Log odds of positive lymph nodes (LODDS)-based novel nomogram for survival estimation in patients with invasive micropapillary carcinoma of the breast.

BACKGROUND: Invasive micropapillary carcinoma (IMPC) of the breast is known for its high propensity for lymph node (LN) invasion. Inadequate LN dissection may compromise the precision of prognostic assessments. This study introduces a log odds of positive lymph nodes (LODDS) method to address this issue and develops a novel LODDS-based nomogram to provide accurate prognostic information. METHODS: The study analyzed data from 1,901 patients with breast IMPC from the Surveillance, Epidemiology, and End Results database. It assessed the relationships between LODDS and the number of excised LN (eLN), positive LN (pLN), and the pLN ratio (pLNR), identifying an optimal threshold value using a restricted cubic spline method. Predictive factors were identified by the Cox least absolute shrinkage and selection operator (Cox-LASSO) regression and validated through multivariate Cox regression to construct a nomogram. The model's accuracy, discrimination, and utility were assessed. The study also explored the consequences of excluding LODDS from the nomogram and compared its effectiveness with the tumor-node-metastasis (TNM) staging system. RESULTS: LODDS improved N status classification by identifying heterogeneity in patients with pLN ratios of 0% (pLN =0) or 100% (pLN =eLN) and setting -1.08 as the ideal cutoff. Five independent prognostic factors for breast cancer-specific survival (BCSS) were identified: tumor size, N status, LODDS, progesterone receptor status, and histological grade. The LODDS-based nomogram achieved a strong concordance index of 0.802 (95% CI: 0.741-0.863), surpassing both the version without LODDS and the conventional TNM staging in all tests. CONCLUSIONS: For breast IMPC, LODDS served as an independent prognostic factor, its effectiveness unaffected by the anatomical LN count, enhancing the accuracy of N staging. The LODDS-based nomogram showed promise in offering more personalized prognostic information.

Targeting the chromatin structural changes of antitumor immunity.

Epigenomic imbalance drives abnormal transcriptional processes, promoting the onset and progression of cancer. Although defective gene regulation generally affects carcinogenesis and tumor suppression networks, tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes, which may have significant implications for the development and application of epigenetic therapy, cancer immunotherapy, and their combinations. Herein, we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes, DNA methylation, histone post-translational modification, and chromatin structure in tumor immunogenicity, and introduce these epigenetic research methods. We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immunotherapy through the complex interaction between cancer epigenetics and cancer immunology.

The pathological roles and potential mechanisms of vascular endothelial growth factor receptor-3 in gastric cancer.

OBJECTIVE: To investigate the roles and underlying mechanisms of vascular endothelial growth factor receptor-3 (VEGFR-3) in gastric cancer (GC). METHODS: VEGFR-3 gene expression profiles in human gastric adenocarcinoma (GAC) tissues were analysed using The Cancer Genome Atlas database. Human GC cell lines and were used for in vitro studies. Mouse models of GC and distant metastasis were used for in vivo studies. Silencing of VEGFR-3 gene expression was achieved using small interfering RNA. RESULTS: VEGFR-3 gene expression was significantly elevated in GAC tissues and GC cells. Higher VEGFR-3 expression was positively correlated with more advanced stages and a greater number of metastatic lymph nodes. In vitro studies in GC cells showed that knockdown of VEGFR-3 gene expression significantly suppressed cell proliferation and migration, but promoted apoptosis. In vivo investigations revealed that silencing of VEGFR-3 gene expression exhibited significant inhibition on tumour growth and metastasis. Further mechanistic studies showed that VEGFR-3 exerted its pathological roles by affecting the key molecules in the apoptotic and epithelial-mesenchymal transition pathways. CONCLUSION: The molecular pathways associated with VEGFR-3-mediated pathological effects could be targets in the development of novel approaches for the diagnosis, prognosis and treatment of GC.

Radiomics-clinical nomogram for preoperative lymph node metastasis prediction in esophageal carcinoma.

OBJECTIVES: This research aimed to develop a radiomics-clinical nomogram based on enhanced thin-section CT radiomics and clinical features for the purpose of predicting the presence or absence of metastasis in lymph nodes among patients with resectable esophageal squamous cell carcinoma (ESCC). METHODS: This study examined the data of 256 patients with ESCC, including 140 cases with lymph node metastasis. Clinical information was gathered for each case, and radiomics features were derived from thin-section contrast-enhanced CT with the help of a 3D slicer. To validate risk factors that are independent of the clinical and radiomics models, least absolute shrinkage and selection operator logistic regression analysis was used. A nomogram pattern was constructed based on the radiomics features and clinical characteristics. The receiver operating characteristic curve and Brier Score were used to evaluate the model's discriminatory ability, the calibration plot to evaluate the model's calibration, and the decision curve analysis to evaluate the model's clinical utility. The confusion matrix was used to evaluate the applicability of the model. To evaluate the efficacy of the model, 1000 rounds of 5-fold cross-validation were conducted. RESULTS: The clinical model identified esophageal wall thickness and clinical T (cT) stage as independent risk factors, whereas the radiomics pattern was built based on 4 radiomics features chosen at random. Area under the curve (AUC) values of 0.684 and 0.701 are observed for the radiomics approach and clinical model, respectively. The AUC of nomogram combining radiomics and clinical features was 0.711. The calibration plot showed good agreement between the incidence of lymph node metastasis predicted by the nomogram and the actual probability of occurrence. The nomogram model displayed acceptable levels of performance. After 1000 rounds of 5-fold cross-validation, the AUC and Brier score had median values of 0.702 (IQR: 0.65, 7.49) and 0.21 (IQR: 0.20, 0.23), respectively. High-risk patients (risk point >110) were found to have an increased risk of lymph node metastasis [odds ratio (OR) = 5.15, 95% CI, 2.95-8.99] based on the risk categorization. CONCLUSION: A successful preoperative prediction performance for metastasis to the lymph nodes among patients with ESCC was demonstrated by the nomogram that incorporated CT radiomics, wall thickness, and cT stage. ADVANCES IN KNOWLEDGE: This study demonstrates a novel radiomics-clinical nomogram for lymph node metastasis prediction in ESCC, which helps physicians determine lymph node status preoperatively.

The Efficacy of Pretreatment 18F-FDG PET-CT-Based Deep Learning Network Structure to Predict Survival in Nasopharyngeal Carcinoma.

Background: Previous studies have shown that the 5-year survival rates of patients with nasopharyngeal carcinoma (NPC) were still not ideal despite great improvement in NPC treatments. To achieve individualized treatment of NPC, we have been looking for novel models to predict the prognosis of patients with NPC. The objective of this study was to use a novel deep learning network structural model to predict the prognosis of patients with NPC and to compare it with the traditional PET-CT model combining metabolic parameters and clinical factors. Methods: A total of 173 patients were admitted to 2 institutions between July 2014 and April 2020 for the retrospective study; each received a PET-CT scan before treatment. The least absolute shrinkage and selection operator (LASSO) was employed to select some features, including SUVpeak-P, T3, age, stage II, MTV-P, N1, stage III and pathological type, which were associated with overall survival (OS) of patients. We constructed 2 survival prediction models: an improved optimized adaptive multimodal task (a 3D Coordinate Attention Convolutional Autoencoder and an uncertainty-based jointly Optimizing Cox Model, CACA-UOCM for short) and a clinical model. The predictive power of these models was assessed using the Harrell Consistency Index (C index). Overall survival of patients with NPC was compared by Kaplan-Meier and Log-rank tests. Results: The results showed that CACA-UOCM model could estimate OS (C index, 0.779 for training, 0.774 for validation, and 0.819 for testing) and divide patients into low and high mortality risk groups, which were significantly associated with OS (P < .001). However, the C-index of the model based only on clinical variables was only 0.42. Conclusions: The deep learning network model based on 18F-FDG PET/CT can serve as a reliable and powerful predictive tool for NPC and provide therapeutic strategies for individual treatment.

Conditional survival nomogram predicting real-time prognosis of locally advanced breast cancer: Analysis of population-based cohort with external validation.

Background: Locally advanced breast cancer (LABC) is generally considered to have a relatively poor prognosis. However, with years of follow-up, what is its real-time survival and how to dynamically estimate an individualized prognosis? This study aimed to determine the conditional survival (CS) of LABC and develop a CS-nomogram to estimate overall survival (OS) in real-time. Methods: LABC patients were recruited from the Surveillance, Epidemiology, and End Results (SEER) database (training and validation groups, n = 32,493) and our institution (testing group, n = 119). The Kaplan-Meier method estimated OS and calculated the CS at year (x+y) after giving x years of survival according to the formula CS(y|x) = OS(y+x)/OS(x). y represented the number of years of continued survival under the condition that the patient was determined to have survived for x years. Cox regression, best subset regression, and the least absolute shrinkage and selection operator (LASSO) regression were used to screen predictors, respectively, to determine the best model to develop the CS-nomogram and its network version. Risk stratification was constructed based on this model. Results: CS analysis revealed a dynamic improvement in survival occurred with increasing follow-up time (7 year survival was adjusted from 63.0% at the time of initial diagnosis to 66.4, 72.0, 77.7, 83.5, 89.0, and 94.7% year by year [after surviving for 1-6 years, respectively]). In addition, this improvement was non-linear, with a relatively slow increase in the second year after diagnosis. The predictors identified were age, T and N status, grade, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER 2), surgery, radiotherapy and chemotherapy. A CS-nomogram developed by these predictors and the CS formula was used to predict OS in real-time. The model's concordance indexes (C-indexes) in the training, validation and testing groups were 0.761, 0.768 and 0.810, which were well-calibrated according to the reality. In addition, the web version was easy to use and risk stratification facilitated the identification of high-risk patients. Conclusions: The real-time prognosis of LABC improves dynamically and non-linearly over time, and the novel CS-nomogram can provide real-time and personalized prognostic information with satisfactory clinical utility.

Asymptomatic uterine metastasis of breast cancer: Case report and literature review.

RATIONALE: Uterine metastasis from breast cancer is extremely rare. Asymptomatic patients with cervical metastases from breast cancer are rarer and more likely to be missed. We present an asymptomatic patient with breast cancer metastasized to the uterus and share opinions on diagnosing and treating for this kind of cases. PATIENT CONCERNS: We present the case of a 64-year-old woman who was diagnosed with both breast cancer and uterine fibroids after examination. She had no symptoms of gynecological disease during breast cancer treatment. A positron emission tomography/computed tomography (PET/CT) scan was performed during reexamination, revealing multiple metastases of the bone throughout the body and an abnormal hypermetabolic mass in the uterus. It was later confirmed as uterine metastasis by pathology. DIAGNOSIS: A diagnosis of metastatic breast invasive lobular carcinoma was established after a uterine curettage. INTERVENTIONS AND OUTCOMES: Treatment of the uterine metastasis included systemic chemotherapy, total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH and BSO), postoperative radiotherapy, and postoperative chemotherapy. The patient eventually refused further treatment for personal reasons and died at home. LESSONS: Breast cancer metastases to the uterus are very rare and further research is needed for their diagnosis and treatment. During reexamination of breast cancer patients, clinicians must be alert to metastasis to gynecologic organs. This is particularly important in hormone receptor-positive patients with asymptomatic distant metastasis.

Subcutaneous soft tissue metastases from esophageal squamous cell carcinoma with neuroendocrine differentiation: Case report and literature review.

Background: Esophageal squamous cell carcinoma is the predominant subtype of esophageal cancer in China and so differs from presentations in Western countries. Common metastatic locations of esophageal cancer include the liver, lung, bone, and brain. In contrast, metastases in subcutaneous soft tissue are exceedingly rare. Case presentation: We present the experience of a 57-year-old man with a complaint of hand and leg dysfunction on the right side. He had a past medical history of esophageal squamous cell carcinoma. Further imaging workup revealed a solitary brain metastasis, thickening of the esophageal wall, swollen lymph nodes in the mediastinum, and right adrenal gland metastasis. Gamma knife radiosurgery of the brain metastasis and intensity-modulated radiotherapy of the esophagus and lymph nodes were administered. After 1.5 months, he was admitted to our hospital again, and nodules were identified in the anterior abdominal wall and left posterior chest wall. Ultrasound, CT, and radical excision of the abdominal wall mass were undertaken and revealed metastatic squamous cell carcinoma with neuroendocrine differentiation. We administered immunotherapy followed by targeted therapy. A PET/CT scan was performed to identify other organ metastases; the scan revealed multiple areas of fluorodeoxyglucose uptake and foci in the esophagus, lung, liver, bone, and right adrenal gland; and in various lymph nodes. In addition, an intensely hypermetabolic lesion was localized in the left posterior thorax. Conclusion: This case highlights the diagnosis and treatment of uncommon metastases of esophageal squamous cell carcinoma. We hope that our clinical experience provides insights into these uncommon metastases.

Epithelial-myoepithelial carcinoma of the nasopharynx: A case report and review of the literature.

Background: Epithelial-myoepithelial carcinoma (EMCa) is a rare low-grade malignant tumor that most commonly occurs in the salivary glands, with approximately 320 cases having been reported worldwide. Here, we report the third case of EMCa occurring in the nasopharynx. Rare cases in the breast, pituitary gland, lacrimal gland, nose, paranasal sinus, nasal cavity, trachea and bronchus, lung, and even the pleura mediastinalis have also been reported. Histopathology and immunohistochemistry are useful for confirming the diagnosis of EMCa, which is characterized by biphasic tubular structures composed of inner ductal and outer clear myoepithelial cells and stains for different markers in each layer. However, because of the rarity of EMCa, the clinicopathological characteristics and treatment of these patients remain unclear. Case presentation: We report a rare case of EMCa of the nasopharynx. A 51-year-old man presented with a 5-month history of pain while swallowing and aggravation accompanied by right ear tinnitus lasting for 1 month. Nasopharyngoscopy and magnetic resonance imaging (MRI) of the nasopharynx and neck revealed a 5.6 cm × 3.4 cm × 3.1 cm mass in the nasopharyngeal space, invasion of the right cavernous sinus, and lymph node enlargement in the right retropharyngeal space. On 17 April 2019, based on the histopathological and immunohistochemical features, a final diagnosis of EMCa of the right nasopharynx was made. The patient underwent concurrent chemoradiotherapy (CCRT), and his symptoms were relieved after treatment. On 10 January 2022, nasopharynx MRI and biopsy revealed local recurrence, but chest and abdominal computed tomography (CT) showed no obvious signs of metastasis. The local recurrence-free survival (LRFS) period was 33 months. Conclusion: To the best of our knowledge, this is the third reported case of EMCa in the nasopharynx and the only case of EMCa in the nasopharynx treated with CCRT, and a partial response was achieved. Therefore, to improve the quality of life and prognosis of patients with unresectable tumors, we believe that CCRT is a suitable option. Further clinical observations are required to elucidate the pathophysiology and prognosis of EMCa.

Bone Metastases of Glioblastoma: A Case Report and Review of the Literature.

BACKGROUND: Glioblastoma (GBM) is the most common primary intracranial tumor and originates from the small pool of adult neural stem and progenitor cells (NSPCs). According to the World Health Organization (WHO) classification of brain tumors, gliomas are classified into grades I-IV, and GBM is defined as the highest grade (IV). GBM can be disseminated by cerebrospinal fluid (CSF), but extracranial metastasis is rare. Additionally, the pathway and mechanism involved remain unclear. CASE PRESENTATION: We report a rare case of left temporal lobe GBM with multiple bone metastases and soft tissue metastasis. This 49-year-old right-handed man who was diagnosed with GBM underwent surgery on May 9, 2017, followed by radiochemotherapy in June 2017. On August 13, 2019, local relapse was found. Then, the patient received a second surgery but not radiochemotherapy. In November 2019, the patient was reported to be suffering from low back pain for nearly 1 month. On December 6, 2019, magnetic resonance imaging (MRI) of the thoracolumbar vertebrae and abdominal computed tomography (CT) confirmed metastases on the ninth posterior rib on the right, the third anterior rib on the left, and the T7 and T10 vertebrae and their appendages. CT-guided rib space-occupying puncture biopsy was performed, and GBM was identified by pathology. CONCLUSION: We should pay attention to extracranial metastasis of GBM. Timely detection and early treatment improve overall quality of patients' life. The extracranial metastasis in this patient may have occurred through the spinal nerve root or intercostal nerve. Further clinical observations are required to clarify the pathway and mechanism involved.

Dural and Multiple Brain Metastases From Basaloid Nasopharyngeal Carcinoma: Case Report and Literature Review.

BACKGROUND: Nasopharyngeal carcinoma is an endemic head and neck cancer in Southern China. The common metastases organs involve bone, lung, and liver. Metastases in the dura and at multiple locations in the brain after a diagnosis of nasopharyngeal carcinoma are extremely rare. CASE PRESENTATION: We present a case of a 66-year-old man who initially complained of nasal congestion, epistaxis, and hearing impairment. The biopsy of the nasopharynx lesion showed basaloid squamous cell carcinoma. Eight months after conventional therapy, the patient was admitted to our hospital again with the complaint of a headache. A PET/CT scan was performed, revealing multiple metastases. A biopsy of subcutaneous soft tissue from the right upper arm was consistent with the previous biopsy. Palliative chemotherapy was administered. Thereafter, the patient had sudden dysfunction of the right side of the body. MRI demonstrated dural and multiple brain metastases. The therapeutic regimen then consisted of whole-brain radiotherapy, anti-angiogenesis therapy, and immunotherapy. CONCLUSIONS: This case highlights the diagnosis and treatment of uncommon metastases of nasopharyngeal carcinoma. Clinicians should remain vigilant for metastases during the treatment and follow-up periods.

A Potential Predictive Biomarker for Miller/Payne Grading: PD-L1 Expression before Neoadjuvant Chemotherapy in Breast Cancer.

BACKGROUND AND OBJECTIVE: The aim of this study was to investigate the value of programmed death ligand 1 (PD-L1) expression as a predictive biomarker for Miller/Payne grading before neoadjuvant chemotherapy (NACT) in breast cancer. PATIENTS AND METHODS: The expression of PD-L1 in pretreatment biopsies of breast cancer was assessed by immunohistochemistry in tissue microarrays. The results were analyzed using SPSS 22.0 statistical software. RESULTS: Of 53 female patients, 10 (18.9%) patients had a grade 5 (G5) response, and 12 (22.6%) patients showed PD-L1 expression, including 7 (13.2%) patients with staining in tumor cells (TCs) and 8 (15.1%) patients with staining in peritumoral lymphocytes (PTLCs). Logistic regression analysis revealed that G5 response to NACT was significantly associated with TCs or PTLCs PD-L1 positivity, whether with univariate analysis (TCs PD-L1: p = 0.00, OR 20.50, 95% CI 3.11-134.94; PTLCs PD-L1: p = 0.02, OR 6.50, 95% CI 1.27-33.20) or with multivariate analysis (TCs PD-L1: p = 0.00, OR 42.23, 95% CI 3.36-530.90; PTLCs PD-L1: p = 0.02, OR 9.07, 95% CI 1.37-60.02). The same trend was found in the luminal subgroup analysis (TCs PD-L1: p = 0.02, OR 23.43, 95% CI 1.66-331.58; PTLCs PD-L1: p = 0.01, OR 47.89, 95% CI 2.47-927.41). CONCLUSION: G5 response to NACT in breast cancer was significantly associated with TCs or PTLCs PD-L1-positive expression in pretreatment biopsies; it can be expected that PD-L1 will become a new independent biomarker of response to NACT in breast cancer.

The Prognostic Value of Deficient Mismatch Repair in Stage II-IVa Nasopharyngeal Carcinoma in the Era of IMRT.

In the era of intensity-modulated radiotherapy (IMRT), it is important to analyse the prognostic value of deficient mismatch repair (dMMR) in nasopharyngeal carcinoma (NPC). In this study, in pretreatment biopsies of 69 patients with stage II-IVa NPC, the expression levels of MMR proteins, including MLH1, MSH2, MSH6 and PMS2, were assessed by immunohistochemistry (IHC). The median follow-up time was 37.5 months (3.1-87.4 months). 50.7% of cases (35/69) showed preserved expression of all 4 MMR proteins, which was interpreted as proficient mismatch repair (pMMR). Only 1.5% of cases (1/69) lost expression of all 4 MMR proteins, 26.1% of cases (18/69) have PMS2 loss alone and 21.7% of cases (15/69) lost expression of both PMS2 and MLH1. Thus, 49.3% of cases (34/69) lost expression of one or more MMR proteins, which was interpreted as dMMR. There was no significant difference (P > 0.05) in terms of sex, age, clinical stage, T category, N category or therapy regimens between the dMMR and pMMR groups. The multivariate Cox regression analysis revealed that dMMR was an independent significant prognostic factor for distant metastasis-free survival (DMFS) (dMMR vs pMMR: P = 0.01, HR = 0.25, 95% CI: 0.09~0.75). Therefore, NPC patients with dMMR had significantly superior DMFS compared with patients with pMMR. It can be expected that dMMR will become a new independent prognostic factor for NPC.

Recombinant adenovirus p53 combined with radiotherapy improves efficacy and safety in the treatment of head and neck lymphoma.

OBJECTIVE: Lymphoma is considered to be a kind of malignant tumour. Gene therapy and radiotherapy have been reported as treatment methods for head and neck lymphoma. This study aims to evaluate the efficacy and safety for the treatment of head and neck lymphoma by a combination of recombinant adenovirus p53 (rAd-p53) and radiotherapy. METHODS: A total of 156 patients with head and neck lymphoma were selected. All patients received an intratumor injection of rAd-p53 of four different doses, namely, 0, 1 × 1010 VP, 1 × 1011 VP and 1 × 1012 VP, once a week for 8 weeks, and radiotherapy was administered 3 days after the rAd-p53 injection using the same dosage and method. Four, eight and twelve weeks after treatment, tumor reduction and complete response (CR) rates, special laboratory examination and adverse reaction assessment were detected to evaluate the efficacy and safety of combined treatment with rAd-p53 injection and radiotherapy for head and neck lymphoma. RESULTS: At week 4, 8 and 12 of treatment with rAd-p53 at the 1 × 1010 VP, 1 × 1011 VP and 1 × 1012 VP doses, the average tumour reduction and CR rates were evidently elevated, the anti rAd-p53 antibody in the serum of patients was expressed positively, and the T cell subsets (CD3/CD4/CD8) increased and interleukin 2 receptor (IL-2R) level decreased markedly. Additionally, rAd-p53 was proven to be clinically safe in the treatment. CONCLUSION: Altogether, we conclude that rAd-p53 combined with radiotherapy improves the efficacy and safety in treating head and neck lymphoma, which has a broad scope in future clinical application.

The expression of HtrA2 and its diagnostic value in patients with hepatocellular carcinoma.

The purpose of this study was to detect the expression of high-temperature requirement A2 (HtrA2) and its diagnostic value in the patients with hepatocellular carcinoma (HCC).The relative serum HtrA2 expression at mRNA and protein level was severally detected by quantitative real-time polymerase chain reaction and western blot analysis in 198 HCC patients and 48 healthy controls. And its association with clinicopathological features was analyzed by chi-square test. The diagnostic value of HtrA2 expression was estimated by establishing a receiver operating characteristic (ROC) curve.Serum HtrA2 was significantly higher in patients with HCC than that in healthy controls both at mRNA and protein levels (P < .05 for both). In addition, the high HtrA2 expression was associated with large tumor size and advanced clinical stage. Furthermore, the value of the area under the ROC curve was 0.808 corresponding with a sensitivity of 65.2% and a specificity of 89.6%, revealed that HtrA2 might be a diagnostic biomarker in HCC.HtrA2 is upregulated and considered to be a potential biomarker for the diagnosis of patients with HCC.

Downregulation of lncRNA UCA1 inhibits proliferation and invasion of cervical cancer cells through miR-206 expression.

Cervical cancer has the second highest incidence rate among cancers in females, accounting for a majority of cancer-related deaths globally. However, the mechanism of cervical cancer pathogenesis is still unclear. UCA1 is considered an oncogene that can transcribe into a long noncoding RNA (lncRNA). This study aimed to determine the function of UCA1 in cervical cancer. A series of experiments involving BrdU, MTS, scratch-adhesion test, and cell invasion assays were conducted to determine the cellular capabilities of proliferation, viability, migration, and invasion, respectively. Binding sites between UCA1 and miR-143 were identified using a luciferase reporter system, whereas mRNA and protein expression of target genes was determined by RT-PCR and immunoblot, respectively. The results shown that the upregulation of lncRNA UCA1 was found in human cervical cancer. Interference of lncRNA UCA1 inhibited cell proliferation, migration, invasion, and viability. Results of the luciferase reporter assay revealed a binding site between lncRNA UCA1 and miR-206. Knockdown of lncRNA UCA1 could directly upregulate miR-206 expression. VEGF downregulation was also observed after knockdown of lncRNA UCA1. Moreover, co-transfection of anti-miR-206 oligodeoxyribonucleotide (AMO-206) in cervical cancer cells reversed the effect of lncRNA UCA1 on VEGF. Therefore, we concluded that LncRNA UCA1 is upregulated in cervical cancer, and its knockdown can upregulate miR-206, thus, suppressing the growth of cervical cancer cells. LncRNA UCA1 is a potential target in cervical cancer treatment.

Promoter Methylation of RASSF1A indicates Prognosis for Patients with Stage II and III Colorectal Cancer Treated with Oxaliplatin-Based Chemotherapy.

BACKGROUND The purpose of this study was to investigate the prognostic significance of methylation of RAS association domain family protein 1 (RASSF1A) in the promoter region for patients with stage II and III colorectal cancer (CRC) receiving oxaliplatin-based chemotherapy. MATERIAL AND METHODS There were 108 eligible CRC patients and 78 healthy controls included in this study. Methylation-specific polymerase chain reaction (MSP) was applied to detect the methylation status of RASSF1A in patients before and after chemotherapy. The effects of RASSF1A methylation on chemotherapy-sensitivity and prognosis for patients were also evaluated in the present study. RESULTS The frequency of RASSF1A methylation was higher in CRC patients than in the healthy controls (48.44% versus 5.13%, p<0.001). After two cycles of chemotherapy, methylation ratio was significantly decreased (21.30%, p<0.001). Promoter methylation of RASSF1A was significantly correlated with tumor stage and pathological differentiation (p=0.008 and p=0.007, respectively). Patients without methylation had a favorable objective response (OR), compared with those with methylation (53.33% versus 25%, p=0.014). Methylation status of RASSF1A could influence progression-free survival and overall survival (log rank test, p<0.05). Cox regression analysis indicated that RASSF1A methylation (HR=2.471, 95% CI=1.125-5.428, p=0.024) and OR (HR=2.678, 95% CI=1.085-6.610, p 0.033) were independently correlated with prognosis for patients treated with oxaliplatin-based chemotherapy. CONCLUSIONS Promoter methylation of RASSF1A can influence sensitivity to oxaliplatin-based chemotherapy, which can be used to predict outcomes for patients with stage II and III CRC. In addition, the aberrant methylation may be a promising target for improving chemotherapy efficacy.

[Relationship between the level of waist circumference and the impaired fasting glucose of pre-diabetes].

OBJECTIVE: To explore the relationship between the level of waist circumference (WC) and the impaired fasting glucose (IFG) in people working for the Kailuan Enterprise. METHODS: A total of 101 510 subjects from the employees of Kailuan Group who took part in the health examination between 2006 to 2007, with fasting plasma glucose (FPG) < 6.1 mmol/L, no history of diabetes, completed data on FPG and WC examination and without using hypoglycemic agents, were selected as the observation cohort. Subjects who did not participate in the health examination from 2010 to 2011 and had incomplete data were finally excluded, ended up with 52 099 subjects available for final analysis. According to the baseline WC measurements and its quartile in the health examinations during 2006 to 2007, people under observation were divided into four groups (first, second, third and the forth quartile groups). Multiple logistic regression analysis was used to test the relation between the increasing of WC and IFG. RESULTS: (1) The incidence rate of IFG in the obese group was higher than that in non-obese group (10.5% vs. 6.8% , P < 0.01), along with an increasing WC noticed in the 4 quartile groups and the incidence rates of IFG were progressively increased, being 6.0%, 7.1%, 8.6% and 11.0% respectively in the total population(7.0%, 7.9%, 9.1% and 11.4% in males, 2.5%, 4.6%, 6.8% and 9.8% in females). (2)Results from the multiple logistic regression analysis showed that, when compared with the first quartile group, the second, third and fourth quartile groups had increased risks of IFG after adjustment on age, gender and other risk factors in the total population, with the OR values being 1.03, 1.15 and 1.30 respectively. After adjusting the above factors in genders, we also noticed the increased risks of IFG, with the OR value being 1.45, 1.66 and 2.08 in males, while 1.00, 1.09 and 1.23 in females, respectively. The influence of the second and third quartile groups on IFG was not significant in females, however. CONCLUSION: The incidence of IFG showed an increasing trend with the increase of WC.

[Effect of constitutive androstane receptor on the cytotoxicity of mitomycin C and 5-(aziridin-1-yl)-3-hydroxymethyl-1-methylindole-4,7-dione].

This study is to evaluate the cytotoxicity of mitomycin C (MMC) and its analogue 5-(aziridin-1-yl)-3-hydroxymethyl-1-methylindole-4,7-dione (629) as well as the effect of transfection of constitutive androstane receptor (CAR) on their biological effects. HepG2 cells were transfected with the plasmids mCAR1/pCR3 mediated by liposome. Vector pCR3 was used as control. Transfected cells were screened by G418 resistance and limiting dilution. The expressions of plasmid mCAR1/pCR3 and CYP2B6 mRNA were detected by RT-PCR; Cytotoxicities of MMC and 629 in vitro were evaluated in g2car cells and HepG2 cells by MTT method under anaerobic and aerobic conditions. mRNA expression of CAR and CYP2B6 can not be detected in HepG2 cells and HepG2/pCR3 cells but can in g2car cells. It is shown that plasmid mCAR1/pCR3 was transfected into g2car cells successfully and target CYP2B6 was transactivated by CAR. To compare with aerobic and anaerobic, the cytotoxicities of MMC and 629 to HepG2 cells and g2car cells had significantly enhanced (P < 0.05), and transfect CAR gene can improve the cytotoxicity of MMC (P < 0.05), but not 629 (P > 0.05). Furthermore, CYP2B6 is one master enzyme for the metabolism of MMC and not 629. Transfection of CAR can increase expression of CYP2B6 mRNA in HepG2 cells, and can affect cytotoxicities of MMC and 629.