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.

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.

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.

Nuclear-cytoplasmic partitioning of cucumber mosaic virus protein 2b determines the balance between its roles as a virulence determinant and an RNA-silencing suppressor.

UNLABELLED: The Cucumber Mosaic Virus (CMV) 2b protein is an RNA-silencing suppressor that plays roles in CMV accumulation and virulence. The 2b proteins of subgroup IA CMV strains partition between the nucleus and cytoplasm, but the biological significance of this is uncertain. We fused an additional nuclear localization signal (NLS) to the 2b protein of subgroup IA strain Fny-CMV to create 2b-NLS and tested its effects on subcellular distribution, silencing, and virulence. The additional NLS enhanced 2b protein nuclear and nucleolar accumulation, but nuclear and nucleolar enrichment correlated with markedly diminished silencing suppressor activity in patch assays and abolished 2b protein-mediated disruption of microRNA activity in transgenic Arabidopsis. Nucleus/nucleolus-localized 2b protein possesses at least some ability to inhibit antiviral silencing, but this was not sufficient to prevent recovery from disease in younger, developing leaves in Arabidopsis. However, enhanced nuclear and nucleolar accumulation of 2b increased virulence and accelerated symptom appearance in older leaves. Experiments with Arabidopsis lines carrying mutant Dicer-like alleles demonstrated that compromised suppressor activity explained the diminished ability of 2b-NLS to enhance virus accumulation. Remarkably, the increased virulence that 2b-NLS engendered was unrelated to effects on microRNA- or short interfering RNA-regulated host functions. Thus, although nucleus- and nucleolus-localized 2b protein is less efficient at silencing suppression than cytoplasm-localized 2b, it enhances CMV virulence. We propose that partitioning of the 2b protein between the cytoplasmic and nuclear/nucleolar compartments allows CMV to regulate the balance between virus accumulation and damage to the host, presumably to maximize the benefit for the virus. IMPORTANCE: In this work, the main finding is that nucleus/nucleolus-localized 2b protein is strongly associated with CMV virulence, which is independent of its effect on small RNA pathways. Moreover, this work supports the contention that the silencing suppressor activity of CMV 2b protein is predominantly exerted by that portion of the 2b protein residing in the cytoplasm. Thus, we propose that partitioning of the 2b protein between the cytoplasmic and nuclear/nucleolar compartments allows CMV to regulate the balance between virus accumulation and damage to the host, presumably to maximize the benefit for the virus.

Using a viral vector to reveal the role of microRNA159 in disease symptom induction by a severe strain of Cucumber mosaic virus.

In transgenic Arabidopsis (Arabidopsis thaliana), expression of the Cucumber mosaic virus (CMV) 2b silencing suppressor protein from the severe subgroup IA strain Fny disrupted microRNA (miRNA)-regulated development but orthologs from mild subgroup II strains (Q and LS) did not, explaining strain-specific differences in symptom severity. However, it is unknown which miRNAs affected by Fny2b critically affect viral symptoms. Observations that Fny2b-transgenic plants phenocopy microRNA159ab (mir159ab) mutant plants and that Fny2b altered miR159ab-regulated transcript levels suggested a role for miR159ab in elicitation of severe symptoms by Fny-CMV. Using restoration of the normal phenotype in transgenic plants expressing an artificial miRNA as a proof of concept, we developed a LS-CMV-based vector to express sequences mimicking miRNA targets. Expressing a miR159 target mimic sequence using LS-CMV depleted miR159 and induced symptoms resembling those of Fny-CMV. Suppression of Fny-CMV-induced symptoms in plants harboring mutant alleles for the miR159ab targets MYB domain protein33 (MYB33) and MYB65 confirmed the importance of this miRNA in pathogenesis. This study demonstrates the utility of a viral vector to express miRNA target mimics to facilitate functional studies of miRNAs in plants.

FasL -844T/C and Fas -1377G/A: mutations of pulmonary adenocarcinoma in South China and their clinical significances.

Apoptosis is an important mechanism of malignant tumor formation and progression. Single nucleotide polymorphisms (SNPs) located within cell death genes may influence cancer risk. We explored the relationship between FasL -844T/C and/or Fas -1377G/A SNPs and pulmonary adenocarcinoma (AD). Two hundred seventy-five patients with pulmonary AD of South China admitted into Zhejiang Cancer Hospital from July 2007 to October 2011 were randomly selected, and their clinicopathological data were collected at the same time. Two hundred ninety-seven cases of healthy individuals were selected as control. FasL -844T/C and Fas -1377G/A SNPs were detected by PCR-RFLP technique to evaluate the relationships between these two SNPs and pulmonary AD. Age, FasL -844 and Fas -1377 SNPs were associated with increased risk of pulmonary AD susceptibility in main effect analysis. FasL -844CC and Fas -1377 AA were associated with an increased risk for the development of pulmonary AD only in age <60 years people, but not in those ≥60 years. FasL -844CC genotype was associated with an increased risk for pulmonary AD (adjusted OR = 2.010, 95 % CI 1.196-3.379, P = 0.008) compared with TT genotype. However, Fas -1377 AA was a risk factor only when FasL -844 genotype was CC. Fas -1377 genotypes showed significant effect modification of pulmonary AD risk by FasL -844 genotype with test of the interaction term adjusting for age, gender, and FasL -844 SNP. Fas -1377G/A was not associated with the clinicopathological factors, while FasL -844C/T was associated with tumor stage and lymph node metastasis in age ≥60 years people and tumor stage in those <60 years. In conclusion, FasL -844 SNP is associated with the susceptibility of pulmonary AD in age <60 years people. Fas -1377 SNP may modify the association of FasL -844 SNP with the risk of pulmonary AD. FasL -844 genotype plays an important role in the occurrence and progression of pulmonary AD.

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.

[Research on expression of somatomedin b domain of proteoglycan 4 and recombinant protein aggregation].

Recombinant protein SMB(PRG4) containing two Somatomedin B domains and a small amount of glycosylation of repetitive sequences of proteoglycan 4 was cloned according to PGR4 gene polymorphism. Mature purification process was established and recombinant protein SMB(PRG4), with high-level expression was purified. By using size-exclusion chromatogaraphy and dynamic light scattering, we found that the recombinant protein self-aggregate to dimeric form. Structure prediction and non-reducing electrophoresis revealed that SMB(PRG4), was a non-covalently bonded dimer.

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.

[Comparison of surgical approaches for thymic disorders: feasibility of VATS thymectomy and comparison with small incision and median sternotomy].

OBJECTIVES: To evaluate the feasibility and safety of video-assisted thoracoscopic surgery (VATS), and to compare surgical results of VATS with standard median sternotomy (MS) and other minimal invasive approaches through various small incisions (SI). METHODS: Totally 111 patients underwent surgery for thymic disorders (maximun diameter ≤ 5 cm, clinical stage I-II for thymic tumors) during March 2010 to June 2012 was retrospectively reviewed. There were 46 male and 65 female patients with a mean age of (51 ± 15) years.Resection via VATS was carried out in 47 patients, via SI in 26 patients, and via MS in 38 patients. Demographic characteristics, operation time, number and cause of conversion, blood loss during operation, duration and amount of chest tube drainage, transfusion, morbidity, and length of hospital stay (LHS) were compared between the three groups. RESULTS: Of the 111 patients, 79 patients had thymic epithelia tumors (stage I 32 patients, stage II 39 patients, stage III 8 patients), 31 patients had benign cysts and 1 patient had tuberculosis.In the VATS group, there were 3 conversions among 38 patients through right-side approach, and 4 conversions among 9 patients through left-side approach. The causes for conversion included dense pleura adhesion, invasion of tumor into adjacent structures (pericardium, lung, or great vessels), and injury of the left inominate vein. There was no significant difference in operative time, blood loss or transfusion during operation, duration or amount of postoperative chest tube drainage among the 3 groups (P > 0.05). Average LHS was significantly shorter in the VATS group (5.7 ± 1.7) days than in the SI group (7.5 ± 2.2) days and the MS group (8.2 ± 1.9) days (F = 3.759, P = 0.002). Total thymectomy was performed in 74 patients, 25 patients (53.2%, 25/47) in VATS group, 11 patients (42.3%, 11/26) in SI group, and 38 patients (100%, 38/38) in MS group. The reset of the patients received tumor resection and partial thymectomy. Among all the subgroups, LHS was the shortest in VATS total thymectomy patients (5.0 ± 1.4) days (F = 5.844, P = 0.001). There was no perioperative mortality. The only major morbidity was a postoperative bleeding necessitating reintervention in SI group. CONCLUSIONS: VATS for benign thymic lesions and early-stage thymic tumors is safe and feasible.It is associated with shorter hospital stay compared with other minimal invasive approaches or standard sternotomy.

[Recurrence pattern of histological node-negative squamous cell carcinoma of the thoracic esophagus after extended radical esophagectomy with lymphadenectomy].

OBJECTIVE: To analyze the clinical and pathologic influencing factors of early recurrence in patients with histological node-negative (pN0 stage) esophageal squamous cell carcinoma after radical esophagectomy. METHODS: A retrospective study on 112 consecutive pN0 stage esophageal squamous cell carcinoma patients who underwent esophagectomy with lymphadenectomy by the same surgical team from January 2004 to December 2010. There were 92 male and 20 female patients, aging from 36 to 80 years with a mean age of 60.3 years. The Cox proportional hazards model was used to determine the independent risk factors for recurrence within 3 years after the operation. RESULTS: Recurrence was recognized in 45 patients (40.2%) within 3 years after operation. The median time to tumor recurrence was 17.4 months. Locoregional recurrence was found in 38 patients (33.9%), and hematogenous metastasis in 7 patients (6.3%). Recurrence closely correlated with tumor location, grade of differentiation, pT stage and pathologic stage (χ(2) = 6.380 to 18.837, P < 0.05). The Cox multivariate analysis showed that tumor location (RR = 1.092, P = 0.049) and pT3-4a stage (RR = 3.296, P = 0.017) were independent risk factors for postoperative locoregional recurrence. CONCLUSIONS: The most common recurrence pattern of patients with pN0 esophageal squamous cell carcinoma would develop recurrence within 3 years after operation is locoregional recurrence. Upper/middle thoracic location and pT3-4a stage are independent risk factors for locoregional recurrence of pN0 esophageal squamous cell carcinoma after operation.

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.

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.

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.

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.

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.

[Clinical implications of the new TNM staging system for thoracic esophageal squamous cell carcinoma].

OBJECTIVE: To evaluate THE clinical significance of the 2009 UICC staging system for thoracic esophageal squamous cell carcinoma. METHODS: Two hundred and nine patients with thoracic esophageal squamous cell carcinoma undergone selective cervico-thoraco-abdominal lymphadenectomy were reviewed retrospectively and restaged according to the new 2009 UICC staging system. The relationship between individual stages and survival were analyzed accordingly. RESULTS: The five-year overall and cause-specific survivals were 35.0% and 38.8%, respectively. Depth of invasion (T, P = 0.004), number of metastatic lymph nodes (N, P < 0.001), distant lymph node metastasis (M, P = 0.003), complete resection (R, P = 0.005) were significantly related to postoperative survival. On the other hand, location of primary tumor (L, P = 0.743) and histological grade (G, P = 0.653) were not significantly related to long-term prognosis. Upon stratification, the 5-year survival for T4a (32.0%) was significantly better than that of T4b (0, P < 0.001), but was similar to that of T3 (28.4%, P = 0.288). Patients without nodal involvement (47.8%, P < 0.001) and those with single station nodal disease (37.5%, P < 0.001) had significantly better survival than patients having 2 or more stations of lymph node metastasis (11.3%). Also patients without nodal involvement and those with metastasis confined to a single field (34.2%) had significantly better survival than patients having nodal diseases in 2 fields (12.1%) and 3 fields (0, P < 0.001). The 5-year survival for cervical metastasis after complete resection was 20.0%. Upon multivariate analysis, depth of tumor invasion (P = 0.001, RR = 1.635), numbers of metastatic nodal stations (P = 0.043, RR = 1.540) and fields (P = 0.010, RR = 2.187) were revealed as independent risk factors for long-term survival. CONCLUSIONS: The new UICC staging system effectively predicts long-term prognosis for thoracic esophageal squamous cell carcinoma. Depth of tumor invasion and extent of lymph node involvement are two most important prognostic factors. To improve surgical outcomes, much effort is needed to increase the accuracy of preoperative staging and to include effective induction therapies into a multidisciplinary setting.

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.

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.

[Optimized perioperative management helps improve the results of thoracotomy in elderly patients].

OBJECTIVES: To optimize perioperative respiratory and circulatory management so as to improve the surgical results of thoracotomy in elderly patients. METHODS: Respiratory and circulatory status was prospectively monitored and postoperative complications were documented in 58 elderly patients aged over 65 years underwent thoracotomy. The results were compared with those from 56 young patients aged under 65 years in the same time period. Based on the study results, the original perioperative management model was modified and prospectively studied in the following 179 elderly patients. Again the results were compared with 477 younger patients concomitantly treated. RESULTS: Through optimized perioperative management, the in-hospital mortality (4.9% vs. 1.1%, P = 0.033) and overall morbidity (58.6% vs. 21.8%, P < 0.01) were significantly decreased. This was most significant in the decrease of functional complications (51.7% vs. 14.5%, P < 0.01), especially the cardiovascular (22.4% vs. 7.3%, P = 0.001) and respiratory complications (20.7% vs. 7.3%, P = 0.004). There was no difference in technical complications between the two time periods. Comparing with the original model, the optimized perioperative management strategy resulted in significant decrease in acute lung injury (17.2% vs. 6.7%, P = 0.016), respiratory failure (6.9% vs. 1.7%, P = 0.041), as well as cardiac arrhythmia (20.7% vs. 7.3%, P = 0.004) in the early postoperative period. CONCLUSIONS: Optimization of perioperative management through careful preoperative functional evaluation, intraoperative protective ventilation, postoperative close monitoring of water balance, and timely intervention, may help improve surgical results in the elderly.