Nanoparticle albumin-bound paclitaxel and PD-1 inhibitor (sintilimab) combination therapy for soft tissue sarcoma: a retrospective study.

BACKGROUND: There is increasing evidence that combination therapy with nanoparticle albumin-bound paclitaxel (nab-paclitaxel) and programmed cell death protein 1 (PD-1) inhibitor is safe and efficacious in treating many types of malignant tumors. However, clinical data demonstrating the effect of this treatment combination for patients with metastatic soft tissue sarcoma (STS) are currently limited. METHODS: The clinical data of patients with metastatic STS who received nab-paclitaxel plus PD-1 inhibitor (sintilimab) therapy between January 2019 and February 2021 were retrospectively analyzed. The effectiveness and safety of the combined treatment were evaluated in terms of the median progression-free survival (PFS), estimated using the Kaplan-Meier method. The univariate Cox proportional hazards model was used to analyze the relationship between clinicopathological parameters and PFS. All statistical analyses were two-sided; P < 0.05 was considered statistically significant. RESULTS: A total of 28 patients treated with nab-paclitaxel plus sintilimab were enrolled in this study. The objective response rate was 25%, the disease control rate was 50%, and the median PFS was 2.25 months (95% CI = 1.8-3.0 months). The most common grade 1 or 2 adverse events (AEs) were alopecia (89.3%; 25/28), leukopenia (25.0%; 7/28), fatigue (21.4%; 6/28), anemia (21.4%; 6/28), and nausea (21.4%; 6/28). The most common grade 3 AEs were neutropenia (10.7%; 3/28) and peripheral neuropathy (10.7%; 3/28). No grade 4 AEs were observed. Among the present study cohort, patients with angiosarcoma (n = 5) had significantly longer PFS (P = 0.012) than patients with other pathological subtypes, including undifferentiated pleomorphic sarcoma (n = 7), epithelioid sarcoma (n = 5), fibrosarcoma (n = 4), synovial sarcoma (n = 3), leiomyosarcoma (n = 2), pleomorphic liposarcoma (n = 1), and rhabdomyosarcoma (n = 1); those who experienced three or more AEs had significantly longer median PFS than those who experienced less than three AEs (P = 0.018). CONCLUSION: Nab-paclitaxel plus PD-1 inhibitor is a promising treatment regimen for advanced STS. Randomized controlled clinical trials are required to further demonstrate its efficacy and optimal application scenario.

Discovery of a crystalline sulforaphane analog with good solid-state stability and engagement of the Nrf2 pathway in vitro and in vivo.

The antioxidant natural product sulforaphane (SFN) is an oil with poor aqueous and thermal stability. Recent work with SFN has sought to optimize methods of formulation for oral and topical administration. Herein we report the design of new analogs of SFN with the goal of improving stability and drug-like properties. Lead compounds were selected based on potency in a cellular screen and physicochemical properties. Among these, 12 had good aqueous solubility, permeability and long-term solid-state stability at 23 °C. Compound 12 also displayed comparable or better efficacy in cellular assays relative to SFN and had in vivo activity in a mouse cigarette smoke challenge model of acute oxidative stress.

Upregulated miR-132 in Lgr5+ gastric cancer stem cell-like cells contributes to cisplatin-resistance via SIRT1/CREB/ABCG2 signaling pathway.

Cisplatin resistance has long been a major problem that restricts its use. A novel paradigm in tumor biology suggests that gastric tumor chemo-resistance is driven by gastric cancer stem cell-like (GCSCs). Growing evidence has indicated that microRNAs (miRNAs) contributes to chemo-resistance in gastric cancer (GC). Here, Lgr5+ cells derived from gastric cancer cell lines displayed stem cell-like features. Flow cytometry demonstrated the presence of a variable fraction of Lgr5 in 19 out of 20 GC specimens. By comparing the miRNA expression profiles of Lgr5+ GCSCs and Lrg5- cells, we established the upregulation of miR-132 in Lgr5+ GCSCs. The enhanced miR-132 expression correlated chemo-resistance in GC patients. Kaplan-Meier survival curve showed that patients with low miR-132 expression survived obviously longer. Functional assays results indicated that miR-132 promoted cisplatin resistance in Lgr5+ GCSCs in vitro and in vivo. Further dual-luciferase reporter gene assays revealed that SIRT1 was the direct target of miR-132. The expression of miR-132 was inversely correlated with SIRT1 in gastric cancer specimens. Furthermore, through PCR array we discovered ABCG2 was one of the downstream targets of SIRT1. Overexpression of SIRT1 down-regulated ABCG2 expression by promoting the de-acetylation of the transcription factor CREB. CREB was further activated ABCG2 via binding to the promoter of ABCG2 to induce transcription. Thus, we concluded that miR-132 regulated SIRT1/CREB/ABCG2 signaling pathway contributing to the cisplatin resistance and might serve as a novel therapeutic target against gastric cancer.

High expression of astrocyte elevated gene-1 is associated with clinical staging, metastasis, and unfavorable prognosis in gastric carcinoma.

More and more evidence has demonstrated that astrocyte elevated gene-1 (AEG-1) is tightly associated with progression, metastasis, and unfavorable prognosis in many malignancies. However, the potential biological role of AEG-1 in gastric carcinoma (GC) has not been thoroughly delineated. In the current study, we found that AEG-1 mRNA and protein levels in GC tissues were significantly higher than those in normal gastric mucosa (P < 0.05). Simultaneously, statistical analysis displayed a significant correlation of high AEG-1 mRNA and protein expressions with differentiation status, TNM staging, invasive depth, and lymph node metastasis (P < 0.05). Most importantly, expressions of AEG-1 mRNA and protein in high clinical staging and metastatic GC tissues were dramatically higher than those in low clinical staging and non-metastatic GC tissues (P < 0.05). Stepwise investigation confirmed that the survival time of the patients with high AEG-1 level was shorter than those with low AEG-1 level or negative AEG-1 staining. Taken altogether, our data presented herein suggest that AEG-1 may be a novel predictor for metastasis and prognosis of the patients with GC.

Synthesis and cellular uptake of folic acid-conjugated cellulose nanocrystals for cancer targeting.

Elongated nanoparticles have recently been shown to have distinct advantages over spherical ones in targeted drug delivery applications. In addition to their oblong geometry, their lack of cytotoxicity and numerous surface hydroxyl groups make cellulose nanocrystals (CNCs) promising drug delivery vectors. Herein we report the synthesis of folic acid-conjugated CNCs for the targeted delivery of chemotherapeutic agents to folate receptor-positive cancer cells. Folate receptor-mediated cellular binding/uptake of the conjugate was demonstrated on human (DBTRG-05MG, H4) and rat (C6) brain tumor cells. Folate receptor expression of the cells was verified by immunofluorescence staining. Cellular binding/uptake of the conjugate by DBTRG-05MG, H4, and C6 cells was 1452, 975, and 46 times higher, respectively, than that of nontargeted CNCs. The uptake mechanism was determined by preincubation of the cells with the uptake inhibitors chlorpromazine or genistein. DBTRG-05MG and C6 cells internalized the conjugate primarily via caveolae-mediated endocytosis, whereas H4 cells internalized the conjugate primarily via clathrin-mediated endocytosis.

Tree barks for retrospective measurement and source appointment of airborne perfluoroalkyl and polyfluoroalkyl substances.

Tree bark is a useful bioindicator of atmospheric pollution. It is specially suitable for airborne perfluoroalkyl and polyfluoroalkyl substances (PFASs) investigation due to persistence of ionic PFASs. The present work firstly systematically studied tree barks as a bioindicator of airborne PFASs. Comparison with the regular active and passive samplers found barks could produce long-term measurement of airborne PFASs, and could record the historical emission of PFASs with retrospective time frame as long as decades. Factors, e.g. tree type, trunk diameter, and sampling depth, can affect PFAS accumulation in barks, and these factors should be kept consistent during sampling. In a study area spatial distribution of airborne PFASs can be obtained by interpolation of bark results, and the concerned region can be located. Properties of the emission sources can be characterized, and the potential sources can be tracked based on the bark results. Their contributions can be further estimated by the source appointment strategies. In the economically and industrially developed study area of the present study, eight cities of southern Jiangsu Province of China, total ionic PFAS concentration of camphor bark samples collected in 34 sites was 0.44-359 ng/g dw (dry weight), dominated by perfluoroalkyl carboxylic acids (PFCAs). Two types of possible sources were characterized as with long-chained PFCAs and PFOA (perfluorooctanoic acid) as the main components respectively. The sources were appointed as fluoropolymer manufacturing and textile industries, the important PFAS application fields, and their relative contribution was estimated as 32.5% and 67.5% respectively. The present study can provide useful advice to the method framework of using barks for long-term occurrence investigation, concerned region location, and emission source appointment of airborne PFASs in a study area. Based on the bark results, effective strategies can be further made for PFAS pollution elimination and risk control.

Frozen inactivated autograft replantation for bone and soft tissue sarcomas.

Background: The frozen inactivation of autologous tumor bones using liquid nitrogen is an important surgical method for limb salvage in patients with sarcoma. At present, there are few research reports related to frozen inactivated autograft replantation. Methods: In this study, we retrospectively collected the clinical data of patients with bone and soft tissue sarcoma treated with liquid nitrogen-frozen inactivated tumor bone replantation, and analyzed the safety and efficacy of this surgical method. The healing status of the frozen inactivated autografts was evaluated using the International Society of Limb Salvage (ISOLS) scoring system. Functional status of patients was assessed using the Musculoskeletal Tumor Society (MSTS) scale. Results: This study included 43 patients. The average length of the bone defect after tumor resection is 16.9 cm (range 6.3-35.3 cm). Patients with autograft not including the knee joint surface had significantly better healing outcomes (ISOLS scores) (80.6% ± 15% vs 28.2% ± 4.9%, P<0.001) and limb function (MSTS score) (87% ± 11.6% vs 27.2% ± 4.4%, P<0.001) than patients with autografts including the knee joint surface. The healing time of the end of inactivated autografts near the metaphyseal was significantly shorter than that of the end far away from the metaphyseal (9.8 ± 6.3 months vs 14.9 ± 6.3 months, P=0.0149). One patient had local recurrence, one had an autograft infection, five (all of whom had an autograft including the knee joint surface) had joint deformities, and seven had bone non-union. Conclusion: Frozen inactivated autologous tumor bone replantation is safe and results in good bone healing. But this method is not suitable for patients with autograft involving the knee joint surface.

Effect of Xeroderma pigmentosum complementation group F polymorphisms and H.pylori infection on the risk of gastric cancer.

OBJECTIVE: We conducted a case-control study by genotyping three potential functional SNPs to assess the association of Xeroderma pigmentosum complementation group F (XPF) polymorphisms with gastric cancer susceptibility, and role of XPF polymorphisms in combination with H.pylori infection in the risk of gastric cancer. METHODOLOGY: A hospital case-control study was conducted. A total of 331 patients with gastric cancer and 355 controls were collected. Three SNPs of XPF, XPF rs180067, rs1799801 and rs2276466, were genotyped by Taqman real-time PCR method with a 7900 HT sequence detector system. RESULTS: The gastric cancer patients were more likely to have smoking habit, a family history of cancer and H.pylori infection. We did not find the significant difference in the genotype distributions of XPF rs180067, rs1799801 and rs2276466 between cases and controls. Multivariate logistic analysis showed a non-significant decreased risk in patients carrying rs180067 G allele, rs1799801 T allele or rs2276466 T allele genotypes. The stratification by H.pylori infection was not significantly different in polymorphisms of XPF rs180067, rs1799801 and rs2276466. CONCLUSION: There was no evidence that polymorphisms in rs180067, rs1799801 and rs2276466 significantly affect the risk of gastric cancer. Further large sample size studies are strongly needed to validate their association.

Argon-helium knife cryoablation plus programmed cell death protein 1 inhibitor in the treatment of advanced soft tissue sarcomas: there is no evidence of the synergistic effects of this combination therapy.

Background: Effective treatment for advanced soft tissue sarcomas (STSs) is necessary for improved outcomes. Previous studies have suggested that cryoablation can have a synergistic effect with programmed cell death protein-1 (PD-1) inhibitor in the treatment of malignancy. This study aimed to clarify the efficacy and safety of argon-helium knife cryoablation in combination with PD-1 inhibitor in the treatment of STSs. Methods: Retrospectively collected and analyzed the clinical data of patients with advanced STS who underwent cryoablation and PD-1 inhibitor between March 2018 and December 2021. Results: This study included 27 patients with advanced STS. In terms of target lesions treated with cryoablation, 1 patient achieved complete response, 15 patients had partial response (PR), 10 patients had stable disease, and 1 patient had progressive disease. This corresponded to an overall response rate of 59.3% and a disease control rate of 96.3%. In terms of distant target lesions untreated with cryoablation, only two patients had a PR compared to the diameter of the lesion before ablation. The combination therapy was relatively well tolerated. None of the patients experienced treatment-related death or delayed treatment due to adverse events. Conclusion: Cryoablation combined with PD-1 inhibitors in the therapy of advanced STS is safe and can effectively shrink the cryoablation-target lesion. However, there is no evidence of the synergistic effects of this combination therapy.

Apatinib plus chemotherapy for non-metastatic osteosarcoma: a retrospective cohort study.

Background: Effective adjuvant therapy for osteosarcoma is necessary for improved outcomes. Previous studies demonstrated that apatinib plus doxorubicin-based chemotherapy may improve the efficacy of neoadjuvant therapy. This study aimed to clarify the effectiveness and safety of apatinib plus doxorubicin and cisplatin (AP) as neoadjuvant therapy for osteosarcoma. Methods: The clinical data of osteosarcoma patients who underwent neoadjuvant therapy and surgery between August 2016 and April 2022 were retrospectively collected and analyzed. Patients were divided into two groups: the apatinib plus AP (apatinib + AP) group and the methotrexate, doxorubicin, and cisplatin (MAP) group. Results: This study included 42 patients with nonmetastatic osteosarcoma (19 and 23 patients in the apatinib + AP and MAP groups, respectively). The 1- and 2-year disease-free survival rates in the apatinib + AP group were higher than those in the MAP group, but the difference was not significant (P=0.165 and 0.283, respectively). Some adverse events were significantly more common in the apatinib + AP group than in the MAP group, including oral mucositis (grades 3 and 4) (52.6% vs. 17.4%, respectively, P=0.023), limb edema (47.4% vs. 17.4%, respectively, P=0.049), hand-foot syndrome (31.6% vs. 0%, respectively, P=0.005), proteinuria (26.3% vs. 0%, respectively, P=0.014), hypertension (21.1% vs. 0%, respectively, P=0.035), and hypothyroidism (21.1% vs. 0%, respectively, P=0.035). No drug-related deaths occurred. There was no statistically significant difference in the incidence of postoperative complications between the groups (P>0.05). Conclusion: The present study suggests that apatinib + AP may be a promising candidate for neoadjuvant therapy for osteosarcoma, warranting further validation in prospective randomized controlled clinical trials with long-term follow-up.

Efficacy and safety of sintilimab plus doxorubicin in advanced soft tissue sarcoma: A single-arm, phase II trial.

Background: Chemoimmunotherapy is safe and efficacious in treating many types of malignant tumors. However, clinical data demonstrating the effect of this combination treatment in patients with metastatic soft tissue sarcoma (STS) are currently limited. This study evaluated the safety and efficacy of a programmed cell death protein 1 (PD-1) inhibitor plus doxorubicin in patients with advanced STS who failed previous systemic therapy. Methods: This was a single-center, single-arm, open-label phase II trial. Patients with unresectable or metastatic STS who had previously failed systemic therapy were enrolled. Patients received up to six cycles of doxorubicin and sintilimab (a PD-1 inhibitor), while sintilimab treatment continued for up to 2 years. Primary outcomes were objective response rate (ORR) and safety. Univariate Cox proportional hazards model was used to analyze the relationship between clinicopathological parameters and progression-free survival (PFS). Results: A total of 38 patients (20 men and 18 women) were enrolled in this study. The overall ORR was 39.5%, disease control rate was 71.1%, and the median PFS was 4.5 months [95% confidence interval (CI), 3.0-8.5 months]. The adverse events (AEs) associated with the combined treatment were mild, manageable, and well-tolerated. The most common grade 3 or higher AEs were hematologic, including leukopenia (21.1%), anemia (18.4%), and thrombocytopenia (18.4%). Patients with undifferentiated pleomorphic sarcoma (UPS) or dedifferentiated liposarcoma had a significantly longer PFS than those with other pathological subtypes [hazard ratio (HR) = 0.42, 95% CI 0.21-0.83; p = 0.013]. There was no significant difference in the median PFS between patients who had previously received anthracycline-based chemotherapy and those who had not (HR = 0.74, 95% CI 0.34-1.58, p = 0.43). Conclusion: Sintilimab plus doxorubicin is a safe and promising treatment for patients with advanced STS who have failed previous systemic therapy (including anthracycline-based chemotherapy). The efficacy of this combination therapy in UPS and dedifferentiated liposarcoma is superior to that in other sarcomas. Clinical Trial Registration: https://www.chictr.org.cn, registration number: ChiCTR1900027009.

Two-dimensional transition metal borides as high activity and selectivity catalysts for ammonia synthesis.

In comparison to defect/doping induced activity in materials, transition metal borides with exposed metal atoms, large specific surface area, and high active site density show advantages as durable and efficient catalysts for specific electrochemical reactions. In this work, ReB2 for N2 reduction reaction (NRR) for ammonia (NH3) with a record-low limiting potential of UL = -0.05 V and high Faraday efficiency (FE) of 100% is screened out from a new class of TMB2. It is concluded that high pressure/temperature is favorable to N2 adsorption and kinetic barrier minimization; the maximal turnover frequency (TOF) at 700 K and 100 bar is 1.24 × 10-2 per s per site, which is comparable to that of the benchmark Fe3/Al2O3 catalysts, achieving an extremely fast reaction rate. In addition, crystal orbital Hamilton population (COHP) of *N2 reveals the intrinsic origin of N2 activation by analyzing the d-2π* interactions, and integrated COHP could be a quantitative descriptor to describe the N2 activation degree. It is evident that our results not only identify an efficient NRR electrocatalyst in particular, paving the way for sustainable NH3 production, but also explain the chemical and physical origin of the activity, advancing the design principle for catalysts for various reactions in general.

Clinical Experience with Apatinib and Camrelizumab in Advance Clear Cell Sarcoma: A Retrospective Study.

PURPOSE: Advanced clear cell sarcoma (CCS) is a rare subtype of sarcoma with few effective treatments. Evidence shows that apatinib is efficacious and safe for CCS. This study aimed to assess the safety and efficacy of apatinib and/or camrelizumab (a PD-1 inhibitor) in treating advanced CCS. METHODS: We retrospectively reviewed 12 patients with advanced CCS who received apatinib and/or camrelizumab therapy between November 2018 and July 2021. Standard descriptive statistics were employed for continuous variables and categorical variables (number and percentage). RESULTS: Of the 12 CCS patients, 3 had a partial response (PR), and 4 had stable disease (SD). Among the 5 patients treated with apatinib monotherapy, 1 PR and 2 SD were found, and the addition or replacement of camrelizumab after progressive disease (PD) did not work. In the 4 patients who received apatinib plus camrelizumab combination therapy, 1 PR and 1 SD were found. All 3 patients who received camrelizumab first had PD, and 1 PR and 1 SD were found after adding apatinib. Grade 3 or 4 adverse events were significantly more common in the apatinib plus camrelizumab combination therapy than in the apatinib or camrelizumab monotherapy, and these included increased aspartate aminotransferase and increased alanine aminotransferase levels. CONCLUSION: Apatinib has promising effectiveness for CCS. Camrelizumab efficacy for the treatment of clear cell sarcoma is inconclusive. The efficacy of apatinib and PD-1 inhibitors in CCS need to be further investigated in prospective clinical trials.

Undifferentiated Pleomorphic Sarcoma with Neoplastic Fever: A Retrospective Study.

BACKGROUND: Although the annual incidence of undifferentiated pleomorphic sarcoma (UPS) is extremely low, it can be subdivided into different subtypes. UPS with fever of unknown origin (also known as neoplastic fever) is a specific subtype of UPS, which shows certain clinical features that differentiate it from other UPS subtypes. However, no studies have focused on this rare UPS subtype. This study retrospectively analyzed the clinical data of patients with UPS to provide a reference for the diagnosis and treatment of UPS with neoplastic fever. METHODS: This study included patients with UPS who were diagnosed and treated between June 2012 and June 2018. We examined whether these patients had a history of neoplastic fever. The characteristics of patients with UPS with neoplastic fever were summarized and analyzed. RESULTS: We reviewed the medical records of 183 patients with UPS. Seven (3.83%) of these patients had neoplastic fever. In patients with UPS with neoplastic fever, the primary lesions were located in the extremities and across the muscle space. In these patients, magnetic resonance imaging showed necrosis within the tumor body and extensive soft tissue edema around the tumor body. Patients with UPS with neoplastic fever had a lower metastasis rate (14.29% vs 44.94%) and a higher 3-year survival rate (85.71% vs 59.55%) than those without neoplastic fever. CONCLUSION: UPS with neoplastic fever is characterized by intratumoral necrosis and extensive edema of the surrounding soft tissues. Patients with UPS with neoplastic fever may have a better prognosis than those without neoplastic fever.

Mixed polybrominated/chlorinated dibenzo-p-dioxins and dibenzofurans in stack gas emissions from industrial thermal processes.

Very little is known about mixed polybrominated/chlorinated dibenzo-p-dioxins and dibenzofurans (PBCDD/F) in industrial thermal processes. In this study, the occurrences and characteristics of PBCDD/F from various incineration and metallurgical processes were investigated. In addition, PBCDD/F analytical protocols based on HRGC/HRMS were developed and optimized. The sum of isomer group concentrations ranged from 1.7-3740 pmol Nm(-3) for PBCDF and 0.2-582 pmol Nm(-3) for PBCDD. For some metallurgical industries, the amounts of PBDD/F and PBCDD/F emitted were similar to or even higher than the amounts of PCDD/F. The sources of bromine and brominated-precursors in these processes should be evaluated. The PBCDD/F characteristics investigated included isomer group patterns, ratio of bromine and chlorine incorporated in PBCDD/F, and ratio of halogenated furans to dioxins. Lower brominated PBCDD/F were binomially distributed. But in some cases, the concentrations of higher brominated PBCDD/F were much higher than predicted from the binomial distribution. The formation mechanisms of PBDD/F, PBCDD/F, and PCDD/F in these processes were also evaluated.

Elemental and individual particle analysis of atmospheric aerosols from high Himalayas.

Atmospheric aerosols were collected during the scientific expedition to Mt. Qomolangma (Everest) in May-June, 2005. The elemental concentrations of the aerosols were determined by inductively coupled plasma mass spectrometry. This yielded data for the concentration of 14 elements: Na, Mg, Al, K, Ca, Ti, V, Cr, Mn, Fe, Ni, Cu, Zn, and Pb. The mean elemental concentrations were generally comparable with those from central Asia and the Arctic, while much higher than those from Antarctic. Size, morphology, and chemical composition of 900 individual aerosol particles were determined by scanning electron microscopy and energy-dispersive X-ray microanalysis. Based on morphology and elemental composition, the particles were clustered into eight groups: soot (8%), tar ball (3%), alumosilicates/silica (55%), calcium sulfate (16%), Ca/Mg carbonate (2%), Fe/Ti-rich particles (3%), Pb-rich particles (1%), and biological particles (12%). The sampling site, located at 6,520 m in the Himalayas, is particularly remote and located at high altitude. Nonetheless, high aerosol enrichment factors for copper, chromium, lead, nickel, vanadium, and zinc all suggest the influence of long-range transported pollution, while enrichment in calcium and the presence of alumino-silicates in individual particle analyses indicates a distinct mineral dust influence. The backward air mass trajectories showed that the northwestern part of India may contribute to the atmospheric aerosol in the central high Himalayas.

Measurements and characteristics of nitrogen-containing compounds in atmospheric particulate matter in Beijing, China.

The total nitrogen (TN) and water-soluble nitrogenous ions were determined by using CHN Elemental Analyzer and ion chromatography method, respectively, from November 24, 1998 to February 12, 1999 in Beijing. The average concentrations of TN, NH(4) (+) and NO(3) (-) were 10.62 microg N m(-3), 6.67 microg m(-3) and 10.01 microg m(-3), respectively. The total inorganic nitrogen (IN) calculated from NH(4) (+) and NO(3) (-) was 7.45 microg N m(-3), accounting for 70% of TN, i.e., 30% of TN existed as organic nitrogen form (ON). The correlation between ON and other pollution tracers showed that, coal combustion, biomass burning, soil humic matter and secondary formation were the important sources of ON in particulate matter in Beijing.

Folic Acid-Conjugated Cellulose Nanocrystals Show High Folate-Receptor Binding Affinity and Uptake by KB and Breast Cancer Cells.

The study evaluates cellulose nanocrystals (CNCs) as nanocarriers for targeted, intracellular delivery of molecular agents. CNCs were labeled with fluorescein-5'-isothiocyanate as an imaging agent and conjugated to folic acid (FA) as a targeting ligand. The CNC conjugates were characterized by UV-vis spectroscopy, ζ-potential analysis, dynamic light scattering, and atomic force microscopy. Cellular binding/uptake of the FA-conjugated CNCs by KB and MDA-MB-468 cells was quantified with cellular uptake assays. Internalization of the particles was confirmed by confocal microscopy. Uptake mechanisms were determined by inhibition studies with chlorpromazine and genistein. Binding affinity was qualitatively assessed with a free folate inhibition assay. Both KB and MDA-MB-468 cells exhibited significant and folate-receptor specific binding/uptake of FA-conjugated CNCs. Clathrin-mediated endocytosis was a significant uptake mechanism in both cell types, whereas caveolae-mediated endocytosis only played a significant role in MDA-MB-468 cells. Uptake inhibition of FA-conjugated CNCs by KB cells required high concentrations (>1 mM) of free FA. The observed FR-specific internalization of FA-conjugated CNCs by FR-positive cancer cells and tumors and their remarkable high affinity for the FR demonstrate the great potential of CNCs as novel nanocarriers for imaging agents and chemotherapeutics in the early detection and treatment of cancer.

Clinical significance of serum total oxidant/antioxidant status in patients with operable and advanced gastric cancer.

PURPOSE: Oxidative stress was significantly associated with the development of malignancies. The purpose of this study was to evaluate the significance of serum total oxidant/antioxidant status in operable advanced gastric cancer patients. MATERIALS AND METHODS: A total of 284 patients who underwent curative resection for primary stage III gastric cancer were enrolled. Total oxidant status, total antioxidant status, and oxidative stress index (OSI) were evaluated within 24 hours before surgery, and compared with 120 healthy donors. The correlation between the OSI and survival outcome was analyzed by the Kaplan-Meier method with log-rank test and Cox's regression methods, respectively. RESULTS: Mean OSI of gastric cancer patients was higher than healthy controls (1.41±0.96 vs 0.78±0.42, P<0.001). All patients were stratified into two groups using the optimal cutoff value (1.42) of OSI using a sensitivity of 94.1% and a specificity of 64.0% as optimal conditions from receiver operating curve analysis. Patients with an OSI ≥1.42 had poorer mean overall survival (45.6 vs 29.8 months, P=0.022) and mean recurrence-free survival (43.3 vs 28.1 months, P=0.011) than patients with an OSI <1.42 in univariate analysis, and OSI was also confirmed as an independent predictor for survival for gastric cancer in multivariate analysis (hazard ratio, 0.541; 95% CI: 0.127-1.102; P=0.01). CONCLUSION: Preoperative OSI can be considered as an independent prognostic factor for operable and advanced gastric cancer.

Brown and black carbon in Beijing aerosol: Implications for the effects of brown coating on light absorption by black carbon.

Brown carbon (BrC) is increasingly included in climate models as an emerging category of particulate organic compounds that can absorb solar radiation efficiently at specific wavelengths. Water-soluble organic carbon (WSOC) has been commonly used as a surrogate for BrC; however, it only represents a limited fraction of total organic carbon (OC) mass, which could be as low as about 20% in urban atmosphere. Using methanol as the extraction solvent, up to approximately 90% of the OC in Beijing aerosol was isolated and measured for absorption spectra over the ultraviolet-to-visible wavelength range. Compared to methanol-soluble OC (MSOC), WSOC underestimated BrC absorption by about 50% at 365nm. The mass absorption efficiencies measured for BrC in Beijing aerosol were converted to the imaginary refractive indices of BrC and subsequently used to compute BrC coating-induced enhancement of light absorption (Eabs) by black carbon. Eabs attributed to lensing was reduced in the case of BrC coating relative to that caused by purely-scattering coating. However, this reduction was overwhelmed by the effect of BrC shell absorption, indicating that the overall effect of BrC coating was an increase in Eabs. Methanol extraction significantly reduced charring of OC during thermal-optical analysis, leading to a large increase in the measured elemental carbon (EC) mass and an apparent improvement in the consistency of EC measurements by different thermal-optical methods.