Recent Advances in 2-Keto-l-gulonic Acid Production Using Mixed-Culture Fermentation and Future Prospects.

Vitamin C, also known as ascorbic acid, is an essential vitamin that cannot be synthesized by the human body and must be acquired through our diet. At present, the precursor of vitamin C, 2-keto-l-gulonic acid (2-KGA), is typically produced via a two-step fermentation process utilizing three bacterial strains. The second step of this traditional two-step fermentation method involves mixed-culture fermentation employing 2-KGA-producing bacteria (Ketogulonicigenium vulgare) along with associated bacteria. Because K. vulgare has defects in various metabolic pathways, associated bacteria are needed to provide key substances to promote K. vulgare growth and 2-KGA production. Unlike previous reviews where the main focus was the interaction between associated bacteria and K. vulgare, this Review presents the latest scientific research from the perspective of the metabolic pathways associated with 2-KGA production by K. vulgare and the mechanism underlying the interaction between K. vulgare and the associated bacteria. In addition, the dehydrogenases that are responsible for 2-KGA production, the 2-KGA synthesis pathway, strategies for simplifying 2-KGA production via a one-step fermentation route, and, finally, future prospects and research goals in vitamin C production are also presented.

The RNA binding protein MEX3A promotes tumor progression of breast cancer by post-transcriptional regulation of IGFBP4.

PURPOSE: Breast cancer (BC) is the most frequent malignant tumor in women worldwide with exceptionally high morbidity. The RNA-binding protein MEX3A plays a crucial role in genesis and progression of multiple cancers. We attempted to explore its clinicopathological and functional significance in BC in which MEX3A is expressed. METHODS: The expression of MEX3A detected by RT-qPCR and correlated the results with clinicopathological variables in 53 BC patients. MEX3A and IGFBP4 profile data of BC patients were downloaded from TCGA and GEO database. Kaplan-Meier (KM) analysis was used to estimate the survival rate of BC patients. Western Blot, CCK-8, EdU, colony formation and flow cytometry were performed to investigate the role of MEX3A and IGFBP4 in BC cell proliferation, invasion and cell cycle in vitro. A subcutaneous tumor mouse model was constructed to analyze in vivo growth of BC cells after MEX3A knockdown. The interactions among MEX3A and IGFBP4 were measured by RNA pull-down and RNA immunoprecipitation. RESULTS: The expression of MEX3A was upregulated in BC tissues compared to adjacent tissues and high expression of MEX3A was associated with poor prognosis. Subsequent in vitro studies demonstrated that MEX3A knockdown inhibited BC cells proliferation and migration, as well as xenograft tumor growth in vivo. The expression of IGFBP4 was significantly negatively correlated with MEX3A in BC tissues. Mechanistic investigation showed that MEX3A binds to IGFBP4 mRNA in BC cells, decreasing IGFBP4 mRNA levels, which further activated the PI3K/AKT and other downstream signaling pathways implicated cell cycle progression and cell migration. CONCLUSION: Our results indicate that MEX3A plays a prominent oncogenic role in BC tumorigenesis and progression by targeting IGFBP4 mRNA and activating PI3K/AKT signaling, which can be used as a novel therapeutic target for BC.

CKAP2L Promotes Esophageal Squamous Cell Carcinoma Progression and Drug-Resistance by Modulating Cell Cycle.

Esophageal squamous cell carcinoma (ESCC) is one of the most common types of cancer and the leading cause of cancer-related mortality worldwide, especially in Asia. In this study, the gene CKAP2L was selected by GEO, TCGA, and GTEx database analysis. The high expression of CKAP2L is related to the occurrence and development of ESCC. In addition, CKAP2L knockdown can inhibit the growth and migration of ESCC cells, while CKAP2L overexpression has the opposite effect. Furthermore, in vivo experiments indicated that down-regulation of CKAP2L can inhibit the tumorigenesis of ESCC cells. KEGG pathway analysis and the STRING database explored the relationship between cell cycle and CKAP2L and verified that depletion of CKAP2L markedly arrested cell cycle in the G2/M phase. Meanwhile, CKAP2L knockdown increased the sensitivity of ESCC cells to flavopiridol, the first CDK inhibitor to be tested in clinical trials, leading to an observable reduction in cell proliferation and an increase in cellular apoptosis. In brief, we identified CKAP2L as a tumor promoter, potential prognostic indicator, and therapeutic target of ESCC, which may play a role in regulating cell cycle progression.

MBD1/HDAC3-miR-5701-FGFR2 axis promotes the development of gastric cancer.

Gastric cancer (GC) remains one of the leading causes of cancer-related deaths worldwide due to the lack of specific biomarkers for the early diagnosis and universal accepted therapy for advanced GC. Lower levels of miR-5701 were found in the GC tissue from the online sequencing data and confirmed in the GC tissues and GC cell lines. Overexpression of miR-5701 inhibited the proliferation and migration of GC cells and promoted the apoptosis of these cells. Bioinformatics analyses and luciferase assay showed that miR-5701 targeted FGFR2, which acted as an oncogene in GC. Nude mice with GC cells overexpressing miR-5701 exhibited smaller tumor sizes and less lung metastases. The miR-5701 expression was directly, transcriptionally inhibited by MBD1 together with HDAC3 by binding together to form a complex. Knocked down MBD1 or HDAC3 increased the miR-5701 expression. These results indicated the potential use of exogenously administered miR-5701 or agents that elevated endogenous miR-5701 to inhibit GC, improving the prognosis of patients with GC.

Ovarian reserve in premenopausal women with breast cancer.

BACKGROUND: As a special reproductive hormone and ovarian reserve indicator, the role of anti-Müllerian hormone (AMH) in premenopausal women with breast cancer deserves further study. METHODS: We conducted an in-depth analysis of the data from the EGOFACT study (NCT02518191), a phase Ⅲ, randomized, controlled trial involving premenopausal female breast cancer patients in two parallel groups: chemotherapy with or without gonadotropin-releasing hormone analogs (GnRHa). Three hundred thirty premenopausal women aged 25-49 years with operable stage I to III breast cancer were included in this study. The characteristics of ovarian reserve changes marked by AMH in the EGOFACT study and the factors affecting ovarian function in premenopausal women with breast cancer were analyzed. RESULTS: The AMH level of the chemotherapy alone group decreased gradually within one year, while the AMH level of the GnRHa group was significantly higher as early as 6 months after chemotherapy and recovered to close to the baseline level 12 months after chemotherapy (F = 34.991, P < 0.001). Correlation analysis showed that the factors affecting AMH levels mainly included age, menarche age, body mass index (BMI), reproductive history, baseline follicle stimulating hormone (FSH) level, pathological stage and GnRHa application, but they had different effects on the incidence of premature ovarian insufficiency (POI) at different periods. Multivariate logistic regression analysis showed that menarche age younger than 14 years (OR 0.470 [0.259, 0.852], P = 0.013), baseline AMH level higher than 0.5 ng/mL (OR 9.590 [3.366, 27.320], P < 0.001), pathological stage Ⅰ(OR 0.315 [0.124, 0.798], P = 0.015) and GnRHa application (OR 0.090 [0.045, 0.183], P < 0.001) were independent factors conducive to protection of ovarian reserve, as well as to recovery of ovarian reserve. CONCLUSIONS: Age, menarche age, baseline AMH level, and GnRHa application are the most important influencing factors for ovarian reserve in premenopausal women with breast cancer. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02518191, registered on Aug 5, 2015.

WITHDRAWN: Stromal Cell-Derived Factor 1 Secreted by Cancer- Associated Fibroblasts Promotes lncRNA Xist through CXCR4 and Facilitates Invasion and Metastasis of Non-Small Cell Lung Cancer

Since the authors are not responding to the editor's requests to fulfill the editorial requirement, therefore, the article has been withdrawn.Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php. Bentham Science Disclaimer: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

Effects of Gonadotropin-Releasing Hormone Analogs on Ovarian Function Against Chemotherapy-Induced Gonadotoxic Effects in Premenopausal Women With Breast Cancer in China: A Randomized Clinical Trial.

IMPORTANCE: Studies of the use of gonadotropin-releasing hormone analogs (GnRHa) to protect ovarian function have shown mixed results. OBJECTIVE: To determine whether administering GnRHa during chemotherapy in premenopausal women with breast cancer can reduce ovarian impairment. DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial, conducted at the Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital and Zhejiang Cancer Hospital in China, was an open-label trial involving premenopausal women aged 18 to 49 years with operable stage I to III breast cancer for which treatment with adjuvant or neoadjuvant cyclophosphamide-containing chemotherapy was planned in 2 parallel groups: treatment with chemotherapy with or without GnRHa. Enrollment occurred from September 2015 to August 2017, and follow-up ended December 2020. The data were analyzed in March 2021. A total of 405 patients were enrolled in the study, among whom 27 patients (6.7%) quit participation voluntarily, 33 (8.1%) did not meet the inclusion criteria and were excluded, and 15 (3.7%) were lost to follow-up. Ultimately 330 patients were included in the primary analysis, including 29 patients with baseline anti-Müllerian hormone levels less than 0.5ng/ mL. INTERVENTIONS: Eligible patients were randomly assigned (1:1) to receive chemotherapy with (n = 165) or without (n = 165) GnRHa. In patients randomized to receive GnRHa, 3.6 mg of goserelin or 3.75 mg of leuprorelin was injected subcutaneously once every 28 days from 1 to 2 weeks before the first cycle of chemotherapy to 4 weeks after the last cycle of chemotherapy. MAIN OUTCOMES AND MEASURES: The primary end point was the rate of premature ovarian insufficiency (POI) at 12 months after chemotherapy. Premature ovarian insufficiency was defined as anti-Müllerian hormone levels of less than 0.5 ng/mL in this study. The secondary end point was overall survival (OS) and tumor-free survival (TFS). RESULTS: A total of 330 eligible patients could be evaluated with complete data, among whom 301 patients (91.2%; GnRHA group: mean [SD] age, 40.6 [6.7] years; control group: mean [SD] age, 40.2 [5.9] years) were eligible for primary end point analysis. At 12 months after the completion of chemotherapy, the POI rate was 10.3% (15 of 146) in the GnRHa group and 44.5% (69 of 155) in the control group (odds ratio, 0.23; 95% CI, 0.14-0.39; P < .001). Anti-Müllerian hormone resumption in the GnRHa group was significantly better than that in the control group (15 of 25 vs 6 of 44; odds ratio, 4.40; 95% CI, 1.96-9.89; P < .001). After a median follow-up of 49 months (range, 25-60 months), the differences in 4-year OS and TFS between the 2 groups were not significant. A post hoc analysis showed that in patients younger than 35 years, the TFS was higher in the GnRHa group than in the control group (93% vs 62%; P = .004; hazard ratio, 0.15; 95% CI, 0.03-0.82; P = .03). CONCLUSIONS AND RELEVANCE: This randomized clinical trial found that administering GnRHa in treatment with chemotherapy for premenopausal patients with breast cancer reduces the risk of POI, which promotes the recovery of ovarian function. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02518191.

LncRNA SNHG17 regulates cell proliferation and invasion by targeting miR-338-3p/SOX4 axis in esophageal squamous cell carcinoma.

Small nucleolar RNA host gene 17 (SNHG17), a novel functional long noncoding RNA, has been demonstrated to play an essential role in the oncogenesis of several tumors. However, for esophageal squamous cell carcinoma (ESCC) the expression pattern and detailed function of SNHG17 are largely unknown. Hence, we conducted this study to explore potential roles and underlying oncogenic mechanisms for SNHG17 in ESCC progression. Results demonstrated SNHG17 to be markedly upregulated in ESCC. Knockdown of SNHG17 significantly suppressed ESCC cell proliferation, invasion, and epithelial-mesenchymal transition in vitro and tumor growth in vivo. Online database software analysis found miR-338-3p to interact with SNHG17 with the level of miR-338-3p negatively correlated with SNHG17 levels in ESCC samples. Further, miR-338-3p was found to directly target SRY-box transcription factor 4 (SOX4) in ESCC cells. Mechanistic analysis suggested that SNHG17 acts as an endogenous "sponge" competing with miR-338-3p to regulate SOX4, thereby promoting tumor progression. These results suggest that these molecular interactions may be potential therapeutic targets for ESCC.

Cancer patient management strategy in a Cancer Center of Zhejiang, China during the COVID-19 pandemic.

BACKGROUND: Due to the increased risk of viral infection and the severe shortage of medical resources during the pandemic of COVID-19, most hospitals in the epidemic areas significantly reduced non-emergency admissions and services, if not closed. As a result, it has been difficult to treat cancer patients on time, which adversely affects their prognosis. To address this problem, cancer centers must develop a strategic plan to manage both inpatients and outpatients during the pandemic, provide them with the necessary treatment, and at the same time prevent the spread of the virus among patients, visitors and medical staff. METHODS: Based upon the epidemic situation in Zhejiang Province, China, the number of running non-emergency medical wards in the Zhejiang Cancer Hospital was gradually increased in a controlled manner. All staff of the hospital received COVID-19 preventive training and was provided with three different levels of protection according to the risks of their services. Only patients without a known history of SARS-CoV-2 contact were eligible to schedule an appointment. Body temperature was measured on all patients upon their arrival at the hospital. Chest CT image, blood cell counting and travel/contact history were investigated in patients with fever. Respiratory tract samples, such as sputum and throat swabs, from all patients, including those clinically suspected of SARS-CoV-2 infection, were collected for nucleic acid detection of SARS-CoV-2 before treatment. RESULTS: A total of 3697 inpatients and 416 outpatients seeking cancer treatment were enrolled from February 1 to April 3, 2020, in compliance with the hospital's infection-control interventions. The clinicopathological parameters of the patients were summarized herein. 4237 samples from 4101 patients produced negative RNA testing results. Four clinically suspected patients all presented negative RNA test results and were excluded from the SARS-CoV-2 infection through follow-up retesting and monitoring. Seven patients with only N-gene positive results were retested, followed by CT scan and SARS-CoV-2 contact history investigation. All of them were finally diagnosed as non-infected patients. There was one outpatient who was confirmed positive by virus RNA test and then followed up. She might be an asymptomatic laboratory-confirmed case. During the study period, there was no SARS-CoV-2 infection among staff, patients and escorts of patients in the Zhejiang Cancer Hospital. CONCLUSION: This study suggested our infection-control interventions, including viral nucleic acid test, could be used as a reliable method to screen cancer patients in the area with moderate COVID-19 prevalence. Cancer may not be a high-risk factor of SARS-CoV-2 infection.

Description of COVID-19 cases along with the measures taken on prevention and control in Zhejiang, China.

Under the outbreak of COVID-19, it was urgent to analyze the cases from clinical features and epidemiological factors, as well as understand the effectiveness of measures taken on disease prevent and control. A retrospective study was applied for descriptive analysis of clinical features and epidemiological factors of confirmed cases in four cities of Zhejiang. The Onset-admission interval was calculated and plotted as well. The provincial measures regarding the response of COVID-19 were summed up and sorted out. The distribution and sex and age were under normality distribution, and the age of 20 to 80 were all in risk of developing the disease. Clinical features of fever and cough were found mostly happen on patients. More than half of the patients had image changed on chest from reported data. The factor of closely contacted with confirmed cases was the most cause to the disease. The median onset-admission interval was 6 days in Zhejiang province. As of the efficient health system, COVID-19 had been successfully prevented and controlled in Zhejiang. Males and females were all vulnerable to COVID-19. Preventing contact with confirmed cases could largely avoid the disease to happen. The government should take emergent and effective measures to prevent and treatment of the pandemic disease.

Cyclin-dependent kinase 6 (CDK6) is a candidate diagnostic biomarker for early non-small cell lung cancer.

BACKGROUND: Cyclin-dependent kinase 6 (CDK6) is an important regulatory protein of the cell cycle and plays an important role in tumor progression. The aim of this study was to investigate the expression of CDK6 in T1 stage non-small cell lung cancer (NSCLC) and to explore the association of CDK6 with the clinicopathological features of the disease. METHODS: CDK6 expression was analyzed by real-time PCR (RT-PCR) and immunohistochemistry (IHC) in tumor tissue samples and the distal normal tissue samples from 56 T1 stage NSCLC patients. The correlation between CDK6 expression and clinicopathological features was analyzed using the independent samples t-test and nonparametric tests. RESULTS: We found CDK6 had a tendency to increase in tumor tissues compared to normal tissues at the transcriptional level (P=0.073). Moreover, the expression of CDK6 protein in NSCLC tissues was also significantly higher than in normal lung tissues (P=0.003). With an increase of smoking quantity, the expression of CDK6 mRNA was increased (P=0.009). Remarkably, CDK6 expression was increased in squamous cell carcinoma (SCC) tissues but decreased in adenocarcinoma (AD) tissues at both the transcription and protein levels (P<0.001). After stratification based on pathological type, CDK6 gene expression was not associated with any clinicopathological features in SCC, while it was negatively associated with tumor diameter in AD (P=0.049). CONCLUSIONS: Taken together, these results indicated that abnormal expression of the CDK6 gene in NSCLC might be associated with pathological type, which may serve as a diagnostic biomarker for NSCLC.

Elevated preoperative platelet distribution width predicts poor prognosis in Esophageal Squamous Cell Carcinoma.

Activated platelets play a multifaceted role in tumorigenesis and progression. Platelet distribution width (PDW) is generally applied platelet parameters from routine blood test. Preoperative PDW has been considered a prognostic factor in many cancers. Nevertheless, the prognostic value of PDW in esophageal squamous cell carcinoma (ESCC) remains unknown. The study aimed to investigate whether preoperative PDW could serve as a prognostic factor in patients with ESCC. A total of 495 patients with ESCC undergoing curative surgery were enrolled. The relationship between PDW and clinical features in ESCC was analyzed using chi-square tests. Receiver operating characteristic (ROC) curve was used to determine the optimal cut-off value. Overall survival (OS) and disease-free survival (DFS) stratified by PDW were evaluated by Kaplan-Meier method and log-rank test. Univariate and multivariate Cox regression were used to evaluate the prognostic effect of PDW. Of the 495 patients, elevated PDW was observed in 241(48.7%) of the patients, respectively. An elevated PDW was correlated with depth of tumor (T stage, P = 0.031), nerve infiltration (P = 0.016), hospital time after operation (P = 0.020), platelet (P < 0.001), red cell distribution width (P < 0.001), and aspartate transaminase (P = 0.001). Moreover, elevated PDW (PDW ≥ 13.4 fL) predicted a worse OS and DFS in patients with ESCC (both P < 0.001). Multivariate analyses revealed that PDW was independently associated with OS (hazard ratios 1.194; 95% confidence interval 1.120-1.273; P < 0.001) and DFS (hazard ratios 2.562; 95% confidence interval 1.733-3.786; P < 0.001). Our findings indicated that elevated PDW could serve as an independent worse survival in ESCC.

Comparative analysis of the serum proteome profiles of thyroid cancer: An initial focus on the lipid profile.

The serum lipid profile and clinical outcomes of cancer patients are commonly correlated in a wide range of carcinomas. However, few studies have investigated the serum lipid profile of patients with thyroid cancer (TC). The present study therefore aimed to analyze the lipid profiles of patients with TC. The serum proteomes of 31 participants with stage I-IV TC were screened using Orbitrap Q Exactive Plus. Analytical data collected between November 1, 2013 and November 11, 2018 from the laboratory information system included the total cholesterol (CHO), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA1), lipoprotein (a) and apolipoprotein B (ApoB) levels that were used to validate the screening results. A total of 3875 outpatients were enrolled in this study. A number of 17 differentially expressed proteins were identified. An Ingenuity pathway analysis identified activation of the liver X receptor/retinoid X receptor (LXR/RXR) activation, which is a crucial pathway involved in lipid metabolism. The results demonstrated that the total CHO levels were significantly different between patients with TC and control groups, both in men and women. In women, the levels of TG, HDL-C, Apo A1 and LDL-C/HDL-C were significantly different between patients with TC and control groups (all P<0.05). Higher concentrations of TG and LDL-C/HDL-C were observed in the cancer group compared with the control group. However, lower levels of Apo A1 and HDL-C were observed in women from the cancer group compared with the control group. The results from the present study revealed the presence of a disordered lipid profile in patients with TC. The molecular mechanism underlying the association between lipid metabolism and cancer requires further investigation and may be used to develop novel diagnostic biomarkers and therapeutic targets in human cancers.

CA125 is a potential biomarker to predict surgically incurable gastric and cardia cancer: A retrospective study.

Preoperative evaluation of the curability of gastric and cardia cancer is important to avoid risks of unnecessary surgery. Our previous study has reported several clinical parameters associated with incurable gastric surgery. In this study, we aimed to evaluate the correlation between CA125 and the curability of gastric and cardia cancer.A total of 297 cases of gastric and cardia cancer were analyzed retrospectively, including 153 cases with radical surgery and 144 with surgery for incurable gastric or cardia cancer. χ test was performed to analyze the associations between curability or incurable factors and clinicopathological data, including CA125 value. ROC curves were generated, and cutoff points for curability, T status, N status, peritoneal metastasis, and distant metastasis were found, respectively. Binary logistic regression was performed to verify the associations between dependent variables (curability, T status, N status, peritoneal metastasis, and distant metastasis) and covariates (related clinicopathological data from step 1 and cutoff points from step 2).Esophageal involvement, T grade, and CA125 were risk factors of curability. T grade and Borrmann type were risk factors of T status. T grade and CA125 were risk factors of N status. Age, esophageal involvement, T grade, and CA125 were risk factors of peritoneal metastasis. CA125 was risk factor of distant metastasis.CA125 is a potential biological marker for curability prediction of gastric and cardia cancer.

CT staging and preoperative assessment of resectability for thymic epithelial tumors.

BACKGROUND: The aim of this study was to determine the computed tomography (CT) features potentially helpful for accurate staging and predicting resectability of thymic epithelial tumors (TET). METHODS: One hundred and thirty-eight consecutive TET patients undergoing surgical resection from April 2010 to November 2011 were prospectively entered into a database. All patients were staged according to the Masaoka-Koga staging system. The relationship between CT features with tumor staging and complete resection was reviewed after surgery. RESULTS: Surgico-pathological staging was stage I in 63, stage II in 32, stage III in 32, and stage IV in 11 patients. Preoperative CT staging was highly consistent with postoperative surgico-pathological staging (Kappa =0.525). Tumor shape, contour, enhancement, with or without invasion of the adjacent structures (mediastinal fat, mediastinal pleura, lung, pericardium, mediastinal vessels, phrenic nerve), and presence of pleural, pericardial effusionor intrapulmonary metastasis were correlated with Masaoka-Koga staging (P<0.05). However, tumor size, internal density or presence of calcification was not associated with staging (P>0.05). Tumor size, presence of calcification and mediastinal lymph node enlargement were not correlated with complete tumor resection (P>0.05). Tumor shape, contour, internal density, enhancement pattern, and invasion of adjacent structures were related to complete resection of the primary tumor in univariate analysis (P<0.05). However, upon multivariate logistic regression, only absence of artery systems invasion was predictive of complete resection (P<0.05). CONCLUSIONS: Clinical staging of TET could be accurately evaluated with CT features including tumor shape, contour, enhancement pattern, with or without invasion of adjacent structures, and presence of pleural, pericardial effusion or intrapulmonary metastasis. Absence of arterial system invasion on CT was the only predictive feature for predicting complete resection of TET.

Analysis of surgery for incurable gastric cancer.

BACKGROUND: It is important to evaluate the curability of and avoid unnecessary exploratory surgery for gastric cancer preoperatively. However, no related research has been reported until now. The aim of this study was to evaluate the factors influencing surgery for incurable gastric cancer. METHODS: 310 cases of T3-4 gastric cancer patients were analyzed retrospectively, including 141 cases with radical surgery and 169 with surgery for incurable gastric cancer. The incurable factors were categorized as T status (unresectable T4 tumor), N status (unresectable lymph node), peritoneal metastasis, and distant metastasis. χ (2) test and logistic regression were performed to analyze the associations between curability, T status, N status, peritoneal metastasis, or distant metastasis and clinicopathological data. RESULTS: Esophageal involvement and T grade were associated with curability. Cardia involvement and Borrmann type were associated with T status. Esophageal involvement and T grade were associated with N status. Gastric body involvement, esophageal involvement, and T grade were associated with peritoneal metastasis. Gastric antrum involvement was associated with distant metastasis. CONCLUSIONS: The influencing factors of surgery for incurable gastric cancer should be analyzed preoperatively. Resectability should be evaluated according to these influencing factors combined with imaging analysis.

Lower serum levels of bilirubin in the newly diagnosed lung cancer patients: A case-control study in China.

PURPOSE: A few prospective studies demonstrated that bilirubin levels were inversely associated with the risk of lung cancer. However, the retrospective study about the relationship between bilirubin levels and lung cancer in China was not available. So, we want to know whether there has a difference in serum bilirubin concentrations between normal people and lung cancer patients. MATERIALS AND METHODS: Using a case-control study, we investigated the bilirubin levels in 317 patients with lung cancer and 317 age-, sex-matched controls from Zhejiang Cancer Hospital. Furthermore, we analyzed the associations between serum bilirubin expressions and baseline clinical features of lung cancer patients using a Wilcoxon rank sum test. RESULTS: Bilirubin levels, including total bilirubin, direct bilirubin, and indirect bilirubin, were significantly lower in human lung cancer serum relative to normal control (P < 0.001), and the older (> 50 years) had higher bilirubin levels compared with the younger (27-50 years) in lung cancer group. Besides, the duration of smoking was negatively related to bilirubin levels, but they did not reach statistical significance except for indirect bilirubin (P = 0.041). However, there was no difference in bilirubin levels between small cell lung cancer (SCLC) and non-SCLC (NSCLC), and we did not find that the bilirubin levels were correlated with sex, drinking status in patients of lung cancer. CONCLUSION: Serum total bilirubin, indirect bilirubin, and direct bilirubin levels of the patients with lung cancer were all significantly lower than those of control group (P < 0.001). Lower levels of bilirubin may be a risk factor for lung cancer, and it could serve as a potential screening biomarker for lung cancer. Large-scale investigations and additional improvements are urgently needed to demonstrate the mechanism and molecular pathway in order to achieve the clinical utility in the future.

Tumor markers CA19-9, CA242 and CEA in the diagnosis of pancreatic cancer: a meta-analysis.

BACKGROUND: Pancreatic cancer has the worst prognosis and early detection is crucial for improving patient prognosis. Therefore, we performed a meta-analysis to evaluate and compare the sensitivity and specificity of single test of CA19-9, CA242, and CEA, as well as combination test in pancreatic cancer detection. METHODS: We searched PubMed, Embase, Medline, and Wanfang databases for studies that evaluated the diagnostic validity of CA19-9, CA242, and CEA between January 1990 and September 2014. Data were analyzed by Meta-Disc and STATA software. RESULTS: A total of 21 studies including 3497 participants, which fulfilled the inclusion criteria were considered for analysis. The pooled sensitivities for CA19-9, CA242, and CEA were 75.4 (95% CI: 73.4-77.4), 67.8 (95% CI: 65.5-70), and 39.5 (95% CI: 37.3-41.7), respectively. The pooled specificities of CA19-9, CA242, and CEA were 77.6 (95% CI: 75.4-79.7), 83 (95% CI: 81-85), and 81.3 (95% CI: 79.3-83.2), respectively. Parallel combination of CA19-9+CA242 has a higher sensitivity (89, 95% CI: 80-95) without impairing the specificity (75, 95% CI: 67-82). CONCLUSIONS: Our meta-analysis showed that CA242 and CA19-9 have better performance in the diagnosis of pancreatic cancer than CEA. Furthermore, parallel combination test of CA19-9+CA242 could be of better diagnostic value than individual CA242 or CA19-9 test.

Comparison of perioperative outcomes between open and minimally invasive esophagectomy for esophageal cancer.

BACKGROUND: To compare surgical outcomes of thoracoscopic and laparoscopic esophagectomy with open esophagectomy in order to study the learning curve of minimally invasive surgery for esophageal cancers. METHODS: Among 109 esophageal cancer patients retrospectively studied, 59 patients underwent minimally invasive esophagectomy (MIE) and 50 underwent open surgery (OE). In the MIE group, the first 30 patients received hybrid procedures, including 16 thoracoscopic esophagectomies and 14 laparoscopic maneuvers. The later 29 patients received thoraco-laparoscopic esophagectomy (TLE). RESULTS: The overall morbidity of MIE and OE was 42.4% (25/59) and 44.0% (22/50), respectively, with no statistical difference. However, the MIE group had a significantly lower incidence of functional complication (1.79%, 1/59) than the OE group (32.0%, 16/50, P < 0.01). The technical complication rate was not significantly different between the two groups (14/59, 23.7% vs. 6/50, 12.0%, P = NS), nor was the overall complication rate between the 30 early period cases and the 29 later cases (P = NS); although the later cases had TLE and there was no recurrent laryngeal nerve injury. CONCLUSION: Minimally invasive approaches may help to decrease the risk of functional complication but not technical problems, after esophagectomy. For esophageal cancer patients to benefit from this minimally invasive surgery, an extended learning curve is necessary to avoid technical problems, such as anastomotic leakage and recurrent laryngeal nerve palsy.

Increased expression of the long non-coding RNA ANRIL promotes lung cancer cell metastasis and correlates with poor prognosis.

BACKGROUND: Emerging evidences indicate that dysregulated long non-coding RNAs (lncRNAs) are implicated in cancer tumorigenesis and progression. LncRNA ANRIL has been shown to promote the progression of gastric cancer. However, the role of lncRNA ANRIL in human non-small cell lung cancer (NSCLC) remains unclear. METHODS: Expression of lncRNA ANRIL was analyzed in 87 NSCLC tissues and three lung cancer cell lines by quantitative real-time PCR (qRT-PCR). The correlation of lncRNA ANRIL with clinicopathological features and prognosis was analyzed. Suppression of lncRNA ANRIL using siRNA treatment was performed in order to explore its role in tumor progression. RESULTS: The expression level of lncRNA ANRIL was higher in NSCLC tissues and lung cancer cells than in adjacent non-tumor tissues and normal human bronchial epithelial cells. Higher expression of lncRNA ANRIL in NSCLC tissues was associated with higher TNM stage and advanced lymph node metastasis. Patients with high lncRNA ANRIL expression had poorer overall survival compared with low lncRNA ANRIL group. Univariate and multivariate analyses suggested that high expression of lncRNA ANRIL was an independent poor prognostic indicator for NSCLC patients. Moreover, knockdown of lncRNA ANRIL expression could inhibit lung cancer cell proliferation, migration and invasion in vitro. CONCLUSIONS: Our results suggested that lncRNA ANRIL was a potential biomarker for NSCLC prognosis, and the dysregulation of lncRNA ANRIL may play an important role in NSCLC progression. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1707061287149690 .