A T-Cell Inspired Sonoporation System Enhances Low-Dose X-Ray-Mediated Pyroptosis and Radioimmunotherapy Efficacy by Restoring Gasdermin-E Expression.

Genome editing has the potential to improve the unsatisfactory therapeutic effect of antitumor immunotherapy. However, the cell plasma membrane prevents the entry of almost all free genome-manipulation agents. Therefore, a system can be spatiotemporally controlled and can instantly open the cellular membrane to allow the entry of genome-editing agents into target cells is needed. Here, inspired by the ability of T cells to deliver cytotoxins to cancer cells by perforation, an ultrasound (US)-controlled perforation system (UPS) is established to enhance the delivery of free genome-manipulating agents. The UPS can perforate the tumor cell membrane while maintaining cell viability via a controllable lipid peroxidation reaction. In vitro, transmembrane-incapable plasmids can enter cells and perform genome editing with the assistance of UPS, achieving an efficiency of up to 90%. In vivo, the UPS is biodegradable, nonimmunogenic, and tumor-targeting, enabling the puncturing of tumor cells under US. With the application of UPS-assisted genome editing, gasdermin-E expression in 4T1 tumor-bearing mice is successfully restored, which leads to pyroptosis-mediated antitumor immunotherapy via low-dose X-ray irradiation. This study provides new insights for designing a sonoporation system for genome editing. Moreover, the results demonstrate that restoring gasdermin expression by genome editing significantly improves the efficacy of radioimmunotherapy.

A Bioinspired Immunostimulatory System for Inducing Powerful Antitumor Immune Function by Directly Causing Plasma Membrane Rupture.

The Gasdermin protein is a membrane disruptor that can mediate immunogenic pyroptosis and elicit anti-tumor immune function. However, cancer cells downregulate Gasdermin and develop membrane repair mechanisms to resist pyroptosis. Therefore, an artificial membrane disruptor (AMD) that can directly mediate membrane rupture in pyroptosis-deficient cells and induce antitumor immune responses in a controllable manner will be valuable in preclinical and clinical research. A micron-scale Ce6-based AMD that can directly induce plasma membrane rupture (PMR) in gasdermin-deficient tumor cells is established. Micron-scale AMDs localize Ce6 specifically to the plasma membrane without labeling other organelles. Compared to free Ce6 molecules, the use of AMDs results in a higher degree of specificity for the plasma membrane. Due to this specificity, AMDs mediate fast and irreversible PMR under 660 nm red light. Furthermore, the AMDs are capable of inducing programmed cell death and lytic cell death in a catalytic manner, demonstrating that the amount of Ce6 used by AMDs is only one-fifth of that used by Ce6 alone when inducing 80% of cancer cell death. In vivo, the AMDs show specificity for tumor targeting and penetration, suggesting that light-driven programmed cell death is specific to tumors. AMDs are applied to antitumor therapy in gasdermin-deficient tumors, resulting in efficient tumor elimination with minimal damage to major organs when combined with anti-PD-1 therapy. Tumor regression is correlated with PMR-mediated inflammation and T-cell-based immune responses. This study provides new insights for designing bioinspired membrane disruptors for PMR and mediating anti-tumor immunotherapy. Additionally, AMD is a dependable tool for examining the immunogenicity of PMR both in vitro and in vivo.

A web-based novel model for predicting prognostic value in patients with invasive micropapillary carcinoma in breast cancer: a real-world data retrospective cohort study.

Invasive micropapillary carcinoma (IMPC) accounts for less than 2% of all invasive breast cancers and usually associates with poor survival, so we investigated the prognostic factors for IMPC using a large population-based database and designed a web-based novel model. Clinicopathological prognostic factors were evaluated using the Surveillance, Epidemiology, and End Results (SEER) database. Multivariate Cox regression analysis was performed to evaluate the prognostic value of variables on the overall survival. A web-based nomogram was finally constructed to predict the survival probability. The model was validated in an external dataset. A web-based model, combined with age, radiation, clinical stage, and hormone receptor (HR) immunochemistry status four prognostic factors, was constructed. The C-index (0.714, 95% CI 0.683-0.741), calibration curves, and decision curves showed that this model was superior in prediction. By determining the cut-off values, high-risk group and low-risk group were divided. The Kaplan-Meier survival curves showed that these two groups had significantly different survival rates (P < 0.0001). The result of C-index, calibration curves, and Kaplan-Meier survival curves were consistent in the validation cohort. The novel nomogram with four risk factors resulted in accurate prognostic prediction for IMPC.

Flavokavain C Suppresses Breast Cancer Cell Viability and Induces Cell Apoptosis by Triggering DNA Damage.

Breast cancer, presented by multiple breast cancer subtypes that coexist within a diagnosed tumor in clinical, has ranked as the most common malignancy in women in recent years. Evidence suggested that limited effective drugs caused the unsatisfactory therapeutic efficacy of breast cancer. Flavokavain C exhibited anticancer activity on colon cancer cells HCT116. It is yet unknown if it can be used to treat breast cancer. This study aims to believe the mechanisms by which Flavokavain C suppresses cell proliferation and the pathways that impact on this effect in breast cancer. 3-(4,5-Dimethythiazol)-2,5-diphenyltetrazolium bromide assay was chosen to evaluate cell cytotoxicity. Colony formation and cell proliferation assays using 5-ethynyl-2'-deoxyuridine staining were performed. Cell cycle progression and apoptosis were examined via flow cytometry and Western blotting, respectively. Five methods (comet assay, immunofluorescence, Western blotting, agarose gel electrophoresis and molecular docking) were used to quantify DNA damage and its cellular response. Compared to cisplatin, Flavokavain C possessed a comparable or more substantial inhibitory effect on breast cancer cell viability while having lower cytotoxicity on human mammary cells. Breast cancer cells treated with Flavokavain C had their colony formation suppressed, DNA replication blocked, the G2/M phase cell cycle arrested, and apoptosis. Furthermore, the results indicated that Flavokavain C would directly interact with DNA and induce DNA cleavage, demonstrating that DNA is an attractive substrate for Flavokavain C. These results suggested that Flavokavain C had strong anticancer activity against multiple subtypes of breast cancer cells.

Novel LncRNA AK023507 inhibits cell metastasis and proliferation in Papillary Thyroid Cancer through ß-catenin/Wnt Signaling Pathway.

INTRODUCTION: Papillary Thyroid Cancer (PTC) represents a commonly encountered type of thyroid malignancy whose occurrence and development is influenced by long non-coding RNA (LncRNA). A novel lncRNA (LncRNA AK023507), known to have tumor suppressive functions, was shown to prevent breast cancer cells from proliferating and metastasizing, but its mechanism in PTC is unclear. METHODS: Using PTC tissues and cell lines, the expression of LncRNA AK023507 was investigated by quantitative Real-time Polymerase Chain Reaction (qRT-PCR). The effects of knockdown or overexpression of LncRNA AK023507 on cell growth and movement were investigated through various cell experiments in vitro. The presence of important functional proteins was determined by Western blotting, with the recovery experiment used for verification. RESULTS: LncRNA AK023507 was found to have low expression in both the PTC cell lines and tissue samples. Knockdown of LncRNA AK023507 in PTC cells significantly promoted cell proliferation, migration, and invasion, while overexpression of LncRNA AK023507 resulted in the opposite effects. Furthermore, LncRNA AK023507 could regulate the expression of ß-catenin/Wnt signaling pathway as confirmed by recovery experiment. CONCLUSION: By acting through the ß-catenin/Wnt signaling pathway, LncRNA AK023507 prevented PTC cells from proliferating and metastasizing. These novel findings indicate that LncRNA AK023507 could be of prognostic and diagnostic value as a potential biomarker of PTC.

Effects of Tamoxifen vs. Toremifene on fatty liver development and lipid profiles in breast Cancer.

BACKGROUND: Tamoxifen (TAM) and Toremifene (TOR), two kinds of selective estrogen receptor modulators (SERMs), have equal efficacy in breast cancer patients. However, TAM has been proved to affect serum lipid profiles and cause fatty liver disease. The study aimed to compare the effects of TAM and TOR on fatty liver development and lipid profiles. METHODS: This study performed a retrospective analysis of 308 SERMs-treated early breast cancer patients who were matched 1:1 based on propensity scores. The follow-up period was 3 years. The primary outcomes were fatty liver detected by ultrasonography or computed tomography (CT), variation in fibrosis indexes, and serum lipid profiles change. RESULTS: The cumulative incidence rate of new-onset fatty liver was higher in the TAM group than in the TOR group (113.2 vs. 67.2 per 1000 person-years, p < 0.001), and more severe fatty livers occurred in the TAM group (25.5 vs. 7.5 per 1000 person-years, p = 0.003). According to the Kaplan-Meier curves, TAM significantly increased the risk of new-onset fatty liver (25.97% vs. 17.53%, p = 0.0243) and the severe fatty liver (5.84% vs. 1.95%, p = 0.0429). TOR decreased the risk of new-onset fatty liver by 45% (hazard ratio = 0.55, p = 0.020) and showed lower fibrotic burden, independent of obesity, lipid, and liver enzyme levels. TOR increased triglycerides less than TAM, and TOR increased high-density lipoprotein cholesterol, while TAM did the opposite. No significant differences in total cholesterol and low-density lipoprotein cholesterol are observed between the two groups. CONCLUSIONS: TAM treatment is significantly associated with more severe fatty liver disease and liver fibrosis, while TOR is associated with an overall improvement in lipid profiles, which supports continuous monitoring of liver imaging and serum lipid levels during SERM treatment.

Long Non-Coding RNA NLIPMT as a Tumor Suppressor and Inhibitor of Cell Proliferation and Metastasis in Papillary Thyroid Carcinoma.

INTRODUCTION: Gene expression association studies of tumor samples have uncovered several long non-coding RNAs (lncRNAs) closely related to various types of cancer. Several lncRNAs have been reported to play essential roles in the progression of papillary thyroid carcinoma (PTC). Novel lncRNA inhibiting proliferation and metastasis (lnc-NLIPMT) is a known regulator of mammary cell proliferation and motility, but its involvement in PTC is unclear. MATERIALS AND METHODS: We investigated the role of lnc-NLIPMT in PTC by quantitative real-time polymerase chain reaction (qRT-PCR) on various PTC tissue samples and cell lines. We assessed the effects of overexpression or knockdown of lnc-NLIPMT on the proliferation, migration, and invasion of PTC cells using CCK-8, cell clone formation, and transwell assays. Changes in the expression of N-cadherin and vimentin were detected by immunoblotting. RESULTS: Our results revealed a downregulation of the expression of lnc-NLIPMT in PTC and a negative correlation between lnc-NLIPMT expression and tumor size (P=0.006). Overexpression of lnc-NLIPMT in TPC-1 and B-CPAP cells significantly suppressed cell proliferation, migration, and invasion, while lnc-NLIPMT knockdown had the opposite effect. In addition, lnc-NLIPMT played an important role in the regulation of the expression of N-cadherin and vimentin. CONCLUSION: lnc-NLIPMT inhibits cell proliferation and metastasis of PTC cells and is a potential diagnostic and prognostic biomarker in PTC.

Randomized controlled trial of cognitive behavioural therapy for depressive and anxiety symptoms in Chinese women with breast cancer.

Depressive and anxiety symptoms are frequently observed in breast cancer survivors. To date, few randomized controlled trials have been conducted on the efficacy of cognitive behavioural therapy (CBT) for depressive and anxiety symptoms in Chinese population. This study aims to verify the efficacy of CBT in Chinese breast cancer survivors. Women (n = 392) with breast cancer were randomly assigned to 3 groups: CBT (n = 98), self-care management (SCM, n = 98), and usual care (UC, n = 196) using the proportion 1:1:2. Women in the CBT and SCM groups received a series of nine sessions for 12 weeks, while women in the UC group received their usual medical care only. Depressive and anxiety symptoms were assessed using the Hamilton Depression Rating Scale (HAMD) and the Hamilton Anxiety Scale (HAMA) score at baseline, 2, 4, 8, 12, 16, and 24 weeks. A significant intergroup difference was found in the HAMD and HAMA scores. Women in the CBT group showed significantly less depressive and anxiety symptoms compared with women in the SCM and UC groups over time. In conclusion, this study supports the efficacy of CBT for depressive and anxiety symptoms in Chinese breast cancer survivors.

Overexpression of novel lncRNA NLIPMT inhibits metastasis by reducing phosphorylated glycogen synthase kinase 3ß in breast cancer.

Long noncoding RNAs (lncRNAs) are considered as regulators of gene expression in cancers. However, cancer profiling has little focused on noncoding genes. Here, we reported that RP11-115N4.1 (here renamed novel lncRNA inhibiting proliferation and metastasis [NLIPMT]) was downregulated in breast cancer tissues. Ectopic expression of NLIPMT inhibited mammary cell proliferation, motility in vitro. Moreover, lnc-NLIPMT reduced the growth of implanted MDA-MB-231 cells in vivo. Mechanistically, glycogen synthase kinase 3ß (GSK3ß) was identified as an effector protein regulated by lnc-NLIPMT. Inhibition of GSK3ß activity restored NLIPMT-induced inhibition of proliferation and motility in breast cancer cells. These data reveal that lnc-NLIPMT functions as a driver of breast cancer progression and might serve as a potential target for antimetastatic therapies.

Effects of cognitive behavioral therapy for depression on improving insomnia and quality of life in Chinese women with breast cancer: results of a randomized, controlled, multicenter trial.

PURPOSE: Cognitive behavioral therapy (CBT) for depression had been found to be effective in reducing depressive and anxiety symptoms in breast cancer survivors. It is not known whether CBT for depression would also improve insomnia and quality of life (QOL). The aim of this study was to investigate whether CBT for depression would improve insomnia and QOL in a randomized controlled multicenter trial. PATIENTS AND METHODS: In this study, breast cancer survivors (n=392) were randomly allocated to the following three groups: CBT (n=98), self-care management (SCM, n=98), and usual care (UC, n=196) in a ratio of 1:1:2. CBT and SCM received a series of nine sessions for 12 weeks, whereas UC received UC only. Insomnia and QOL were evaluated using Athens Insomnia Scale (AIS) and Functional Assessment of Cancer Therapy-Breast (FACT-B) questionnaire at baseline, 4, 12, and 24 weeks. RESULTS: There was a significant intergroup difference in AIS and FACT-B scores (both P<0.01). CBT showed less insomnia problems and better overall QOL compared with those in SCM and UC (both P<0.01). No significant differences were found between SCM and UC in insomnia problems and overall QOL. Moreover, the effects of CBT on insomnia and QOL were maintained during the follow-up period. CONCLUSION: CBT for depression can be effective in improving insomnia problems and QOL in the Chinese breast cancer survivors.

MicroRNA-193a inhibits breast cancer proliferation and metastasis by downregulating WT1.

In many cancers, microRNA-193a (miR-193a) is a suppressor miRNA, but its underlying anti-oncogenic activity in breast cancer is not known. In this study, we found decreased miR-193a (specifically, miR-193a-5p) expression not only in breast cancer cell lines but also in breast cancer tissues as compared with the adjacent non-tumor tissues. Ectopic miR-193a overexpression inhibited the proliferation, colony formation, migration, and invasion of MDA-MB-231 and BT549 cells. miR-193a reduced Wilms' tumor 1 (WT1) expression and repressed luciferase reporter activity by binding WT1 coding region sequences; mutation of the predicted miR-193a binding site abolished this effect. miR-193a and WT1 expression were significantly inversely correlated in breast cancer tissues. Importantly, the anti-cancer activity induced by miR-193a was partially reversed by WT1 overexpression, indicating an important role for WT1 in such activity related to miR-193a. Our results reveal that miR-193a-WT1 interaction plays an important role in breast cancer metastasis, and suggest that restoring miR-193a expression is a therapeutic strategy in breast cancer.

ß3-tubulin is a good predictor of sensitivity to taxane-based neoadjuvant chemotherapy in primary breast cancer.

The objective of this study was to explore the relationship between ß3-tubulin expression and sensitivity to taxane-based neoadjuvant chemotherapy in primary breast cancer patients. A total of 48 local advanced breast cancer patients that received taxane-containing neoadjuvant chemotherapy were studied. The levels of ß3-tubulin expression were tested by immunohistochemistry before chemotherapy and at the end of cycles 2, 4 and 6. The correlation between the efficacy of the chemotherapy and ß3-tubulin expression and changes in ß3-tubulin expression over the course of chemotherapy was examined. ß3-tubulin protein expression before chemotherapy was significantly and negatively correlated with the response rate. The overall response rate was 31.8 % in the high ß3-tubulin expression group, whereas it was 84.6 % in the low ß3-tubulin expression group. At the end of cycles 2, 4 and 6 during the treatment course, the average expression rates of ß3-tubulin were showed an increasing trend with ß3-tubulin expression level at the end of cycle 4 being significantly different from that before chemotherapy. Nine patients that had a low ß3-tubulin expression level preneoadjuvant chemotherapy changed to a high ß3-tubulin expression level postneoadjuvant chemotherapy, and they had lower response rate than patients with consistent low. In conclusion, ß3-tubulin is a good predictor of chemosensitivity to taxane for breast cancer, and the change of its expression level during chemotherapy may be an important cause of secondary resistance to taxane. Detection of ß3-tubulin expression before and throughout the chemotherapy will help with selection of the chemotherapy treatment plan.

Long non-coding RNA HOTAIR modulates c-KIT expression through sponging miR-193a in acute myeloid leukemia.

HOTAIR is significantly overexpressed in various cancers and facilitates tumor invasion and metastasis. However, whether HOTAIR plays oncogenic roles in acute myeloid leukemia (AML) is still unknown. Here, we report that HOTAIR expression was obviously increased in leukemic cell lines and primary AML blasts. Clinically, AML patients with higher HOTAIR predicted worse clinical outcome compared with those with lower HOTAIR. Importantly, HOTAIR knockdown by small hairpin RNA inhibited cell growth, induced apoptosis, and decreased number of colony formation. Finally, HOTAIR modulated c-KIT expression by competitively binding miR-193a. Collectively, our data suggest that HOTAIR plays an important oncogenic role in AML and might serve as a marker for AML prognosis and a potential target for therapeutic intervention.

Targeting rho guanine nucleotide exchange factor ARHGEF5/TIM with auto-inhibitory peptides in human breast cancer.

The oncogenic protein ARHGEF5/TIM has long been known to express specifically in human breast cancer and other tumors, which is an important member of Rho guanine nucleotide exchange factors that activate Rho-family GTPases by promoting GTP/GDP exchange. The activation capability of TIM is auto-inhibited by a putative helix N-terminal to Dbl homology (DH) domain, which is stabilized by intramolecular interaction of Src homology 3 domain with a poly-proline sequence that locates between the helix and DH domain. Here, we attempted to target TIM DH domain using the modified versions of its auto-inhibitory helix. In the procedure, bioinformatics techniques were used to investigate the intramolecular interaction of DH domain with auto-inhibitory helix and, based on obtained knowledge, to optimize physicochemical property and structural conformation for the helix. We also performed affinity assay to determine the binding strength of modified peptides to DH domain. Consequently, two modified peptides, namely, DALYEEYNLVV and EVLYEEYQLVV were found as good binders of DH domain with dissociation constants K d of 0.35 and 2 µM, respectively. Structural analysis revealed that the charge neutralization and electrostatic interaction confer additional stability for these two peptide complexes with DH domain.

Hashimoto's thyroiditis, microcalcification and raised thyrotropin levels within normal range are associated with thyroid cancer.

BACKGROUND: To confirm whether clinical and biochemical parameters or Hashimoto's thyroiditis (HT) could predict the risks of malignancy among subjects who underwent thyroidectomy, as well as to determine the influence of HT on the biological behavior of papillary thyroid cancer (PTC). METHODS: A total of 2,052 patients who underwent initial thyroidectomy were enrolled between June 2006 and August 2008. Serum free T4, free T3, thyrotropin (TSH), thyroglobulin, thyroglobulin antibody, antimicrosomal antibody, tumor-associated status, and thyroid disorders were documented. RESULTS: Binary logistic regression analysis was performed to define the risk predictors for thyroid cancer. Finally, calcification, HT, TSH, and age, were entered into the multivariate model. Multivariate logistic regression analysis revealed the risk of thyroid cancer increases in parallel with TSH concentration within normal range, and the risk for malignancy significantly increased with serum TSH 1.97-4.94 mIU/L, compared with TSH less than 0.35 mIU/L (OR = 1.951, 95% CI = 1.201-3.171, P = 0.007). Increased risks of thyroid cancer were also detected among the patients with HT (OR = 3.732, 95% CI = 2.563-5.435), and microcalcification (OR = 14.486, 95% CI = 11.374-18.449). The effects of HT on the aggressiveness of PTC were not observed in extrathyroidal invasion (P = 0.347), capsular infiltration (P = 0.345), angioinvasion (P = 0.512), and lymph node metastases (P = 0.634). CONCLUSIONS: The risk of malignancy increases in patients with higher level TSH within normal range, as well as the presence of HT and microcalcification. No evidence suggests that coexistent HT alleviates the aggressiveness of PTC.

Adjuvant combined systemic chemotherapy and intraperitoneal chemotherapy for locally advanced gastric cancer.

The optimal adjuvant treatment modality for gastric cancer has not been well defined. The aim of this study was to evaluate the efficacy and feasibility of adjuvant combined systemic and intraperitoneal chemotherapy (ACSIP) in high-risk patients with locally advanced gastric cancer. Between June 2003 and December 2008, 62 eligible patients with serosa-infiltrating and/or node-positive gastric cancer following curative gastrectomy with D2 lymphadenectomy received ACSIP, consisting of intravenous oxaliplatin 85 mg/m(2) on day 1 followed by leucovorin (LV) 200 mg/m(2) and 5-fluorouracil (5-FU) 450 mg/m(2) on days 1-3, intraperitoneal 5-FU 600 mg/m(2) on days 4-5 and cisplatin (CDDP) 40 mg/m(2) on day 5. Survival rates, the sites of first treatment failure and safety were analyzed. At a median follow-up of 45 months (range 7-101), the 3-year disease-free survival (DFS) and overall survival (OS) rates were 66.1 and 74.2%, respectively. Initial peritoneal and hepatic failures were found in 6 (24.0%) and 3 (12.0%) of the 25 patients with recurrence, respectively. Neutropenia, gastrointestinal side effects and peripheral neuropathy were the most common grade 3-4 toxicities; however, they were all infrequent and manageable. No serious surgical complications or treatment-related mortality was observed. The results of this study indicate that ACSIP is effective and feasible for locally advanced gastric cancer with encouraging survival rates and possibly decreased peritoneal and hepatic recurrences. The benefits of this promising combined adjuvant treatment modality warrant further studies.

[Targeted detecting HER2 expression with recombinant anti HER2 ScFv-GFP fusion antibody].

To verify the reliability of targeted detecting HER2 positive cancer cells and clinical pathological tissue specimens with a recombinant anti HER2 single chain antibody in single chain Fv fragment (scFv) format, we have constructed the fusion variable regions of the ScFv specific for HER2/neu. labeled a green-fluorescent protein(GFP). The humanized recombinant Anti HER2 ScFv-GFP gene was inserted into pFast Bac HT A, and expressed in insect cells sf9. Then the recombinant fusion protein Anti HER2 ScFv-GFP was properly purified with Ni2+-NTA affinity chromatography from the infected sf9 cells used to test the specificity of the fusion antibody for HER2 positive cancer cells. Firstly, the purified antibody incubated with HER2 positive breast cancer cells SKBR3, BT474 and HER2 negative breast cancer cells MCF7 for 12 h/24 h/48 h at 37 degrees C, in order to confirm targeted detecting HER2 positive breast cancer cells by Laser Confocal Microscopy. Furthermore, the same clinical pathological tissue samples were assessed by immunohistochemistry (IHC) and the fusion antibody Anti HER2 ScFv-GFP in the meanwhile. The data obtained indicated that the recombinant eukaryotic expression plasmid pFast Bac HT A/Anti HER2 ScFv-GFP was constructed successfully In addition, obvious green fluorescent was observed in insect cells sf9. When the purified fusion antibody was incubated with different cancer cells, much more green fluorescent was observed on the surface of the HER2 positive cancer cells SKBR3 and BT474. In contrast, no green fluorescent on the surface of the HER2 negative cancer cells MCF7 was detected. The concentration of the purified fusion antibody was 115.5 microg/mL, of which protein relative molecular weight was 60 kDa. The analysis showed the purity was about 97% and the titer was about 1:64. The detection results of IHC and fusion antibody testing indicated the conformity. In summary, the study showed that the new fusion antibody Anti HER2 ScFv-GFP can test HER2 positive cancer cells, indicating a potential candidate method for clinical HER2 positive specimens detection.

[Clinical significance of CC3/TIP30 expression in breast carcinoma and its correlation with HER-2/neu].

OBJECTIVE: To explore the clinical significance of CC3/TIP30 protein's expression in breast carcinoma and its correlation with HER-2/neu. METHODS: The expression of CC3/TIP30 and HER-2/neu protein was detected in 112 breast cancer tissues which was collected from January 2004 to January 2005 by immunohistochemistry and the relationship with clinic pathological parameters and prognosis was analyzed. Small interfering RNA (siRNA) which target to knock out CC3/TIP30 were transfected into SK-BR-3 cells. Real-time PCR were used to detect the level of CC3/TIP30 and HER-2/neu mRNA. RESULTS: The results of immunohistochemistry showed CC3/TIP30 protein was correlated with TNM stage, lymph node status, HER-2 status and molecule classification (P = 0.048, 0.019, 0.027, 0.011), but there was no association with age, tumor size, estrogen receptor and progesterone receptor. Real-time PCR results revealed that CC3/TIP30 siRNA down-regulation the level of its mRNA, accompanied by a decline in the expression of HER-2/neu gene mRNA, the difference was statistically significant (F = 56.797, P = 0.000; F = 165.101, P = 0.000). In addition, Kaplan-Meier curves of disease-specific survival analysis showed a marked difference in the subtype of HER-2 protein positive between CC3/TIP30 positive group and negative group (χ(2) = 10.732, P = 0.001). CONCLUSIONS: The loss of CC3/TIP30 is related to occurrence and development in breast cancer, suggesting early onset of metastasis and recurrence. Perhaps CC3/TIP30 can be considered as a sub-typing indicator in HER-2 positive breast cancer.

Traumatic neuroma in a patient with breast cancer after mastectomy: a case report and review of the literature.

The incidence of traumatic neuroma is extremely low, especially in those patients with breast cancer after mastectomy. There are only 10 cases reported in the literature. We report a patient who developed a palpable nodular mass near the mastectomy scar. The result of excisional biopsy was traumatic neuroma. Review of the literature reveal 10 cases with breast cancer of traumatic neuromas after mastectomy. Traumatic neuroma is a benign lesion and a reparative response of the nerve to injury, either direct/indirect trauma or chronic inflammation. Benign lesions as traumatic neuromas are more rarely seen after mastectomy. However, in order to manage patients' treatment, the most critical problem is to distinguish it from recurrent breast carcinoma. Although assistant examination methods such as ultrasound and computed tomography are valuable to a certain extent, the final diagnosis can only be confirmed on pathologic examination.