Cancer nutritional-immunotherapy with NIR-II laser-controlled ATP release based on material repurposing strategy.

Enlightened by the great success of the drug repurposing strategy in the pharmaceutical industry, in the current study, material repurposing is proposed where the performance of carbonyl iron powder (CIP), a nutritional intervention agent of iron supplement approved by the US FDA for iron deficiency anemia in clinic, was explored in anti-cancer treatment. Besides the abnormal iron metabolic characteristics of tumors, serving as potential targets for CIP-based cancer therapy under the repurposing paradigm, the efficacy of CIP as a catalyst in the Fenton reaction, activator for dihydroartemisinin (DHA), thus increasing the chemo-sensitivity of tumors, as well as a potent agent for NIR-II photothermal therapy (PTT) was fully evaluated in an injectable alginate hydrogel form. The CIP-ALG gel caused a rapid temperature rise in the tumor site under NIR-II laser irradiation, leading to complete ablation in the primary tumor. Further, this photothermal-ablation led to the significant release of ATP, and in the bilateral tumor model, both primary tumor ablation and inhibition of secondary tumor were observed simultaneously under the synergistic tumor treatment of nutritional-photothermal therapy (NT/PTT). Thus, material repurposing was confirmed by our pioneering trial and CIP-ALG-meditated NT/PTT/immunotherapy provides a new choice for safe and efficient tumor therapy.

An immune-related adverse event of Behcet's-like syndrome following pembrolizumab treatment.

BACKGROUND: In recent years, the emergence of immunotherapy has renewed therapeutic modality. Different from traditional anti-tumor therapy, immune-related adverse events of skin, gastrointestinal tract, liver, lung, endocrine glands commonly occurred. At present, only one case of immune-related adverse event of Behcet's-like syndrome following pembrolizumab treatment was reported in USA, and no one is reported in China. CASE PRESENTATION: Here, we report a rare case of Behcet's-like symptom following pembrolizumab treatment. A 43-year-old female was diagnosed as lymph node and bone metastasis of adenocarcinoma with unknown primary lesion, probably being of pulmonary origin. She was treated with pembrolizumab 200 mg every three weeks in combination with chemotherapy for 6 cycles, followed by pembrolizumab monotherapy maintenance. However, she developed Behcet's-like syndrome with oral ulcer, genital uler, phlebitis, and vision loss after 9 cycles of pembrolizumab treatment. She was treated with prednisone 5 mg orally three times a day. Two weeks later, dose of glucocorticoid gaven to the patient gradually decreased with improved symptoms. After a treatment-free withdrawal period, the patient requested to continue pembrolizumab treatment. Unfortunately, the above symptoms recurred on the second day following pembrolizumab treatment, and glucocorticoid was taken once again. The symptoms improved and the condition was under control. CONCLUSIONS: In view of the exponential growth of immunocheckpoint inhibitors (ICIs) in a variety of tumors, we should be alert to related adverse events, especially the rare rheumatic manifestations.

Coupled scRNA-seq and Bulk-seq reveal the role of HMMR in hepatocellular carcinoma.

Background: Hyaluronan-mediated motility receptor (HMMR) is overexpressed in multiple carcinomas and influences the development and treatment of several cancers. However, its role in hepatocellular carcinoma (HCC) remains unclear. Methods: The "limma" and "GSVA" packages in R were used to perform differential expression analysis and to assess the activity of signalling pathways, respectively. InferCNV was used to infer copy number variation (CNV) for each hepatocyte and "CellChat" was used to analyse intercellular communication networks. Recursive partitioning analysis (RPA) was used to re-stage HCC patients. The IC50 values of various drugs were evaluated using the "pRRophetic" package. In addition, quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to confirm HMMR expression in an HCC tissue microarray. Flow cytometry (FCM) and cloning, Edu and wound healing assays were used to explore the capacity of HMMR to regulate HCC tumour. Results: Multiple cohort studies and qRT-PCR demonstrated that HMMR was overexpressed in HCC tissue compared with normal tissue. In addition, HMMR had excellent diagnostic performance. HMMR knockdown inhibited the proliferation and migration of HCC cells in vitro. Moreover, high HMMR expression was associated with "G2M checkpoint" and "E2F targets" in bulk RNA and scRNA-seq, and FCM confirmed that HMMR could regulate the cell cycle. In addition, HMMR was involved in the regulation of the tumour immune microenvironment via immune cell infiltration and intercellular interactions. Furthermore, HMMR was positively associated with genomic heterogeneity with patients with high HMMR expression potentially benefitting more from immunotherapy. Moreover, HMMR was associated with poor prognosis in patients with HCC and the re-staging by recursive partitioning analysis (RPA) gave a good prognosis prediction value and could guide chemotherapy and targeted therapy. Conclusion: The results of the present study show that HMMR could play a role in the diagnosis, prognosis, and treatments of patients with HCC based on bulk RNA-seq and scRAN-seq analyses and is a promising molecular marker for HCC.

Apoptosis and Paraptosis Induced by Disulfiram-Loaded Ca2+/Cu2+ Dual-Ions Nano Trap for Breast Cancer Treatment.

Regarded as one of the hallmarks of tumorigenesis and tumor progression, the evasion of apoptotic cell death would also account for treatment resistance or failure during cancer therapy. In this study, a Ca2+/Cu2+ dual-ion "nano trap" to effectively avoid cell apoptosis evasion by synchronously inducing paraptosis together with apoptosis was successfully designed and fabricated for breast cancer treatment. In brief, disulfiram (DSF)-loaded amorphous calcium carbonate nanoparticles (NPs) were fabricated via a gas diffusion method. Further on, the Cu2+-tannic acid metal phenolic network was embedded onto the NPs surface by self-assembling, followed by mDSPE-PEG/lipid capping to form the DSF-loaded Ca2+/Cu2+ dual-ions "nano trap". The as-prepared nanotrap would undergo acid-triggered biodegradation upon being endocytosed by tumor cells within the lysosome for Ca2+, Cu2+, and DSF releasing simultaneously. The released Ca2+ could cause mitochondrial calcium overload and lead to hydrogen peroxide (H2O2) overexpression. Meanwhile, Ca2+/reactive oxygen species-associated mitochondrial dysfunction would lead to paraptosis cell death. Most importantly, cell paraptosis could be further induced and strengthened by the toxic dithiocarbamate (DTC)-copper complexes formed by the Cu2+ combined with the DTC, the metabolic products of DSF. Additionally, the released Cu2+ will be reduced by intracellular glutathione to generate Cu+, which can catalyze the H2O2 to produce a toxic hydroxyl radical by a Cu+-mediated Fenton-like reaction for inducing cell apoptosis. Both in vitro cellular assays and in vivo antitumor evaluations confirmed the cancer therapeutic efficiency by the dual ion nano trap. This study can broaden the cognition scope of dual-ion-mediated paraptosis together with apoptosis via a multifunctional nanoplatform.

Single-nucleus RNA sequencing reveals that macrophages and smooth muscle cells promote carotid atherosclerosis progression through mitochondrial autophagy.

Carotid atherosclerotic plaques are the manifestation of atherosclerosis in the carotid arteries and can significantly increase the incidence of cerebrovascular disease. Macrophages and smooth muscle cells are crucial for their development. To reveal the mechanism of carotid atherosclerotic plaque formation, we performed single-nucleus RNA sequencing of the carotid plaque tissue and identified 11 cell types, and the macrophages were divided into 5 different macrophage subpopulations. The macrophages and smooth muscle cells in the patients with symptomatic carotid atherosclerotic plaques caused intraplaque cell death via the mitochondrial autophagic pathway, resulting in plaque instability and rupture, which in turn led to clinical cardiovascular and cerebrovascular events. The findings provide new insights into carotid atherosclerosis formation, and this may provide new directions for the prevention and treatment of carotid atherosclerosis.

Multi-omics reveals the role of ENO1 in bladder cancer and constructs an epithelial-related prognostic model to predict prognosis and efficacy.

α-Enolase (ENO1) is a crucial molecular target for tumor therapy and has emerged as a research hotspot in recent decades. Here, we aimed to explore the role of ENO1 in bladder cancer (BLCA) and then construct a signature to predict the prognosis and treatment response of BLCA. Firstly, we found ENO1 was highly expressed in BLCA tissues, as verified by IHC, and was associated with poor prognosis. The analysis of the tumor immune microenvironment by bulk RNA-seq and scRNA-seq showed that ENO1 was associated with CD8+ T-cell exhaustion. Additionally, the results in vitro showed that ENO1 could promote the proliferation and invasion of BLCA cells. Then, the analysis of epithelial cells (ECs) revealed that ENO1 might promote BLCA progression by metabolism, the cell cycle and some carcinogenic pathways. A total of 249 hub genes were obtained from differentially expressed genes between ENO1-related ECs, and we used LASSO analysis to construct a novel signature that not only accurately predicted the prognosis of BLCA patients but also predicted the response to treatment for BLCA. Finally, we constructed a nomogram to better guide clinical application. In conclusion, through multi-omics analysis, we found that ENO1 was overexpressed in bladder cancer and associated with poor prognosis, CD8+ T-cell exhaustion and epithelial heterogeneity. Moreover, the prognosis and treatment of patients can be well predicted by constructing an epithelial-related prognostic signature.

Efficacy and safety of fluzoparib combined with anlotinib in extensive stage small cell lung cancer after first-line platinum-based chemotherapy: a multi-center, single-arm prospective phase II clinical study (STAMP study).

BACKGROUND: Small-cell lung cancer (SCLC) is a highly aggressive and lethal malignancy that accounts for 10-15% of lung cancers, and it is generally divided into limited and extensive stage. The standard of care for patients with newly diagnosed extensive-stage SCLC (ES-SCLC) is still platinum-based chemotherapy and as maintenance therapy scheme. Although most parts of patients experience a significant tumor response to first-line therapy, the disease recurs invariably. Anlotinib hydrochloride, a novel oral multitarget tyrosine kinase inhibitor, has significant inhibitory activity against angiogenesis-related kinases, such as VEGFR, FGFR, PDGFR, and c-Kit kinase associated with tumor cell proliferation. Fluzoparib is a type of inhibitor of poly ADP ribose polymerase (PARP, including PARPl, PARP2 and PARP3). Previous studies have shown that Fluzoparib has a strong inhibitory effect on PARP1 activity at the molecular and cellular levels. METHODS: This is a multi-center, prospective, single-arm phase II clinical study. A total of 50 ES-SCLC patients who experienced disease progression after first-line standard platinum-based chemotherapy with/without immune checkpoint inhibitors scheme, or within 6 months after the completion of treatment will be recruited. Those who had prior treatment with any PARP inhibitor or antiangiogenic agent includes anlotinib, bevacizumab, sorafenib, and thalidomide are excluded. Eligible patients will receive oral anlotinib 8 mg once daily and oral fluzoparib 150 mg twice daily until disease progression or intolerable toxicity. The primary endpoint is objective response rate (ORR). DISCUSSION: The addition of fluzoparib to anlotinib is expected to increase the clinical benefit in ES-SCLC patients after platinum-based chemotherapy. TRIAL REGISTRATION: This study protocol was prospectively registered on June 17, 2021. CLINICALTRIALS: gov Identifier: NCT04933175 .

Identification of glutamyl-prolyl-tRNA synthetase as a new therapeutic target in hepatocellular carcinoma via a novel bioinformatic approach.

Background: Hepatocellular carcinoma (HCC) has a high incidence, and current treatments are ineffective. We aimed to explore potential diagnostic and prognostic biomarkers for HCC by conducting bioinformatics analysis on genomic and proteomic data. Methods: Genome and proteome data were downloaded from The Cancer Genome Atlas (TCGA) and ProteomeXchange databases, respectively. Differentially expressed genes was determined using limma package. Functional enrichment analysis was conducted by Database for Annotation, Visualization, and Integrated Discovery (DAVID). Protein-protein analysis was established by STRING dataset. Using Cytoscope for network visualization and CytoHubba for hub gene identification. The gene mRNA and protein levels were validated using GEPIA and HPA, as well as RT-qPCR and Western blot. Results: A total of 127 up-regulated and 80 down-regulated common DEGPs were identified between the genomic and proteomic data, Mining 10 key genes/proteins(ACLY, ACACB, EPRS, CAD, HSPA4, ACACA, MTHFD1, DMGDH, ALDH2, and GLDC) through protein interaction networks. in addition, Glutamyl-prolyl-tRNA synthetase (EPRS) was highlighted as an HCC biomarker that is negatively correlated with survival. Differential EPRS expression analysis in HCC and paracancerous tissues showed that EPRS expression was elevated in HCC. RT-qPCR and Western blot analysis results showed that EPRS expression was upregulated in HCC cells. Conclusions: Our results suggest that EPRS is a potential therapeutic target for inhibiting HCC tumorigenesis and progression.

Evaluation of the effect of 3D-bioprinted gingival fibroblast-encapsulated ADM scaffolds on keratinized gingival augmentation.

BACKGROUND AND OBJECTIVES: The keratinized gingiva plays an important role in maintaining healthy periodontal and peri-implant tissue. Acellular dermal matrix (ADM), as a substitute biomaterial, has a porous structure and good biocompatibility. 3D-bioprinting has the potential for tissue engineering because it enables precise loading of cells layer-by-layer. Herein, we bioprinted ADM scaffold encapsulating gingival fibroblasts (GFs) and evaluated its efficacy in keratinized gingiva augmentation in vivo to assess its potential for clinical periodontal tissue regeneration. METHODS: GFs were extracted from the gingiva of beagles and transfected with a green fluorescent protein (GFP). The ADM scaffold (ADM cell-free group) was constructed using ADM, gelatin, and sodium alginate mixed at an appropriate ratio via 3D-bioprinting. The ADM cell scaffold (ADM cell group) was established by adding extra GFs in the same manner. Six beagles were divided into blank control, ADM cell-free, and ADM cell groups; and implant surgery was performed. The keratinized gingiva was clinically and histologically evaluated at baseline and after 2 months. RESULTS: GFs transfected with GFPs expressed green fluorescence and were present in new tissue in the ADM cell group and not observed in the ADM cell-free group. At 2 months after surgery, the keratinized gingival augmentation in the ADM cell group was significantly more than that in the ADM cell-free group. Attached gingival augmentation was also observed more in the ADM cell group than that in the ADM cell-free group. Histological staining showed that the tissue in the ADM cell group displayed a more integrated structure and higher expression of COL I, COL III, and VEGF-A than those in the ADM cell-free group. CONCLUSION: 3D-bioprinted GF-encapsulated ADM scaffolds increased the amount of keratinized gingiva in vivo, suggesting that 3D-bioprinting has great potential for oral soft tissue regeneration.

Nanoheterostructure by Liquid Metal Sandwich-Based Interfacial Galvanic Replacement for Cancer Targeted Theranostics.

Nanoheterostructures with exquisite interface and heterostructure design find numerous applications in catalysis, plasmonics, electronics, and biomedicine. In the current study, series core-shell metal or metal oxide-based heterogeneous nanocomposite have been successfully fabricated by employing sandwiched liquid metal (LM) layer (i.e., LM oxide/LM/LM oxide) as interfacial galvanic replacement reaction environment. A self-limiting thin oxide layer, which would naturally occur at the metal-air interface under ambient conditions, could be readily delaminated onto the surface of core metal (Fe, Bi, carbonyl iron, Zn, Mo) or metal oxide (Fe3 O4 , Fe2 O3 , MoO3 , ZrO2 , TiO2 ) nano- or micro-particles by van der Waals (vdW) exfoliation. Further on, the sandwiched LM layer could be formed immediately and acted as the reaction site of galvanic replacement where metals (Au, Ag, and Cu) or metal oxide (MnO2 ) with higher reduction potential could be deposited as shell structure. Such strategy provides facile and versatile approaches to design and fabricate nanoheterostructures. As a model, nanocomposite of Fe@Sandwiched-GaIn-Au (Fe@SW-GaIn-Au) is constructed and their application in targeted magnetic resonance imaging (MRI) guided photothermal tumor ablation and chemodynamic therapy (CDT), as well as the enhanced radiotherapy (RT) against tumors, have been systematically investigated.

Development and characterization of anti-HPV16 monoclonal antibodies for assembly of an HPV16 detection kit.

Quality control is very important during the development of 3-valent (16/18/58), 9-valent (6/11/16/18/31/33/45/52/58), and 15-valent human papillomavirus (HPV) vaccines (6/11/16/18/31/33/35/39/45/52/56/58/59/68). All 3-valent, 9-valent, and 15-valent HPV vaccines contain the HPV16 antigen; therefore, a detection method that can specifically identify HPV16 in vaccines is urgently required. This study aimed to develop and characterize monoclonal antibodies to assemble a highly specific HPV16 detection kit. The HPV16 L1 pentameric protein developed as an immunogen was used to prepare monoclonal antibodies. From the pool of prepared monoclonal antibodies, we selected 4G12 and 5A6 to screen and evaluate their subtypes, specificity, neutralizing activity, serum competition, binding affinity, and gene sequencing. After these characterizations, an enzyme-linked immunosorbent assay kit for these monoclonal antibodies was developed, and excellent quality was demonstrated in the assessment of linearity, repeatability, and specificity. The developed detection kit has great potential for wide use in clinical testing and quality control in vaccine production processes.

Development of HPV58 type-specific antibodies and detection kit.

Currently, human papillomavirus (HPV) vaccines are in short supply, so the development of HPV vaccines has a broad market prospect. The 3-, 9-, and 15-valent HPV vaccines developed by ourselves all contain HPV58-derived antigen components. It is important to detect HPV 58 during vaccine production. Here, we introduced a development process of HPV58 type-specific antibodies and a detection kit. Briefly, HPV58 L1-Virus Like Particles (VLPs) were used as antigens to immunize mice, followed by extraction of the ascites to prepare hybridoma cells. After culturing, the supernatants containing secreted antibodies were harvested, purified, and screened to obtain monoclonal antibodies (mAbs). In the pool of attained monoclonal antibodies, we selected 2F7 and 2G7 to evaluate their subtypes, specificity, neutralizing activity, serum competition, binding affinity and gene sequencing. Finally, an enzyme-linked immunosorbent assay (ELISA) detection kit was assembled with 2F7 and 2G7 mAbs which possessed high specificity to HPV58 L1-VLPs. The detection kit developed by 2F7 and 2G7 could be adopted to specifically detect HPV58 L1 protein with good linearity and detection range, which could be widely used in clinical testing and quality control in the production of HPV vaccines.Abbreviations: BSA: Bovine serum albumin; CDRs: Complementarity-determining regions; CV: Coefficient of variation; DTT: Dithiothreitol; ELISA: Enzyme-linked immunosorbent assay; HAT: Hypoxanthine-aminopterin-thymidine; HPV: Human Papillomavirus; IC50: 50% inhibition rate; IC90: 90% inhibition rate; mAbs: Monoclonal antibodies; VLP: Virus-like particle.

Analysis of exosomal competing endogenous RNA network response to paclitaxel treatment reveals key genes in advanced gastric cancer.

Background: Exosome is an important component of the tumor immune microenvironment and plays critical role in cancer pathogenesis. The exosome transcriptome of gastric cancer (GC) response to paclitaxel chemotherapy has not been investigated in the past. Methods: ceRNA microarrays were performed in exosomes from six advanced GC patients before and after paclitaxel treatment. Bioinformatics tools were used to identify differential expressing genes and construct competing endogenous RNA (ceRNA) networks. The importance of hub genes in the ceRNA network was confirmed by survival analysis and functional analysis. Results: A total of 213 differential mRNAs, 370 lncRNAs, and 376 circRNAs were identified, and hub genes in ceRNA networks were screened. The differential genes were associated with GO terms SNAP complex, gap junction, protein transporter activity, cytokine receptor, and KEGG pathways synaptic vesicle cycle, propanoate metabolism, Epstein-Barr virus infection, heparin, and steroid biosynthesis, and beta-alanine metabolism. ULK2, CYP2R1, BTLA, and miR-105-5p are prognostic genes for overall survival. Paclitaxel may target ULK2 which is involved in mitosis and cell cycle. miR-105-5p may target ULK2 3'UTR. Conclusion: The work for the first time identified exosomal RNA biomarkers and constructed a ceRNA network in GC response to paclitaxel, revealed novel molecular mechanisms of GC, and provided new candidates for GC diagnosis and treatment.

A novel acidic polysaccharide from blackened jujube: Structural features and antitumor activity in vitro.

Liver cancer is one of the most common cancers, with increasing trends in incidence and mortality. A novel acidic polysaccharide (BJP-2) obtained from blackened jujube was extracted by hot water followed by chromatographic purification employing DEAE-cellulose 52 and Sephadex G-100 column. And then BJP-2 was identified by SEC-MALLS-RI, GC-MS, methylation and NMR for the following characteristics: molecular weight of 6.42 × 104 Da, monosaccharide composition of glucuronic acid (GalA), arabinose (Ara), galactose (Gal), rhamnose (Rha), xylose (Xyl), glucuronic acid (GlcA), glucose (Glc), fucose (Fuc) and mannose (Man) with the percentage of 39.78, 31.93, 16.86, 6.43, 1.86, 1.28, 1.02, 0.61, and 0.23%, as well as the main chain of → 5)-α-L-Araf (1 → 4)-ß-D-Gal(1 → , T-α-L-Araf (1 → 4)-ß-D-Gal(1 → , and → 4)-α-L-6MeGalAp(1 → . The effect of BJP-2 on the apoptosis of HepG2 cells and its anti-tumor mechanism were further explored. The analysis by MTT and flow cytometry showed that BJP-2 suppressed cell proliferation by inducing apoptosis in a concentration-dependent manner. Cell scratching and Transwell revealed that BJP-2 was able to block the invasion and metastasis of tumor cells. Western blot results demonstrated that BJP-2 exhibited antitumor activity through a mitochondria-dependent pathway, as evidenced by overexpression of Bax, Cleaved Caspase-3/Caspase-3 and Cleaved Caspase-9/Caspase-9 and downregulation of Bcl-2. Therefore, BJP-2 has broad research prospects as a tumor preventive or therapeutic agent.

Identification and Characterization of Fibronectin-Binding Peptides in Gelatin.

Collagen and fibronectin (FN) are important components in the extracellular matrix (ECM). Collagen-FN binding belongs to protein-protein interaction and plays a key role in regulating cell behaviors. In this study, FN-binding peptides were isolated from gelatin (degraded collagen) using affinity chromatography, and the amino acid sequences were determined using HPLC-MS. The results indicated that all FN-binding peptides contained GPAG or GPPG. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and dual-polarization interferometry (DPI) were used to analyze the effects of hydroxylation polypeptide on FN binding activity. DPI analysis indicated that peptides with molecular weight (MW) between 2 kDa and 30 kDa showed higher FN-binding activity, indicating MW range played an important role in the interaction between FN and peptides. Finally, two peptides with similar sequences except for hydroxylation of prolines were synthesized. The FN-binding properties of the synthesized peptides were determined by MALDI-TOF MS. For peptide, GAPGADGP*AGAPGTP*GPQGIAGQR, hydroxylation of P8 and P15 is necessary for FN-binding. For peptide, GPPGPMGPPGLAGPPGESGR, the FN-binding process is independent of proline hydroxylation. Thus, FN-binding properties are proline-hydroxylation dependent.

Quantitation of Collagen Type V in Tissues by High-Performance Liquid Chromatography Coupled to Mass Spectrometry.

A method for quantifying the bovine collagen type V (Col. V) was established based on high-performance liquid chromatography coupled to mass spectrometry by the marker peptide external standard. High-purity Col. V was extracted by the acid-enzyme hydrolysis process, and the marker peptide of Col. V was identified by LCQ mass spectrometry as GPAGPMGLTGR. A broad linear range (0.01-5.00 µg/mL) with a correlation coefficient of 0.9984 was achieved, and the limit of detection and limit of quantification were found to be 3.00 × 10-3 and 6.25 × 10-3 µg/mL, respectively. The method precision was 1.49%. The recovery rate was determined as 97.1-109.6% with a relative standard deviation less than 5%. The proposed method was successfully applied for the determination of Col. V contents in the bovine heart, lung, and cornea, which were 0.72 ± 0.01%, 0.23 ± 0.01%, and 2.89 ± 0.00%, respectively. The results show that the proposed method is more suitable for measuring the content of Col. V in tissue samples compared with the enzyme-linked immunosorbent assay. The marker peptide method has high accuracy and great reproducibility, and will lay a foundation for the extraction and application of Col. V. Impact statement The accurate quantitative method for collagen type V (Col. V) is particularly important in scientific research, disease diagnosis and treatment, and industrial production. In this article, we proposed a high-performance liquid chromatography coupled to mass spectrometry method based on the external standard marker peptide to quantify bovine Col. V. This method shows a higher accuracy and recovery rate than enzyme-linked immunosorbent assay (ELISA), indicating that it is more suitable for measuring the content of Col. V in tissue samples than ELISA. The establishment of this method has laid a solid foundation for the extraction and application of Col. V.

Local Destruction of Tumors for Systemic Immunoresponse: Engineering Antigen-Capturing Nanoparticles as Stimulus-Responsive Immunoadjuvants.

Immunotherapy has established a new paradigm for cancer treatment and made many breakthroughs in clinical practice. However, the rarity of immune response suggests that additional intervention is necessary. In recent years, it has been reported that local tumor destruction (LTD) can cause cancer cell death and induce an immunologic response. Thus, the combination of immunotherapy and LTD methods will be a promising approach to improve immune efficiency for cancer treatment. Herein, a nanobiotechnology platform to achieve high-precision LTD for systemic cancer immunotherapy has been successfully constructed. Possessing radio-sensitizing and photothermal properties, the engineered immunoadjuvant-loaded nanoplatform, which could precisely induce radiotherapy (RT)/photothermal therapy (PTT) to eliminate local tumor and meanwhile lead to the release of tumor-derived protein antigens (TDPAs), has been facilely fabricated by commercialized SPG membrane emulsification technology. Further on, the TDPAs could be captured and form personal nanovaccines in situ to serve as both reservoirs of antigen and carriers of immunoadjuvant, which can effectively improve the immune response. The investigations suggest that the combination of RT/PTT and improved immunotherapy using adjuvant-encapsulated antigen-capturing nanoparticles holds tremendous promise in cancer treatments.

Loss of ATP5A1 enhances proliferation and predicts poor prognosis of colon adenocarcinoma.

BACKGROUND: ATP Synthase F1 Subunit Alpha (ATP5F1A), also named as ATP5A1, is a subunit of mitochondrial ATP synthase. Dysregulated expression of ATP5A1 has been reported in several malignancies, nevertheless it showed either oncogenic or tumor-suppressing roles in different cancer types. Here we aimed to initially investigate the expression and role of ATP5A1 in colon adenocarcinoma. METHODS: We firstly evaluated the transcription and mRNA levels of ATP5A1 using data from The Cancer Genome Atlas (TCGA). Besides, we tested its mRNA and protein expression in our enrolled retrospective cohort (n = 115). Univariate and multivariate analyzes were conducted to assess its prognostic value. Cellular experiments and xenografts in mice model were performed to validate the role of ATP5A1 in colon cancer. RESULTS: ATP5A1 showed a significant lower level in colon adenocarcinoma than in adjacent nontumorous tissue. Advanced tumor stage was characterized with lower ATP5A1 level. Lower ATP5A1 was associated with poor prognosis in both TCGA dataset (P = 0.041) and our cohort (P = 0.001). Furthermore, Cox regression analysis demonstrated that ATP5A1 was a novel independent prognostic factor for colon cancer patients (HR=0.43, P = 0.018). Finally, cellular and xenografts data confirmed that overexpressing ATP5A1 can remarkably attenuate colon cancer growth. CONCLUSION: Low expression of ATP5A1 may be a potential molecular marker for poor prognosis in colon cancer. DATA AVAILABILITY: Data will be available upon request.

NUDT15 genetic testing-guided 6-mercaptopurine dosing in children with ALL likely to be cost-saving in China.

OBJECTIVE: The cost-effectiveness of NUDT15 genetic testing-guided initial 6-mercaptopurine (6-MP) dosing in children with acute lymphoblastic leukemia (ALL) was evaluated. METHODS: A decision tree model was used to evaluate the cost to China's medical system per quality-adjusted life-year (QALY) gained and cost per case of severe leukopenia avoided of NUDT15 genetic testing using public clinical data. RESULTS: Genetic testing-guided initial 6-MP dosing reduced overall costs by $518.61, and prevented 0.221 cases of Grade III-IV leukopenia and increased QALY by 0.00136 per patient. Results were robust in one-way analyses and probabilistic sensitivity analyses. CONCLUSION: NUDT15 genetic testing prior to the initial administration of 6-MP in pediatric ALL patients in China is less expensive than standard dosing without genetic testing.