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Most of the nanomedicines can reduce the side effects of anti-tumor chemical drugs but do not have good enough therapeutic efficacy, largely due to the sustained drug release profile. It might be a promising alternative strategy to develop a cascade-responsive nanoplatform against tumor with the burst release of chemotherapeutics based on the highly efficient tumor cell targeting delivery. In this work, we constructed innovative nanoparticles (PMP/WPH-NPs) consisting of two functional polymers. PMP contained the MMP-2 enzyme sensitive linker and disulfide bond, which could respond to the tumor-overexpressing enzyme MMP-2 and high-level glutathione. While WPH promoted tumor penetration and acid-responsive drug release by modifying cellular penetrating peptides and polymerizing L-histidine. PMP/WPH-NPs exhibited outstanding features including longer blood circulation time, promoted tumor-specific accumulation, enhanced tumor penetration and efficient escape from lysosomes. Subsequently, the model drug paclitaxel (PTX), widely used in the tumor chemotherapy, was encapsulated into PMP/WPH-NPs via an emulsion solvent evaporation method. Within a short period of time, PTX-PMP/WPH-NP in simulated tumor cellular microenvironment could release 8 times more PTX than that in the physiological environment, demonstrating a good potential in tumor cell-specific burst drug release. In addition, PTX-PMP/WPH-NPs exhibited stronger anti-tumor activity than PTX in vitro and in vivo, which also had good biocompatibility according to the hemolysis assay and H&E staining. In summary, our work has succeeded in designing an original polymeric nanoplatform for programmed burst drug release based on the tailored tumor targeting delivery system. This new approach would facilitate the clinical translation of more anti-tumor nanomedicines. STATEMENT OF SIGNIFICANCE: Biomaterials responsive to the tumor-specific stimulus has conventionally used in the targeted-delivery of anti-tumor drugs. However, the levels of common stimulus are not uniformly distributed and not high enough to effectively trigger drug release. In an effort to achieve a better specific drug release and promote the chemotherapeutic efficacy, we constructed a cascade responsive nanoplatform with tumor cell-specific drug burst release profile. The tailored biomaterial could overcome the bio-barriers in vivo and succeeded in the programmed burst drug release based on the tumor cell-specific delivery of chemotherapeutics., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier Ltd.)

Introducing donor and acceptor into conjugated system can facilitate the intersystem crossing (ISC) rate to increase the generation of ROS. Twisted intramolecular charge transfer (TICT) state could favor enhance the nonradiative transition and photothermal conversion efficiency (PCE). Herein, diketopyrrolopyrrole (DPP) core functionalized benzene (PDDP), thiophene (TDPP), triphenylamine-conjugated benzene (TPA-PDDP) and thiophene (TPA-TDPP) derivatives were designed and synthesized. Electrochemistry experiments revealed the heavy atom effect and the introduction of triphenylamine reduced the energy level of TPA-TDPP and improved the ability to generate 1 O 2 ( 1 O 2 QY = 50%). In addition, in the aggregated state, introduction of thiophene, triphenylamine, and long alkyl chains promoted the twisting effect, preventing the intermolecular π-π interaction and enhancing the PCE of TPA-TDPP (38.7%). In vivo fluorescence imaging showed that TPA-TDPP NPs can target the tumor site with the enhanced permeability and retention (EPR) effect and presented excellent synergistic photodynamic/photothermal therapy., Competing Interests: Conflicts of interest statement There are no conflicts to declare., (Copyright © 2022. Published by Elsevier Masson SAS.)

CRISPR-Cas13a holds enormous potential for developing precise RNA editing. However, spatial manipulation of CRISPR-Cas13a activity remains a daunting challenge for elaborately regulating localized RNase function. Here, we designed hierarchical self-uncloaking CRISPR-Cas13a-customized RNA nanococoons (RNCOs-D), featuring tumor-specific recognition and spatial-controlled activation of Cas13a, for precise cancer synergistic therapy. RNCOs-D consists of programmable RNA nanosponges (RNSs) capable of targeted delivery and caging chemotherapeutic drug, and nanocapsules (NCs) anchored on RNSs for cloaking Cas13a/crRNA ribonucleoprotein (Cas13a RNP) activity. The acidic endo/lysosomal microenvironment stimulates the outer decomposition of NCs with concomitant Cas13a RNP activity revitalization, while the inner disassembly through trans-cleavage of RNSs initiated by cis-recognition and cleavage of EGFR variant III (EGFRvIII) mRNA. RNCOs-D demonstrates the effective EGFRvIII mRNA silencing for synergistic therapy of glioblastoma cancer cells in vitro and in vivo. The engineering of RNSs, together with efficient Cas13a activity regulation, holds immense prospect for multimodal and synergistic cancer therapy.

Individuals with intellectual disabilities (ID) may require assistance in accessing healthcare services, including cancer screening. A better understanding of the factors affecting cancer screening utilisation among these individuals is needed for the development of strategies to promote screening uptake in them. This review aimed to explore the facilitators of and barriers to cancer screening utilisation among people with ID. A literature search was conducted using five databases, and an additional snowball search yielded 16 studies for inclusion in the review. Overall, the methodological quality of these studies was good (43-100%). In this review, we noted barriers to screening among individuals with ID, including perceptions of fear, distress, and embarrassment; unpreparedness for screening; negative interactions with healthcare professionals; a lack of knowledge about cancer screening; mobility issues; a high severity of ID; and a lack of ability to provide consent and communicate verbally. Facilitators to screening among these individuals were also identified, including living in a supervised setting, prior use of other healthcare services, being educated about screening via social media, having carers accompany them to screening appointments, and having dual insurance coverage or a higher income. Our review highlights the current needs of individuals with ID undergoing cancer screening. Strategies should be developed to address these needs, such as the provision of training to healthcare professionals on how to conduct screening for people with ID., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Chemotherapy, as an important clinical treatment, has greatly enhanced survival in cancer patients, but the side effects and long-term sequelae bother both patients and clinicians. 5-Fluorouracil (5-FU) has been widely used as a chemotherapeutic agent in the clinical treatment of various cancers, but several studies showed its adverse effects on reproduction. Reproductive toxicity of 5-FU often associates with developmental block, malformation and ovarian damage in the females. In males, 5-FU administration alters the morphology of sexual organs, the levels of reproductive endocrine hormones and the progression of spermatogenesis, ultimately reducing sperm numbers. Mechanistically, 5-FU exerts its effect through incorporating the active metabolites into nucleic acids directly, or inhibiting thymidylate synthase to disrupt the function of DNA and RNA, leading to profound effects on cellular metabolism and viability. However, some studies suggested that the toxicity of 5-FU on reproduction is reversible and certain drugs used in combination with 5-FU during chemotherapy could protect reproductive systems from 5-FU damage both in females and males. Herein, we summarise the recent findings and discuss underlying mechanisms of the 5-FU-induced reproductive toxicity, providing a reference for future research and clinical treatments.

Objective: Few studies have investigated the associations of sleep duration and sleep quality with incident cardiovascular diseases (CVDs), cancer, and mortality in the same large population. This study aimed at estimating the independent risk factors of long or short sleep durations and several typical characteristics of poor sleep quality for incident CVDs, cancer, and mortality., Methods: In this prospective cohort study, 407 500 individuals were enrolled. Cox proportional hazards models were used to calculate the adjusted hazard ratios and 95% confidence intervals (HR, 95%CI) of associations of sleep duration and quality with incident CVDs, cancer, and mortality., Results: Compared with the sleep duration of 7 h, sleep duration of ≤5 h and ≥9 h were both associated with higher risk of all-cause mortality (HR = 1.25, 95% CI: 1.16-1.34 and HR = 1.30, 95% CI: 1.22-1.38, respectively), CVD mortality (HR = 1.27, 95% CI: 1.09-1.49 and HR = 1.32, 95% CI: 1.16-1.50, respectively), and CVD incidence (HR = 1.23, 95% CI: 1.16-1.31 and HR = 1.08, 95% CI: 1.02-1.15, respectively). Additionally, long sleep duration (≥9 h) was associated with a higher risk of cancer mortality (HR = 1.19, 95% CI: 1.10-1.30) and cancer incidence (HR = 1.08, 95% CI: 1.04-1.12). Moreover, CVD incidence was significantly associated with snoring, insomnia and narcolepsy, increasing the risk by 7%, 26%, and 20%, respectively., Conclusion: Long sleep durations may substantially increase the risk of mortality and morbidity. Snoring, insomnia, and narcolepsy were independent risk factors for incident CVD., (Copyright © 2021 Elsevier B.V. All rights reserved.)

From December 2017 to December 2018, 3 509 subjects who had regular physical examination in Health Management Center, Tianjin Medical University General Hospital were enrolled in our study, including 399 cancer patients, 1 555 chronic disease patients, and 1 555 healthy control, respectively. The mean age was (55.87±11.98) years, and 31.38% were men. The prevalence of MS among chronic disease group (42.44%) was higher than that of cancer group (34.59%) and healthy control group (18.65%) ( P <0.001). Compared with healthy control group, the OR (95% CI ) values of MS risk in cancer group and chronic disease group were 2.13 (1.61-2.83) and 2.85 (2.23-3.66), respectively; the OR (95% CI ) values of MS risk were 3.56 (2.04-6.21) and 2.77 (1.46-5.25) in breast cancer and thyroid cancer, respectively.

Background: Plasmacytoma variant translocation 1 (PVT1), an oncogenic long noncoding RNA located in a recognized cancer-risk gene region-8q24, is significantly overexpressed in various cancers. Many studies have found that high expression of PVT1 was correlated with poor prognosis., Methods: This meta-analysis was performed by searching electronic databases Pubmed, Web of Science, Chinese National Knowledge Infrastructure, WanFang, and ChongQing VIP for eligible papers on the prognostic impact and clinicopathological characteristics of PVT1 expression in cancer from inception to January 31, 2017. The hazard ratio (HR) and odds ratio (OR) with 95% confidence intervals (CI) were computed to estimate the pooled effect of PVT1 on prognosis of cancers using Stata 12.0 version software., Results: Thirteen studies were finally included in this review with a total of 1559 patients. The pooled result indicated that overexpressed PVT1 predicts a poorer prognosis of cancerous patients for overall survival (HR = 1.91, 95% CI: 1.61 - 2.26, p < 0.001) and disease-free survival (HR = 1.90, 95% CI: 1.46 - 2.48, p < 0.001) or recurrencefree survival (HR = 1.77, 95% CI: 1.24 - 2.52, p = 0.002) or progression-free survival (HR = 2.84, 95% CI: 1.67 - 4.82, p < 0.001). High expression of PVT1 was closely associated with tumor-node-metastasis (TNM) stage (III/IV vs. I/II: OR = 3.19, 95% CI: 2.43 - 4.18, p < 0.001), and the significant correlation between PVT1 expression and TNM stage is found in T classification (T3/4 vs. T1/2: OR = 6.48, 95% CI: 2.93 - 14.31, p < 0.001) and lymph node metastasis (present vs. absent: OR = 2.56, 95% CI:1.36 - 4.80, p = 0.003), but not in distant metastasis of patients with cancers (yes vs. no: OR = 2.50, 95% CI: 0.72 - 8.66, p = 0.15). Furthermore, the cancerous patients with high PVT1 expression had a worse histological differentiation than those with low PVT1 expression (undifferentiated/poorly vs. moderately/well: OR = 1.48, 95% CI: 1.02 - 2.14, p = 0.039)., Conclusions: PVT1 could serve as a potent predicator of prognosis in different types of cancers.

Background: In treatment planning for intensity-modulated proton therapy (IMPT), we aim to deliver the prescribed dose to the target yet minimize the dose to adjacent healthy tissue. Mixed-integer programming (MIP) has been applied in radiation therapy to generate treatment plans. However, MIP has not been used effectively for IMPT treatment planning with dose-volume constraints. In this study, we incorporated dose-volume constraints in an MIP model to generate treatment plans for IMPT., Methods: We created a new MIP model for IMPT with dose volume constraints. Two groups of IMPT treatment plans were generated for each of three patients by using MIP models for a total of six plans: one plan was derived with the Limited-memory Broyden-Fletcher-Goldfarb-Shanno (L-BFGS) method while the other plan was derived with our MIP model with dose-volume constraints. We then compared these two plans by dose-volume histogram (DVH) indices to evaluate the performance of the new MIP model with dose-volume constraints. In addition, we developed a model to more efficiently find the best balance between tumor coverage and normal tissue protection., Results: The MIP model with dose-volume constraints generates IMPT treatment plans with comparable target dose coverage, target dose homogeneity, and the maximum dose to organs at risk (OARs) compared to treatment plans from the conventional quadratic programming method without any tedious trial-and-error process. Some notable reduction in the mean doses of OARs is observed., Conclusions: The treatment plans from our MIP model with dose-volume constraints can meet all dose-volume constraints for OARs and targets without any tedious trial-and-error process. This model has the potential to automatically generate IMPT plans with consistent plan quality among different treatment planners and across institutions and better protection for important parallel OARs in an effective way., (© 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Finding a valid antibody to detect mouse programmed death ligand 1 (PDL-1) by immunohistochemistry or immunofluorescence staining has been notoriously difficult. Successful validation of an antibody requires the use of multiple detection methods with the ability to compare appropriate positive and negative controls. Here, we describe in detail the protocols used to validate a mouse-specific PDL-1 antibody used in immunohistochemistry staining with an mRNA in situ hybridization on adjacent sections of mouse B16 tumor. This validation is supported by immunohistochemistry staining of PDL-1 on B16 cell pellets either treated or not treated with IFN-gamma.

Background: In hyperthermia for cancer therapy, thermal parameters related to tumor response have not yet been clarified. We investigated thermal parameters that could predict tumor response to hyperthermia combined with radiotherapy in locally advanced malignancies., Methods: Fifty-four patients with locally advanced malignancies who were treated by hyperthermia in combination with radiation therapy were enrolled in this study. Local hyperthermia was induced by ultrasound heating equipment for 60 min, within 30 min after irradiation, twice a week, for a total of six to ten sessions. Radiation therapy was administered with a conventional fractionation regimen, at a total dose of 40-70 Gy. Multi-point thermometry results were obtained with every 10-s temperature data acquisition. An average of seven interstitial sites per tumor was monitored for each treatment. Univariate logistic regression analysis was used to investigate the relationship between tumor response and minimum, maximum, and average intratumor temperature (Tmin, Tmax, Tav); the cumulative minutes of treatment at temperatures exceeded by 90%, 50%, and 10% of the measured intratumoral temperatures (T90, T50, T10); and cumulative minutes of the temperature that achieved above the index temperature value in the tumor center ((Cum min T(center) > T(index))., Results: Complete and partial response rates were 32.6% and 46.2%, respectively. Univariate logistic regression analysis revealed that the temperature parameters with predictive probability were highest for Cum min T(center) > 42.5 degrees C, followed by > 42 degrees C and > 41 degrees C; and T90. Cum min T(center) > 42.5 degrees C was most significantly associated with complete tumor response (P < 0.001)., Conclusion: These results strongly suggest that hyperthermia is a useful adjunct to radiotherapy for increasing the local control of advanced malignancies, and that Cum min T(center) > 42.5 degrees C could be an important thermal parameter for predicting tumor response.