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However, it is still difficult for clinicians to establish prognostic stratifications and therapeutic strategies because of the lack of tools for predicting the survival of triple-negative breast cancer patients with liver metastases (TNBC-LM). Based on clinical data from large populations, a sensitive and discriminative nomogram was developed and validated to predict the prognosis of TNBC patients with LM at initial diagnosis or at the later course. Introduction/background: Liver metastasis (LM) in TNBC patients is associated with significant morbidity and mortality. The objective of this study was to construct a clinical model to predict the survival of TNBC-LM patients. Materials and methods: Clinicopathologic data were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database and the Fifth Affiliated Hospital of Sun Yat-Sen University (FAFSYU). Based on patients with newly diagnosed TNBC with LM (nTNBC-LM) from the SEER database, a predictive nomogram was established and validated. Its predictive effect on TNBC patients with LM at later disease course by enrolling TNBC patients from FAFSYU who developed LM later. The prognostic effect of different treatment for nTNBC-LM was further assessed. Results: A prognostic model was developed and validated to predict the prognosis of TNBC-LM patients. For LM patients diagnosed at the initial or later treatment stage, the C-index (0.712, 0.803 and 0.699 in the training, validation and extended groups, respectively) and calibration plots showed the acceptable prognostic accuracy and clinical applicability of the nomogram. Surgical resection on the primary tumour and chemotherapy were found to be associated with significantly better overall survival (OS). Conclusion: A sensitive and discriminative model was developed to predict OS in TNBC-LM patients both at and after initial diagnosis.

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In-situ chemical oxidation (ISCO) is a commonly used method for the remediation of environmental contaminants in groundwater systems. However, traditional ISCO methods are associated with several limitations, including safety and handling concerns, rebound of groundwater contaminants, and difficulty in reaching all areas of contamination. To overcome these limitations, novel Controlled-Release Biodegradable Polymer (CRBP) pellets containing the oxidant KMnO4 were designed and tested. The CRBP pellets were encapsulated in Polyvinyl Acetate (CRBP-PVAc) and Polyethylene Oxide (CRBP-PEO) at different weight percentages, baking temperatures, and time. Their release efficiency was tested in water, soil, and water and soil mixture media. Results showed that CRBP-PVAc pellets with 60 % KMnO4 and baked at 120 °C for 2 min had the highest release percentage and rate across different conditions tested. Natural organic matter was also found to be an important factor to consider for in-field applications due to its potential reducing effect with MnO4-. Overall, the use of CRBP pellets offers an innovative and sustainable solution to remediate contaminated groundwater systems, with the potential to overcome traditional ISCO limitations. These findings suggest that CRBP pellets could provide sustained and controlled release of the oxidant, reducing the need for multiple injections and minimizing safety and handling concerns. This study represents an important step towards developing a new and effective approach for ISCO remediation.

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BACKGROUND: Brain metastasis (BM) in triple-negative breast cancer (TNBC) patients is associated with significant morbidity and mortality. In this research we aimed to develop a nomogram to predict the prognosis of TNBC patients with BMs (TNBC-BM) and explore the potential risk factors. METHODS: We used data from the Surveillance, Epidemiology, and End Results (SEER) database. A prognostic nomogram was built and validated based on patients with BM at newly diagnosed TNBC (nTNBC-BM). Its effect on TNBC patients with BM was also validated in an extended group. The prognostic effect of treatment and risk factors for nTNBC-BM were further tested. RESULTS: A nomogram was constructed and validated to predict overall survival (OS) in TNBC-BM patients. For patients with BM diagnosed at the initial treatment or later course, the C-index (0.707, 0.801, and 0.685 in the training, validation, and extended groups, respectively) and calibration plots showed the acceptable prognostic accuracy and clinical applicability of the model. Surgery on the primary tumor and chemotherapy were found to confer significantly better OS (11 months vs. 4 months; 5 months vs. 3 months, respectively). In addition, advanced tumor/nodal stage and bilateral cancer were associated with a higher risk of nTNBC-BM. CONCLUSION: We developed a sensitive and discriminative nomogram to predict OS in TNBC-BM patients, both at initial diagnosis and the latter course. nTNBC-BM patients may benefit more from surgery and chemotherapy than from radiotherapy. In addition, in the predictive model, TNBC patients harboring advanced tumor/nodal stages and bilateral tumors were more likely to have BM at initial diagnosis.

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[This corrects the article on p. 355 in vol. 23, PMID: 32908787.].

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PURPOSE: Four and a half LIM protein 1 (FHL1) is involved in breast cancer (BC) development, but the regulatory mechanism involved remain unclear. In the present study, we examined the role of FHL1 in BC development. METHODS: The expression of FHL1, miR-183-5p, and miR-96-5p in BC tissues was analyzed using StarBase analysis. FHL1 expression in BC tissues, a normal human breast epithelial cell line, and BC cell lines was detected using quantitative reverse transcription polymerase chain reaction (qRT-PCR). The relationship between FHL1 and miR-183-5p/miR-96-5p was analyzed via Pearson's rank correlation, TargetScan, and a dual-luciferase reporter assay. BT549 and MDA-MB-231 cells were transfected with either FHL1 and miR-183-5p mimics, or siFHL1 and a miR-183-5p inhibitor, respectively. The viability, colony number, migration, invasion, and tube length of BT549 and MDA-MB-231 cells were examined using cell counting kit-8, colony formation, wound-healing, Transwell, and tube formation assays, respectively. The levels of FHL1, vascular endothelial growth factor (VEGF), p53, E-cadherin, N-cadherin, and vimentin were quantified using western blotting and qRT-PCR. RESULTS: FHL1 expression was downregulated in BC tissues and cells, whereas miR-183-5p and miR-96-5p were upregulated in BC tissues (negative correlation with FHL1 expression). FHL1 overexpression inhibited the viability, colony number, migration, and invasion of BC cells and the expression of VEGF, N-cadherin, and vimentin, and increased the expression of FHL1, p53, and E-cadherin in BT549 cells. Furthermore, a miR-183-5p mimic reversed these effects of FHL1 overexpression, whereas FHL1 silencing caused opposite results to those observed in MDA-MB-231 cells; however, this was reversed by a miR-183-5p inhibitor. CONCLUSION: Our study suggests that miR-183-5p promotes cell proliferation, metastasis, and angiogenesis by negatively regulating FHL1 in BC.

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BACKGROUND: The long non-coding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) is involved in various cancers and often functions through microRNAs. The pro-survival protein PTP1B is known to play important roles in cancer development. However, the connection between UCA1 and PTP1B in breast cancer is not well studied. METHODS: In this study, we first evaluated the correlation between UCA1 level and PTP1B expression in breast tissues, which showed the expression of PTP1B were much higher in the breast tumor tissues than in the peritumor normal tissues. The UCA1 level was positively associated with PTP1B expression in breast tumor tissues. RESULTS: We observed that UCA1 could up-regulate PTP1B expression in breast cancer cells. We also found that miR-206 could inhibit the expression of PTP1B by directly binding to the 3'-UTR of its mRNA. Interestingly, UCA1 could increase the expression of PTP1B through sequestering miR-206 at post-transcriptional level. The results also suggested that UCA1-induced PTP1B expression facilitated the proliferation of breast cancer cells. CONCLUSIONS: We conclude that UCA1 can up-regulates PTP1B to enhance cell proliferation through sequestering miR-206 in breast cancer. Our finding provides new insights into the mechanism of breast cancer regulation by UCA1, which could be a potential target for breast cancer treatment.Trial registration 2012N5hSYSU48573. Registered at Oct 12, 2012.

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PURPOSE: To compare the expressions of p53, a tumor suppressor gene, KI67, a proliferating cell nuclear antigen, and breast cancer 1 (BRCA1), a breast cancer susceptibility gene, in patients with different molecular subtypes of breast cancer (BC) and investigate their relationships with pathology and prognosis. METHODS: A total of 134 BC postoperative tissue specimens preserved from January 2012 to August 2013 were selected. The expressions of p53, KI67, and BRCA1 in different molecular subtypes of BC were compared, their relationships with pathological features were explored, and the expression correlations among p53, KI67, and BRCA1 were analyzed at the same time. RESULTS: P53 expression was the lowest in Luminal A subtype and similar in human epidermal growth factor receptor 2 (HER-2)-overexpression subtype and triple-negative subtype, with higher expression rates than those in other molecular subtypes. The expression of KI67 was the lowest in Luminal A subtype, showing a significant difference (p<0.05) from that in other molecular subtypes and it was the highest in Luminal B subtype (p<0.05). BRCA1 exhibited the lowest expression in Luminal B-like subtype but the highest expression in Luminal A subtype. The protein expressions of p53 and KI67 were not related to age but correlated with tumor size, histological grade, lymph node metastasis, estrogen receptor (ER)/progesterone receptor (PR) status, and HER-2 status. The expression of p53 was increased with larger tumor size, higher histological grade, presence of lymph node metastasis (n), lower expression of ER/PR, and higher expression of HER-2. BRCA1 expression had no relation with age, tumor size, histological grade, lymph node metastasis (n), ER/PR status, and HER-2 status. A positive correlation was found between p53 and KI67 (r=0.893, p=0.021). There were negative correlations between p53 and BRCA1 (r=-0.921, p=0.011), and between KI67 and BRCA1 (r=-0.821, p=0.032). The median survival time of patients with positive expressions of p53, KI67 and BRCA1 was significantly shorter than those of patients with negative expressions. CONCLUSION: The expressions of p53, KI67 and BRCA1 in different molecular subtypes of BC are evidently different and related to pathological features. The above protein expressions are helpful in predicting the prognosis, diagnosis, and treatment of BC.

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Arpin, a negative regulator of the actin-related protein-2/3 (Arp2/3) complex, is downregulated and predicts poor prognosis in breast cancer patients. However, its biological relevance in breast cancer is still unclear. This study was conducted to investigate the roles of Arpin in breast cancer growth and invasion. We overexpressed Arpin expression in MCF-7 and MDA-MB-231 breast cancer cells and examined the effects of restoration of Arpin on cell proliferation, colony formation, cell cycle distribution, invasion in vitro and tumorigenesis in vivo. The related molecular mechanism(s) was determined. It was found that ectopic expression of Arpin significantly decreased cell proliferation, colony formation, and tumorigenicity. Flow cytometric analysis showed that overexpression of Arpin significantly increased the percentage of G0/G1-phase cells and decreased the percentage of S-phase cells. Moreover, restoration of Arpin impaired the invasiveness of breast cancer cells, as determined by Transwell invasion assays. Mechanistically, overexpression of Arpin inhibited the phosphorylation of Akt in breast cancer cells. Co-expression of a constitutively active form of Akt blunted the suppression of cell proliferation and invasion by Arpin. Taken together, we provide evidence that Arpin acts as a tumor suppressor in breast cancer, which is associated with inhibition of Akt signaling. Restoration of Arpin may represent a promising therapeutic strategy against breast cancer progression.

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BACKGROUND: With recent improvements in operative techniques, many studies have reported that resection is safe for hepatocellular carcinoma (HCC) patients with portal hypertension (PHT). However, no direct evidence exists to compare resection with ablation in patients with hepatitis B virus (HBV)-related PHT. METHODS: Of 259 HBV-related PHT patients who met the Milan criteria, 123 patients underwent resection and 136 underwent ablation as a primary treatment. Complications were graded with the Clavien-Dindo system, and oncologic outcomes were analyzed with a propensity score matching (PSM) method. RESULTS: Compared with the ablation group, the resection group showed larger tumors, greater white blood cell counts, greater platelet counts, lower γ-glutamyltransferase levels, and lower model of end stage liver disease scores (all P < .05). Although more frequent complications occurred in the resection group (P < .001), the difference was significant for the Grade I complications but not for Grade II-V complications. The recurrence-free survival (RFS) and overall survival (OS) rates were greater in the resection group than in the ablation group (P = .001 and P = .010, respectively). After one-to-one PSM, 77 resection patients and 77 ablation patients were selected for further analyses. The advantages of resection over ablation were still observed in RFS (P = .002) and OS (P = .012). Grade I-V complications were comparable between the 2 groups (all P > .100). CONCLUSION: Resection is safe and confers a survival advantage over ablation in HBV-related PHT patients. Resection may be recommended as an optimal treatment for these patients.

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OBJECTIVE: To explore the clinicopathological characteristics, diagnosis, treatment outcomes and survival of hepatocellular carcinoma (HCC) and nasopharyngeal multiple primary cancers. METHODS: The clinical data of 12 male patients with hepatocellular and nasopharyngeal multiple primary cancers were retrospectively analyzed. RESULTS: Second primary cancer was diagnosed with a median age of 54.5 years. Hepatitis B surface antigen (HBsAg) was detected in 7 patients (58.3%) and 6 cases (50.0%) had a family history of cancer. The treatments included radiochemotherapy (n = 5), radiotherapy (n = 6) and non-therapy (n = 1). And the interventions included hepatic surgery (n = 6), interventional treatment (n = 4) and conservative (n = 2). The 1, 3 and 5-year overall survival rates were 90.9%, 81.8% and 58.4% and the HCC-specific survival rates 80.0% at 1 year and 57.1% at 3 years respectively. The HCC-specific survival rates of surgery group were significantly better than those of the non-surgical group. The 1, 3-year HCC-specific survival rates were 100.0%, and 100.0%vs 50.0% and 0 respectively (P = 0.002). CONCLUSIONS: HCC and nasopharyngeal multiple primary cancers are not rare and careful follow-ups are necessary . The co-existence of HCC and nasopharyngeal multiple primary cancers does not imply a worse prognosis. And radical resection of HCC is considered.

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The support vector machine (SVM) is one of the most widely used approaches for data classification and regression. SVM achieves the largest distance between the positive and negative support vectors, which neglects the remote instances away from the SVM interface. In order to avoid a position change of the SVM interface as the result of an error system outlier, C-SVM was implemented to decrease the influences of the system's outliers. Traditional C-SVM holds a uniform parameter C for both positive and negative instances; however, according to the different number proportions and the data distribution, positive and negative instances should be set with different weights for the penalty parameter of the error terms. Therefore, in this paper, we propose density-based penalty parameter optimization of C-SVM. The experiential results indicated that our proposed algorithm has outstanding performance with respect to both precision and recall.

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BACKGROUND: The prolonged survival of individuals diagnosed with cancer has led to an increase in the number of secondary primary malignancies. We undertook to perform a definitive study to characterize and predict prognosis of multiple primary malignancies (MPM) involving hepatocellular carcinoma (HCC), due to the scarcity of such reports. METHODS: Clinicopathological data were analyzed for 68 MPM patients involving HCC, with 35 (target group) underwent curative liver resection. Additional 140 HCC-alone patients with hepatectomy were selected randomly during the same period as the control group. RESULTS: Of the 68 patients with extrahepatic primary malignancies (EHPM), 22 were diagnosed synchronously with HCC, and 46 metachronously. The most frequent EHPM was nasophageal carcinoma, followed by colorectal and lung cancer. Univariate analysis demonstrated that synchronous (P = 0.008) and non-radical treatment for EHPM (P < 0.001) were significant risk factors associated with poorer overall survival (OS). While, Cox modeling revealed that the treatment modality for EHPM, but not the synchronous/metachronous determinant, was an independent factor for OS, and that therapeutic option for HCC was an independent factor for HCC-specific OS. Moreover, no HCC-specific overall and recurrence-free survival benefit were observed in the control group when compared with that of the target group (P = 0.607, P = 0.131, respectively). CONCLUSIONS: Curative treatment is an independent predictive factor for OS and HCC-specific OS, and should been taken into account both for synchronous and metachronous patients. MPM patients involving HCC should not be excluded from radical resection for HCC.

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OBJECTIVE: Patients with hepatocellular carcinoma (HCC) presenting with nonmicronodular or micronodular cirrhosis are usually treated by hepatectomy. The value of resection for patients with hepatitis B virus-related macronodular cirrhosis, however, remains unknown because of potentially fatal complications of this procedure. METHODS: Clinicopathological data were analyzed for 85 resected HCC patients with hepatitis B virus-related macronodular cirrhosis. An additional 255 patients with nonmicronodular and micronodular cirrhosis were randomly selected during the same period as the control group. RESULTS: Compared with nonmicronodular and micronodular cirrhosis patients, macronodular cirrhotic patients exhibited elevated alanine aminotransferase, aspartate aminotransferase, and γ-glutamyltransferase levels, higher Child-Pugh classification, higher indocyanine green retention rate at 15 min (ICG R15), and more number of total complications. No significant differences were observed between the two groups with regard to major complications, mortality, overall survival, and recurrence-free survival. The morbidity rate was relatively low in patients exhibiting low ICG R15 (<10%). Cox analysis identified small tumors (≤ 5 cm) and radical resection as independent prognostic factors that could predict long-term overall survival. Radical resection can result in high recurrence-free survival in macronodular cirrhotic patients. CONCLUSION: Resection is safe for macronodular cirrhotic HCC patients, and radical resection provides a positive outcome. Small-sized patients are good candidates for hepatectomy. Macronodular cirrhosis should not rule out hepatectomy in patients with low ICG R15.

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BACKGROUND & OBJECTIVE: Appendix carcinoid tumor is a rare disease, and lack of classic clinical features. This study was to explore clinical characteristics and treatment principles of appendix carcinoid tumor. METHODS: Clinical data, surgical procedures, and prognosis of 13 patients with appendix carcinoid tumor received appendectomy from 1985 to 2000 in our hospital were analyzed retrospectively. RESULTS: The diagnosis was established through operation and pathology. Patients with appendix carcinoid tumor comprised 0.29% of 4483 patients underwent appendectomy during the same period. The tumors were located at the tip and the middle of appendix in 12 patients(92.3%). The diameter of tumor in 12 patients(92.3%) was less than 2 cm. Single appendectomy was performed on 11 patients, right-side colonectomy was performed on 2 patients. Nine patients were alive and remained free of tumor recurrence and metastasis, 3 were lost of follow up, and 1 died of heart disease. The 5-year survival rate is 100%. CONCLUSIONS: Appendix carcinoid tumor has no specific clinical symptom, and located at the tip and the middle of appendix; tumor with diameter of < 1 cm may be resected by single appendectomy.

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