Search

We assessed the accessibility to health care services and treatment for people with noncommunicable diseases (NCDs) in Northwest Syria after more than eleven years of the worst humanitarian crisis in Syria. Included in this cross-sectional study were people with one or more of cardiovascular diseases, diabetes, cancer, or chronic obstructive pulmonary diseases; people from both Aleppo and Idleb governorates; and residents from both inside and outside the camp. Data were collected in November 2022 via face-to-face interviews. The findings were obtained from 674 respondents (52.8% female). Respondents in Idleb were 6.5 times more likely to access health care services than Aleppo (p = 0000). In-camp residents were 1.5 times more likely to access outreach health services (p = 0.020). Respondents with higher income were three times more likely to access health care services compared to respondents with lower income (p = 0.000). Having any of the surveyed NCDs made the respondents less likely to get the required services. The study findings added more evidence about the inequity in terms of accessing health care services in Northwest Syria and identified the barriers. It was clear that a perceived group of people with NCDs do not have access to the health care services, including outreach health services and free medications. [ABSTRACT FROM AUTHOR]

Calcium ions (Ca2+) participate in the regulation of cellular apoptosis as a second messenger. Calcium overload, which refers to the abnormal elevation of intracellular Ca2+ concentration, is a factor that can lead to cell death. Here, based on the unique biological effects of Ca2+, hollow mesoporous calcium peroxide nanoparticles (HMCPN) were developed by a facile hydrolysis-precipitation method for drug-free tumor calcicoptosis therapy. The average pore size of the optimized HMCPN17 is 6.4 nm, and the surface area is 81.3 m2/g, which enables HMCPN17 with high drug loading capability. The Ca2+ release from HMCPN17 is much faster at pH 6.8 than that at pH 7.4, which can be ascribed to the acid-triggered conversion of HMCPN17 to Ca2+ and H 2 O 2 , indicating a pH-responsive decomposition behavior of HMCPN17. The high drug loading contents of doxorubicin (DOX) and/or sorafenib (SFN) indicate that HMCPN17 can be employed as a generic drug delivery system (DDS). The in vitro and in vivo results reinforce the high calcicoptosis therapeutic efficacy of tumors by our HMCPN17 without drug loading, which can be attributed to the efficient accumulation in tumors and the ability of H 2 O 2 and Ca2+ production at acidic TME. Our HMCPN17 has broad application prospect for construction of multi-drug-loaded composite nanomaterials with diversified functions for the treatment of tumors. The combination of hollow mesoporous nanomaterials and calcium peroxide nanoparticles has a wide range of applications in the synergistic treatment of tumors. In this study, hollow mesoporous calcium peroxide nanoparticles (HMCPN) were developed based on a simple hydrolysis-precipitation method for tumor calcicoptosis therapy without drug loading. The high drug loading contents of DOX and/or SFN indicate that our HMCPN can serve as a generic DDS. The experimental results demonstrated the high calcicoptosis therapeutic efficacy of HMCPN on tumors even without drug loading. [Display omitted] [ABSTRACT FROM AUTHOR]

Introduction: Although oncology has seen large scientific and clinical advances over the last decade, it also has one of the lowest success rates for novel agents across therapeutic areas. Adaptive clinical trial design has been a popular option for increasing clinical trial efficiency and the chances of trial success. Seamless clinical trial design are studies in which two or more clinical trial phases are combined into a single study with a pre-specified transition between stages. This integration of phases may enhance efficiency. Methods: To understand the precedent for the use of seamless designs, this working group was formed to conduct a comprehensive literature search on seamless clinical trials conducted with confirmatory intent in oncology. Trial design features were extracted into a database and analyzed with descriptive statistics. Results: A literature search identified 68 clinical trials meeting inclusion and exclusion criteria. The most common design feature was a gate on treatment efficacy, where the trial would only proceed to the second stage if sufficient efficacy was observed in the first. The next most common feature was a selection of a dose or treatment regimen. Inferentially and operationally seamless designs were approximately equally represented. Discussion: Key statistical considerations for seamless phase II/III designs include optimizing design choices by evaluating and comparing operating characteristics across design alternatives as well as showing control of overall Type I error rates. Executing the transition between phases should be evaluated for issues related to accrual, drug production, and procedures to maintain trial integrity. Conclusions: While there are unique statistical, regulatory, and operational considerations for seamless designs they are also uniquely suited to many development settings. These include, for example, addressing dose selection under FDA's Project Optimus and addressing the growing use of biomarkers and personalized medicine approaches in cancer treatment. [ABSTRACT FROM AUTHOR]

Immunotherapy has become the cornerstone of current malignant tumor treatment. However, the response of different patients to immunotherapy is highly heterogeneous, and not all patients can benefit from it. There is an urgent need to find biomarkers that can effectively predict the efficacy of immunotherapy. C-C chemokine ligand 4 (CCL4) is a cytokine, belonging to the inflammatory CCL subfamily. It is mainly secreted by immune cells and tumor cells and shows low or no expression in normal tissues but abnormally high expression in various malignant tumor tissues. After binding to CCL4 and its receptor C-C chemokine receptor type 5 (CCR5), it can recruit and mediate immune cell migration, destroy the stability of the tumor microenvironment (TME), participate in carcinogenesis and promote the development of tumors. In the tumor immune microenvironment, CCL4 can mediate and recruit the directed migration of key immune cells such as monocytes, macrophages, natural killer (NK) cells, and T cells, which makes it a potentially important element affecting the efficacy of immunotherapy and has specific value. This paper reviews the research progresses of CCL4's effects on immune escape in TME, in order to provide clues and references for basic research and clinical diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Sonodynamic therapy (SDT) is emerging as a promising modality for cancer treatment. However, improving the tumor bioavailability and anti-hypoxia capability of sonosensitizers faces a big challenge. In this work, we present a tumor microenvironment (TME)-mediated nanomorphology transformation and oxygen (O 2) self-production strategy to enhance the sonodynamic therapeutic efficacy of tumors. A smart probe Ce6-Leu@Mn2+ that consists of a glutathione (GSH) and leucine amino peptidase (LAP) dual-responsive unit, a 2-cyanobenzothiazole (CBT) group, and a Mn2+-chelated Ce6 as sonosensitizer for tumor SDT was synthesized, and its SDT potential for liver tumor HepG2 in living mice was systematically studied. It was found that the probes could self-assemble into large nanoparticles in physiological condition and spontaneously transformed into small particles under the dual stimulation of GSH and LAP in TME resulting in enhanced tumor accumulation and deep penetration. More notably, Ce6-Leu@Mn2+ could convert endogenous hydrogen peroxide to O 2 , thereby alleviating the hypoxia and achieving effective SDT against hypoxic tumors under the excitation of ultrasound. We thus believe this smart TME-responsive probe may provide a noninvasive and efficient means for malignant tumor treatment. Sonodynamic therapy (SDT) is emerging as a promising therapeutic modality for cancer treatment. However, how to improve the tumor bioavailability and anti-hypoxia capability of sonosensitizers remains a huge challenge. Herein, we rationally developed a theranostic probe Ce6-Leu@Mn2+ that can transform into small-size nanoparticles from initial large particles under the dual stimulation of LAP and GSH in tumor microenvironment (TME) resulting in enhanced tumor accumulation, deep tissue penetration as well as remarkable O 2 self-production for enhanced sonodynamic therapy of human liver HepG2 tumor in living mice. This smart TME-responsive probe may provide a noninvasive and efficient means for hypoxic tumor treatment. [Display omitted] [ABSTRACT FROM AUTHOR]

Single-domain antibodies (sdAbs), initially identified in camelids or sharks and commonly referred to as nanobodies or VNARs, have emerged as a promising alternative to conventional therapeutic antibodies. These sdAbs have many superior physicochemical and pharmacological properties, including small size, good solubility and thermostability, easier accessible epitopes, and strong tissue penetration. However, the inherent challenges associated with the animal origin of sdAbs limit their clinical use. In recent years, various innovative humanization technologies, including complementarity-determining region (CDR) grafting or complete engineering of fully human sdAbs, have been developed to mitigate potential immunogenicity issues and enhance their compatibility. This review provides a comprehensive exploration of sdAbs, emphasizing their distinctive features and the progress in humanization methodologies. In addition, we provide an overview of the recent progress in developing drugs and therapeutic strategies based on sdAbs and their potential in solid tumor treatment, such as sdAb–drug conjugates, multispecific sdAbs, sdAb-based delivery systems, and sdAb-based cell therapy. This review provides a comprehensive exploration of sdAbs, emphasizing the progress in humanization methodologies and their distinctive applications in solid tumor treatment. [Display omitted] [ABSTRACT FROM AUTHOR]

Selective activation of Pt(IV) prodrugs within tumors has emerged as a promising strategy in tumor treatment. Although progress has been made with photo- and ultrasound-activated Pt(IV) prodrugs, concerns remain over the non-specific activation of photosensitizers (PS) and the potential for phototoxicity and chemical toxicity. In this study, a sequential dual-locked Pt(IV) nano-prodrug that can be activated by both the acidic tumor microenvironment and light was developed. The Pt(IV) prodrug was prepared by conjugating PS-locked Pt(IV) to a polymeric core, which was then chelated with metallo iron to lock its photoactivity and form a metallo-nano prodrug. Under acidic tumor microenvironment conditions, the metallo-nano prodrug undergoes dissociation of iron, triggering a reduction process in oxaliplatin under light irradiation, resulting in the activation of both chemotherapy and photodynamic therapy (PDT). Additionally, the prodrug could induce metallo-triggered ferroptosis and polarization of tumor-associated macrophages (TAM), thereby enhancing tumor inhibition. The dual-lock strategy employed in a nanoparticle delivery system represents an expansion in the application of platinum-based anticancer drugs, making it a promising new direction in cancer treatment. A novel sequential dual-locking using photoactivated Pt(IV)-based metallo-nanoprodrug is reported. The dual-locking Pt(IV) drug was sequentially excited by acid condition and red light. [Display omitted] [ABSTRACT FROM AUTHOR]

The current status of clinical trials utilizing nanoparticle drug delivery system (NDDS) for brain tumors was summarized. [Display omitted] [ABSTRACT FROM AUTHOR]

The construction and optimization of a single phototherapeutic agent with photoluminescence, type I photodynamic therapy (PDT), and photothermal therapy (PTT) functions remain challenging. In this study, we aimed to design and synthesize four donor–acceptor (D-A) type aggregation-induced emission molecules: PSI, TPSI, PSSI, and TPSSI. We employed phenothiazine as an electron donor and 1,3-bis(dicyanomethylidene)indan as a strong electron acceptor in the synthesis process. Among them, TPSSI exhibited efficient type I reactive oxygen species generation, high photothermal conversion efficiency (45.44 %), and near-infrared emission. These observations can be attributed to the introduction of a triphenylamine electron donor group and a thiophene unit, which resulted in increased D–A strengths, a reduced singlet-triplet energy gap, and increased free intramolecular motion. TPSSI was loaded into bovine serum albumin to prepare biocompatible TPSSI nanoparticles (NPs). Our results have indicated that TPSSI NPs can target lipid droplets with negligible dark toxicity and can efficiently generate O 2 •− in hypoxic tumor environments. Moreover, TPSSI NPs selectively targeted 4T1 tumor tissues and exhibited a good PDT-PTT synergistic effect in vitro and in vivo. We believe that the successful preparation of multifunctional phototherapeutic agents will promote the development of efficient tumor diagnosis and treatment technologies. The construction of a single phototherapeutic agent with photoluminescence, type I photodynamic therapy, and photothermal therapy functions, and its optimization remain challenging. In this study, we construct four donor–acceptor aggregation-induced emission molecules using phenothiazine as an electron donor and 1,3-Bis(dicyanomethylidene)indan as a strong electron acceptor. By optimizing the molecular structure, an integrated phototherapy agent with fluorescence imaging ability and high photodynamic / photothermal therapy performance was prepared. We believe that the successful preparation of multifunctional phototherapeutic agents will promote the development of efficient tumor diagnosis and treatment technology. [Display omitted] [ABSTRACT FROM AUTHOR]

Cancer is a leading cause of morbidity and mortality worldwide, necessitating exploring novel preventive and therapeutic strategies. Over the years, the potential of natural agents in cancer prevention and treatment has garnered considerable attention. This review highlights the current understanding of the molecular mechanical bases underlying the role of natural agents and their therapeutic potential in combating cancer. The molecular mechanisms through which these natural agents exert their anti-cancer activities are elucidated, encompassing modulation of signaling pathways involved in cell proliferation, apoptosis, angiogenesis, metastasis, and immune response. Additionally, the review delves into the emerging research on the epigenetic modifications induced by natural agents, providing a deeper insight into their anti-cancer properties. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is a clinically approved treatment for tumors, and it relies on the phototoxicity of photosensitizers by producing reactive oxygen species (ROS) to destroy cancer cells under light irradiation. However, such phototoxicity is a double-edged sword, which is also harmful to normal tissues. To manipulate phototoxicity and improve the therapy effect, herein we have proposed a dressing-undressing strategy for de-activating and re-activating therapy functions of photosensitizer nanoparticles. One kind of metal organic framework (PCN-224), which is composed of Zr(IV) cation and tetrakis (4-carboxyphenyl) porphyrin (TCPP), has been prepared as a model of photosensitizer, and it has size of ∼70 nm. These PCN-224 nanoparticles are subsequently coated with a mesoporous organic silica (MOS) shell containing tetrasulfide bonds (-S-S-S-S-), realizing the dressing of PCN-224. MOS shell has the thickness of ∼20 nm and thus can block 1O 2 (diffusion distance: <10 nm), deactivating the phototoxicity and preventing the damage to skin and eyes. Furthermore, PCN-224@MOS can be used to load chemotherapy drug (DOX·HCl). When PCN-224@MOS-DOX are mixed with glutathione (GSH), MOS shell with -S-S-S-S- bonds can be reduced by GSH and then be decomposed, which results in the undressing and then confers the exposure of PCN-224 with good PDT function as well as the release of DOX. When PCN-224@MOS-DOX dispersion is injected into the mice and accumulated in the tumor, endogenous GSH also confers the undressing of PCN-224@MOS-DOX, realizing the in-situ activation of PDT and chemotherapy for tumor. Therefore, the present study not only demonstrates a general dressing-undressing strategy for manipulating phototoxicity of photosensitizers, but also provide some insights for precise therapy of tumors without side-effects. Photosensitizers can generate reactive oxygen species (ROS) under light radiation to destroy cancer cells. However, this phototoxicity is a double-edged sword and also harmful to normal tissues such as the skin and eyes. To control phototoxicity and improve therapeutic efficacy, we prepared a PCN-224@MOS-DOX nanoplatform and proposed a dressing and undressing strategy to deactivate and reactivate the therapeutic function of the photosensitizer nanoparticles. The MOS shell can block the diffusion of 1O 2 , eliminate phototoxicity, and prevent damage to the skin and eyes. When injected into mice and accumulated in tumors, PCN-224@MOS-DOX dispersions are endowed with an endogenous GSH-driven undressing effect, achieving in situ activation of PDT and tumor chemotherapy. [Display omitted] [ABSTRACT FROM AUTHOR]

Hypoxia is a common feature of most solid tumors, which promotes the proliferation, invasion, metastasis, and therapeutic resistance of tumors. Researchers have been developing advanced strategies and nanoplatforms to modulate tumor hypoxia to enhance therapeutic effects. A timely review of this rapidly developing research topic is therefore highly desirable. For this purpose, this review first introduces the impact of hypoxia on tumor development and therapeutic resistance in detail. Current developments in the construction of various nanoplatforms to enhance tumor treatment in response to hypoxia are also systematically summarized, including hypoxia-overcoming, hypoxia-exploiting, and hypoxia-disregarding strategies. We provide a detailed discussion of the rationale and research progress of these strategies. Through a review of current trends, it is hoped that this comprehensive overview can provide new prospects for clinical application in tumor treatment. As a common feature of most solid tumors, hypoxia significantly promotes tumor progression. Advanced nanoplatforms have been developed to modulate tumor hypoxia to enhanced therapeutic effects. In this review, we first introduce the impact of hypoxia on tumor progression. Current developments in the construction of various nanoplatforms to enhance tumor treatment in response to hypoxia are systematically summarized, including hypoxia-overcoming, hypoxia-exploiting, and hypoxia-disregarding strategies. We discuss the rationale and research progress of the above strategies in detail, and finally introduce future challenges for treatment of hypoxic tumors. By reviewing the current trends, this comprehensive overview can provide new prospects for clinical translatable tumor therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

Cancer treatments, including chemotherapy, surgery, and radiotherapy, present distinct challenges to reproductive health. Ovarian function might undergo various degrees of impairment, leading to a significantly diminished ovarian reserve, even without persistent amenorrhea. The return of menses post-chemotherapy might not mirror the full extend of follicular damage. Ovarian reserve testing is indicated in reproductive-aged cancer survivors. The magnitude of follicle depletion can be influenced by factors such as age, initial ovarian reserve, and specific treatment modalities. Radiotherapy, dependent on its target, can introduce risk to both ovarian and uterine health. Moreover, radiotherapy targeting the brain can disrupt the hypothalamic-pituitary-reproductive axis, adding another layer of reproductive complication. As cancer survival rates improve, addressing these multifaceted reproductive concerns has become essential. [ABSTRACT FROM AUTHOR]

Children receiving cancer therapy have particular dietary needs. Most have issues with eating. The combination of extended duration of treatment, high frequency admissions and prolonged length of stay impacts more on this group of children than most others. With advancements in more effective diagnosis and tailored multimodal therapy more children than ever are being treated with increasingly intense therapeutic regimens. Hence, more children are also surviving new second and third line treatments for relapsed disease. This has increased the number of children with cancer who are susceptible to nutritional problems associated with their disease treatment and survivorship. It is important that health professionals are aware of predisposing factors which can lead to inadequate nutrition. Understanding can help alleviate them and prompt recognition and treatment can help prevent nutrition becoming a problem for these children. This article provides an overview of the particular problems faced by children with cancer obtaining adequate nutrition, nutritional risk factors and highlights why good nutrition status is essential for any child undergoing cancer therapy. The aims of nutritional therapy, a guide to nutritional assessment/interventions and long-term nutritional considerations are discussed. [ABSTRACT FROM AUTHOR]

Advancements in genomics have had a significant impact on our ability to diagnose and treat several health conditions, notably cancer. In this article, we discuss the evolution of genomic methods from the early first-generation genome sequencing methods such as Sanger sequencing to the latest technology. We also discuss how clinicians can decide which test to use depending on what type of result is required. We discuss the clinical significance of genomic testing including identification of cancer predispositions syndromes, the role of genomics in accurately diagnosing a number of cancers, as well as the utility of genomic data to predict response to targeted therapies. Finally, we detail some of the targeted therapies currently available to treat the various types of childhood cancers. The expansion of genomic testing within the NHS and the essential nature of genomic data to accurately diagnose and optimally treat childhood cancers also poses challenges to the healthcare system both in terms of infrastructure and personnel. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the most common tumor types and remains a major clinical challenge. Increasing evidence has revealed that mitophagy inhibitors can enhance the effect of chemotherapy on HCC. However, few mitophagy inhibitors have been approved for clinical use in humans. Pyrimethamine (Pyr) is used to treat infections caused by protozoan parasites. Recent studies have reported that Pyr may be beneficial in the treatment of various tumors. However, its mechanism of action is still not clearly defined. Here, we found that blocking mitophagy sensitized cells to Pyr-induced apoptosis. Mechanistically, Pyr potently induced the accumulation of autophagosomes by inhibiting autophagosome-lysosome fusion in human HCC cells. In vitro and in vivo studies revealed that Pyr blocked autophagosome-lysosome fusion by upregulating BNIP3 to inhibit synaptosomal-associated protein 29 (SNAP29)-vesicle-associated membrane protein 8 (VAMP8) interaction. Moreover, Pyr acted synergistically with sorafenib (Sora) to induce apoptosis and inhibit HCC proliferation in vitro and in vivo. Pyr enhances the sensitivity of HCC cells to Sora, a common chemotherapeutic, by inhibiting mitophagy. Thus, these results provide new insights into the mechanism of action of Pyr and imply that Pyr could potentially be further developed as a novel mitophagy inhibitor. Notably, Pyr and Sora combination therapy could be a promising treatment for malignant HCC. [Display omitted] • Pyr regulates mitophagy by interfering with autophagosome-lysosome formation. • Pyr blocks autolysosomes formation by inhibiting SNAP29-VAMP8 interactions. • Pyr upregulates BNIP3 and induces the interaction of SNAP29 with BNIP3. • Restoration of the interaction between SNAP29 and VAMP8 by BNIP3 depletion. • Pyr enhances the sensitivity of HCC to Sora in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Advance care planning (ACP) is a continuous process where individuals discuss and document their end-of-life preferences with trusted caregivers and health care providers. Caregivers are pivotal to include in ACP discussions because they assist loved ones to navigate serious medical illness. The purpose of this study was to examine caregivers' engagement in ACP decision making with their loved ones with cancer. A qualitative descriptive design was used, informed by Engel's biopsychosocial model, with a convenience sample of 14 caregivers in North Carolina. Virtual interviews were conducted using a semistructured interview guide. Using prevalence logic, the overarching theme of “Changing Life Plans” was explained by two subthemes, “Learning the Diagnosis” and “Keeping Them on Track.” The timing and location of ACP conversations were important considerations. Over half of the participants (64%) had no knowledge or had misconceptions about ACP, and 5 had accurate knowledge. Nurses could develop partnerships with community leaders trained in palliative care principles to begin conversations early with community members. Advocacy groups might hold events, such as the Hello Game, in community settings to facilitate early ACP conversations. [ABSTRACT FROM AUTHOR]

Phototherapy, such as photothermal therapy (PTT) and photodynamic therapy (PDT), has been considered an elegant solution to eradicate tumors due to its minimal invasiveness and low systemic toxicity. Nevertheless, it is still challenging for phototherapy to achieve ideal outcomes and clinical translation due to its inherent drawbacks. Owing to the unique biological functions, diverse gases have attracted growing attention in combining with phototherapy to achieve super-additive therapeutic effects. Specifically, gases such as nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H 2 S) have been proven to kill tumor cells by inducing mitochondrial damage in synergy with phototherapy. Additionally, several gases not only enhance the thermal damage in PTT and the reactive oxygen species (ROS) production in PDT but also improve the tumor accumulation of photoactive agents. The inflammatory responses triggered by hyperthermia in PTT are also suppressed by the combination of gases. Herein, we comprehensively review the latest studies on gas-synergized phototherapy for cancer therapy, including (1) synergistic mechanisms of combining gases with phototherapy; (2) design of nanoplatforms for gas-synergized phototherapy; (3) multimodal therapy based on gas-synergized phototherapy; (4) imaging-guided gas-synergized phototherapy. Finally, the current challenges and future opportunities of gas-synergized phototherapy for tumor treatment are discussed. 1. The novelty and significance of the work with respect to the existing literature. (1) Strategies to design nanoplatforms for gas-synergized anti-tumor phototherapy have been summarized for the first time. Meanwhile, the integration of various imaging technologies and therapy modalities which endow these nanoplatforms with advanced theranostic capabilities has been summarized. (2) The mechanisms by which gases synergize with phototherapy to eradicate tumors are innovatively and comprehensively summarized. 2. The scientific impact and interest. This review elaborates current trends in gas-synergized anti-tumor phototherapy, with special emphases on synergistic anti-tumor mechanisms and rational design of therapeutic nanoplatforms to achieve this synergistic therapy. It aims to provide valuable guidance for researchers in this field. [Display omitted] [ABSTRACT FROM AUTHOR]

Despite significant advances in medical technology and antitumour treatments, the diagnosis and treatment of tumours have undergone remarkable transformations. Noninvasive phototherapy methods, such as photodynamic therapy (PDT) and photothermal therapy (PTT), have gained significant interest in antitumour medicine. However, traditional photosensitisers or photothermal agents face challenges like immune system recognition, rapid clearance from the bloodstream, limited tumour accumulation, and phototoxicity concerns. Researchers combine photosensitisers or photothermal agents with natural cell membranes to overcome these obstacles to create a nano biomimetic therapeutic platform. When used to coat nanoparticles, red blood cells, platelets, cancer cells, macrophages, lymphocytes, and bacterial outer membranes could provide prolonged circulation, tumour targeting, immune stimulation, or antigenicity. This article covers the principles of cellular membrane biomimetic nanotechnology and phototherapy, along with recent advancements in applying nano biomimetic technology to PDT, PTT, PCT, and combined diagnosis and treatment. Furthermore, the challenges and issues of using nano biomimetic nanoparticles in phototherapy are discussed. Currently, there has been significant progress in the field of cell membrane biomimetic technology. Researchers are exploring its potential application in tumor diagnosis and treatment through phototherapy. Scholars have conducted extensive research on combining cell membrane technology and phototherapy in anticancer diagnosis and treatment. This review aims to highlight the mechanisms of phototherapy and the latest advancements in single phototherapy (PTT, PDT) and combination phototherapy (PCT, PRT, and PIT), as well as diagnostic approaches. The review provides an overview of various cell membrane technologies, including RBC membranes, platelet membranes, macrophage cell membranes, tumour cell membranes, bacterial membranes, hybrid membranes, and their potential for anticancer applications under phototherapy. Lastly, the review discusses the challenges and future directions in this field. [Display omitted] [ABSTRACT FROM AUTHOR]

Copyright of Nosileftiki is the property of Hellenic Nurses' Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

• This review summarizes the Mg alloys developed for antitumor applications, which has dual function of antitumor and tissue regeneration. • The antitumor effects of Mg alloys are mainly due to their degradation products. • The mechanisms of Mg alloys on tumor inhibition are discussed. Cancer is a major threat to human life worldwide. Traditional cancer treatments, such as chemotherapy and surgery, have major limitations and can cause irreversible damage to normal tissues while killing the cancer cells. Magnesium (Mg) alloys are widely reported novel potential biomedical materials with acceptable mechanical properties and good osteogenic and angiogenic properties. In this review, we summarize the Mg alloys for antitumor applications, including pure Mg and Mg alloys (Mg-Ag, Mg-Gd, Mg-Li-Zn, Mg-Ca-Sr-Zn, et al.) fabricated by casting and extruding, selective laser melting methods. Mg alloys can exhibit antitumor effect on bone tumor, breast cancer, and liver tumor, etal. What's more, after tumor tissue is eliminated, Mg alloys prevent tumor recurrence, fill tissue defects and promote tissue regeneration. The antitumor effects of Mg alloys are mainly due to their degradation products. Overall, Mg alloys show great potential in tumor treatments due to the dual function of antitumor and tissue regeneration. [ABSTRACT FROM AUTHOR]

Immunotherapy is an emerging antitumor modality with high specificity and persistence, but its application for resected tumor treatment is impeded by the low availability of tumor-specific antigens and strong immunosuppression in the wound margin. Here a nanoengineered hydrogel is developed for eliciting robust cooperative ferroptosis-immunotherapeutic effect on resected tumors. Specifically, β-cyclodextrin (β-CD) is first grafted onto oxidized sodium alginate (OSA) through Schiff base ligation, which could trap cRGD-modified redox-responsive Withaferin prodrugs (WA-cRGD) to obtain the hydrogel building blocks (Gel@WA-cRGD). Under Ca2+-mediated crosslinking, Gel@WA-cRGD rapidly forms physiologically stable hydrogels, of which the porous network is used to deliver programmed cell death ligand 1 antibodies (aPD-L1). After injection into the post-surgical wound cavity, the β-CD-entrapped WA-cRGD is detached by the local acidity and specifically internalized by residual tumor cells to trigger ferroptosis, thus releasing abundant damage-associated molecular patterns (DAMPs) and tumor-derived antigens for activating the antigen-presenting cell-mediated cross-presentation and downstream cytotoxic T cell (CTL)-mediated antitumor responses. Furthermore, aPD-L1 could block PD-1/PD-L1 interaction and enhance the effector function of CTLs to overcome tumor cell-mediated immunosuppression. This cooperative hydrogel-based antitumor strategy for ferroptosis-immunotherapy may serve as a generally-applicable approach for postoperative tumor management. To overcome the immunosuppressive microenvironment in resected solid tumors for enhanced patient survival, here we report a nanoengineered hydrogel incorporated supramolecular redox-activatable Withaferin prodrug and PD-L1 antibody, which could elicit robust cooperative ferroptosis-immunotherapeutic effect against residual tumor cells in the surgical bed to prevent tumor relapse, thus offering a generally-applicable approach for postoperative tumor management. [Display omitted] [ABSTRACT FROM AUTHOR]

NO gas therapy is a supplementary approach for tumor treatment due to the advantages of minimal invasion, little drug resistance, low side effect and amplified efficacy. l -Arginine (L-Arg), a natural NO source with good biocompatibility, can release NO under the stimulation of H 2 O 2 in tumor microenvironment. However, the conventional l -Arg delivery systems via noncovalent loading usually lead to inevitable premature leakage of nano-cargos during blood circulation. In this work, an efficient l -Arg self-delivery supramolecular nanodrug (SDSND) for tumor treatment is demonstrated by combining Mannich reaction and π-π stacking. l -Arg links to (-)-epigallocatechin gallate (EGCG) with the assistance of formaldehyde through Mannich reaction, and then assembles into nanometer-sized particles via π-π stacking. The guanidine group of l -Arg and the phenolic hydroxyl groups of EGCG are preserved in the SDSNDs, which allows for accomplishing gas therapy by provoking tumor cell apoptosis and combining with EGCG to amplify apoptosis, respectively. In addition, the SDSNDs exhibit high biocompatibility and avoid the premature leakage of l -Arg in blood circulation, providing an alternative l -Arg delivery system for NO gas therapy. NO gas therapy has attracted emerging interest in tumor treatment. However, the controlled NO release and the avoidance of premature leakage of NO donors remain challenging. In this work, L-Arginine (L-Arg) self-delivery supramolecular nanodrug for efficient tumor therapy is demonstrated through the Mannich reaction of L-Arg, (-)-epigallocatechin gallate (EGCG) and formaldehyde. Stimulated by tumor microenvironment, the guanidine groups of L-Arg allow for accomplishing NO release and thus provoking tumor cell apoptosis. The nanodrug also avoids the premature leakage of L-Arg in blood circulation. Moreover, the preserved phenolic hydroxyl groups of EGCG combine with L-Arg to amplify apoptosis. The nanodrug exhibits high biocompatibility and good therapeutic effect, providing an alternative L-Arg delivery system for NO gas therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

Cerenkov radiation-induced photodynamic therapy (CR-PDT) gets rid of the limited tissue penetration depth of the external light source and provides a feasible scheme for the PDT excited by the internal light. However, due to the low luminescence intensity of Cerenkov radiation, CR-PDT alone cannot effectively inhibit tumor growth, curbing the potential clinical translation of CR-PDT. Herein, we reported an AIE-PS/bacteria biohybrid (EcN@TTVP) composed of Escherichia coli Nissle 1917 (EcN) loaded with aggregation-induced emission photosensitizer (AIE-PS) termed TTVP, which enhanced CR-PDT by activating anti-tumor immunity for synergistic tumor treatment. The preferential tumor-colonized EcN@TTVP and radiopharmaceutical 18F-fluorodeoxyglucose (18F-FDG) were administered sequentially to enable them to co-enrich in the tumor site, thereby triggering CR-PDT and promoting immunogenic tumor cell death. Most importantly, EcN acting as immunoadjuvants enhanced the maturation of dendritic cells (DCs) and priming of cytotoxic T cells (CTLs). Therefore, under the synergistic treatment of CR-PDT and immunotherapy, AIE-PS/bacteria biohybrids resulted in either efficient tumor remission or a survival prolongation in tumor-bearing mice, which presented significant advantages over single CR-PDT. Remarkably, no obvious toxic effects were observed during the treatment. In this study, we proposed a synergistic therapeutic strategy based on EcN@TTVP for combined CR-PDT and immunotherapy against tumors. Moreover, this strategy may have great potential in clinical translation and provide references for deep-seated tumor treatment. PDT is restricted due to the shallow penetration depth of light into tumor tissues. Using CR as the excitation light source for PDT can overcome the aforementioned issue and greatly expand the application of PDT. However, the low efficacy of single CR-PDT limits further its applications. Therefore, the design and development of feasible strategies to improve the efficacy of CR-PDT are of immediate importance. Introducing probiotics to our study can be used not only as tumor-targeting carriers of photosensitizers but also as immunoadjuvants. Under co-stimulation by immunogenic tumor cell death triggered by CR-PDT and probiotics acting as immunoadjuvants, anti-tumor immune responses were effectively activated, thus remarkably enhancing the efficacy of CR-PDT. [Display omitted] [ABSTRACT FROM AUTHOR]

DNAzyme-based gene regulation shows great potential for the therapy of many cancers. However, ineffective delivery and insufficient cofactor supply pose challenges for potent gene therapy. In this study, we constructed a smart metal-polyphenol-DNAzyme nanoplatform (TA-Mn@Dz NPs) with intrinsic stability, effective delivery, and cofactor self-supply ability for gene-chemodynamic synergistic tumor therapy. Tannic acid, a plant-derived polyphenol, acts as an intermediate structural unit to mediate the assembly of Mn2+/DNAzyme and tumor acid environment-responsive nanocarriers. Intracellularly, the acidic environment triggers the decomposition of TA-Mn@Dz NPs to release DNAzyme and Mn2+. The Mn2+ ion not only boosts the catalytic cleavage of surviving mRNA for effective gene therapy but also activates chemodynamic therapy (CDT), generating highly toxic ·OH from endogenous H 2 O 2. When tail intravenously injected into MCF-7 tumor-bearing mice, the TA-Mn@Dz NPs display desirable synergistic gene-chemodynamic antitumor effects, paving the way for developing DNAzyme-based multifunctional theranostic platforms for biomedical applications. 1. A smart metal-polyphenol-DNAzyme nanoplatform was constructed for gene-chemodynamic synergistic tumor therapy. 2. Tannic acid act as intermediate structural units to mediate the assembly of Mn2+/DNAzyme and tumor acid environment-responsive nanocarriers. 3. The Mn2+-ion could not only boost the catalytic cleavage of surviving mRNA for effective gene therapy, but also catalyze endogenous H 2 O 2 to form cytotoxic hydroxyl radicals for chemodynamic therapy. 4. Our work paves an extremely simple way to integrate gene therapy with CDT for the dual-catalytic tumor treatment. [Display omitted] [ABSTRACT FROM AUTHOR]

The excessive copper in tumor cells is crucial for the growth and metastasis of malignant tumor. Herein, we fabricated a nanohybrid to capture, convert and utilize the overexpressed copper in tumor cells, which was expected to achieve copper dependent photothermal damage of primary tumor and copper-deficiency induced metastasis inhibition, generating accurate and effective tumor treatment. The nanohybrid consistsed of 3-azidopropylamine, 4-ethynylaniline and N-aminoethyl-N'-benzoylthiourea (BTU) co-modified gold nanoparticles (AuNPs). During therapy, the BTU segment would specifically chelate with copper in tumor cells after endocytosis to reduce the intracellular copper content, causing copper-deficiency to inhibit the vascularization and tumor migration. Meanwhile, the copper was also rapidly converted to be cuprous by BTU, which further catalyzed the click reaction between azido and alkynyl on the surface of AuNPs, resulting in on-demand aggregation of these AuNPs. This process not only in situ generated the photothermal agent in tumor cells to achieve accurate therapy avoiding unexpected damage, but also enhanced its retention time for sustained photothermal therapy. Both in vitro and in vivo results exhibited the strong tumor inhibition and high survival rate of tumor-bearing mice after application of our nanohybrid, indicating that this synergistic therapy could offer a promising approach for malignant tumor treatment. The distinctive excessive copper in tumor cells is crucial for the growth and metastasis of tumor. Therefore, we fabricated intelligent gold nanoparticles to simultaneously response and reverse this tumorigenic physiological microenvironment for the synergistic therapy of malignant tumor. In this study, for the first time we converted and utilized the overexpressed Cu2+ in tumor cells to trigger intracellular click chemistry for tumor-specific photothermal therapy, resulting in accurate damage of primary tumor. Moreover, we effectively manipulated the content of Cu2+ in tumor cells to suppress the migration and vascularization of malignant tumor, resulting in effective metastasis inhibition. [Display omitted] [ABSTRACT FROM AUTHOR]

The detection of tumor markers has significant importance in the early diagnosis of cancer. It is an important indicator for evaluating the extent of the disease and monitoring the efficacy of tumor treatment. Therefore, it is meaningful to find a convenient, fast, and sensitive method to detect tumor markers. Carbohydrate antigen 19–9 (CA19-9) is the first discovered carbohydrate antigen tumor marker with the highest sensitivity and specificity for pancreatic cancer. Carcinoembryonic antigen (CEA), as the most widely spectrum carbohydrate antigen tumor marker, can show an upward trend in many tumors. In this work, an electrochemical immunosensing platform was proposed for the detection of CEA and CA199. Nano-silicon sphere-cyclodextrin was synthesized for antibody capture. Graphene and gold nanoparticles were used to modify the electrode, improving the electronic conductivity of the electrode. The synthesized sensor can be used for highly sensitive detection of two tumor markers. This method also provides a new platform for clinical immune analysis of other biomolecules. [ABSTRACT FROM AUTHOR]

Various c-mesenchymal-to-epithelial transition (c-MET) inhibitors are effective in the treatment of non-small cell lung cancer; however, the inevitable drug resistance remains a challenge, limiting their clinical efficacy. Therefore, novel strategies targeting c-MET are urgently required. Herein, through rational structure optimization, we obtained novel exceptionally potent and orally active c-MET proteolysis targeting chimeras (PROTACs) namely D10 and D15 based on thalidomide and tepotinib. D10 and D15 inhibited cell growth with low nanomolar IC 50 values and achieved picomolar DC 50 values and >99% of maximum degradation (D max) in EBC-1 and Hs746T cells. Mechanistically, D10 and D15 dramatically induced cell apoptosis, G1 cell cycle arrest and inhibited cell migration and invasion. Notably, intraperitoneal administration of D10 and D15 significantly inhibited tumor growth in the EBC-1 xenograft model and oral administration of D15 induced approximately complete tumor suppression in the Hs746T xenograft model with well-tolerated dose-schedules. Furthermore, D10 and D15 exerted significant anti-tumor effect in cells with c-METY1230H and c-METD1228N mutations, which are resistant to tepotinib in clinic. These findings demonstrated that D10 and D15 could serve as candidates for the treatment of tumors with MET alterations. Novel exceptionally potent and orally active c-MET degrader namely D10 and D15 were developed. D10 and D15 significantly inhibited tumor cells growth and induced potent c-MET degradation in vitro and in vivo. [Display omitted] [ABSTRACT FROM AUTHOR]

Mitogen-activated protein kinase (MEK) inhibitors and oncolytic virotherapy are identified as promising cancer therapies that can enhance the efficacy of other cancer treatments. A few studies demonstrate that cancer cells proliferate when exposed to virotherapy with MEK inhibitors in an integer order model or without them in a fractional order model. None of them are intended to investigate tumor cell growth under the combined treatment strategy of chemo-virotherapy with a MEK inhibitor in a fractional order model. In this paper, a mathematical model based on fractional order ordinary differential equations (ODEs) is developed for the mutual interactions among tumor cells, as well as a therapeutic combination of chemotherapy, oncolytic viruses and the functional consequence of MEK inhibitor, to investigate how virotherapy could enhance chemotherapy under the action of MEK inhibitor. The numerical results show that virus burst size and MEK inhibitors have a noticeable impact on regulating the trend of tumor cell proliferation. While virotherapy responses to tumor cell proliferation are undoubtedly quicker than chemotherapeutic treatment responses, MEK intensity clearly affects the success of the treatment regimen. The results of this study can contribute to the development of a therapeutic strategy that combines MEK inhibitor functional monitoring with tumor cell growth control. [ABSTRACT FROM AUTHOR]

Posterior fossa tumor (PFT) survivors have difficulty learning new skills. Procedural memory is a skill learning system that allows, through training, the automatization of procedures and progressive improvement of performance. It underlies most of the motor procedures in everyday life that we perform automatically, such as riding a bike or writing. Motor procedural memory is divided into two components: motor sequence learning involving mainly cortico-striatal networks, and motor adaptation involving mainly cortico-cerebellar networks. The aim of this work was to explore the impact of a tumor and its treatment during childhood on procedural learning hypothesizing that sequence learning would be impaired in PFT survivors who have been treated with radiotherapy, whereas motor adaptation would be impaired in all PFT survivors. 22 irradiated survivors of PFT, 17 non-irradiated survivors and 21 healthy controls from the IMPALA study (NCT04324450) performed a motor sequence learning task and a motor adaptation task. Doses received by striatal and cerebellar structures were reported from the initial dosimetry plans. Sequence learning was preserved in both tumor groups, but at the individual level 7/22 irradiated, and 4/17 non-irradiated participants failed to learn the motor sequence. Motor adaptation was impaired in both tumor groups, predominantly in the irradiated group. This study sheds new light on the long-term impact of PFT treatments in childhood on a rarely-studied part of memory, which is perceptual-motor procedural learning. Our results suggest that the cerebellum and striatum could be considered as organs at risk with regard to procedural learning. [Display omitted] • Motor sequence learning is globally preserved in posterior fossa tumor survivors. • Motor adaptation is altered in posterior fossa tumor survivors. • Radiotherapy is a risk factor for impaired performance in procedural memory. • Young age at treatment and cerebellar deficit are risk factors for motor adaptation. • Striatum and cerebellum should be considered as organs at risk for learning. [ABSTRACT FROM AUTHOR]

Treatment of jaw tumors usually involves enucleation, curettage, or resection, to remove the pathology. Vascularized bone graft is known as the gold standard for large defects which ensures adequate healing reconstruction plate can be used to reconstruct mandibular continuity defects which provides a cheaper and simpler alternative with no need of dual team surgery. However, differences of quality of life and clinical outcomes in patients treated with either approach is not well studied. This study aims to compare quality of life and clinical outcomes between different reconstruction method of mandibular defects. The included literatures were searched on three databases, PubMed, ScienceDirect, and EBSCOhost, without any restriction according to PRISMA guidelines. Four studies were included as eligible study for further analysis in terms of pathological condition, surgery and graft used, and outcomes. There is no significant difference of quality of life between reconstruction groups, but significant difference were observed on the complication rate between groups. This study showed that quality of life alone should not be a sole consideration for deciding which modalities to choose to reconstruct mandibular defects. [ABSTRACT FROM AUTHOR]

In Australia participation rate in Advance Care Directives is 14%, and research is limited on Advance Care Planning (ACP) invitations and uptake among the patients with advanced cancer (PwAC). This study identifies the prevalence and types of documented ACP discussions in PwAC who died within two or four weeks of receiving chemotherapy. A retrospective audit was conducted. Statistical analysis was calculated in SPSS. Difference in ACP invitation and utilization between three groups [control, <2-weeks, and –4 weeks] was measured by Kruskal–Wallis and Chi-square (or Fisher-Exact) tests. Post-hoc follow-up pair-wise comparisons were performed. Adjusted prevalence ratios were estimated using two logistic regression models. This study was conducted in XXX Coast University Hospital, Australia. The records of 339 patients were examined and 320 patients were found eligible. Of the 320 PwAC [male: 55%; median age: 65 years], 227 (71%) received ACP invitation, and among the invited patients, 89% used Acute Resuscitation Plan; 54% used Enduring Power-of-Attorney; and 20% completed Advance Health Directives. From 7.5% [n = 24] of the patients who received chemotherapy in their last 2-weeks of life, 42% had not received an ACP invitation, 29% didn't have Acute Resuscitation Plan and only 4% completed Advance Health Directives. There were significant differences among Control, <2-weeks, and 2–4 weeks groups in completing Acute Resuscitation Plan (P = 0.003) and Advance Health Directives (P = 0.045). A significant difference was also observed between control and <2-weeks groups in number of days since Acute Resuscitation Plan used. Completing an Acute Resuscitation Plan was associated with a lower risk of dying within two-weeks of chemotherapy (OR = 0.246; P = 0.008). Low rates of ACP invitation and use in PwAC, especially who received chemotherapy in 2-weeks of dying confirm a need for embedding and regularly revisiting ACP framework in cancer care and educating staff, patients, and their family caregivers to increase uptake. [ABSTRACT FROM AUTHOR]

Mucoepidermoid carcinoma (MEC) is the most common salivary gland adenocarcinoma, more frequently affecting female patients in the fifth decade of life. When MEC arises in the minor salivary glands, the palate is the primary site. This case report describes an MEC on the palate of a 30-year-old woman. The lesion was initially treated as a pyogenic granuloma, but the final diagnosis based on histopathology was low-grade MEC. The patient was referred for cancer treatment, and no recurrence was observed during 3 years of follow-up. Some malignant tumors can mimic nonneoplastic reactive lesions clinically, which highlights the importance of biopsy and proper microscopic analysis of the resulting specimens. [ABSTRACT FROM AUTHOR]

The antioxidant system of tumor cells severely impairs reactive oxygen species (ROS)-mediated tumor therapy. Despite extensive attempts to attenuate the antioxidant capacity by eliminating ROS scavengers such as glutathione (GSH), nicotinamide adenine dinucleotide phosphate (NADPH) over-expressed in the tumor microenvironment can regenerate GSH from glutathione disulfide (GSSG), hence weakening ROS-induced oxidative damage. Therefore, engineering a nanoplatform capable of depleting both NADPH and GSH is extremely significant for improving ROS-mediated tumor treatment. Herein, a synergetic antioxidant inhibition strategy is proposed to attenuate intracellular antioxidant capacity for hypoxic tumor therapy. In this context, both porous Prussian blue nanoparticles (PPB NPs) and cisplatin prodrug [cis-Pt (IV)] in the nanoplatform can oxidize GSH to directly reduce GSH levels, while PPB NPs also enable NADPH depletion by peroxidase-mimicking to impair GSH regeneration. Furthermore, PPB NPs with catalase-mimicking activity catalyze H 2 O 2 decomposition to alleviate tumor hypoxia, thus reducing the generation of GSH and boosting singlet oxygen (1O 2) production by Chlorin e6 (Ce6) for enhancing oxidative damage. Experimental results prove that the nanoplatform, denoted as PPB-Ce6-Pt, can induce remarkable tumor cells apoptosis and ferroptosis. Importantly, a simple loading method and the use of Food Drug Administration (FDA)-approved materials make PPB-Ce6-Pt have great potential for practical applications. The antioxidant system in tumor cells disables ROS-mediated tumor therapy. Besides, extensive attempts aim at depleting GSH without considering their regeneration. Therefore, we developed a synergetic strategy to attenuate intracellular antioxidant capacity for hypoxic tumor therapy. PPB-Ce6-Pt nanoplatform could not only directly reduce GSH levels but also deplete NADPH by peroxidase-mimicking to impair GSH regeneration. In addition, PPB-Ce6-Pt nanoplatform could catalyze H 2 O 2 decomposition to alleviate tumor hypoxia, thus reducing the generation of GSH and boosting 1O 2 production by Chlorin e6 (Ce6) for increasing oxidative damage. Then, intracellular ROS boost and redox dyshomeostasis induced remarkable tumor cells apoptosis and ferroptosis. Importantly, a simple loading method and the use of biosafety materials made the nanoplatform have great potential for practical applications. [Display omitted] [ABSTRACT FROM AUTHOR]

Gold nanoparticles (AuNPs) are prospective tools for nano-based medicine that can directly target cellular biological processes to influence cell fate and function. Studies have revealed the essential role of AuNPs in metabolic remodeling for macrophage polarization. Nevertheless, as a hallmark of cancer cells, metabolic changes in tumor cells in response to AuNPs have not yet been reported. In the present study, polymer- and folate-conjugated AuNPs with satisfactory biocompatibility and tumor-targeting activity were synthesized to investigate their underlying roles in tumor metabolism. Tumor cells were significantly suppressed by AuNPs in vitro and in vivo , with little cytotoxicity in non-tumor cells. Subcellular localization showed that AuNPs localized in the mitochondria of tumor cells and impaired their structure and function, leading to excessive oxidative stress and mitochondrial apoptosis. Metabolic stress, with decreased glycolysis and insufficient nutrients, was also caused by AuNPs exposure in tumor cells. Mechanistically, the key enzymes (GLUT1 and HK2) for glycolysis modulation were remarkably reduced by AuNPs in a c-Myc-dependent manner. The present study demonstrated a new mechanism for AuNPs in the inhibition of tumor growth, that is, via directly targeting glycolysis and depriving energy. These findings provide new strategies for the design of nano-based medicines and anti-glycolytic therapeutics to inhibit the development of malignant tumors. Gold nanoparticles (AuNPs) have acquired ever-increasing interest for applications in cancer treatment and diagnosis due to their high biosafety and facile surface modification. Recent studies have shown that AuNPs can work as active agents to directly target the cellular processes and harbor antitumor properties, while the underlying mechanisms remain largely unknown. From the present findings, the stabilized AuNPs showed direct inhibition effects on tumor growth by glycolysis inhibition and energy deprivation. These results provide new insights of AuNPs for tumor treatments, which will further contribute to the development of promising nano-based medicines and anti-glycolytic therapies. [Display omitted] [ABSTRACT FROM AUTHOR]

Guidelines for oligometastatic breast cancer (OMBC) propagate multimodality treatment including polychemotherapy and local ablative treatment (LAT) of all lesions. The aim of this approach is prolonged disease remission, or even cure. Long-term outcomes in OMBC and factors associated with prognosis are largely unknown, due to the rarity of this condition. We report overall survival (OS), event-free survival (EFS), and prognostic factors in a large real-world cohort of patients with OMBC. Patients with breast cancer and 1–3 distant metastatic lesions, treated in the Netherlands Cancer Institute between 1997 and 2020, were identified via text mining of medical files. We collected patient, tumor and treatment characteristics. The Kaplan-Meier method was used to calculate OS and EFS estimates, and Cox regression analyses to assess prognostic factors. The cohort included 239 patients, of whom 54% had ERpos/HER2neg, 20% HER2pos and 20% triple negative disease. Median follow-up was 88.0 months (95% confidence interval (CI) 82.9–93.1) during which 107 patients died and 139 developed disease progression/recurrence; median OS was 93.0 months (95%CI 66.2–119.8). Factors associated with OS in multivariable analysis were subtype, disease-free interval and radiologic response to first-line systemic therapy; LAT was associated with EFS, but not OS. In this large real-world cohort of patients with OMBC, OS and EFS compare favorably to survival in the general MBC population. Radiologic complete response to first-line systemic therapy was associated with favorable OS and EFS, indicating the importance of early optimal systemic therapy. The value of LAT in OMBC requires further study. [Display omitted] • Patients with OMBC have favorable prognosis compared to the general MBC population. • Complete response to first-line systemic therapy is associated with better OS and EFS. • Optimizing systemic therapy for patients with OMBC should be a research priority. • The value of local ablative therapy in OMBC is unclear and requires further study. [ABSTRACT FROM AUTHOR]

Background: General practitioners (GPs) have a key role in palliative care provision for patients with advanced cancer. Continuity is valued by patients with such needs but is limited within current primary care systems. Exploration of the facilitators of and barriers to continuity in this complex context is required. Aim: To identify facilitators of and barriers to continuity with GPs in primary palliative care among people with advanced cancer and/or their close persons. Design: Mixed-methods systematic review with content and thematic analyses. Data sources: Keyword searches were carried out in five databases (Ovid MEDLINE(R), Ovid EMBASE(R), CINAHL, Web of Science, and Cochrane), policy documents and grey literature search engines in December 2020. Evidence was reviewed using relevant quality appraisal tools; data were extracted and tabulated. Findings were reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, and the review was prospectively registered on PROSPERO. Results: Seventeen studies were included. Six studies originated from the UK; six from Europe; three from Canada; and two from Australia. Two studies were mixed-methods, four presented quantitative data, and 11 papers reported on qualitative studies. Four themes were developed: (1) the role of GPs in facilitating continuity; (2) the role of patients and/or close persons in facilitating continuity; (3) changing needs throughout the disease trajectory; and (4) the organisational context in primary care. Conclusions: Facilitators of and barriers to continuity in primary palliative care are outlined. Further research is required to explore how patients and/or their close persons experience continuity in primary palliative care. Specifically, the work required of them to achieve their desired level of continuity, and their capacity for action in this context, needs further attention. [ABSTRACT FROM AUTHOR]

Cancer immunotherapy has significantly flourished and revolutionized the limited conventional tumor therapies, on account of its good safety and long-term memory ability. Discouragingly, low patient response rates and potential immune-related side effects make it rather challenging to literally bring immunotherapy from bench to bedside. However, it has become evident that, although the immunosuppressive tumor microenvironment (TME) plays a pivotal role in facilitating tumor progression and metastasis, it also provides various potential targets for remodeling the immunosuppressive TME, which can consequently bolster the effectiveness of antitumor response and tumor suppression. Additionally, the particular characteristics of TME, in turn, can be exploited as avenues for designing diverse precise targeting nanomedicines. In general, it is of urgent necessity to deliver nanomedicines for remodeling the immunosuppressive TME, thus improving the therapeutic outcomes and clinical translation prospects of immunotherapy. Herein, we will illustrate several formation mechanisms of immunosuppressive TME. More importantly, a variety of strategies concerning remodeling immunosuppressive TME and strengthening patients' immune systems, will be reviewed. Ultimately, we will discuss the existing obstacles and future perspectives in the development of antitumor immunotherapy. Hopefully, the thriving bloom of immunotherapy will bring vibrancy to further exploration of comprehensive cancer treatment. This review provides main strategies for remodeling immunosuppressive tumor microenvironment. The focus is on current advances in tumor targeting nanomedicines for enhanced cancer immunotherapy. [Display omitted] [ABSTRACT FROM AUTHOR]

Many tumors, such as types of sarcoma and breast cancer, stiffen as they grow in a host healthy tissue, while individual cancer cells are becoming softer. Tumor stiffening poses major pathophysiological barriers to the effective delivery of drugs and compromises treatment efficacy. It has been established that normalization of the mechanical properties of a tumor by targeting components of the tumor microenvironment (TME) enhances the delivery of anti-cancer agents and consequently the therapeutic outcome. Consequently, there is an urgent need for the development of biomarkers, which characterize the mechanical state of a particular tumor for the development of personalized treatments or for monitoring therapeutic strategies that target the TME. In this work, Atomic Force Microscopy (AFM) was used to assess human and murine nanomechanical properties from tumor biopsies. In the case of murine tumor models, the nanomechanical properties during tumor progression were measured and a TME normalization drug (tranilast) along with chemotherapy doxorubicin were employed in order to investigate whether AFM has the ability to capture changes in the nanomechanical properties of a tumor during treatment. The nanomechanical data were further correlated with ex vivo characterization of structural components of the TME. The results highlighted that nanomechanical properties alter during cancer progression and AFM measurements are sensitive enough to capture even small alterations during different types of treatments, namely normalization and chemotherapy. The identification of unique AFM-based nanomechanical properties can lead to the development of biomarkers for treatment prediction and monitoring. Cancer progression is associated with vast remodeling of the tumor microenvironment resulting in changes in the mechanical properties of the tissue. Indeed, many tumors stiffen as they grow and this stiffening compromises treatment efficacy. As a result, a number of treatments target tumor microenvironment in order to normalize its mechanical properties. Consequently, there is an urgent need for the development of innovative tools that can assess the mechanical properties of a particular tumor and monitor tumor progression and treatment outcomes. This work highlights the use of atomic force microscopy (AFM) for assessing the elasticity spectrum of solid tumors at different stages and during treatment. This knowledge is essential for the development of AFM-based nanomechanical biomarkers for treatment prediction and monitoring. [Display omitted] [ABSTRACT FROM AUTHOR]

The introduction of digital radiography has revolutionized medical imaging practice with increased efficiency of operational workflows, image quality, and patient care. However, concerns in relation to inadequate collimation practices have been reported. Studies exploring radiation-induced cancer risks to patients due to poor collimation practices during diagnostic imaging are limited. The purpose of the present study was to evaluate the radiation-induced cancer risk associated with increased radiation field size when imaging the chest of neonates, with the rationale to encourage effective collimation in clinical practice. A computer-based Monte Carlo program was used to simulate the dose profile of a newborn phantom. In the simulation, the phantom was positioned for an anterior-posterior (AP) chest X-ray, and the image field size was set to include just above the lung apices to T12/L1. Subsequently, the field sizes were varied at different distances, and the impact of the extra field coverages in terms of cancer risk was estimated for a number of key anatomical organs with reference to the combined absolute and relative risk models of the BEIR VII Committee. The result showed that increasing the radiation field size by 2cm in all directions, or head-to-foot, doubles the risk of colon cancer in both genders. Moreover, the risk of bladder cancer tripled in males and increased by 64% in females when the radiation field size increased by 1cm in the head-to-feet direction. The use of optimal field size is a key factor in reducing patient dose and the potential risk of radiation-induced cancer. Clear standard operating procedures and policies relating to best practices for collimation in clinical practice should be encouraged among the clinical radiology workforce and enforced through periodic audits, education, and training. [ABSTRACT FROM AUTHOR]

Proton therapy is increasingly recognized for its superior dosimetric advantages over photon. However, it is essential to have a photon backup plan in place for cases treated with proton therapy to account for any potential machine breakdowns. Generating backup plans manually can be laborious. Therefore, this study investigates the efficacy of RayStation Fallback planning for efficient and high-quality photon backup plan creation. Five prostate cancer patients previously treated with radiotherapy were selected for this retrospective study. The RayStation treatment planning system was employed to generate proton plans, while its fallback (FB) planning module was utilised to generate the backup plans using TomoTherapy (FB-TOMO) and volumetric modulated arc therapy (FB-VMAT). Plan evaluation was conducted utilizing dose-volume histogram parameters for targets (TV) and organs-at-risk (OAR). Average planning time for FB-TOMO and FB-VMAT was 226.8 seconds and 227.4 seconds respectively. Both types of FB plans demonstrated satisfactory coverage of the clinical target volume (CTV). Compared to original proton plans, both FB-TOMO and FB-VMAT exhibited improved OAR sparing but compromised target dose homogeneity and plan robustness. When comparing the 2 FB plans, FB-TOMO demonstrated lower hotspot volumes, better conformity and homogeneity of target dose, whereas FB-VMAT generally achieved lower OAR doses, except for high doses in the rectum and femoral heads. One FB-VMAT plan failed rectal V38Gy constraint, and another plan failed femoral head constraints. This pilot study highlights the potential of the FB planning module to efficiently generate photon contingency plans based on proton plans, particularly favoring FB-TOMO. Further validation on a larger scale is necessary to comprehensively evaluate the feasibility of this approach across disease sites. In addition to contingency planning, the FB module could also facilitate timely multi-modality plan evaluations. [ABSTRACT FROM AUTHOR]

With the lifestyle change and environmental pollution, tumors have become one of the most serious diseases that threaten human health. However, therapeutic and drug resistances during tumor treatment have forced us to search for alternative harnessing methods. Recently, considerable evidence has demonstrated that polysaccharides are a promising antitumor agent with high efficiency and low or no side effects. Nonetheless, the effect of structural features on the antitumor activity of polysaccharides is usually overlooked, which limits the development and exploitation of antitumor polysaccharides. Therefore, this work reviews the effect of structural features (including monosaccharide composition and proportion, molecular weight, glycosidic linkage, spatial structure, and chemical modification) on the antitumor activity of plant and microbial polysaccharides. Meanwhile, the possible antitumor mechanism of plant and microbial polysaccharides induced by their structural features is provided. This work is not only helpful for rapidly screening plant and microbial polysaccharides with antitumor activity on the basis of their structural features, but also offers good guidance for improving the antitumor activity of plant and microbial polysaccharides or polysaccharide-based derivatives via chemical, physical, and enzymatic modifications. Furthermore, it will provide help for the application of plant and microbial polysaccharide-based food in tumor treatment or prevention. [ABSTRACT FROM AUTHOR]

Nanophotothermolysis (NPhT) effect is considered to be an approach for the development of highly selective modalities for anticancer treatment. Herein, we evaluated an antitumor efficacy of NPhT with intravenously injected zinc phthalocyanine particles (ZnPcPs) in murine subcutaneous syngeneic tumor models. In S37 sarcoma-bearing mice a biodistribution of ZnPcPs was studied and the high antitumor efficacy of ZnPcPs-mediated NPhT was shown, including a response of metastatic lesions. The morphological investigation showed the main role of a local NPhT-induced vascular damage in the tumor growth and tumor spread inhibition. Murine tumors of different histological origin were not equally sensitive to the treatment. The results demonstrate a potential of ZnPcPs-mediated NPhT for treatment of surface tumors. Confined photothermal effect of nanophotothermolysis (NPhT) with zinc phthalocyanine particles (ZnPcPs; size of 75–150 nm) induced by high-energy nanosecond laser irradiation leads to a critical injury of blood vessels in the tumor bed and is able to provide a highly selective and long-term antitumor effect in subcutaneous murine syngeneic tumor models. [Display omitted] [ABSTRACT FROM AUTHOR]