Towards precision medicine based on a continuous deep learning optimization and ensemble approach.

We developed a continuous learning system (CLS) based on deep learning and optimization and ensemble approach, and conducted a retrospective data simulated prospective study using ultrasound images of breast masses for precise diagnoses. We extracted 629 breast masses and 2235 images from 561 cases in the institution to train the model in six stages to diagnose benign and malignant tumors, pathological types, and diseases. We randomly selected 180 out of 3098 cases from two external institutions. The CLS was tested with seven independent datasets and compared with 21 physicians, and the system's diagnostic ability exceeded 20 physicians by training stage six. The optimal integrated method we developed is expected accurately diagnose breast masses. This method can also be extended to the intelligent diagnosis of masses in other organs. Overall, our findings have potential value in further promoting the application of AI diagnosis in precision medicine.

Value of Contrast-Enhanced Ultrasound in Differentiating Clinically Atypical Subacute Thyroiditis from Papillary Thyroid Carcinomas.

Our objective was to provide the various sonographic characteristics of clinically atypical subacute thyroiditis (CAST) in distinguishing CAST from papillary thyroid carcinomas (PTCs) by using conventional ultrasound (US) and contrast-enhanced ultrasound (CEUS). Forty-six CAST patients and 50 PTC patients were enrolled in this study. We evaluated the size, shape, margin, echogenicity, calcification, vascularity and CEUS parameters for each nodule. The final diagnosis of CAST was confirmed via fine-needle aspiration (FNA) or surgery. Of the 46 CASTs, 13 (28.3%) were confirmed by surgery to be benign, and 33 (71.7%) were proven by FNA to be benign. Univariate analysis indicated that compared with PTCs, CAST lesions more frequently had wider-than-taller shapes, blurred margins, the absence of microcalcifications, peripheral high echogenicity, the absence of internal vascularity, hypo-enhancement, centrifugal perfusion and a peak intensity index <1 and area under the curve index <1 on pre-operative US and CEUS. A multivariate analysis revealed that clear margins, microcalcifications and centripetal perfusion were independent characteristics related to PTCs for their differentiation from CAST (all p values <0.05). Our study indicated that the pre-operative multiparameter US characteristics may serve as a useful tool for distinguishing CAST from malignant thyroid nodules to avoid surgical excisions or unnecessary FNAs.

Sonographic Characteristics of Papillary Thyroid Carcinoma With Coexistent Hashimoto's Thyroiditis in the Preoperative Prediction of Central Lymph Node Metastasis.

The purpose of this study was to evaluate the usefulness of the sonographic characteristics of papillary thyroid carcinoma (PTC) with Hashimoto's thyroiditis (HT) for predicting central lymph node metastasis (CLNM). One hundred thirty-three patients who underwent thyroidectomy and central cervical lymph node dissection for PTC with coexistent HT were retrospectively analyzed. All PTCs with HT were preoperatively evaluated by ultrasound (US) regarding their nodular number, size, component, shape, margin, echogenicity, calcification, capsule contact with protrusion, vascularity and contrast enhanced ultrasound (CEUS) parameters. Univariate analysis demonstrated that patients with PTCs with HT and CLNM more frequently had age ≤ 45 years, size > 10 mm, a wider than tall shape, microcalcification, hypo-enhancement and peak intensity index < 1 than those without CLNM (all p<0.05). Binary logistic regression analysis demonstrated that size > 10 mm and CEUS hypo-enhancement were independent characteristics for the presence of CLNM. Our study indicated that preoperative US characteristics could offer help in predicting CLNM in PTCs with coexistent HT.

Behavioral, Histopathologic, and Molecular Biological Responses of Nanoparticle- and Solution-Based Formulations of Vincristine in Mice.

Clinical use of the chemotherapeutic agent vincristine (VCR) is limited by chemotherapy-induced peripheral neuropathy (CiPN). A new formulation of VCR encapsulated by nanoparticles has been proposed and developed to alleviate CiPN. We hypothesized in nonclinical animals that the nanoparticle drug would be less neurotoxic due to different absorption and distribution properties to the peripheral nerve from the unencapsulated free drug. Here, we assessed whether VCR encapsulation in nanoparticles alleviates CiPN using behavioral gait analysis (CatWalk), histopathologic and molecular biological (RT-qPCR) approaches. Adult male C57BL/6 mice were assigned to 3 groups (empty nanoparticle, nano-VCR, solution-based VCR, each n = 8). After 15 days of dosing, animals were euthanized for tissue collection. It was shown that intraperitoneal administration of nano-VCR (0.15 mg/kg, every other day) and the empty nanoparticle resulted in no changes in gait parameters; whereas, injection of solution-based VCR resulted in decreased run speed and increased step cycle and stance (P < 0.05). There were no differences in incidence and severity of degeneration in the sciatic nerves between the nano-VCR-dosed and solution-based VCR-dosed animals. Likewise, decreased levels of a nervous tissue-enriched microRNA-183 in circulating blood did not show a significant difference between the nano- and solution-based VCR groups (P > 0.05). Empty nanoparticle administration did not cause any behavioral, microRNA, or structural changes. In conclusion, this study suggests that the nano-VCR formulation may alleviate behavioral changes in CiPN, but it does not improve the structural changes of CiPN in peripheral nerve. Nanoparticle properties may need to be optimized to improve biological observations.

Contrast-Enhanced Ultrasound of Primary Squamous Cell Carcinoma of the Thyroid: A Case Report.

Introduction: Primary squamous cell carcinoma of the thyroid (ThyPSCC) is an extremely rare aggressive malignancy with a poor prognosis. However, almost no report thus far has investigated the microvasculature of ThyPSCC imaged using contrast-enhanced ultrasound. Case Report: A 59-year-old male patient presented to our hospital with progressively worsening hoarse voice symptoms for 20 days and was diagnosed with left unilateral vocal fold palsy. Ultrasonography revealed a solitary marked hypoechoic thyroid nodule with an unclear boundary in the inferior part of the left lobe. Color Doppler flow imaging showed a poor blood flow signal inside this nodule. Contrast-enhanced ultrasound images showed a persistent low peak enhancement of the nodule from its periphery to its center. The time-intensity curve displayed a wash-in time of 10 s, a time to peak of 37 s, a peak signal intensity of 24.5%, and a wash-out time of 70 s for the thyroid tumor. Finally, left hemithyroidectomy of the thyroid tumor was performed, and histopathologic and immunohistochemical evaluations confirmed the diagnosis of ThyPSCC. Postoperatively, the patient received a combination therapy of chemotherapy, radiotherapy, and targeted therapy, but the patient died 4 months after surgery. Conclusion: Primary squamous cell carcinoma of the thyroid is a rare but aggressive malignancy of the thyroid. Herein, we reported a case of ThyPSCC and its ultrasonography and pathologic findings.

Petal-Like Calcifications in Thyroid Nodules on Ultrasonography: A Rare Morphologic Characteristic of Calcification Associated With Aggressive Biological Behavior.

This study investigated a rare ultrasonographically detected thyroid petal-like calcification and its relationship with thyroid carcinoma and biological behavior. We described the clinical and ultrasonographical features of thyroid nodules with petal-like calcifications in 18 patients undergoing thyroid surgery and cervical lymph node dissection. All of the thyroid nodules with petal-like calcifications were papillary thyroid carcinomas (PTCs). Of the 18 patients, 13 (72.2%) had cervical central lymph node metastasis, and five (27.8%) had cervical lateral lymph node metastasis. Petal-like calcifications occurred in malignant thyroid nodules with a high incidence of lymph node metastasis, which may be a specific ultrasonographic feature associated with the aggressive biological behavior of PTC.

Circulating microRNA and automated motion analysis as novel methods of assessing chemotherapy-induced peripheral neuropathy in mice.

Chemotherapy-induced peripheral neuropathy (CiPN) is a serious adverse effect in the clinic, but nonclinical assessment methods in animal studies are limited to labor intensive behavioral tests or semi-quantitative microscopic evaluation. Hence, microRNA (miRNA) biomarkers and automated in-life behavioral tracking were assessed for their utility as non-invasive methods. To address the lack of diagnostic biomarkers, we explored miR-124, miR-183 and miR-338 in a CiPN model induced by paclitaxel, a well-known neurotoxic agent. In addition, conventional and Vium's innovative Digital Vivarium technology-based in-life behavioral tests and postmortem microscopic examination of the dorsal root ganglion (DRG) and the sciatic nerve were performed. Terminal blood was collected on days 8 or 16, after 20 mg/kg paclitaxel was administered every other day for total of 4 or 7 doses, respectively, for plasma miRNA quantification by RT-qPCR. DRG and sciatic nerve samples were collected from mice sacrificed on day 16 for miRNA quantification. Among the three miRNAs analyzed, only miR-124 was statistically significantly increased (5 fold and 10 fold on day 8 and day 16, respectively). The increase in circulating miR-124 correlated with cold allodynia and axonal degeneration in both DRG and sciatic nerve. Automated home cage motion analysis revealed for the first time that nighttime motion was significantly decreased (P < 0.05) in paclitaxel-dosed animals. Although both increase in circulating miR-124 and decrease in nighttime motion are compelling, our results provide positive evidence warranting further testing using additional peripheral nerve toxicants and diverse experimental CiPN models.

Sonographic Characteristics of Papillary Thyroid Carcinoma with Coexistent Hashimoto's Thyroiditis: Conventional Ultrasound, Acoustic Radiation Force Impulse Imaging and Contrast-Enhanced Ultrasound.

Our objective was to provide the various sonographic characteristics of papillary thyroid carcinomas for Hashimoto's thyroiditis (HT) patients, including conventional ultrasound (US), acoustic radiation force impulse Virtual Touch imaging and quantification (ARFI-VTIQ) and contrast-enhanced ultrasound (CEUS). Sixty-nine HT patients with 85 thyroid nodules (TNs) (49 malignant and 36 benign) were enrolled in this study. We evaluated the size, shape, margin, echogenicity, presence of halo, calcification, vascularity and ARFI-VTIQ and CEUS parameters for each nodule and compared the findings with the reference standards of histopathological and/or cytologic results. Univariate analysis indicated that compared with benign TNs with HT, papillary thyroid carcinomas with HT more often had taller-than-wider shapes, ill-defined margins, microcalcifications, peripheral vascularity, relatively harder stiffness with a higher shear wave speed, hypo-enhancement, peak intensity index <1 and area under the curve index <1 at pre-operative US, ARFI-VTIQ and CEUS. Multivariate analysis revealed that ill-defined margins, microcalcifications and peak intensity index <1 are independent characteristics related to malignant TNs for their differentiation from benign TNs (all p < 0.05). Our study indicated that pre-operative multiparameter US characteristics may serve as a useful tool to identify malignant TNs in HT patients.

Mummified Thyroid Nodules: Conventional and Contrast-Enhanced Ultrasound Features.

OBJECTIVES: The purpose of our study was to highlight the conventional and contrast-enhanced ultrasound (US) features of mummified thyroid nodules, which should help differentiate them from histologically proven papillary thyroid carcinomas (PTCs). METHODS: Thirty-one patients with 33 mummified thyroid nodules, which showed suspicious US findings that were suggestive of malignancy, as well as 33 patients with 38 surgically confirmed PTCs were enrolled in this study. We evaluated the size, shape, margin, echogenicity, presence of shadowing and halo, presence of punctate echogenic foci, vascularity, and contrast enhancement parameters for each nodule. The final diagnosis of mummified thyroid nodules was confirmed via fine-needle aspiration (FNA) or surgery. RESULTS: Of the 33 mummified thyroid nodules, 9 (27.3%) were confirmed by surgery to be benign, and 24 (72.7%) were proven by FNA to be benign. A univariate analysis indicated that the mummified thyroid nodules more frequently showed wider-than-tall shapes, marked hypoechogenicity, the presence of posterior shadowing, the absence of nodular vascularity, hypoenhancement or no enhancement, and peak index and area under the curve indices of less than 1 in the findings of preoperative US and contrast-enhanced US compared to PTCs. A multivariate analysis showed that marked hypoechogenicity and an area under the curve index of less than 1 were independent characteristics related to mummified nodules for discriminating from PTCs (all P < .05). CONCLUSIONS: Benign thyroid nodules may display shrinkage over time and may reveal malignant US features. Awareness of these findings and their connection with initial and follow-up US examinations should help identify mummified thyroid nodules and to avoid surgical excision or unnecessary FNA.

Contrast-enhanced ultrasound of small cell carcinoma in urinary bladder: a case report and review of literature.

BACKGROUND: Small cell carcinoma of the urinary bladder (SCCB) is a relatively rare malignant bladder tumor, and few reports have investigated the microvasculature of SCCB imaged using contrast-enhanced ultrasound (CEUS). CASE PRESENTATION: A 63-year-old female was admitted to our hospital after experiencing painless gross hematuria for one week. The gray-scale ultrasound (US) demonstrated a 4.8 × 3.4 × 3.6-cm3 hypoechoic mass in the apex of the urinary bladder with a wide base and an irregular surface; the mass did not move with changes in body position. Color Doppler flow imaging (CDFI) showed rich blood flow in the mass. CEUS with low mechanical index (MI) of 0.06 confirmed a highly enhanced 5.0 × 3.3 × 3.8 cm3 mass within the bladder at the apex wall. The time-intensity curves (TICs) showed a wash-in time of 10 s, a time to peak (TTP) of 33 s, a signal intensity (SI) of 62.7% and a wash-out time > 60 s. Finally, the transurethral resection of the bladder tumor (TURBT) was performed, and the pathological examination proved the diagnosis of SCCB. CONCLUSION: CEUS can provide valuable information related to the rich microvasculature of SCCB, which may be helpful in its diagnosis.

Near-infrared induced phase-shifted ICG/Fe3O4 loaded PLGA nanoparticles for photothermal tumor ablation.

Near-infrared (NIR) laser-induced photothermal therapy (PTT) uses a photothermal agent to convert optical energy into thermal energy and has great potential as an effective local, minimally invasive treatment modality for killing cancer cells. To improve the efficacy of PTT, we developed poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) encapsulating superparamagnetic iron oxide (Fe3O4), indocyanine green (ICG), and perfluoropentane (PFP) as synergistic agents for NIR laser-induced PTT. We fabricated a novel type of phase-shifting fluorescent magnetic NPs, Fe3O4/ICG@PLGA/PFP NPs, that effectively produce heat in response to NIR laser irradiation for an enhanced thermal ablation effect and a phase-shift thermoelastic expansion effect, and thus, can be used as a photothermal agent. After in vitro treatment of MCF-7 breast cancer cells with Fe3O4/ICG@PLGA/PFP NPs and NIR laser irradiation, histology and electron microscopy confirmed severe damage to the cells and the formation of many microbubbles with iron particles at the edge or outside of the microbubbles. In vivo experiments in mice with MCF-7 tumors demonstrated that Fe3O4/ICG@PLGA/PFP NPs could achieve tumor ablation upon NIR laser irradiation with minimal toxicity to non-irradiated tissues. Together, our results indicate that Fe3O4/ICG@PLGA/PFP NPs can be used as effective nanotheranostic agents for tumor ablation.

Laser irradiated fluorescent perfluorocarbon microparticles in 2-D and 3-D breast cancer cell models.

Perfluorocarbon (PFC) droplets were studied as new generation ultrasound contrast agents via acoustic or optical droplet vaporization (ADV or ODV). Little is known about the ODV irradiated vaporization mechanisms of PFC-microparticle complexs and the stability of the new bubbles produced. In this study, fluorescent perfluorohexane (PFH) poly(lactic-co-glycolic acid) (PLGA) particles were used as a model to study the process of particle vaporization and bubble stability following excitation in two-dimensional (2-D) and three-dimensional (3-D) cell models. We observed localization of the fluorescent agent on the microparticle coating material initially and after vaporization under fluorescence microscopy. Furthermore, the stability and growth dynamics of the newly created bubbles were observed for 11 min following vaporization. The particles were co-cultured with 2-D cells to form 3-D spheroids and could be vaporized even when encapsulated within the spheroids via laser irradiation, which provides an effective basis for further work.

Clinical literature review of 1858 Crohn's disease cases requiring surgery in China.

AIM: To summarize the clinical characteristics of Crohn's disease (CD) patients who underwent surgery in China. METHODS: We searched four main Chinese electronic databases: CBM, VIP, CNKI, and Wanfang (from January 1990 to October 2013). Then, we selected and carefully read 97 studies and extracted the surgical data for CD. We found that 1858 patients with CD underwent surgery between 1961 and 2012. The patients were stratified into two groups according to the year of surgery: 1961-2000 and 2000-2012. The clinical characteristics of these CD cases were compared between the two groups. RESULTS: The mean age at the time of surgery was 38.13 years. The most common locations of disease were the small intestine (40.84%), the colon (33.60%) and the ileocolon (23.09%). The primary indications for surgery were intestinal obstruction or stricture (23.84%), failure of drug therapy (14.80%), acute abdominal disease (13.46%), abdominal mass (10.93%), intestinal fistulae (9.90%), intestinal perforation (8.45%), perianal disease (6.73%), gastrointestinal bleeding (4.79%), and abdominal abscess (4.04%). The rate of diagnosis of CD before surgery was low (34.78%), and the misdiagnosis rate was 20.49%. The predominant surgical procedure for CD was bowel resection (69.54%). The rate of surgical complications was 20.34%, and the primary complications of surgery were infection (39.44%) and intestinal fistulae (26.09%). The relapse rate after surgery was 27.71%. For the periods of 1961-2000 and 2000-2013, the rates of both misdiagnosis before surgery and surgery related-death decreased (34.90% vs 12.10%, P < 0.001, and 23.53% vs 5.26%, P < 0.001, respectively). CONCLUSION: The rates of surgical complications and misdiagnosis were higher, whereas the rate of CD-associated tumor and the relapse rate were lower in China than in West countries.

Echocardiographic follow-up and pregnancy outcome of fetuses with cardiac asymmetry at 18-22 weeks of gestation.

OBJECTIVE: The goal of our study was to evaluate the evolution of cardiac findings and assess the pregnancy outcome of fetuses with cardiac asymmetry at midgestation. METHODS: We reviewed all fetuses with cardiac asymmetry at echocardiograms performed at 18-22 weeks of gestation from 2006 to 2013. The data collected included the gestational age at diagnosis, serial echocardiographic findings, karyotype testing, and pregnancy outcome. Excluded were cases of classical hypoplastic left heart syndrome (HLHS) at initial echocardiogram (i.e., aortic (AO) and/or mitral atresia or dysplasia with normal intracardiac connections), heterotaxy syndrome, twin pregnancy, fetal growth restriction, and coarctation of the aorta. RESULTS: Our study included 278 fetuses with cardiac asymmetry (defined as Z-scores of left ventricle length or diameter of less than -2). A total of 202 (72%) fetuses had normal variations in cardiac growth by prenatal and neonatal echocardiography, 69 (25%) fetuses were confirmed to have HLHS variant by autopsy or neonatal echocardiography (with an overall survival of 4.3%), and seven (3%) fetuses were terminated before 24 weeks of gestation because of abnormal karyotypes. None of the cardiac measurements at the initial echocardiogram was significantly different between HLHS variant and normal cases. In the 69 fetuses ultimately diagnosed with HLHS variant, but not in the 202 normals, the Z-scores of all measured left heart structures decreased progressively between the first and the last prenatal echocardiograms (P < 0.01). CONCLUSIONS: The majority of the fetuses with cardiac asymmetry at 18-22 weeks have a good outcome. A minority of them progress to develop HLHS variant with advancing gestation.

Increased hepatic stiffness as consequence of high hepatic afterload in the Fontan circulation: a vascular Doppler and elastography study.

UNLABELLED: Hepatic dysfunction is a recognized complication after Fontan palliation of congenital heart disease. We sought to quantitatively measure hepatic stiffness and vascular Doppler indices using ultrasound (US) and shear wave elastography (SWE) in a Fontan cohort. Subjects were prospectively recruited for echocardiography and real-time hepatic duplex US with SWE for hepatic stiffness (kPa). Doppler peak velocities, velocity time integral, resistive, pulsatility, acceleration indices (RI, PI, AI), and flow volume were measured in celiac artery, superior mesenteric artery, and main portal vein (MPV). A subset underwent cardiac catheterizations with liver biopsy. Correlations were explored between SWE, duplex, hemodynamic, and histopathologic data. In all, 106 subjects were studied including 41 patients with Fontan physiology (age 13.8 ± 6 years, weight 45.4 ± 23 kg) and 65 controls (age 15.0 ± 8.4 years, weight 47.9 ± 22 kg). Patients with Fontan physiology had significantly higher hepatic stiffness (15.6 versus 5.5 kPa, P < 0.0001), higher celiac RI (0.78 versus 0.73, P = 0.04) superior mesenteric artery RI (0.89 versus 0.84, P = 0.005), and celiac PI (1.87 versus 1.6, P = 0.034); while MPV flow volume (287 versus 420 mL/min in controls, P = 0.007) and SMA AI (829 versus 1100, P = 0.002) were lower. Significant correlation was seen for stiffness with ventricular end-diastolic pressure (P = 0.001) and pulmonary artery wedge pressure (P = 0.009). Greater stiffness correlated with greater degrees of histopathologic fibrosis. No significant change was seen in stiffness or other duplex indices with age, gender, time since Fontan, or ventricular morphology. CONCLUSION: Elevated hepatic afterload in Fontan, manifested by high ventricular end-diastolic pressures and pulmonary arterial wedge pressures, is associated with remarkably increased hepatic stiffness, abnormal vascular flow patterns, and fibrotic histologic changes. The MPV is dilated and carries decreased flow volume, while the celiac and superior mesenteric arterial RI is increased. SWE is feasible in this population and shows promise as a means for predicting disease severity on liver biopsy.

Echocardiographic measurement methods for left ventricular linear dimensions in children result in predictable variations in results.

Precise quantification of left ventricular (LV) cavity dimensions assumes great importance in clinical cardiology. Pediatric guidelines recommend the left parasternal short axis (PSA) imaging plane for measuring LV cavity dimensions, while measuring from the long axis (PLA) plane is the convention in adult echocardiography. We sought to compare measurements obtained by two-dimensional (2D) and M-mode (MM) techniques in the two imaging planes. Healthy subjects were prospectively recruited for research echocardiography. Complete 2D, spectral and color flow Doppler examinations were performed in a non-sedated state. All subjects had structurally and functionally normal hearts. LV cavity dimensions were obtained in PLA and PSA views using 2D and MM yielding four measurement sets for each subject: PLA direct 2D; PLA 2D-guided MM, PSA direct 2D, PSA 2D-guided MM. A commercially available ultrasound system (Vivid E9, GE) was used and data stored digitally for subsequent analysis (EchoPAC BT11, GE). Acquisition and measurements were made by a single observer from at least three consecutive cardiac cycles, and averaged for each of the four categories. The study cohort consisted of 114 subjects (mean age 9 years, range 1-18; mean BSA 1.1 m(2), range 0.42-2.6). The smallest estimate of LV end-diastolic dimension (LVED) was obtained by PLA 2D, with larger estimates by PLA MM, PSA 2D, and PSA MM. Largest estimates of LV end-systolic dimension (LVES) are by 2D methods, with smaller estimates by both MM techniques. The smallest shortening fraction (SF) was by PLA 2D; other methods yielded larger SF. Temporal resolution is limited in 2D methodology and may account for the smaller LVED, larger LVES and smaller SF observed. Long axis methodology may predispose to off-center or non-perpendicular data acquisition and the potential for dimensional underestimation, particularly in diastole. Consistency in method for assessment of LV dimensions in children is an important factor for serial comparisons.

[Velocity vector imaging assessment of early epirubicin-induced myocardial damage].

OBJECTIVE: To assess the left ventricular (LV) longitudinal systolic and diastolic function in patients treated by epirubicin by velocity vector imaging (VVI) and to discuss the important clinical value of VVI in quantitatively evaluating the regional longitudinal function. METHODS: Thirty patients with breast cancer treated with epirubicin chemotherapy and 30 normal controls were included in the study. Dynamic images of apical long axis, four-chamber and two chamber view were obtained in all subjects, and the longitudinal systolic and diatolic parameters were measured in all subjects, including systolic maximum velocity (Vs), systolic maximum strain (SS), systolic maximum strain rate (SSR), diastolic maximum velocity (Vd), and diastolic maximum strain rate (DSR). The parameters were compared between the 2 groups. The conventional echcardiographic parameters were also obtained. RESULTS: There was no significant change in all baseline parameters before the chemotherapy in 30 breast cancer patients compared with the normal controls (P>0.05). After the second chemotherapy cycle, DSR was lower in every segment, Vd was lower in the free wall, mainly the lateral, anterior and inferior wall (P<0.05), while Vd didn't change significantly in the septum wall (P>0.05). After the third chemotherapy cycle, Vd, DSR and SSR decreased significantly in all segments (P<0.05). Vs and SS didn't change significantly (P>0.05). CONCLUSION: VVI can monitor the epirubicin cardiotoxicity early and is more sensitive than echocardiograph.

Specific inhibition of Notch1 signaling enhances the antitumor efficacy of chemotherapy in triple negative breast cancer through reduction of cancer stem cells.

Recent evidence suggests that Notch signaling may play a role in regulation of cancer stem cell (CSC) self-renewal and differentiation hence presenting a promising target for development of novel therapies for aggressive cancers such as triple negative breast cancer (TNBC). We generated Notch1 monoclonal antibodies (mAbs) that specifically bind to the negative regulatory region of human Notch1. Notch1 inhibition in TNBC Sum149 and patient derived xenograft (PDX) 144580 models led to significant TGI particularly in combination with docetaxel. More interestingly, Notch1 mAbs caused a reduction in mammosphere formation and CD44+/CD24-/lo cell population. It also resulted in decreased tumor incidence upon re-implantation and delay in tumor recurrence. Our data demonstrated a potent antitumor efficacy of Notch1 mAbs, with a remarkable activity against CSCs. These findings suggest that anti-Notch1 mAbs may provide novel therapies to improve the efficacy of conventional therapies by directly targeting the CSC niche. They may also delay tumor recurrence and hence have a major impact on cancer patient survival.