Treatment Of Cancer Research Articles

Tumour cell-released autophagosomes promote lung metastasis by upregulating PD-L1 expression in pulmonary vascular endothelial cells in breast cancer.

Establishing an immunosuppressive premetastatic niche (PMN) in distant organs is crucial for breast cancer metastasis. Vascular endothelial cells (VECs) act as barriers to transendothelial cell migration. However, the immune functions of PMNs remain unclear. Tumour cell-released autophagosomes (TRAPs) are critical modulators of antitumour immune responses. Herein, we investigated the mechanism through which TRAPs modulate the immune function of pulmonary VECs in lung PMN in breast cancer. Immortalised mouse pulmonary microvascular endothelial cells were incubated with TRAPs in vitro. RNA sequencing, flow cytometry, and western blotting were employed to assess immunosuppressive function and mechanism. In vivo, TRAP-trained and autophagy-deficient tumour mice were used to detect immunosuppression, and high-mobility group box 1 (HMGB1)-deficient TRAP-trained and TLR4 knockout mice were utilised to investigate the underlying mechanisms of pulmonary VECs. Additionally, the efficacy of anti-programmed cell death ligand-1 (PD-L1) immunotherapy was evaluated in early tumour-bearing mice. HMGB1 on TRAPs surfaces stimulated VECs to upregulate PD-L1 via a TLR4-MyD88-p38/STAT3 signalling cascade that depended on the cytoskeletal movement of VECs. Importantly, PD-L1 on TRAP-induced VECs can inhibit T cell function, promote lung PMN immunosuppression, and result in more pronounced lung metastasis. Treatment with anti-PD-L1 reduces lung metastasis in early stage tumour-bearing mice. These findings revealed a novel role and mechanism of TRAP-induced immunosuppression of pulmonary VECs in lung PMN. TRAPs and their surface HMGB1 are important therapeutic targets for reversing immunosuppression, providing a new theoretical basis for the treatment of early stage breast cancer using an anti-PD-L1 antibody.

The use of focal therapy for the treatment of prostate cancer in Canada

Introduction: Focal therapy is an emerging treatment for localized prostate cancer. The objectives of this review were to: 1) review how focal therapies are regulated and approved; 2) summarize the scope and quality of the literature regarding safety, efficacy, and side-effects; and 3) outline ongoing clinical trials of focal therapy in Canada. Methods: Using the PRISMA framework for scoping reviews, we searched PubMed, Embase, and Cochrane from 2021–2024, complementing Hopstaken et al's search up to 2020. We focused on studies reporting functional and oncologic outcomes. Additionally, we examined the FDA database for regulatory details and ongoing trials in Canada via ClinicalTrial.gov. Results: FDA approval for prostate tissue ablation was granted to high-intensity focused ultrasound (HIFU) in 2015 via the de novo pathway; other therapies followed the 510(k) route, citing equivalence to predicate devices. Most studies are in early stages, primarily single-arm, prospective cohort designs. Oncologic outcomes like cancer detection and survival rates, alongside functional data, such as adverse events and erectile function, were assessed. Recurrence-free survival at 48 months ranged from 58–92%, pad-free rates were greater than 95%, and rates of new-onset erectile dysfunction were variable, ranging from no change to 50%. Rates of serious adverse events (SAEs) were low, ranging from 0–14%. Three Canadian clinical trials are actively enrolling participants, and five private clinics were found offering private HIFU, irreversible electroporation (IRE), or transurethral ultrasound ablation (TULSA). Conclusions: Focal therapy technologies have gained regulatory approval for prostate tissue ablation, and, aside from provincial support for cryoablation in Alberta, are available to Canadians through private payment or clinical trials. Many studies demonstrate promising cancer control and impressive functional outcomes but are limited by their short followup and lack of comparator group. Clinical trial or registry participation should be prioritized to ensure an evidence-based integration into current prostate cancer treatment approaches.

Advancements in prostate zone segmentation: integrating attention mechanisms into the nnU-Net framework

Abstract Prostate cancer is one of the most lethal cancers in the world. Early diagnosis is essential for successful treatment of prostate cancer. Segmentation of prostate zones in magnetic resonance images is an important task in the diagnosis of prostate cancer. Currently, the state-of-the-art method for this task is no-new U-Net. In this paper, a method to incorporate the attention U-Net architecture into no-new U-Net is proposed and compared with a classical U-net architecture as research. The experimental results indicate that there is no significant statistical difference between the proposed modification of no-new U-Net with the generalizability of the attention mechanism or the ability to achieve more accurate results. Moreover, two novel workflows are proposed for prostate segmentation, transitional zone segmentation and peripheral zone calculation workflow, and separate models for peripheral zone and transitional zone segmentation workflow. These workflows are compared with a baseline single peripheral zone and transitional zone segmentation model workflow. The experimental results indicate that separate models for peripheral zone and transitional zone segmentation workflow generalizes better than the baseline between data sets of different sources. In peripheral zone segmentation separate models for peripheral zone and transitional zone segmentation workflow achieves 1.9% higher median Dice score coefficient than the baseline workflow when using the attention U-Net architecture and 5.6% higher median Dice score coefficient when using U-Net architecture. Moreover, in transitional zone segmentation separate models for peripheral zone and transitional zone segmentation workflow achieves 0.4% higher median Dice score coefficient than the baseline workflow when using the attention U-Net architecture and 0.7% higher median Dice score coefficient when using U-Net architecture. Meanwhile, prostate segmentation, transitional zone segmentation and peripheral zone calculation workflow generalizes worse than the baseline. In peripheral zone segmentation prostate segmentation, transitional zone segmentation and peripheral zone calculation workflow achieves 4.6% lower median Dice score coefficient than the baseline workflow when using the attention U-Net architecture and 3.6% lower median Dice score coefficient when using U-Net architecture. In transitional zone segmentation prostate segmentation, transitional zone segmentation and peripheral zone calculation workflow achieves a similar median Dice score coefficient to the baseline workflow.

Effects and mechanisms of Helicobacter pylori on cancers development and immunotherapy

Tumor immunotherapy has been widely used in clinical treatment of various cancers. However, some patients of these cancers do not respond to immunotherapy effectively. And H. pylori infection has been considered to be related to the efficacy of immunotherapy. This review aims to summarize the different effects and mechanisms of H. pylori infection on immunotherapy in different kinds of cancers. We searched the relevant literature on H. pylori and tumor immunotherapy, and summarized to form a review. Generally, H. pylori infection plays a role in affecting kinds of cancers’ development, besides gastric cancer. Current evidence suggests that H. pylori infection may reduce the efficacy of immunotherapy for colorectal cancer, non-small cell lung cancer and melanoma, but due to the lack of sufficient evidence, more data is needed to prove that. While for gastric cancer, the effects remain controversial. The H. pylori regulation effects and metabolisms involved in systematic related cancers should be paid attention to. Whether H. pylori should be eradicated when immunotherapy performed may be a critical consideration for some kinds of tumors.

CACA guidelines for holistic integrative management of prostate cancer

Prostate cancer (PC) is an epithelial malignancy occurring in the prostate. PC ranks second in incidence among all male malignancies globally by the latest statistics from the World Health Organization. Notably, China has seen a more rapid increase in PC incidence compared to developed European and American nations. By 2022, the newly reported cases and deaths due to PC in China increased to 134,200 and 47,500, respectively. Thus, early diagnosis and standardized treatment for prostate cancer in China remain far-reaching objectives. Burgeoning research on advanced PC and castration-resistant prostate cancer in recent years have paved the way for a new era of integrated treatment methods including novel endocrine drugs, chemotherapy, targeted therapy, and immunotherapy. Future therapies involve precision treatment guided by genetic testing and individualized integrated treatment as part of a multidisciplinary integrated diagnosis and treatment model for PC. The Genitourinary Oncology Committee of the China Anti-Cancer Association (CACA-GU) has invited multidisciplinary experts across fields including surgery, oncology, pathology, radiology, herbal medicine, physiatry, and psychology to collaboratively write, discuss, and revise guidelines on managing PC. The CACA Guidelines for Holistic Integrative Management of Prostate Cancer includes epidemiology, screening and diagnosis, treatment for localized PC, diagnosis and treatment of PC recurrence after radical prostatectomy, management of metastatic PC, traditional Chinese medicine diagnosis and treatment of PC, and rehabilitation from PC. This guideline aims to standardize the clinical diagnosis and treatment management of PC in China. It is more aligned with China’s clinical practice, highlights Chinese characteristics, and bears significant clinical importance.

The Role of Contrast-Enhanced Imaging Methods in Breast Cancer Early Diagnostics and Treatment Planning

Оn March 27, 2023, а multidisciplinary Advisory Board meeting was held in Moscow with the participation of Е.V. Artamonova, Е.А. Busko, V.V. Didenko, А.D. Zikiryakhodzhaev, М.S. Karpova, G.Е. Kvetenadze, P.V. Krivorot’ko, М.L. Mazo, А.V. Petrovsky, О.S. Puchkova, S.V. Serebryakova under the chairmanship of I.Е. Tyurin and N.I. Rozhkova. The participants discussed different issues of early diagnostics and treatment planning of breast cancer. We present the conclusion made by the Advisory Board.

Retrospective analysis of multiparametric MRI in predicting complete pathologic response of neo-adjuvant chemotherapy in bladder cancer

BackgroundMuscle invasive bladder cancer (MIBC) treatment combines systemic therapy and radical cystectomy (RC) or local (chemo-)radiotherapy. Response to systemic therapy is an important outcome predictor but is difficult to assess pre-operatively.MethodsWe analyzed multiparametric MRI (mpMRI) in consecutive MIBC patients receiving cisplatin-based neo-adjuvant chemotherapy at our institution. Two readers, blinded for pathological outcome, independently scored mpMRI before and after 2 and 4 cycles using both a qualitative 3-step method and nacVI-RADS. We analyzed accuracy of mpMRI scores to predict pathologic complete response (pCR) and inter-observer agreement.ResultsWe analyzed 46 patients receiving NAC, 6 patients did not undergo RC after NAC and were excluded. Eleven out of 40 (28%) patients showed a pCR. mpMRI could be assessed in over 90% of patients. Radiologic complete response (rCR) using both methods was significantly associated with pCR, with an overall specificity of 96% and sensitivity of 36% and a high inter-observer agreement. rCR as assessed by the 3-step score was significantly associated with disease free survival (DFS) benefit.ConclusionThe use of nacVI-RADS can predict pCR after NAC with high specificity but low sensitivity and a high inter-observer agreement. A 3-step score adds value in determining local residual disease, rCR assessed by this method could correlate with DFS benefit. mpMRI scores should be prospectively assessed in future trials of multimodal management of MIBC and can be a predictive asset in routine clinical management.

Yoga Intervention and Inflammatory Homoeostasis in Breast Cancer Patients

Objectives: Yoga, renowned for its ability to maintain physical, mental and spiritual well-being, has recently gained prominence as a supportive therapy during conventional breast cancer (BC) treatment. This paradigm shift reflects a growing trend of people embracing yoga to enhance their overall health and aid in managing BC. The objective of this study was to determine the yoga intervention and inflammatory homoeostasis in newly diagnosed BC patients. Materials and Method: This study recruited 44 newly diagnosed BC patients at stages II, III and IV (without distant metastasis or other inflammatory diseases), all admitted for neoadjuvant chemotherapy followed by surgery. A prospective non-randomised control design was employed. Baseline assessments were conducted before the first chemotherapy cycle, with follow-ups before the 2nd and 3rd chemotherapy cycles, before surgery, and 2 months post-surgery. The outcome was compared with the control group. Results: The study showed significant within-subject effects in the yoga intervention group on serum tumour necrosis factor-alpha, interleukin (IL)-1-beta and IL-6 levels, while no significant changes were observed in the control group. Although between groups did not show statistically significant, the mean values indicated a consistent downregulation of proinflammatory markers over time in the yoga group. Conclusion: Incorporating yoga as a complementary therapy alongside conventional BC treatment significantly improved the health outcomes of BC patients by modulating proinflammatory markers.

Myricetin inhibits CYP3A4, GST, and MRP1 in hepatic cancer cells

AbstractHerbal and nutritional supplements are widely used to prevent and treat many diseases, including cancer. Tumor cells modify metabolic enzyme systems like CYP3A4 and GST. They also overexpress MRP1, an ATP-binding cassette transporter subfamily G (ABCG2) member. Drug efflux may increase, reducing tumor cell drug accumulation and developing drug resistance that leads to significant obstacles in cancer care. Natural products' ability to overcome cancer's multidrug resistance is interesting. Their ability to affect several targets makes them valuable in addressing drug resistance from diverse approaches. The potential of natural flavonoid; Myricetin (MYR) to modulate CYP3A4, GST, and MRP1 activity and expression in hepatic cancer cells was evaluated to prove its targeting and preventing these pathways of multidrug resistance. The cell proliferation of MYR was determined using an MTT assay. Specific enzyme assays, efflux assay, and gene expression using RT-PCR were used to evaluate MYR effect in hepatic cell lines HepG-2 and Huh-7. MYR has a noteworthy cytotoxic effect compared to doxorubicin (DOX) with IC50 > 100 μM in HepG-2 and Huh-7 cells. MYR showed potent inhibition of CYP3A4 and GST enzyme activity and MRP1 efflux function and downregulated their gene expression in a dose-dependent manner in both cells. MYR100 dose was the most significant effective dose. MRY100 decreased CYP3A4 activity by 67.5% (P < 0.05) and 55% (P < 0.01) and downregulated the gene by 0.2-fold (P < 0.001) and 0.3-fold (P < 0.001) in HepG-2 and Hub-7 cells, respectively. After treatment with MRY100, GST activity decreased significantly in both cells, reaching 47.6% (P < 0.001) and 33.2% and GST gene downregulation was 0.12 and 0.21-fold (P < 0.001). MRY100 inhibited MRP1 efflux pump 2.3 times (P < 0.001) and 1.9 times (P < 0.001) more effectively than PC, resulting in a 0.23-fold and 0.12-fold downregulation of MRP1 genes in HepG-2 and Hub-7 cells. The result will validate the use of MYR to interact with the metabolism phases and could be used as adjuvant therapy in cancer prevention and treatment approaches.

An engineered model of metastatic colonization of human bone marrow reveals breast cancer cell remodeling of the hematopoietic niche

Incomplete understanding of metastatic disease mechanisms continues to hinder effective treatment of cancer. Despite remarkable advancements toward the identification of druggable targets, treatment options for patients in remission following primary tumor resection remain limited. Bioengineered human tissue models of metastatic sites capable of recreating the physiologically relevant milieu of metastatic colonization may strengthen our grasp of cancer progression and contribute to the development of effective therapeutic strategies. We report the use of an engineered tissue model of human bone marrow (eBM) to identify microenvironmental cues regulating cancer cell proliferation and to investigate how triple-negative breast cancer (TNBC) cell lines influence hematopoiesis. Notably, individual stromal components of the bone marrow niche (osteoblasts, endothelial cells, and mesenchymal stem/stromal cells) were each critical for regulating tumor cell quiescence and proliferation in the three-dimensional eBM niche. We found that hematopoietic stem and progenitor cells (HSPCs) impacted TNBC cell growth and responded to cancer cell presence with a shift of HSPCs (CD34+CD38-) to downstream myeloid lineages (CD11b+CD14+). To account for tumor heterogeneity and show proof-of-concept ability for patient-specific studies, we demonstrate that patient-derived tumor organoids survive and proliferate in the eBM, resulting in distinct shifts in myelopoiesis that are similar to those observed for aggressively metastatic cell lines. We envision that this human tissue model will facilitate studies of niche-specific metastatic progression and individualized responses to treatment.

Painful Realities: Navigating the Complexities of Head and Neck Cancer Pain.

Head and neck cancer (HNC) and its treatments can cause significant pain, which can profoundly impact patients' quality of life and treatment outcomes. Understanding the full scope of HNC pain is essential for effective management and improved patient care. This review aims to comprehensively analyze the multifaceted nature of pain experienced by individuals with HNC, including its various etiologies and management strategies. HNC pain can arise from tumor extent, treatment-related toxicity, or comorbid conditions. The pathophysiology involves complex interactions between nociceptive, neuropathic, and inflammatory mechanisms. Optimal pain control requires a multimodal patient-tailored approach utilizing both pharmacological and non-pharmacological therapies. Enhancing our understanding of HNC pain and optimizing its management is imperative for improving the overall well-being and treatment outcomes of affected individuals. Future research should focus on understanding detailed pain mechanisms, with the goal of developing personalized pain management strategies and exploring novel therapeutic targets. By implementing comprehensive approaches to HNC pain management, healthcare providers can better support patients through their cancer treatment journey.

A comparison of the acoustic waves generated in proton and carbon ion therapy

Hadron therapy, which employs particles such as protons and carbon-ions, is a promising method of cancer treatment due to its unique ability to deliver maximum energy at the Bragg peak near the tumor, sparing surrounding healthy tissue. Ionoacoustic waves, generated by thermal expansion from electronic collisions and localized heating, can be detected to optimize dose delivery and verify particle range, thus improving treatment precision. These waves offer a unique opportunity for comparative studies of different particle therapies. In this study, a mathematical model and computational simulations are used to compare the characteristics of ionoacoustic waves generated in tissue by proton and carbon-ion beams. In particular, we assess the impact of the nuclear fragmentation tail on the ionoacoustic signals generated in carbon-ion therapy. Our approach will allow us to make some important observations to study the comparative effects of proton and carbon-ion therapy. The aim of this work is to perform a comprehensive comparative analysis of ionoacoustic waves from proton and carbon-ion treatments, focusing on their potential for in-vivo range verification. This research addresses the current gap in understanding the use of ionoacoustic signals for range verification in ion beam therapy, which is critical given the growing clinical application of carbon ion therapy and its under-explored acoustic properties. This study pioneers the feasibility of using acoustic imaging from carbon-ion beams to detect the Bragg peak position and measure tumor dose in real-time. Carbon-ion dose mapping and relative biological effectiveness (RBE) assessment can be facilitated by real-time signal monitoring. Our study aims to significantly advance the field by addressing the lack of a verification technique for carbon-ion beams, focusing on the considerable impact of the nuclear fragmentation tail on ionoacoustic signal waveforms, which provides crucial insights into the unique energy deposition properties of carbon-ions.

Severe bleeding events among critically ill patients with haematological malignancies

BackgroundBleeding events are common complications in critically ill patients with haematological malignancies. The objective of this study was to assess the incidence and identify determinants of ICU-acquired severe bleeding events in critically ill patients with haematological malignancies. We conducted a single-center retrospective study including all adult patients with a history of haematological malignancy requiring unplanned ICU admission over a 12-year period (2007–2018). The primary endpoint was the occurrence of ICU-acquired (i.e. after the first 24 h in the ICU) severe bleeding events, as defined as grades 3 or 4 of the World Health Organization classification.ResultsA total of 1012 patients were analysed, mainly with a diagnosis of lymphoma (n = 434, 42.9%) and leukaemia or myelodysplastic syndrome (n = 266, 26.3%). Most patients were recently diagnosed (n = 340, 33.6%) and under active cancer treatment within the last 3 months (n = 604, 59.7%). The main cause for admission was infection (n = 479, 47.3%), but a significant proportion of patients were admitted for a primary haemorrhage (n = 99, 10%). ICU-acquired severe bleeding events occurred in 109 (10.8%) patients after 3.0 days [1.0–7.0] in the ICU. The main source of bleeding was the gastrointestinal tract (n = 44, 40.3%). Patients experiencing an ICU-acquired severe bleeding event displayed prolonged in-ICU length of stay (9.0 days [1.0–6.0] vs. 3.0 [3.5–15.0] in non-bleeding patients, p < 0.001) and worsened outcomes with increased in-ICU and in-hospital mortality rates (55% vs. 18.3% and 65.7% vs. 33.1%, respectively, p < 0.001). In multivariate analysis, independent predictors of ICU-acquired severe bleeding events were chronic kidney disease (cause-specific hazard 2.00 [1.19–3.31], p = 0.008), a primary bleeding event present at the time of ICU admission (CSH 4.17 [2.71–6.43], p < 0.001), non-platelet SOFA score (CSH per point increase 1.06 [1.01–1.11], p = 0.02) and prolonged prothrombin time (CSH per 5-percent increase 0.90 [0.85–0.96], p = 0.001) on the day prior to the event of interest.ConclusionsMajor bleeding events are common complications in critically ill patients with haematological malignancies and are associated with a worsened prognosis. We identified relevant risk factors of bleeding which may prompt closer monitoring or preventive measures.

Microfluidic Modulation of Microvasculature in Microdissected Tumors.

The microvasculature within the tumor microenvironment (TME) plays an essential role in cancer signaling beyond nutrient delivery. However, it has been challenging to control the generation and/or maintenance of microvasculature in ex vivo systems, a critical step for establishing cancer models of high clinical biomimicry. There have been great successes in engineering tissues incorporating microvasculature de novo (e.g., organoids and organs-on-chip), but these reconstituted tissues are formed with non-native cellular and molecular components that can skew certain outcomes such as drug efficacy. Microdissected tumors, on the other hand, show promise in preserving the TME, which is key for creating cancer models that can bridge the gap between bench and bedside. However, microdissected tumors are challenging to perfuse. Here, we developed a microfluidic platform that allows for perfusing the microvasculature of microdissected tumors. We demonstrate that, compared to diffusive transport, microfluidically perfused tissues feature larger and longer microvascular structures, with a better expression of CD31, a marker for endothelial cells, as analyzed by 3D imaging. This study also explores the effects of nitric oxide pathway-related drugs on endothelial cells, which are sensitive to shear stress and can activate endothelial nitric oxide synthase, producing nitric oxide. Our findings highlight the critical role of controlled perfusion and biochemical modulation in preserving tumor microvasculature, offering valuable insights for developing more effective cancer treatments.

Comparative Analysis of Transradial and Transfemoral Approaches in Transarterial Radioembolization for Liver Tumors: A Systematic Review and Meta-Analysis.

Transarterial radioembolization (TARE) is a minimally invasive therapy combining embolization and radiation for cancer treatment. This meta-analysis compares radiation exposure, quality of life, and safety of the transradial (TRA) versus transfemoral (TFA) approaches in TARE for liver tumors. We searched PubMed, SCOPUS, Cochrane, EMBASE, and Web of Science for studies comparing TRA versus TFA in TARE for liver tumors. Our primary outcomes focused on various measures of patient radiation exposure, including procedure time, fluoroscopy time, air kerma, and dose-area product (DAP). For secondary outcomes, we evaluated safety parameters, such as overall pain experienced during the procedure, pain in the recovery room post-procedure, the incidence of adverse events, and the impact on quality of life. Study quality was assessed using Cochrane's ROB 2 tool for RCTs and the Newcastle-Ottawa scale for observational studies. Data analysis was conducted with REVMAN 5.4.1 software. Six studies, comprising one RCT and five cohort studies with 1,209 patients, underwent comprehensive analysis. The aggregated findings revealed a significant reduction in procedure duration associated with TRA (MD =- 6.30, 95% CI [- 9.88, - 2.73], P = 0.005). However, no statistically significant differences were found between TRA and TFA groups concerning fluoroscopy time, recovery time, air kerma, DAP, pain in the recovery room, overall pain during the procedure, quality of life measuring mental health and physical function or adverse events. TRA and TFA showed comparable results in TARE for liver tumors, but TRA offered a shorter procedure time. Further RCTs with larger samples are needed to confirm these findings. Future studies should assess long-term efficacy for a more complete evaluation.

Engineered microparticles modulate arginine metabolism to repolarize tumor-associated macrophages for refractory colorectal cancer treatment

BackgroundArginase is abundantly expressed in colorectal cancer and disrupts arginine metabolism, promoting the formation of an immunosuppressive tumor microenvironment. This significant factor contributes to the insensitivity of colorectal cancer to immunotherapy. Tumor-associated macrophages (TAMs) are major immune cells in this environment, and aberrant arginine metabolism in tumor tissues induces TAM polarization toward M2-like macrophages. The natural compound piceatannol 3ʹ-O-glucoside inhibits arginase activity and activates nitric oxide synthase, thereby reducing M2-like macrophages while promoting M1-like macrophage polarization.MethodsThe natural compounds piceatannol 3ʹ-O-glucoside and indocyanine green were encapsulated within microparticles derived from tumor cells, termed PG/ICG@MPs. The enhanced cancer therapeutic effect of PG/ICG@MP was assessed both in vitro and in vivo.ResultsPG/ICG@MP precisely targets the tumor site, with piceatannol 3ʹ-O-glucoside concurrently inhibiting arginase activity and activating nitric oxide synthase. This process promotes increased endogenous nitric oxide production through arginine metabolism. The combined actions of nitric oxide and piceatannol 3ʹ-O-glucoside facilitate the repolarization of tumor-associated macrophages toward the M1 phenotype. Furthermore, the increase in endogenous nitric oxide levels, in conjunction with the photodynamic effect induced by indocyanine green, increases the quantity of reactive oxygen species. This dual effect not only enhances tumor immunity but also exerts remarkable inhibitory effects on tumors.ConclusionOur research results demonstrate the excellent tumor-targeting effect of PG/ICG@MPs. By modulating arginine metabolism to improve the tumor immune microenvironment, we provide an effective approach with clinical translational significance for combined cancer therapy.

Transformative insights: Image-based breast cancer detection and severity assessment through advanced AI techniques

Abstract In the realm of image-based breast cancer detection and severity assessment, this study delves into the revolutionary potential of sophisticated artificial intelligence (AI) techniques. By investigating image processing, machine learning (ML), and deep learning (DL), the research illuminates their combined impact on transforming breast cancer diagnosis. This integration offers insights into early identification and precise characterization of cancers. With a foundation in 125 research articles, this article presents a comprehensive overview of the current state of image-based breast cancer detection. Synthesizing the transformative role of AI, including image processing, ML, and DL, the review explores how these technologies collectively reshape the landscape of breast cancer diagnosis and severity assessment. An essential aspect highlighted is the synergy between advanced image processing methods and ML algorithms. This combination facilitates the automated examination of medical images, which is crucial for detecting minute anomalies indicative of breast cancer. The utilization of complex neural networks for feature extraction and pattern recognition in DL models further enhances diagnostic precision. Beyond diagnostic improvements, the abstract underscores the substantial influence of AI-driven methods on breast cancer treatment. The integration of AI not only increases diagnostic precision but also opens avenues for individualized treatment planning, marking a paradigm shift toward personalized medicine in breast cancer care. However, challenges persist, with issues related to data quality and interpretability requiring continued research efforts. Looking forward, the abstract envisions future directions for breast cancer identification and diagnosis, emphasizing the adoption of explainable AI techniques and global collaboration for data sharing. These initiatives promise to propel the field into a new era characterized by enhanced efficiency and precision in breast cancer care.

Second malignancy in advanced or recurrent non-small cell lung cancer after the advent of molecular targeted drugs and immunotherapy.

This study aimed to investigate the characteristics of patients with recurrent or advanced non-small cell lung cancer (NSCLC) treated with tyrosine kinase inhibitors (TKIs) or immune-checkpoint inhibitors (ICIs) who developed secondary malignancies, as well as evaluate the impact of these secondary malignancies on the course of lung cancer. This study included 112 patients with postoperative recurrent or advanced NSCLC, who received TKIs, ICIs, or immune combination therapy as the primary treatment modality between April1, 2013, and March 31, 2020, and achieved long-term survival (≥2 years). Secondary malignancies were defined as newly diagnosed cancers in other organs occurring after NSCLC treatment initiation. Among the 112 patients, 10 (8.9%) developed 12 carcinomas, including third primary malignancies. Univariate analysis, considering secondary malignancies as the outcome, revealed a non-significant trend towards a higher incidence of secondary malignancies in smokers compared to non-smokers. This study found that 8.9% of patients with advanced NSCLC who received TKIs, ICIs, or immune combination therapy and survived ≥2 years developed secondary malignancies. This underscores the importance of early diagnosis and treatment, even during lung cancer treatment, to identify suspicious lesions in other organs either via imaging or physical examinations.

Cancer-associated fibroblast-secreted exosomal miR-454-3p inhibits lipid metabolism and ferroptosis in breast cancer by targeting ACSL4.

Cancer-associated fibroblasts (CAFs) participate in the development of the tumor microenvironment through the secretion of exosomes. Acyl-CoA synthetase long-chain family member 4 (ACSL4) is an essential component of ferroptosis. However, the regulatory mechanism of ACSL4 in breast cancer remains unexplored. The study aimed to determine the influence of exosomal miR-454-3p from CAFs on lipid metabolism and ferroptosis. CAF-derived exosomes (CAF-exo) were isolated from breast cancer tissue of breast cancer patients and characterized using transmission electron microscopy (TEM) and Western blot. Luciferase reporter assay and RNA immunoprecipitation (RIP) were used to demonstrate the relationship between miR-454-3p and ACSL4. Cell viability and ferroptosis-related markers were detected by CCK-8 and Western blot. Malondialdehyde (MDA), glutathione (GSH), and iron levels were detected. Reverse transcription-quantitative PCR (RT-qPCR) and fluorescence in situ hybridization (FISH) were used to assess miR-454-3p expression. miR-454-3p and ACSL4 levels were abnormally expressed in breast cancer tissues. CAF-exo significantly enhanced cell viability and GSH levels and suppressed MDA, and iron levels. CAF-exo upregulated ferroptosis suppressor protein 1 (FSP1) and glutathione peroxidase 4 (GPX4) expression, and reduced ACSL4 levels. miR-454-3p was strongly expressed in CAF-exo, and exosomal miR-454-3p suppressed lipid metabolism and ferroptosis in breast cancer cells. The effects of miR-454-3p inhibitor on lipid metabolism and ferroptosis were eliminated by ACSL4 knockdown. CAF-secreted exosomal miR-454-3p inhibited lipid metabolism and ferroptosis by targeting ACSL4 in breast cancer. This study revealed a novel molecular mechanism that offers a potential therapeutic intervention in breast cancer treatment.

Prognostic Significance of Programmed Cell Death-Ligand 1 Expression in Tobacco Associated Oral Squamous Cell Carcinoma: An Immunohistochemical Based Cross-Sectional Study.

Advancements in immuno-oncology have dramatically transformed cancer treatment. Immunotherapy, targeting immune check point proteins, notably Programmed cell death ligand 1 (PD-L1) and its receptor Programmed Cell Death-1 (PD-1) which modulate the activity of immune response in Head and Neck squamous cell carcinomas (HNSCC), is an area of much research. The immunohistochemical expression of PD-L1 in cancer cells has been proposed as a predictive biomarker for selecting candidates for immunotherapy. Thus, the present study was undertaken to study the expression of PD-L1 in the primary tumour cells and evaluate its correlation with various clinicopathological parameters and prognosis in tobacco associated oral squamous cell carcinomas (OSCC). Expression of PD-L1 was investigated in 75 surgically resected cases of OSCC by immunohistochemistry and its association with different clinicopathological features and prognosis was analysed. PD-L1 protein was detected in 68% (51 cases) of cases. Tumour stage (p = 0.04), lymph node (LN) metastasis (p < 0.01) and moderate to marked tumour infiltrating lymphocytes (TILs) (p < 0.05), significantly correlated with the PD-L1 expression in the primary tumour. PD-L1 expression did not show a significant association with overall survival (OS) rate, however, patients with positive PD-L1 expression showed a poorer survival rate. Patients exhibiting nodal positivity had the worst prognosis (p < 0.005). These data demonstrated a significant association of ≥ 5% PD-L1 expression in the primary tumour and the presence of LN metastasis, moderate to marked TILs and advancing tumour stage, thus, making it a plausible immunotherapeutic target molecule in OSCC patients.