An In Vivo Dual-Observation Method to Monitor Tumor Mass and Tumor-Surface Blood Vessels for Developing Anti-Angiogenesis Agents against Submillimeter Tumors.

Managing metastasis at the early stage and detecting and treating submillimeter tumors at early metastasis are crucial for improving cancer prognosis. Angiogenesis is a critical target for developing drugs to detect and inhibit submillimeter tumor growth; however, drug development remains challenging because there are no suitable models for observing the submillimeter tumor mass and the surrounding blood vessels in vivo. We have established a xenograft subcutaneous submillimeter tumor mouse model with HT-29-RFP by transplanting a single spheroid grown on radiation-crosslinked gelatin hydrogel microwells. Here, we developed an in vivo dual-observation method to observe the submillimeter tumor mass and tumor-surface blood vessels using this model. RFP was detected to observe the tumor mass, and a fluorescent angiography agent FITC-dextran was administered to observe blood vessels via stereoscopic fluorescence microscopy. The anti-angiogenesis agent regorafenib was used to confirm the usefulness of this method. This method effectively detected the submillimeter tumor mass and tumor-surface blood vessels in vivo. Regorafenib treatment revealed tumor growth inhibition and angiogenesis downregulation with reduced vascular extremities, segments, and meshes. Further, we confirmed that tumor-surface blood vessel areas monitored using in vivo dual-observation correlated with intratumoral blood vessel areas observed via fluorescence microscopy with frozen sections. In conclusion, this method would be useful in developing anti-angiogenesis agents against submillimeter tumors.

Rare case report: a 26-year-old man with Eales' disease.

Purpose: To report the case of a 26-year-old male with bilateral Eales' disease that led to total blindness in the left eye and legal blindness in the right eye in a short time. Methods: A total clinical systemic examination, computed tomography, magnetic resonance imaging, genetic testing, and optical coherence tomography were performed in the reported case. Results: The eye condition was managed by scatter laser treatment, Anti-VEGF injections, anterior chamber paracentesis and trabeculectomy. Non-steroidal eye drops, as well as prostaglandin analogues, beta-blockers, and carbonic anhydrase inhibitors, have been used as local treatment. Systemic treatment included an intravenous methylprednisolone course, oral corticosteroids, azathioprine, mycophenolate mofetil and a total amount of 12 Anti-VEGF injections. Conclusion: Despite the aggressive treatment with oral steroids, immunosuppressants, and anti-VEGF injections, there were many exacerbations, and remission was not achieved. As a result, aggressive neovascular glaucoma developed, which led to total blindness in the left eye and legal blindness in the right eye. Abbreviations: HLA = human leukocyte antigens, Anti-VEGF = vascular endothelial growth factor inhibitors, BCVA = best corrected visual acuity, FA = fundus angiography, HBsAg = hepatitis B surface antigen, Anti-HCV = hepatitis C antibodies, TPHA = Treponema Pallidum hemagglutination assay, PCR = polymerase chain reaction, HSV = Herpes simplex virus, VZV = Varicella zoster virus, CMV = cytomegalovirus, IOP = intraocular pressure.

Association between Carotid Intraplaque Neovascularization Detected by Contrast-Enhanced Ultrasound and the Progression of Coronary Lesions in Patients Undergoing Percutaneous Coronary Intervention.

BACKGROUND: It is thought that the progression of vulnerable plaque is due in part to neovascularization, and plaque vulnerability is a useful approach for classifying cardiovascular risk. The aim of this retrospective study was to evaluate the correlation between carotid intraplaque neovascularization (IPN) detected on contrast-enhanced ultrasound and the progression of coronary lesions in patients undergoing percutaneous coronary intervention (PCI). METHODS: Contrast-enhanced ultrasound and angiography were performed in 131 patients undergoing PCI. All patients had angiograms obtained ≥12 months after PCI, and progression was defined using those angiograms. On the basis of angiographic images, patients were divided into progression and nonprogression groups. IPN was graded from 0 to 3 according to each plaque's microbubble appearance and extent, detected using contrast-enhanced ultrasound. The plaque with the highest IPN was used for analysis. Logistic regression and receiver operating characteristic analyses were applied to evaluate risk factors for predicting the progression of coronary lesions in patients undergoing PCI. RESULTS: In the progression group, the numbers of patients with IPN values of 0, 1, 2, and 3 were one (3.3%), nine (30.0%), 16 (53.3%), and four (13.3%), respectively. Significant differences were found in maximum plaque height and IPN between groups. IPN and maximum plaque height were independent risk contributors to coronary lesion progression in patients undergoing PCI. The sensitivity, specificity, positive predictive value, and negative predictive value of IPN of 1.5 and to predict the progression of coronary lesions were 67%, 91%, 68%, and 89%, respectively. The area under the curve was 0.822. CONCLUSIONS: Carotid plaque neovascularization was correlated with the progression of coronary lesions in patients undergoing PCI. IPN is a clinically useful tool for detecting the progression of coronary lesions and for risk stratification, especially in patients >60 years old.

Risk factors for ocular neovascularization after central retinal artery occlusion.

BACKGROUND: To report the incidence and risk factors associated with ocular neovascularization (NV) in patients with central retinal artery occlusion (CRAO). METHODS: This retrospective study included patients diagnosed with acute CRAO in a single tertiary center. Medical charts were reviewed for ocular NV occurrences. We analyzed systemic and ocular conditions on first visit and demographic data. RESULTS: Eighty-seven eyes were eligible for this study. Among these, 13 eyes had ocular NV after CRAO, with an incidence of 15%. The prevalences of hypertension, diabetes mellitus, history of stroke, chronic kidney disease (CKD), and age at first visit were higher among patients with ocular NV than among patients without ocular NV after CRAO. Moreover, most patients with CKD in the ocular NV group had undergone dialysis. A multivariate regression analysis revealed that CKD (hazard ratio [HR]: 9.27, 95% CI, 1.87-46.05, p = 0.006) and glaucoma history (HR: 7.52, 95% CI, 1.14-49.46, p = 0.036) were significant risk factors for developing ocular NV among patients with CRAO. CONCLUSION: CKD and glaucoma history were significant risk factors for developing ocular NV after CRAO, particularly among patients that underwent dialysis.

The role of galectins­1, 3, 7, 8 and 9 as potential diagnostic and therapeutic markers in ovarian cancer (Review).

The incidence of ovarian cancer is increasing, particularly throughout the highly developed countries, while this cancer type remains a major diagnostic and therapeutic challenge. The currently poorly recognized lectins called galectins have various roles in interactions occurring in the tumor microenvironment. Galectins are involved in tumor­associated processes, including the promotion of growth, adhesion, angiogenesis and survival of tumor cells. Results of research studies performed so far point to a complex role of galectins­1, 3, ­7, ­8 and ­9 in carcinogenesis of ovarian cancer and elucidation of the mechanisms may contribute to novel forms of therapies targeting the proteins. In particular, it appears important to recognize the reasons for changes in expression of galectins. Galectins also appear to be a useful diagnostic and prognostic tool to evaluate tumor progression or the efficacy of therapies in patients with ovarian cancer, which requires further study.

Impact of Chemotherapy and Radiation Therapy on Inflammatory Response, Neovascularization, and Capsule Formation of Acellular Dermal Matrix in Breast Reconstruction: Analysis of the BREASTrial Biopsy Specimens.

BACKGROUND: The Breast Reconstruction Evaluation of Acellular Dermal Matrix as a Sling Trial is a single-center, blinded, prospective, randomized, controlled trial established to compare outcomes using two popular types of acellular dermal matrices, AlloDerm and DermaMatrix, in tissue expander breast reconstruction. This study used the acellular dermal matrix biopsy specimens from the trial to evaluate how adjuvant therapy influences inflammation, neovascularization, and capsule formation of the acellular dermal matrix. METHODS: Punch biopsy specimens were taken at the time of expander exchange and were analyzed by a blinded pathologist. The inflammatory response was quantified by the number of fibroblasts, giant cells, and lymphocytes. Neovascularization and capsule formation were similarly quantified by the number of new capillaries and capsule presence and thickness, respectively. RESULTS: Histology specimens were collected from 109 patients (170 breasts). In the absence of adjuvant therapy, there was no significant difference between AlloDerm and DermaMatrix in terms of inflammation, neovascularization, or capsule thickness. Both acellular dermal matrices showed a significant decrease in inflammation and neovascularization with adjuvant therapy. When chemotherapy and radiation therapy were used, the decrease in inflammation was greatest for the group reconstructed with DermaMatrix (p < 0.039). CONCLUSIONS: Adjuvant therapy influences the inflammatory response, neovascularization, and capsule formation in both acellular dermal matrices. Adjuvant therapy has a protective effect on the inflammatory response toward both acellular dermal matrices in breast reconstruction. In the setting of chemotherapy and radiation therapy, DermaMatrix produced the greatest reduction in inflammation. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

Classifying neovascular age-related macular degeneration with a deep convolutional neural network based on optical coherence tomography images.

Neovascular age-related macular degeneration (nAMD) is among the main causes of visual impairment worldwide. We built a deep learning model to distinguish the subtypes of nAMD using spectral domain optical coherence tomography (SD-OCT) images. Data from SD-OCT images of nAMD (polypoidal choroidal vasculopathy, retinal angiomatous proliferation, and typical nAMD) and normal healthy patients were analyzed using a convolutional neural network (CNN). The model was trained and validated based on 4749 SD-OCT images from 347 patients and 50 healthy controls. To adopt an accurate and robust image classification architecture, we evaluated three well-known CNN structures (VGG-16, VGG-19, and ResNet) and two customized classification layers (fully connected layer with dropout vs. global average pooling). Following the test set performance, the model with the highest classification accuracy was used. Transfer learning and data augmentation were applied to improve the robustness and accuracy of the model. Our proposed model showed an accuracy of 87.4% on the test data (920 images), scoring higher than ten ophthalmologists, for the same data. Additionally, the part that our model judged to be important in classification was confirmed through Grad-CAM images, and consequently, it has a similar judgment criteria to that of ophthalmologists. Thus, we believe that our model can be used as an auxiliary tool in clinical practice.

Letter to the Editor: Reply to Manuscript "Role of Ultra-widefield Imaging in Eales' Disease: A Case Series".

We read with interest the article "Role of Ultra-widefield Imaging in Eales' Disease: A Case Series" by Agarwal et al. We would like to congratulate the authors for their nice work and make few observations.We noted few discrepancies between the results and conclusions. Results revealed disease activity in 10/57 (17.5%), 20/57 (35%), and 29/57 (50.9%) patient visits with clinical examination, UWF Optos imaging, and wide-field FFA respectively. However, authors conclude that "ultra-widefield imaging is a very helpful tool in the management of a patient with Eales'disease." This is in spite of the fact that widefield FA resulted in better documentation in 56% of the patient visits in their series. Widefield FA detected significantly more number of active vasculitis as compared to Optos, and alteration in the treatment plan was done in 18/57 (31.6%) patient visits based on FA.

Proteomic Distributions in CD34+ Microvascular Niche Patterns of Glioblastoma.

The poor clinical prognosis and microvascular patterns of glioblastoma (GBM) are of serious concern to many clinicians and researchers. However, very few studies have examined the correlation between microvascular niche patterns (MVNPs) and proteomic distribution. In this study, CD34 immunofluorescence staining and matrix-assisted laser desorption ionization-mass spectrometry imaging (MALDI-IMS) technology were used to investigate the protein distributions in MVNPs. CD34+ microvascular phenotype could be divided into four types: microvascular sprouting (MS), vascular cluster (VC), vascular garland (VG), and glomeruloid vascular proliferation (GVP). Based on such characteristics, MVNPs were divided into two types by cluster analysis, namely, type I, comprising primarily MS and VC, and type II, comprising many VGs and GVPs. Survival analysis indicated the type of MVNPs to be an independent prognostic factor for progression-free and overall survival in GBM. MALDI-IMS results showed the peaks at m/z 1037 and 8960 to exhibit stronger ion signals in type II, while those at m/z 3240 and 3265 exhibited stronger ion signals in type I. The findings may assist future research on therapy and help predict prognosis in GBM. However, due to the limited number of studies, more well-designed studies are warranted to further verify our results.

Arteriogenesis and Therapeutic Angiogenesis-An Update.

Vascular occlusive diseases such myocardial infarction, peripheral artery disease of the lower extremities, or stroke still represent a substantial health burden worldwide [...].

Development and Validation of a Model Including Distinct Vascular Patterns to Estimate Survival in Hepatocellular Carcinoma.

Importance: Because of tumor heterogeneity, traditional clinical variables remain insufficient to predict recurrence, which impairs long-term survival among patients undergoing radical hepatectomy for hepatocellular carcinoma (HCC). Vessels encapsulating tumor clusters (VETC) constitute a novel vascular pattern distinct from microvascular invasion (MVI), representing biological aggressiveness of HCC. Objective: To establish a model to estimate individualized recurrence-free survival (RFS) in HCC by integrating VETC and MVI. Design, Setting, and Participants: This prognostic study included 498 patients undergoing radical hepatectomy for HCC from 5 academic centers in China from January 1, 2013, to December 31, 2016, and consisted of 3 cohorts: training (243 [48.8%]), internal validation (122 [24.5%]), and external validation (133 [26.7%]). Follow-up was completed on March 30, 2020, and the data were analyzed from December 1 to 31, 2020. Exposures: VETC, MVI, tumor number, and maximum tumor size. Main Outcomes and Measures: The primary end point was RFS. The risk score for relative recurrence and nomogram for absolute RFS probability were derived from the final model, which contained variables recommended by multivariate least absolute shrinkage and selection operator Cox proportional hazards regression analysis. Their performance was quantified using the Harrell concordance index (C index), the time-dependent area under the receiver operating characteristic curve, and calibration curves and was compared with 6 prognostic systems. Recurrence-free survival was estimated by the Kaplan-Meier method, and RFS curves were compared using a log-rank test. Results: Among the 498 patients, 432 (86.7%) were men; the mean (SD) age at diagnosis was 51.4 (11.3) years. Independent predictors for RFS identified included VETC, MVI, tumor number, and maximum tumor size, which were incorporated into the multivariate model (VMNS model). The C index (0.702; 95% CI, 0.653-0.752) for the VMNS score of the training cohort was significantly higher than those of 6 conventional systems (0.587 [95% CI, 0.535-0.638] to 0.657 [95% CI, 0.606-0.708]). Different recurrence risk groups defined by the VMNS score showed significantly different 2-year RFS (low-risk group, 81.4% [SE, 0.036]; medium-risk group, 62.1% [SE, 0.054]; high-risk group, 30.1% [SE, 0.079]; P < .001). Calibration curves of the VMNS nomogram showed good agreement between the nomogram-predicted RFS probability and actual RFS proportion. The internal and external validation cohorts confirmed the results. Conclusions and Relevance: The VMNS model enabled individualized prognostication of RFS in patients with HCC undergoing curative resection.

Radiology- and gene-based risk stratification in small renal cell carcinoma: A preliminary study.

PURPOSE: Most small renal cell carcinomas (small RCCs) will remain indolent after detection, but some stage I RCCs still metastasize. There are no risk-stratification imaging factors that could be used to identify poor-prognosis patients based on genomic profiling. Here, we evaluated the relationships between imaging parameters and RNA expressions in small RCC and attempted to identify imaging factors that could be used as effective biomarkers. METHODS: We acquired biopsy specimens of 18 clear cell carcinomas that had undergone perfusion CT (pCT) and MRI between April 2018 and March 2019. We performed RNA sequencing, assessed RNA expressions, and calculated each tumor's cell-cycle progression (CCP) score, which has prognostic value in predicting metastatic progression. We classified the tumors into two groups: clear cell type A (ccA) and type B (ccB). CcA has better survival compared to ccB. We evaluated the following characteristics of each tumor: tumor size, presence of pseudocapsule, and fat. We used the pCT and MRI to measure each tumor's volume transfer constant (Ktrans), rate constant (Kep), extracellular extravascular volume fraction (VE), fractional plasma volume (VP), and apparent diffusion coefficient (ADC). The correlations between these small RCC imaging parameters and the tumor size and RNA expressions were determined. RESULTS: The tumor size was significantly correlated with Kep and inversely correlated with VE, VP, ADC, and hallmark angiogenesis. The CCP score was significantly inversely correlated with Ktrans and Kep. The ccA tumors tended to show a pseudocapsule on MRI. CONCLUSION: Tumor size was correlated with low perfusion, but not with prognostic factors based on genomic profiling. Imaging parameters (e.g., Ktrans and Kep) and tumor characteristics (e.g., pseudocapsule) may enable gene-based risk stratification in small RCC.

Artificial intelligence-based predictions in neovascular age-related macular degeneration.

PURPOSE OF REVIEW: Predicting treatment response and optimizing treatment regimen in patients with neovascular age-related macular degeneration (nAMD) remains challenging. Artificial intelligence-based tools have the potential to increase confidence in clinical development of new therapeutics, facilitate individual prognostic predictions, and ultimately inform treatment decisions in clinical practice. RECENT FINDINGS: To date, most advances in applying artificial intelligence to nAMD have focused on facilitating image analysis, particularly for automated segmentation, extraction, and quantification of imaging-based features from optical coherence tomography (OCT) images. No studies in our literature search evaluated whether artificial intelligence could predict the treatment regimen required for an optimal visual response for an individual patient. Challenges identified for developing artificial intelligence-based models for nAMD include the limited number of large datasets with high-quality OCT data, limiting the patient populations included in model development; lack of counterfactual data to inform how individual patients may have fared with an alternative treatment strategy; and absence of OCT data standards, impairing the development of models usable across devices. SUMMARY: Artificial intelligence has the potential to enable powerful prognostic tools for a complex nAMD treatment landscape; however, additional work remains before these tools are applicable to informing treatment decisions for nAMD in clinical practice.

Unaffected fellow eye neovascularization in patients with type 3 neovascularization: Incidence and risk factors.

PURPOSE: To evaluate the incidence and risk factors of neovascularization in unaffected fellow eyes of patients diagnosed with type 3 neovascularization in Korea. METHODS: This retrospective study included 93 unaffected fellow eyes of 93 patients diagnosed with type 3 neovascularization. For initial type 3 neovascularization diagnosis, optical coherence tomography and angiography were conducted. These baseline data were compared between patients with and without neovascularization in their fellow eyes during the follow-up period. RESULTS: The mean follow-up period was 66.1±31.1 months. Neovascularization developed in 49 (52.8%) fellow eyes after a mean period of 29.5±19.6 months. In the fellow eye neovascularization group, the incidence of soft drusen and reticular pseudodrusen was significantly higher than that in the non-neovascularization group (83.7% vs. 36.5%, p<0.001; 67.3% vs. 40.9%, p = 0.017, respectively), but the choroidal vascularity index (CVI) showed a significantly lower value (60.7±2.0% vs. 61.7±2.5%; p = 0.047). The presence of reticular pseudodrusen was related with the duration from baseline to development of fellow eye neovascularization (p = 0.038). CONCLUSION: Neovascularization developed in 52.8% of unaffected fellow eyes. The presence of soft drusen, reticular pseudodrusen, and lower CVI values can be considered risk factors of neovascularization in unaffected fellow eyes of patients with type 3 neovascularization. The lower CVI values suggest that choroidal ischemic change may affect the development of choroidal neovascularization in these patients.

Diagnostic accuracy of ultrasound shear wave elastography combined with superb microvascular imaging for breast tumors: A protocol for systematic review and meta-analysis.

BACKGROUND: Shear wave elastography (SWE) is a new ultrasonic elastography technique for evaluating the hardness of living tissue by measuring the propagation velocity of shear wave in tissue, which is characterized by real-time, non-invasive and quantitative. The SWE technique can be used to diagnose the lesions of different tissues and organs, and the quantitative measurement of SWE is considered as more objective information about breast masses. Superb microvascular imaging (SMI) is a new noninvasive Doppler ultrasound imaging method, which can display blood flow information with high spatial resolution and high frame rate, while keeping the minimum low-speed blood flow components. Therefore, SMI can diagnose diseases closely related to angiogenesis at a relatively early stage. However, the results of these studies have been contradictory. The present meta-analysis aimed at determining the accuracy of SWE combined with SMI in the differential diagnosis between benign and malignant breast lesions. METHODS: We will search PubMed, Web of Science, Cochrane Library, and Chinese biomedical databases from their inceptions to the April 18, 2021, without language restrictions. Two authors will independently carry out searching literature records, scanning titles and abstracts, full texts, collecting data, and assessing risk of bias. Review Manager 5.2 and Stata14. 0 software will be used for data analysis. RESULTS: This systematic review will determine the accuracy of shear wave elastography combined with superb microvascular imaging in the differential diagnosis between benign and malignant breast tumors. CONCLUSION: Its findings will provide helpful evidence for the accuracy of shear wave elastography combined with superb microvascular imaging in the differential diagnosis between benign and malignant breast tumors. SYSTEMATIC REVIEW REGISTRATION: INPLASY202150075.

Differential roles of farnesoid X receptor (FXR) in modulating apoptosis in cancer cells.

Cancer is one of the leading causes of mortality in the world. The conventional treatment strategies of cancer are surgery, radiation, and chemotherapy. However, in the advanced stage of the disease chemotherapy is the prime treatment and it is effective in only less than 10% of the patients. Therefore, there is an urgent need to find out novel therapeutic targets and delineate the mechanism of action of these targets for better management of this disease. Recent studies have shown that some of the proteins have differential role in different cancers. Therefore, it is pertinent that the targeting of these proteins should be based on the type of cancer. The nuclear receptor, FXR, is one of the vital proteins that regulate cell apoptosis. Besides, it also regulates other processes such as cell proliferation, angiogenesis, invasion, and migration. Studies suggest that the low or high expression of FXR is associated with the progression of carcinogenesis depending on the cancer types. Due to the diverse expression, it functions as both tumor suppressor and promoter. Previous studies suggest the overexpression of FXR in breast, lung, esophageal, and prostate cancer, which is related to poor survival and poor prognosis in patients. Therefore, targeting FXR with agonists and antagonists play different outcome in different cancers. Hence, this review describes the role of FXR in different cancers and the role of its inhibitors and activators for the prevention and treatment of various cancers.

Effects of High Fat Versus Normal Diet on Extracellular Vesicle-Induced Angiogenesis in a Swine Model of Chronic Myocardial Ischemia.

Background Mesenchymal stem cell-derived extracellular vesicles (EVs) promote angiogenesis in the ischemic myocardium. This study examines the difference in vascular density, myocardial perfusion, molecular signaling, and gene expression between normal diet (ND) and high fat diet (HFD) groups at baseline and following intramyocardial injection of EVs. Methods and Results Intact male Yorkshire swine fed either an ND (n=17) or HFD (n=14) underwent placement of an ameroid constrictor on the left circumflex coronary artery. Subsequently, animals received either intramyocardial injection of vehicle-saline as controls; (ND-controls n=7, HFD-controls, n=6) or EVs; (ND-EVs n=10, HFD-EVs n=8) into the ischemic territory. Five weeks later, myocardial function, perfusion, vascular density, cell signaling, and gene expression were examined. EVs improved indices of myocardial contractile function, myocardial perfusion, and arteriogenesis in both dietary cohorts. Interestingly, quantification of alpha smooth muscle actin demonstrated higher basal arteriolar density in HFD swine compared with their ND counterparts; whereas EVs were associated with increased CD31-labeled endothelial cell density only in the ND tissue, which approached significance. Levels of total endothelial nitric oxide synthase, FOXO1 (forkhead box protein O1) , transforming growth factor-ß, phosphorylated VEGFR2 (vascular endothelial growth factor receptor 2), and phosphorylated MAPK ERK1/ERK2 (mitogen-activated protein kinase) were higher in ischemic myocardial lysates from ND-controls compared with HFD-controls. Conversely, HFD-control tissue showed increased expression of phosphorylated endothelial nitric oxide synthase, phosphorylated FOXO1, VEGFR2, and MAPK ERK1/ERK2 with respect to ND-controls. Preliminary gene expression studies indicate differential modulation of transcriptional activity by EVs between the 2 dietary cohorts. Conclusions HFD produces a profound metabolic disorder that dysregulates the molecular mechanisms of collateral vessel formation in the ischemic myocardium, which may hinder the therapeutic angiogenic effects of EVs.

The tumorigenic and therapeutic functions of exosomes in colorectal cancer: Opportunity and challenges.

Most cells release extracellular vesicles (EVs) mediating intercellular communication via transferring various biomolecules including proteins, nucleic acids, and lipids. A subset of EVs is exosomes that promote tumorigenesis. Different tumour cells such as colorectal cancer (CRC) cells produce exosomes that participate in the progression of CRC. Exosomes cargo including proteins and miRNAs not only support proliferation and metastasis of tumour cells but also mediate chemoresistance, immunomodulation and angiogenesis. In addition, as exosomes are present in most body fluids, they can hold the great capacity for clinical usage in early diagnosis and prognosis of CRC. Exosomes from CRC (CRC-Exo) differentially contain proteins and miRNAs that make them a promising candidate for CRC diagnosis by a simple liquid-biopsy. Despite hopeful results, some challanges about exosomes terminology and definition remains to be clarified in further experiments. In addition, there are little clinical trials regarding the application of exosomes in CRC treatment, therefore additional studies are essential focusing on exosome biology and translation of preclinical findings into the clinic. The present study discusses the key role of exosomes in CRC progression and diagnosis. Furthermore, it describes the opportunity and challenges associated with using exosomes as tumour markers.

Recanalization-Like Neovascularization of Placental Intervillous Hematoma: First Two Reports.

Placental intervillous hematomas have not previously been reported to undergo any sort of change, maturation, or healing. In this article, we present the first 2 case reports of recanalization-like neovascularization within placental hematomas: a 0.15 cm focus in an intervillous fibrin thrombus and a 0.2 cm focus in a subchorionic hematoma. Increased recognition and further studies are needed to gain a better understanding of this seemingly rare phenomenon and the factors that govern the lack of typical organization in placental hematomas. This might lead to a deeper knowledge of the repair process in general and shed light on how to control it in diseases caused by excessive repair.

Role of A Novel Angiogenesis FKBPL-CD44 Pathway in Preeclampsia Risk Stratification and Mesenchymal Stem Cell Treatment.

CONTEXT: Preeclampsia is a leading cardiovascular complication in pregnancy lacking effective diagnostic and treatment strategies. OBJECTIVE: To investigate the diagnostic and therapeutic target potential of the angiogenesis proteins, FK506-binding protein like (FKBPL) and CD44. DESIGN AND INTERVENTION: FKBPL and CD44 plasma concentration or placental expression were determined in women pre- or postdiagnosis of preeclampsia. Trophoblast and endothelial cell function was assessed following mesenchymal stem cell (MSC) treatment and in the context of FKBPL signaling. SETTINGS AND PARTICIPANTS: Human samples prediagnosis (15 and 20 weeks of gestation; n ≥ 57), or postdiagnosis (n = 18 for plasma; n = 4 for placenta) of preeclampsia were used to determine FKBPL and CD44 levels, compared to healthy controls. Trophoblast or endothelial cells were exposed to low/high oxygen, and treated with MSC-conditioned media (MSC-CM) or a FKBPL overexpression plasmid. MAIN OUTCOME MEASURES: Preeclampsia risk stratification and diagnostic potential of FKBPL and CD44 were investigated. MSC treatment effects and FKBPL-CD44 signaling in trophoblast and endothelial cells were assessed. RESULTS: The CD44/FKBPL ratio was reduced in placenta and plasma following clinical diagnosis of preeclampsia. At 20 weeks of gestation, a high plasma CD44/FKBPL ratio was independently associated with the 2.3-fold increased risk of preeclampsia (odds ratio = 2.3, 95% confidence interval [CI] 1.03-5.23, P = 0.04). In combination with high mean arterial blood pressure (>82.5 mmHg), the risk further increased to 3.9-fold (95% CI 1.30-11.84, P = 0.016). Both hypoxia and MSC-based therapy inhibited FKBPL-CD44 signaling, enhancing cell angiogenesis. CONCLUSIONS: The FKBPL-CD44 pathway appears to have a central role in the pathogenesis of preeclampsia, showing promising utilities for early diagnostic and therapeutic purposes.