Treatment Of Tumors Research Articles

Use of traditional Chinese medicine bezoars and bezoar-containing preparations in hepatocarcinoma

This manuscript used network pharmacology and experimental verification to analyze the anti-hepatocarcinoma mechanism of action of bezoars in traditional Chinese medicine (TCM), discovering that it can affect the immune cells within the tumor microenvironment and related pathways to produce inhibitory effects in liver cancer. In TCM, bezoars have a unique therapeutic advantage in the prevention and treatment of tumors. They play an anti-tumorigenic role by regulating the immune microenvironment through multi-component, multi-target and multi-pathway mechanisms. With the application of nanotechnology, bezoars and their compound preparations have been developed into anti-cancer drugs with unique therapeutic advantages, providing novel treatment options for tumor patients.

Temozolomide and capecitabine regimen as first-line treatment in advanced gastroenteropancreatic neuroendocrine tumors at a Latin American reference center

BACKGROUND Numerous studies have indicated that the temozolomide and capecitabine regimen (TEMCAP) exhibits a certain level of efficacy in treating advanced, well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NET). However, published data from Peru are limited. We hypothesize that this regimen could be a viable therapeutic option for advanced GEP-NET in the Peruvian population. AIM To evaluate overall survival (OS) in patients diagnosed with advanced GEP-NET treated with TEMCAP at the Instituto Nacional de Enfermedades Neoplásicas (INEN) in Lima-Perú. METHODS A retrospective review was conducted to identify patients with GEP-NEN treated with the TEMCAP regimen between 2011 and 2021 at the INEN. A total of thirty-eight patients were included in the final analysis: Thirty-five received TEMCAP as a first-line treatment, and three as a second-line treatment. The primary objective was to evaluate OS. The efficacy and safety of TEMCAP were assessed until the occurrence of unacceptable toxicity or disease progression. Survival outcomes were estimated using the Kaplan-Meier method. RESULTS The median age of the patients was 52 years (range 24-77 years), and 53.3% were female. The most common symptoms at diagnosis were abdominal pain in 31 patients (81.6%). Primary tumors included 12 in the rectum (31.6%), 11 in the pancreas (28.9%), 3 in the ileum (7.9%), 2 in the mesentery (5.3%), 2 in the small intestine (5.3%), 1 in the appendix (2.6%), 1 in the stomach (2.6%) and 6 cases of liver metastasis of unknown primary (15.8%). Five were neuroendocrine tumors (NET) G1 (13.2%), 33 were NET G2 (86.8%), five had Ki67 < 3% (13.2%), and 33 had Ki67 between 3% and 20% (86.8%). TEMCAP was administered to 35 (92.1%) patients as first-line treatment. OS at 12, 36, and 60 months was estimated in 80%, 66%, and 42%, respectively, with a median OS of 49 months. CONCLUSION TEMCAP therapy is a viable first-line option regarding efficacy and tolerability in areas where standard therapy is inaccessible.

Spinal Intramedullary Tumors.

Intramedullary tumors are a subgroup of spinal tumors and are associated with high morbidity and mortality. The estimated incidence of spinal tumors in general is 0.74 to 1.6 per 100 000 persons per year, with intramedullary tumors making up 10% to 30% of the total. The diagnosis is often delayed because of the insidious onset of symptoms, which are often nonspecific at first. This review is based on pertinent publications about intramedullary tumors that were retrieved by a selective search in the PubMed database. Intramedullary tumors often cause diffuse neurologic symptoms of gradually increasing severity, progressing, in advanced cases, to a complete spinal cord transection syndrome. Magnetic resonance imaging of the spine without and with intravenous contrast is the standard diagnostic technique. The histopathological origin of most intramedullary tumors is from glial cells, but other types of intramedullary tumor exist as well. The primary treatment of all intramedullary tumors is surgical resection. 9% to 34% of patients may experience a worse neurological deficit after surgery than before, but such problems resolve completely in 25% to 41% of cases. The extent of resection is the main factor affecting the risk of tumor recurrence and progression. The extent of resection also determines the possible indication for adjuvant treatment, which is needed, in particular, for high-grade and subtotally resected tumors, and for those that display progression. The treatment of intramedullary tumors is based on case series, retrospective analyses, and case reports, as randomized trials are lacking. Patients with intramedullary tumors should be cared for, as much as possible, in the setting of prospective, uniform studies of their spontaneous course and the outcomes after treatment. This will yield better evidence on the treatment of these tumors in the future.

Pharmacological Advancements of PRC2 in Cancer Therapy: A Narrative Review

Polycomb repressive complex 2 (PRC2) is known to regulate gene expression and chromatin structure as it methylates H3K27, resulting in gene silencing. Studies have shown that PRC2 has dual functions in oncogenesis that allow it to function as both an oncogene and a tumor suppressor. Because of this, nuanced strategies are necessary to promote or inhibit PRC2 activity therapeutically. Given the therapeutic vulnerabilities and associated risks in oncological applications, a structured literature review on PRC2 was conducted to showcase similar cofactor competitor inhibitors of PRC2. Key inhibitors such as Tazemetostat, GSK126, Valemetostat, and UNC1999 have shown promise for clinical use within various studies. Tazemetostat and GSK126 are both highly selective for wild-type and lymphoma-associated EZH2 mutants. Valemetostat and UNC1999 have shown promise as orally bioavailable and SAM-competitive inhibitors of both EZH1 and EZH2, giving them greater efficacy against potential drug resistance. The development of other PRC2 inhibitors, particularly inhibitors targeting the EED or SUZ12 subunit, is also being explored with the development of drugs like EED 226. This review aims to bridge gaps in the current literature and provide a unified perspective on promising PRC2 inhibitors as therapeutic agents in the treatment of lymphomas and solid tumors.

Cryogenic treatment of bladder tumors in canines: Transitional cell carcinoma and fibrosarcoma

Bladder tumors in dogs are rare, accounting for 1-2% of all cases. Most of these tumors are malignant and of epithelial origin. This study examines various surgical approaches for the complete resection of transitional cell carcinomas of the bladder, showing a recurrence rate of 60%. Surgery may be used as an emergency therapy to relieve partial or complete ureteral obstruction, but owners should be informed that it is only palliative and associated with a high likelihood of early metastasis. Cryosurgery is a local method that relies on the tissue-destructive effects of extremely low temperatures. While intrabdominal cryosurgery is common in human medicine, it is not widespread in veterinary practice. This study presents three canine oncology cases treated through conventional laparotomy and cystotomy, employing similar cryosurgical techniques. Treatments included: i) primary transitional cell carcinoma (TCC) with previous tumor freezing, cytoreduction by debulking, and base cryoablation; ii) primary TCC with cryoablation only; and iii) poorly differentiated fibrosarcoma (STBs) with tumor excision and base cryoablation. Cold diffusion was controlled through visual observation of the 0°C isotherm and simultaneous tactile palpation. Cryoablation was performed using liquid nitrogen with a portable CRY-AC 700 Brymill device, while radiofrequency ablation was carried out with an Ellman Surgitron device. Treatment was ambulatory, well-tolerated, and resulted in rapid resolution of clinical signs.

Research progress on pathogenic germline mutations in malignant tumors

Malignant tumors are closely related to various genetic and environmental factors. Pathogenic germline gene mutations play a key role in the occurrence and development of some malignant tumors. Some germline mutations can increase the risk of malignant tumors. For example, those with homologous recombination repair gene BRCA1/2 mutations are prone to breast cancer, ovarian cancer, etc., and some germline mutations are associated with genetic syndromes. For instance, 80% of hereditary non-polyposis colon cancers are associated with mutations in mismatch repair genes such as MLH1 and MLH2. In addition, 70% of Li-Fraumeni syndrome patients have harbored germline TP53 mutations. With the development of next-generation sequencing technology, more and more germline gene mutations have been discovered recently, which is of great significance for the prevention, screening, and treatment of tumors. This article has provided a review for common germline mutations, detection methods, and advances in drug therapy.

Novel Flavin Mononucleotide-Functionalized Cerium Fluoride Nanoparticles for Selective Enhanced X-Ray-Induced Photodynamic Therapy

X-ray-induced photodynamic therapy (X-PDT) represents a promising new method of cancer treatment. A novel type of nanoscintillator based on cerium fluoride (CeF3) nanoparticles (NPs) modified with flavin mononucleotide (FMN) has been proposed. A method for synthesizing CeF3-FMN NPs has been developed, enabling the production of colloidal, spherical NPs with an approximate diameter of 100 nm, low polydispersity, and a high fluorescence quantum yield of 0.42. It has been demonstrated that CeF3-FMN NPs exhibit pH-dependent radiation-induced redox activity when exposed to X-rays. This activity results in the generation of reactive oxygen species, which is associated with the scintillation properties of cerium and the transfer of electrons to FMN. The synthesized NPs have been demonstrated to exhibit minimal cytotoxicity towards normal cells (NCTC L929 fibroblasts) but are more toxic to tumor cells (epidermoid carcinoma A431). Concurrently, the synthesized NPs (CeF3 and CeF3-FMN NPs) demonstrate a pronounced selective radiosensitizing effect on tumor cells at concentrations of 10−7 and 10−3 M, resulting in a significant reduction in their clonogenic activity, increasing radiosensitivity for cancer cells by 1.9 times following X-ray irradiation at a dose of 3 to 6 Gy. In the context of normal cells, these nanoparticles serve the function of antioxidants, maintaining a high level of clonogenic activity. Functional nanoscintillators on the basis of cerium fluoride can be used as part of the latest technologies for the treatment of tumors within the framework of X-PDT.

Abstract IA020: Discovery of brain-penetrant inhibitors for the treatment of BRAF mutant tumors

Abstract Many tumors are driven by oncogenic kinases. While a majority of the most prevalent oncogenic kinases currently have existing targeted therapies available, most of the molecules were not designed to be CNS penetrant and are therefore unable to control CNS metastatic tumors. By employing principles for the design of CNS penetrant molecules, we discovered two brain-penetrant BRAF inhibitors, which both progressed into clinical trials. The first candidate, ARRY-461, was designed to inhibit class I mutant BRAF V600E tumors. The second candidate, ARRY-440, was designed to inhibit class I, II, III, and indel mutant BRAF tumors. Additionally, ARRY-440 was designed to overcome both the paradoxical activation of BRAF as well as inhibit mBRAF:wtCRAF heterodimers, two features that most 1st generation BRAF V600E inhibitors lack. Finally, we were pleased to see that ARRY-440 led to clinical responses in a variety of different BRAF V600E tumors, including in some tumors that harbored both a BRAF V600E mutation and an oncogenic NRAS mutation. Citation Format: Dean Kahn. Discovery of brain-penetrant inhibitors for the treatment of BRAF mutant tumors [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Optimizing Therapeutic Efficacy and Tolerability through Cancer Chemistry; 2024 Dec 9-11; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(12_Suppl):Abstract nr IA020.

Abstract IA013: Discovery of the dual A2A/A2B receptor antagonist MK-1088 for the treatment of solid tumors

Abstract In the tumor microenvironment (TME), adenosine levels have been shown to be elevated relative to normal tissues. This increase in adenosine levels renders an immunosuppressive effect via direct effects on T cells via agonism of the A2A receptor and indirect effects via agonism of both A2A and A2B receptors on myeloid cells. With these observations as a backdrop, we sought to develop a dual A2A/A2B receptor antagonist with properties that would enable maintenance of high levels of target engagement of the A2A and A2B receptors even at trough concentration. Drawing on our organization’s significant prior experience developing A2A receptor antagonists for the potential treatment of Parkinson’s disease, we developed MK-1088, a highly potent A2A/A2B dual receptor antagonist that was purposefully designed to possess excellent selectivity over the related A1 and A3 receptors. This presentation will detail the discovery and development strategy that was employed to identify molecules that met the profile exemplified by this molecule. A single ascending dose study of MK-1088 in healthy human volunteers demonstrated our ability to achieve, at trough concentration, >99% target engagement (TE) at the A2A receptor and >90% TE at the A2B receptor. Details of the pharmacokinetics, safety, and tolerability from this study will be highlighted. Citation Format: Duane E. DeMong, Sheila Ranganath, Jared Cumming, Matthew Larsen, Yonglian Zhang, Christopher Plummer, Amjad Ali, Anthony Palmieri, Evan Barry, Pierre Daublain, Pranav Gupta, Manash Chatterjee, Jeremy Presland, Sebastian Schneider, Paul Ciaccio, Daniel Tatosian, Aaron Sather, Ben Turnbull, Steven Silverman, Harry Chobanian, Harini Krishnamurthy, Richard Wnek, Stephen Crowley, Alita Miller, Mark Ayers, Marlene Hinton, Jill Chrencik, Sylvie Rottey, Jennifer O'Neil. Discovery of the dual A2A/A2B receptor antagonist MK-1088 for the treatment of solid tumors [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Optimizing Therapeutic Efficacy and Tolerability through Cancer Chemistry; 2024 Dec 9-11; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(12_Suppl):Abstract nr IA013.

Targeting APE1: Advancements in the Diagnosis and Treatment of Tumors.

With the emergence of the precision medicine era, targeting specific proteins has emerged as a pivotal breakthrough in tumor diagnosis and treatment. Apurinic/apyrimidinic Endonuclease 1 (APE1) is a multifunctional protein that plays a crucial role in DNA repair and cellular redox regulation. This article comprehensively explores the fundamental mechanisms of APE1 as a multifunctional enzyme in biology, with particular emphasis on its potential significance in disease diagnosis and strategies for tumor treatment. Firstly, this article meticulously analyzes the intricate biological functions of APE1 at a molecular level, establishing a solid theoretical foundation for subsequent research endeavors. In terms of diagnostic applications, the presence of APE1 can be detected in patient serum samples, biopsy tissues, and through cellular in situ testing. The precise detection methods enable changes in APE1 levels to serve as reliable biomarkers for predicting tumor occurrence, progression, and patient prognosis. Moreover, this article focuses on elucidating the potential role of APE1 in tumor treatment by exploring various inhibitors, including nucleic acid-based inhibitors and small molecule drug inhibitors categories, and revealing their unique advantages in disrupting DNA repair function and modulating oxidative-reduction activity. Finally, the article provides an outlook on future research directions for APE1 while acknowledging major technical difficulties and clinical challenges that need to be overcome despite its immense potential as a target for tumor therapy.

An Activatable Heavy-Atom-Free Upconversion Photosensitizer for Targeted Imaging and Treatment of Tumors.

Photodynamic therapy (PDT) is an innovative and promising method for treating tumors that has attracted significant interest but still faces several challenges, such as a lack of selectivity, deep penetration of light, and efficient ROS generation. To address these challenges, we optimized and synthesized a series of photosensitizers and successfully developed a heavy-atom-free near-infrared FUCL photosensitizer NFh-NMe-2. This photosensitizer can generate singlet oxygen (1O2) and induce cellular apoptosis under 808 nm light. For the safe ablation of microtumors in vivo, an activatable FUCL photosensitizer NFh-NTR was developed based on the overexpression of nitroreductase (NTR). NFh-NTR could be activated by NTR, leading to the release of the photosensitizer NFh-NMe-2, restoring the fluorescence signal, and effectively killing tumor cells under 808 nm light irradiation. This work opens new possibilities in the chemical design of an FUCL photosensitizer for cancer treatment.

Radioresistance-related gene signatures identified by transcriptomics characterize the prognosis and immune landscape of pancreatic cancer patients

BackgroundRadiotherapy (RT) is an important means of local treatment of solid tumors, and radioresistance is the main reason for RT failure for tumors, especially pancreatic cancer (PC). It is urgent to distinguish key genes and mechanisms of radioresistance in PC.MethodsWe acquired the data from The Cancer Genome Atlas (TCGA), obtained the gene modules associated with radioresistance by weighted gene coexpression network analysis (WGCNA), and identified differentially expressed genes (DEGs) between normal and tumor samples. Radioresistance-related genes (RRRGs) were determined with the intersection of WGCNA and DEGs. The hub RRRGs associated with prognosis were distinguished by the least absolute shrinkage and selection operator (LASSO) regression. We established a risk score model using multivariate Cox regression. Immune cell infiltration and drug sensitivity were evaluated through the CIBERSORT algorithm and the “OncoPredict” software package, respectively. The association of the key gene RIC3 and PC clinical features was verified in public databases, and its biological behaviors were explored in vitro.ResultsThe intersection of DEGs and WGCNA confirmed 14 RRRGs, then six hub RRRGs were identified using LASSO. A key four genes (DUSP4, ADORA2B, SCGB2A1, and RIC3) risk score model was constructed and proved to be capable of independently estimating the prognosis of PC. There is no significant difference between risk score groups in various immune cell infiltration and response to immunotherapy. Although the low-risk group seemed to exhibit greater sensitivity to antitumor drugs, the four drugs (5-fluorouracil [5-FU], leucovorin, irinotecan, and oxaliplatin) currently used for PC patients had no statistical difference for the low- and high- group. The overexpression of RIC3 had a synergy effect with irradiation on inhibited malignant biological properties of PC cells, which was verified by detecting the proliferation ability, apoptosis rate, cell cycle distribution, and migration ability of PANC-1 cells.ConclusionsWe herein presented signature genes correlated with radioresistance in PC and established a risk score model competent in estimating patients’ clinical outcomes and response to antitumor drugs. The above evidence could contribute to comprehending the mechanisms of radioresistance and identifying the underlying therapy targeting.

Cell membrane fusion composite lipid nanocarrier: preparation and evaluation of anti-tumor effects.

With the advancements in nanotechnology and biomaterials science, the development of nanodrug delivery systems (Nano-DDSs) has provided opportunities for the realization of precise targeted treatment of malignant tumors. Liposomes have become a type of DDS with early clinical application and mature development due to their excellent tissue-targeting capacity and outstanding biocompatibility. However, several obstacles remain, such as recognition and clearance by the immune system, a short half-life, and poor tumor targeting. To address these problems, we propose a new method to transform liposomes, using fusion to reassemble the extracted natural cell membranes and artificial phospholipids to form a composite nanolipid carrier (recombined lipid nanocarriers (RLNs)). We evaluated the different types of cell membrane composite lipid nanocarriers based on parameters such as particle size, stability, drug loading and release capabilities, in vitro and in vivo tumor-targeting efficacy, and safety. The results indicated that these novel tumor cell-derived membrane fusion lipid nanocarriers exhibited promising antitumor effects and safety profiles, offering insights for precision cancer treatment.

Comparison of accuracy of brain biopsy simulation between 3-dimensional-printed guides and neuronavigation in skull-brain tumor models of dogs and cats.

This study aimed to compare the accuracy of brain biopsies in skull-brain tumor models (SBTMs) of dogs and cats using 2 techniques: 3-D-printed brain biopsy guides (3D-BBGs) and electromagnetic (EM) neuronavigation. Based on the CT data from 12 dogs and 3 cats, a total of 30 SBTMs were created using 3-D-printing technology, with 2 models per data set. Thirty brain biopsies were performed: 15 using 3D-BBGs and 15 using EM neuronavigation. The accuracy of the brain biopsies was assessed by comparing the prebiopsy and postbiopsy models using computer-aided design software. The median needle placement error for all biopsies was 1.75 mm (range: 0.82 to 3.16 mm), with 1.79 mm (range: 0.94 to 2.94 mm) for the 3D-BBG group and 1.68 mm (range: 0.82 to 3.16 mm) for the EM neuronavigation group. There was no significant difference in accuracy between the 2 methods. In the EM neuronavigation group, the needle placement error correlated significantly with the total needle length, but no such correlation was observed in the 3D-BBG group. Both methods successfully retrieved samples from brain tumor models. There was no significant difference in the accuracy of brain biopsies performed using 3D-BBGs and EM neuronavigation. This suggests that the choice of method depends on veterinarian preference, available hospital resources, and patient-specific considerations. This study demonstrates that both 3D-BBG and EM neuronavigation are viable options for performing brain biopsies in veterinary practice, potentially improving the diagnosis and treatment of brain tumors in small animals.

Unproven added benefit due to late changes to the appropriate comparator therapy

As part of the early benefit assessment, the added benefit of new medicinal products protected by documentation is assessed in comparison to the appropriate comparator therapy (ACT). At the request of the pharmaceutical company (MAH), the Federal Joint Committee (G-BA) discusses the documents to be submitted and the ACT. The G-BA can adjust the zVT determined in the course of a consultation over time. This can also be done after the start of a benefit assessment. In this paper, examples are presented that show how the change of the zVT in the ongoing benefit assessment procedure can lead to a usable randomised controlled trial (RCT) not being considered by the G-BA, which in turn leads to an unproven added benefit. Results: In this analysis, four practical cases were presented in which the manufacturer was confronted with the situation of an unsuitable study comparator due to a zVT amendment in the ongoing benefit assessment procedure. For example, drugs for the treatment of head and neck tumours, multiple sclerosis or chronic rhinosinusitis were denied the additional benefit initially determined by the Institute for Efficiency and Quality in Health Care (IQWiG) in the procedure in the final G-BA decision due to short-term changes to the zVT.

Ionizable cationic lipid nanoparticles loaded with miRNA-125b/BLZ945 for pancreatic cancer treatment.

In prior research, both miRNA-125b and BLZ945 have shown potential in effectively inhibiting M2 macrophage polarization and producing antitumor effects. Nevertheless, their physicochemical characteristics present significant challenges for efficient in vivo delivery. Ionizable cationic lipid nanoparticles (LNPs), recognized for their superior biocompatibility and drug-loading capacity, serve as a novel carrier for nucleic acid-based therapeutics. In our study, we successfully encapsulated both agents within LNPs and conducted a thorough characterization. Subsequently, we investigated their potential to repolarize M2 macrophages in vitro and evaluated their in vivo distribution, biosafety, and antitumor efficacy. The findings revealed that the LNPs maintained excellent drug-loading efficiency, consistent particle size, and stable zeta potential. All formulations effectively inhibited M2 macrophage polarization in vitro. Upon administration in vivo, the LNPs not only demonstrated favorable biosafety profiles but also accumulated efficiently in tumor tissues, substantially reducing tumor burden, particularly notable in co-loaded LNPs. Our results affirm that LNPs are an effective carrier for miRNA-125b and BLZ945, highlighting this encapsulation approach as promising for the treatment of solid tumors and meriting further investigation. Practitioner points: (i) Ionizable cationic nanoparticles provide high and stable encapsulation rates to efficiently load nucleic acid polymers into the LNP, avoiding the rapid accumulation of circulating macrophages, which can lead to reduced penetration of the LNP into target tissues. Therefore, it can be used as a novel drug delivery method to benefit clinical patients. (ii) miRNA-125b LNP/BLZ945 LNP attenuated the depleting effect of BLZ945 on macrophages and significantly inhibited macrophage M2 polarization. It could be effectively distributed in tumors and showed good biosafety while exerting antitumor effects, bringing hope to clinical pancreatic tumor patients.

An engineered α1β1 integrin-mediated FcγRI signaling component to control enhanced CAR macrophage activation and phagocytosis

Treatment of solid tumors remains difficult, and therefore there has been increased focus on chimeric antigen receptor macrophages (CAR-M) to challenge solid tumors. However, CAR domain design of of adoptive cell therapy, which leads to differences in antitumor activity and triggered antitumor potential, remains poorly understood for macrophages. We developed an α1β1 integrin-mediated Fc-gamma receptor I (FcγRI) signaling component for CAR-M specific activation and its antitumor potential. We evaluated CAR-M effects with α1β1 integrin-mediated FcγRI signaling (ACT CAR-M) on the activation and antitumor phagocytic response of macrophages in vitro. Subcutaneous tumor model in BALB/c mice and carcinomatosis model in immunodeficient mice were used to test the antitumor effect of ACT CAR-M compared with CD3ζ CAR-M. The α1β1 integrin-mediated FcγRI signaling engagement of CAR-M was associated with enhanced macrophage activation and specific phagocytosis in primary human macrophages, and significantly improved tumor control and survival in multiple cancer models when compared to CD3ζ CAR-M. RNA-sequencing suggested that α1β1 integrin-mediated FcγRI engagement increased antitumor immunity by enhancing pro-inflammatory M1 phenotype-associated pathways, such as Toll-like receptor signaling, tumor necrosis factor signaling, and IL-17 signaling. α1β1 integrin-mediated FcγRI signaling engagement markedly enhanced antitumor effects of CAR-M immunotherapy, which is proposed as an advanced engineering CAR domain material to expand the clinical application of CAR-M.

MR-guided online adaptive stereotactic body radiotherapy (MRgSBRT) of primary lung tumors and lung oligometastases.

Stereotactic body radiotherapy is pivotal in the treatment of lung tumors, demonstrating effective local control. However, challenges persist with intra-fractional anatomical changes and organs at risk during delivery. Magnetic resonance-guided online adaptive stereotactic body radiotherapy (MRgSBRT) represents anovel technique promising to achieve safe delivery of ablative doses with improved outcomes for primary lung tumors or lung oligometastases. In this single-institution retrospective analysis, we evaluated 64patients (92lesions) with primary lung cancer or lung oligometastases treated with MRgSBRT. Using Kaplan-Meier method and log-rank test; we estimated local control (LC), local progression-free survival (LPFS), distant progression-free survival (DPFS), and overall survival (OS). Atotal of 64patients (92lesions) treated with MRgSBRT were included comprising 14.1% primary lung cancer lesions and 85.9% lung oligometastases. Median total dose, fraction number, fraction dose and BED10 were 50 Gy (range, 21-70 Gy), 5(range, 1-10), 10 Gy (range, 6-34 Gy), 100 Gy (range, 48-180.0 Gy) respectively. Of the 420 fractions administered, 88.6% (n = 372) involved on-table adapted plans. Median LPFS was not reached and the 1‑ and 3‑year LPFS rates were 96.3% (95% CI 92.4-100.0%) and 86.4% (95% CI 76.9-95.9%), respectively. No local recurrences were observed post-treatment with atotal dose of > 50 Gy, BED10 > 100 Gy, fractional dose of > 10 Gy or aCCI > 0.96. Our study of MRgSBRT in 92lung lesions revealed a1-year and 3‑year LPFS rates of 96.3 and 86.4%, respectively without ≥ grade3 toxicity. Future prospective studies evaluating lung MRgSBRT are awaited.

Ultrasound-induced rapid electron movement on ZnO/MoS2 heterojunction for high performance tumor therapy

Conventional methods for treating tumors not only have limited therapeutic efficacy but also cause harm to patients, so there is an urgent need to develop a new therapeutic approach. Sonodynamic therapy (SDT), with its strong tissue penetration and few side effects, is considered to be an effective means of treating tumors. However, the reactive oxygen species (ROS) produced by a single piezoelectric material is often limited and does not achieve a complete tumor cure. In this paper, a ZnO/MoS2 heterojunction is synthesized by hydrothermal immobilization of MoS2 on ZnO to enhance the effect of SDT. Meanwhile, due to the electron exchange between ZnO and MoS2, a layer of ZnS is formed between ZnO and MoS2. Under ultrasound (US) irradiation, the ZnO/MoS2 heterojunction can effectively eliminate breast cancer cells within 10 min. This is mainly due to the better piezoelectric catalytic ability of ZnO/MoS2 than pure ZnO. Electrochemical and Uv–vis tests show that the formation of heterojunction accelerates the separation of electrons and holes and inhibits carrier complexation, so that more oxygen substrates will react with electron-hole pairs to generate ROS. This work provides a novel idea to take the treatment of tumors by enhancing piezoelectric catalysis through the construction of heterojunction interfaces.

Permanent alopecia after radiotherapy of primary brain tumours: The most influential factors

PurposeAlopecia is a distressing side effect of radiotherapy in patients undergoing treatment for primary brain tumours. This study aimed to investigate the most influential clinical, demographic, and dosimetric factors associated with permanent scalp alopecia in patients with brain tumours treated with intensity-modulated radiations. Patients and methodsEighty patients with brain tumors treated with intensity-modulated radiations were enrolled. Inclusion criteria were having a primary brain tumour and patients with at least 18 months of radiotherapy. Scalp alopecia was evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. The scalp location with hair loss was marked and delineated on their follow-up MRI, and the planning dosimetric parameters, including D0.1cm3 (as maximum dose), mean dose, and various volumetric parameters such as V16Gy-43Gy (with about 5Gy interval) were recorded. In addition, receiver operating characteristic (ROC) curve analysis was employed to identify predictive parameters for chronic alopecia. ResultsThe hair loss severity was grade 1 for 70 % of cases, and grade 2 for 30 %. Male gender, history of chemotherapy, and family history of hair loss were significantly associated with increased volume of hair loss follicles. The correlation and ROC analysis revealed that regions receiving doses of 30Gy or higher (i.e., V30Gy) were associated with a higher risk of developing grade 2 alopecia. The resulting areas under the curve of 0.694 were indicators for moderate correlations between the considered dose–volume histogram parameters and patients’ permanent alopecia. Even if these results were not statistically significant, these findings suggest that specific dosimetric parameters, such as V30Gy to V43Gy, maybe the strongest predictors of grade 2 chronic radiation-induced alopecia. The cut-off values were also about 13.5 to 8 cm3 for V30Gy to V43Gy, respectively, which can be played as an indicator of the dose–volume histogram threshold above which permanent alopecia will be expected after brain intensity-modulated radiotherapy. ConclusionThe incidence of permanent alopecia after intensity-modulated radiotherapy is influenced by demographic, dosimetric, and clinical factors such as gender, history of chemotherapy, and family history, and the skull follicle regions receiving doses of 30Gy or higher.