The use of peripheral CD3+γδ+Vδ2+ T lymphocyte cells in combination with the ALBI score to predict immunotherapy response in patients with advanced hepatocellular carcinoma: a retrospective study.

BACKGROUND: Currently, there is a lack of effective indicators for predicting the efficacy of immunotherapy in patients with advanced hepatocellular carcinoma (HCC). This study aimed to investigate the expression and prognostic value of peripheral T lymphocyte subsets in advanced HCC. METHODS: Patients with advanced HCC who were treated with immune checkpoint inhibitors (ICIs) from December 2021 to December 2023 were included in the study. Flow cytometry was used to detect lymphocyte subsets before treatment. The patients were divided into disease control (DC) and nondisease control (nDC) groups based on treatment efficacy. Relationships between the clinical characteristics/peripheral T lymphocytes and immunotherapy efficacy were analyzed. The effectiveness of peripheral T lymphocyte subsets in predicting immunotherapy efficacy for patients with advanced HCC was analyzed using receiver operating characteristic (ROC) curves. RESULTS: A total of 40 eligible patients were included in this study. Non-DC was significantly associated with higher albumin-bilirubin (ALBI) scores. The percentages of γδ+Vδ2+PD1+ T cells and γδ+Vδ2+Tim3+ T cells were greater in the nDC group than in the DC group. Multivariable regression analysis revealed that the ALBI score and T lymphocytes expressing γδ+Vδ2+PD1+ and γδ+Vδ2+Tim3+ were founded to be independent influencing factors. The area under the ROC curve (AUC) values for these combinations was 0.944 (95% CI, 0.882 ~ 1.000). CONCLUSIONS: The calculation of the ALBI score and determination of the percentages CD3+γδ+Vδ2+PD1+ T lymphocytes and CD3+γδ+Vδ2+Tim3+ T lymphocytes in the peripheral blood of patients with advanced HCC are helpful for predicting the patients' responses to ICIs, helping to screen patients who may clinically benefit from immunotherapy. RETROSPECTIVELY REGISTERED: number: ChiCTR2400080409, date of registration: 2024-01-29.

Mitochondria-Targeting Metallodrugs for Cancer Therapy: Perspectives from Cell Death Modes.

Mitochondria, recognized as the cellular powerhouses, are indispensable organelles responsible for crucial cellular processes, such as energy metabolism, material synthesis, and signaling transduction. Their intricate involvement in a broad spectrum of diseases, particularly cancer, has propelled the exploration of mitochondria-targeting treatment as a promising strategy for cancer therapy. Since the groundbreaking discovery of cisplatin, the trajectory of research on the development of metal complexes have been marked by continuous advancement, giving rise to a diverse array of metallodrugs characterized by variations in ligand types, metal center properties, and oxidation states. By specifically targeting mitochondria, these metallodrugs exhibit the remarkable ability to elicit various programmed cell death pathways, encompassing apoptosis, autophagy, and ferroptosis. This review primarily focuses on recent developments in transition metal-based mitochondria-targeting agents, offering a comprehensive exploration of their capacity to induce distinct cell death modes. The aim is not only to disseminate knowledge but also to stimulate an active field of research toward new clinical applications and novel anticancer mechanisms.

Enhancing Extracellular Electron Transfer of a 3D-Printed Shewanella Bioanode with Riboflavin-Modified Carbon Black Bioink.

3D printing of a living bioanode holds the potential for the rapid and efficient production of bioelectrochemistry systems. However, the ink (such as sodium alginate, SA) that formed the matrix of the 3D-printed bioanode may hinder extracellular electron transfer (EET) between the microorganism and conductive materials. Here, we proposed a biomimetic design of a 3D-printed Shewanella bioanode, wherein riboflavin (RF) was modified on carbon black (CB) to serve as a redox substance for microbial EET. By introducing the medicated EET pathways, the 3D-printed bioanode obtained a maximum power density of 252 ± 12 mW/m2, which was 1.7 and 60.5 times higher than those of SA-CB (92 ± 10 mW/m2) and a bare carbon cloth anode (3.8 ± 0.4 mW/m2). Adding RF reduced the charge-transfer resistance of a 3D-printed bioanode by 75% (189.5 ± 18.7 vs 47.3 ± 7.8 Ω), indicating a significant acceleration in the EET efficiency within the bioanode. This work provided a fundamental and instrumental concept for constructing a 3D-printed bioanode.

Mechanism of Intestinal Epithelial Absorption and Electrophysiological Regulation of the Shrimp Peptide QMDDQ.

We investigated the absorption mechanism of the shrimp peptide QMDDQ in small intestines, explored its physiological function in inhibiting neuronal hyperactivity, and verified its entry into the brain in vivo to display functional activity. The everted rat sac model and a Caco-2 paracellular absorption monolayer model were used, indicating that QMDDQ has a good absorption capacity with an apparent permeability coefficient (Papp) > 1 × 10-6 cm/s and the absorption of QMDDQ was concentration-dependent. When the concentration of QMDDQ was 1 mM and the transport time was 180 min, the highest absorption concentration of QMDDQ was 41.17 ± 3.48 µM (P < 0.05). The myosin light-chain kinase (MLCK)-specific inhibitor ML-7 and activator MPA, Western blotting, and immunofluorescence results showed that QMDDQ absorption takes place by mediating the MLCK-p-MLCK-MLC signaling pathway, reversibly opening the zonula occludens-1 (ZO-1), occludin in tight junctions (TJs), upregulating claudin-2 expression, and reaching targets through blood to inhibit neuronal overactivity. Results of fluorescence imaging in vivo verified that QMDDQ could enter the brain 4 h after oral administration. The results provide a theoretical foundation for the mechanism of paracellular absorption of active peptides and a starting point for the development of functional foods for Alzheimer's disease intervention.

Paget's disease of the nipple with underlying occult invasive carcinoma detected by magnetic resonance imaging and second-look ultrasound: Case report.

INTRODUCTION: Paget's disease of the nipple (PDN) is a rare and often misdiagnosed condition characterized by the infiltration of adenocarcinoma cells into the nipple epidermis. It poses substantial diagnostic and therapeutic challenges due to its similarity to benign dermatological conditions and its association with in situ or invasive carcinoma. CASE PRESENTATION: This report details the case of a 47-year-old woman with persistent nipple itching, rash, and occasional bloody discharge. No abnormalities were seen on the mammogram and ultrasound scans; punch biopsy was performed to confirm PDN. A small lesion missed by other imaging methods was detected via breast magnetic resonance imaging (MRI). A second-look ultrasound with needle localization enabled precise surgery. The pathology report after breast-conserving surgery (BCS) revealed invasive ductal carcinoma with no metastasis in the sentinel lymph node biopsy. DISCUSSION: PDN often mimics benign skin conditions, leading to delayed diagnosis. Furthermore, timely identification is crucial as PDN is frequently associated with underlying breast malignancies. Additional imaging, such as breast MRI, is essential for comprehensive evaluation, as it can reveal hidden lesions previously undetected by conventional mammography and ultrasound. A second-look ultrasound guided needle placement for tumor localization, enhancing surgical precision, aesthetics, and reducing patient harm. Surgical management, including mastectomy, BCS with radiotherapy, and oncoplastic surgery, offers suitable options without affecting recurrence or survival in selected patients. CONCLUSION: This case emphasizes the importance of employing additional imaging tools, such as breast MRI and second-look ultrasound for the early detection and surgical management of PDN.

miR-6076 targets BCL6 in SH-SY5Y cells to regulate amyloid-ß-induced neuronal damage.

Amyloid-ß1-42 (Aß1-42 ) is strongly associated with Alzheimer's disease (AD). The aim of this study is to elucidate whether and how miR-6076 participates in the modulation of amyloid-ß (Aß)-induced neuronal damage. To construct the neuronal damage model, SH-SY5Y cells were treated with Aß1-42 . By qRT-PCR, we found that miR-6076 is significantly upregulated in Aß1-42 -treated SH-SY5Y cells. After miR-6076 inhibition, p-Tau and apoptosis levels were downregulated, and cell viability was increased. Through online bioinformatics analysis, we found that B-cell lymphoma 6 (BCL6) was a directly target of miR-6076 via dual-luciferase reporter assay. BCL6 overexpression mediated the decrease in elevated p-Tau levels and increased viability in SH-SY5Y cells following Aß1-42 treatment. Our results suggest that down-regulation of miR-6076 could attenuate Aß1-42 -induced neuronal damage by targeting BCL6, which provided a possible target to pursue for prevention and treatment of Aß-induced neuronal damage in AD.

Elucidating the clinical and immunological value of m6A regulator-mediated methylation modification patterns in adrenocortical carcinoma.

N6-methyladenosine methylation (m6A) is a common type of epigenetic alteration that prominently affects the prognosis of tumor patients. However, it is unknown how the m6A regulator affects the tumor microenvironment (TME) cell infiltration in adrenocortical carcinoma (ACC) and how it affects the prognosis of ACC patients yet. The m6A alteration patterns of 112 ACC patients were evaluated, furthermore, the association with immune infiltration cell features was investigated. The unsupervised clustering method was applied to typify the m6A alteration patterns of ACC patients. The principal component analysis (PCA) technique was taken to create the m6A score to assess the alteration pattern in specific malignancies. We found two independent patterns of m6A alteration in ACC patients. The TME cell infiltration features were significantly in accordance with phenotypes of tumor immune-inflamed and immune desert in both patterns. The m6Ascore also served as an independent predictive factor in ACC patients. The somatic copy number variation (CNV) and patients prognosis can be predicted by m6A alteration patterns. Moreover, the ACC patients with high m6A scores had better overall survival (OS) and higher efficiency in immune checkpoint blockade therapy. Our work demonstrated the significance of m6A alteration to the ACC patients immunotherapy. The individual m6A alteration patterns analysis might contribute to ACC patients prognosis prediction and immunotherapy choice.

Strategies to prolong drug retention in solid tumors by aggregating Endo-CMC nanoparticles.

Developing a highly effective nano-drug delivery system with sufficient drug permeability and retention in tumors is still a major challenge for oncotherapy. Herein, a tumor microenvironment responsive, aggregable nanocarriers embedded hydrogel (Endo-CMC@hydrogel) was developed to inhibit the tumoral angiogenesis and hypoxia for enhanced radiotherapy. The antiangiogenic drug (recombinant human endostatin, Endo) loaded carboxymethyl chitosan nanoparticles (Endo-CMC NPs) was wrapped by 3D hydrogel to comprise the Endo-CMC@hydrogel. After peritumoral injection, the Endo-CMC NPs were released, invaded deeply into the solid tumor, and cross-linked with intratumoral calcium ions. The cross-linking process enabled these Endo-CMC NPs to form larger particles, leading to long retention in tumor tissue to minimize premature clearance. This Endo-CMC@hydrogel, integrating the abilities of good tumoral penetration, long retention of anti-drug, and alleviation of hypoxia in tumor tissue, greatly improved the therapeutic effect of radiotherapy. This work provides a proof-of-concept of tumor microenvironment-responding and an aggregable nano-drug delivery system as promising antitumor drug carriers for effective tumor therapy.

Multimodal Treatment with Cognitive Behavioral Therapeutic Intervention Plus Bladder Treatment Is More Effective than Monotherapy for Patients with Interstitial Cystitis/Bladder Pain Syndrome-A Randomized Clinical Trial.

(1) Background: Introduction: Interstitial cystitis/bladder pain syndrome (IC/BPS) not only induces physiological damage but also greatly affects psychological stress. Multidisciplinary therapy has been recommended for IC/BPS treatment, but clinical trial data of combined bladder therapy and cognitive behavioral therapy (CBT) are lacking. This study evaluated CBT efficacy in patients with IC/BPS. (2) Methods: Patients with IC/BPS were randomized to the bladder monotherapy (BT) or combined CBT (CBT) group. The primary endpoint was the self-reported outcome by global response assessment (GRA). Secondary endpoints included IC symptoms and problem index, bladder pain score, Beck's anxiety inventory (BAI), and depression inventory, and objective parameters were also compared. (3) Result: A total of 30 patients receiving BT and 30 receiving CBT therapy were enrolled. Significant improvement of the BAI at 8 (p = 0.045) and 12 weeks (p = 0.02) post-treatment was observed in the CBT group, with significantly greater GRA scores at 12 weeks (p < 0.001). Repeated measures analysis of variance showed a significant effect within the CBT group on IC/BPS patients' self-reported treatment outcomes (p = 0.001) and anxiety severity BAI scores (p = 0.033). (4) Conclusion: A multimodal treatment of CBT combined with suitable bladder treatment more effectively improves anxiety severity and treatment outcomes in patients with IC/BPS.

MiR-135a is highly expressed and aggravates inflammatory response in sepsis by targeting MYOM1.

BACKGROUND: Our research attempted to explore the effect of miR-135a on lipopolysaccharide (LPS)-induced THP-1cells damage and its potential mechanism. METHODS: LPS (1 µg/mL) was selected to mimic the injury of sepsis in vitro. qRT-PCR was used to detect miR-135a expression. The association between miR-135a and Myomesin 1 (MYOM1) was speculated bythe predication website and confirmed by the dual-luciferase assay. MYOM1 expression was observed by qRT-PCR and western blotting assays. The biological properties of THP-1cells were analyzed by cell counting kit-8 and flow cytometry assays. The concentration of TNF-α, IL-6 and IL-8 in cell supernatant was calculated by enzyme-linked immunosorbent assay. RESULTS: A marked augmentation of miR-135a was observed in LPS-induced THP-1 cells. Moreover, depletion of miR-135a alleviated the LPS-induced THP-1 cells injury from the perspective of improving cell viability and reducing cell apoptosis. Importantly, MYOM1, which was under expressed in LPS-induced THP-1 cells, was identified as a target of miR-135a and negatively regulated by miR-135a. Additionally, the mitigative impact of miR-135a inhibitor on THP-1cells damage triggered by LPS was suppressed by MYOM1 depletion. CONCLUSIONS: Our study suggested that the protective effect of miR-135a inhibitor on LPS-induced THP-1 cells injury was realized by regulation of MYOM1, which might afford a pair of novel molecules for sepsis clinical diagnosis.

Performance of Ir(III)-Based Anticancer Agents in the Treatment of Cisplatin-Resistant Cancer Cells.

The resistance of cancer cells to cisplatin has dramatically blocked the further application of this drug in practical treatment settings. The generation of cisplatin resistance is a complex physiological process, and several mechanisms have been reported for this. New metal-based agents with distinct anticancer mechanisms are still highly desired. In this concept article, we describe Ir(III)-based anticancer agents and their underlying anticancer mechanisms, which could inhibit the proliferation of cisplatin-resistant tumors. This work could be beneficial in developing more effective Ir(III)-based agents to combat cisplatin resistance.

Automatic Brain Midline Surface Delineation on 3D CT Images With Intracranial Hemorrhage.

Brain midline delineation plays an important role in guiding intracranial hemorrhage surgery, which still remains a challenging task since hemorrhage shifts the normal brain configuration. Most previous studies detected brain midline on 2D plane and did not handle hemorrhage cases well. We propose a novel and efficient hemisphere-segmentation framework (HSF) for 3D brain midline surface delineation. Specifically, we formulate the brain midline delineation as a 3D hemisphere segmentation task, and employ an edge detector and a smooth regularization loss to generate the midline surface. We also introduce a distance-weighted map to keep the attention on the midline. Furthermore, we adopt rectification learning to handle various head poses. Finally, considering the complex situation of ventricle break-in for hemorrhages in bilateral intraventricular (B-IVH) cases, we identify those cases via a classification model and design a midline correction strategy to locally adjust the midline. To our best knowledge, it is the first study focusing on delineating the brain midline surface on 3D CT images of hemorrhage patients and handling the situation of ventricle break-in. Extensive validation on our large in-house datasets (519 patients) and the public CQ500 dataset (491 patients), demonstrates that our method outperforms state-of-the-art methods on brain midline delineation.

A High-Performance Deep Neural Network Model for BI-RADS Classification of Screening Mammography.

Globally, the incidence rate for breast cancer ranks first. Treatment for early-stage breast cancer is highly cost effective. Five-year survival rate for stage 0-2 breast cancer exceeds 90%. Screening mammography has been acknowledged as the most reliable way to diagnose breast cancer at an early stage. Taiwan government has been urging women without any symptoms, aged between 45 and 69, to have a screening mammogram bi-yearly. This brings about a large workload for radiologists. In light of this, this paper presents a deep neural network (DNN)-based model as an efficient and reliable tool to assist radiologists with mammographic interpretation. For the first time in the literature, mammograms are completely classified into BI-RADS categories 0, 1, 2, 3, 4A, 4B, 4C and 5. The proposed model was trained using block-based images segmented from a mammogram dataset of our own. A block-based image was applied to the model as an input, and a BI-RADS category was predicted as an output. At the end of this paper, the outperformance of this work is demonstrated by an overall accuracy of 94.22%, an average sensitivity of 95.31%, an average specificity of 99.15% and an area under curve (AUC) of 0.9723. When applied to breast cancer screening for Asian women who are more likely to have dense breasts, this model is expected to give a higher accuracy than others in the literature, since it was trained using mammograms taken from Taiwanese women.

Caregivers' Technology Acceptance of an In-Home Care Management App: A Mixed-Methods Study.

Taiwan faces challenges in providing long-term family care as its population rapidly ages. This study aimed to construct a health application that could effectively meet family caregivers' needs in providing home care. Mixed methods were adopted to explore their acceptance of the application, as well as to gather their suggestions for improving the application. A nonrandomized controlled group pretest-posttest design was utilized. The participants were family caregivers who were recruited via purposive sampling at a regional hospital in Taipei, Taiwan. The caregivers used the application to monitor and manage the health of those they were caring for. Elderly family caregivers scored 1.57 and 1.16 points higher than their middle-aged counterparts in terms of performance expectancy (0.61-2.53, P = .01) and effort expectancy (0.25-2.06, P = .01), respectively. The caregivers opined that it was convenient to use the application for managing the health data of their patients, and resources and solutions for overcoming problems when using the application were easily within their reach. They also suggested that relevant information for promoting patient mental health could also be included in the application. Thus, the software is acceptable to all the family caregivers regardless of age, indicating that it can assist family caregivers in the future in performing home care management.

SMARCC1 expression is positively correlated with pathological grade and good prognosis in renal cell carcinoma.

BACKGROUND: Renal cell carcinoma (RCC), which is derived from the renal tubular epithelium, is now the most common urological cancer. Of the four RCC subtypes, clear cell RCC (ccRCC) is the most common subtype and accounts for 75-80% of all RCC cases. SMARCC1, also known as BAF155, together with SMARCA4, SMARCA2, and SMARCB1, comprises the SWI/SNF protein family. It has been reported that the expression of SMARCC1 was correlated with some human cancers including prostate cancer, colon cancer, and pancreatic cancer. However, the mechanisms and regulatory roles of SMARCC1 in ccRCC are not well defined. METHODS: Our current study primarily investigated the expression of SMARCC1 and its clinical importance in two common histological types of ccRCC using microarrays (HKidE180Su02, MecDNA-HKidE030CS01). RESULTS: The results showed that the expression of SMARCC1 in ccRCC tissues was significantly decreased compared with that in corresponding para-tumor tissue (4.370±2.036 vs. 6.167±1.162, P=0.001). SMARCC1 expression was positively correlated with pathological grade (r=0.224, P=0.011). Moreover, ccRCC patients with high SMARCC1 expression had a better prognosis than those with low SMARCC1 expression (40.0% vs. 95.2%, P=0.000) in the following sub-groups: pathological grade (III and IV), male sex (73.5% vs. 95.3%, P=0.004), and tumor size >5 cm (62.5% vs. 89.5%, P=0.044). CONCLUSIONS: A further study is necessary to explain the mechanism of the occurrence and progression of ccRCC.

AW-SDRLSE: Adaptive Weighting and Scalable Distance Regularized Level Set Evolution for Lymphoma Segmentation on PET Images.

Accurate lymphoma segmentation on Positron Emission Tomography (PET) images is of great importance for medical diagnoses, such as for distinguishing benign and malignant. To this end, this paper proposes an adaptive weighting and scalable distance regularized level set evolution (AW-SDRLSE) method for delineating lymphoma boundaries on 2D PET slices. There are three important characteristics with respect to AW-SDRLSE: 1) A scalable distance regularization term is proposed and a parameter q can control the contour's convergence rate and precision in theory. 2) A novel dynamic annular mask is proposed to calculate mean intensities of local interior and exterior regions and further define the region energy term. 3) As the level set method is sensitive to parameters, we thus propose an adaptive weighting strategy for the length and area energy terms using local region intensity and boundary direction information. AW-SDRLSE is evaluated on 90 cases of real PET data with a mean Dice coefficient of 0.8796. Comparative results demonstrate the accuracy and robustness of AW-SDRLSE as well as its performance advantages as compared with related level set methods. In addition, experimental results indicate that AW-SDRLSE can be a fine segmentation method for improving the lymphoma segmentation results obtained by deep learning (DL) methods significantly.

Circular RNA microarray expression profile and potential function of circ0005875 in clear cell renal cell carcinoma.

Background: Circular RNAs (circRNAs), a novel class of endogenous noncoding RNAs, are involved in a variety of diseases, including several types of cancers. We hypothesized that circRNAs are involved in the tumorigenesis and development of clear cell renal cell carcinoma (ccRCC). Methods: To verify our hypothesis, we explored the circRNA expression profiles in 4 pairs of ccRCC tissues and their adjacent non-carcinoma tissues via microarray analysis. Selected circRNAs were further validated by qPCR. Moreover, hsa_circ_0005875 was selected for further study and the potential clinical values of hsa_circ_0005875 were investigated in 60 pairs of ccRCC tissues and adjacent normal controls. In addition, the role of hsa_circ_0005875 in ccRCC progression were performed using colony formation assay, Transwell assay and Martrigel-Transwell assay respectively. Finally, interactions between the circRNAs and miRNAs were predicted using Arraystar's miRNA target prediction software. Luciferase reporter assays were performed to evaluate the interaction between hsa_circ_0005875 and hsa_miR-145-5p. Results: The microarray data showed 1988 circRNAs were significantly dysregulated circRNAs, including 1033 upregulated and 955 downregulated ones in the ccRCC tissues. Hsa_circ_0005875 was confirmed to be significantly upregulated in the ccRCC tumor tissues and renal carcinoma cells. Further analysis revealed that hsa_circ_0005875 expression was associated with tumor size, pathological TNM stage, histological differentiation, and lymphatic metastasis. Functional experiments demonstrated that overexpression of hsa_circ_0005875 increased proliferation, migration and invasion abilities. Moreover, bioinformatics analysis and luciferase reporter assays suggest that hsa_circ_0005875 may serve as a ceRNA (competing endogenous RNA) of miR-145-5p to relieve the repressive effect of miR-145-5p on target ZEB2. Conclusions: These data indicate that hsa_circ_0005875 might play a role in promoting tumor growth and metastasis and be a potential biomarker of ccRCC.

Clinical Characteristics and Management of Functional Pancreatic Neuroendocrine Neoplasms: A Single Institution 20-Year Experience with 286 Patients.

BACKGROUND: Functional pancreatic neuroendocrine neoplasms (PanNENs) are very rare disorders but have complex spectrum, including insulinoma, gastrinoma, glucagonoma, somatostatinoma, and VIPoma. Patients with PanNENs usually present with characteristic symptoms caused by corresponding hormone hypersecretion. It has always been challenging in dealing with such rare but complicated disorders. In this report, we analyzed the clinical characteristics of functional PanNENs in a large cohort of Chinese patients and summarized our clinical experience in diagnosis and treatment. METHODS: The retrospective analysis was performed in patients with a definite diagnosis of functional PanNENs hospitalized in Chinese PLA General Hospital between 2000 and 2020. The clinical characteristics, surgical information, and pathological findings were extracted from their medical records and were analyzed. RESULTS: Totally, 286 patients (gender: male 103 and female 183; age: 45.55 ± 15.23 years old) were diagnosed with definite functional PanNENs. The most frequent functional PanNENs were insulinoma (266/286) followed by glucagonoma (10/286), somatostatinoma (3/286), adrenocorticotropic hormone- (ACTH-) producing tumor (3/286), gastrinoma (2/286), and VIPoma (2/286). Nine patients were diagnosed with multiple endocrine neoplasia type 1 (MEN1) in which all the associated functional PanNENs were insulinomas. The duration from symptoms' onset to confirmed diagnosis was 3.67 ± 4.28 years. Two hundred and eighty patients with tumor localized in pancreatic or with limited metastasis underwent surgery. The symptoms associated with hormonal oversecretion were improved significantly after surgery. Five patients with unresectable metastases or tumor recurrence after surgery were administrated with systemic chemotherapy or other targeted therapies. With these various therapies, the symptoms were also partially relieved. According to findings in pathological and immunochemical examination, all the functional PanNENs were categorized into NEN-G1 (41.95%), NEN-G2 (54.90%), NEN-G3 (3.15%), and NEC-G3 (0%). CONCLUSION: Patients with suspected functional PanNENs should have a systematic endocrine examination at diagnosis. Multidisciplinary collaborations are essential for precise diagnosis and tumor localization. A successful surgery or other targeted therapies can improve the prognosis of patients with such rare but complex disorders.

Overcoming Hypoxia-Restrained Radiotherapy Using an Erythrocyte-Inspired and Glucose-Activatable Platform.

Radiotherapy (RT) as one of the most powerful cancer treatment strategies has been greatly restricted by tumor hypoxia. A mounting effort has been devoted to develop oxygen delivery systems for boosting the RT effect. Unluckily, those systems only supplied modest oxygen, which could not afford more than once and long-time RT. Herein, we describe the development of a glucose-regulated drug release platform, allowing for a long-term tumor normoxic microenvironment and repeated RT for a long time. The repeated cycles resulted in sustained high Endostar plasma levels, which dramatically normalized the tumor vasculature and chronically reversed tumor hypoxia. Taking advantage of the inexhaustible supply of oxygen, Endo@GOx-ER enabled RT achieved an impressive cancer treatment output. To the best of our knowledge, our strategy is the initial attempt to overcome tumor-hypoxia-limited RT through the normalization of tumor vasculature by using an erythrocyte-inspired and glucose-activatable platform and it visually casts a light on the clinical development.

SQSTM1/p62 is involved in docosahexaenoic acid-induced cellular autophagy in glioblastoma cell lines.

Docosahexaenoic acid (DHA) is the most abundant n-3 polyunsaturated fatty acid in the human brain and works as an anticancer agent to induce cell cycle arrest and apoptosis in glioblastoma multiforme (GBM) cell lines. However, little is known about the connection between DHA and autophagy in GBM cells. We found that high-dose DHA caused cellular autophagy in cultured U251 and U118 GBM cell lines, but there was no effect with a low dose. Moreover, after treatment with a high dose of DHA at 12, 24, and 48 h, the protein expression of SQSTM1/p62 decreased in DHA-treated U251 cells at 12 and 24 h, but increased at 48 h, while in DHA-treated U118 cells, the protein expression increased at all time points. Interestingly, the level of SQSTM1/p62 mRNA was elevated in both DHA-treated U251 and U118 cells at all time points, indicating that DHA activated SQSTM1/p62 transcription in both cell lines. Furthermore, downregulation of SQSTM1/p62 by siRNA attenuated DHA-induced cellular autophagy in both cell lines. This report confirms that high-dose DHA induces cellular autophagy in GBM cells, and demonstrates that SQSTM1/p62 acts as a regulator and participates in DHA-induced autophagy.