Notes

Bone fragments morphogenetic necessary protein 2 upregulates SERPINE2 phrase via noncanonical SMAD2/3 and also p38 MAPK signaling pathways inside human granulosa-lutein cells.
In this article, we summarized and analyzed the multi-dimensional epigenetic effects of all 6 subtypes of flavonoids (including flavonols, flavones, isoflavones, flavanones, flavanols, and anthocyanidin) in different cancer types. Additionally, our report also provides new insights and a promising direction for future research and development of flavonoids in tumor prevention and treatment via epigenetic modification, in order to realize their potential as cancer therapeutic agents.ROS1 rearrangements have been identified as driver mutations, accounting for 1-2% of lung adenocarcinoma, but are extremely rare in case of lung squamous cell carcinoma. In this work, we report a lung squamous cell carcinoma in a patient with peripheral lung cancer radiological manifestation, harboring ROS1 rearrangement, with high sensitivity to crizotinib. Y-27632 price Our findings suggest that clinicians should pay more attention toward the occurrence of ROS1 rearrangements and the application of crizotinib for lung squamous cell carcinoma treatment.
We compared treatment outcomes and toxicities of photon radiotherapy
proton beam therapy (PBT) and evaluated radiation field effects for T1-3 squamous cell carcinoma of the thoracic esophagus (EC) without lymph node metastasis.

Medical records of 77 patients with T1-3N0M0 thoracic EC treated with radiotherapy between 2011 and 2019 were retrospectively analyzed. Among these patients, 61 (79.2%) individuals had T1 EC. The initial clinical target volume encompassed the whole esophagus with or without supraclavicular and/or abdominal lymph nodes (extended-field radiotherapy; 67 patients, 87.0%) or the area 3-5 cm craniocaudally and 1-2 cm radially from the gross tumor volume (involved-field radiotherapy; 10 patients, 13.0%). The final clinical target volume included margins of at least 1cm from the gross tumor volume, with total radiation doses of 50-66 (median, 66) cobalt gray equivalent. Three-dimensional conformal radiotherapy, intensity-modulated radiotherapy, and PBT were used in twenty-four, five, and forty-eight patients, respectively. Concurrent chemotherapy was administered to 17 (22.0%) patients overall and only five (8.0%) T1 patients.

PBT showed significantly lower lung and heart radiation exposure in mean dose, V5, V10, V20, and V30 than photon radiotherapy. The median follow-up for all patients was 46 (interquartile range, 22-72) months. The 5-year progression-free survival and overall survival rates were 56.5 and 64.9%, respectively, with no significant survival difference between photon radiotherapy and PBT. In patients with T1 EC, 5-year progression-free survival and overall survival rates were 62.6 and 73.5%, respectively.

Extended-field radiotherapy using modern radiotherapy techniques without chemotherapy showed satisfactory clinical outcomes for lymph node-negative T1 EC.
Extended-field radiotherapy using modern radiotherapy techniques without chemotherapy showed satisfactory clinical outcomes for lymph node-negative T1 EC.Hypopharyngeal squamous-cell carcinoma (HSCC) is a relatively rare head and neck cancer, with great variation in patient outcomes. This study aimed to develop a prognostic nomogram for patients with HSCC. From the Surveillance, Epidemiology, and End Results (SEER) database, we retrieved the clinical data of 2198 patients diagnosed with HSCC between 2010 and 2016. The patients were randomly assigned at a 41 ratio to the training set or the validation set. An external validation was performed by a set of 233 patients with locally advanced HSCC treated at our center. A Cox proportional hazards regression model was used to assess the relationship between each variable and overall survival (OS). Cox multivariate regression analysis was performed, and the results were used to develop a prognostic nomogram. The calibration curve and concordance index (C-index) were used to evaluate the accuracy of the prognostic nomogram. With a median overall follow-up time of 41 months (interquartile range 20 to 61), the median OS for the entire cohort of SEER database was 24 months. The 3-year and 5-year OS rates were 41.3% and 32.5%, respectively. The Cox multivariate regression analysis of the training set showed that age, marital status, race, T stage, N stage, M stage, TNM stage, local treatment, and chemotherapy were correlated with OS. The nomogram showed a superior C-index over TNM stage (training set 0.718 vs 0.627; validation set 0.708 vs 0.598; external validation set 0.709 vs 0.597), and the calibration curve showed a high level of concordance between the predicted OS and the actual OS. The nomogram provides a relatively accurate and applicable prediction of the survival outcome of patients with HSCC.Glioblastoma is the most common primary brain malignancy with limited treatment options. EphA2 is a tumor-associated-antigen overexpressed in glioblastoma. Pre-clinical studies have demonstrated the promise of EphA2-redirected CAR T-cells against glioblastoma. We conduct the first-in-human trial of EphA2-redirected CAR T-cells in patients with EphA2-positive recurrent glioblastoma and report the results of three patients enrolled as the first cohort receiving the starting dosage (1×106 cells/kg). A single infusion of EphA2-redirected CAR T-cells was administrated intravenously, with the lymphodepletion regimen consisting of fludarabine and Cyclophosphamide. In two patients, there was grade 2 cytokine release syndrome accompanied by pulmonary edema, which resolved completely with dexamethasone medication. Except that, there was no other organ toxicity including neurotoxicity. In both the peripheral blood and cerebral-spinal-fluid, we observed the expansion of CAR T-cells which persisted for more than four weeks. In one patient, there was a transit diminishment of the tumor. Among these three patients, one patient reported SD and two patients reported PD, with overall survival ranging from 86 to 181 days. At the tested dose level (1×106 cells/kg), intravenously infusion of EphA2-rediretected CAR T-cells were preliminary tolerable with transient clinical efficacy. Future study with adjusted dose and infusion frequency of CAR T-cells is warranted.
NCT03423992.
NCT03423992.To explore the value of apparent diffusion coefficient (ADC), intravoxel incoherent motion (IVIM), and diffusional kurtosis imaging (DKI) based on diffusion weighted magnetic resonance imaging (DW-MRI) in differentiating benign and malignant breast lesions. A total of 215 patients with breast lesions were prospectively collected for breast MR examination. Single exponential, IVIM, and DKI models were calculated using a series of b values. Parameters including ADC, perfusion fraction (f), tissue diffusion coefficient (D), perfusion-related incoherent microcirculation (D*), average kurtosis (MK), and average diffusivity (MD) were compared between benign and malignant lesions. ROC curves were used to analyze the optimal diagnostic threshold of each parameter, and to evaluate the diagnostic efficacy of single and combined parameters. ADC, D, MK, and MD values were significantly different between benign and malignant breast lesions (P less then 0.001). Among the single parameters, ADC had the highest diagnostic efficiency (sensitivity 91.45%, specificity 82.54%, accuracy 88.84%, AUC 0.915) and the best diagnostic threshold (0.983 μm2/ms). The combination of ADC and MK offered high diagnostic performance (sensitivity 90.79%, specificity 85.71%, accuracy 89.30%, AUC 0.923), but no statistically significant difference in diagnostic performance as compared with single-parameter ADC (P=0.268). The ADC, D, MK, and MD parameters have high diagnostic value in differentiating benign and malignant breast lesions, and of these individual parameters the ADC has the best diagnostic performance. Therefore, our study revealed that the use of ADC alone should be useful for differentiating between benign and malignant breast lesions, whereas the combination of MK and ADC might improve the diagnostic performance to some extent.Surgery for pituitary adenomas (PAs) with cavernous sinus (CS) invasion in Knosp grade 4 is a great challenge and whether to adopt a conservative or aggressive surgical strategy is controversial. The aim of this study is to provide the outcomes and complications of an aggressive resection strategy for Knosp grade 4 PAs with transsphenoidal endoscopic surgery. Outcomes and complications were retrospectively analyzed in 102 patients with Knosp grade 4 PAs. Among them, primary PAs were seen in 60 patients and recurrent PAs were seen in 42 cases. Gross total resection (GTR) of the entire tumor was achieved in 72 cases (70.6%), subtotal tumor resection (STR) in 18 cases (17.6%), and partial tumor resection (PTR) in 12 cases (11.8%). Additionally, GTR of the tumor within the CS was achieved in 82 patients (80.4%), STR in 17 patients (16.7%), and PTR in 3 patients (2.9%). Statistical analyses showed that both recurrent tumors and firm consistency tumors were adverse factors for complete resection (P less then 0.05). Patients with GTR of the entire tumor were more likely to have favorable endocrine and visual outcomes than those with incomplete resection (P less then 0.05). Overall, the most common surgical complication was new cranial nerve palsy (n=7, 6.8%). The incidence of internal carotid artery (ICA) injury and postoperative cerebrospinal fluid (CSF) leakage was 2.0% (n=2) and 5.9% (n=6), respectively. Six patients (5.9%) experienced tumor recurrence postoperatively. For experienced neuroendoscopists, an aggressive tumor resection strategy via transsphenoidal endoscopic surgery may be an effective and safe option for Knosp grade 4 PAs.Multiple myeloma (MM) is a cancer of terminally differentiated plasma cells (PCs) that develop at multiple sites within the bone marrow (BM). MM is treatable but rarely curable because of the frequent emergence of drug resistance and relapse. Increasing evidence indicates that the BM microenvironment plays a major role in supporting MM-PC survival and resistance to therapy. The BM microenvironment is a complex milieu containing hematopoietic cells, stromal cells, endothelial cells, immune cells, osteoclasts and osteoblasts, all contributing to the pathobiology of MM, including PC proliferation, escape from immune surveillance, angiogenesis and bone disease development. Small extracellular vesicles (EVs) are heterogenous lipid structures released by all cell types and mediate local and distal cellular communication. In MM, EVs are key mediators of the cross-talk between PCs and the surrounding microenvironment because of their ability to deliver bioactive cargo molecules such as lipids, mRNAs, non-coding regulatory RNA and proteins. Hence, MM-EVs highly contribute to establish a tumor-supportive BM niche that impacts MM pathogenesis and disease progression. In this review, we will first highlight the effects of RNA-containing, MM-derived EVs on the several cellular compartments within the BM microenvironment that play a role in the different aspects of MM pathology. We will also touch on the prospective use of MM-EV-associated non-coding RNAs as clinical biomarkers in the context of "liquid biopsy" in light of their importance as a promising tool in MM diagnosis, prognosis and prediction of drug resistance.
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