Angiogenesis, a marker of cancer development, affects response to radiotherapy sensibility. This preclinical study aims to understand the receptor tyrosine kinase-mediated angiogenesis in head neck ...squamous cell carcinoma (HNSCC). The receptor tyrosine kinase activity in a transgenic mouse model of HNSCC was assessed. The anti-tumorigenetic and anti-angiogenetic effects of cetuximab-induced epidermal growth factor receptor (EGFR) inhibition were investigated in xenograft and transgenic mouse models of HNSCC. The signaling transduction of Notch1 and hypoxia-inducible factor-1α (HIF-1α) was also analyzed. EGFR was overexpressed and activated in the Tgfbr1/Pten deletion (2cKO) mouse model of HNSCC. Cetuximab significantly delayed tumor onset by reducing tumor angiogenesis. This drug exerted similar effects on heterotopic xenograft tumors. In the human HNSCC tissue array, increased EGFR expression correlated with increased HIF-1α and micro vessel density. Cetuximab inhibited tumor-induced angiogenesis in vitro and in vivo by significantly downregulating HIF-1α and Notch1. EGFR is involved in the tumor angiogenesis of HNSCC via the HIF-1α and Notch1 pathways. Therefore, targeting EGFR by suppressing hypoxia- and Notch-induced angiogenesis may benefit HNSCC therapy.
LaF
3
nanocrystals (NCs) are usually used as good host matrix for down-conversion phosphors owing to their impressive photophysical properties. In this study, Pr
3+
-activated LaF
3
with hollow ...hexagon nanostructures (HHNs) is achieved by a green and eco-friendly hydrothermal method without any catalyst, template, or surfactant. The pore structure of the LaF
3
HHNs is greatly affected by the content of Pr
3+
ions and hydrothermal reaction time. The LaF
3
: Pr
3+
NCs excited by 467 nm light show strong emission peaks locating in visible light region (centered at 612 and 635 nm) and the first biological window region (existed in 689 and 721 nm), respectively. The relative photoluminescence (PL) intensity of LaF
3
: Pr
3+
NCs from 20 to 60 °C (biological temperature) decreases slightly and decreases only 20% at 120 °C. The PL emission intensity could reach the maximal value with doping ~ 1.5% Pr
3+
ions. Based on the outstanding photophysical properties, LaF
3
: Pr
3+
NCs will be used for both warm white light-emitting diodes and bio-imaging.
Viral infections contribute to approximately 12% of cancers worldwide, with the vast majority occurring in developingcountries and areas. Two DNA viruses, Epstein-Barr virus （EBV） and human ...papillomavirus （HPV）, are associated with38% of all virus-associated cancers. The probability of one patient infected with these two distinct types of viruses isincreasing. Here, we summarize the co-infection of EBV and HPV in human malignancies and address the possiblemechanisms for the co-infection of EBV and HPV during tumorigenesis.
A series of Co
3
O
4
catalysts was prepared by ammonia (Co-AP) and oxalate (Co-OP) precipitation, sol–gel (Co-SG), and urea hydrothermal (Co-UH) methods, and their physicochemical properties were ...characterised by numerous techniques including X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), nitrogen sorption, X-ray photoelectron spectroscopy (XPS), temperature-programmed reduction of H
2
(H
2
-TPR), temperature-programmed desorption of O
2
(O
2
-TPD), and temperature-programmed desorption of NH
3
(NH
3
-TPD). The catalytic activity of each catalyst was estimated for the catalytic combustion of vinyl chloride (VC) emissions. The crystallite size of the Co
3
O
4
catalyst was found to be well correlated with the amounts of surface-adsorbed oxygen species and number of acid sites on the catalyst surface, and consequently, determined several physicochemical properties of the catalyst. Of the catalysts studied here, the Co-AP catalyst exhibits the smallest crystallite size, which increases the specific surface area and the concentration of Co
2+
on the catalyst surface. This, in turn, enhances the redox property, oxygen mobility, and the number of acid sites associated with the Co-AP catalyst. In fact, the Co-AP catalyst exhibits the best catalytic activity for VC combustion at 360 °C and does not produce any chlorinated by-products.
Graphic abstract
To explore the potential pathogenesis and clinical features of second primary glioblastoma (spGBM) following first primary renal cell carcinoma (fpRCC).
Patients with spGBM after fpRCC were enrolled ...from our institution and the SEER dataset. Sanger sequencing, whole genome sequencing, and immunehistochemistry were used to detect molecular biomarkers.
Four and 122 cases from our institution and the SEER dataset, respectively, were collected with an overall median age of 69 years at spGBM diagnosis following fpRCC. The median interval time between fpRCC and spGBM was 50.7 months and 4 years, for the four and 122 cases respectively. The median overall survival time was 11.2 and 6.0 months for the two datasets. In addition, spGBM patients of younger age (< 75 years) or shorter interval time (< 1 year) had favorable prognosis (p = 0.081 and 0.05, respectively). Moreover, the spGBM cases were molecularly classified as TERT only paired with TP53 mutation, PIK3CA mutation, EGFR alteration, low tumor mutation burden, and stable microsatellite status.
This is the first study to investigate the pathogenesis and clinical features of spGBM following spRCC. We found that spGBMs are old-age related, highly malignant, and have short survival time. Moreover, they might be misdiagnosed and treated as brain metastases from RCC. Thus, the incidence of spGBMs after fpRCC is underestimated. Further studies are needed to investigate the underlying molecular mechanisms and clinical biomarkers for the development of spGBM following fpRCC.
Realgar is a type of mineral drug containing arsenic. The nervous system toxicity of realgar has received extensive attention. However, the underlying mechanisms of realgar-induced neurotoxicity have ...not been clearly elucidated. To explore the mechanisms that contribute to realgar-induced neurotoxicity, weanling rats were exposed to realgar (0, 0.3, 0.9, 2.7 g/kg) for 6 weeks, and cognitive ability was tested using the Morris water maze (MWM) test and object recognition task (ORT). The levels of arsenic in the blood and hippocampus were monitored. The ultrastructures of hippocampal neurons were observed. The levels of glutamate (Glu) and glutamine (Gln) in the hippocampus and hippocampal CA1 region; the activities of glutamine synthetase (GS) and phosphate-activated glutaminase (PAG); the mRNA and protein expression of glutamate transporter 1 (GLT-1), glutamate/aspartate transporter (GLAST), and
N
-methyl-
d
-aspartate (NMDA) receptors; and the level of intracellular Ca
2+
were also investigated. The results indicate that the rats developed deficiencies in cognitive ability after a 6-week exposure to realgar. The arsenic contained in realgar and the arsenic metabolites passed through the blood-brain barrier (BBB) and accumulated in the hippocampus, which resulted in the excessive accumulation of Glu in the extracellular space. The excessive accumulation of Glu in the extracellular space induced excitotoxicity, which was shown by enhanced GS and PAG activities, inhibition of GLT-1 mRNA and protein expression, alterations in NMDA receptor mRNA and protein expression, disturbance of intracellular Ca
2+
homeostasis, and ultrastructural changes in hippocampal neurons. In conclusion, the findings from our study indicate that exposure to realgar induces excitotoxicity and that the mechanism by which this occurs may be associated with disturbances in Glu metabolism and transportation and alterations in NMDA receptor expression.
Communication between tumors and lymph nodes carries substantial significance for antitumor immunotherapy. Remodeling the immune microenvironment of tumor-draining lymph nodes (TdLN) plays a key role ...in enhancing the anti-tumor ability of immunotherapy. In this study, we constructed a biomimetic artificial lymph node structure composed of F127 hydrogel loading effector memory T (T
) cells and PD-1 inhibitors (aPD-1). The biomimetic lymph nodes facilitate the delivery of T
cells and aPD-1 to the TdLN and the tumor immune microenvironment, thus realizing effective and sustained anti-tumor immunotherapy. Exploiting their unique gel-forming and degradation properties, the cold tumors were speedily transformed into hot tumors via T
cell supplementation. Meanwhile, the efficacy of aPD-1 was markedly elevated compared with conventional drug delivery methods. Our finding suggested that the development of F127@T
@aPD-1 holds promising potential as a future novel clinical drug delivery technique. STATEMENT OF SIGNIFICANCE: F127@T
@aPD-1 show unique advantages in cancer treatment. When injected subcutaneously, F127@T
@aPD-1 can continuously supplement T
cells and aPD-1 to tumor draining lymph nodes (TdLN) and the tumor microenvironment, not only improving the efficacy of ICB therapy through slow release, but also exhibiting dual regulatory effects on the tumor and TdLN.
Many bacterial pathogens employ the type III secretion system (T3SS) to translocate effector proteins into eukaryotic cells to overcome host defenses. To date, most of our knowledge about the T3SS ...molecular architecture comes from the studies on animal pathogens. In plant pathogens, nine Hrc proteins are believed to be structural components of the T3SS, of which HrcC and HrcJ form the outer and inner rings of the T3SS, respectively. Here, we demonstrated that a novel outer membrane-bound protein (HpaM) of Xanthomonas campestris pv. campestris is critical for the type III secretion and is structurally and functionally conserved in phytopathogenic Xanthomonas spp. We showed that the C-terminus of HpaM extends into the periplasm to interact physically with HrcJ and the middle part of HpaM interacts physically with HrcC. It is clear that the outer and inner rings compose the main basal body of the T3SS apparatus in animal pathogens. Therefore, we presume that HpaM may act as a T3SS structural component, or play a role in assisting assembling or affecting the stability of the T3SS apparatus. HpaM is a highly prevalent and specific protein in Xanthomonas spp., suggesting that the T3SS of Xanthomonas is distinctive in some aspects from other pathogens.
We present a dual-mode imaging system operating on visible and long-wave infrared wavelengths for achieving the noncontact and nonobtrusive measurements of breathing rate and pattern, no matter ...whether the subjects use the nose and mouth simultaneously, alternately, or individually when they breathe. The improved classifiers in tandem with the biological characteristics outperformed the custom cascade classifiers using the Viola-Jones algorithm for the cross-spectrum detection of face and nose as well as mouth. In terms of breathing rate estimation, the results obtained by this system were verified to be consistent with those measured by reference method via the Bland-Altman plot with 95% limits of agreement from −2.998 to 2.391 and linear correlation analysis with a correlation coefficient of 0.971, indicating that this method was acceptable for the quantitative analysis of breathing. In addition, the breathing waveforms extracted by the dual-mode imaging system were basically the same as the corresponding standard breathing sequences. Since the validation experiments were conducted under challenging conditions, such as the significant positional and abrupt physiological variations, we stated that this dual-mode imaging system utilizing the respective advantages of RGB and thermal cameras was a promising breathing measurement tool for residential care and clinical applications.
We present herein a rare case of large vascular and cardiac metastases of low-grade endometrial stromal sarcoma (LG-ESS) in a female patient, which occurred after misdiagnosis of endometrial stromal ...nodule (ESN) as submucosal leiomyoma 7 years ago. Preoperative three-dimensional CT reconstruction was used to assess the extent of the lesion. The patient underwent radical resection: thrombectomy and total hysterectomy with bilateral salpingo-oophorectomy without establishing the cardiopulmonary bypass. Intraoperative transesophageal ultrasound (TEE) was used to monitor whether the intracardiac mass was removed completely. To date, this patient is alive without any evidence of recurrence 3 years after surgery. The differential diagnosis of ESN and LG-ESS is often difficult. A clear distinction can only be reliably made after histological analysis of the tumor’s entire interface with the neighboring myometrium. This case highlights that follow-ups of patients with ESN are important. Regular follow-up can detect metastasis and recurrence of misdiagnosed LG-ESS as early as possible. Distant metastasis of LG-ESS is rare, especially involving large vessels or the heart. The treatment should largely rely on multidisciplinary cooperation. Although the surgery is traumatic, the perioperative mortality rate is low, and patients can avoid death from congestive heart failure or sudden death.
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