Treatment Of Tumors Research Articles

Unusual Cutaneous Reaction with Erlotinib: A Brief Report with Current Review of Management of Tyrosine Kinase Inhibitor-associated Cutaneous Toxicity

ABSTRACT Tyrosine kinase inhibitors (TKIs) have emerged as the preferred choice of treatment for various tumors as a result of better outcomes and quality of life without the debilitating side effects of cytotoxic chemotherapy. Erlotinib is a TKI against epidermal growth factor receptor that is commonly used in lung cancer and pancreatic cancer. The most common adverse effect expected is cutaneous toxicity, which occurs as acneiform rash. Here, we present a case of 71-year-old man with metastatic lung cancer who had an atypical squamous-crusted eruption with intense itching and pain on his forehead that resolved spontaneously after withholding erlotinib along with supportive care. The present case depicts unusual cutaneous toxicity with the use of TKI.

TMOD-27. RECURRENT GLIOBLASTOMA AFTER LASER ABLATION OF THE PRIMARY TUMOR IN A PRECLINICAL ORTHOTOPIC MODEL EXHIBIT INCREASED GENETIC SIGNATURES OF CELL CYCLE AND CELL MOTILITY

Abstract Image-guided laser interstitial thermal therapy (LITT) is a minimally invasive tumor cytoreductive treatment for recurrent gliomas and tumors in eloquent loci. We have adapted this technique to develop an image-guided glioblastoma (GBM) ablation model, its recurrence and have tested the efficacy of imaging biomarkers in evaluating tumor ablation and recurrence. The cytopathology and molecular signatures of the primary and recurrent tumors were compared. Immune-compromised female rats were implanted with U251N tumor cells in one brain hemisphere (n=20). Tumor growth was monitored using magnetic resonance imaging (MRI). When tumors reached about 4 mm in diameter, they were ablated using a clinical LITT system (Visualase®), under MRI guidance. Five other rats implanted with U251N tumors were used as unablated controls. MRI data were acquired at 24 h post-LITT, and at 2 and 4 weeks. Rats were sacrificed for histopathology at 2 and 4 weeks, and brain sections stained for hematoxylin and eosin, human major histocompatibility complex, Ki67, a cell proliferation marker and sex determining region Y)-box 2 (SOX2), a stem cell transcription factor. An additional cohort of rats with primary (n=4) and post-LITT recurrent (n=4) U251N tumors were used for analysis of their molecular composition using RNA-Seq approach. In the treated groups, MRI showed little tumor tissue at 24 h, evidence of recurrence at 2 weeks and significant tumor tissue at 4 weeks. Tumor DCE-MRI parameters showed elevated intra-tumoral vascular permeability (i.e., Ktrans) values at pre-LITT imaging, that shifted to peri-ablation periphery at 24 h. A trend of progressive decrease in Ktrans was seen until 1-week post-ablation. Increasing Ktrans values at 2 weeks and after 4 weeks coincided with tumor recurrence. RNA-Seq data showed that cell cycle, cellular movement and inflammatory disease genes were the most differentially expressed genes in the recurrent tumors suggesting increased infiltration may primarily underlie treatment resistance.

Medium-term oncological outcome endoscopic surgery malignant tumors of the nasal cavity and paranasal sinuses

Introduction. Transnasal endoscopic resection of sinonasal tumors is currently used in many clinics around the world. Short- and long-term oncological outcomes primarily depend on tumor histology. However, most currently existing studies are based on a small number of observations due to the rarity and heterogeneity of sinonasal malignancy.Aim. To evaluate short- and medium-term oncological outcomes of treatment of malignant sinonasal tumors. Materials and methods. The study is based on retrospective analysis of 95 patients who underwent endoscopic surgery for sinonasal malignancy between 2014 and 2023 at the N.N. Blokhin National medical Research Center of Oncology. Squamous cell carcinoma was diagnosed in 27 (28.4 %) patients, olfactory neuroblastoma in 13 (13.7 %), mucosal melanoma in 30 (31.6 %), adenocarcinoma in (6.3 %), adenoid cystic carcinoma in 7 (7.3 %), sarcomas in 12 (12.7 %). Results. In the study group, 2-years overall survival and recurrence-free survival were 81.3 and 61.4 % respectively, survival without local recurrence was 87.5 %. The outcomes significantly depended on tumor histology.Conclusion. Oncological outcomes of endoscopic resections of sinonasal tumors significantly depend on tumor histology, but in general they allow to achieve good local control. Small number of observations, variety of histological forms, and short follow-up periods do not allow to accurately evaluate the effectiveness of this approach for each tumor type. further research in large populations is needed to establish risk factors.

RADT-05. VASCULAR OVERLAP PROVIDES PROTECTION FROM GAMMA-KNIFE-INDUCED RADIATION NECROSIS IN A METASTATIC BRAIN TUMOR COHORT

Abstract INTRODUCTION Radiation necrosis (RN) is a long-term complication of Gamma-Knife (GK) Radiosurgery, an established treatment for metastatic brain tumors. Few dosimetric parameters have shown to predict RN, including tumor target volume, treatment dose, and V12 Gy (volume of normal brain receiving 12 Gy). Vascularity has yet to be explored as an independent predictor of RN. OBJECTIVE To evaluate the role of vascular overlap in GK-induced RN. METHODS All metastatic brain tumor patients treated with GK between 2014-2019 were retrospectively screened for post-treatment radiographic RN. Vascular overlap, defined by the MCA-ACA and MCA-PCA border regions, was determined by two blinded neurosurgeons and one radiation oncologist. Multivariate logistic regression analysis was performed to determine factors predictive of RN using variables determined significant by univariate analysis and clinical relevance. Covariates included V12 as a binary variable (≥8 vs. <8 cm3), vascular overlap, supratentorial location, and eloquent location. RESULTS 6% (20/321) of all metastatic brain tumor patients developed RN and were included for analysis, with the final cohort being 60% (12/20) female with a mean age of 59 years, comprising 77 lesions. V12 (≥8 cm3) showed a significant increase in risk of developing RN [OR = 8.18; (coef, 95% CI: 2.10 (0.49, 3.72), p=0.011)]. Conversely, vascular overlap showed a protective effect against RN [OR = 0.23 (-1.49 (-2.79, -0.19), p=0.024)], with a lower rate of RN in areas of vascular overlap (10%) than non-vascular overlap (26%). Neither supratentorial location [OR = 3.31 (1.20 (-0.76, 3.16), p=0.231)] nor location within eloquent brain [OR = 0.96 (-0.04 (-1.48, 1.39), p=0.95)] showed significance. CONCLUSION For the first time, we show that patients with metastatic brain lesions in anatomical regions of vascular overlap treated with GK are less likely to develop RN. Future work should validate these findings with the goal of optimizing radiation dosing to mitigate RN incidence and recurrence rates.

NIMG-33. HIGH-RESOLUTION SODIUM MRI OF HUMAN GLIOMAS AT 3T USING PHYSICS-BASED GENERATIVE AI

Abstract BACKGROUND Sodium neuroimaging is a promising technique for diagnosing and monitoring brain tumors, providing insights into microenvironment and metabolism. However, at 3T, it is limited by low signal-to-noise ratio and resolution, resulting in long acquisition times and low-quality images. To address these limitations, we developed a physics-informed generative adversarial network (GAN) approach for high-resolution sodium neuroimaging of brain tumors at 3T. METHODS 5,078 anatomical sequences from 1,330 brain tumor patients undergoing routine proton MRI were used to create a synthetic dataset with physics-based simulated artifacts, including B0 magnetic susceptibility artifacts, chemical shift artifacts, Nyquist aliasing artifacts, Gibbs artifacts, and low-resolution images, with Rician noise added during training to augment the dataset. By using multiple proton MRI contrasts, we hypothesized that the GAN model would learn to correct artifacts while preserving the inherent contrast information. We employed a transfer learning approach with a modified Pix2PixGAN architecture and an Attention-R2UNet generator. Twenty glioma patients consented to participate in this IRB-approved prospective study. Sodium and proton MRIs were acquired in the same sessions using a 3T Siemens scanner using a dual-tuned head coil, with a 3D spoiled gradient-echo sequence optimized for short TE. Sodium-proton exchanger (NHE1) expression was tested with immunohistochemistry from image-guided surgical biopsies. RESULTS High-resolution synthetic-sodium MR images were generated using the GAN model. The proposed method successfully reconstructed high-resolution synthetic-sodium MR images with improved SNR compared to traditional sodium images. Synthetic and native measurements were strongly correlated (R2=0.8539, P<0.0001). A significant correlation was seen between synthetic-sodium MR measurements and relative NHE1 tissue expression (ρ=0.5817, P=0.0036). CONCLUSION Results suggest that high-resolution synthetic-sodium MRI retains much of the inherent information from native sodium MR while accurately representing NHE1 expression. This approach could make high-resolution sodium neuroimaging at 3T feasible in the clinical environment, potentially improving diagnosis, monitoring, and treatment of brain tumors.

NIMG-56. MAGNETIC RESONANCE SPECTROSCOPY IN THE POST-TREATMENT METABOLIC CHARACTERIZATION OF BRAIN TUMORS OF GLIAL ORIGIN OF CENTRAL NERVOUS SYSTEM

Abstract BACKGROUND and Purpose Central Nervous System tumors have a very low incidence worldwide, however they constitute an important source of mortality and morbidity. Treatment for these types of tumors in adults may include surgery, radiosurgery, radiation therapy, chemotherapy, and targeted treatment. These treatments in brain tumors of glial origen in adults can produce changes in the pathophysiology of the tumor. The purpose of this study was to characterize the different metabolic patterns as effect of treatment and identify tumor recurrences. Materials and METHODS A prospective study was conducted with patients with low- and high-grade tumors treated, subjecting them to the single-voxel MRS and multivoxel MRSI protocol at 1.5 T. RESULTS Of the 44 patients included, 21 were histopathologically diagnosed as low-grade tumors and 23 as high-grade tumors. Of the low-grade tumors, 11 were caracterized as low-grade (mean Cho/NAA and NAA/Cr ratios 1.49 ((p=0.036) and 0.92 (p=0.038) respectively), 8 cases presented gliosis (mean Cho/NAA and NAA/Cr ratios 1.57 (p=0.028) and 1.36 (p=0.026) respectively), and 4 cases presented radiation necrosis (mean Cho/Cr ratios 2.14 (p=0.03)), (mean Cho/Cr and NAA/Cr ratios 1.25 (p=0.01) and 1.25 (p=0.00)) respectively). Furthermore, tumor recurrence that presented high Cho/NAA ratio were observed in 11 cases. Of the high-grade tumors, 13 were caracterized as high-grade (mean Cho/NAA and Cho/Cr ratios 2.24 (p=0.026) and 4.48 (p=0.026) respectively), 13 cases presented gliosis (mean Cho/NAA and NAA/Cr ratios 1.82 (p=0.028) and 0.64 (p=0.026)) respectively) and radiation necrosis was detected in 10 cases (mean Cho/Cr ratio 1.47 (p=0.03), (mean Cho/Cr and NAA/Cr ratios 2.25 (p=0.01) and 0.97 (p=0.00) respectively). Moreover, tumor recurrence that presented high Cho/NAA ratio were observed in 9 cases. CONCLUSION MRS and MRSI contribute to identifying the recurrences, to characterizing the different metabolic patterns as an effect of the treatment and differentiate between low and high grade tumors.

NCOG-26. THERAPEUTIC POTENTIAL OF FECAL MICROBIOME TRANSPLANT TO IMPROVE COGNITIVE DYSFUNCTION INDUCED BY CRANIAL IRRADIATION IN MICE

Abstract Radiation therapy (RT) is a crucial treatment for brain tumors, but radiation-induced cognitive dysfunction (RICD) affects 50-90% of patients, significantly impacting their quality of life. Evidence suggests that gut microbiome dysfunction may contribute to progressive cognitive dysfunction (CD). Prior studies in aging and stroke models show that fecal microbiome transplants (FMT) from healthy hosts can promote recovery and improve cognition. To investigate the link between RICD and the gut microbiome, we subjected mice to Sham/9Gy/15Gy cranial irradiation, followed by cognitive tests using the Y-maze and Novel Object Recognition Test (NORT) at various time points. Both 9Gy and 15Gy irradiation resulted in significant cognitive dysfunction, as indicated by altered performance in both tests at 7 and 30 days post-irradiation. Fecal samples were collected before irradiation and at 10 and 30 days post-RT. Microbial DNA was extracted, and the 16S rRNA gene was sequenced and analyzed using the bioinformatics visualization toolkit, ATIMA. Significant gut dysbiosis was observed in both 9Gy and 15Gy irradiated mice compared to pre-irradiation samples, with the 15Gy group showing more pronounced and consistent changes in fecal microbiome diversity, particularly at 30 days post-RT. We hypothesized that FMT from healthy hosts (non-radiated mice) could prevent or ameliorate RICD by modulating microbial, metabolomic, and immunologic profiles. To test this, a separate cohort of mice received 15Gy cranial irradiation and FMT via oral gavage. After a 20-day post-irradiation period, cognitive and gut permeability tests were conducted. The FMT group exhibited significantly improved gut permeability and cognitive performance compared to controls. Our findings suggest that gut dysbiosis plays a crucial role in RICD and that FMT may be a potential strategy to mitigate RICD and improve the quality of life in brain tumor patients undergoing cranial RT.

RBIO-09. EFFECTS OF RADIATION ON THE HIPPOCAMPUS AND HIPPOCAMPAL NEUROGENESIS: A SYSTEMATIC REVIEW OF INJURY MECHANISMS AND INTERVENTION STRATEGIES

Abstract PURPOSE To understand how radiation affects the hippocampus and hippocampal neurogenesis. Radiotherapy is a common modality in the treatment of brain tumors that targets malignant cells with radiation. However, unintended iatrogenic injury may extend to adjacent healthy cells. The hippocampus is a particular area of concern, given its vital role in memory and learning and capacity for neurogenesis. METHODS We searched the PubMed, Embase, and Web of Science databases for studies assessing the effects of radiation on the hippocampus and hippocampal neurogenesis, adhering to PRISMA guidelines. Animal studies were evaluated according to the ARRIVE guidelines for pre-clinical studies. The SYRCLE risk of bias tool was utilized to examine potential bias among studies. Study characteristics, including study design, sample size, experimental methods, radiation dose, and results were collected and synthesized. RESULTS Ninety-two studies met inclusion criteria, and the majority of studies investigated rat and/or mouse models (n = 91, 98.9%). Across studies, cranial irradiation was consistently found to be associated with detrimental effects on hippocampal function and structure through molecular alterations to gene and protein expression, neuronal cell apoptosis, disruption of dendritic spines, and initiation of pro-inflammatory processes. The consequences for neurogenesis were mostly focused on the dentate gyrus of the hippocampus. These effects manifested as cognitive deficits in hippocampus-dependent tasks such as memory and learning. Behavioral (e.g., running) and pharmacological (e.g., PPARα agonists) interventions against the deleterious effects of radiation suggest the potential to address radiation-induced hippocampal disruption and cognitive deficits. The majority of studies were found to have an unclear risk of bias. CONCLUSIONS This systematic review highlights the effects of cranial radiation on hippocampal neurogenesis and their association with disruptions in memory and learning. Future research should continue to focus on delivering radiotherapy that spares susceptible regions in the brain, preserving patients’ cognitive function and quality of life.

Advances in Carbon Dot Based Enhancement of Photodynamic Therapy of Tumors.

Photodynamic therapy has advantages of high selectivity, less invasiveness, and high lethality for cancer cells compared with traditional treatment methods. However, some problems have hindered the development of photodynamic therapy, such as limited penetration depth, lack of oxygen, and toxicity. Carbon dots are widely used in the imaging and treatment of tumors due to their excellent optical and physicochemical properties, so effective methods have been explored to address the issues in photodynamic therapy via carbon dots. This review aims to elucidate the role of carbon dots in photodynamic therapy of cancer. Moreover, we summarize and discuss some strategies to harness carbon dots to enhance photodynamic therapy. Finally, we summarize many cancer synergistic therapeutic modalities involving carbon dots such as chemodynamic therapy, photothermal therapy, and immunotherapy in combination with photodynamic therapy to achieve more effective and safer treatments.

Bioorthogonal Janus microparticles for photothermal and chemo‐therapy

AbstractBioorthogonal chemistry, recognized as a highly efficient tool in chemical biology, has shown significant value in cancer treatment. The primary objective is to develop efficient delivery strategies to achieve enhanced bioorthogonal drug treatment for tumors. Here, Janus microparticles (JMs) loaded with cyclooctene‐modified doxorubicin prodrug (TCO‐DOX) and tetrazine‐modified indocyanine green (Tz‐ICG) triggers are reported. Besides activating TCO‐DOX, Tz‐ICG is also a photothermal agent used in photothermal therapy (PTT), enabling the simultaneous use of biorthogonal chemotherapy and PTT. Additionally, the DOX could be significantly reduced in systemic toxicity with the modification of cyclooctene. Thus, the developed drug‐carrying JMs system exhibits effective tumor cell killing in vitro and effectively inhibits tumor local progress and distant lung metastasis after postoperative treatment with good safety. These results demonstrate that the prepared JMs provide a paradigm for bioorthogonal prodrug activation and localized delivery, and hold great promise for cancer therapy as well as other related applications.

The impact of surgical treatment of benign ovarian tumors on the reproductive health of women, taking into account the International Classification of Functioning

The article presents a systematic analysis of studies evaluating the impact of surgical treatment of benign ovarian tumors on reproductive health, taking into account the criteria stated by the International Classification of Functioning, Disability and Health. To identify articles, foreign and domestic scientific databases were used (PubMed, Cochrane, eLibrary). After the initial identification of 704 scientific publications, 46 articles were selected using inclusion and exclusion criteria.The conducted systemic analysis allows us to formulate the conclusion that surgical interventions performed for benign ovarian tumors contribute to damage to ovarian tissue, and as a result, a decrease in the ovarian reserve of patients, which is associated with impaired fertility. A number of authors have demonstrated some recovery of anti-Mullerian hormone (AMH) levels 3-12 months after surgery. A significant portion of the studies have demonstrated a more pronounced postoperative decrease in AMH rates in patients with endometriomas compared with women operated on for non-endometrioid ovarian tumors. Lower AMH rates were noted in women with bilateral surgeries for bilateral ovarian tumors compared to patients who had unilateral surgeries. The performed systemic analysis showed higher postoperative AMH rates in patients with intraoperative suture hemostasis in comparison with the use of bipolar energy; in addition, there is a relationship between the number of coagulations and the severity of the decrease in AMH rates. In a few studies, it was noted that patients who underwent surgical treatment of ovarian tumors experienced an earlier onset of menopause. In connection with these possible functional disorders, further clinical studies of a high level of evidence are needed, aimed at developing effective strategies for preserving the functioning of the reproductive system after surgical treatment of benign ovarian tumors.

Albumin-Chaperoned Deep-NIR Triarylmethane Dyes for High-Contrast In Vivo Imaging and Photothermal Therapy.

Fluorophores absorbing/emitting in the deep near-infrared (deep NIR) spectral region, that is, 800 nm and beyond, hold great promise for in vivo bioimaging, diagnosis, and phototherapy due to deeper tissue penetration. The bottleneck is the lack of bright, stable, and readily synthesized deep NIR fluorophores. Here, it is reported that the albumin-chaperon strategy is a viable one-for-all strategy to address these difficulties. A focused library of deep-NIR absorbing dyes (EA5) is easily synthesized via a two-step cascade. They are neither very stable nor bright in phosphate bufferdue to a propeller-type flexible scaffold. Through screening, EA5_c3 is found to exhibit a high affinity toward bovine serum albumin (BSA). Binding-associated structural rigidification resulted in a gigantic 26-fold fluorescence enhancement. The albumin chaperone also greatly improved the stability of EA5_c3 by shielding the bisbenzannulated triarylmethane core from nucleophilic or oxidative species. The resulting EA5_c3@BSA exhibits high biocompatibility. It offered high-resolution vasculature, lymph systems, tumors, and other tissue imaging with its bright deep NIR emission. At the same time, it exhibits prominent potential in photoacoustic imaging and photothermal treatment of subcutaneous and orthotopic breast tumors. These findings provide insights into robust and high-performance fluorophores with deep NIR regions for theranostic against aggressive cancers.

Clinical Presentation, Treatment, and Outcomes of Pediatric Brain Tumors: A 5-Year Single-Center Experience in Istanbul

Background: Brain tumors are the most common solid tumors in childhood. With the help of increased clinical awareness, improvements in imaging methods, and the identification of molecular characteristics, advances have been made in both diagnosis and treatment. Objectives: In our study, we aimed to discuss the childhood brain tumor cases followed in our clinic, along with their clinical and epidemiological features and treatment outcomes. Methods: The study group comprised children younger than 18 years old who were followed in the Pediatric Hematology and Oncology Clinic of Istanbul Medical Faculty and diagnosed with a brain tumor over the past 5 years (2018 - 2023). Symptoms, age at diagnosis, treatment options (surgery, radiotherapy, chemotherapy), and side effects were reviewed retrospectively. Results: Thirty children were diagnosed with brain tumors. Of the patients, 14 (47%) were male and 16 (53%) were female. The mean age of the children was 8.8 ± 3.1 years, and the mean age at diagnosis was 65.6 ± 37.7 months. The most common symptom was vomiting (40%). The mean duration between the onset of symptoms and diagnosis was 3.8 months, with a median of 1 month. Of the patients, 60% were diagnosed with glial tumors and 40% with non-glial tumors. Gross total resection (GTR) was performed in 26% of patients, subtotal resection (STR) in 37%, and 37% of patients did not undergo surgery. Seventy-seven percent of the patients received chemotherapy, and 57% received radiotherapy. Of the patients, 57% were considered responsive to treatment (complete/partial), 30% had stable disease, and 13% had progressive disease. The overall brain tumor mortality rate in our clinic was 13%. While 73% of our 26 patients had no or mild neurological deficits, 27% had moderate to severe disabilities (gait impairment, hearing impairment, visual impairment). Conclusion: Although the sample size was limited, it may be speculated that the surgery rate was low and long-term side effects were notable. Insufficient surgical resection can affect the treatment response and increase the risk of neurological sequelae and functional impairment. Molecular profiling should be expanded, and a palliative care team should be involved as early as possible to address long-term side effects and improve the quality of life for patients.

The concept of the liquid biopsy in the treatment of malignant eye tumours

The liquid biopsy is acutting-edge technique that involves analysing non-solid biological tissues, primarily blood but also ocular fluids, for the presence of cancer cells or fragments of tumour DNA. Unlike traditional biopsies, liquid biopsies are usually minimally invasive and can be performed more frequently, enabling continuous monitoring of disease progression and treatment efficacy. This article (and the associated series of articles) outlines the key developments in liquid biopsy, which include the analysis of circulating tumor DNA (ctDNA), circulating tumor cells (CTC) and exosomal RNA and protein biomarkers. Techniques, such as digital droplet PCR and next-generation sequencing (NGS) have made it possible to detect even very low levels of ctDNA, which is crucial for early cancer detection and monitoring minimal residual disease. The detection of rare CTCs is enhanced by techniques, such as microfluidic devices and immunomagnetic separation. Multiomic approaches, whereby exosomal RNA, protein and ctDNA analyses are combined, help to create amore comprehensive picture of tumour biology, including insights into tumour heterogeneity, potentially leading to better diagnostic and prognostic tools and helping to predict treatment response and resistance. The challenges of liquid biopsy application, which will be described in the following article, include (a)standardization, (b)cost and accessibility, (c)validation and clinical utility. However, the liquid biopsy represents apromising frontier in the application of precision ocular oncology, with ongoing research likely to expand its applications and improve its effectiveness in the coming years.

Enhancing Tumor Targeted Therapy: The Role of iRGD Peptide in Advanced Drug Delivery Systems

Chemotherapy remains the primary therapeutic approach in treating cancer. The tumor microenvironment (TME) is the complex network surrounding tumor cells, comprising various cell types, such as immune cells, fibroblasts, and endothelial cells, as well as ECM components, blood vessels, and signaling molecules. The often stiff and dense network of the TME interacts dynamically with tumor cells, influencing cancer growth, immune response, metastasis, and resistance to therapy. The effectiveness of the treatment of solid tumors is frequently reduced due to the poor penetration of the drug, which leads to attaining concentrations below the therapeutic levels at the site. Cell-penetrating peptides (CPPs) present a promising approach that improves the internalization of therapeutic agents. CPPs, which are short amino acid sequences, exhibit a high ability to pass cell membranes, enabling them to deliver drugs efficiently with minimal toxicity. Specifically, the iRGD peptide, a member of CPPs, is notable for its capacity to deeply penetrate tumor tissues by binding simultaneously integrins ανβ3/ανβ5 and neuropilin receptors. Indeed, ανβ3/ανβ5 integrins are characteristically expressed by tumor cells, which allows the iRGD peptide to home onto tumor cells. Notably, the respective dual-receptor targeting mechanism considerably increases the permeability of blood vessels in tumors, enabling an efficient delivery of co-administered drugs or nanoparticles into the tumor mass. Therefore, the iRGD peptide facilitates deeper drug penetration and improves the efficacy of co-administered therapies. Distinctively, we will focus on the iRGD mechanism of action, drug delivery systems and their application, and deliberate future perspectives in developing iRGD-conjugated therapeutics. In summary, this review discusses the potential of iRGD in overcoming barriers to drug delivery in cancer to maximize treatment efficiency while minimizing side effects.

Discovery of SZJK-0421: A Novel Potent, Low Toxicity, Selective Second Generation of CRM1 Inhibitor for the Treatment of Both Hematological and Solid Tumors.

Nuclear export factor chromosome region maintenance 1 (CRM1) mediated the transport of various growth-regulatory proteins and was frequently overexpressed in many hematologic and solid tumors. Selinexor (KPT-330) was the only approved CRM1 inhibitor, but the severe gastrointestinal and central nervous system toxicities limited its clinical application. In this manuscript, a series of novel second-generation CRM1 inhibitors were designed, in which SZJK-0421 was a more reversible inhibitor than KPT-330. The treatment of various tumor cells with SZJK-0421 significantly inhibited the function of CRM1. SZJK-0421 displayed good liver microsome stabilities and pharmacokinetic properties. Most importantly, SZJK-0421 reduced the direct damage to the gastrointestinal mucosa, and the brain plasma distribution ratio of SZJK-0421 was very low in Sprague-Dawley (SD) rats (3%), which avoided gastrointestinal reactions such as central nausea and vomiting caused by large permeability of blood-brain barrier. In addition, SZJK-0421 exhibited strong anticancer efficacy in xenograft models of both solid and hematological tumors.

Perioperative Observations and Outcome in Surgical Treatment of Malignant Peripheral Nerve Sheath Tumors

Perioperative Observations and Outcome in Surgical Treatment of Malignant Peripheral Nerve Sheath Tumors

Modular Assembly of Photoactive Lipid Nanoparticles on Red Blood Cells toward Enhanced Phototherapy Efficacy.

Photodynamic therapy has been developed as a promising treatment for malignant tumors, which inspires research into photosensitizers. However, the therapeutic efficacy of individual photosensitizers is often hampered by the physiological environment. The assembly of biological materials with synthetic molecules offers a strategy to enhance functionality while improving tolerance to varying physiological conditions. Herein, we present a biohybrid system for enhanced phototherapy efficacy through a simple two-step assembly process. Photoactive lipid nanoparticles were assembled based on synthesized conjugated molecules and lipophilic prodrugs, which were then modularly assembled with red blood cells (RBCs). Driven by hydrophobic and electrostatic interactions, hydrophobic conjugated molecules were efficiently incorporated into the RBCs, while lipophilic prodrugs were simultaneously inserted into the cell membranes. The engineered RBCs harnessed the natural oxygen transport capability, enabling the internal conjugated molecules to effectively produce reactive oxygen species (ROSs) even under oxygen-poor conditions. Meanwhile, the use of ROS-cleavable linkers in prodrugs enhanced drug release for chemotherapy, which is a perfect complement to photodynamic therapy. In vitro and in vivo experiments proved the improved phototherapy efficacy of the biohybrid system. Furthermore, the changes in aggregation directed Förster resonance energy transfer between conjugated molecules and fluorescent drugs provided a mechanism to track drug release from engineered RBCs. Therefore, the modular assembly of biohybrid systems can offer multiple functionalities required for phototherapy, on-demand drug release, and imaging.

The effect of melatonin and probiotics on radiation-induced enteritis in experimental rat models

Radiotherapy plays an important role in the treatment of tumors, and enteritis is a common side effect of this therapy. The aim of present study was to evaluate the protective effect of melatonin and probiotics on radiation-induced intestinal tissue damage in rats. Histopathological, biochemical and microbiological samples were examined. Thirty-two Wistar Albino rats were randomly distributed into four groups: the control group, only radiotherapy (RT) group, radiotherapy plus melatonin (RT + MEL) groups and radiotherapy plus probiotics (RT + PROB) groups. The abdominal-pelvic region of the experimental rat was irradiated with in a single dose of 16 Gy. The melatonin was administered at a single dose of 50 mg/kg through intraperitoneal injection, 15 min before radiation exposure. The probiotic was administered orally every day to the rats for 5 days starting before radiotherapy. There was a statistically significant changes in histopathological (villus atrophy, mitotic activity, apoptotic index, goblet cell swelling, degenerative changes, atypia) and biochemical (oxidant and antioxidant status, IL-1β, IL-6 and TNF- α levels) parameters in the small intestine in the radiotherapy group G2 compared to the G1 control group (p < 0.05). However, a significant decrease was observed with the administration of probiotics and melatonin (p < 0.05). In addition, although positive bacterial growth was detected in the mesenteric lymph node of all rats in the radiotherapy group, there was no statistically significant difference between all groups (p > 0.05). Melatonin and probiotics were found to have a potent radioprotective effect against radiotherapy-induced acute small intestinal tissue damage. However, their superiority over each other was not observed.

Current Trends in the Surgical Management of Yolk Sac Tumors

Mediastinal yolk sac tumors (YST) constitute a highly malignant subtype of primary non-seminomatous germ cell tumors, which are often locally advanced and unresectable at diagnosis. Due to their rarity and aggressiveness, there is not yet a standard optimal treatment approach. A widely employed multimodal strategy involves neoadjuvant cisplatin-based combination chemotherapy followed by consolidation surgery. Tumor infiltration into the lungs and adjacent cardiovascular structures is common, such that surgical intervention typically requires extensive resections, performed either by sternotomy or thoracotomy. For this review, we extensively searched the PubMed and Embase medical databases, identifying articles describing surgical treatment of mediastinal yolk sac tumors. The current literature provides limited details regarding the utilized surgical procedures, leaving clinicians without comprehensive guidance about the demanding nature of these resections. Here, we present a narrative description of the range of current surgical procedures. By highlighting these techniques, we provide a comprehensive overview of the current surgical landscape, thereby helping clinicians understand the potential complexities and considerations involved in managing these rare and aggressive tumors.