ABSTRACT
OBJECTIVES@#Genetic mutation is one of the important causes for tumor genesis and development, but genetic mutation in nasopharyngeal carcinoma (NPC) has rarely been reported. This study explored the role of phosphatidylinositol 3 kinase-protein kinase B (PI3K-Akt), mammalian target of rapamycin (mTOR), and adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway in the efficacy and prognosis in patients with NPC.@*METHODS@#A total of 31 patients with advanced NPC, who came from the Affiliated Cancer Hospital of Xiangya School of Medicine of Central South University/Hunan Provincial Cancer Hospital, were enrolled. All of the exons of 288 genes, introns of 38 genes and promoters or fusion breakpoint regions from the nasopharyngeal biopsy tissues before treatment were detected by the gene sequencing platform Illumina NextSeq CN500. The coding regions of 728 genes were carried out a high-depth sequencing of target region capture, and the 4 variant types of tumor genes (including point mutations, insertion deletions of small fragments, copy number variations, and currently known fusion genes) were detected. All of 31 patients received platinum-based induction chemotherapy combined with concurrent chemoradiotherapy and were followed up for a long time.@*RESULTS@#The 3-year regional failure-free survival (RFFS) and disease-free survival (DFS) in patients with PI3K-Akt pathway mutation were significantly lower than those in unmutated patients (χ2=6.647, P<0.05). The 3-year RFFS and DFS in patients with mTOR pathway mutations were significantly lower than those in unmutated patients, and there was significant difference (χ2=5.570, P<0.05). The rate of complete response (CR) in patients with unmutated AMPK pathway was significantly higher than that in patients with mutation at 3 months after treatment (P<0.05), and the 3-year RFFS and DFS in patients with AMPK pathway mutation were significantly lower than those in unmutated patients (χ2=4.553, P<0.05). PI3K-Akt/mTOR/AMPK signaling pathway mutations and pre-treatment EB virus DNA copy numbers were independent prognostic factors for 3-year RFFS and DFS in patients with NPC (both P<0.05).@*CONCLUSIONS@#The NPC patients with PI3K-Akt/mTOR/AMPK signaling pathway mutation have poor prognosis, and the detection of PI3K-Akt, mTOR, AMPK driver genes and signaling pathways by next-generation sequencing is expected to provide new idea for basic research and targeted therapy of NPC.
Subject(s)
Humans , AMP-Activated Protein Kinases/metabolism , DNA Copy Number Variations , Mutation , Nasopharyngeal Carcinoma/genetics , Nasopharyngeal Neoplasms/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Prognosis , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , Sirolimus , TOR Serine-Threonine Kinases/metabolismABSTRACT
Objective@#To analyze the differentially expressed genes related to the chemosensitivity with the TPF regimen for hypopharyngeal squamous cell carcinoma and to measure potential functional targeting genes expressions.@*Methods@#Twenty-nine patients with primary hypopharyngeal cancer who underwent induction chemotherapy with TPF from January 2013 to December 2017 in Beijing Tongren Hospital were enrolled for microarray analysis, including 28 males and 1 female, aged from 43 to 73 years old. Among them, 16 patients were sensitive to chemotherapy while 13 patients were non-sensitive. Illumina Human HT-12 Bead Chip was applied to analyze the gene expressions and online bioinformatics analysis was used to analyze the differentially expressed genes. Reverse transcription and quantitative real-time PCR (RT-qPCR) was used to measure the mRNA expression of potential functional genes of TPF induction chemotherapy in 43 samples, 29 from original patients and 14 from additional patients. Graphpad prism 7.0 software was used for statistical analysis.@*Results@#A total of 1 381 significantly differentially expressed genes were screened out. By GO analysis, up-regulated genes included sequestering in extracellular matrix, chemokine receptor binding and potassium channel regulator activity; down-regulated genes included regulation of angiogenesis, calcium ion binding and natural killer cell activation involved in immune response. With KEGG database analysis, down-regulated pathways included ECM-receptor interaction and peroxisome and up-regulated pathways included Glutathione metabolism and PPAR signaling pathway. The expressions of CD44 and IL-6R were significantly different and appeared biologically significant. CD44 was significantly upregulated in insensitive tissues (0.54±0.06) compared with sensitive tissues (0.33±0.04)(P<0.01). IL-6R was significantly downregulated in insensitive tissues (0.44±0.03) compared with sensitive tissues. (0.68±0.03) (P<0.01).@*Conclusion@#CD44 and IL-6R may be potentially functional genes of TPF induction chemotherapy in hypopharyngeal squamous cell carcinoma.
ABSTRACT
Objective@#To establish a laryngeal squamous cell carcinoma (LSCC) cell line through primary cell culture and observe its biological characteristics.@*Methods@#Tissue block culture method was used for primary cell culture. After LSCC cells passed 25 times in vitro, the morphology of cells was observed, keratin was stained histochemically, cell cycle was tested by PI-FACS, and the specie of cells was detected by PCR and short tandem repeat(STR) typing.@*Results@#This newly established LSCC cell line was named as TR-LCC-1, most of the cancer cells were polygonal shape, like the cobblestone, loss of contact inhibition and with overlapping growth. Cell size was large and cell pleomorphism was very obvious. Cytokeratin staining was positive. After 6 months of continuous culture in vitro, the TR-LCC-1 cells passed more than 30 times, and cell doubling time was 201.2h. Cell cycle assay indicated that G1 phase accounted for 51.71%, S phase was 44.56%, and G2 phase was 2.28%. Mycoplasma test showed no mycoplasma contamination. Cell species identification identified TR-LCC-1 was human-derived cells. STR detection showed P26 and P6 were same, and they were different from the STR typing of disclosed cells.@*Conclusion@#The establish ment of the new laryngeal squamous carcinoma cell line TR-LCC-1 can be helpful to the research for laryngeal squamous cell cancer.
ABSTRACT
OBJECTIVE To study the effect of the free anterolateral thigh myocutaneous flap on the appearance and functions after maxillectomy.METHODS The clinical data of 5 patients with malignant maxillary tumors from June,2016 to June 2017 were analyzed retrospectively.The 5 cases were T3-4N0M0 lesions.All of them received the maxillectomy and then were reconstructed with the free anterolateral thigh myocutaneous flap,and the flap was about 1.25 times of the defect in volume.RESULTS The needed volumes for the reconstruction were from 165 ml to 225 ml and the operation time of reconstruction were between 80-95 minutes.All the free flaps survived after operation.Although the reconstructed side looked swelling obviously in the first month after surgery,the appearance became good and symmetrical after the radiotherapy.No diplopia occurred and the functions of breathing,swallowing and speaking were normal.No movement disorders happened caused by the donor of thigh flap.CONCLUSION The free anterolateral thigh myocutaneous flap as the reconstructive tissue has many merits.The volume is adequate and can be regulated according to the defect.The forward appearance is better than the free anterolateral thigh flap without muscles.So the reconstruction of free anterolateral thigh myocutaneous flap is an ideal material for reconstruction because of the good functions and being easy to operate.
ABSTRACT
OBJECTIVE To evaluate the survival and functional outcomes of advanced laryngeal squamous cell carcinoma after modified supracricoid partial laryngectomy(SCPL).METHODS We selected 65 laryngeal cancer patients treated with modified supracricoid partial laryngectomy from 2002 to 2015 in our hospital.Among them,62 cases were males,3 cases were females with an age ranged from 35 to 80 years(median age 58 years)There were 26 cases with T2 stage,32 cases with T3 stage and 7 cases with T4 stage.We selected 120 laryngeal cancer patients treated with vertical partial laryngectomy at the same period as control.Then we evaluated the functional outcomes of modified supracricoid partial laryngectomy group compared with vertical partial hemilaryngectomy group.RESULTS The 5-year cumulative survival rate and decannulation rate were 82.3％ and 98.3％ for supracricoid laryngectomy group respectively.Decannulation ratewas 86.1％ for vertical partial hemilaryngectomy group(P＜0.05).However,there was no significant difference between supracricoid partial laryngectomy group and vertical partial laryngectomy group in pronunciation evaluation and abnormal deglutition.CONCLUSION Modified supracricoid partial laryngectomy is a good choice for local advanced laryngeal squamous cell carcinoma.
ABSTRACT
OBJECTIVE The purpose of this study was to analyze the screened miRNAs related to tumorigenesis using miRNA array in laryngeal squamous cell carcinoma (LSCC), and provide a set of miRNAs that may be useful for the development of novel diagnostic markers and/or more effective therapeutic strategies from the screened miRNAs in LSCC. METHODS A total number of 5 patients who underwent surgery for primary laryngeal squamous cell carcinoma were recruited for miRNA array analysis. LSCC tissues compared with corresponding adjacent non-neoplastic tissues were analyzed by the Affymetrix GeneChip miRNA Array 3.0 to screen effective miRNAs, and the raw dataset had been submitted to Gene Expression Omnibus. Then mirfocus 3.0 database was adopted to analyze putative regulated miRNAs related to MCM4, a gene related to tumorigenesis we had studied previously in LSCC. Moreover, the selected putative regulated miRNAs were also validated by qRT-PCR in another 21 patients diagnosed as LSCC. RESULTS Analyzed by the miRNAs arrays, there were 127 miRNAs significantly related to tumorigenesis, and 78 showed a higher expression in tumor than in non-tumor tissue while 49 presented the contrasting pattern (P<0.01). Then analyzed by mirfocus 3.0 database, there were 2 putative regulated miRNAs, hsa-miR-24-3p and hsa-miR-183-5p, related to the expression of MCM4. Another miRNA we should focus on was hsa-miR-30a-5p, which was down-expressed obviously analyzed by the miRNA array. The expression of the 3 putative regulated miRNAs were also validated by qRT-PCR in another 21 patients, and the result was the same with that in miRNA array (P<0.05). CONCLUSION The 3 putative miRNAs based on miRNA array analysis, hsa-miR-24-3p, hsa-miR-183-5p and hsa-miR-30a-5p, could be considered as potential diagnostic and therapeutic markers in LSCC. The result will contribute to the understanding of the molecular basis of LSCC and help to improve the treatment.
ABSTRACT
[ABSTRACT]OBJECTIVEThe purpose of this study was to analyze the screened miRNAs related to the chemosensitivity for the TPF regimen of hypopharyngeal squamous cell carcinoma by miRNA array, and provide a set of miRNAs that may be useful for the development of novel diagnostic markers and more effective therapeutic strategies from the screened miRNAs.METHODSA total number of 21 patients who underwent TPF induction chemotherapy for primary hypopharyngeal squamous cell carcinoma were recruited for miRNA array analysis. 12 patients are sensitive to chemotherapy, and 9 patients are not. Moreover, the selected putative regulated miRNAs were also validated by RT-PCR in another 24 patients (14 patients are sensitive to chemotherapy, and others are not).RESULTSThere were 24 miRNA significantly differencial to the sensitivity to chemotherapy, and 6 miRNAs were up-regulated in the TPF group while 18 miRNA were down-regulated (P<0.05). To identify typical miRNA, mirfocus 3.0 database selected four miRNAs hsa-miR-211-3p, hsa-miR-4253, hsa-miR-4443, and hsa-miR-193b-3p, which were significant down-regulated in TPF-sensitive group. QRT-PCR further validated that only three miRNA (hsa-miR-4253、hsa-miR-4443、hsa-miR-193b-3p) were under-expressed in TPF-sensitive group of another 24 tissue samples (P<0.05).CONCLUSIONMiRNA hsa-miR-193b-3p, hsa-miR-4253, hsa-miR-4443 were identified in TPF-sensitive tissues by microarrays, and further validated by RT-PCR. These down-regulated miRNAs may act as novel biomarkers to classify TPF sensitivity of hypopharyngeal squamous cell carcinoma patients and will contribute to the understanding of the molecular basis of the chemosensitivity in the disease.
ABSTRACT
[ABSTRACT]OBJECTIVETo explore the efficacy and safety of localization for parathyroid glands with intravenous low dosage of methylene blue in thyroidectomy. METHODSWe retrospectively reviewed the clinical data of 41 patients who suffered from thyroid papillary carcinoma between Aug, 2014 and Jan, 2015 (9 males and 32 females, with a median age of 46 years). Thirty eight patients underwent primary thyroidectomy and 3 patients underwent second operation. A variety of thyroidectomy was performed in all patients, and who also underwent intravenous (3-4) mg/kg methylene blue in operation. RESULTSEighty four parathyroid glands were stained. Among 39 patients who's parathyroid glands were stained, the mean dyeing time was (31.27±9.41) min. Dyeing rates and dyeing time were not significantly different between 3 mg/kg group and 4 mg/kg group (t=0.24 and 0.20, all P>0.05). None of patients had the hypoparathyroidism problem such as peri-oral numbness, tingling, muscle aches and spasms. According to postoperative monitoring of parathyroid hormone, all of patients had no permanent hypofunction of the parathyroid gland. Neurotoxic effects and other serious side effects were not observed in all patients. CONCLUSIONIntravenous low-dose methylene blue in thyroidectomy is a safe, easy, and effective technique that facilitates rapid identification of parathyroid gland.
ABSTRACT
OBJECTIVE@#To study the definition, etiology, diagnosis, treatment and prognosis in patients with multiple primary malignant tumor of upper aerodigestive tract cancer and thyroid cancer.@*METHOD@#Retrospectively analyze the events of 7 cases with multiple primary malignant tumors of upper aerodigestive tract cancer and thyroid cancer.@*RESULT@#Lesions of upper aerodigestive tract cancer and thyroid cancer located on the same side. After 4 to 8 years of follow-up, 2 cases of hypopharyngeal cancer and thyroid cancer got poor prognosis, prognosis of other patients with early stage laryngeal cancer and thyroid cancer is better.@*CONCLUSION@#The prognosis of multiple primary malignant tumors in patients with upper aerodigestive tract cancer and thyroid cancer depends on the biological behavior of aerodigestive tract cancer.
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Follow-Up Studies , Neoplasms, Multiple Primary , Prognosis , Retrospective Studies , Thyroid NeoplasmsABSTRACT
<p><b>OBJECTIVE</b>To identify the genes differentially expressed and underlying molecular mechanism in laryngeal squamous cell carcinoma by using cDNA microarrays.</p><p><b>METHODS</b>Using Illumina Human HT-12 BeadChip, gene expressions were detected in ten pairs of laryngeal cancer tissues and adjacent normal tissues. Total RNA was extracted and reverse-transcribed into cDNA. Labeled cDNA were hybridized with cDNA microarray, data were read and images were scanned. All the samples had passed quality control testing.</p><p><b>RESULTS</b>Through Illumina Genomstudio 1.9.0 Data processing software (P < 0.05 or diffscore>13, diffscore<-13) and multiple displacement t test(FDR<0.05), 426 genes showed statistically significant differences in expressions between laryngeal tumor tissues and corresponding adjacent normal tissues, with 222 up-regulated genes and 204 down-regulated genes in laryngeal cancer tissues. These up- or down-regulated genes were indicated to involve in cellular processes relevant to the cancer phenotype, such as proliferation, cell cycle, chromosome segregation, mitosis and meiosis. These differentially expressed genes also took part in cancer related signaling pathways as well, for instance, metabolic pathways, cell cycle, DNA replication, glutathione metabolism, mucin type O-Glycan biosynthesis, drug metabolism-cytochrome P450 and so on.</p><p><b>CONCLUSION</b>The set of genes identified here and their functional annotations contribute to a better understanding of the pathogenesis of laryngeal squamous cell carcinoma from the view of multiple gene interactions and provide candidate markers for improving diagnosis, prognosis and treatment of this cancer.</p>
Subject(s)
Aged , Aged, 80 and over , Humans , Male , Middle Aged , Carcinoma, Squamous Cell , Genetics , Gene Expression , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Genome-Wide Association Study , Head and Neck Neoplasms , Genetics , Laryngeal Neoplasms , Genetics , Oligonucleotide Array Sequence AnalysisABSTRACT
Objective In this paper,we selected the ultrasound features of the malignant thyroid nodules to evaluate the preoperative diagnostic value of ultrasound-guided fine needle aspiration biopsy ( US-FNAB )in the preoperative evaluation of thyroid nodules.Methods Thirty-nine patients with thyroid nodules managed in the department of otolaryngology-head and neck surgery,Beijing Tongren Hospital,Captial Medical University from Dec.2010 to Aug.2011 were studied.All of them were undertaken the ultrasonic examination,ultrasound-guided fine needle aspiration biopsy and surgical treatment subsequently.The ultrasonic features,fine needle aspiration biopsy results and postoperative pathological results were analyzed to draw out the characteristics of sonographic features of thyroid malignant nodules.Results The sensitivity,specificity,misdiagnosis and missed diagnosis of fine needle aspiration biopsy were 80.0％,89.4％,11.0％ and 20.0％ respectively.Solid nodules,shape/dimension ratio ≥ 1,calcifications ＜ 2 mm,irregular shape,blurred margins,type Ⅲ vascularity were correlated significantly with the malignant nodules of thyroid.The specificity of shape to dimension ratio and outline of the nodules were relatively higher than others (90.5％and 85.7％ respectively).But there were no single ultrasound feature that could carry a high sensitivity and positive predictive value in the diagnosis of thyroid nodules.Conclusions Two ultrasonographic characteristics could be used together as a select indicator to screen malignant nodules which can reduce the chance of undertaking the fine needle aspiration biopsy in thyroid nodules.
ABSTRACT
Along with the improvement of the diagnosis techniques and the popularization of the health examination,the incidence of the thyroid nodule is growing rapidly.The management methods of the nodules depend on the correct diagnosis of the thyroid nodules,which could save the limited resources of the healthcare system.The diagnostic methods of the thyroid nodules developed in recent years are reviewed in this paper.
ABSTRACT
@#Objective To explore the rehabilitation effect of group education intervention in self-control on schizophrenic patients. Methods 112 schizophrenic patients were divided into study group (56 cases) and control group (56 cases). Two groups were treated with antipsychotics. The control group was subjected to general healthy education, while the study group received education intervention of self-control. All patients of two groups were assessed by Self-care Behavior Questionnaire(SCBQ), Brief Psychiatric Rating Scale(BPRS) and Social Disability Screening Schedule(SDSS) before and affter intervention, and drug-compliance was also assessed.Results After one year, the total score of SCBQ was significantly higher in the study group than in the control group, while the total scores of BPRS and SDSS were significantly lower in the study group than in the control group (P<0.01); Drug-compliance was significantly more in the study group than in the control group(P<0.01).Conclusion Group education intervention of self-control can improve distinctly the ability of self-control disease, have positive effect on remission psychical symptom, and improve the social function and retention psychosomatic healthy.