Construct a Magnetic Pt/Ru Alloy Peroxidase Mimic As a Reusable and Cost-Effective "Signal-Off" Sensing Platform for Sensitive and Wide-Linear-Range Assay.

"Signal-off" nanozyme sensing platforms are usually employed to detect analytes (e.g., ascorbic acid (AA) and alkaline phosphatase (ALP)), which are mostly based on oxidase (OXD) nanozymes. However, their drawbacks, like dissolved oxygen-dependent catalysis capability, relatively low enzyme activity, limited amount, and kind, may not favor sensing platforms' optimization. Meanwhile, with the need for sustainable development, a reusable "signal-off" sensing platform is essential for cutting down the cost of the assay, but it is rarely developed in previous studies. Magnetic peroxidase (POD) nanozymes potentially make up the deficiencies and become reusable and better "signal-off" sensing platforms. As a proof of concept, we first construct Fe3O4@polydopamine-supported Pt/Ru alloy nanoparticles (IOP@Pt/Ru) without stabilizers. IOP@Pt/Ru shows high POD activity with Vmax of 83.24 × 10-8 M·s-1 for 3,3',5,5'-Tetramethylbenzidine (TMB) oxidation. Meanwhile, its oxidation rate for TMB is slower than the reduction of oxidized TMB by reducers, favorable for a more significant detection signal. On the other hand, IOP@Pt/Ru possesses great magnet-responsive capability, making itself be recycled and reused for at least 15-round catalysis. When applying IOP@Pt/Ru for AA (ALP) detection, it performs better detectable adaptability, with a linear range of 0.01-0.2 mM (0.1-100 U/L) and a limit of detection of 0.01 mM (0.05 U/L), superior to most of OXD nanozyme-based ALP sensing platform. Finally, IOP@Pt/Ru's reusable assay was demonstrated in real blood samples for ALP assay, which has never been explored in previous studies. Overall, this study develops a reusable "signal-off" nanozyme sensing platform with superior assay capabilities than traditional OXD nanozymes, paves a new way to optimize nanozyme-based "signal-off" sensing platforms, and provides an idea for constructing inexpensive and sustainable sensing platforms.

Effects of Talaromyces marneffei on Complete Blood Count by a Sysmex XN-9000 Analyzer.

BACKGROUND: Talaromyces marneffei (T. marneffei) infection detected in the peripheral blood smears has been described by several reports. We studied the effects of T. marneffei in peripheral blood samples on complete blood count (CBC) using a Sysmex XN-9000 analyzer. METHODS: In a simulated T. marneffei infection model, blood samples with and without infectious diseases were selected, with high, medium, and low levels of white blood cell (WBC) and platelet (PLT) count, respectively. All samples were detected immediately and after a warm bath of 37℃ for 2 hours. RESULTS: WBC count of all samples was significantly increased by T. marneffei from a certain concentration and higher. For all samples, the effect of T. marneffei on WBC count after warm bath was significantly reduced compared to that on immediate WBC count from 4 - 6 x 109/L T. Marneffei and higher (p < 0.05). The presence of T. marneffei in all blood samples did not affect the results of PLT count. For all samples, the obvious effects of T. marneffei on WBC differential (WDF) and white cell nucleated red blood cell (WNR) scatter plots were from 4 - 6 x 109 T Marneffei and higher. CONCLUSIONS: As a kind of intracellular yeast, T. marneffei may affect WBC count, NRBC count, and WBC differential count of peripheral blood samples when the yeast concentration is (4 - 6) x 109 T Marneffei and higher. Moreover, the unique scatter plot cloud on WDF and WNR scatter plots caused by T. marneffei, may become an important clue pointing toward T. marneffei in peripheral blood.

[Research progress of c-di-GMP in the regulation of Escherichia coli biofilm].

Escherichia coli biofilm is a complex membrane aggregation produced by the adhesion and secretion of extracellular polymeric substances by E. coli cells aggregated on specific media. Pathogenic E. coli will evade the immune system and the impact of various harmful factors in the environment after the formation of biofilm, causing sustained and even fatal damage to the host. Cyclic diguanosine monophosphate (c-di-GMP) is a second messenger ubiquitous in bacteria and plays a crucial role in regulating biofilm formation. This paper reviewed the recent studies about the role of c-di-GMP in the movement, adhesion, and EPS production mechanism of E. coli during biofilm formation, aiming to provide a basis for inhibiting E. coli biofilm from the perspective of c-di-GMP.

Multicenter phase II trial of Camrelizumab combined with Apatinib and Eribulin in heavily pretreated patients with advanced triple-negative breast cancer.

In the later-line setting or for patients with PD-L1-negative tumors, immunotherapy-based regimens remain ineffective against advanced triple-negative breast cancer (TNBC). In this multicentered phase II trial (NCT04303741), 46 patients with pretreated advanced TNBC were enrolled to receive camrelizumab 200 mg (day 1), and apatinib 250 mg daily, plus eribulin 1.4 mg/m2 (day 1 and 8) on a 21-day cycle until progression, or unacceptable toxicity. Primary endpoint was objective response rate (ORR) according to RECIST 1.1. Secondary endpoints included toxicities, disease control rate (DCR), clinical benefit rate, progression-free survival (PFS), and 1-year overall survival. With a median of 3 lines of prior chemotherapy in the advanced setting, 17.4% had received PD-1/PD-L1 blockade plus chemotherapy for advanced disease. The ORR was 37.0% (17/46, 95% CI 23.2-52.5). The DCR was 87.0% (40/46, 95% CI 73.7-95.1). Median PFS was 8.1 (95% CI 4.6-10.3) months. Tertiary lymphoid structure was associated with higher ORR. Patients with lower tumor PML or PLOD3 expression had favorable ORR and PFS. PD-L1 status was not associated with ORR/PFS. Grade 3/4 treatment-related adverse events occurred in 19 (41.3%) of 46 patients. Camrelizumab plus apatinib and eribulin shows promising efficacy with a measurable safety profile in patients with heavily pretreated advanced TNBC.

Non-structural proteins of bovine viral diarrhea virus.

Bovine viral diarrhea virus (BVDV) belongs to the family Flaviviridae genus pestivirus. The viral genome is a single-stranded, positive-sense RNA that encodes four structural proteins (i.e., C, Erns, E1, and E2) and eight non-structural proteins (NSPs) (i.e., Npro, p7, NS2, NS3, NS4A, NS4B, NS5A, and NS5B). Cattle infected with BVDV exhibit a number of different clinical signs including diarrhea, abortion, and other reproductive disorders which have a serious impact on the cattle industry worldwide. Research on BVDV mainly focuses on its structural protein, however, progress in understanding the functions of the NSPs of BVDV has also been made in recent decades. The knowledge gained on the BVDV non-structural proteins is helpful to more fully understand the viral replication process and the molecular mechanism of viral persistent infection. This review focuses on the functions of BVDV NSPs and provides references for the identification of BVDV, the diagnosis and prevention of Bovine viral diarrhea mucosal disease (BVD-MD), and the development of vaccines.

Recent Progress on Tick-Borne Animal Diseases of Veterinary and Public Health Significance in China.

Ticks and tick-borne diseases pose a growing threat to human and animal health, which has brought great losses to livestock production. With the continuous expansion of human activities and the development of natural resources, there are more and more opportunities for humans to contract ticks and tick-borne pathogens. Therefore, research on ticks and tick-borne diseases is of great significance. This paper reviews recent progress on tick-borne bacterial diseases, viral diseases, and parasitic diseases in China, which provides a theoretical foundation for the research of tick-borne diseases.

An on-line detection system for screening small molecule inhibitors of α-Amylase and α-Glucosidase in Prunus mume.

High-throughput screening of inhibitors from natural products is an efficient approach to target key enzymes in diabetes progression. In this study, an on-line detection system was established for the first time to rapidly screen inhibitors of α-amylase and α-glucosidase from Prunus mume. Among 28 identified compounds, 26 and 21 compounds showed strong inhibitory effect against α-amylase and α-glucosidase, respectively. Their inhibitory effects were validated by in vitro enzyme assay and fluorescence quenching which demonstrated that these inhibitors effectively interfered enzyme active sites. The inhibition kinetics suggested that chemical structures are of great importance for interfering the enzyme structures and their microenvironment polarity. Among evaluated compounds, isorhamnetin-3-O-glucoside (19) showed the strongest binding activities to α-amylase and α-glucosidase (6.34×106·nmol-1 and 6.28×106·nmol-1, respectively) by the on-line detection system. Its IC50 values were 0.16 ± 0.06 and 0.09 ± 0.01 µM against α-amylase and α-glucosidase, respectively. 19 gave a much higher Ki for α-amylase (0.1307 mM) than α-glucosidase (0.0063 mM), indicating its selectivity towards α-glucosidase. This reported method was rapid and reliable to identify prototype inhibitors against key enzymes in diabetes, and thus might serve as a general platform to screen enzyme inhibitors from natural products.

Low-Dose Anti-Angiogenic Therapy Sensitizes Breast Cancer to PD-1 Blockade.

PURPOSE: Despite its enormous successes, the overall response rate of cancer immunotherapy remains suboptimal, especially in breast cancer. There is an increased interest in combining immune checkpoint inhibitor with targeted agents to enhance antitumor effect. Anti-angiogenic drugs have been shown to synergize with immune checkpoint blockades, but the optimal setting for combining these two modalities and the underlying mechanisms of synergistic responses are not fully understood. EXPERIMENTAL DESIGN: We tested the combination of anti-PD-1 and different doses of VEGFR2-targeting agents in syngeneic breast cancer mouse models. Tumor-infiltrated immune cell subsets were profiled by flow cytometry. A cytokine array was carried out to identify inflammatory changes in different treatment conditions. The efficacy of combined anti-angiogenic and anti-PD-1 therapy was further evaluated in patients with advanced triple-negative breast cancer (TNBC). RESULTS: Blockade of VEGFR2 sensitizes breast tumors to PD-1 blockade in a dose-dependent manner. Although both conventional and low-dose anti-VEGFR2 antibody treatments normalize tumor vessels, low-dose VEGFR2 blockade results in more robust immune cell infiltration and activation and promotes the secretion of osteopontin (OPN) by CD8+ T cells. OPN subsequently induces tumor cell production of TGF-ß, which in turn upregulates PD-1 expression on immune cells. In patients with advanced TNBC, combined treatment with low-dose anti-VEGFR2 inhibitor and anti-PD-1 demonstrated excellent tolerability and efficacy. Higher OPN and TGF-ß expressions correlated with improved treatment responses. CONCLUSIONS: Together, these results demonstrate a dose-dependent synergism between anti-angiogenic therapy and immune checkpoint blockade, thus providing important insights into the optimal strategies for combining immunotherapy with molecular-targeted agents.

One injection to profile the chemical composition and dual-antioxidation activities of Rosa chinensis Jacq.

An on-line high-performance liquid chromatography-diode-array-detector-electrospray ionization-ion-trap-time-of-flight-mass spectrometry-total antioxidant capacity detection (HPLC-DAD-ESI-IT-TOF-MS-TACD) system was applied for the identification and evaluation of antioxidants in Rosa chinensis Jacq., an edible flower in food industry and a widely used traditional Chinese medicine. With the help of this platform, the HPLC fingerprint, mass fragmentations, and sample activity profiles against 1,1-diphenylpicryl-2-hydrazyl radical (DPPH•) and ferric reducing antioxidant power (FRAP) were recorded after one injection. Using this technique, 80 compounds were separated and identified by their LC/MS behaviors with the assistance of standard compounds. In addition, 11 different Rosa chinensis Jacq. samples were profiled and then quantified for their DPPH• and FRAP activities. Interestingly, a total of 52 compounds showed antioxidative effects against DPPH• and 61 were active against FRAP. The results demonstrated that the on-line system is a powerful technique for antioxidant discovery in Rosa chinensis Jacq. and other food resources.

Quantitative Analysis of Polysaccharide Composition in Polyporus umbellatus by HPLC-ESI-TOF-MS.

Polyporus umbellatus is a well-known and important medicinal fungus in Asia. Its polysaccharides possess interesting bioactivities such as antitumor, antioxidant, hepatoprotective and immunomodulatory effects. A qualitative and quantitative method has been established for the analysis of 12 monosaccharides comprising polysaccharides of Polyporus umbellatus based on high-performance liquid chromatography coupled with electrospray ionization-ion trap-time of flight-mass spectrometry. The hydrolysis conditions of the polysaccharides were optimized by orthogonal design. The results of optimized hydrolysis were as follows: neutral sugars and uronic acids 4 mol/L trifluoroacetic acid (TFA), 6 h, 120 °C; and amino sugars 3 mol/L TFA, 3 h, 100 °C. The resulting monosaccharides derivatized with 1-phenyl-3-methyl-5-pyrazolone have been well separated and analyzed by the established method. Identification of the monosaccharides was carried out by analyzing the mass spectral behaviors and chromatography characteristics of 1-phenyl-3-methyl-5-pyrazolone labeled monosaccharides. The results showed that polysaccharides in Polyporus umbellatus were composed of mannose, glucosamine, rhamnose, ribose, lyxose, erythrose, glucuronic acid, galacturonic acid, glucose, galactose, xylose, and fucose. Quantitative recoveries of these monosaccharides in the samples were in the range of 96.10-103.70%. This method is simple, accurate, and sensitive for the identification and quantification of monosaccharides, and can be applied to the quality control of Polyporusumbellatus as a natural medicine.

Comparison of breast-conserving surgery and mastectomy in early breast cancer using observational data revisited: a propensity score-matched analysis.

Recent observational studies showed that breast-conserving surgery (BCS) resulted in superior survival compared to mastectomy in breast cancer patients. This study compared the clinical outcomes of BCS and mastectomy using propensity score (PS) matching analysis, which had advantages over conventional methods in reducing bias. Nonmetastatic breast cancer patients who underwent BCS and mastectomy were matched 1:1 based on their PS. We used the Kaplan-Meier method and Cox-regression model to estimate the treatment effects. A total of 2,866 patients with a median follow-up time of 67 months were included in the original study population. Although the mastectomy cohort (N=1,219) had more advanced disease compared to the BCS cohort (N=1,647), LRFS was similar between the two groups (93.8% vs. 92.4%, P>0.05). BCS (vs. mastectomy) was associated with improved DFS (73.8% vs. 58.7%, P<0.01) and CSS (91% vs. 78.2%, P<0.01) in the original population. In the PS-matched population (N=1,668), clinicopathological features were equally distributed between the two cohorts. BCS (vs. mastectomy) was not associated with improved DFS (70.7% vs. 66.9%, P>0.05) or CSS (87.5% vs. 84.9%, P>0.05). We found that PS methods reduce bias when estimating treatment effects using observational data. BCS and mastectomy show equivalent outcomes in nonmetastatic breast cancer patients.

Impact of a 21-Gene Recurrence Score Test on the Choice of Adjuvant Chemotherapy for Hormone Receptor-positive Early-stage Breast Cancer: A Prospective Study.

BACKGROUND: Studies have recommended a 21-gene recurrence score (RS) to optimize adjuvant treatment for patients with early-stage breast cancer (EBC) with hormone receptor-positive (HR+) and human epidermal growth factor receptor-2 negative (HER2-) tumors. This study aimed to prospectively evaluate the impact of this RS in Chinese patients with breast cancer. PATIENTS AND METHODS: We prospectively collected 227 patients with EBC with estrogen receptor-positive (ER+) and HER2- tumors. We used one-way analysis of variance to compare the distribution of different risk groups based on a 21-gene RS assay. A Kruskal-Wallis test and either a chi-square or Fisher's exact test were used as appropriate to compare continuous and categorical variables, respectively. RESULTS: Of the 227 eligible women enrolled, 61.2%, 30%, and 8.8% of patients were in the low (≤17), intermediate (18-30) and high (≥31) RS groups, respectively. Of the patients with a low RS, 74.8% were overestimated into the intermediate-risk group by St. Gallen risk. The overall impact of the 21-gene RS was reduced use of chemotherapy (78/227, 34.4%). In addition, Ki67 expression was positively associated with the 21-gene RS (R=0.68). CONCLUSION: Among patients with ER+/HER2- EBC, the 21-gene RS was an effective method for making a chemotherapy decision. Ki67 was associated with 21-gene RS.

Prospective comparison of Sapylin and Avitene for reducing hydrops after axillary lymphadenectomy in breast cancer patients.

BACKGROUND: This study compared the efficacy of Sapylin and Avitene in reducing postoperative axillary seroma formation and effusion when applied topically after axillary lymphadenectomy. METHODS: A total of 224 patients were randomly divided into a Sapylin treatment group (STG), an Avitene treatment group, and a control group (CG). All patients underwent axillary lymphadenectomy and were treated during surgery with Sapylin, Avitene, or neither according to their group assignment. The duration and amount of postoperative drainage, as well as the occurrence of seromas were recorded. Outcomes were compared by one-way analysis of variance and chi-square tests. RESULTS: Baseline patient data, including age, body mass index, history of neoadjuvant chemotherapy, type of surgery, number of resected lymph nodes, and number of positive metastases did not differ among the three groups. Patients in both the STG and the Avitene treatment group experienced significantly fewer days of drainage than those in the CG; there was no significant difference in drainage tube retention time between the two treated groups. The STG experienced significantly less drainage volume than the CG. Fewer patients in both treatment groups required seroma treatment or experienced complications compared with CG patients. CONCLUSIONS: Both Sapylin and Avitene effectively reduced postoperative subcutaneous fluid accumulation after axillary lymphadenectomy. These treatments may be particularly useful for breast cancer patients at high risk of seroma formation, especially those with hypertension, diabetes mellitus, or a high body mass index who undergo axillary lymphadenectomy.

Prognostic significance of Ki67 in Chinese women diagnosed with ER+/HER2- breast cancers by the 2015 St. Gallen consensus classification.

BACKGROUND: This study evaluated the distribution pattern of the Ki67-labeling index (LI) among patients at a Chinese breast cancer center, and analyzed its prognostic significance in the 2015 St Gallen consensus breast cancer classification, estrogen receptor-positive and human epidermal growth factor receptor 2-negative(ER+/HER2-)subtype. METHODS: We classified 939 women with ER+/HER2- breast cancer into three groups by Ki67-LI levels, and followed their clinicopathologic characteristics and prognoses. RESULTS: In the 939 eligible subjects, 342 had Ki67-LI ≤10% (Ki67Low), 281 had Ki67-LI between 10 and 30% (Ki67Medium), and 316 had Ki67-LI ≥30% (Ki67High). Although the Ki67High group had less favorable clinicopathologic factors, the Ki67Medium group's factors varied considerably. Kaplan-Meier estimates showed that disease-free survival(DFS) for the Ki67Medium group was significantly shorter than the Ki67Low group but longer than the Ki67High group. Ki67-LI had independent prognostic significance in multivariate analysis. Other diagnostic factors, including tumor size >2 cm, positive lymph nodes, and grade III disease, were significantly associated with poorer disease-free survival only in the Ki67Medium group. CONCLUSIONS: For patients with ER+/HER2- breast cancer, we confirmed three distinct risk patterns by Ki67-LI levels according to the 2015 St Gallen consensus. For patients with clearly low or high Ki67-LI, straightforward clinical decisions could be offered, but for patients with intermediate Ki67-LI, other factors might provide valuable information.

Comparison of the Therapeutic Efficacy of the Early and the Delayed Use of Vinorelbine-Based Regimens for Patients with Advanced Breast Cancer.

BACKGROUND: The aim of this study was to evaluate the efficacy of vinorelbine-based regimens as first-, second- and more-line therapies in advanced breast cancer (ABC) and to analyze the best timing of vinorelbine treatment. METHODS: A total of 71 ABC patients were retrospectively reviewed. Of these, 35 patients were treated with vinorelbine-based regimens as first-line chemotherapy, and 36 patients were treated with vinorelbine-based regimens as second-line or more-line therapy. The primary end point of the study was progression-free survival (PFS). RESULTS: No difference was found in baseline characteristics between the two groups (p > 0.1 for all comparisons). There was a significant difference in the objective response rate (ORR; p = 0.006) and clinical benefit rate (CBR; p = 0.013) between the first-line group and the second- or more-line groups. In the vinorelbine first-line group, the ORR was 68.6% (24 patients), and in the second-line or more-line groups the ORR was 36.1% (13 patients). A significant difference in PFS between the first-line group and the second-line or more-line groups was also observed (p = 0.030). The median PFS in the overall population was 6.3 ± 1.32 months (95% CI 3.69-8.90). The median PFS was 11.1 ± 3.76 months (95% CI 3.73-18.47) in the first-line group compared with 5.2 ± 1.35 months (95% CI 2.54-7.85) in the second-line or more-line groups. In patients treated with vinorelbine-trastuzumab combination as the first-line therapy, a complete response was observed in 1 patient (12.5%) and partial response in 5 patients (62.5%), giving an ORR of 75.0%. Progressive disease was observed in 1 patient (12.5%), and stable disease in 1 patient (12.5%), leading to a CBR of 87.5%. The median PFS was 13.8 ± 2.75 months (95% CI 8.42-19.18), and median OS was 37.0 ± 11.6 months (95% CI 14.18-59.82). No significant difference was found in overall survival (OS) between the groups (p = 0.612). CONCLUSION: For ABC patients, no significant difference in median OS was found between the early use and delayed use of vinorelbine-based regimens, but the short-term efficacy and PFS of vinorelbine-based regimens were significantly better in the early use group than in the delayed use group.

A combination of Nottingham prognostic index and IHC4 score predicts pathological complete response of neoadjuvant chemotherapy in estrogen receptor positive breast cancer.

Pathologic complete response (pCR) prediction after neoadjuvant chemotherapy (NAC) is important for clinical decision-making in breast cancer. This study investigated the predictive value of Nottingham prognostic index (NPI), Immunohistochemical four (IHC4) score and a new predictive index combined with them in estrogen-positive (ER+) breast cancer following NAC. We retrospectively gathered clinical data of 739 ER+ breast cancer patients who received NAC from two cancer centers. We developed a new predictive biomarker named NPI+IHC4 to predict pCR in ER+ breast cancer in a training set (n=443) and validated it in an external validation set (n=296). The results showed that a lower IHC4 score, NPI and NPI+IHC4 were significantly associated a high pCR rate in the entire cohort. In the study set, NPI+IHC4 showed a better sensitivity and specificity for pCR prediction (AUC 0.699, 95% CI 0.626-0.772) than IHC4 score (AUC 0.613, 95% CI 0.533-0.692), NPI (AUC 0.576, 95% CI 0.494-0.659), tumor size (AUC 0.556, 95% CI 0.481-0.631) and TNM stage (AUC 0.521, 95% CI 0.442-0.601). In the validation set, NPI+IHC4 had a better predictive value for pCR (AUC 0.665, 95% CI 0.579-0.751) than IHC4 score or NPI alone. In addition, ER+ patients with lower IHC4, NPI and NPI+IHC4 scores had significantly better DFS in both study and validation sets. In summary, NPI+IHC4 can predict pCR following NAC and prognosis in ER+ breast cancer, which is cost-effect and potentially more useful in guiding decision-making regarding NAC in clinical practice. Further validation is needed in prospective clinical trials with larger cohorts of patients.

Phosphoinositide-3-Kinase Enhancers, PIKEs: Their Biological Functions and Roles in Cancer.

Phosphoinositide 3-kinase enhancer (PIKE) belongs to a family of GTP-binding proteins, including three isoforms, PIKE-S, PIKE-L and PIKE-A. PIKE-S and PIKE-L interact with PI3K to enhance the activity of PI3K, but PIKE-A directly binds to AKT and up-regulates its activity. PIKEs also interacts with a variety of signaling molecules in addition to PI3K and AKT, to trigger multiple physiological functions. Overexpression or mutation of PIKE has been observed in a variety of tumors, especially PIKE-A, which acts as a proto-oncogene, promoting cancer cell growth, transformation and invasion through AKT signaling. Knockdown of PIKE-A or blocking of PIKE-A/AKT interactions enhances apoptosis, inhibits cancer cell proliferation, migration and invasion. Moreover, PIKE plays an important role in tumorigenesis through other signaling pathways, such as focal adhesion kinase, signal transducer and activator of transcription 5A, and nuclear factor kappa-light-chain-enhancer of activated B cells. The current review explores the functional role of PIKE and its potential in cancer therapy.

The Peripheral Blood Neutrophil-To-Lymphocyte Ratio Is Superior to the Lymphocyte-To-Monocyte Ratio for Predicting the Long-Term Survival of Triple-Negative Breast Cancer Patients.

PURPOSE: The peripheral hematologic parameters of patients can be prognostic for many malignant tumors, including breast cancer, although their value has not been investigated among the different molecular subtypes of breast cancer. The purpose of this study was to examine the prognostic significance of the neutrophil-to-lymphocyte ratio (NLR) and the lymphocyte-to-monocyte ratio (LMR) in different molecular subtypes of breast cancer. METHODS: A retrospective cohort of 1570 operable breast cancer patients was recruited between January 2000 and December 2010. The counts of peripheral neutrophils, lymphocytes, monocytes and platelets were collected and applied to calculate the NLR and the LMR. Univariate and multivariate Cox proportional hazard analyses were used to assess the relationship of the NLR and the LMR with disease-free survival (DFS) and overall survival (OS) in all patients and triple negative breast cancer (TNBC) patients. RESULTS: Univariate analysis revealed that lower NLR (≤2.0) and higher LMR (>4.8) were significantly associated with superior DFS in all patients (NLR, P = 0.005; LMR, P = 0.041) and in TNBC patients (NLR, p = 0.007; LMR, P = 0.011). However, multivariate analysis revealed that only lower NLR was a significant independent predictor of superior DFS and OS in all breast cancer patients (DFS, HR = 1.50 95% CI: 1.14-1.97, P = 0.004; OS, HR = 1.63, 95% CI: 1.07-2.49, P = 0.022) and in TNBC patients (DFS, HR = 2.58, 95% CI: 1.23-5.42, P = 0.012; OS, HR = 3.05, 95% CI: 1.08-8.61, P = 0.035). Both univariate and multivariate analysis revealed that neither the NLR nor the LMR significantly predicted DFS and OS among the patients with other molecular subtypes of breast cancer. CONCLUSIONS: A higher pretreatment peripheral NLR significantly and independently indicated a poor prognosis for breast cancer and TNBC, and this measurement exhibited greater prognostic value than a lower LMR. The NLR was not a prognostic factor for other breast cancer subtypes.

Reduced Let-7a Is Associated with Chemoresistance in Primary Breast Cancer.

Chemotherapy resistance remains an important problem in the breast cancer clinic. The ability to predict the patients who would respond to a distinct therapy would help to optimize tailored treatment options. miRNAs can mediate a number of genes in response to drug-induced acute cellular stress. Several studies suggest that let-7 miRNA may be involved in the chemosensitivity of cancer cell lines in vitro. However, it is not known whether this phenomenon occurs in clinical breast tumors. The present study showed that lower let-7a expression was associated with epirubicin resistance in primary breast tumors. Moreover, upregulation of let-7a expression sensitized resistant breast tumor cell lines to epirubicin by enhancing cellular apoptosis in vitro. Collectively, these findings indicate that lower expression of let-7a miRNA can induce chemoresistance in breast cancer by enhancing cellular apoptosis and suggest that let-7a may be used as a therapeutic target to modulate epirubicin-based chemotherapy resistance.

HER-2 positive breast cancer is associated with an increased risk of positive cavity margins after initial lumpectomy.

BACKGROUND: The effect of breast cancer subtype on margin status after lumpectomy remains unclear. This study aims to determine whether approximated breast cancer subtype is associated with positive margins after lumpectomy, which could be used to determine if there is an increased risk of developing local recurrence (LR) following breast-conserving surgery. METHODS: We studied 1,032 consecutive patients with invasive cancer who received lumpectomies and cavity margin (CM) assessments from January 2003 to November 2012. The following data were collected: patient age, cT stage, pT stage, grade, status of CM, lymph node status, menopausal status, ER, PR, HER-2, and Ki67, as well as the presence of extensive intraductal component (EIC) and lymphovascular invasion (LVI). A χ2 test was used to compare categorical baseline characteristics. Univariate and multivariate logistic regression analyses were performed to evaluate associations between pathologic features of CM status. Kaplan-Meier actuarial cumulative rates of LR (ipsilateral in-breast) were calculated. RESULTS: A total of 7,884 pieces of marginal tissue were collected from 1,032 patients, and 209 patients had positive CMs. Of the patients tested, 52.3% had luminal A subtype, 14.9% were luminal B, 12.8% were luminal-HER-2, 8.1% were HER-2 enriched, and 11.8% were triple negative. Univariate analysis showed that EIC (P < 0.001), LVI (P = 0.026), pN stage (N1 vs. N0: P = 0.018; N3 vs. N0: P < 0.001), and luminal B (P = 0.001) and HER-2 (P < 0.001) subtypes were associated with positive CMs. Multivariable analysis indicated that only EIC (P < 0.001), pN stage (P = 0.003), and HER-2 subtype (P < 0.001) were significantly correlated with positive CMs. On multivariable analysis, HER-2 subtype was an independent prognostic factor in LR (P = 0.031). CONCLUSIONS: The HER-2 subtype was the predictive factor most associated with positive CMs and an independent prognostic factor for LR. This result suggests that the increased risk of LR in HER-2 breast cancer is due to an increased microscopic invasive tumor burden, which is indicated by margin status after lumpectomy.