Volatile organic compounds (VOCs) are essential pollutants affecting ambient air quality. In the Pearl River Delta of China, furniture manufacturing contributes significantly to VOCs emissions, ...mainly from coatings. Therefore, the source substitution of coatings is the most effective way to reduce VOCs emissions. In this study, eight typical furniture enterprises with five different coatings types (traditional solvent coatings (solvent and solvent ultraviolet (UV) coatings) and low VOCs content coatings (waterborne, waterborne UV, and powder coatings)) were selected for field monitoring to reveal differences in VOCs emission characteristics, environmental impacts and health risks between traditional solvent coatings and low-VOCs coatings. The results showed that solvent coating VOCs have the highest concentration (143.32 mg/m3) and are much higher than that of solvent UV coating (45.96 mg/m3) and other coatings (≤11.81 mg/m3). The highest proportion of VOCs of solvent (UV) coating is aromatic hydrocarbons (50.73% (44.05%)). While oxygenated VOCs rank first in low-VOCs coatings (47.81%–59.20%). Compared with other coatings, the solvent coating has the greatest contribution to the formation potential of ozone and secondary organic aerosols. Meanwhile, the solvent coating has the highest carcinogenic risk of ethylbenzene in the spraying workshop (8.53 × 10−6), and only solvent coating in the spraying workshop has the non-carcinogenic risk of xylene (1.07). Finally, through scenario analysis, the environmental benefits of low-VOCs coatings substituting solvent coating were quantified. The study will help accelerate the process of source substitution of coatings and promote cleaner production in the furniture industry.
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•VOCs spectra of five different coating types in furniture industry were obtained.•Solvent coating has a much higher contribution to secondary pollutants than others.•Solvent (ultraviolet) coatings exist a carcinogenic risk of ethylbenzene.•Only solvent coating in spraying workshop has a non-carcinogenic risk of xylene.•The environmental benefits of low-VOCs coatings substitution were quantified.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
BackgroundPD-1/L1 inhibitors are treatment options for patients with HCC who have progressed after first-line sorafenib treatment. Tislelizumab, an anti-PD-1 monoclonal antibody, has demonstrated ...single-agent antitumor activity in patients with advanced, previously treated HCC in two early phase studies (NCT02407990, NCT04068519). Association of biomarkers, including PD-L1 expression and gene expression profiles (GEP), with response and resistance to tislelizumab were explored.MethodsPD-L1 expression was evaluated on tumor cells (TC) using the VENTANA PD-L1 (SP263) assay in baseline tumor samples collected before or after sorafenib treatment. GEP were assessed using the 1392-gene HTG GEP EdgeSeq panel. Signature scores were calculated using the Gene Set Variation Analysis package with publicly available gene signatures (GS). Wilcoxon rank-sum test was used to analyze differential gene signatures (DEG); GS association with PFS and OS was evaluated using Cox proportional hazards models.ResultsSingle-agent tislelizumab demonstrated antitumor activity in advanced, previously treated HCC (ORR=13%; CB PR+SD >6 months=31%, median PFS=3.3 months; median OS=13.3 months). PD-L1+ (TC≥1%) prevalence and GEP showed different patterns in samples collected before and after sorafenib exposure (figure 1). While non-exposed samples (n=16) were enriched for immune suppressive signatures, sorafenib-exposed samples (n=41) showed higher PD-L1+ prevalence (53.7% vs 25%; P=0.08) and immune-cell activation signatures along with co-inhibition molecules. In sorafenib-exposed samples, PD-L1 expression was positively correlated with CB (P=0.0027) and a trend of longer PFS (HR=0.56, 95% CI:0.28–1.13). ORR was higher in PD-L1+ than PD-L1− sorafenib-exposed samples (23.8% vs 0%; P=0.049). DEG analysis in sorafenib-exposed samples demonstrated that NK-mediated cytotoxicity GS was positively correlated with CB (P=0.03), as well as a trend of longer PFS (HR=0.43, 95% CI:0.17–1.06). Across the different analyses, no correlation with OS was observed. Patients considered non-responders (NRs) were found clustered into three distinct GEP subgroups (NR1, NR2, NR3). Compared with responders, NR1 had enhanced angiogenesis signatures (P=0.01), including TEK, KDR, HGF, and EGR1. Despite high inflamed tumor signatures, NR2 had increased expression of T-cell inhibition GS scores (P=0.01), including CD274, CTLA4, TIGIT, and CD96. The NR3 subgroup showed higher cell-cycle GS scores compared with responders (P=0.05), including E2F7, FOXA1, and FANCD2.Abstract 77 Figure 1Median difference in gene signatures before and after sorafenib exposureConclusionsPrior sorafenib exposure appears to be associated with increased PD-L1 expression and tumor microenvironment-related GS, as well as response and PFS from tislelizumab in advanced HCC patients. Elevated angiogenesis, immune exhaustion, and cell-cycle GS levels may indicate resistance to single-agent PD-1 inhibitors and is suggestive of potential treatment strategies. Validation is warranted in future clinical trials (NCT03412773).AcknowledgementsThis study was sponsored by BeiGene, Ltd. Writing and editorial assistance was provided by Regina Switzer, PhD, and Elizabeth Hermans, PhD (OPEN Health Medical Communications, Chicago. IL), and funded by the study sponsor.Trial RegistrationNCT02407990, NCT04068519
Summary
Purpose
Preclinical data showed that trientine, a copper-lowering agent, re-sensitized cancer cells to carboplatin through
enhanced human copper transporter 1
(hCtr1) -mediated platinum ...uptake.
Experimental Design
We studied carboplatin and trientine in patients (
n
= 55; 45 who had failed platinum) with advanced malignancies (Phase I, modified 3 + 3 design).
Results
The most common cancers were head and neck (
n
= 13), non-small cell lung (
n
= 10) and epithelial ovarian (
n
= 8). The median number of prior regimens was four. No dose-limiting toxicity or treatment-related deaths were observed at doses up to carboplatin AUC 6 given with trientine. Eight patients achieved stable disease (SD) ≥ 6 months (six platinum failures) and one patient with platinum-resistant ovarian cancer, partial response (PR) (total SD ≥ 6 months/PR = 9, 16.4 %). The mean nadir serum copper level in the nine patients with SD ≥ 6 months/PR was 0.55 μg/mL (95 % CI, 0.34–0.75) versus 1.22 μg/mL (95 % CI, 1.02–1.42) (
p
< 0.001) in 38 tested patients with progression. In patients who maintained their ceruloplasmin (major copper-carrying protein) levels at 5–15 mg/dL (
n
= 9), the median progression-free and overall survivals were 9.2 and 15.2 months versus 1.9 (
p
= 0.001) and 5.7 months (
p
= 0.033) in patients who did not (
n
= 38), respectively.
Conclusions
The combination of a copper-lowering agent with carboplatin was well tolerated and associated with antitumor activity, especially in patients in whom copper and/or ceruloplasmin levels were lowered. Further investigation of this strategy for reversing platinum resistance is warranted.
PROBLEM PRESENTEDSarcomatoid carcinoma (SaCa) is a rare variant of squamous cell carcinoma (SCC) with sarcomatoid features. This study investigated the clinical presentation and outcomes of head and ...neck SaCa. In addition, reconstructive outcome for a subset of patients was also evaluated.
STUDIES UNDERTAKENSeventy-eight SaCa cases including 72 men and 6 women were identified from 13,777 head and neck SCC cases. Clinical outcomes were evaluated based on locoregional control, distant metastases, and multivariate analyses. Reconstructive outcome was evaluated by flap survival rate.
RESULTOf the 78 cases, 71% (55) of cases were located in the oral mucosa; 64% (50) of patients were classified as T3 or T4 at the time of diagnosis. The 5-year survival was only 16%. Multivariate analysis revealed better outcomes only when the patient had a history of previous SCC. Forty-five patients underwent flap reconstruction, with 98% flap survival rate but the functional result varied because of the inevitable adjuvant radiotherapy and advanced stage of tumor.
CONCLUSIONSSarcomatoid carcinoma is a different entity from the conventional SCC of the head and neck. Sarcomatoid carcinoma carries a poorer prognosis despite aggressive surgical intervention and concurrent adjuvant therapies. It remains a great challenge for clinical oncologists, and the optimal treatment strategy requires further studies. Free flap is still preferred for defect reconstruction but the design should be simplified to avoid complications.
Background: Desmoid tumor and leiomyoma are abdominal wall tumors with similar clinical, radiographic, and histological features. However, differentiation between these two diseases is important ...because each may be linked to different systemic diseases, and their managements are entirely different. We proposed that misdiagnosis is possible in some cases.
Patients and Methods: Between 1983 and 2010, patients with a history of uterine surgeries and diagnosed with either abdominal wall desmoid tumors or leiomyomas were studied. All the images reviewed by an independent radiologist and surgical specimen were reexamined by immunohistochemistry (IHC) techniques as a standard method to confirm the diagnoses.
Results: Fifteen female patients (desmoid tumors, n = 10; leiomyomas, n = 5) were included. The diagnosis of IHC revealed that two cases initially thought to be leiomyomas were desmoid tumors, whereas the remaining 13 cases maintained their initial diagnoses. The accuracy of hematoxylin and eosin staining was 86.7%. All tumors excised without complications, except for one desmoid tumor that recurred and underwent another excision.
Conclusion: Preoperative magnetic resonance imaging (MRI) can be considered to differentiate the two diseases, as well as the elimination of other associated systemic diseases should be performed routinely. If MRI is inaccessible or unavailable, preoperative fine-needle biopsy is recommended. Optional IHC staining is required if the primary histological assessment is equivocal or inconclusive.
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•GP cross-linked EW was prepared for ageing ECM biomimetic microenvironment in cell culture.•The porosity and mechanical properties of the ECM-mimetic GP cross-linked EW facilitated ...cell proliferation and aggregation.•Prevention and treatment of cancers should focus on drugs that can prevent age-induced degenerative changes in the ECM.
Cancer is closely associated with aging of the body. Aging of the extracellular matrix (ECM) leads to a fibrotic microenvironment and increasing stiffness of ECM. In this study, the porosity and stiffness were advantageous to the proliferation and aggregation of ovarian SKOV-3 cancer cells. Both the porosity and stiffness increase could lead to enhancement of proliferation and aggregation of ovarian SKOV-3 cancer cells. Further studies aimed at preventing tumoral invasion and metastasis should focus on drugs that can prevent age-induced degenerative changes in the ECM.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
High-grade epithelial ovarian cancer (HG-EOC) is the most lethal gynecologic malignancy worldwide Once patients develop chemoresistance, effective novel strategies are required to improve prognosis ...We analyzed characteristics and outcomes of 242 consecutive patients with HG-EOC participating in 94 phase I clinical trials at The University of Texas MD Anderson Cancer Center. Baseline lactate dehydrogenase levels, albumin levels, and number of metastatic sites were independent predictors of overall survival (OS). Receiving more than 1 phase I protocol was associated with improved OS (p < 0.001). Regimens including a chemotherapeutic agent plus bevacizumab or Aurora A kinase inhibitor led to a median progression-free survival (PFS) duration of more than 6 months. Although patients receiving bevacizumab-based regimens in the phase I clinical trials had significantly longer PFS than those receiving other anti-angiogenic therapies (p = 0.017), patients treated with vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs) had significantly longer OS (12.2 months) than those not treated with VEGFR-TKIs (8.6 months, p = 0.015).In conclusion, anti-angiogenic therapy is one of the most important strategies for the treatment of HG-EOC, even in those who have already experienced tumor progression. Therefore, eligible patients with HG-EOC should be encouraged to participate in novel phase I studies of anti-angiogenic therapies, even after disease progression.
We evaluated clinical outcomes of patients with metastatic cervical cancer referred to a Phase I Clinical Trials Program.
We reviewed the electronic medical records of 54 consecutive phase I patients ...with metastatic cervical cancer over 6.5 years and analyzed the correlation between clinical outcome and potential predictors.
All patients had received at least one systemic therapy for metastatic disease before referral. Only two patients declined phase I trial therapy. The median progression-free (PFS) and overall (OS) survivals were 3.6 and 10.6 months, respectively. Patients harboring phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutations or phosphatase and tensin homolog loss, and those with more than two sites of metastasis who received more than one prior systemic chemotherapy before the referral had median PFS of 6.7 and 1.8 months, and median OS of 12.6 and 2.9 months, respectively.
Patients with more than two metastatic sites who had received more than one prior system therapy had dismal outcomes. An aberrant PI3K pathway was frequently identified and associated with favorable outcome, providing a promising target.
Purpose
Cancer patients with predominantly hepatic metastases have poor outcomes and limited options. Hepatic arterial infusion (HAI) of a therapeutic agent may be an appropriate option for producing ...increased drug concentrations at the tumor sites while reducing systemic adverse effects in normal tissues.
Methods
Patients with predominantly hepatic metastases (
n
= 48) were placed in 6 groups according to nanoparticle albumin-bound paclitaxel (
nab
-
paclitaxel
) dose level using a 3 + 3 design plus dose expansion for responsive tumor types. We evaluated the toxicity, antitumor activity, and pharmacokinetics of
nab
-
paclitaxel
delivered via HAI.
Results
Thirty-eight and ten patients underwent HAI over 1 and 4 h, respectively, at doses of up to 300 mg/m
2
. The treatment was safe and exhibited antitumor activity. Pharmacokinetic analyses revealed that HAI of
nab
-
paclitaxel
over 4 h resulted in markedly lower peak drug concentrations (
C
max
) and longer times to peak concentration (
T
max
) than that over 1 h. The self-control pharmacokinetic studies showed that HAI of
nab
-
paclitaxel
led to much lower
C
max
and areas under the curve (AUC), compared with intravenous infusion.
Conclusions
HAI of
nab
-
paclitaxel
at up to 300 mg/m
2
over 4 h was well tolerated. Pharmacokinetic evaluation of
C
max
,
T
max
, and AUC implied that 4-h HAI enhanced hepatic extraction of
nab
-
paclitaxel
. Further preclinical and clinical studies are required to develop reliable methods of evaluation of hepatic extraction (clinicaltrials.gov registration number NCT00732836, first registered on August 8, 2008, and last updated on October 27, 2014).
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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