Technology in Cancer Research & Treatment最新文献

This review summarizes the intricate relationship between the microbiome and cancer initiation and development. Microbiome alterations impact metabolic pathways, immune responses, and gene expression, which can accelerate or mitigate cancer progression. We examine how dysbiosis affects tumor growth, metastasis, and treatment resistance. Additionally, we discuss the potential of microbiome-targeted therapies, such as probiotics and fecal microbiota transplants, to modulate cancer metabolism. These interventions offer the possibility of reversing or controlling cancer progression, enhancing the efficacy of traditional treatments like chemotherapy and immunotherapy. Despite promising developments, challenges remain in identifying key microbial species and pathways and validating microbiome-targeted therapies through large-scale clinical trials. Nonetheless, the intersection of microbiome research and cancer initiation and development presents an exciting frontier for innovative therapies. This review offers a fresh perspective on cancer initiation and development by integrating microbiome insights, highlighting the potential for interdisciplinary research to enhance our understanding of cancer progression and treatment strategies.

IntroductionMultiple targets with varying distances are common in radiotherapy. Reducing treatment time in the plan design helps minimize patient movement and discomfort during the treatment process. This retrospective study aimed to investigate the impact of varying intertarget distances (ITDs) on the dosimetric differences and delivery efficiency of two single-isocenter techniques.MethodsITDs for 15 patients with dual-site vertebral metastases undergoing volume-modulated arc therapy (VMAT) were modified using Matlab 2019a. Distances of 2, 4, 6, 8, and 10 cm were considered. The VMAT plans were designed with a prescription dose of 40 Gy/20f on Infinity Linac and Monaco 5.40.01. Single-isocenter with jaw tracking (VMAT1) and fixed jaw (VMAT2) were compared in terms of dosimetry and delivery efficiency under different ITDs.ResultsResults showed that both VMAT plans exhibited dosimetric parameters meeting clinical requirements. The conformity index (CI) of VMAT1 plans was smaller than that of VMAT2 at ITD = 4, 6, and 8 cm (P = 0.007, 0.020, and 0.039, respectively), with no significant differences in other planning target volume dosimetry parameters. In terms of delivery efficiency, the treatment time of VMAT1 increased significantly when ITD > 2 cm compared with that at ITD = 2 cm (P = 0.000). Conversely, VMAT2 exhibited no significant change in treatment time at different ITDs (P = 0.073). For ITD = 2 cm, the treatment time of VMAT1 was shorter than that of VMAT2, with a median difference of 77 s. For ITD > 2 cm, the treatment time of VMAT2 was shorter than that of VMAT1, with a median difference ranging from 65 s to 121 s.ConclusionThe experimental results showed that the single-isocenter with jaw tracking is recommended in the planning design when ITDs are less than 2 cm. However, for ITDs greater than 2 cm, the single-isocenter with fixed jaw demonstrates high delivery efficiency.5075.

Immunotherapy has emerged as a pivotal advancement in oncological therapeutics, representing a paradigm shift from conventional treatment modalities including surgery, radiotherapy, and chemotherapy. This innovative approach demonstrates considerable clinical potential through its capacity to enhance systemic anti-tumor responses via active or passive immunomodulation. Compared to traditional therapies, immunotherapy offers distinct advantages such as broad applicability, rapid therapeutic onset, and reduced adverse effects. However, critical challenges persist in clinical implementation, particularly concerning treatment safety and efficacy optimization. Current limitations, including drug off-target effects and biological delivery barriers, frequently result in suboptimal therapeutic outcomes and severe complications such as autoimmune disorders and nonspecific inflammation. Recently advancements in drug delivery systems (DDS) present transformative solutions to these challenges. Sophisticated DDS platforms enable precise spatiotemporal delivery of tumor antigens, immunotherapeutic agents, and immunostimulatory molecules, thereby achieving targeted modulation of diverse immune cell populations. This technological innovation not only enhances therapeutic efficacy but also significantly mitigates adverse reactions, while facilitating synergistic combinations with conventional cancer treatments. In this review, we outline the application of new drug delivery platforms in major malignancies (including but not limited to melanoma, non-small cell lung cancer, hormone receptor-positive breast cancer, and hepatocellular carcinoma). We further propose evidence-based optimization strategies for next-generation delivery platforms, aiming to bridge the gap between preclinical development and clinical implementation in cancer immunotherapy.

AimsThis review aims to synthesize the existing literature on palliative radiotherapy (RT) delivered in two daily fractions for patients with advanced cancer, focusing on its impact on symptom alleviation, treatment tolerance, and the implications for clinical practice and future research.MethodsAn international team conducted this narrative review, adhering to SANRA guidelines. Studies published in English on palliative RT delivered in two daily fractions were selected without date restrictions. The literature search, using a combination of specific key terms, led to a comprehensive examination of relevant studies. Data on study objectives, treatment approaches, palliative effectiveness, and toxicity were extracted and qualitatively analyzed.ResultsThe review included 29 publications, showing consistent efficacy in symptom reduction (63.0%-100% palliative response rate) and general tolerability across various cancer types. These studies highlighted the potential radiobiological advantages and practicality of accelerated multi-fractionated regimens, which provide rapid tumor response with reduced late toxicity risks. Furthermore, the logistical benefits of such treatments, including shorter hospital stays and minimized travel requirements, were noted as particularly valuable during challenging times such as recent pandemics.ConclusionsThe evidence supports the integration of evidence-based, accelerated-hypofractionated RT into palliative care strategies, ensuring effective symptom management with minimal patient burden. Future research should focus on comparative studies on single versus multiple-cycle treatments, optimal intervals between treatment cycles, and the integration of advanced RT techniques.

IntroductionRenal cancer, particularly Kidney Renal Clear Cell Carcinoma (KIRC), remains a major clinical challenge due to its aggressive nature and poor prognosis. Identifying reliable biomarkers for tumor progression and survival is critical for improving patient outcomes. This study aimed to investigate the role of Centromere Protein F (CENPF) as a potential prognostic biomarker for renal cancer.MethodData from the TCGA database, including Kidney Chromophobe (KICH), Kidney Renal Papillary Cell Carcinoma (KIRP), and KIRC, were analyzed to identify differentially expressed genes. Molecular Complex Detection (MCODE) was used to identify significant gene modules among upregulated genes, and univariate Cox regression analyses assessed the prognostic value of hub genes. Retrospective qPCR was conducted on tissue and plasma samples from KIRC patients to validate findings. Single-cell sequencing data from the GSE159115 dataset were analyzed, and the CIBERSORT algorithm was applied to evaluate the composition of tumor immune infiltrating cells (TIICs).ResultsCENPF was identified as a hub gene significantly upregulated in renal cancer subtypes, with overexpression linked to worse survival outcomes in KIRC patients. Retrospective qPCR confirmed high CENPF expression was associated with poorer prognosis. Single-cell sequencing revealed that CENPF is predominantly expressed in T-cell clusters. TIIC analysis showed a negative correlation between CENPF and resting mast cells, but positive correlations with follicular helper T-cells and memory-activated CD4T-cells. Prognostic analysis indicated that high follicular helper T-cell expression predicted poorer survival, while high plasma cell expression correlated with better outcomes.ConclusionCENPF plays a critical role in tumor progression and the modulation of the tumor immune microenvironment in KIRC. These findings suggest that CENPF could serve as a valuable prognostic biomarker and potential target for therapeutic intervention in renal cancer.

Background: The prognostic value of the Geriatric 8 (G8) screening score in metastatic renal cell carcinoma (mRCC) patients receiving first-line immunotherapy remains unclear. This study aimed to evaluate the prognostic role of G8 within the context of the Meet-URO classification in mRCC patients treated with first-line ipilimumab-nivolumab.

Methods: This retrospective multicentre study analysed 106 mRCC patients treated with first-line ipilimumab-nivolumab. G8 and Meet-URO scores were calculated before treatment initiation. Primary endpoint was overall survival (OS), defined as duration from first administration of Nivolumab to death. OS was analysed in relation to age groups, G8 scores, and Meet-URO score categories, with data censored for patients still alive at the last follow-up. The secondary endpoint, progression-free survival (PFS), was measured from initiating Nivolumab to the earliest instance of disease progression or death. OS and PFS were assessed using Kaplan-Meier methods and Cox regression analyses. The reporting of this study conforms to the REMARK guidelines.

Results: Patients with G8 > 14 had more favorable IMDC and Meet-URO risk classifications and lower neutrophil-to-lymphocyte ratios. While PFS did not differ significantly between G8 ≤ 14 and >14 groups (1-year 29.3% vs 46.2%, p = 0.2), OS was significantly longer in G8 > 14 group (1-year 76.1% vs 58.6%, p = 0.006). In multivariable analysis, G8 ≤ 14 was independently associated with worse OS (HR 2.36, 95% CI 1.06-5.08, p = 0.03) but not PFS. The Meet-URO score was prognostic for both PFS and OS. In patients ≥70 years, G8 lost its prognostic value, while Meet-URO remained prognostic for OS.

Conclusions: The G8 score is an independent prognostic factor for OS but not PFS in mRCC patients receiving first-line ipilimumab-nivolumab. The Meet-URO score shows consistent prognostic ability for PFS and OS across age groups. These findings suggest that while G8 may be useful for individual patient-level OS prediction, the Meet-URO score may be superior for guiding treatment decisions in clinical practice.

Osteosarcoma (OS) is the most common primary bone malignancy, with lung metastasis being the leading cause of mortality. The metastatic process is driven by complex biological mechanisms, including tumor cell-specific adaptations of growth pathways, immune modulation within the tumor microenvironment, and reactivation of metastatic cells from dormancy. This scoping review captures overlooked and under researched pathways, supporting mainstream therapeutic targets while shedding light on novel ones, reinforcing and revising conclusions drawn in previous literature, and guiding future research. MEDLINE, Embase, and Cochrane CENTRAL were searched with a publication date limit from 2019 onwards using relevant MeSH terms combined with Boolean operators, truncations, and keyword searches. The search culminated in 43 reports, including 30 in vivo, 8 in vitro, and 5 observational studies. This study conforms to the PRISMA-ScR guidelines. Tumor cell adaptations, including epithelial-mesenchymal transition (EMT) and enhanced migratory and proliferative signaling via JAK/STAT and TGF-β pathways, are critical drivers of OS lung metastasis. Manipulated upstream ligand-driven signaling promotes transcriptional changes that increase cell cycle proteins and mesenchymal markers, conferring chemoresistance and advancing OS cells toward a metastatic state. The tumor microenvironment also plays a key role; interactions between OS cell-derived cytokines and tumor-infiltrating immune cells lead to tumor associated macrophages and neutrophils (TAMs/TANs), which help establish a pre-metastatic niche and provoke immune remodeling. However, the impact of TAMs on OS survival remains ambiguous due to their dual pro- and anti-tumor roles. Lung-induced dormancy links tumor intrinsic and immune-driven mechanisms, allowing tumor cells to evade immunity or pause progression. Inflammatory pathways and immune activation can reverse dormancy, promoting further OS dissemination. The reviewed evidence supports targeting intracellular signaling and immune pathways to mitigate OS metastasis. The paucity of longitudinal data on lung dormancy warrants caution, emphasizing integrated approaches and better controlled studies with focus on combinatorial therapies for more conclusive outcomes.

IntroductionTo investigate the efficacy of a knowledge-based planning (KBP) model in optimizing dose distribution, and identify the inter-institutional variation in radiotherapy of recurrent nasopharyngeal carcinoma (rNPC).MethodsA total of 70 rNPC patients treated with intensity-modulated radiotherapy (IMRT) were recruited to build a KBP model. Following model refinement, 36 patients were retrospectively enrolled for dosimetric comparison between manually optimized and KBP-generated plans. Ten experienced physicists from six different institutions were engaged to independently design manual plan for a representative case, to assess inter-institutional variations, and differences between KBP and manual plans.ResultsThe refined KBP model provided significant reduced dose in brainstem D_1cc (the dose received by the "hottest"1 cm³ volume, 41.14 ± 8.51 Gy vs 38.48 ± 8.60 Gy, P < 0.001) and spinal cord D_1cc (17.48 ± 9.38Gy vs 12.23 ± 6.56Gy, P < 0.001). In addition, The mean dose (D_mean) of brainstem, spinal cord, mandible, parotid, temporomandibular joint and inner ear were statistically decreased (P < 0.05). In validation cohort, KBP model eliminated the hotspot (0.57 ± 0.01% vs 0.00 ± 0.00%, P < 0.001), improved target homogeneity (HI: 0.06 ± 0.00 vs 0.08 ± 0.00, P < 0.001), and performed superior to the manual plans in sparing organs. While all institutions achieved comparable target coverage, manual plans exhibited substantial variability in sparing brainstem. KBP implementation reduced inter-institutional dose disparities for brainstem (46.30 ± 10.08 Gy vs 41.80 ± 5.80 Gy, P = 0.041) and spinal cord (26.08 ± 7.06 Gy vs 18.19 ± 1.98 Gy, P = 0.002). Additionally, planning efficiency increased by 48.7% (39 vs 76 min).ConclusionsThis KBP framework optimized rNPC reirradiation from three dimensions: 1) Enhanced OARs' protection; 2) Improved target homogeneity; 3) Improved the multi-institutional consistency and efficiency of planning. These advancements established a clinically actionable paradigm for precision reirradiation.

BackgroundEndometrial carcinoma (EC) represents a unique clinical challenge. Fertility-sparing treatments rely on achieving complete response (CR) through progesterone-based therapy. We sought to investigate the prognostic value of molecular subtyping and immunohistochemical (IHC) markers in predicting three-month treatment outcomes and recurrence in EC patients undergoing fertility-sparing therapy.MethodsA retrospective cohort of 68 patients diagnosed with early-stage EC received hysteroscopic surgery and conservative treatment whose paraffin-embedded tissue blocks preserved in our hospital between Jan. 2010 and Oct. 2022 was evaluated. Molecular subtyping based on TCGA classification identified low copy-number (CNL), microsatellite instability-high (MSI-H), and copy-number high (CNH) subtypes. IHC markers, including PTEN, PIK3CA, β-catenin, ARID1A, estrogen receptor (ER), and progesterone receptor (PR) were analyzed for their association with CR and recurrence. Transcriptome sequencing gene chips were used to study patients who achieved or did not achieve CR after three months, those who experienced recurrence within one year, and those who did not recur within two years. Differential genes were then mapped to KEGG pathways to explore the underlying mechanisms of progesterone therapy efficacy.ResultsAmong the 68 patients classified through TCGA molecular typing, 65 cases (95.6%) were CNL subtype, two (2.9%) were MSI-H subtype, and one (1.5%) was CNH subtype. Following a three-month treatment, the CR rate for the CNL subtype was 75.4% (49/65), the MSI-H subtype was 50.0% (1/2), and the CNH subtype was 0% (0/1). In CNL subtype endometrial carcinoma, individuals with high PTEN and PR expression were more likely to achieve CR after three months (P < .05). Conversely, those with elevated CA199 levels and increased PIK3CA expression were more prone to recurrence after CR.ConclusionMSI-H and p53-mutant subtypes of endometrial carcinoma are not suitable for fertility preservation therapy. PTEN/PI3K-AKT-mTOR pathway activation contributes to reduced progesterone sensitivity, underscoring the need for targeted therapeutic strategies to improve patient outcomes.