animals , B7-H1 Antigen/immunology , Cell Line, Tumor , Diacylglycerol Kinase/antagonists & inhibitors , Drug Resistance, Neoplasm , Humans , Immunotherapy/methods , Lymphocytes, Tumor-Infiltrating/immunology , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Neoplasms/drug therapy , Neoplasms/immunology , Neoplasms/metabolism , Programmed Cell Death 1 Receptor/immunology , Tumor Microenvironment/immunology
2.
Front Oncol ; 10: 535893, 2020.
Article in English | MEDLINE | ID: mdl-33178574

ABSTRACT

BACKGROUND: Few reports from China provide confirmed evidence of the effectiveness of the larynx preservation strategy compared with surgery on the treatment of laryngeal and hypopharyngeal cancers. This study assessed the clinical outcomes of patients with locally advanced laryngeal and hypopharyngeal cancers treated with larynx preservation and determined the optimal larynx preservation procedure. METHODS: Data of 1,494 patients treated with total laryngectomy or larynx preservation between 2006 and 2014 were retrieved from the database of Sun-Yat Sen University Cancer Center in Guangzhou, China, and 366 eligible patients were selected for final analysis. The clinical outcomes of 228 patients received total laryngectomy and 138 patients received larynx preservation treatments, which comprises induction followed by radiotherapy and concurrent radio-chemotherapy, were compared. RESULTS: There was no statistical difference in the 3-, 5-, and 10-year PFS and OS in patients received larynx preservation compared with patients treated with laryngectomy. With respect to T stage, a better overall OS in T2-stage disease (P = 0.036) but poorer PFS (P = 0.005) in T3-stage disease was observed in the larynx preservation group compared with the surgery group in Univariate analysis. T3-stage disease had poorer PFS in multivariable analysis (P = 0.022). With larynx preservation intent, induction chemotherapy followed by radiotherapy showed no advantage in the control of disease progression and survival compared with concurrent chemoradiotherapy. The patient subpopulations who received efficacy assessment after induction chemotherapy exhibited significantly longer PFS and OS compared with those without efficacy assessment. CONCLUSIONS: This is the largest sample size study on larynx preservation treatment for laryngeal and hypopharyngeal cancers in China. Our results indicated that larynx preservation treatments did not jeopardize the survival of patients with advanced resectable laryngeal or hypopharyngeal cancers. Efficacy assessment should be emphasized in induction chemotherapy.

3.
Genomics ; 112(6): 4959-4967, 2020 11.
Article in English | MEDLINE | ID: mdl-32919020

ABSTRACT

There is a compelling need to identify novel genetic variants for papillary thyroid cancer (PTC) susceptibility. The Cancer Genome Atlas (TCGA) data showed associations between SPP1 and SPARC mRNA overexpression and aggressive behaviors of PTC, which prompted us to assess potential associations between genetic variants in these genes and PTC risk. Three highly linked SPARC loci (rs1054204, rs3210714, and rs3549) contributed to reduced PTC risk under a codominant model (odds ratio [OR], 0.79-0.80). Variant CAG alleles at these loci significantly enhanced SPARC transcription activation upon cotransfection with miR-29b and miR-495 when compared to the common alleles GGC (all P < 0.05). The three SPARC polymorphisms interacted with SPP1 rs4754, with elevated joint ORs of 2.43, 2.52, and 2.52, respectively. Additionally, interaction between SPP1 rs2358744 and SPARC rs2304052 was observed. Our study revealed associations between SPP1 and SPARC polymorphisms that, individually or in combination, are involved in PTC susceptibility.


Subject(s)
Osteonectin/genetics , Osteopontin/genetics , Thyroid Cancer, Papillary/genetics , Thyroid Neoplasms/genetics , 3' Untranslated Regions , Female , Genetic Predisposition to Disease , Humans , Male , MicroRNAs/metabolism , Middle Aged , Models, Genetic , Osteonectin/metabolism , Osteopontin/metabolism , Polymorphism, Single Nucleotide , RNA, Messenger/metabolism , Thyroid Cancer, Papillary/metabolism , Thyroid Cancer, Papillary/pathology , Thyroid Neoplasms/metabolism , Thyroid Neoplasms/pathology
4.
Front Oncol ; 10: 60, 2020.
Article in English | MEDLINE | ID: mdl-32117723

ABSTRACT

MicroRNAs (miRs) play important roles in tumor progression. miR-936 has been reported to suppress cell invasion and proliferation of glioma and non-small cell lung cancer. Nevertheless, the function of miR-936 in laryngeal squamous cell carcinoma (LSCC) remains undiscovered. Hence, our study was to investigate the role of miR-936 in LSCC. In our present research, we have testified that miR-936 was substantially downregulated in LSCC tissues compared with adjacent normal tissues. Furthermore, miR-936 could inhibit proliferation, migration and invasion, and improve the sensitivity to doxorubicin and cisplatin of LSCC cells. Additionally, luciferase reporter assays were performed to confirm that GPR78 was a novel target of miR-936, and the protein expression of GPR78 was obviously inhibited by miR-936 in LSCC cells. In summary, our study indicates that the miR-936/GPR78 axis could be both a diagnostic marker and a therapeutic target for LSCC.

5.
Cell Death Dis ; 10(12): 916, 2019 12 04.
Article in English | MEDLINE | ID: mdl-31801947

ABSTRACT

The burgeoning functions of many microRNAs (miRs) have been well study in cancer. However, the level and function of miR-1205 in laryngeal squamous cell cancer remains unknown. In the current research, we validated that miR-1205 was notably downregulated in human laryngeal squamous cell carcinoma (LSCC) samples in comparison with tissues adjacent to LSCC, and correlated with T stage, lymph node metastasis, and clinical stage. Using Kaplan-Meier analysis indicates that high expression of miR-1205 has a favorable prognosis for patients with LSCC. Functional assays show that enforced miR-1205 expression attenuates the migration, growth, and invasion of LSCC cells. And E2F1 is verified to be a target of miR-1205, while E2F1 binds to miR-1205 promoter and transcriptionally inhibits miR-1205 expression. Overexpression of E2F1 reverses the inhibitory impacts of miR-1205 on LSCC cells in part. Importantly, E2F1 is abnormally increased in LSCC tissues, and its protein levels were inversely relevant to miR-1205 expression. High E2F1 protein level is in connection with clinical stage, T stage, lymph node metastasis, and poor prognosis. Consequently, reciprocal regulation of miR-1205 and E2F1 plays a crucial role in the progression of LSCC, suggesting a new miR-1205/E2F1-based clinical application for patients of LSCC.


Subject(s)
Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Disease Progression , E2F1 Transcription Factor/genetics , Gene Expression Regulation, Neoplastic , Laryngeal Neoplasms/genetics , Laryngeal Neoplasms/pathology , MicroRNAs/genetics , 3' Untranslated Regions/genetics , Animals , Base Sequence , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Cyclin E/metabolism , Down-Regulation/genetics , E2F1 Transcription Factor/metabolism , HEK293 Cells , Humans , Lymphatic Metastasis , Mice, Inbred BALB C , Mice, Nude , MicroRNAs/metabolism , Neoplasm Invasiveness , Neoplasm Staging , Prognosis , Survivin/metabolism , Up-Regulation/genetics
6.
Int J Biol Markers ; 34(4): 398-405, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31674884

ABSTRACT

OBJECTIVE: To investigate the role of programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1), and P16 in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: A total of 95 paraffin-embedded samples of tumorous tissue of HNSCC were collected. Expression levels of PD-1, PD-L1, and P16 were determined by immunohistochemistry. RESULTS: A significantly higher proportion of PD-1 among patients infected with the human papillomavirus was found. PD-L1 expression is closely associated with the primary site of the tumor, postoperative recurrence, survival, PD-1 expression and P16 expression. Univariable analysis indicated that T stage, N stage, tumor node metastasis stage, tumor differentiation, and PD-L1 expression were all shown to be prognostic variables for overall survival in patients with HNSCC. In the multivariate analysis, only N stage (P = 0.010) and PD-L1 expression (P = 0.001) were found to be independent prognostic variables for overall survival. In addition, for disease recurrence, multivariate analysis showed that only PD-L1 expression was the associated independent risk factor. For the patients with negative PD-L1 expression, Kaplan-Meier analysis revealed that they had significantly worse outcomes in terms of overall survival (P = 0.001). Similarly, compared with the patients with positive PD-L1 expression, those with negative PD-L1 expression had a higher probability of recurrence (P = 0.026). CONCLUSIONS: The expression of PD-L1, PD-1, and P16 in HNSCC is significantly correlated. Human papillomavirus infection (P16 positive) is negatively related to postoperative recurrence. HNSCC patients with positive PD-L1/PD-1 expression tend to have better overall survival outcomes and lower probability of recurrence, providing more evidence for the PD-l-targeted immunotherapy of HNSCC.


Subject(s)
B7-H1 Antigen/biosynthesis , Head and Neck Neoplasms/immunology , Programmed Cell Death 1 Receptor/biosynthesis , Squamous Cell Carcinoma of Head and Neck/immunology , B7-H1 Antigen/immunology , Female , Head and Neck Neoplasms/genetics , Head and Neck Neoplasms/mortality , Head and Neck Neoplasms/pathology , Humans , Male , Middle Aged , Prognosis , Programmed Cell Death 1 Receptor/immunology , Squamous Cell Carcinoma of Head and Neck/genetics , Squamous Cell Carcinoma of Head and Neck/mortality , Survival Analysis
7.
Cancer Biomark ; 26(4): 461-470, 2019.
Article in English | MEDLINE | ID: mdl-31658048

ABSTRACT

This study aimed to evaluate the association of potential functional tagging single nucleotide polymorphisms (tagSNPs) in BRAF and TSHR with papillary thyroid cancer (PTC). Two tagSNPs (rs6464149 and rs7810757) in BRAF and six tagSNPs (rs17630128, rs2075179, rs7144481, rs2371462, rs2268477, and rs2288496) in TSHR were genotyped in 300 cases of PTC and 252 healthy controls. There was no difference in the genotype frequencies of BRAF and TSHR between PTC patients and control subjects, suggesting no contribution of BRAF or TSHR polymorphisms to the susceptibility to PTC. We observed that a tagSNP located in the 3' untranslated region of TSHR, rs2288496, could affect the incidence of lymph node metastasis (LNM). The variant TC and TC + CC genotypes conferred an increased risk of LNM (for TC vs. TT: odds ratio (OR) = 2.01, 95% confidence interval (CI): 1.07-3.77; P= 0.030; for TC + CC vs. TT: OR = 1.87, 95% CI: 1.04-3.39, P= 0.038). Moreover, subjects carrying variant genotypes had higher TSH levels and lower thyroxine (T4) and Anti-TG levels compared with those in subjects carrying common genotypes. Our findings showed that PTC patients carrying the TSHR rs2288496 TC and CC variants were associated with higher TSH level and lower T4 and Anti-TG levels and were prone to developing LNM. To confirm these results, additional studies and functional experiments, especially in other ethnic populations, are needed.


Subject(s)
Receptors, Thyrotropin/genetics , Thyroid Cancer, Papillary/genetics , Thyroid Neoplasms/genetics , Adult , Female , Genetic Predisposition to Disease , Humans , Lymphatic Metastasis , Male , Polymorphism, Single Nucleotide , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins B-raf/metabolism , Receptors, Thyrotropin/metabolism , Thyroid Cancer, Papillary/metabolism , Thyroid Cancer, Papillary/pathology , Thyroid Hormones/metabolism , Thyroid Neoplasms/metabolism , Thyroid Neoplasms/pathology
8.
Cell Death Dis ; 10(5): 356, 2019 05 01.
Article in English | MEDLINE | ID: mdl-31043585

ABSTRACT

To estimate the value of FSCN1 in evaluating the prognosis and guiding the targeted therapy for patients with tongue squamous cell carcinoma (TSCC). Using the Oncomine database, we found some genes especially FSCN1 differentially expressed between TSCC samples and tongue normal samples. So we compared FSCN1 expression between TSCC and normal cell lines and knocked down FSCN1 in TSCC cells to observe its influence on the viability and trans-migration in vitro and tumor growth in vivo. Then we measured FSCN1 expression in human cancer tissues and adjacent non-carcinoma tissues (ANT) and explored the relationship between FSCN1 expression and clinical pathological factors and prognosis in TSCC patients. We found that FSCN1 is expressed higher in TSCC cells than in normal cells. Knockdown of FSCN1 reduced TSCC cell viability and trans-migration in vitro and impaired tumor growth in vivo. FSCN1 also expressed higher in human TSCC than in ANT. In addition, FSCN1 expression was related to N classification, clinical stage and relapse. TSCC patients with over-expression of FSCN1 had worse prognosis. In conclusion, over-expression of FSCN1 indicates worse prognosis for patients with TSCC and FSCN1 may be a potential prognostic biomarker and therapeutic target in TSCC.


Subject(s)
Biomarkers, Tumor/genetics , Carcinoma, Squamous Cell/genetics , Carrier Proteins/genetics , Microfilament Proteins/genetics , Neoplasm Recurrence, Local/genetics , Tongue Neoplasms/genetics , Adult , Animals , Biomarkers, Tumor/metabolism , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/mortality , Carrier Proteins/antagonists & inhibitors , Carrier Proteins/metabolism , Cell Line, Tumor , Cell Movement , Epithelial-Mesenchymal Transition/genetics , Female , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Heterografts , Humans , Male , Mice , Mice, Nude , Microfilament Proteins/antagonists & inhibitors , Microfilament Proteins/metabolism , Middle Aged , Neoplasm Recurrence, Local/diagnosis , Neoplasm Recurrence, Local/metabolism , Neoplasm Recurrence, Local/mortality , Neoplasm Staging , Prognosis , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism , Survival Analysis , Tongue Neoplasms/diagnosis , Tongue Neoplasms/metabolism , Tongue Neoplasms/mortality , Tumor Microenvironment/genetics
9.
J Exp Clin Cancer Res ; 38(1): 167, 2019 Apr 17.
Article in English | MEDLINE | ID: mdl-30995931

ABSTRACT

BACKGROUND: Xenotropic and polytropic retrovirus receptor 1 (XPR1), a previously identified cellular receptor for several murine leukemia viruses, plays a role in many pathophysiological processes. However, the role of XPR1 in human cancers has not yet been characterized. METHODS: Real-time PCR and western blotting assay were used to measure the expression of XPR1 in tongue squamous cell carcinoma (TSCC) tissues. Expression of XPR1 and p65 in clinical specimens was analyzed using immunohistochemical assay. The function of XPR1 on progression of TSCC was explored using in vitro and in vivo experiments. The molecular mechanism by which XPR1 helps to cancer progression was investigated by luciferase reporter activity, ELISA, PKA activity assay, immunofluorescence, western blotting and qPCR assay. RESULTS: Herein, we find that XPR1 is markedly upregulated in TSCC tissues compared to normal tongue tissues. High expression of XPR1 significantly correlates with the malignant features and poor patient survival in TSCC. Ectopic expression of XPR1 increases, while silencing of XPR1 reduces the proliferation, invasion and anti-apoptosis capacities of TSCC cells. Importantly, silencing of XPR1 effectively inhibits the tumorigenecity of TSCC cells. Moreover, we identified that XPR1 increased the concentration of intracellular cAMP and activated PKA. Thus, XPR1 promoted phosphorylation and activation of NF-κB signaling, which is required for XPR1-mediated oncogenic roles and significantly correlates with XPR1 expression in clinical specimens. CONCLUSIONS: These findings uncover a critical role of XPR1 in TSCC progression via activation of NF-κB, and suggest that XPR1 might be a potential prognostic marker or therapeutic target.


Subject(s)
NF-kappa B/genetics , Receptors, G-Protein-Coupled/genetics , Receptors, Virus/genetics , Squamous Cell Carcinoma of Head and Neck/genetics , Tongue Neoplasms/genetics , Transcription Factor RelA/genetics , Animals , Apoptosis/genetics , Biomarkers, Tumor/genetics , Carcinogenesis/genetics , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Disease Progression , Enzyme-Linked Immunosorbent Assay , Epithelial-Mesenchymal Transition/genetics , Female , Gene Expression Regulation, Neoplastic , Humans , Male , Mice , Middle Aged , Neoplasm Invasiveness/genetics , Neoplasm Invasiveness/pathology , Prognosis , Signal Transduction/genetics , Squamous Cell Carcinoma of Head and Neck/pathology , Tongue Neoplasms/pathology , Xenograft Model Antitumor Assays , Xenotropic and Polytropic Retrovirus Receptor
10.
Laryngoscope ; 129(2): 387-395, 2019 02.
Article in English | MEDLINE | ID: mdl-30325027

ABSTRACT

OBJECTIVE: To compare survival effects of comprehensive neck dissection (CND) and selective neck dissection (SND) for patients with nasopharyngeal carcinoma (NPC) with only regional failure. METHODS: A total of 294 recurrent T0N1-3M0 NPC patients who underwent neck dissection in Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China, between January 1984 and February 2014, were enrolled in the survival and interaction analyses. Using propensity scores to adjust for potential prognostic factors, an additional well-balanced cohort of 210 patients was constructed by matching each patient who received SND with one patient who underwent CND (1:1); the differences were then compared between SND and CND in terms of overall survival (OS), local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), and distant metastasis-free survival (DMFS). RESULTS: Both univariate and multivariate analyses showed that SND was not inferior to CND (P > 0.05) but demonstrated that extracapsular spread (ECS) (hazard ratio [HR] 3.49, 95% confidence interval [CI] 2.30-5.29, P < 0.001), recurrent N stage (rN stage) (HR 1.96, 95% CI 1.29-2.97, P = 0.002), and positive margins (HR 3.67, 95% CI 2.40-5.62, P < 0.001) were independent poor prognostic factors for OS. The interaction effects between the dissection style and each independent factor were not significant for OS, LRFS, RRFS, or DMFS (P > 0.05). Furthermore, no survival differences were found between SND and CND in the case-matched cohort in terms of OS, LRFS, RRFS, or DMFS (P = 0.550, 0.930, 0.214, and 0.146, respectively). CONCLUSION: With a similar radical dissection extent around the tumor rather than dissection of extensive lymph region distal to the lesion, SND is not inferior to CND for patients with NPC with only cervical failure. ECS, rN stage, and positive margins were adverse independent prognostic factors for patients with NPC. LEVEL OF EVIDENCE: 4 Laryngoscope, 129:387-395, 2019.


Subject(s)
Nasopharyngeal Carcinoma/surgery , Nasopharyngeal Neoplasms/surgery , Neck Dissection/mortality , Neck Dissection/methods , Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Nasopharyngeal Carcinoma/mortality , Nasopharyngeal Carcinoma/pathology , Nasopharyngeal Neoplasms/mortality , Nasopharyngeal Neoplasms/pathology , Neck/pathology , Neck/surgery , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Prognosis , Proportional Hazards Models , Radiotherapy, Adjuvant/mortality , Retrospective Studies , Treatment Outcome , Young Adult
11.
Front Pharmacol ; 9: 1041, 2018.
Article in English | MEDLINE | ID: mdl-30323762

ABSTRACT

WEE1 is a tyrosine kinase that regulates G2/M cell cycle checkpoint and frequently overexpressed in various tumors. However, the expression and clinical significance of WEE1 in human laryngeal squamous cell carcinoma (LSCC) are still unknown. In this study, we found that WEE1 was highly expressed in LSCC tissues compared with adjacent normal tissues. Importantly, overexpression of WEE1 was correlated with T stages, lymph node metastasis, clinical stages and poor prognosis of LSCC patients. Furthermore, inhibition of WEE1 by MK-1775 induced cell growth inhibition, cell cycle arrest and apoptosis with the increased intracellular reactive oxygen species (ROS) levels in LSCC cells. Pretreatment with ROS scavenger N-acetyl-L-cysteine could reverse MK-1775-induced ROS accumulation and cell apoptosis in LSCC cells. MK-1775 also inhibited the growth of LSCC xenografts in nude mice. Altogether, these findings suggest that WEE1 is a potential therapeutic target in LSCC, and inhibition of WEE1 is the prospective strategy for LSCC therapy.

12.
Cancer Manag Res ; 10: 4523-4535, 2018.
Article in English | MEDLINE | ID: mdl-30349385

ABSTRACT

BACKGROUND: Global data demonstrate minimal improvement in the survival rate for oral cavity cancer (OCC) patients. We wished to know whether or not clinical features and survival rate have changed over time for OCC patients receiving initial treatment and follow-up at a large cancer center in China. METHODS: Clinical features and survival data were collected on patients diagnosed during the successive decades of 1960-1969 (n=253), 1970-1979 (n=497), 1980-1989 (n= 659), 1990-1999 (n=793), and 2000-2009 (n=1,160) at the Sun Yat-sen University Cancer Center. RESULTS: Over time, the overall 5-year survival rate for OCC patients was 52.0%. According to tumor localization, this rate was 71.4% for lip cancer, 56.3% for oral tongue cancer, and 42.7% for other parts of the oral cavity. From the 1960s to the 2000s, the 5-year survival rate steadily improved from 47.8% to 55.6% (P<0.001). Survival steadily decreased with age and was higher for women than for men in the 3 most recent decades. The survival rate for male patients was constant over time, while the rate for female patients improved dramatically. Obvious trends in clinical features over time included the following: increasing age of patients, increasing proportions of localized disease at diagnosis, decreasing proportions of diagnoses of lip cancer, decreasing proportions of diagnoses of squamous cell carcinoma, and decreasing proportions of non-surgical treatment approaches. CONCLUSION: The survival rate has steadily improved for OCC patients at this cancer center.

13.
Oncotarget ; 9(62): 31945-31957, 2018 Aug 10.
Article in English | MEDLINE | ID: mdl-30174788

ABSTRACT

Anaplastic thyroid cancer (ATC), an undifferentiated subtype of thyroid cancer, is one of the most malignant endocrine cancer with low survival rate, and resistant to chemotherapy and radiation therapy. Here we found that UHRF1 was highly expressed in human ATC compared with normal tissue and papillary thyroid cancer (PTC). Knockdown of UHRF1 inhibited proliferation of ATC in vitro and in vivo. Consistently, overexpression of UHRF1 promoted the proliferation of thyroid cancer cells. Moreover, UHRF1 suppression induced differentiation of three-dimensional (3D) cultured ATC cells and down-regulated the expression of dedifferentiation marker (CD97). The stem cell markers (Sox2, Oct4 and Nanog) were suppressed simultaneously. In addition, UHRF1 knockdown reduced the transcription of cytokines (IL-8, TGF-α and TNF-α), which might relieve the inflammatory reaction in ATC patients. This study demonstrated a role of UHRF1 in ATC proliferation, dedifferentiation and inflammatory reaction, presenting UHRF1 as a potential target in ATC therapy.

14.
Oral Oncol ; 84: 20-24, 2018 09.
Article in English | MEDLINE | ID: mdl-30115471

ABSTRACT

INTRODUCTION: Clinically, we have observed that some oral cancer patients have a history of radiotherapy for head and neck cancer; we have named this condition radiotherapy-associated cancer (RAC). Gingival cancer, which is usually juxtaposed with other oral cancer subtypes, is seldom reported individually, and there are few reports on the association between the incidence of oral cancer and history of radiation therapy. Therefore, this study aimed to elucidate the clinicopathological features and prognosis of second primary gingival squamous cell carcinoma after head and neck radiotherapy. MATERIALS AND METHODS: The data collected included 450 patients diagnosed with gingival squamous cell carcinoma from 1964 to 2012 at Sun Yat-sen University Cancer, among whom 52 patients had a history of radiotherapy for head and neck cancer. We retrospectively analysed the differences in the clinicopathological characteristics and prognosis between sporadic gingival squamous cell carcinoma and radiation-associated gingival carcinoma, with an emphasis on gingival carcinoma. RESULTS: Sporadic gingival squamous cell carcinoma is less likely to have more advanced T stage, and the second primary tumour is more likely to be located in the molar area of the maxillary gingiva than in the mandibular gingiva (75.6% vs 24.4%, P < 0.05). The 5-year overall survival of patients with second primary gingival carcinoma was influenced by age distribution, T classification, N classification, clinical TNM stage, histological grade and radiation history in head and neck. Mandibular gingival carcinoma was more likely to have an increased neck lymph node metastasis than maxillary gingival carcinoma (P = 0.001), but there was no significant difference in 5-year overall survival between these two groups (P = 0.828). The main therapy for gingiva carcinoma is surgery or comprehensive treatment based on surgery. CONCLUSIONS: Second primary gingival squamous cell carcinoma after radiotherapy demonstrated particular clinicopathologic features, such as prominent sites and TNM stage; and there was statistically significant difference in 5-year overall survival and prognosis between second primary gingival carcinoma after radiotherapy and sporadic gingival carcinoma.


Subject(s)
Gingival Neoplasms/etiology , Head and Neck Neoplasms/radiotherapy , Neoplasms, Second Primary/etiology , Radiation Injuries/etiology , Squamous Cell Carcinoma of Head and Neck/radiotherapy , Adult , Aged , Aged, 80 and over , Female , Gingival Neoplasms/epidemiology , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasms, Second Primary/epidemiology , Propensity Score , Radiation Injuries/epidemiology , Radiotherapy/adverse effects , Retrospective Studies , Tongue Neoplasms/epidemiology , Tongue Neoplasms/etiology
15.
J Hematol Oncol ; 10(1): 32, 2017 01 25.
Article in English | MEDLINE | ID: mdl-28122647

ABSTRACT

The emerging roles of microRNAs (miRs) have been deeply investigated in cancer. However, the role of miR-194 in human laryngeal squamous cell carcinoma (LSCC) is still unclear. Here, we have demonstrated that miR-194 is significantly downregulated in LSCC tissues and cells, and overexpression of miR-194 inhibits the proliferation, migration, invasion, and drug resistance in LSCC cells. Moreover, Wee1 is identified as a novel direct target of miR-194. Ectopic expression of Wee1 at least in part overcomes the suppressive impacts of miR-194 on the malignant phenotypes of LSCC. Overall, our study provides new sights into the role of miR-194/Wee1 axis in LSCC and suggests a novel miR-194/Wee1-based clinical application for LSCC patients.


Subject(s)
Carcinoma, Squamous Cell/pathology , Cell Cycle Proteins/metabolism , Laryngeal Neoplasms/pathology , MicroRNAs/physiology , Nuclear Proteins/metabolism , Protein-Tyrosine Kinases/metabolism , Biopsy , Cell Cycle Proteins/antagonists & inhibitors , Cell Line, Tumor , Cell Movement , Cell Proliferation , Drug Resistance, Neoplasm , Gene Expression Regulation, Neoplastic , Humans , MicroRNAs/metabolism , Neoplasm Invasiveness , Nuclear Proteins/antagonists & inhibitors , Protein-Tyrosine Kinases/antagonists & inhibitors
16.
PLoS One ; 11(10): e0164840, 2016.
Article in English | MEDLINE | ID: mdl-27760217

ABSTRACT

INTRODUCTION: Although anaplastic thyroid carcinoma (ATC) is rare, it is one of the most aggressive human cancers. The optimal multimodal therapy policy of ATC is still debated, and a standardized treatment strategy remains to be established. This study aimed to evaluate the management aspect and prognosis of ATC. MATERIALS AND METHODS: The data were analyzed retrospectively for 50 patients with ATC to evaluate the clinical characters, management and factors influencing survival. Survival analysis was performed by Kaplan-Merier method and log-rank test, and multivariate analysis was performed using Cox proportional hazard model. RESULTS: The 1-year and 2-year overall survival rates (OS) were 48.0% and 26.0% respectively in all patients, with the 2-year OS of 40.0% and 31.0% and 6.3% for stage IVA, IVB and IVC respectively (P <0.05). In stage IVA and IVB patients, combined surgery with radiotherapy improved overall survival, and the 2-year OS were 50.0% and 35.7% respectively in the group with combined surgery with radiotherapy and the group with surgery with only (P <0.05). Postoperative radiotherapy improved local control rate in stage IVA and IVB patients (P <0.05). However, surgery, radiotherapy or chemotherapy could not improve the survival of stage IVC patients. Multivariate analysis showed that distant metastases, surgery, radiotherapy and tumor residue could predict the prognosis. CONCLUSION: Combined surgery and radiotherapy could improve overall survival in stage IVA and IVB patients. Patients with ATC have a bad prognosis. Distant metastases, surgery, radiotherapy and tumor residue are the most important factors affecting the prognosis.


Subject(s)
Thyroid Carcinoma, Anaplastic/diagnosis , Thyroid Carcinoma, Anaplastic/therapy , Thyroid Neoplasms/diagnosis , Thyroid Neoplasms/therapy , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Multivariate Analysis , Neoplasm Staging , Prognosis , Retrospective Studies , Survival Rate , Thyroid Carcinoma, Anaplastic/pathology , Thyroid Neoplasms/pathology
17.
Medicine (Baltimore) ; 95(11): e2962, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26986105

ABSTRACT

Pinato prognostic nutritional index (PNI) adequately predicts long-term outcomes of various malignancies. However, its value in predicting outcomes in laryngeal squamous cell carcinoma (LSCC) is unknown. All patients newly diagnosed with LSCC presenting to the Department of Head and Neck Oncology at Sun Yat-sen University Cancer Center between January 1, 1990 and July 31, 2010 were eligible. The PNI was calculated as serum albumin (g/L) + 5 × total lymphocyte count/L. The Cutoff Finder software program was used to classify the patients into 3 groups for which the PNI score was at least 70% sensitive, at least 70% specific, or equivocal. Cancer-specific survival was estimated using the Kaplan-Meier method, and predictors were assessed with Cox regression analysis. Median time between surgery and PNI administration for the 975 eligible patients was 83 months. Index score groups were significantly associated with age, T stage, TNM stage, and type of surgery. Five-year CSS and OS were 57.3% and 56.6% in patients with PNI scores below 48.65 (low-probability of survival), 72.8% and 71.3% with scores between 48.65 and 56.93 (moderate-probability of survival), and 77.6% and 75.3% with scores above 56.93 (high-probability of survival); 10-year CSS and OS were 44.2% and 42.7%, 61.6% and 55.6%, 68.3% and 63.5%, respectively. The PNI score groups significantly predicted CSS and OS (P < 0.001). The PNI is an inexpensive and readily available score that predicted survival in patients with LSCC after curative laryngectomy.


Subject(s)
Carcinoma, Squamous Cell , Laryngeal Neoplasms , Laryngectomy/methods , Nutrition Assessment , Age Factors , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/physiopathology , Carcinoma, Squamous Cell/surgery , China/epidemiology , Female , Humans , Kaplan-Meier Estimate , Laryngeal Neoplasms/mortality , Laryngeal Neoplasms/pathology , Laryngeal Neoplasms/physiopathology , Laryngeal Neoplasms/surgery , Male , Neoplasm Staging , Nutritional Status , Outcome Assessment, Health Care , Predictive Value of Tests , Preoperative Care/methods , Prognosis , Retrospective Studies , Survival Analysis
18.
Chin J Cancer ; 35: 24, 2016 Mar 03.
Article in English | MEDLINE | ID: mdl-26940066

ABSTRACT

BACKGROUND: Oral cancer is a common type of head and neck cancers. Knowing its epidemiologic characteristics is crucial to preventing, diagnosing, and treating this cancer. This study aimed to explore the epidemiologic characteristics of oral cancer in South China. METHODS: We retrospectively analyzed data from 4097 oral cancer patients treated at the Sun Yat-sen University Cancer Center between 1960 and 2013. We compared the age of onset, sex ratio, pathologic type, and primary tumor location among three subcultural areas (Guangfu, Hakka, and Chaoshan) and between an economically developed region and a less-developed one in Guangdong. RESULTS: Overall, oral cancer had a male-to-female ratio of approximately 2:1, and this ratio decreased over time. Oral cancer occurred mostly in patients of 45-64 years old (54.5%), and the percentage of older patients gradually increased over time. The most common tumor location was the tongue. Squamous cell carcinoma was the predominant pathologic type. The percentage of blood type O in oral cancer patients was lower than that in the healthy population. The male-to-female ratio in the Chaoshan area was higher than that in the Guangfu and Hakka areas, whereas the age of disease onset in Guangfu was higher than that in Hakka and Chaoshan. The male-to-female ratio was lower and the age of disease onset was higher in the economically developed region than in the less-developed region. CONCLUSION: The incidence of oral cancer in South China presents typical characteristics to which doctors should pay attention when diagnosing and treating oral cancer patients.


Subject(s)
Carcinoma, Squamous Cell/epidemiology , Carcinoma, Squamous Cell/pathology , Mouth Neoplasms/epidemiology , Mouth Neoplasms/pathology , Adolescent , Adult , Age of Onset , Aged , Aged, 80 and over , Cancer Care Facilities , Child , Child, Preschool , China/epidemiology , Female , Hospitals, University , Humans , Male , Middle Aged , Retrospective Studies , Young Adult
19.
Chin J Cancer ; 34(4): 184-8, 2015 Apr 08.
Article in English | MEDLINE | ID: mdl-25963193

ABSTRACT

INTRODUCTION: Metabolic syndrome (MS) is associated with several cancers, but it is not clear whether MS affects the prognosis of tongue squamous cell carcinoma (TSCC). This study aimed to evaluate the prognostic value of MS in TSCC. METHODS: Clinical data from 252 patients with TSCC who were initially treated at the Sun Yat-sen University Cancer Center between April 1998 and June 2011 were collected, and the associations between MS and clinicopathologic factors were retrospectively analyzed. Prognostic outcomes were examined by Kaplan-Meier analysis and Cox regression analysis. RESULTS: Of the 252 patients, 48 were diagnosed with MS. MS was associated with early N category in TSCC (P < 0.001). The patients with MS showed longer survival than those without MS (P = 0.028). MS was an independent prognostic factor for patients with TSCC. CONCLUSIONS: MS is associated with early N category in TSCC. It is an independent prognostic factor for better survival in patients with TSCC.


Subject(s)
Carcinoma, Squamous Cell , Metabolic Syndrome , Prognosis , Tongue Neoplasms , Humans , Kaplan-Meier Estimate , Mortality , Retrospective Studies
20.
Cancer Biol Med ; 12(4): 394-400, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26779376

ABSTRACT

OBJECTIVE: Patients with head and neck cancer often suffer from malnutrition. This study aims to investigate the influence of body mass index (BMI) on the prognosis of laryngeal squamous cell carcinoma (LSCC). METHODS: A total of 473 patients with LSCC initially treated at Sun Yat-sen University Cancer Center between January 2005 and July 2009 were retrospectively reviewed. Survival analysis was performed by the Kaplan-Meier method and Cox regression model. RESULTS: Low BMI before treatment was significantly associated with poor overall survival in patients with LSCC (P<0.001). BMI was an independent prognostic factor for patients with LSCC. CONCLUSION: Leanness before treatment was associated with poor prognosis in patients with LSCC. Good nutritional status is favorable to improve survival in patients with LSCC.

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