Suppression of tumor metastasis is a key strategy for successful cancer interventions. Previous studies indicated that rapamycin (sirolimus) may promote tumor regression activity or enhance immune ...response against tumor targets. However, rapamycin also exhibits immunosuppressant effects and is hence used clinically as an organ transplantation drug. We hypothesized that the immunosuppressive activities of rapamycin might also negatively mediate host immunity, resulting in promotion of tumor metastasis. In this study, the effects of rapamycin and phytochemical shikonin were investigated in vitro and in vivo in a 4T1 mouse mammary tumor model through quantitative assessment of immunogenic cell death (ICD), autophagy, tumor growth and metastasis. Tumor-bearing mice were immunized with test vaccines to monitor their effect on tumor metastasis. We found that intraperitoneal (ip) administration of rapamycin after a tumor-resection surgery drastically increased the metastatic activity of 4T1 tumors. Possible correlation of this finding to human cancers was suggested by epidemiological analysis of data from Taiwan's National Health Insurance Research Database (NHIRD). Since our previous studies showed that modified tumor cell lysate (TCL)-pulsed, dendritic cell (DC)-based cancer vaccines can effectively suppress metastasis in mouse tumor models, we assessed whether such vaccines may help offset this rapamycin-promoted metastasis. We observed that shikonin efficiently induced ICD of 4T1 cells in culture, and DC vaccines pulsed with shikonin-treated TCL (SK-TCL-DC) significantly suppressed rapamycin-enhanced metastasis and Treg cell expansion in test mice. In conclusion, rapamycin treatment in mice (and perhaps in humans) promotes metastasis and the effect may be offset by treatment with a DC-based cancer vaccine.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The use of triglycerides as an important class of biomass is an effective strategy to realize a more sustainable society. Herein, three heterogeneous catalytic methods are reported for the selective ...one‐pot transformation of triglycerides into value‐added chemicals: i) the reductive amination of triglycerides into fatty amines with aqueous NH3 under H2 promoted by ZrO2‐supported Pt clusters; ii) the amidation of triglycerides under gaseous NH3 catalyzed by high‐silica H‐beta (Hβ) zeolite at 180 °C; iii) the Hβ‐promoted synthesis of nitriles from triglycerides and gaseous NH3 at 220 °C. These methods are widely applicable to the transformation of various triglycerides (C4–C18 skeletons) into the corresponding amines, amides, and nitriles.
Three ways are better than one: Three heterogeneous catalytic methods for the selective one‐pot transformation of triglycerides into value‐added chemicals are presented: i) the reductive amination of triglycerides into fatty amines with aqueous NH3 and H2, ii) the amidation of triglycerides with gaseous NH3, and iii) the direct synthesis of nitriles with gaseous NH3.
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•A sonochemical synthesis of SrTiO3/NGO electrode materials without any toxic reducing agents.•The morphological, chemical and electrochemical characterizations of the SrTiO3/NGO ...composite was carried out.•SrTiO3/NGO/LIGE exhibits excellent electrochemical sensing ability towards anti-cancer drug.•SrTiO3/NGO/LIGE platform is successfully applied to practicality in biological fluids.
A sonochemical based green synthesis method playa powerful role in nanomaterials and composite development. In this work, we developed a perovskite type of strontium titanate via sonochemical process. SrTiO3 particles were incorporated with nitrogen doped graphene oxide through simple ultrasonic irradiation method. The SrTiO3/NGO was characterized by various analytical methods. The nanocomposite of SrTiO3/NGO was modified with laser-induced graphene electrode (LIGE). The SrTiO3/NGO/LIGE was applied for electrochemical sensor towards chemotherapeutic drug detection (nilutamide). Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) techniques have been used to examine the electrochemical performance of nilutamide (anti-cancer drug). DPV was found to be more sensitive and found to exhibit a sensitivity 8.627 µA µM−1 cm−2 for SrTiO3/NGO/LIGE with a wide linear range (0.02–892 µM) and low Limit of detection (LOD: 1.16 µM). SrTiO3/NGO/LIGE has been examined for the detection of nilutamide in blood serum and urine samples and obtained a good recovery in the range of 97.2–99.72 %. The enhanced stability and selectivity and practical application results indicates the suitability of SrTiO3/NGO/LIGE towards the detection of nilutamide drug in pharmaceutical industries.
On ocular surface, corneal epithelial stem cells (SC) reside in limbus between cornea and conjunctiva. Pax6, an evolutionally conserved transcription factor essential for eye development, is ...expressed in post-natal corneal and limbal epithelia progenitors (LEPC) but not in underlying stroma. Because Pax6 is transiently expressed in developing corneal stroma and a subset of limbal and corneal stromal progenitors, we examined the role of Pax6 in limbal niche cells (LNC) in maintaining the phenotype of neural crest (NC) progenitors to support LEPC. Our results showed that nuclear Pax6 staining was found in freshly isolated LNC but not corneal stromal cells. Serial passaged LNC resulted in gradual loss of nuclear Pax6 (46 kDa) staining and neural crest progenitor status defined by the expression of embryonic SCs and NC markers, neurosphere formation, and differentiation into neurons, oligodendrocytes and astrocytes. Gain of function of 46 kDa Pax6 in late-passaged LNC resulted in nuclear Pax6 staining and promotion of the aforementioned NC progenitor status. In an in vitro reunion assay, early passaged LNC and late passaged LNC with overexpression of Pax6 inhibited the expression of corneal epithelial differentiation marker and promoted holoclone by LEPC. Therefore, expression of nuclear 46 kDa Pax6 in LNC plays an important developmental role in maintaining NC progenitor status to support self-renewal of corneal epithelial SCs in the limbal niche.
Human population growth has led to biodiversity declines in tropical cities. While habitat loss and fragmentation have been the main drivers of urban biodiversity loss, man-made interventions to ...reduce health risks have also emerged as an unintentional threat. For instance, insecticide fogging to control mosquito populations has become the most common method of preventing the expansion of mosquito-borne diseases such as Dengue. However, the effectiveness of fogging in killing mosquitoes has been called into question. One concern is the unintended effect of insecticide fogging on non-target invertebrates that are crucial for the maintenance of urban ecosystems. Here, we investigate the impacts of fogging on: (1) target invertebrate taxon (Diptera, including mosquitoes); (2) non-target invertebrate taxa; and (3) the foraging behavior of an invertebrate pollinator taxon (Lepidoptera) within an urban tropical forest.
We carried out fogging with Pyrethroid insecticide (Detral 2.5 EC) at 10 different sites in a forest situated in the state of Selangor, Peninsular Malaysia. Across the sites, we counted the numbers of knocked-down invertebrates and identified them based on morphology to different taxa. We constructed Bayesian hierarchical Poisson regression models to investigate the effects of fogging on: (1) a target invertebrate taxon (Diptera) 3-h post-fogging; (2) selected non-target invertebrate taxa 3-h post-fogging; and (3) an invertebrate pollinator taxon (Lepidoptera) 24-h post-fogging.
A total of 1,874 invertebrates from 19 invertebrate orders were knocked down by the fogging treatment across the 10 sites. Furthermore, 72.7% of the invertebrates counted 3-h post-fogging was considered dead. Our regression models showed that given the data and prior information, the probability that fogging had a negative effect on invertebrate taxa 3-h post-fogging was 100%, with reductions to 11% of the pre-fogging count of live individuals for the target invertebrate taxon (Diptera), and between 5% and 58% of the pre-fogging count of live individuals for non-target invertebrate taxa. For the invertebrate pollinator, the probability that fogging had a negative effect 24-h post-fogging was also 100%, with reductions to 53% of the pre-fogging count of live individuals.
Our Bayesian models unequivocally demonstrate that fogging has detrimental effects on one pollinator order and non-target invertebrate orders, especially taxa that have comparatively lower levels of chitinisation. While fogging is effective in killing the target order (Diptera), no mosquitos were found dead in our experiment. In order to maintain urban biodiversity, we recommend that health authorities and the private sector move away from persistent insecticide fogging and to explore alternative measures to control adult mosquito populations.
The effect of computer-aided polyp detection (CADe) on adenoma detection rate (ADR) among endoscopists-in-training remains unknown.
We performed a single-blind, parallel-group, randomized controlled ...trial in Hong Kong between April 2021 and July 2022 (NCT04838951). Eligible subjects undergoing screening/surveillance/diagnostic colonoscopies were randomized 1:1 to receive colonoscopies with CADe (ENDO-AIDOIP-1) or not (control) during withdrawal. Procedures were performed by endoscopists-in-training with <500 procedures and <3 years’ experience. Randomization was stratified by patient age, sex, and endoscopist experience (beginner vs intermediate level, <200 vs 200–500 procedures). Image enhancement and distal attachment devices were disallowed. Subjects with incomplete colonoscopies or inadequate bowel preparation were excluded. Treatment allocation was blinded to outcome assessors. The primary outcome was ADR. Secondary outcomes were ADR for different adenoma sizes and locations, mean number of adenomas, and non-neoplastic resection rate.
A total of 386 and 380 subjects were randomized to CADe and control groups, respectively. The overall ADR was significantly higher in the CADe group than in the control group (57.5% vs 44.5%; adjusted relative risk, 1.41; 95% CI, 1.17–1.72; P < .001). The ADRs for <5 mm (40.4% vs 25.0%) and 5- to 10-mm adenomas (36.8% vs 29.2%) were higher in the CADe group. The ADRs were higher in the CADe group in both the right colon (42.0% vs 30.8%) and left colon (34.5% vs 27.6%), but there was no significant difference in advanced ADR. The ADRs were higher in the CADe group among beginner (60.0% vs 41.9%) and intermediate-level (56.5% vs 45.5%) endoscopists. Mean number of adenomas (1.48 vs 0.86) and non-neoplastic resection rate (52.1% vs 35.0%) were higher in the CADe group.
Among endoscopists-in-training, the use of CADe during colonoscopies was associated with increased overall ADR. (ClinicalTrials.gov, Number: NCT04838951).
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Background Poor nutritional status has been associated with worse patient survival in maintenance hemodialysis patients. Anthropometric values are important nutritional measures, incorporating muscle ...and fat mass. However, the association of changes in anthropometry, including midarm circumference (MAC) and skinfold measurements, with mortality in hemodialysis patients remains unknown. Accordingly, we explored this association in the Hemodialysis (HEMO) Study. Study Design Post hoc analysis of cohort data from a clinical trial. Setting & Participants 1,846 hemodialysis patients enrolled in the HEMO Study. Predictors MAC and skinfold measurements. Outcomes Longitudinal changes in MAC and skinfolds were jointly modeled using repeated measures and survival modeling. Time-to-event outcomes were all-cause mortality, cardiac death and hospitalization, and infection-related death. Results Mean MAC was 30.1 cm, and mean baseline sum of subscapular, biceps, and triceps skinfolds was 42.4 mm. During a median follow-up of 2.5 years, there were 845 deaths. During follow-up, MAC and the skinfold measurement declined 0.26 cm and 1.1 mm per year, respectively. Declines in MAC (per cm) and skinfold (per mm) measurements were associated with higher all-cause mortality (HRs of 1.58 95% CI, 1.29-1.94; P < 0.001 and 1.06 95% CI, 0.99-1.13; P = 0.09, respectively), poorer cardiac outcomes (HRs of 1.49 95% CI, 1.23-1.81; P < 0.001 and 1.05 95% CI, 0.99-1.10; P = 0.09, respectively), and higher infection-related hospitalization (HRs of 2.45 95% CI, 1.55-3.88; P < 0.001 and 1.16 95% CI, 0.98-1.37; P = 0.08, respectively). The association between declining MAC and skinfold with patient survival was most notable for those with body mass index (BMI) ≤25 kg/m2 (HRs of 2.41 95% CI, 1.81-3.19; P < 0.001 and 1.22 95% CI, 1.10-1.35; P < 0.001, respectively). Limitations Prevalent dialysis patients only, excluding individuals weighing >85 kg. Conclusions Declines in skinfold thickness were not associated significantly with outcomes except for participants with BMI ≤25 kg/m2 . Declines in MAC are associated significantly with all-cause mortality and cardiac outcomes in hemodialysis patients, most notably in those with BMI ≤25 kg/m2.
Liquid biopsy, including the detection of circulating tumor cells (CTCs), has emerged as a promising tool for cancer diagnosis and monitoring. However, the prognostic value of CTCs in nasopharyngeal ...carcinoma (NPC) remains unclear due to the lack of phenotypic characterization. The expression of Excision Repair Cross-Complementation Group 1 (ERCC1) and CTCs epithelial-mesenchymal transition (EMT) have been associated with treatment efficacy. In this study, we aimed to evaluate the prognostic significance of ERCC1 expression on CTCs and their EMT subtypes before treatment in NPC.
We retrospectively analyzed 108 newly diagnosed locally advanced NPC patients who underwent CanPatrol™ CTC testing between November 2018 and November 2021. CTCs were counted and classified into epithelial, epithelial-mesenchymal hybrid, and mesenchymal subtypes. ERCC1 expression was divided into negative and positive groups. Clinical features and survival outcomes were analyzed.
The positive rate of CTCs was 92.6% (100/108), with an ERCC1 positivity rate of 74% (74/100). Further analysis of the subtypes showed that positive ERCC1 on mesenchymal CTCs was associated with a later N stage (
= .01). Positive ERCC1 expression was associated with poor overall survival (OS;
= .039) and disease-free survival (DFS;
= .035). Further analysis of subtypes showed that the positive ERCC1 on mesenchymal-type CTCs was associated with poor OS (
= .012) and metastasis-free survival (MFS;
= .001).
Our findings suggest that ERCC1 expression on CTCs may serve as a new prognostic marker for NPC patients. Evaluating CTCs subtypes may become an auxiliary tool for personalized and precise treatment.
Background: Bortezomib-induced peripheral neuropathy (BIPN) is a common and debilitating side effect. Our pilot study demonstrated that acupuncture is safe and can decrease total neuropathic ...symptoms. However, there is lack of knowledge in which individual BIPN symptoms benefited from acupuncture. Purpose: To characterize individual symptoms reduced by acupuncture in patients with BIPN. Methods: Patients with multiple myeloma treated with bortezomib who developed BIPN grade 2 or above, based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), were enrolled and received 10 acupuncture treatments over 10 weeks. Self-reported BIPN-associated symptoms assessments were collected weekly at baseline, during, and after acupuncture treatment using the Neuropathy Pain Scale (NPS) and the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group–Neurotoxicity (FACT/GOG-Ntx) questionnaires. Changes in individual symptoms were analyzed based on FACT/GOG-Ntx and NPS scores. Results: There were statistically significant reductions in individual symptoms in both NPS and FACT/GOG-Ntx. The FACT/GOG-Ntx reductions were most pronounced in hand/feet numbness/tingling, discomfort, and trouble walking. The sensory symptoms, such as tingling and numbness, especially in the feet, reduced the most (P < .0001), and motor dysfunction also reduced significantly (P = .0001). Both hearing and dysfunction scores were also statistically significantly increased, indicating improved symptoms. The NPS scores showed significant symptom relief in all 10 items from the NPS assessment, particularly in cold sensitivity and an unpleasant feeling. Conclusions: Acupuncture can improve multiple symptoms associated with BIPN, particularly numbness and tingling in hands and feet, cold sensitivity, and an unpleasant feeling. Further randomized control trials are warranted to confirm our findings.
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