Lei Zhang
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Publication
Journal: Cellular signalling
November/3/2019
Abstract
Although gankyrin has been identified as a vital regulator of tumorigenesis, its role and regulatory mechanism in osteosarcoma (OS) remain unclear.QRT-PCR, western blot and IHC staining were conducted to detect the expression of gankyrin in OS. Pearson's χ² test was adopted to examine the associations between gankyrin expression and clinicopathologic characteristics. Kaplan-Meier method was used to investigate the relationship between gankyrin expression and overall survival of patients with OS. Next, a series of in vitro and in vivo assays were performed to determine the positive feedback loop between gankyrin and YAP in OS.We first reported that gankyrin is upregulated in human OS specimens and cell lines and predicts OS progression and poor prognosis. Furthermore, we demonstrated that gankyrin protects miR-200a-mediated yes-associated protein (YAP) downregulation through p53 and establishes a positive feedback loop to regulate YAP signaling in U2OS and MG63 cells. Intriguingly, gankyrin interacts with YAP to promote OS cell growth in vitro. In addition, our results showed that gankyrin promotes OS tumor growth and regulates YAP levels in vivo. Notably, we also observed a positive correlation between gankyrin and YAP expression in human OS tissues, and co-upregulation of gankyrin and YAP indicated a poor prognosis.Our results identify that gankyrin acts as an oncogene in OS by forming a positive feedback loop with YAP, and disrupting the gankyrin-YAP regulation may be beneficial for controlling OS tumorigenesis.
Publication
Journal: Cell death and differentiation
October/31/2019
Abstract
The retrosplenial cortex (Rsp) is a transitional cortex located between the neocortex and archicortex, but the molecular mechanism specifying Rsp from the archicortex remains elusive. We here report that the transcription factor Satb2 is required for specifying Rsp identity during its morphogenesis. In Satb2 CKO mice, the boundary between the Rsp and archicortex [i.e., subiculum (SubC)] disappears as early as E17.5, and Rsp efferent projection is aberrant. Rsp-specific genes are lost, whereas SubC-specific genes are ectopically expressed in Rsp of Satb2 CKO mice. Furthermore, cell-autonomous role of Satb2 in maintaining Rsp neuron identity is revealed by inactivation of Satb2 in Rsp neurons. Finally, Satb2 represses the transcription of Nr4a2. The misexpression of Nr4a2 together with Ctip2 induces expression of SubC-specific genes in wild-type Rsp, and simultaneous knockdown of these two genes in Rsp Satb2-mutant cells prevents their fate transition to SubC identity. Thus, Satb2 serves as a determinant gene in the Rsp regionalization by repressing Nr4a2 and Ctip2 during cortical development.
Publication
Journal: MethodsX
October/31/2019
Abstract
Random forests (RF) is a powerful species distribution model (SDM) algorithm. This ensemble model by default can produce categorical and numerical species distribution maps based on its classification tree (CT) and regression tree (RT) algorithms, respectively. The CT algorithm can also produce numerical predictions (class probability). Here, we present a detailed procedure involving the use of the CT and RT algorithms using the RF method with presence-only data to model the distribution of species. CT and RT are used to generate numerical prediction maps, and then numerical predictions are converted to binary predictions through objective threshold-setting methods. We also applied simple methods to deal with collinearity of predictor variables and spatial autocorrelation of species occurrence data. A geographically stratified sampling method was employed for generating pseudo-absences. The detailed procedural framework is meant to be a generic method to be applied to virtually any SDM prediction question using presence-only data. •How to use RF as a standard method for generic species distributions with presence-only data•How to choose RF (CT or RT) methods for the distribution modeling of species•A general and detailed procedure for any SDM prediction question.
Publication
Journal: IEEE transactions on cybernetics
October/21/2019
Abstract
The self-expressive property of data points, that is, each data point can be linearly represented by the other data points in the same subspace, has proven effective in leading subspace clustering (SC) methods. Most self-expressive methods usually construct a feasible affinity matrix from a coefficient matrix, obtained by solving an optimization problem. However, the negative entries in the coefficient matrix are forced to be positive when constructing the affinity matrix via exponentiation, absolute symmetrization, or squaring operations. This consequently damages the inherent correlations among the data. Besides, the affine constraint used in these methods is not flexible enough for practical applications. To overcome these problems, in this article, we introduce a scaled simplex representation (SSR) for the SC problem. Specifically, the non-negative constraint is used to make the coefficient matrix physically meaningful, and the coefficient vector is constrained to be summed up to a scalar s<1 to make it more discriminative. The proposed SSR-based SC (SSRSC) model is reformulated as a linear equality-constrained problem, which is solved efficiently under the alternating direction method of multipliers framework. Experiments on benchmark datasets demonstrate that the proposed SSRSC algorithm is very efficient and outperforms the state-of-the-art SC methods on accuracy. The code can be found at https://github.com/csjunxu/SSRSC.
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Publication
Journal: Chemosphere
October/19/2019
Abstract
Some studies have revealed thyrotoxicity of phthalates; however, associations of phthalate exposure with papillary thyroid cancer (PTC) remain unclear. We conducted a pair-matching case-control study of 111 PTC cases and 111 age- and sex-matched non-PTC controls to examine associations between urinary concentrations of phthalate metabolites and PTC. Phthalate metabolites were determined in fasting urine specimens by ultra-performance liquid chromatography - tandem mass spectrometry (UPLC-MS/MS). After adjusting for potential confounders and other phthalate metabolites, the concentrations of the sum of di (2-ethylhexly) phthalate (DEHP) metabolites in urine were positively associated with PTC [odds ratio (OR) = 5.35; 95% confidence interval (CI): 1.61-17.83], suggesting the effect of phthalates exposure on PTC development. The findings require confirmation.
Publication
Journal: Muscle & nerve
October/6/2019
Abstract
The abduction range of the little finger in the long exercise test (ET) has rarely been reported in patients with hypokalemic periodic paralysis (HypoPP) during inter-attack periods, and the diagnostic value requires clarification.The long ET was performed in 43 HypoPP patients during inter-attack periods and in 20 healthy controls (HCs). The compound muscle action potential (CMAP) and the abduction range of the little finger were recorded concurrently.There were significant differences in the percent changes of the CMAP amplitudes and the abduction ranges after exercise between HypoPP patients and the HCs. The curve of percent changes in abduction ranges overlapped substantially with that of the CMAP amplitudes, and the sensitivity, specificity and cut-off values were 0.860, 0.900 and 22.6%, respectively.The abduction range of the little finger can serve as a novel parameter in the long ET for the diagnosis of HypoPP during inter-attack periods. This article is protected by copyright. All rights reserved.
Publication
Journal: The Annals of thoracic surgery
September/14/2019
Abstract
Pulmonary arterial aneurysm (PAA) is a rare condition involving a focal dilation of the pulmonary artery and all three layers of the vessel wall. Few reports have described managing this anomaly using video-assisted thoracoscopic surgery (VATS). Here, we report a 60-year-old woman with a PAA in the truncus superior of the right pulmonary artery. The patient underwent a two-port VATS with a right upper lobectomy. The postoperative course was uneventful. She maintained a good prognosis for 4 months after surgery, and we continue to take great care throughout her follow-up.
Publication
Journal: International journal of environmental research and public health
August/15/2019
Abstract
The association between adverse childhood experiences (ACEs) and pubertal timing has been a topic of enduring controversy. A systematic search of PubMed and Web of Science databases was undertaken to quantify the magnitude of total and specific forms of ACEs effects on early pubertal timing among girls. Our search identified 3280 records, of which 43 studies with 46 independent data sets met inclusion criteria. We estimated pooled effect sizes (Cohen's ds) for the association between ACEs with early pubertal timing. Total ACEs was not associated with early pubertal timing. When we examined the specific types of ACEs, associations were small to medium for father absence (d = -0.40, 95% confidence interval [CI]: -0.63, -0.16) and small for sexual abuse (d = -0.13, CI: -0.17, -0.10) and family dysfunction (d = -0.08, CI: -0.11, -0.02). We identified considerable heterogeneity between estimates for almost all of the outcomes. ACEs exposure may affect female reproductive reproduction, particularly father absence, sexual abuse, and family dysfunction. We propose that future research in this area test a theoretical model linking adversity with earlier reproductive strategy, which includes early pubertal timing as a core component linking early adversity and stress physiology with poor health outcomes later in life in females.
Publication
Journal: Human brain mapping
August/9/2019
Abstract
Identifying factors for the prediction of depression is a long-standing research topic in psychiatry and psychology. Perceived stress, which reflects the tendency to appraise one's life situations as stressful and overwhelming, has emerged as a stable predictor for depressive symptoms. However, the neurobiological bases of perceived stress and how perceived stress influences depressive symptoms in the healthy brain remain largely unknown. Here, we investigated these issues in 217 healthy adolescents by estimating the fractional amplitude of low-frequency fluctuations (fALFFs) via resting-state functional magnetic resonance imaging. A whole-brain correlation analysis showed that higher levels of perceived stress were associated with greater fALFF in the left superior frontal gyrus (SFG), which is a core brain region for cognitive control and emotion regulation-related processes. Mediation analysis further indicated that perceived stress mediated the link between the fALFF in the left SFG and depressive symptoms. Importantly, our results remained significant even when excluding the influences of head motion, anxiety, SFG gray matter structure, and school environment. Altogether, our findings suggested that the fALFF in the left SFG is a neurofunctional marker of perceived stress in adolescents and revealed a potential indirect effect of perceived stress on the association between the SFG spontaneous activity and depressive symptoms.
Publication
Journal: European radiology
August/2/2019
Abstract
To compare visualization of joint intracranial and carotid vessel walls between 5× compressed sensing accelerated three-dimensional DANTE-SPACE sequence (CS VWI) acquired in 5 min and the same sequence accelerated by 2.7× parallel imaging (PI VWI) which takes 9-10 min currently.Following institutional review board approval and informed consent, 28 subjects including 20 stroke patients underwent PI and CS VWI examinations with an acquired spatial resolution of isotropic 0.55 mm and joint coverage of intracranial and carotid arteries. Quantitative wall thickness measurements of CS VWI and PI VWI were compared on healthy volunteers and patients with wall thickening respectively. Subjective wall visualizations of the two VWI methods on patients were scored by two radiologists blindly and independently using a 4-point scale followed by inter-rater reproducibility analysis.Linear regression analysis of wall thickness measurements showed excellent agreement between CS VWI and PI VWI in both healthy volunteers (r = 0.99) and stroke patients with wall thickening (r = 0.99). Subjective wall visualization score of CS VWI was slightly lower than PI VWI (3.13 ± 0.41 vs. 3.31 ± 0.79) but still had good diagnostic quality (> 3 based on a 4-point scale). The two radiologists' scores agreed excellently, evidenced by the intraclass correlation coefficient (ICC) values being higher than 0.75 (p < 0.001).Compressed sensing expedients joint intracranial and carotid VWI acquired at an isotropic resolution of 0.55 mm in 5 min without compromising quantitative vessel wall thickness measurement or diagnostic wall visualization.• CS VWI facilitates comprehensive visualization of intracranial and carotid vessel walls at an acquired isotropic resolution of 0.55 mm in a single 5-min scan. • CS VWI affords comparable vessel wall visualization and morphology measurement as PI VWI with a shortened acquisition time by 45%. • CS VWI alleviates the intensive trade-off between imaging resolution and scan time, and benefits the scan efficiency, motion robustness, and patient tolerance of high-resolution joint intracranial and carotid VWI.
Publication
Journal: Medical science monitor : international medical journal of experimental and clinical research
July/18/2019
Abstract
BACKGROUND This study aimed to evaluate superb microvascular imaging (SMI) as an adjunctive imaging method to evaluate mesenteric lymph nodes in children with mesenteric lymphadenitis compared with healthy children. MATERIAL AND METHODS A retrospective study compared children with mesenteric lymphadenitis (n=27) and healthy children (n=30). Lymph node size was determined using grayscale ultrasonography and parameters of lymph node vascularity were compared using color Doppler flow imaging (CDFI) and SMI. The diagnostic performance of ultrasound (US), US combined with SMI, and US combined with CDFI were compared. RESULTS Lymph nodes from children with mesenteric lymphadenitis (n=77) and normal lymph nodes (n=84) were evaluated by SMI, which showed that the least diameter of lymph nodes in cases of mesenteric lymphadenitis was 0.58±0.15 mm and of normal mesenteric lymph nodes was 0.47±0.08 mm (p<0.001). SMI identified 92.6% of abnormal mesenteric lymph nodes while CDFI detected 85.2%. US combined with SMI had the highest sensitivity (81.5%), and specificity (78.9%) compared with US alone (sensitivity, 63.0%; specificity, 64.9%), and compared with US combined with CDFI (sensitivity, 74.1%; specificity, 75.4%). US combined with SMI and US combined with CDFI achieved the same specificity (76.7%), which was higher than that of US alone (66.7%). CONCLUSIONS SMI was superior to color Doppler flow imaging in evaluating the microvasculature in lymphadenopathy in mesenteric lymphadenitis. SMI may be used as an adjunct to grayscale ultrasonography to assist in identifying mesenteric lymphadenopathy in pediatric patients.
Publication
Journal: Bioresource technology
July/14/2019
Abstract
The degradation of fipronil was investigated in microbial fuel cells (MFCs). Almost 79% of 30 mg/L fipronil was rapidly degraded within 12 h by MFC biofilm. Based on the constructed quadratic polynomial model, a maximum fipronil degradation rate of 94.22% could be theoretically achieved at pH of 7.01, 33.39 °C, and the initial fipronil concentration 74 mg/L after incubation for 72 h. The high acute toxicity of fipronil toward zebrafish was largely eliminated after degradation by the MFC. In addition, the MFC biofilm showed catabolic versatility to 4-chloronitrobenzene, sulfanilamide, fluoroglycofen, and azoxystrobin. The microbial community analysis revealed that the functional bacteria Sphaerochaeta, Pseudomonas, Azospirillum, Azoarcus, and Chryseobacterium were major predominant bacteria in the anodic biofilm. Therefore, the MFC offers a promising approach in treating the environmental contaminants due to its abilities of energy capture from waste substances and catabolic versatility to different organic compounds.
Publication
Journal: Cell stem cell
July/4/2019
Abstract
Following injury, differentiated epithelial cells can serve as a stem cell-independent source for tissue regeneration by undergoing reprogramming into other cell types. The intrinsic molecular basis underlying plasticity of differentiated cells remains largely unaddressed. Here we show that Arid1a, a key component of the SWI/SNF chromatin remodeling complex, controls liver regeneration and gene expression associated with emergence of injury-induced liver-progenitor-like cells (LPLCs). Hepatocyte-specific Arid1a ablation reduces LPLC gene expression in several models of periportal liver injury and impairs liver regeneration, leading to organ dysfunction. Arid1a establishes a permissive chromatin state at LPLC-enriched genes during homeostasis, suggesting it endows hepatocytes with competence to respond to injury-induced signals. Consistently, Arid1a facilitates binding of YAP, a critical regeneration signaling pathway, to LPLC-enriched genes, and Arid1a deletion prevents their YAP-associated induction following injury. Together, these findings provide a framework for studying the contributions of injury-induced LPLCs to periportal liver regeneration.
Publication
Journal: Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine
July/2/2019
Abstract
This study aimed to evaluate the clinical value of the elastographic Q-analysis score (EQS) in assisting real-time elastography- and transrectal US-guided prostate biopsy.A total of 125 patients with 301 lesions were enrolled in this study; all were confirmed by pathologic results. The patients underwent transrectal US and elastographic examinations before biopsy. Elastographic Q-analysis score analysis software was used for measuring the mean EQS of the elastic images. First, the suspicious regions on elastography underwent biopsy. Then 12-core systematic prostate biopsy was performed. An EQS curve was used to calculate the mean EQS, and a receiver operating characteristic curve was drawn to find the cutoff point for the EQS to predict prostate cancer.Of the 301 lesions in this study, 125 were malignant, and 176 were benign. The mean EQS values of benign and malignant lesions ± SD were 1.47 ± 0.75 and 2.98 ± 1.06, respectively. The difference was statistically significant (P < .05). The area under the receiver operating characteristic curve was 0.87. When the cutoff point was 1.95 for diagnosing malignant and benign lesions, the sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio were 83.5%, 84.4%, 76.8%, 89.2%, 5.35, and 0.20.The EQS could be used as a way to predict benign and malignant lesions and thus could serve as guidance for adding targeted biopsy.
Publication
Journal: EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology
June/20/2019
Abstract
This study aimed to provide a simple index for predicting the definite indication for transcatheter closure of atrial septal defect (ASD) with pulmonary arterial hypertension(PAH).A positive responseafter attempted occlusion was defined as mean pulmonary artery pressure (MPAP) ≤ 30 mmHg or the decrement percentage of it ≥20% compared with the baseline. If a positive response was achieved, the occluder would be released, and the procedure was defined as successful. In 209 patients underwent successful procedure without PAH-specific medicine, there was a dramatic decrease in the percentage of patients with pulmonary arterial systolic pressure (PASP) ≥ 50 mmHg from baseline to the one-year follow-up (79.4% to 14.0%, P&lt;0.001). The optimalcut-offvalue of MPAP to predict a positive response without PAH-specific medicine was 35.0 mmHg, with an area under the curve (AUC) of 0.919 (P &lt;0.001). Administration of inhaled iloprost extended the cut-off point to 50.0 mmHg to reach a positive response, with an AUC of 0.774 (P=0.003).This large-scale studyindicated that MPAP could be a simple but powerful index to predict benefit from closure in adult ASD patients with PAH.
Publication
Journal: Nature communications
May/25/2019
Abstract
Anisotropy in crystals arises from different lattice periodicity along different crystallographic directions, and is usually more pronounced in two dimensional (2D) materials. Indeed, in the emerging 2D materials, electrical anisotropy has been one of the recent research focuses. However, key understandings of the in-plane anisotropic resistance in low-symmetry 2D materials, as well as demonstrations of model devices taking advantage of it, have proven difficult. Here, we show that, in few-layered semiconducting GaTe, electrical conductivity anisotropy between x and y directions of the 2D crystal can be gate tuned from several fold to over 103. This effect is further demonstrated to yield an anisotropic non-volatile memory behavior in ultra-thin GaTe, when equipped with an architecture of van der Waals floating gate. Our findings of gate-tunable giant anisotropic resistance effect pave the way for potential applications in nanoelectronics such as multifunctional directional memories in the 2D limit.
Publication
Journal: Journal of immigrant and minority health
May/17/2019
Abstract
Colorectal Cancer (CRC) is common in Lao Americans, but screening is suboptimal. To investigate CRC screening rates of Lao Americans in Minnesota, and how predisposing characteristics, enabling resources, and perceived need are associated with screening. We conducted a convenience-sample cross-sectional survey of 50-75-year-old Lao Americans, using step-wise multivariate logistic regression to identify factors associated with ever being screened. Of the 118 survey participants, 45% ever received CRC screening. In univariate regression, some enabling resources (having a primary care provider, higher self-efficacy in pursuing screening) and perceived needs (knowledge of who should be screened, higher number of chronic illnesses) were associated with screening. In multivariate logistic regression, the odds of ever being screened was 12.4 times higher for those with a primary care provider than for those without (p = 0.045). The findings reinforce a need for developing culturally tailored interventions focused on Lao-American immigrants to promote CRC screening.
Publication
Journal: IEEE/ACM transactions on computational biology and bioinformatics
May/16/2019
Abstract
Publishing biological data in XML formats is attractive for organizations who would like to provide their bioinformatics resources in an extensible and machine-readable format. In the era of big data, massive XML-based biological data management is emerged as a challengeable issue. With the continuous growth of the XML-based biological data sets, it is usually frustrating to use traditional declarative query languages to provide efficient query capabilities in terms of processing speed and scale. In this study, we report a novel platform to store and query massive XML-based biological data collections. A prototype tool for constructing HBase tables from XML-based biological data collections is firstly developed, and then a formal approach to transform the XML query model into the MapReduce query model is proposed. Finally, an evaluation of the query performance of the proposed approach on the existing XML-based biological databases is presented, showing that the performance advantages of the proposed solution. The source code of the massive XML-based biological data management platform is freely available at https://github.com/lyotvincent/X2H.
Publication
Journal: International journal of molecular sciences
April/30/2019
Abstract
Retinoic acid (RA) plays a key role in pluripotent cell differentiation. In F9 embryonic carcinoma cells, RA can induce differentiation towards somatic lineages via the Ras-extracellular signal-regulated kinase (Ras/Erk) pathway, but the mechanism through which it induces the Erk1/2 phosphorylation is unclear. Here, we show that miR-485 is a positive regulator that targets α/β-hydrolase domain-containing protein 2 (Abhd2), which can result in Erk1/2 phosphorylation and triggers differentiation. RA up-regulates miR-485 and concurrently down-regulates Abhd2. We verified that Abhd2 is targeted by miR-485 and they both can influence the phosphorylation of Erk1/2. In summary, RA can mediate cell differentiation by phosphorylating Erk1/2 via miR-485 and Abhd2.
Publication
Journal: Chinese medical journal
April/25/2019
Publication
Journal: The Annals of thoracic surgery
April/22/2019
Abstract
When multiple target lung nodules exist, the computed tomography (CT)-guided percutaneous localization procedure becomes complicated. In this study, a three-dimensional (3D)-printed template was designed that could guide hook wire localization of multiple lung nodules. The pilot study aimed for preliminary validation of the feasibility of template-guided localization for multiple lesions.Patients with multiple lung nodules (<2 cm) and who were scheduled for surgical resection were recruited for participation in this study. After securing their preadmission CT images, the study investigators reconstructed a 3D thorax model from which they designed a digital model as a navigational template. A physical template was then printed for guiding the percutaneous localization of lung nodules. The localization accuracy was evaluated on the basis of the deviation between the localizer and the nodule.From April 2018 to November 2018, the study enrolled 16 patients with 34 lung nodules. All nodules were successfully localized under template guidance, with a median procedural time of 10.0minutes (interquartile range [IQR], 8.5-12.6 minutes) and a median radiation exposure of 235 mGy • cm (IQR, 195-254 mGy • cm). The median deviation from the hook wires and nodule centers was 9.0 mm (IQR, 6.2-11.8 mm). Except for 2 cases of pneumothorax without need for further intervention, no complications occurred.Navigational templates built using 3D printing may serve as an effective approach for facilitating localization of multiple lung nodules.
Publication
Journal: Fish physiology and biochemistry
April/19/2019
Abstract
We assessed the effects of light intensity and spectrum on the growth and survival of Takifugu rubripes larvae from 30 to 69 days after hatching. Five lighting regimes were applied using 0.5, 1.5, and 3.0 W m-2 full spectrum white (W0.5, W1.5, W3.0), 0.5 W m-2 yellow (Y0.5), and 0.5 W m-2 blue light (B0.5). At the end of the experiment, body length, wet weight, and specific growth rate from day 0 to day 39 were significantly greater in larvae reared under W3.0 than under B0.5 (P ˂ 0.05). No significant differences were observed among W0.5, W1.5, and W3.0, or among W0.5, Y0.5, and B0.5 (P > 0.05). Survival rate was significantly higher in larvae reared under W1.5 than W0.5 (P ˂ 0.05), but no significant differences were observed among W0.5, Y0.5, and B0.5 (P > 0.05). Additionally, light conditioning did not affect the total thickness of the retina. Although the ratio of the thickness of the retinal pigment epithelium layer/total thickness (TT) was significantly higher in larvae exposed to W3.0 compared with those exposed to other light conditions, and the thickness of the outer nuclear layer/TT was significantly lower in larvae exposed to W3.0 compared with those exposed to W0.5 (P < 0.05), no relationship was confirmed between the structure of the retina and the growth performance of the T. rubripes larvae. Expression patterns of two stress-related and seven growth-related genes were also compared with the biometric parameters investigated in the experimental groups. No significant differences in the aanat1a, crh, ss1, igf1, or igf2 expression were observed among the five treatments. Pomc expression was significantly lower in larvae exposed to W1.5 than the larvae exposed to W0.5, and it was significantly lower in larvae exposed to Y0.5 than in larvae exposed to W0.5 or B0.5 (P < 0.05). Significant differences were also found in the expression of gh, with the highest levels being observed under W3.0, while the lowest levels were observed in B0.5 (P < 0.05). Ghrh expression was significantly higher in W3.0 (P < 0.05). These results should be considered when designing rearing protocols for fugu larvae in aquaculture systems.
Publication
Journal: Molecular cancer therapeutics
April/9/2019
Abstract
Although inhibiting EGFR-mediated signaling proved to be effective in treating certain types of cancers, a quickly evolved mechanism that either restores the EGFR signaling or activates an alternative pathway for driving the proliferation and survival of malignant cells limits the efficacy and utility of the approach via suppressing the EGFR functionality. Given the fact that overexpression of EGFR is commonly seen in many cancers, an EGFR-targeting antibody-drug conjugate (ADC) can selectively kill cancer cells independently of blocking EGFR-mediated signaling. Herein, we describe SHR-A1307, a novel anti-EGFR ADC, generated from an anti-EGFR antibody with prolonged half-life, and conjugated with a proprietary toxin payload that has increased index of EGFR targeting-dependent versus EGFR targeting-independent cytotoxicity. SHR-A1307 demonstrated strong and sustained antitumor activities in EGFR-positive tumors harboring different oncogenic mutations on EGFR, KRAS, or PIK3CA. Antitumor efficacy of SHR-A1307 correlated with EGFR expression levels in vitro and in vivo, regardless of the mutation status of EGFR signaling mediators and a resultant resistance to EGFR signaling inhibitors. Cynomolgus monkey toxicology study showed that SHR-A1307 is well tolerated with a wide therapeutic index. SHR-A1307 is a promising therapeutic option for EGFR-expressing cancers, including those resistant or refractory to the EGFR pathway inhibitors.
Publication
Journal: Oncology letters
March/18/2019
Abstract
Safety and feasibility of the self-made thoracic needled suspending device with a snare in the uniportal video-assisted thoracic lobectomy and segmentectomy for the treatment of non-small cell lung cancer were explored. In total, 80 pulmonary lung major resections (including lobectomy and segmental resections) with systematic mediastinal lymphadenectomy were retrospectively analyzed. Patients were randomly divided into an observation group and a control group. In the observation group, the device was used to hang affected lungs, left and right vagus nerve at the level of tracheal bifurcation, the arch of azygos vein, left phrenic nerve and left and right bronchus on the chest wall to offer a better exposure of the operation field. In the control group, the conventional uniportal video-assisted thoracic surgery was performed without using the self-made device. Systematic mediastinal lymphadenectomy was performed in both groups. Operation time, intraoperative blood loss, postoperative extubation time, hospital stay and perioperative complications in the early stage of patients in both groups were compared. The operation time 120.2±40.32 min, intraoperative blood loss 100.51±50.23 ml, and postoperative suction drainage volume 208±97.56 ml/day in the observation group were significantly different from those in the control group (P<0.05), and there were no significant differences in postoperative extubation time, hospital stay and perioperative complications between the two groups (P>0.05). The self-made thoracic needled suspending device with a snare is an excellent helper for uniportal video-assisted thoracic surgery, because it helps to expose surgical field and has no postoperative cicatrisation at puncture point on the wall of the chest. The device and its use are worthy of promotion.
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