The development, progression, and curative efficacy of head and neck squamous cell carcinoma (HNSCC) are influenced by complex interactions between epithelial and immune cells. Nevertheless, the specific changes in the nature of these interactions and their underlying molecular mechanisms in HNSCC are not yet fully understood. Cuproptosis, a form of programmed cell death that is dependent on copper, has been implicated in cancer pathogenesis. However, the understanding of cuproptosis in the context of HNSCC remains limited. In this study, we have discovered that cuproptosis-related long non-coding RNAs (CRLs) known as JPX play a role in promoting the expression of the oncogene urokinase-type plasminogen activator (PLAU) by competitively binding to miR-193b-3p in HNSCC. The increased activity of the JPX/miR-193b-3p/PLAU axis in malignant epithelial cells leads to enhanced cell proliferation, migration, and invasion in HNSCC. Moreover, the overexpression of PLAU in tumor epithelial cells facilitates its interaction with the receptor PLAUR, predominantly expressed on macrophages, thereby influencing the abnormal epithelial-immune interactome in HNSCC. Notably, the JPX inhibitor Axitinib and the PLAU inhibitor Palbociclib may not only exert their effects on the JPX/miR-193b-3p/PLAU axis that impacts the malignant tumor behaviors and the epithelial-immune cell interactions but also exhibit synergistic effects in terms of suppressing tumor cell growth and arresting cell cycle by targeting epidermal growth factor receptor (EGFR) and cyclin-dependent kinase (CDK4/6) for the treatment of HNSCC.
Humans ; MicroRNAs/metabolism* ; RNA, Long Noncoding/metabolism* ; Head and Neck Neoplasms/metabolism* ; Cell Proliferation ; Squamous Cell Carcinoma of Head and Neck/genetics* ; Urokinase-Type Plasminogen Activator/genetics* ; Cell Movement ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Carcinoma, Squamous Cell/genetics* ; Neoplasm Invasiveness

OBJECTIVE: To investigate the surgical efficacy and prognostic factors of T3NxM0 middle-low rectal cancer without neoadjuvant therapy. METHODS: Clinical data of patients with middle-low rectal cancer undergoing TME surgery with T3NxM0 confirmed by postoperative pathology at Colorectal Surgery Department of Changhai Hospital from January 2008 to December 2010 were analyzed retrospectively. INCLUSION CRITERIA: (1)no preoperative neoadjuvant chemoradiotherapy (nCRT); (2) complete preoperative evaluation, including medical history, preoperative colonoscopy or digital examination, blood tumor marker examination, and imaging examination; (3) distance between tumor lower margin and anal verge was ≤ 10 cm; (4) negative circumferential resection margin (CRM-). Finally, a total of 331 patients were included in this study. According to the number of metastatic lymph node confirmed by postoperative pathology, the patients were divided into N0 group without regional lymph node metastasis (190 cases) and N+ group with regional lymph node metastasis (141 cases). The perioperative conditions, local recurrence, distant metastasis and prognostic factors were analyzed. RESULTS: Compared to N0 group in the perioperative data, N+ group had higher ratio of tumor deposit [29.8%(42/141) vs. 0, χ²=64.821, P<0.001] and vascular invasion [7.1%(10/141) vs. 0.5%(1/190),χ²=10.860, P<0.001]. There were no significant differences in tumor diameter, number of lymph nodes detected, positive nerve invasion, degree of tumor differentiation, morbidity of postoperative complication and postoperative adjuvant chemotherapy rate between the two groups (all P>0.05). The median follow-up period was 73.4 months. The merged 5-year local recurrence rate was 2.7%(9/331), 5-year distant metastasis rate was 23.3% (77/331), 5-year disease-free survival (DFS) rate was 73.4%, and 5-year overall survival (OS) rate was 77.2%. Multivariate analysis showed that lymph node metastasis (HR=3.120, 95%CI: 1.918 to 5.075, P<0.001), nerve invasion (HR=0.345, 95%CI: 0.156 to 0.760, P=0.008) and vascular invasion (HR=0.428, 95%CI: 0.189 to 0.972, P=0.043) were independent risk factors for DFS in patients with T3NxM0 rectal cancer after operation. Preoperative carcinoembryonic antigen level (HR=1.858, 95%CI:1.121 to 3.079, P=0.016), lymph node metastasis (HR=3.320, 95%CI: 1.985 to 5.553, P<0.001) and nerve invasion (HR=0.339, 95%CI: 0.156 to 0.738, P=0.006) were independent risk factors for OS in patients with T3NxM0 rectal cancer after operation. CONCLUSIONS Optimal local control rate of middle-low rectal cancer patients with T3NxM0 and CRM- can be achieved by standard TME surgery alone. For patients with preoperative elevated blood carcinoembryonic antigen level, regional lymph node metastasis, or neurovascular invasion confirmed by pathology after surgery, adjuvant chemoradiotherapy should be actively applied after surgery to improve prognosis.
Humans ; Lymph Node Excision ; Lymph Nodes ; pathology ; surgery ; Lymphatic Metastasis ; Mesocolon ; surgery ; Neoadjuvant Therapy ; Neoplasm Staging ; Proctectomy ; methods ; Prognosis ; Rectal Neoplasms ; pathology ; surgery ; Retrospective Studies

Objective To analyze copy number variance (CNV) in whole genome by using gene chip technology, and to screen the radiosensitivity associated genes on esophageal squamous cell carcinoma (ESCC). Methods The patients with ESCC who received radiotherapy alone in Anyang Tumor Hospital from December 2013 to August 2016 were selected, and biopsy paraffin samples were preserved in the center of pathology. The patients were divided into radiosensitivity group (group S) and radio-resistance group (group R). DNA was extracted from these paraffin samples in both groups. Whole human genome CNV was detected by using genechip from OncoScan Array platform designed by Affymetrix company, and the differences of gene segments were screened in the two groups. Results Nineteen samples of ESCC patients were collected to extract DNA in this study. To balance pair analysis in the two groups, 10 samples were selected from the qualified patients, including 5 cases in group S and 5 cases in group R respectively. There were no statistical differences in gender, age, lesion site, lesion length, radiation dose of the two groups (all P> 0.05). Loss of heterozygosity (LOH) was the main type of CNV. The analysis results showed that LOH in q24.32-q24.33 of chromosome 10 and LOH in q21.2-q21.31 of chromosome 18 had high frequencies (100 ％) in group R, however, none were detected in group S. LOH in q27-q28.1 of chromosome 4 had a high frequency (80％) in group S , however, none were detected in group R. Conclusion LOH in 10q/18q is related to radio-resistance in ESCC, and LOH in 4p is associated with radiosensitivity in ESCC.

Objective: To evaluate the visual outcomes of patients with visual impairment after resecting skull base tumor via an endoscopic endonasal approach, and to analyze the factors affecting visual recovery. Methods: One hundred and fifty-three patients with skull base tumor who suffered from preoperative visual impairment from Skull Base Surgery Center of Xuanwu Hospital were operated through an endoscopic endonasal approach. Both preoperative and postoperative visual function outcomes as well as factors that might have affected their visual recovery were analyzed retrospectively by Chi square test and Logistic regression analysis. Results: Complete resection was achieved in 85.6% of the patients using this technique. The rate of postoperative visual recovery in the female group (86.1%) was higher than that in the male group (73.9%), the benign group (90.2%) higher than the malignant group (20.0%), the group without optic atrophy (97.1%) higher than the one with (51.2%), and the acute group (96.6%) higher than the chronic group (80.0%). Significant differences were found between the abovementioned groups (χ² value was 5.849, 87.860, 79.757, 4.745, respectively, all P<0.05). The degree of optic atrophy and the property of tumors were significantly associated with visual improvement after treatment (Wold χ² value was 18.597 and 35.623, all P<0.001). Conclusions Our results indicate that endoscopic endonasal surgery shows its ability both to resect skull base tumors and to improve visual function in the majority of patients. The timing of treatment for patients suffered from preoperative visual impairment should be selected in early stage before optic atrophy occurs.

OBJECTIVETo compare the clinicopathological features and prognosis between left-sided colon cancer (LC) and right-sided colon cancer (RC).

METHODSClinicopathological and follow-up data of 2 174 colon carcinoma cases undergoing resection at Shanghai Changhai Hospital of The Second Military Medical University from January 2000 to December 2010 were retrospectively analyzed. Patients with transverse colon cancer, overlapping position, unknown location, recurrent cancer, multiple primary cancer, concomitant malignant tumors, preoperative chemotherapy, local resection, incomplete clinical data and missed follow up were excluded. Finally, a total of 1 036 patients, whose primary tumors were radically removed, were enrolled, with 563 patients in LC group (including carcinoma in cecum, ascending colon and hepatic flexure) and 473 in RC group (including carcinoma in splenic flexure, descending colon and sigmoid colon). The clinicopathological features and survival, including median overall survival, 5-year overall survival rate, tumor specific median overall survival, cancer specific 5-year overall survival rate, were compared between LC and RC groups. Tumor specific overall survival was defined as the period between operation date to the date of death caused by cancer progression. Multivariate Cox regression analysis was used to analyze the influencing factors of survival. Propensity score matching was carried out to balance the clinicopathological factors between the two groups with the SAS 9.3, taking the following parameters into consideration (age, gender, gross appearance, tumor diameter, invasion depth, lymph node metastasis, distant metastasis, TNM stages, differentiation, CEA and CA199-9). Patients in RC group and LC group were matched according to the propensity scores and the clinicopathological characteristics and prognosis of two groups were compared again.

RESULTSNo significant differences were identified between the two groups in age, distant metastasis and serum CEA level. Compared with RC group, LC group had more male patients [60.9%(343/563) vs. 51.0%(241/473), P=0.001], more ulcerative tumors [71.9% (405/563) vs. 65.3%(309/473), P=0.006], better differentiation [well/moderately differentiated: 87.5%(493/563) vs. 73.8%(349/473), P=0.000], lower infiltration depth [T1-2: 17.1%(96/563) vs. 10.1%(48/473), P=0.001], higher lymph node metastasis rate [N0: 53.3%(300/563) vs. 62.4%(295/473), P=0.013], lower TNM stage [stage I(: 13.3%(75/563) vs. 7.8%(37/473), P=0.000], lower serum CA199 level [<37 kU/L: 68.4% (385/563) vs. 62.6% (296/473), P=0.022] and smaller tumor diameter [<5.0 cm: 55.1%(310/563) vs. 38.3%(181/473), P=0.000]. The median overall survival was 82 months and 76 months in LC and RC groups, respectively, and the 5-year overall survival rate was 58.3% and 50.9%(P=0.038). The median tumor specific survival was 84 months and 78 months in LC and RC groups, respectively, and the 5-year tumor specific overall survival rate was 60.6% and 52.9% (P=0.031). Multivariate Cox regression analysis showed that tumor location (LC vs. RC) was not associated with overall survival (P=0.106) and tumor specific survival (P=0.091). After propensity score matching, no significant difference was found in clinicopathological factors and propensity score (0.458±0.129 vs. 0.459±0.129, P=0.622) between LC and RC group. After matching, there was no significant difference in overall survival rate (54.0% vs. 51.7%, P=0.982) and tumor specific overall survival rate(56.4% vs. 53.1%, P=0.819) between two groups.

CONCLUSIONSignificant difference exists between RC and LC in clinicopathological factors, but not in survival.

BACKGROUND:Hemiarthroplasty is a proven method for reconstruction of the hip joint function, especialy for the elderly patients who cannot tolerate the total hip arthroplasty. However, for the patients with osteoporosis, there are stil more controversial in clinical practice about using cemented or cementless femoral prosthesis for hemiarthroplasty. OBJECTIVE: To observe the repair effect of cemented or cementless femoral prosthesis when were used for hemiarthroplasty in patients with osteoporosis. METHODS:The clinical data from 105 patients treated with hemiarthroplasty were retrospectively analyzed. Osteoporosis was diagnosed in these patients using the dual energy X-ray absorptiometry before surgery.Patients were divided into bone cement group (n=56) and cementless group (n=49) depending on different types of femoral stem prosthesis. The difference of efficacy between cemented or cementless femoral prosthesis when were used for hemiarthroplasty in patients with osteoporosis was analyzed by comparing the operative time, volume of drainage, post-operative Harris scores of hip joint function and radiographic assessment (prosthesis subsidence, osteolysis, severe stress shielding, heterotopic ossification) during the folow-up after the replacement. RESULTS AND CONCLUSION:In the process of hemiarthroplasty in patients with osteoporosis, the operative time in the cement group was significantly longer than that in the cementless group (P < 0.05). However, there was no significant difference in the postoperative volume of drainage between these two groups (P > 0.05). At the 1, 3, 6 and 12 of folow-up after replacement, there were no significant differences in the Harris score of hip joint function, total effective rate and radiographic assessment between these two groups (P> 0.05). These results suggest that in the process of hemiarthroplasty in patients with osteoporosis, the clinical efficacy of cementless femoral prosthesis is similar to the cement femoral prosthesis, therefore two prostheses can al be selected; however, the operative time of the cement femoral prosthesis is longer than the cementless femoral prosthesis, so we can give priority to the cementless femoral prosthesis for patients with osteoporosis who can’t tolerate a long operative time because of the poor basic condition.

Although methyltransferase has been recognized as a major element that governs the epigenetic regulation of the genome during temozolomide (TMZ) chemotherapy in glioblastoma multiforme (GBM) patients, its regulatory effect on glioblastoma chemoresistance has not been well defined. This study investigated whether DNA methyltransferase (DNMT) expression was associated with TMZ sensitivity in glioma cells and elucidated the underlying mechanism. DNMT expression was analyzed by western blotting. miR-20a promoter methylation was evaluated by methylation-specific PCR. Cell viability and apoptosis were assessed using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and TdT-mediated dUTP-biotin nick end labeling assays, respectively. The results showed that compared with parental U251 cells, DNMT1 expression was downregulated, miR-20a promoter methylation was attenuated and miR-20a levels were elevated in TMZ-resistant U251 cells. Methyltransferase inhibition by 5-aza-2\'-deoxycytidine treatment reduced TMZ sensitivity in U251 cells. In U251/TM cells, DNMT1 expression was negatively correlated with miR-20a expression and positively correlated with TMZ sensitivity and leucine-rich repeats and immunoglobulin-like domains 1 expression; these effects were reversed by changes in miR-20a expression. DNMT1 overexpression induced an increase in U251/TM cell apoptosis that was inhibited by the miR-20a mimic, whereas DNMT1 silencing attenuated U251/TM cell apoptosis in a manner that was abrogated by miR-20a inhibitor treatment. Tumor growth of the U251/TM xenograft was inhibited by pcDNA-DNMT1 pretreatment and boosted by DNMT1-small hairpin RNA pretreatment. In summary, DNMT1 mediated chemosensitivity by reducing methylation of the microRNA-20a promoter in glioma cells.
Animals ; Antineoplastic Agents, Alkylating/*pharmacology/therapeutic use ; Apoptosis/drug effects ; Brain/drug effects/metabolism/pathology ; Brain Neoplasms/drug therapy/*genetics/pathology ; DNA (Cytosine-5-)-Methyltransferase/antagonists & inhibitors/*genetics/metabolism ; DNA Methylation ; Dacarbazine/*analogs & derivatives/pharmacology/therapeutic use ; Drug Resistance, Neoplasm ; Female ; Gene Expression Regulation, Neoplastic ; Glioma/drug therapy/*genetics/pathology ; Humans ; Mice, Inbred C57BL ; MicroRNAs/*genetics ; Promoter Regions, Genetic