Exposure status, spatial variation, and health risk assessment of selected heavy metal(loid)s in common commercial fish species of the Beibu Gulf.

Fishes are considered as biological indicators of heavy metal(loid)s pollution. In this study, contents of seven heavy metal(loid)s, including Cu, Cr, Cd, Pb, Zn, As, and Hg, in the muscles of ten common fish species in the Beibu Gulf were analyzed to figure out the pollutants status and their health risk. Results showed all species were largely contaminated by arsenic. Under conservative estimation scenario, target hazard quotient and health index revealed no health risk of species except Alepes kleinii. Under pessimistic estimation scenario, target cancer risk and estimated daily intake showed that, except Saurida undosquamis, Saurida tumbil, and Trachinotus ovatus, the remaining species were at risk of causing cancer for their consumers. Daily intake of arsenic and mercury in most species by residents in the Beibu Gulf exceeded provisional maximum tolerable amount recommended by FAO, suggesting the need of moderate consumption of these species.

Prognostic Significance of Neutrophil-to-Lymphocyte Ratio and C-Reactive Protein/Albumin Ratio in Luminal Breast Cancers With HER2-Negativity.

Purpose: This study was determined to evaluate the prognostic value of neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein/albumin ratio (CAR) prior to surgery in luminal breast cancers (BC) with HER2-negativity. Methods: The clinical data of 708 HER2-negative luminal BC patients from January 2013 to December 2016 were retrospectively collected and analyzed. The optimal cut-off value of NLR and CAR were determined via receiver operating characteristic (ROC) curve. The disease-free survival (DFS) and cancer specific survival (CSS) rates were estimated using the Kaplan-Meier method. Cox univariate and multivariate proportional hazards regression models were performed to identify significant predictors of DFS and CSS simultaneously. Results: The mean age of the patients diagnosed was 52.43 years (range, 15-95 years), and the median follow-up was 62.71 months (range, 12-92 months). Univariate and multivariate analysis confirmed that NLR ≥2.2 was significantly associated with worse DFS (HR=2.886, 95%CI=1.756-4.745, p<0.001), and same results were obtained in terms of CSS (HR=3.999, 95%CI=2.002-7.987, p<0.001). Similarly, CAR ≥0.07 was independently and significantly associated with poor DFS (HR=3.858, 95%CI=2.346-6.345, p<0.001) and CSS (HR=6.563, 95%CI=3.558-12.106, p<0.001). Conclusion: Preoperative evaluation of NLR and CAR were significant and independent prognostic indicators for luminal breast cancers with HER2-negativity.

Pegylated Liposomal Doxorubicin Versus Epirubicin as Adjuvant Therapy for Stage I-III Breast Cancer.

Background: Conventional anthracyclines, like epirubicin, are cornerstone drugs for breast cancer treatment of all stages, but their cumulative toxicity could cause life-threatening side effects. Pegylated liposomal doxorubicin (PLD), an effective anti-breast cancer drug, has lower toxicity than conventional anthracyclines. This retrospective study compared the efficacy and toxicity profiles between PLD and epirubicin as adjuvant therapy for breast cancer. Patients and Methods: A total of 1,471 patients diagnosed with stage I-III breast cancer between 2000 and 2018 were included in this study, among which 661 were treated with PLD and 810 with epirubicin, with 45.9 months as the median follow-up time. Anti-breast cancer efficacy was assessed with overall survival (OS) and disease-free survival (DFS), while cardiac toxicity was assessed with left ventricular ejection fraction (LVEF) and electrocardiogram (ECG). Results: The Kaplan-Meier method and Cox proportional hazards model revealed that there was no statistical difference in OS or DFS between patients treated with PLD and epirubicin, regardless of cancer stages or molecular subtypes (all p-values > 0.05). In addition, patients had significantly better LEVF and ECG data after adjuvant therapy with PLD (both p-values < 0.05). Conclusion: Based on the large sample size and the long follow-up time of this study, we conclude that PLD has a similar anti-breast cancer efficacy as epirubicin while inducing lower level of cardiac toxicity in Han Chinese. This study suggests that PLD-based adjuvant chemotherapy could be a better option than epirubicin for breast cancer patients especially with existing cardiac disease.

PLAC8 promotes adriamycin resistance via blocking autophagy in breast cancer.

Adriamycin (ADM) is currently one of the most effective chemotherapeutic agents in breast cancer treatment. However, growing resistance to ADM could lead to treatment failure and poor outcome. PLAC8 was reported as a novel highly conserved protein and functioned as an oncogene or tumour suppressor in various tumours. Here, we found higher PLAC8 expression was correlated with worse outcome and aggressive phenotype in breast cancer. Breast cancer patients with higher PLAC8 expression showed potential ADM resistance. In vitro experiments further confirmed that PLAC8 inhibited by siRNA or enforced overexpression by infecting pcDNA3.1(C)-PLAC8 plasmid correspondingly decreased or increased ADM resistance. Subsequently, we demonstrated that ectopic PLAC8 expression in MCF-7/ADMR cell blocked the accumulation of the autophagy-associated protein LC3 and resulted in cellular accumulation of p62. Rapamycin-triggered autophagy significantly increased cell response to ADM, while the autophagy inhibitor 3-MA enhanced ADM resistance. 3-MA and PLAC8 could synergistically cause ADM resistance via blocking the autophagy process. Additionally, the down-regulation of p62 by siRNA attenuated the activation of autophagy and PLAC8 expression in breast cancer cells. Thus, our findings suggest that PLAC8, through the participation of p62, inhibits autophagy and consequently results in ADM resistance in breast cancer. PLAC8/p62 pathway may act as novel therapeutic targets in breast cancer treatment and has potential clinical application in overcoming ADM resistance.

The influence of preoperative biopsy on the surgical method in breast cancer patients: a single-center experience of 3,966 cases in China.

BACKGROUND: The National Surgical Adjuvant Breast and Bowel Project (NSABP) B32 trial reported that the detection rate of sentinel lymph nodes by core needle biopsy (CNB) is higher than that by segmental resection. However, there are few reports regarding the detection rate of sentinel lymph nodes by vacuum-assisted breast biopsy (VABB). Therefore, we analyzed the impact of preoperative biopsy methods on the surgical modes of 3,966 patients with breast cancer in our center. METHODS: In total, 3,966 female breast cancer patients [clinical tumor node metastasis (TNM) stage I-III] were enrolled in this study. Preoperative pathological diagnosis methods included fine needle aspiration (FNA) biopsy, CNB, excision biopsy, and VABB. According to the time of diagnosis. The data were analysis by chi square test, variance analysis and the Kaplan-Meier time series in SPSS 22.0. RESULTS: There was a decrease in the number of patients that underwent excision biopsy (7.3% to 2.7%) and intraoperative freezing (89.4% to 28.9%) over time, while CNB exhibited an increasing trend (1.6% to 55.3%). The positive rates of VABB, CNB, excision biopsy, and FNA were 99.5%, 97.1%, 97.9%, and 82.2%, respectively, and the false negative rates were 0%, 1.8%, 0.34%, and 8.9%, respectively. The overall breast-conserving rate was 36.7%, while the breast-conserving rate for VABB was 57.1%. The axillary sentinel lymph node biopsy rate of cN0 patients was 48.3%, and the intraoperative frozen group (36.7%) and excision biopsy group (39.5%) were lower than the CNB (57.1%) and VABB (77.9%) groups. Until December 2019, there were 350 cases with tumor recurrence or metastasis. The methods of biopsy were not correlated to the cumulative survival time. CONCLUSIONS: Changes to the diagnosis and treatment of breast cancer has a profound impact on the method of tumor biopsy. VABB biopsy offers advantages such as accurate diagnosis, a greater volume of tissue taken at one time, minimally invasive and repeatable, and does not affect the surgical approach and prognosis of patients. It will gradually become the primary method of preoperative pathological evaluation of breast cancer.

Evaluation of the diagnostic value of circulating tumor cells with CytoSorter® CTC capture system in patients with breast cancer.

PURPOSE: In this study, we aimed to investigate the viability of utilizing CytoSorter® system to detect circulating tumor cells (CTCs) and to evaluate the diagnostic value of CTCs in breast cancer (BC). METHODS: A total of 366 females patients suspected of having BC and 30 healthy female volunteers were enrolled in this study. CTCs were enriched by CytoSorter® , a microfluidic-based CTCs capturing platform. CTC detection was performed before operation or biopsy. Based on the biopsy results, patients were divided into two groups, namely patients with BC and patients with benign breast diseases (BBD). Patients with BBD and healthy volunteers were serving as controls. The correlation between CTC enumeration and patients' clinicopathological characteristics was evaluated. The receiver operating characteristic (ROC) curve was plotted to assess the diagnostic potency of CytoSorter® system in BC. RESULTS: Based on the biopsy results, 130 BC patients at different cancer stages and 236 patients with BBD were enrolled in the study. Seven subjects were dropped out from the study. CTCs were detected in 109 of 128 BC patients, in one of 29 healthy volunteers, and in 37 of 232 patients with BBD. Maximum CTC counts detected in BC patients, healthy volunteers, and patients with BBD were 8, 1, and 4, respectively. Statistical analysis showed CTCs could be used to distinguish BC patients from healthy volunteers and patients with BBD (P < .0001). Circulating tumor cells were statistically associated with patients' cancer stage (P = .0126), tumor size (tumor node metastasis [TNM] T stage, P = .0253), cancer type (invasive vs noninvasive, P = .0141), and lymph node metastasis (P = .0436). More CTCs were found in patients at advanced cancer stage or TNM T stage and in patients with invasive tumor or lymph node metastasis. Furthermore, CTC detection rates in BC patients at Tis and T1-4 stages were 50%, 81.67%, 91.07%, 100%, and 100%, respectively. When the CTC cut-off value was set to 2, the ROC curve gave an area under the curve (AUC) of 0.86 with a specificity and sensitivity of 95.4% and 76.56%, respectively. Taken together, CTCs could be used as a diagnostic aid in assistance of cancer screening and staging. CONCLUSION: Circulating tumor cells were successfully isolated in BC patients using CytoSorter® system. CTCs can be used to differentiate BC patients from the patients with BBD or healthy volunteers, and as a diagnostic aid for early cancer diagnosis and cancer staging.

The Expression Profiles of MicroRNA Let-7a in Peripheral Blood Mononuclear Cells from Patients of Gastric Cancer with Neoadjuvant Chemotherapy.

BACKGROUND: The microRNA let-7a contains three copies of genes and is associated with various types of cancer, including gastric cancer. In this study, we aim to investigate the differential expression patterns of microRNA let7a in PBMCs from patients of gastric cancer (GC) before and after neoadjuvant chemotherapy. METHODS: The differential expression levels of let-7a were detected in PBMCs from 22 patients with GC before and after neoadjuvant chemotherapy by reverse transcription quantitative polymerase chain reaction (RT-qPCR). The statistical analysis was performed with t-test and one-way AVOVA. RESULTS: MicroRNA let-7a level was significantly decreased in patients with GC after neoadjuvant chemotherapy (p < 0.05). In patients with GC, microRNA let-7a has different expression patterns with different neoadjuvant chemotherapy cycles. CONCLUSIONS: Our study demonstrated that microRNA let-7a was expressed differentially in patients with GC before and after neoadjuvant chemotherapy. These data supported that microRNA let-7a may have a potential role in efficacy assessment in patients with GC with neoadjuvant chemotherapy.

The novel KLF4/PLAC8 signaling pathway regulates lung cancer growth.

Accumulating evidence suggests that placenta-specific 8 (PLAC8) plays an important role in normal cellular process and human diseases, including multiple types of human tumors, and its role is highly relied upon in cellular and physiologic contexts. However, there are no reports on its expression profile and biological roles during lung cancer development. In the current study, both the clinical implications and biological effects of PLAC8 in lung cancer (LC) progression were investigated, and we identified and described the novel Krüppel-like factor 4 (KLF4)/PLAC8 regulatory pathway in cancer progression. Elevated PLAC8 levels were positively correlated with tumor size, histological grade, and tumor node metasis (TNM) stage, and LC patients with high PLAC8 expression suffered poor outcomes. In vitro and in vivo assays further revealed that endogenous PLAC8 promoted cell proliferation and tumor formation. We also found downregulated PLAC8 protein in several LC cell lines following the induction of KLF4, and immunohistochemistry analysis of LC tissues by microarray indicated a potential inverse correlation between PLAC8 and KLF4 expression. Luciferase reporter analysis and chromatin immunoprecipitation assays determined that KLF4 negatively regulated PLAC8 promoter activity via directly binding to the promoter region. Furthermore, the growth inhibition resulting from KLF4 overexpression was partially rescued by ectopic PLAC8 expression. Together, our data uncovered a previously unidentified role of PLAC8 as a central mediator in LC progression. PLAC8 was transcriptionally repressed by KLF4, and the novel KLF4/PLAC8 axis may act as a promising candidate target for LC diagnosis and therapy.

MLN4924 neddylation inhibitor promotes cell death in paclitaxel-resistant human lung adenocarcinoma cells.

Acquired resistance to first-line chemotherapeutics, including paclitaxel (PTX), is a primary factor contributing to chemotherapy failure in non-small cell lung cancer (NSCLC) patients. Previous studies have identified that targeting NEDD8-activating enzyme (NAE) with MLN4924 effectively overcomes platinum resistance in preclinical models of ovarian cancer. However, the underlying mechanisms are yet to be fully elucidated. The present study demonstrates that the inhibition of the neddylation pathway with MLN4924 an NAE inhibitor inhibited protein neddylation, inactivated cullin-RING E3 ligase and exhibited a potent antiproliferative effect on PTX-resistant A549 and H460 cells (A549/PTX and H460/PTX). The application of MLN4924 promotes apoptosis and DNA damage in A549/PTX and H460/PTX cells. Additionally, MLN4924 abrogated the 3-dimensional growth potential of these cells and inhibited the formation of the A549/PTX and H460/PTX spheroids. Notably, combining MLN4924 with PTX did not exhibit synergy in PTX-resistant NSCLC cells. Taken together, the results of the current study suggest that MLN4924 may be utilized as an effective strategy for the treatment of PTX-resistant NSCLC.

KLF4 overcomes tamoxifen resistance by suppressing MAPK signaling pathway and predicts good prognosis in breast cancer.

Tamoxifen resistance represents a daunting challenge to the successful treatment for breast cancer. Krüppel-like factor 4 has critical roles in the development and progression of breast cancer, but its expression, function and regulation in the efficacy of TAM therapy in breast cancer have yet to be investigated. Here, we examined the clinical significance and biologic effects of KLF4 in breast cancer. Firstly, higher expression of KLF4 correlated with increased TAM sensitivity in breast cancer cells, and analysis of GEO datasets indicated that KLF4 expression was positively correlated with ERα and enhanced expression of KLF4 sensitized breast cancer patients to endocrine therapy. Knockdown of KLF4 in MCF-7 and BCAP37 cells led to increased TAM resistance, while ectopic KLF4 expression promoted the responsiveness to TAM in T47D and TAM-resistant MCF-7/TAM cells. Secondly, ectopic KLF4 overexpression suppressed MCF-7/TAM cell growth, invasion and migration. Moreover, KLF4 expression was down-regulated in breast cancer tumor tissues and high expression of KLF4 was associated with favorable outcomes. Mechanistically, KLF4 may enhance the responsiveness of breast cancer cells to TAM through suppressing mitogen-activated protein kinase (MAPK) signaling pathway. We found that ERK and p38 were more activated in MCF-7/TAM compared with MCF-7, and treatment with MAPK-specific inhibitors significantly suppressed cell viability. Knockdown of KLF4 activated ERK and p38 and drove MCF-7 cells to become resistant to TAM. Conversely, overexpression of KLF4 in MCF-7/TAM cells suppressed ERK and p38 signaling and resulted in increased sensitivity to TAM. Therefore, our findings suggested that KLF4 contributed to TAM sensitivity in breast cancer via phosphorylation modification of ERK and p38 signaling. Collectively, this study highlighted the significance of KLF4/MAPK signal interaction in regulating TAM resistance of breast cancer, and suggested that targeting KLF4/MAPK signaling may be a potential therapeutic strategy for breast cancer treatment, especially for the TAM-resistant patients.

Exosome: emerging biomarker in breast cancer.

Exosomes are nano-sized membrane vesicles released by a variety of cell types, and are thought to play important roles in intercellular communications. In breast cancer, through horizontal transfer of various bioactive molecules, such as proteins and mRNAs, exosomes are emerging as local and systemic cell-to-cell mediators of oncogenic information and play an important role on cancer progression. This review outlines the current knowledge and concepts concerning the exosomes involvement in breast cancer pathogenesis (including tumor initiation, invasion and metastasis, angiogenesis, immune system modulation and tumor microenvironment) and cancer therapy resistance. Moreover, the potential use of exosomes as promising diagnostic and therapeutic biomarkers in breast cancer are also discussed.

Structure and function of corneal surface of mudskipper fishes.

Vertebrate corneal epithelium cell plays an important role for imaging, and the cell density, together with the appearance or type of affiliated microstructures, is considered as a result of evolution adapting to alternate terrestrial or aquatic environment. In this paper, we investigated the corneal cells of both larvae and adult amphibious mudskippers Boleophthalmus pectinirostris and Periophthalmus magnuspinnatus, to testify the relationship between morphology and function. The cell density values of the two species were 31,137 and 31,974 cells per mm(2) in larvae and then significantly decreased to 15,826 and 25,954 cells per mm(2) in adult (p < 0.001), respectively, which could be explained as the habitat change from aquatic to different degrees of terrestrial environment. The corneal epithelium cells were ridge type in larvae and differentiated into ridge type and reticular type in adult P. magnuspinnatus and ridge type, reticular type and ridge-reticular type in adult B. pectinirostris. Four kinds of microstructures as microridge, microvilli, microplicae and microhole appeared in both species. The difference of microridge width and its separation indicated that a dense cell connection was requested in a saltier and more terrestrial environment.

KLF4 downregulates hTERT expression and telomerase activity to inhibit lung carcinoma growth.

Krüppel-like factor 4 (KLF4) is a transcription factor that contributes to diverse cellular processes and serves as a tumor suppressor or oncogene in various cancers. Previously, we have reported on the tumor suppressive function of KLF4 in lung cancer; however, its precise regulatory mechanism remains elusive. In this study, we found that KLF4 negatively regulated hTERT expression and telomerase activity in lung cancer cell lines and a mouse model. In addition, the KLF4 and hTERT expression levels were significantly related to the clinicopathological features of lung cancer patients. Promoter reporter analyses revealed the decreased hTERT promoter activity in cells infected with Ad-KLF4, and chromatin immunoprecipitation analysis demonstrated that endogenous KLF4 directly bound to the promoter region of hTERT. Furthermore, the MAPK signaling pathway was revealed to be involved in the KLF4/hTERT modulation pathway. Forced expression of KLF4 profoundly attenuated lung cell proliferation and cancer formation in a murine model. Moreover, hTERT overexpression can partially rescue the KLF4-mediated suppressive effect in lung cancer cells. Taken together, these results demonstrate that KLF4 suppresses lung cancer growth by inhibiting hTERT and MAPK signaling. Additionally, the KLF4/hTERT/MAPK pathway is a potential new therapeutic target for human lung cancer.

Ku80 cooperates with CBP to promote COX-2 expression and tumor growth.

Cyclooxygenase-2 (COX-2) plays an important role in lung cancer development and progression. Using streptavidin-agarose pulldown and proteomics assay, we identified and validated Ku80, a dimer of Ku participating in the repair of broken DNA double strands, as a new binding protein of the COX-2 gene promoter. Overexpression of Ku80 up-regulated COX-2 promoter activation and COX-2 expression in lung cancer cells. Silencing of Ku80 by siRNA down-regulated COX-2 expression and inhibited tumor cell growth in vitro and in a xenograft mouse model. Ku80 knockdown suppressed phosphorylation of ERK, resulting in an inactivation of the MAPK pathway. Moreover, CBP, a transcription co-activator, interacted with and acetylated Ku80 to co-regulate the activation of COX-2 promoter. Overexpression of CBP increased Ku80 acetylation, thereby promoting COX-2 expression and cell growth. Suppression of CBP by a CBP-specific inhibitor or siRNA inhibited COX-2 expression as well as tumor cell growth. Tissue microarray immunohistochemical analysis of lung adenocarcinomas revealed a strong positive correlation between levels of Ku80 and COX-2 and clinicopathologic variables. Overexpression of Ku80 was associated with poor prognosis in patients with lung cancers. We conclude that Ku80 promotes COX-2 expression and tumor growth and is a potential therapeutic target in lung cancer.

Effect of intensity modulated radiotherapy combined with s-1-based chemotherapy in locally advanced gastric cancer patients.

BACKGROUND: The optimal radiotherapy technique and combination with systemic therapy in locally advanced gastric cancer patients are far from being resolved despite the fact that radiochemotherapy is becoming more attractive in contemporary clinical practice. PATIENTS AND METHODS: 40 patients with locally advanced gastric cancer received intensity-modulated radiotherapy (IMRT) at a dosage of 45-50.4 Gy concurrent with chemotherapy using S-1 solely or with a combination of oxaliplatin. Surgery was recommended for those who were evaluated as resectable. Sequential chemotherapy with various regimens was adopted based on the efficacy and tolerance of radiochemotherapy. RESULTS: The overall response rate was 75% according to Response Evaluation Criteria in Solid Tumors and Japanese Gastric Cancer Association criteria. 24 finally underwent surgery, with 22 (91.7%) receiving an R0 resection (resection for cure or complete remission). The overall pathological response rate was 37.5% (9/24). Patients receiving an R0 resection had a higher 2-year overall survival rate (64.7 vs. 16.2%, p = 0.001) and local relapse-free survival rate (90.2 vs. 29.3%, p = 0.000), while there was no difference in distant metastasis-free survival rate (66.1 and 48.1% p = 0.231). Hematological and gastrointestinal toxicities of grade 1 or grade 2 were relatively common. CONCLUSION: The high rate of R0 resections and low rate of locoregional recurrence suggest that IMRT combined with S-1-based chemotherapy is an effective treatment for locally advanced gastric cancer patients.

FOLFOX versus EOX as a neoadjuvant chemotherapy regimen for patients with advanced gastric cancer.

Neoadjuvant chemotherapy is the preferred treatment of advanced gastric cancer. However, the choice of an optimal regimen remains controversial. The present study aimed to assess the effectiveness of preoperative chemotherapy with EOX and FOLFOX in Chinese patients with advanced gastric cancer. A total of 87 and 26 patients underwent FOLFOX and EOX regimens, respectively, for advanced gastric cancer between July 2004 and September 2012. Clinicopathological characteristics, pathological T stage, N stage and pathological response to tumour regression were retrospectively compared between the two groups. Following neoadjuvant chemotherapy, a higher number of patients manifested deeper invasive cancer in the FOLFOX group than those in the EOX group (P=0.047). In addition, a higher number of patients also exhibited metastatic lymph nodes in the FOLFOX group (67.8%) than in the EOX group (57.7%) (P=0.000). In the FOLFOX and EOX groups, 4 (4.6%) and 3 (11.5%) cases of complete regression were observed, respectively. A higher number of patients (38.5%) also exhibited tumour regression grades of 3 and 4 in the EOX group than in the FOLFOX group (19.5%) (P=0.047). Results of the present study suggest that the EOX regimen may be more effective than the FOLFOX regimen as preoperative chemotherapy for Chinese patients with advanced gastric cancer. The EOX regimen may be suitable for younger patients subjected to individual neoadjuvant chemotherapy.

Endocrine resistance in breast cancer: Current status and a perspective on the roles of miRNAs (Review).

Current endocrine therapies for females with estrogen receptor-positive breast cancer have facilitated substantial improvements in outcomes. The effectiveness of endocrine therapy is limited by either initial de novo resistance or acquired endocrine resistance. Multiple mechanisms responsible for endocrine resistance have been proposed, including deregulation of various components of the estrogen receptor (ER) pathway, alterations in cell cycle and cell survival signaling molecules, and the activation of escape pathways. Dysregulation of miRNA expression has been associated with experimental and clinical endocrine therapy resistance. miRNAs are pivotal to understanding the complex biological mechanism of endocrine resistance, and may serve as novel candidate predictive and prognostic surrogates and therapeutic targets. This review focuses on current progress concerning the roles of miRNAs in endocrine resistance, and discusses the challenges and opportunities for implementing miRNA-based assays and treatment for patients with endocrine-resistant breast cancer.

Lin28 mediates radiation resistance of breast cancer cells via regulation of caspase, H2A.X and Let-7 signaling.

Resistance to radiation therapy is a major obstacle for the effective treatment of cancers. Lin28 has been shown to contribute to breast tumorigenesis; however, the relationship between Lin28 and radioresistance remains unknown. In this study, we investigated the association of Lin28 with radiation resistance and identified the underlying mechanisms of action of Lin28 in human breast cancer cell lines. The results showed that the expression level of Lin28 was closely associated with resistance to radiation treatment. The T47D cancer cell line, which highly expresses Lin28, is more resistant to radiation than MCF7, Bcap-37 or SK-BR-3 cancer cell lines, which have low-level Lin28 expression. Transfection with Lin28 siRNA significantly led to an increase of sensitivity to radiation. By contrast, stable expression of Lin28 in breast cancer cells effectively attenuated the sensitivity to radiation treatment. Stable expression of Lin28 also significantly inhibited radiation-induced apoptosis. Moreover, further studies have shown that caspases, H2A.X and Let-7 miRNA were the molecular targets of Lin28. Stable expression of Lin28 and treatment with radiation induced H2AX expression, while inhibited p21 and γ-H2A.X. Overexpression of Let-7 enhanced the sensitivities to radiation in breast cancer cells. Taken together, these results indicate that Lin28 might be one mechanism underlying radiation resistance, and Lin28 could be a potential target for overcoming radiation resistance in breast cancer.

[Prognostic effect of postoperative resection-margin status for intraoperative positive resection margins in patients with advanced gastric cancer].

OBJECTIVES: To investigate prognostic effect of postoperative resection-margin status for intraoperatively positive resection margin in advanced gastric cancer and discuss the treatment choice for intraoperatively positive resection margins. METHODS: A retrospective study was investigated in 64 advanced gastric cancer patients with positive resection margin after potentially curative resection. The survival between 50 patients who was re-excised to a negative resection margin (NR group) and 14 patients who were left with positive resection margin (PR group) was compared. Prognostic factors were analyzed using univariate and multivariate Cox regression model analysis. RESULTS: The median survival in the PR group was 17.0 months (95%CI: 11.6 - 22.4) as compared with 23.0 months (95%CI: 20.5 - 25.5) in the NR group (P = 0.045). However, resection-margin status lost significance on multivariate analysis. In the subgroup of D2 lymphadenectomy, the median survival in the PR group and NR group were 17.0 months (95%CI: 12.0 - 22.0) and 24.0 months (95%CI: 19.8 - 28.1) respectively; multivariate analysis further identified resection margin status as an independent prognostic factor. CONCLUSIONS: Re-excision for intraoperatively positive margin to negative margin improves the prognosis of the patients with advanced gastric cancer, and re-excision is the first choice when intraoperative frozen section detects a positive margin. Routine frozen section of resection margin should be mandatory in all advanced gastric cancer undergoing potentially curative surgery.

Malignant granular cell tumor with breast metastasis: A case report and review of the literature.

Malignant granular cell tumors (MGCT) are rare mesenchymal soft tissue neoplasms of Schwann cell origin without adequate follow-up. This study describes a case of MGCT with right breast metastasis following two local recurrences. The patient consented to a right breast lumpectomy with right axillary dissection, a right abdominal wall lumpectomy and a right inguinal lumpectomy with dissection. Pathological examination revealed that the two initial lesions were consistent with benign histological performance. The later lesions were classified as malignant due to the observation of spindling of the tumor cells, vesicular nuclei with large nucleoli and increased mitotic rate. Immunohistochemical study of the lesions revealed positivity for S100 protein. The Ki-67 proliferation index increased from 1 to 10%. Twenty-seven months after surgery, the patient was in good health with no sign of further tumor development. We recommend wide local excision with regional lymph node dissection as the first choice of treatment for MGCT.