OPALIN is an LGI1 receptor promoting oligodendrocyte differentiation.

Leucine-rich glioma-inactivated protein 1 (LGI1), a secretory protein in the brain, plays a critical role in myelination; dysfunction of this protein leads to hypomyelination and white matter abnormalities (WMAs). Here, we hypothesized that LGI1 may regulate myelination through binding to an unidentified receptor on the membrane of oligodendrocytes (OLs). To search for this hypothetic receptor, we analyzed LGI1 binding proteins through LGI1-3 × FLAG affinity chromatography with mouse brain lysates followed by mass spectrometry. An OL-specific membrane protein, the oligodendrocytic myelin paranodal and inner loop protein (OPALIN), was identified. Conditional knockout (cKO) of OPALIN in the OL lineage caused hypomyelination and WMAs, phenocopying LGI1 deficiency in mice. Biochemical analysis revealed the downregulation of Sox10 and Olig2, transcription factors critical for OL differentiation, further confirming the impaired OL maturation in Opalin cKO mice. Moreover, virus-mediated re-expression of OPALIN successfully restored myelination in Opalin cKO mice. In contrast, re-expression of LGI1-unbound OPALIN_K23A/D26A failed to reverse the hypomyelination phenotype. In conclusion, our study demonstrated that OPALIN on the OL membrane serves as an LGI1 receptor, highlighting the importance of the LGI1/OPALIN complex in orchestrating OL differentiation and myelination.

A novel Lgi1 mutation causes white matter abnormalities and impairs motor coordination in mice.

Leucine-rich glioma-inactivated protein 1 (LGI1) is known to play a key role in autosomal dominant lateral temporal lobe epilepsy (ADLTE). The ADLTE is an inherited disease characterized by focal seizures with distinctive auditory or aphasic symptoms. A large number of mutations on the Lgi1 gene have been reported and are believed to be the genetic cause for ADLTE. We identified a novel missense mutation, c.152A>G (p.Asp51Gly), on Lgi1 from a Chinese ADLTE patient who manifests locomotor imbalance and white matter reduction. However, it remains unknown how mutant LGI1 causes white matter abnormalities at molecular and cellular levels. Here, we generated a knock-in mouse bearing this Lgi1 mutation. We found that Lgi1D51G/D51G mice exhibited impaired defective white matter and motor coordination. We observed that Lgi1D51G/D51G mice displayed a reduced number of mature oligodendrocytes (OLs) and deficient OL differentiation in the white matter. However, the population of oligodendrocyte precursor cells was not affected in Lgi1D51G/D51G mice. Mechanistically, we showed that the Lgi1D51G mutation resulted in altered mTOR signaling and led to decreased levels of Sox10. Given that Sox10 is a key transcriptional factor to control OL differentiation, our results strongly suggest that the Lgi1D51G mutation may cause white matter abnormalities via inhibiting Sox10-dependent OL differentiation and myelination in the central nervous system.

A Hierarchical Spatial-Temporal Cross-Attention Scheme for Video Summarization Using Contrastive Learning.

Video summarization (VS) is a widely used technique for facilitating the effective reading, fast comprehension, and effective retrieval of video content. Certain properties of the new video data, such as a lack of prominent emphasis and a fuzzy theme development border, disturb the original thinking mode based on video feature information. Moreover, it introduces new challenges to the extraction of video depth and breadth features. In addition, the diversity of user requirements creates additional complications for more accurate keyframe screening issues. To overcome these challenges, this paper proposes a hierarchical spatial-temporal cross-attention scheme for video summarization based on comparative learning. Graph attention networks (GAT) and the multi-head convolutional attention cell are used to extract local and depth features, while the GAT-adjusted bidirection ConvLSTM (DB-ConvLSTM) is used to extract global and breadth features. Furthermore, a spatial-temporal cross-attention-based ConvLSTM is developed for merging hierarchical characteristics and achieving more accurate screening in similar keyframes clusters. Verification experiments and comparative analysis demonstrate that our method outperforms state-of-the-art methods.

Determination of multiple pesticide residues in teas by gas chromatography with accurate time-of-flight mass spectrometry.

In this work, gas chromatography tandem with electron ionization and full-scan high-resolution mass spectrometry with a time-of-flight mass analyzer was evaluated for analyzing pesticide residues in teas. The relevant aspects for mass spectrometry analysis, including the resolution and mass accuracy, acquisition rate, temperature of ion source, were investigated. Under acquisition condition in 2-GHz extended dynamic range mode, accurate mass spectral library including 184 gas chromatography detectable pesticides was established and retrieval parameters were optimized. The mass spectra were consistent over a wide concentration range (three orders) with good match values to those of NIST (EI-quadrupole). The methodology was verified by the validation of 184 pesticides in four tea matrices. A wide linear range (1-1000 µg/kg) was obtained for most compounds in four matrices. Limit of detection, limit of quantification, and limit of identification values acquired in this study could satisfy the requirements for maximum residue levels prescribed by the European Community. Recovery studies were performed at three concentrations (10, 50, and 100 µg/kg). Most of the analytes were recovered at an acceptable range of 70-120% with relative standard deviations ≤ 20% in four matrices. The potential extension of qualitative screening scope makes gas chromatography tandem with electron ionization and mass spectrometry with a time-of-flight mass analyzer a more powerful tool compared with gas chromatography with tandem mass spectrometry.

Predictive factors for the local recurrence and distant metastasis of phyllodes tumors of the breast: a retrospective analysis of 192 cases at a single center.

The local recurrence rate of phyllodes tumors of the breast varies widely among different subtypes, and distant metastasis is associated with poor survival. This study aimed to identify factors that are predictive of local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS) in patients with phyllodes tumors of the breast. Clinical data of all patients with a phyllodes tumor of the breast (n = 192) treated at Sun Yat-sen University Cancer Center between March 1997 and December 2012 were reviewed. The Pearson Χ² test was used to investigate the relationship between clinical features of patients and histotypes of tumors. Univariate and multivariate Cox regression analyses were performed to identify factors that are predictive of LRFS, DMFS, and OS. In total, 31 (16.1%) patients developed local recurrence, and 12 (6.3%) developed distant metastasis. For the patients who developed local recurrence, the median age at the diagnosis of primary tumor was 33 years (range, 17-56 years), and the median size of primary tumor was 6.0 cm (range, 0.8-18 cm). For patients who developed distant metastasis, the median age at the diagnosis of primary tumor was 46 years (range, 24-68 years), and the median size of primary tumor was 5.0 cm (range, 0.8-18 cm). In univariate analysis, age, size, hemorrhage, and margin status were found to be predictive factors for LRFS (P = 0.009, 0.024, 0.004, and 0.001, respectively), whereas histotype, epithelial hyperplasia, margin status, and local recurrence were predictors of DMFS (P = 0.001, 0.007, 0.007, and < 0.001, respectively). In multivariate analysis, independent prognostic factors for LRFS included age [hazard ratio (HR) = 3.045, P = 0.005], tumor size (HR = 2.668, P = 0.013), histotype (HR = 1.715, P = 0.017), and margin status (HR = 4.530, P< 0.001). Histotype (DMFS: HR = 4.409, P = 0.002; OS: HR = 4.194, P = 0.003) and margin status (DMFS: HR = 2.581, P = 0.013; OS: HR = 2.507, P = 0.020) were independent predictors of both DMFS and OS. In this cohort, younger age, a larger tumor size, a higher tumor grade, and positive margins were associated with lower rates of LRFS. Histotype and margin status were found to be independent predictors of DMFS and OS.

Changes in Flavor-Related Biomarkers in Pacific Oysters (Crassostrea gigas) Following Microplastic Exposure.

Microplastics have been an emerging threat to filtering species and the ingestion and impacts of microplastics on oysters are a cause for concern. However, much remains unknown about the effects of microplastics on flavor-related biomarkers in oysters. Herein, a laboratory microplastic exposure with concentrations of 1, 10, and 100 mg/L for 15 days was performed to investigate the impacts of microplastics on the flavor parameters of oysters. Exposure to microplastics changed the odor characteristics of oysters. Microplastic exposure had minor effects on the fatty acid composition; however, significant alterations in free amino acids and nucleotides were observed under the 1 and 10 mg/L exposure groups, respectively. The overall results indicated 10 mg/L of microplastic exposure significantly increased the equivalent umami value of oysters. These findings stressed the effects of microplastics on oysters and would be an important reference for the assessment of the potential risks associated with microplastics in marine edible species.

An overview of microplastics in oysters: Analysis, hazards, and depuration.

Microplastic pollution has become an emergent global environmental issue because of its ubiquitous nature and everlasting ecological impacts. In marine ecosystems, microplastics can serve as carriers to absorb various contaminants and the ingestion of microplastics in oysters is of concern because they can induce several adverse effects. The analytical process of microplastics in oysters commonly consists of separation, quantification, and identification. Quantification of microplastics is difficult since information regarding the analytical methods is incoherent, therefore, standard microplastic analytical methods for shellfish should be established in the future. The depuration process can be used to reduce the level of microplastics in oysters to ensure safe consumption of oysters and longer depuration time facilitates improved depuration efficacy. In summary, this review aims to help better understand microplastic pollution in oysters and provide useful suggestions and guidance for future research.

Effects of liquid nitrogen freezing at different temperatures on the quality and flavor of Pacific oyster (Crassostrea gigas).

This study aimed to evaluate the effects of different liquid nitrogen freezing (LNF) temperatures (-20, -40, -60, -80, and -100 °C) on the water holding capacity, texture, microstructure, and flavor of Crassostrea gigas (C. gigas). The results showed that -40 °C LNF, -60 °C LNF, and -80 °C LNF improved the water holding capacity of C. gigas (P < 0.05); -60 °C LNF and -80 °C LNF could effectively maintain the hardness of the body trunk and adductor muscles. Compared with -20 °C refrigerator freezing (RF), the LNF group could form smaller ice crystals and thus reduce the damage to the muscle cell structure damage, especially LNF at -80 °C. Gas chromatography-ion mobility spectrometry (GC-IMS) and e-nose results indicated that -80 °C LNF maintained the flavor profile of few aldehydes and alcohols compared to other freezing groups. Therefore, -80 °C LNF effectively improved the quality and maintain the flavor characteristics of frozen C. gigas.

Comparison of the metabolomic and proteomic profiles associated with triterpene and phytosterol accumulation between wild and cultivated ginseng.

Wild ginseng is thought to be superior in its medicinal quality to cultivated ginseng, potentially owing to the differences in active components. This study was designed accordingly to assess the differences in secondary metabolite components and their synthesis in wild and cultivated ginseng by using quantitative proteomics combined with secondary metabolomics approaches. A total of 72 secondary metabolites were found to be differentially abundant, of which dominant abundant in wild ginseng primarily included triterpenoid saponins (ginsenosides) and phytosterols. Ginsenoside diversity was increased in wild ginseng, particularly with respect to rare ginsenosides. Ginsenoside Rk1, F1, Rg5, Rh1, PPT, Rh2, and CK enriched in wild ginseng were validated by HPLC. In addition to ginsenosides, stigmasterol and ß-sitosterol were accumulated in wild ginseng. 102 differentially expressed proteins between wild and cultivated ginseng were identified using iTRAQ labeling technique. Among them, 25 were related to secondary metabolism, mainly involved in sesquiterpene and triterpene biosynthesis, which was consistent with metabolomics results. Consistently, the activity levels of HMGR, FDPS, SS, SE, DS, CYP450, GT and CAS, which are key enzymes related to ginsenoside and phytosterol biosynthesis, were confirmed to be elevated in wild ginseng.The biosynthesis of ginsenosides and phytosterols in wild ginseng is higher than that in cultivated ginseng, which may be related to natural growth without artificial domestication. To some extent, this study explained the accumulation of pharmacodynamic components and overall quality of ginseng, which could provide reference for the germplasm improvement and planting of ginseng.

Distribution, clinicopathologic features and survival of breast cancer subtypes in Southern China.

Breast cancer research and treatment by different subtypes is an inevitable trend. We investigated the clinicopathologic features and outcomes of different breast cancer subtypes in Southern China. A total of 5809 patients with invasive ductal carcinomas were identified. Immunohistochemical (IHC) markers for estrogen receptor (ER), progesterone receptor (PR), Her2/neu, and Ki-67 proliferation index were used to classify cases into five molecular subtypes. Clinicopathologic characteristics and survival rates were analyzed retrospectively. Of all patients, 31.1% were luminal A subtype, 30.4% luminal B (high Ki-67), 13.1% luminal B (Her2/neu+), 9.0% Her2/neu and 16.5% triple negative subtype. Luminal B (high Ki-67) presented primarily in premenopausal patients with the lowest average age (43.0 years). Her2/neu positive tumors were more closely associated with aggressive features including increased tumor size, positive lymph node status and lymphvascular invasion (LVI). Triple negative subtype was characterized by poorer histologic grade. Her2/neu positive cases had presented the worst 5-year disease-free survival (DFS) and overall survival (OS). Multivariate analyses of OS and DFS suggested that there were different negative prognostic factors for the five subtypes. The benefit of the cyclophosphamide, methotrexate, and 5-fluorouracil (5FU) (CMF) regimen was equal to that of anthracycline-based and Taxane-based regimens for patients with luminal A subtype and triple negative subtype, but inferior to anthracycline-based and Taxane-based regimens for those with two luminal B subtypes and Her2/neu subtype. The prognostic significance of traditional markers may differ among subtypes. This study revealed the distinct clinicopathologic characteristics, systemic therapy benefits, prognostic factors and survival rate among different breast cancer subtypes.

Ginsenosides improve reproductive capability of aged female Drosophila through mechanism dependent on ecdysteroid receptor (ECR) and steroid signaling pathway.

Aging ovaries caused diminished fertility and depleted steroid hormone level. Ginsenosides, the active ingredient in ginseng, had estrogen-like hormonal effects. Although ginsenosides were well known for their ability to alleviate many age-related degenerative diseases, the effect of ginsenosides on the decline in reproductive capability caused by aging, as well as the mechanism, are unknown. We found that ginsenosides improved the quantity and quality of the offspring, prolonged life and restored muscle ability in aged female Drosophila. In addition, ginsenosides inhibited ovarian atrophy and maintained steroid hormone 20-Hydroxyecdysone (20E) and juvenile-preserving hormone (JH)) levels. Ginsenosides activated ecdysteroid receptor (ECR) and increased the expression of the early transcription genes E74 and Broad (Br), which triggered steroid signaling pathway. Meanwhile, ginsenosides promoted JH biosynthesis by increasing the expression of Hydroxyl-methylglutaryl-CoA reductase (HMGR) and juvenile hormone acid O-methyltransferase (JHAMT). Subsequently, JH was bound to Methoprene Tolerant (Met) and activated the transcription of the responsive gene Kruppel Homolog 1 (Kr-h1), which coordinated with 20E signaling to promote the reproduction of aged female Drosophila. The reproductive capacity and steroid hormone levels were not improved and the steroid signaling pathway was not activated in ginsenoside-treated ECR knockout Drosophila. This suggested that ginsenosides played a role dependent on targeted ECR. Furthermore, 17 kinds of ginsenoside monomers were identified from the total ginsenosides. Among them, Rg1, Re and Rb1 improved the reproductive capacity and steroid hormone levels of aged female Drosophila, which has similar effects to the total ginsenoside. These results indicated that ginsenosides could enhance the reproductive capacity of aged female Drosophila by activating steroid signals dependent on nuclear receptor ECR. In addition, ginsenoside monomers Rg1, Rb1 and Re are the main active components of total ginsenosides to improve reproductive ability. This will provide strong evidence that ginsenosides had the potential to alleviate age-induced reproductive degradation.

A novel LGI1 mutation causing autosomal dominant lateral temporal lobe epilepsy confirmed by a precise knock-in mouse model.

AIMS: This study aimed to explore the pathomechanism of a mutation on the leucine-rich glioma inactivated 1 gene (LGI1) identified in a family having autosomal dominant lateral temporal lobe epilepsy (ADLTE), using a precise knock-in mouse model. METHODS AND RESULTS: A novel LGI1 mutation, c.152A>G; p. Asp51Gly, was identified by whole exome sequencing in a Chinese family with ADLTE. The pathomechanism of the mutation was explored by generating Lgi1D51G knock-in mice that precisely phenocopied the epileptic symptoms of human patients. The Lgi1D51G/D51G mice showed spontaneous recurrent generalized seizures and premature death. The Lgi1D51G/+ mice had partial epilepsy, with half of them displaying epileptiform discharges on electroencephalography. They also showed enhanced sensitivity to the convulsant agent pentylenetetrazole. Mechanistically, the secretion of Lgi1 was impaired in the brain of the D51G knock-in mice and the protein level was drastically reduced. Moreover, the antiepileptic drugs, carbamazepine, oxcarbazepine, and sodium valproate, could prolong the survival time of Lgi1D51G/D51G mice, and oxcarbazepine appeared to be the most effective. CONCLUSIONS: We identified a novel epilepsy-causing mutation of LGI1 in humans. The Lgi1D51G/+ mouse model, precisely phenocopying epileptic symptoms of human patients, could be a useful tool in future studies on the pathogenesis and potential therapies for epilepsy.

Clinical features and survival analysis of different subtypes of patients with breast cancer brain metastases.

BACKGROUND AND OBJECTIVE: The brain is one of the most common metastatic sites of breast cancer. Brain metastases develop in 10%-15% of patients with breast cancer and are associated with poor prognosis. The purpose of this retrospective study was to analyze the clinical characteristics and survival of patients with brain metastases due to breast cancer of different subtypes and to identify the prognostic factors that affect clinical outcome. METHODS: A total of 89 patients with breast cancer brain metastases diagnosed between October 1997 and July 2008 at Sun Yat-sen University Cancer Center were included in this study. Among the 89 patients, the number of luminal A, luminal B, human epidermal growth factor receptor 2 (HER-2), and triple-negative (TN) subtypes were 30, 20, 16, and 14, respectively; 9 patients had an unknown subtype. The clinical characteristics, pathologic features, and prognostic factors were analyzed both at the initial diagnosis and at the diagnosis of brain metastases. Endocrine therapy for patients with luminal subtypes was further studied. RESULTS: The median age of patients was 46 years (range 28-74 years). The median survival time was 8.0 months (range, 0-80 months), the 1-year survival rate was 32% and the 5-year survival rate was 4%. The time to brain metastasis differed according to clinical stage at the initial diagnosis, and the time for patients with the luminal A subtype was the longest (P < 0.001). Multivariate analysis demonstrated that performance status score > 1, multiple brain metastases and without whole brain radiotherapy (WBRT) in combination with chemotherapy were associated with poor prognosis. Compared with the luminal A subtype, features of the HER-2 and TN subtypes included early metastases, rapid progression after first-line treatment (8.0 months vs. 11.0 months), and poor overall survival (25.0 months vs. 63.0 months). The luminal A subtype showed a tendency for good prognosis and slow growth. Tamoxifen could improve the survival of luminal A/B subtypes (median survival 24.0 months vs. 7.0 months, respectively, P = 0.002). CONCLUSIONS: The prognosis of brain metastases from breast cancer was poor, especially in patients with HER-2 and TN subtypes. Generally, WBRT in combination with chemotherapy was the standard treatment modality. Patients with the luminal subtypes could benefit from tamoxifen.

Enkephalinergic Circuit Involved in Nociceptive Modulation in the Spinal Dorsal Horn.

Enkephalin (ENK) has been implicated in pain modulation within the spinal dorsal horn (SDH). Revealing the mechanisms underlying ENK analgesia entails the anatomical and functional knowledge of spinal ENK-ergic circuits. Herein, we combined morphological and electrophysiological studies to unravel local ENK-ergic circuitry within the SDH. First, the distribution pattern of spinal ENK-ergic neurons was observed in adult preproenkephalin (PPE)-GFP knock-in mice. Next, the retrograde tracer tetramethylrhodamine (TMR) or horseradish peroxidase (HRP) was injected into the parabrachial nucleus (PBN) in PPE-GFP mice. Immunofluorescent staining showed I-isolectin B4 (IB4) labeled non-peptidergic afferents were in close apposition to TMR-labeled PBN-projecting neurons within lamina I as well as PPE-immunoreactivity (-ir) neurons within lamina II. Some TMR-labeled neurons were simultaneously in close association with both IB4 and PPE-ir terminals. Synaptic connections of these components were further confirmed by electron microscopy. Finally, TMR was injected into the PBN in adult C57BL/6 mice. Whole-cell patch recordings showed that δ-opioid receptor (DOR) agonist, [D-Pen2,5]-enkephalin (DPDPE, 1 µM), significantly reduced the frequency of miniature excitatory postsynaptic current (mEPSC) and decreased the activity of TMR-labeled neurons. In conclusion, spinal ENKergic neurons receive direct excitatory inputs from primary afferents, which might be directly recruited to release ENK under the condition of noxious stimuli; ENK could inhibit the glutamatergic transmission towards projecting neurons via presynaptic and postsynaptic DORs. These morphological and functional evidence may explain the mechanisms underlying the analgesic effects exerted by ENK within the SDH.

Histone deacetylase 2 is involved in µ­opioid receptor suppression in the spinal dorsal horn in a rat model of chronic pancreatitis pain.

Chronic pain occurs in ~85-90% of chronic pancreatitis (CP) patients. However, as the pathogenesis of CP pain remains to be fully understood, the current therapies for CP pain remain inadequate. Emerging evidence has suggested that the epigenetic modulations of genes are involved in chronic pain. In the present study, intrapancreatic trinitrobenzene sulfonic acid infusions were used to establish a CP model in rats. Mechanical allodynia was measured with von Frey filaments. Immunofluorescent staining analysis was used to observe the expression changes of histone deacetylase 2 (HDAC2) and µ­opioid receptor (MOR), and intrathecal administration of the selective HDAC2 inhibitor AR­42 was used to assess the underlying mechanisms. The expression levels of c­Jun N­terminal kinase (JNK) in the thoracic spinal cord were detected by western blotting, and the mRNA expression levels of interleukin (IL)1­ß, IL­6 and tumor necrosis factor (TNF)­α were detected by reverse transcription­quantitative polymerase chain reaction. The results demonstrated that HDAC2 expression was upregulated during the course of CP induction, while MOR activity in the thoracic spinal dorsal horn was significantly suppressed. Intrathecal infusion of AR­42 significantly attenuated CP­induced mechanical allodynia, with rescued MOR activity. Additionally, HDAC2 facilitated the release of inflammatory cytokines, including IL­1ß, IL­6 and TNF­α. These results suggested that the underlying mechanisms of HDAC2 regulating MOR activity under CP induction may occur via promoting the release of inflammatory cytokines, thus activating the JNK signaling pathway. The present study suggested that the epigenetic­regulated disturbance of MOR is dependent on the endogenous analgesia system in CP, which may a provide novel therapeutic strategy for treating pain in CP.

Effectiveness of capecitabine with or without docetaxel therapy for the treatment of patients with advanced urothelial carcinoma: a single-institution experience.

PURPOSE: The purpose of this study was to evaluate the effectiveness and toxicity of capecitabine (C) chemotherapy regimen with or without (w/o) docetaxel (D) in patients with advanced urothelial carcinoma (UC). RESULTS: Clinical benefit rate were similar in two arms (C arm vs DC arm: 38.9% vs 45.5%, p = 0.411). There were two cases achieved partial response in DC arm. In C arm, the median PFS was 3.0 months (95% CI 2.5-3.5 months) and median OS was 11.3 months (95% CI 8.6-14.1 months). In DC arm, the median PFS was 2.2 months (95% CI 1.7-2.7 months) and median OS was 18 months (95% CI 6.8-29.9 months). Adverse events were mostly acceptable, including myelosuppession, hand-foot syndrome and mucositis. Anemia and leukopenia was found more in the DC arm than in the C arm. MATERIALS AND METHODS: This is a one-center, observational, retrospective study. From April 2009 to March 2015, a total of 29 patients with metastatic UC were included in the study. Survivals, response rates and toxicities were collected retrospectively. CONCLUSIONS: The result showed the activity and toxicity of C w/o D. As DC treatment did not reveal better outcome, C or D single-agent might be an option in platinum-failed patients with advanced urothelial carcinoma. Further clinical trials are warranted.

Clinicopathologic characteristics and prognostic factors for HER2-positive patients with metastatic breast cancer in southern China.

INTRODUCTION: The aim of the study was to analyze clinicopathologic characteristics and survival and to identify prognostic factors for Chinese patients with HER2-positive metastatic breast cancer. MATERIAL AND METHODS: A total of 243 patients with HER2-positive metastatic breast cancer, treated during the period 2002 to 2009, were followed up from initial disease diagnosis to death or date of last follow-up (December 2011). Cumulative survival curves were created using Kaplan-Meier analysis with the log-rank test. Prognostic factors were analyzed by univariate and multivariate Cox proportional hazards regression analysis. RESULTS: During follow-up, 205 patients died, with a median OS of 27 months (95% CI: 23.5, 30.5 months), and the 1-, 3-, and 5-year survival rates were 84.4%, 38.6%, and 18.1%, respectively. The median OS of HR+ patients was significantly higher than that of HR- patients (p < 0.001). Surgery (hazard ratio = 0.60, p = 0.002), endocrine therapy (hazard ratio = 0.53, p < 0.01), and anti-HER2 therapy (hazard ratio = 0.63, p = 0.003) were favorable independent prognostic factors for patients with HER2-positive metastatic breast cancer. CONCLUSIONS: These results indicated that surgical intervention, endocrine therapy, and anti-HER2 therapy were good for these HER2 positive patients with metastatic breast cancer, but ECOG performance status < 1 and metastasis to brain were unfavorable independent prognostic factors. HR status was not an independent prognostic factor.

HER2-positive breast cancer patients receiving trastuzumab treatment obtain prognosis comparable with that of HER2-negative breast cancer patients.

PURPOSE: The efficacy of trastuzumab in Chinese breast cancer (BC) patients has rarely been reported. This study was designed to compare the clinical outcomes of HER2-positive BC patients receiving or not receiving trastuzumab treatment and HER2-negative BC patients. PATIENTS AND METHODS: This study involved three groups of patients. The first group was 115 human epidermal growth factor receptor 2 (HER2)-positive BC patients treated with trastuzumab who were enrolled at Sun Yat-sen University Cancer Center between January 2002 and July 2010; the second group was a matched control group of 115 HER2-positive patients who did not receive trastuzumab treatment; the third group was a matched group of 115 HER2-negative patients who received conventional therapy in the adjuvant setting. The primary endpoint was 3-year and 5-year disease-free survival (3-DFS and 5-DFS, respectively). The Kaplan-Meier method, log-rank test, and multivariate Cox proportional hazard regression model were used for survival analysis. The differences in survival rates among the three groups were also analyzed according to two different periods: 2002-2006 and 2007-2010. RESULTS: The median duration of follow-up was 36 months (range, 12-111 months). The 3-DFS rates in the HER2-negative group, the HER2-positive group who received trastuzumab treatment, and the HER2-positive group who did not receive trastuzumab treatment were 82.6%, 89.6%, and 67.0%, respectively. The 3-DFS rate for the total study population was statistically significant (P < 0.001). Further analysis indicated a statistically significant difference in 3-DFS between either of the first two groups and the third group (P < 0.01), but the difference between the first two groups was not statistically significant (P = 0.157). Among the three groups, the 3-DFS rates during 2002-2006 did not have a significant difference compared with that during 2007-2010. CONCLUSION: This study has further confirmed the efficacy of trastuzumab for HER2-positive operable BC in Chinese patients. It has also demonstrated that the 3-DFS and 5-DFS rates between HER2-positive patients receiving trastuzumab treatment and HER2-negative patients are comparable.

EGFR expression correlates with decreased disease-free survival in triple-negative breast cancer: a retrospective analysis based on a tissue microarray.

The aim of this study was to analyze the prognostic value of EGFR expression for patients with triple-negative breast cancer (TNBC). Clinical data of these patients were collected and analyzed, and immunohistochemical staining for EGFR was performed on tissue microarrays of operable breast cancer from 287 patients with TNBC, who were treated at Sun Yat-sen University Cancer Center from January 1995 to December 2008. EGFR expression was found in 36.2% of the cases with TNBC. A significant correlation was found between EGFR expression and disease-free survival (DFS). Univariated analysis indicated that EGFR expression had a significant prognostic value in TNBC patients, whereas multivariate analysis indicated that EGFR was a significant independent prognostic factor of DFS (P = 0.011) in all patients. Our results suggested that EGFR was an independent prognostic factor of DFS in patients with TNBC. Therefore, EGFR could become a good therapeutic target in the treatment of TNBC.

Classical CMF regimen as adjuvant chemotherapy for triple-negative breast cancer may be more effective compared with anthracycline or taxane-based regimens.

Patients suffering from triple-negative breast cancer (TNBC) have poor prognosis mainly because no standard treatment is currently available. Our objectives were to explore the prognostic factors for first relapse of patients with TNBC. A cohort of 687 patients with TNBC, diagnosed and treated between January 1995 and December 2008 at Sun Yat-sen University Cancer Center, were retrospectively analyzed. Cox proportional hazards models were fitted to explore factors that predict relapse development. Survival rate was computed using the Kaplan-Meier product limit method. The median age of the 687 patients was 46 (range 16-76 years), and 64.8% of the patients were pre-menopausal. The median follow-up time was 56 months (range 14-156 months), in which 194 patients had recurrence, and 115 died. The median recurrence-free time was 25 months (range 4-143 months), with 118 (60.8%) of the cases first relapsing at a single site. The three- and five-year disease-free survival rates were 79.7 and 72.6%, respectively. Primary tumor size at diagnosis, lymph node status, and type of regimen used in the (neo)adjuvant chemotherapy were considered independent predictors of first relapse. CMF-containing adjuvant chemotherapy significantly decreased recurrence compared with the anthracycline- or taxane-based regimens (RR = 0.66, 95%; CI 0.45-0.96; P = 0.030). The median time from first relapse to death was 26 months (range 2-121 months). The two- and five-year survival rates were 60.6 and 36.6%, respectively. Liver metastasis at first recurrence and progression-free survival over 12 months after first-line therapy were two important factors that affected survival rate after recurrence. The median relapse time of TNBC was about 2 years after diagnosis. CMF regimens for TNBC patients may be more effective than anthracycline- or taxane-based regimens. Liver metastasis at first recurrence signifies unfavorable prognosis.