Expression and prognostic value of transcription-associated cyclin-dependent kinases in human breast cancer.

The expression and prognostic significance of transcription-associated cyclin-dependent kinases (TA-CDKs) in breast cancer have not been systematically investigated. Using Oncomine, GEPIA2, the Human Protein Atlas, the Kaplan-Meier Plotter, cBioPortal, Metascape, and DAVID 6.8, we profiled the expression of TA-CDKs in breast cancer, inferred their biological functions, and assessed their effect on prognosis. The expression of CDK7/10/13/19 mRNAs in breast cancer tissues was significantly higher than in normal breast tissues. Survival analysis of breast cancer patients revealed that increased CDK8 expression was associated with inferior overall survival (OS), higher expression of CDK7 or CDK8 was associated with inferior relapse-free survival (RFS), but higher expression of CDK13 was associated with favorable RFS and OS. In addition, a high genetic alteration rate (56%) in TA-CDKs was associated with shorter OS. On functional enrichment analysis, top GO enrichment items for TA-CDKs and their neighboring genes included cyclin-dependent protein serine/threonine kinase activity and transferase complex. The top KEGG pathways included cell cycle and mismatch repair. These results suggest that CDK7/8/13 are potential prognostic biomarkers for breast cancer patients and provide novel insight for future studies examining their usefulness as therapeutic targets.

Prognostic Value of Hepatitis B Virus Infection in Very Young Patients With Curatively Resected Breast Cancer: Analyses From an Endemic Area in China.

Background: Hepatitis B virus (HBV) infection has been associated with the risk and prognosis of many malignancies. Nevertheless, the association between HBV and the prognosis of breast cancer is unclear. The objectives of this study were to investigate the prognostic role of hepatitis B surface antigen (HBsAg) and to integrate HBsAg to establish nomograms for better prognostic prediction of very young patients with breast cancer. Methods: This analysis was performed retrospectively in a cohort of 1,012 consecutive very young (≤35 at diagnosis) patients who received curative resection for breast cancer. The significance of HBsAg in the prognosis of these patients was investigated. Univariate and multivariate analyses were used to identify independent variables for disease-free survival (DFS) and overall survival (OS). Nomograms were built based on those identified variables. Results: Overall, 140 of the 1,012 patients (13.8%) were seropositive for HBsAg. The median follow-up was 67.9 (95% CI, 64.4-71.4) months for the entire population. The HBsAg-positive cohort had significantly inferior DFS (HR, 1.66; 95% CI, 1.07-2.56; P = 0.021) and OS (HR, 1.75; 95% CI, 1.10-2.79; P = 0.016) as compared with the HBsAg-negative cohort. The rates of 10-year DFS and OS were 77.4 and 73.0% in the HBsAg-positive group and 84.1 and 85.6% in the HBsAg-negative group, respectively. In multivariable analysis, HBsAg status was identified as an independent significant unfavorable prognostic factor for DFS (P = 0.01) and OS (P = 0.04) in very young patients with breast cancer. Nomograms were established and displayed good calibration and acceptable discrimination. The C-index values for DFS and OS were 0.656 (95% CI: 0.620-0.691) and 0.738 (95% CI: 0.697-0.779), respectively. Based on the total prognostic scores (TPS) of the nomograms, 3 different prognosis groups were identified for DFS and OS. Conclusions: HBsAg is an independent unfavorable prognostic factor for DFS and OS in very young patients with curatively resected breast cancer, and nomograms integrating HBsAg provide individual survival prediction to benefit prognosis evaluation and individualized therapy.

Correction to: Elevated expression of CST1 promotes breast cancer progression and predicts a poor prognosis.

In Figure 7f the panel for c-myc of MDA-MB-468 was erroneously duplicated. The corrected version of the figure is shown in this paper. This correction does not influence the conclusion of the study and we sincerely apologize for this oversight.

Survival outcomes of patients with lobular carcinoma in situ who underwent bilateral mastectomy or partial mastectomy.

AIM: To compare the survival outcomes between patients treated with bilateral mastectomy and partial mastectomy alone as the initial surgical management for primary lobular carcinoma in situ (LCIS). PATIENTS AND METHODS: Patients with histologically confirmed LCIS underwent partial mastectomy alone or bilateral mastectomy were identified by the SEER*Stat database (version 8.3.2) released in 2016. The primary outcome measure was all-cause mortality and the secondary outcome measure was breast cancer-specific mortality. RESULTS: Of the 5964 cases included in the analysis, 208 cases underwent bilateral mastectomy and 5756 cases underwent partial mastectomy alone. The 1-, 5- and 10-year estimated overall survival rates were 99.7%, 96.7% and 91.7%, respectively. Univariate and multivariate proportional hazards regression (Cox) analyses showed no significant difference between the risk of all-cause mortality in the bilateral mastectomy group compared with the partial mastectomy group (HR = 1.106, 95% confidence interval [CI] 0.350-3.500, P = 0.86). In propensity score-matched model, bilateral mastectomy still did not show benefit to overall mortality (HR = 2.248, 95% CI 0.451-11.200). Patients older than 60 years of age showed a higher risk of all-cause mortality (HR = 7.593, 95% CI 5.357-10.764, P < 0.0001). No risk factors, including surgery type, were identified for breast cancer-specific survival. CONCLUSIONS: Survival outcomes of patients with LCIS who underwent partial mastectomy without radiotherapy were not inferior to patients who underwent bilateral prophylactic mastectomy. Breast cancer-specific mortality in patients with LCIS was extremely low; aggressive prophylactic surgery like bilateral prophylactic mastectomy should not be advocated for most patients with LCIS.

Elevated expression of CST1 promotes breast cancer progression and predicts a poor prognosis.

Cystatin SN (CST1) belongs to the type 2 cystatin (CST) superfamily, which restricts the proteolytic activities of cysteine proteases. CST1 has been recently considered to be involved in the development of several human cancers. However, the prognostic significance and function of CST1 in breast cancer remains unknown. In the current study, we found that CST1 was generally upregulated in breast cancer at both mRNA and protein level. Furthermore, overall survival (OS) and disease-free survival (DFS) in the low CST1 expression subgroup were significantly superior to the high CST1 expression subgroup (OS, p < 0.001; DFS, p < 0.001), which indicated that CST1 expression level was closely correlated to the survival risk of these patients. Univariate and multivariate analyses demonstrated that CST1 expression was an independent prognostic factor, the same as ER status and nodal status. Next, CST1 overexpression promoted breast cancer cell proliferation, clonogenicity, migration, and invasion abilities. By contrast, knockdown of CST1 attenuated these malignant characteristics in breast cancer cells. Collectively, our study indicates that CST1 cannot only serve as a significant prognostic indicator but also as a potential therapeutic target for breast cancer. KEY MESSAGES: High CST1 expression is negatively correlated with survival of breast cancer patients. CST1 promotes cell proliferation, clone formation, and metastasis in breast cancer cells. CST1 is a novel potential prognostic biomarker and therapeutic target for breast cancer.

Activation of GPER suppresses epithelial mesenchymal transition of triple negative breast cancer cells via NF-κB signals.

The targeted therapy for triple-negative breast cancer (TNBC) is a great challenge due to our poor understanding on its molecular etiology. In the present study, our clinical data showed that the expression of G-protein coupled estrogen receptor (GPER) is negatively associated with lymph node metastasis, high-grade tumor and fibronectin (FN) expression while positively associated with the favorable outcome in 135 TNBC patients. In our experimental studies, both the in vitro migration and invasion of TNBC cells were inhibited by GPER specific agonist G-1, through the suppression of the epithelial mesenchymal transition (EMT). The G-1 treatment also reduced the phosphorylation, nuclear localization, and transcriptional activities of NF-κB. While over expression of NF-κB attenuated the action of G-1 in suppressing EMT. Our data further illustrated that the phosphorylation of GSK-3ß by PI3K/Akt and ERK1/2 mediated, at least partially, the inhibitory effect of G-1 on NF-κB activities. It was further confirmed in a study of MDA-MB-231 tumor xenografts in nude mice. The data showed that G-1 inhibited the in vivo growth and invasive potential of TNBC via suppression of EMT. Our present study demonstrated that an activation of GPER pathway elicits tumor suppressive actions on TNBC, and supports the use of G-1 therapeutics for TNBC metastasis.

The utility of breast cone-beam computed tomography, ultrasound, and digital mammography for detecting malignant breast tumors: A prospective study with 212 patients.

PURPOSE: Breast cone-beam computed tomography (BCBCT) is a flat-panel detector (FPD)-based X-ray imaging system that provides high-quality images of the breast. The purpose of this study was to investigate the ability to detect breast abnormalities using non-contrast BCBCT and contrast-enhanced BCBCT (BCBCT and CE-BCBCT) compared to ultrasound (US) and digital mammography (MG). MATERIALS AND METHODS: A prospective study was performed from May 2012 to August 2014. Ninety-two patients (172 lesions) underwent BCBCT alone, and 120 patients (270 lesions) underwent BCBCT and CE-BCBCT, all the patients underwent US and MG. RESULTS: Cancer diagnosis was confirmed pathologically in 102 patients (110 lesions). BCBCT identified 97 of 110 malignant lesions, whereas 93 malignant lesions were identified using MG and US. The areas under the receiver operating curves (AUCs) for breast cancer diagnosis were 0.861 (BCBCT), 0.856 (US), and 0.829 (MG). CE-BCBCT improved cancer diagnostic sensitivity by 20.3% (78.4-98.7%). The AUC values were 0.869 (CE-BCBCT), 0.846 (BCBCT), 0.834 (US), and 0.782 (MG). CONCLUSION: In this preliminary study, BCBCT was found to accurately identify malignant breast lesions in a diagnostic setting. CE-BCBCT provided additional information and improved cancer diagnosis in style c or d breasts compared to the use of BCBCT, US, or MG alone.

Inhibition of ERRα suppresses epithelial mesenchymal transition of triple negative breast cancer cells by directly targeting fibronectin.

Triple-negative breast cancer (TNBC) patients have poor prognosis due to the aggressive metastatic behaviors. Our study reveals that expression of estrogen related receptor α (ERRα) is significantly (p < 0.01) positively associated with high grade tumors and lymph node metastasis, while negatively correlated with overall survival (OS), in 138 TNBC patients. Targeted inhibition of ERRα by its inverse agonist XCT-790 or si-RNA obviously inhibits in vitro motility of TNBC cells. While over expression of ERRα triggers the invasion and migration of TNBC cells. Further, si-ERRα and XCT-790 inhibit the epithelial mesenchymal transition (EMT) of TNBC cells with increasing the expression of E-cadherin and decreasing fibronectin (FN) and vimentin. While XCT-790 has no effect on the expression of EMT related transcription factors such as Snail or Slug. Further, inhibitors of MAPK, PI3K/Akt, NF-κB signal molecules, which are activated by XCT-790, can not attenuate the suppression effects of XCT-790 on EMT. Alternatively, luciferase reporter gene assays and ChIP analysis indicate that ERRα can directly bind with FN promoter at ERR response element-3 (ERRE-1), ERRE-3, and ERRE-4, while XCT-790 reduces this bond. In vivo data show that ERRα expression is significantly (p < 0.05) correlated with FN in clinical TNBC patients. In MDA-MB-231 tumor xenograft models, XCT-790 decreases the expression of FN, inhibits the growth and lung metastasis, and suppresses the EMT. Our results demonstrate that ERRα functions as a metastasis stimulator and its targeted inhibition may be a new therapeutic strategy for TNBC treatment.

Blood-brain barrier permeability of gefitinib in patients with brain metastases from non-small-cell lung cancer before and during whole brain radiation therapy.

INTRODUCTION: To explore the ability of gefitinib to penetrate blood brain barrier (BBB) during whole brain radiation therapy (WBRT). PATIENTS AND METHODS: Enrolled in this study were eligible patients who were diagnosed with BM from NSCLC. Gefitinib was given at 250 mg/day for 30 days, then concurrently with WBRT (40 Gy/20 F/4 w), followed by maintenance. Serial CSF and blood samples were collected on 30 day after gefitinib administration, and at the time of 10, 20, 30 and 40 Gy following WBRT. CSF and plasma samples of 13 patients without BM who were treated with gefitinib were collected as control. CSF and plasma gefitinib levels were measured by LC-MS/MS. RESULTS: Fifteen BM patients completed gefitinib plus WBRT. The CSF-to-plasma ratio of gefitinib in patients with BM was higher than that in patients without BM (1.34% vs. 0.36%, P < 0.001). The CSF-to-plasma ratio of gefitinib increased with the increased dose of WBRT and reached the peak (1.87 ± 0.72%) at 30 Gy, which was significantly higher than that 1.34 ± 0.49% at 0 Gy (P = 0.01). The median time to progression of brain lesions and the median overall survival were 7.07 and 15.4 months, respectively. CONCLUSION: The BBB permeability of gefitinib increased in accordance with escalated dose of WBRT.

[Expression of suppressor of cytokine signaling-3 and caspase-3 in endometriosis and their correlation].

OBJECTIVE: To investigate the expression of suppressor of cytokine signaling(SOCS)-3 and caspase-3 and their correlative significance in endometriosis. METHODS: Immunohistochemical EnVision method was used to detect the SOCS-3 and caspase-3 protein expression in ectopic and eutopic endometrium (n = 32) of patients with endometriosis, as well as normal endometrium (n = 30) of women without endometriosis. RESULTS: SOCS-3 and caspase-3 proteins were expressed in all three groups and not affected by the menstrual cycles. The expression of SOCS-3 in ectopic endometrium (5.54 ± 2.12) was significantly lower than that in eutopic (7.39 ± 1.09, P = 0.001) and control group (7.48 ± 1.26, P < 0.01), but without difference between the eutopic and control group (P = 0.756). SOCS-3 expression in ectopic and eutopic endometrium was significantly lower in III/IV stages than that in I/II stages of endometriosis (P < 0.05). Significantly lower expression of caspase-3 protein was found in ectopic (3.20 ± 1.24) and eutopic endometrium (3.88 ± 1.93) as compared with the control group (6.49 ± 1.85, P < 0.01), however ectopic and eutopic endometrium showed no significant difference (t = 1.66, P = 0.10). There was no significant difference of the expression of caspase-3 in ectopic and eutopic endometrium at different disease stages (P > 0.05). Positive correlation was found between the expression of SOCS-3 and caspase-3 proteins in ectopic endometrium (r = 0.655, P < 0.01). CONCLUSION: SOCS-3 may be involved in the development of endometriosis through inhibition of apoptosis of ectopic endometrial cells.

Metastatic axillary lymph node ratio (LNR) is prognostically superior to pN staging in patients with breast cancer--results for 804 Chinese patients from a single institution.

The number of axillary lymph nodes involved and retrieved are important prognostic factors in breast cancer. The purpose of our study was to investigate whether the lymph node ratio (LNR) is a better prognostic factor in predicting disease-free survival (DFS) for breast cancer patients as compared with pN staging. The analysis was based on 804 breast cancer patients who had underwent axillary lymph node dissection between 1999 and 2008 in Sun Yat-Sen University Cancer Center. Optimal cutoff points of LNR were calculated using X-tile software and validated by bootstrapping. Patients were then divided into three groups (low-, intermediate-, and high-risk) according to the cutoff points. Predicting risk factors for relapse were performed according to Cox proportional hazards analysis. DFS was estimated using the Kaplan-Meier method and compared by the log-rank test. The 5-year DFS rate decreased significantly with increasing LNRs and pN. Univariate analysis found that the pT , pN, LNR, molecule type, HER2, pTNM stage and radiotherapy well classified patients with significantly different prognosis. By multivariate analysis, only LNR classification was retained as an independent prognostic factor. Furthermore, there was a significant prognostic difference among different LNR categories for pN2 category, but no apparent prognostic difference was seen between different pN categories in any LNR category. Therefore, LNR rather than pN staging is preferable in predicting DFS in node positive breast cancer patients, and routine clinical decision-making should take the LNR into consideration.

Signet-ring cell carcinoma of the breast: a case report.

Signet-ring cell carcinoma (SRCC) can arise from virtually all organs. However, primary SRCC of the breast is very rare. Until 2003, SRCC was placed under 'mucin-producing carcinomas' and separated from other carcinomas by the World Health Organization (WHO). To date, only a few cases have been reported. A case of a 46-year-old woman with primary SRCC of the breast is presented in this report. The patient underwent a right modified radical mastectomy with axillary lymph node dissection. Characteristic features and differential diagnosis of this tumor are discussed in the light of pertinent literature.

Low expression of tyrosine-protein phosphatase nonreceptor type 12 is associated with lymph node metastasis and poor prognosis in operable triple-negative breast cancer.

BACKGROUND: Low tyrosine-protein phosphatase nonreceptor type 12 (PTPN12) expression may be associated with breast cancer growth, proliferation, and metastasis. However, the prognostic value of PTPN12 in breast cancer has not been clearly identified. PATIENTS AND METHODS: 51 triple-negative breast cancer (TNBC) patients and 83 non-TNBC patients with a histopathology diagnosis from October 2001 to September 2006 were included in this study. Immunohistochemical staining for PTPN12 on tissue microarrays was conducted. RESULTS: High PTPN12 expression was seen in 39.2% of TNBC and 60.2 % of non-TNBC cases. Low PTPN12 expression was associated with lymph node status (p = 0.002) and distant metastatic relapse (p = 0.002) in TNBC patients. Similarly, low PTPN12 expression in non-TNBC patients was significantly correlated with lymph node status (p = 0.002), stage (p = 0.002) and distant metastatic relapse (p = 0.039). The high PTPN12 expression group was associated with longer DFS and OS compared with low PTPN12 expression group only in TNBC cases (p = 0.005, p = 0.015), according to univariate Cox regression analysis. CONCLUSION: These findings provide evidence that low expression of PTPN12 is associated with worse prognosis and may be used as a potential prognostic biomarker in TNBC patients.

Clinical characteristics and survival analysis of breast cancer molecular subtypes with hepatic metastases.

BACKGROUND: The liver is one of the most common metastatic sites of breast cancer, hepatic metastases developing in 6%-25% of patients with breast cancer and being associated with a poor prognosis. The aim of this study was to analyze the survival and clinical characteristics of patients with hepatic metastases from breast cancer of different molecular subtypes and to investigate the prognostic and predictive factors that effect clinical outcome. METHODS: We retrospectively studied the charts of 104 patients with breast cancer hepatic metastases diagnosed at Sun Yat-sen University Cancer Center from December 1990 to June 2009. Subtypes were defined as luminal A, luminal B, human epidermal growth factor receptor 2 (HER2) enriched, triple-negative (TN). Prognostic factor correlations with clinical features and treatment approaches were assessed at the diagnosis of hepatic metastases. RESULTS: The median survival time was 16.0 months, and the one-, two- three-, four-, five- year survival rates were 63.5%, 31.7%, 15.6%, 10.8%, and 5.4%, respectively. Median survival periods after hepatic metastases were 19.3 months (luminal A), 13.3 months (luminal B), 18.9 months (HER2-enriched), and 16.1 months (TN, P=0.11). In multivariate analysis, a 2 year-interval from initial diagnosis to hepatic metastasis, treatment with endocrine therapy, and surgery were independent prognostic factors. Endocrine therapy could improve the survival of luminal subtypes (P=0.004) and was a favorable prognostic factor (median survival 23.4 months vs. 13.8 months, respectively, P=0.011). Luminal A group of patients treated with endocrine therapy did significantly better than the Luminal A group of patients treated without endocrine therapy (median survival of 48.9 vs. 13.8 months, P=0.003). CONCLUSIONS: Breast cancer subtypes were not associated with survival after hepatic metastases. Endocrine therapy was a significantly favorable treatment for patients with luminal subtype.

Triplet platinum-based combination sequential chemotherapy improves survival outcome and quality of life of advanced non-small cell lung cancer patients.

BACKGROUND: Maintenance chemotherapy is one strategy pursued in recent years with intent to break through the chemotherapy plateau for advanced non-small cell lung cancer (NSCLC). However, given the toxicity, platinum-based combinations are rarely given for this purpose. We carried out the present prospective study of triplet platinum-based combination sequential chemotherapy in advanced NSCLC to investigate if patients could tolerate and benefit from such intensive treatment. METHODS: From Dec 2003 to Dec 2007, 190 stage IIIB and IV NSCLC patients in Sun yat-sen University sequentially received the 3 platinum-based combination (TP- NP-GP) treatment (T: paclitaxol 175 mg/m2 d1; N: vinorelbine 25 mg/m2 d1 and 8; G: gemcitabine 1 g/m2 d1 and 8; P: cisplatin 20 mg/m2 d1-5; repeated every 3 weeks). Patients were followed up to at least 3 years to obtain survival data. Treatment toxicities and the quality of life (QOL) were assessed during the whole treatment. RESULTS: There were 187 patients evaluable. The TP, NP and GP response rates with sequential use were 42.8% (80/187), 41.1% (65/158) and 28.8% (21/73) respectively. Median survival time was 18.2 months and the 1, 2 and 3 year overall survival (OS) rates were 78.7%, 38.5% and 21.3%. Patients receiving>6 cycles of chemotherapy had significantly longer OS and TTP (MST 25.3 vs. 14.5 months, TTP 15.1 vs. 9.1 months). The QOL on the whole for the patients was improved after chemotherapy. CONCLUSIONS: The sequential chemotherapy strategy with triplet platinum-based combination regimens can improve the survival outcome and the quality of life of advanced non-small cell lung cancer patients.

A case report of primary small cell carcinoma of the breast and review of the literature.

Primary small cell carcinoma (SCC) of the breast, an exceedingly rare and aggressive tumor, is often characterized by rapid progression and poor prognosis. We report a case of primary SCC of the breast that was diagnosed through pathologic and immunohistochemical examinations. Computed tomography (CT) scans failed to reveal a non-mammary primary site. Due to the scant number of relevant case summaries, this type of tumor is proved to be a diagnostic and therapeutic challenge. Therefore, we also reviewed relevant literature to share expertise in diagnosis, clinicopathologic characteristics, treatment, and prognosis of this type of tumor. Future studies with more cases are required to define more appropriate treatment indications for this disease.

Chemotherapy with concurrent brain and thoracic radiotherapy in brain-only metastases of treatment naive small-cell lung cancer: a phase II study.

To study the treatment outcomes of brain-only metastases from small-cell lung cancer (SCLC) at initial diagnose treated by chemotherapy with concurrent brain and thoracic radiotherapy (RT). From Jan 2004 to Jan 2009, 36 treatment-naïve SCLC patients with brain-only metastases in Sun yat-sen University were enrolled. Treatment contained initial EP chemotherapy with concurrent whole-brain radiotherapy (WBRT). EP regimen consisted of etoposide 100 mg/m(2) IV d1-3, cisplatin 80 mg/m(2) IV d1, repeated every 3 weeks. WBRT with total dose of 30 Gy in 10 fractions was started within 1 week from the beginning of chemotherapy followed by thoracic RT including 2 Gy once daily to a total dose of 60 Gy. Treatment responses were evaluated after 3 cycles of chemotherapy. EP regimen was given totally 6 cycles for no tumor progression. Thirty-four patients were evaluable. All of the 20 CNS symptomatic patients experienced symptoms relief. Objective responses in the brain and primary thoracic lesions were observed in 26 (76.5%, 16CR + 10PR) and 29 (85.3%, 23CR + 6PR) patients, respectively. The median survival time (MST) was 19.2 months, and the 1-and 2-year overall survival rates (OS) were 70.6 and 29.4%, respectively, in all patients. Patients with CR response had the longest MST of 21.9 months and 1-and 2-year OS of 93.8 and 43.8%, respectively. Treatment toxicity profiles were acceptable. The treatment strategy of concurrent chemotherapy with brain and thoracic RT might achieve promising survival outcomes comparable to limited-stage SCLC in initially diagnosed SCLC with brain-only metastases.

Histone deacetylase inhibitor MS-275 treatment alters immune molecule content and categories in hepatocarcinoma exosomes / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the effects of the histone deacetylase inhibitor, MS-275, on the immune molecule content and categories in hepatocarcinoma exosomes.</p><p><b>METHODS</b>Exosomes were isolated from the human hepatocarcinoma cell lines, HepG2 and Hep3b, and purified by a combination technique of ultrafiltration centrifugation and sucrose gradient ultracentrifugation. The expressions of heat shock protein (HSP)70, human leukocyte antigen (HLA)-I, HLA-DR, cluster of differentiation (CD) 80 and NY-ESO-1 on exosomes were analyzed with immunoelectron microscopy and Western blotting before and after MS-275 treatment. Intergroup differences were statistically analyzed by the Student's paired t-test.</p><p><b>RESULTS</b>MS-275 treatment of both HepG2 and Hep3b cell types significantly increased the numbers of exosomes, their total protein content, and expression of HSP70, HLA-I and CD80 (per 100 exosomes), as compared to non-treated cells (all, P less than 0.01). MS-275 was also found to induce de novo expression of HLA-DR, but had no significant effect on NY-ESO-1 expression (P more than 0.05). The findings from immunoelectron microscopy confirmed those from Western blotting.</p><p><b>CONCLUSION</b>The histone deacetylase inhibitor, MS-275, can significantly alter the immune molecule content and categories in exosomes of hepatocarcinoma cells. The differential expression profile may reflect an anti-cancer immune response and represent molecular targets for novel anti-hepatoma therapeutic or preventative strategies.</p>

[Establishment and evaluation of a prognostic prediction model for patients after complete resection of non-small cell lung cancer and multidisciplinary therapy].

OBJECTIVE: A bias may be produced when only TNM stage is used to predict the prognosis of non-small cell lung cancer (NSCLC) after complete resection and multidisciplinary treatment. The reason is that histological type, differentiation, and postoperative treatment which may also affect the survival are excluded in the prognosis prediction. The aim of this study is to establish and evaluate a prognostic prediction model for NSCLC patients based on pathological parameters after completely resection and postoperative treatment. METHODS: According to the theory of Nottingham index model, a prognostic prediction model was established based on the pathological parameters and postoperative management of 899 NSCLC patients after complete resection and multidisplinary treatment in our hospital from Jan.1, 1997 to April, 2001, and its efficiency and feasibility were evaluated. RESULTS: Univariate analysis and multivariate analysis showed that histological type (H), T stage (T), N stage (N), M stage (M), and postoperative mediastinal radiotherapy for positive lymph node (R) were independent factors affecting the survival of NSCLC after complete resection and multidisciplinary treatment. The prognostic prediction model based on these parameters is: S = 0.338H + 0.178T + 0.549N + 0.647M-0.361R. The high and low risks of prognostic index (PI) were 1.6695 and 1.1160, respectively. The 5-year survival rates of the patients in the low, middle and high risk groups stratified by this model were 70.1%, 54.5%, and 22.5%, respectively, with a significant difference among the groups (chi(2) = 132.091, P = 0.000). CONCLUSION: A model based on the pathological parameters and postoperative management has been established, which may be helpful in predicting the prognosis for NSCLC after complete resection and multidisciplinary management.

[Multivariate survival analysis of 899 patients with non-small cell lung cancer after complete resection].

BACKGROUND & OBJECTIVE: Multi-disciplinary management for non-small cell lung cancer (NSCLC) has been applied for more than ten years. The progresses in the diagnosis and management of NSCLC might change the factors affecting prognosis. This study was to explore the prognostic factors of NSCLC after complete resection. METHODS: Clinical data of 899 NSCLC patients, underwent complete resection from Jan. 1997 to Apr. 2001 at Cancer Center of Sun Yat-sen University, were reviewed. The patients were followed up till 31st Mar. 2006. Survival rates were calculated by Kaplan-Meier method. The prognosis was analyzed by Cox proportional hazards model. RESULTS: The 5-year survival rate of the 899 patients was 43.5% and the median survival time was 48 months. The 5-year survival rates were 81.0% for the patients at stage IA, 60.3% for stage IB, 56.9% for stage IIA, 45.7% for stage IIB, 23.5% for stage IIIA, 20.8% for stage IIIB, and 13.0% for stage IV. Univariate analysis showed that T stage, N stage, M stage, histological type, differentiation, chemotherapy for adenocarcinoma (ADC) at stages II and IV, and mediastinal radiotherapy for ADC at stage N2 were prognostic factors. Multivariate analyses showed that histological type, T stage, N stage, M stage and mediastinal radiotherapy for ADC at stage N2 were independent prognostic factors. CONCLUSION: Besides T stage, N stage, and M stage, histological type and mediastinal radiotherapy for ADC at stage N2 are also independent prognostic factors of NSCLC after complete resection.