Technology in Cancer Research & Treatment最新文献

The contemporary concept of carcinogenesis summarizes the role of hypoxia, neoangiogenesis, and hemostasis, including in the stage of progression and metastasis of the tumor process. Metastatic disease is a serious therapeutic challenge for any oncological condition. The purpose of this study was to evaluate the dynamics of specific indicators of neoangiogenesis and hypoxia as potential biomarkers for therapeutic efficacy or risk of disease progression in patients with brain metastases (BM) undergoing robotic stereotactic radiosurgery. Two groups of patients (lung cancer and other types of cancers) with oligometastatic disease and brain metastases were included. The patients (n = 66) were treated CyberKnife system. Human Angiopoietin-2, Hypoxia inducible factor 1 α (HIF-1α) and human Vascular Endothelial Growth Factor-А (VEGF-А) were measured in this prospective longitudinal study. Analysis of human Angiopoietin-2, HIF-1α, human VEGF-A in the post-treatment period showed a statistically significant decrease between the baseline and the 6 months post-treatment time point in both patient groups. The baseline value of serum VEGF-А in the group with lung cancer decreased by 40%, Аngiopoietin-2-by 48%, HIF-1α -by 43%. In the group with other types of cancers, VEGF-А decreased by 54.75%, Аngiopoietin-2-by 52%, HIF-1α -by 39.5%. Despite the significant reduction, the levels remained significantly higher in both groups than in healthy controls. This study underscores the potential of integrating molecular markers like VEGF-A, Angiopoietin-2, and HIF-1α into clinical decision-making to enhance outcomes for patients with brain metastases undergoing RSRS.

Background: Doxorubicin (DOX) is a potent chemotherapeutic agent for breast cancer, but its effectiveness is often diminished by resistance mechanisms, particularly through p-glycoprotein (P-gp) mediated drug efflux. Clarithromycin (CAM), a macrolide antibiotic, inhibits multiple metabolic pathways including CYP3A and P-gp, potentially countering DOX resistance.

Objective: This study aimed to evaluate the potentiation of DOX and its effectiveness against the MCF-7 breast cancer cell line by encapsulating both DOX and CAM in PEGylated liposomes.

Methods: PEGylated liposomes containing DOX and CAM were prepared using the thin film hydration method. The physicochemical properties of the liposomes, including average particle size, polydispersity index (PDI), and zeta potential, were characterized. Encapsulation efficiencies for CAM and DOX were assessed, and stability of the liposomes was evaluated over 9 days at room temperature. Cell viability was measured using an IC₅₀ assay, and P-gp expression levels were determined by ELISA.

Results: The CAM/DOX-PEGylated liposomes exhibited optimal average particle size (238 ± 26.7 nm), PDI (0.29 ± 0.107), and zeta potential (-20.9 ± 2.17 mV). These liposomes maintained good stability regarding size and charge over 9 days. Encapsulation efficiencies were 81.05% for CAM and 78.13% for DOX. The IC50 value for CAM/DOX-PEGylated liposomes was 0.13 µM, representing a significant reduction compared to the physical mixture of CAM and DOX (0.25 µM) and free DOX (0.21 µM) against MCF-7 cells. ELISA analysis showed a reduction in P-gp expression of approximately 5% with CAM/DOX-PEGylated liposomes compared to 1.61% with free DOX.

Conclusion: The results indicate that CAM encapsulated in PEGylated liposomes enhances the effectiveness of DOX against breast cancer cells, likely through the inhibition of p-glycoprotein. This approach may offer a promising strategy to overcome DOX resistance and improve chemotherapy outcomes.

Background: NUPR1 is a small molecule protein that plays an important role in tumor progression and drug resistance. Our previous study found that NUPR1 promotes the progression of bladder cancer, but the specific mechanism is still unclear. MYH11 encodes the smooth muscle myosin heavy chain and belongs to the conventional myosin family. MYH11 has been found to be associated with a variety of malignant tumors.

Methods: We identified MYH11 as an upstream regulator of NUPR1 using a bioinformatics approach and tested this hypothesis by knocking down MYH11 and ChIP-qPCR. Subsequently, we verified the association of MYH11 and NUPR1 with the PI3 K/AKT pathway by WB. In addition, gene enrichment results showed that the effect of NUPR1 on bladder cancer was related to ferroptosis and M2 macrophage polarization. We examined ferroptosis metabolites in bladder cancer cells overexpressing NUPR1 and expression of the M2 macrophage marker CD206 in NUPR1 overexpression or MYH11 knockdown bladder cancer cells.

Results: Bioinformatics results showed that MYH11 was positively correlated with NUPR1, and there may be a mutual binding site at the promoter of NUPR1. Knockdown of MYH11 decreased NUPR1 expression, and ChIP-qPCR showed that MYH11 bound to the promoter of NUPR1. Subsequently, WB results showed that MYH11 knockdown inhibited the PI3 K/AKT pathway, whereas NUPR1 overexpression activated this pathway. After adding ferroptosis activator, the viability of bladder cancer cells decreased, and the content of Fe²⁺ and MDA increased. However, ferroptosis was significantly inhibited after overexpression of NUPR1. Knockdown of MYH11 inhibited M2 macrophage polarization, while overexpression of NUPR1 promoted this process.

Conclusion: This study suggests that MYH11 activates the PI3 K/AKT pathway by up-regulating the expression of NUPR1, and promotes bladder cancer progression by inhibiting ferroptosis and promoting M2 polarization of macrophages.

Objectives: We conducted a systematic review to compile the findings of all published studies on the use of percutaneous laser ablation (PLA) in the treatment of early-stage breast cancer. We aimed to identify appropriate methodology as well as parameters for the selection of suitable patients to optimize outcomes with the use of PLA. Additionally, we aimed to analyze whether this method is a viable alternative to current surgical treatments employed. Methods: The PRISMA 2020 method was applied. The terms "laser ablation" AND "breast cancer" were used to select all articles published up to January 2024 on the PubMed and Embase platforms. Articles in English were included. Only original articles were considered for this systematic review. Review articles, editorials, letters, and studies ex-vivo or not performed in humans were excluded. Results: Seventeen articles, including 308 patients were analyzed. Among the studies describing the complete response rate to assess treatment success, there was no residual tumor after ablation in 74.4% of the patients. MRI was the best exam to evaluate the effectiveness of the ablative procedure with a NPV of 92% to 100%. Skin burn was the most commonly observed complication, occurring in 6% of patients. Other less frequent complications were hematoma/bleeding, pain, nodulation, erythema, seroma, and fat necrosis. Conclusions: The use of PLA remains restricted to cases with specific indications or within the context of research protocols. However, future studies may validate this promising technique for the local treatment of early-stage breast cancer. This study was registered at INPLASY (registration number: INPLASY2024100045).

Background: Small cell lung cancer is sensitive to chemotherapy and radiotherapy, but local recurrence and distant metastasis occur shortly after treatment. This study aimed to evaluate the real-world value of anlotinib as a maintenance therapy in patients with extensive-stage small cell lung cancer (ES-SCLC) after first-line chemotherapy and consolidative thoracic radiotherapy (CTRT).

Patients and methods: A total of 150 patients with ES-SCLC treated with first-line chemotherapy and CTRT from April 2017 to December 2021 were retrospectively analyzed. After the completion of chemoradiotherapy, patients received anlotinib according to their desire. The primary endpoints were progression-free survival (PFS) and overall survival (OS) after the first diagnosis, and the secondary endpoints were prognostic factors and safety.

Results: The ORR and DCR of patients with ES-SCLC were 50.0% and 80.3%, respectively, in the anlotinib group and 42.9% and 69.0% in the no-maintenance therapy group. The 3-year OS rates were 27.6% and 12.6% in the anlotinib and observation groups (HR = 2.52, P = 0.003), and the median OS times were 23.8 months and 15.3 months. The 3-year PFS rates were 18.2% and 8.8% in the anlotinib and observation groups (HR = 1.76, P = 0.034) with median PFS times of 11.5 months and 8.8 months. After stratification on the basis of clinical response, patients who achieved CR plus PR after chemoradiotherapy had a longer median OS in the anlotinib and observation groups (34.0 months vs 24.8 months, HR = 2.40, P = 0.009). There were higher incidence rates of hand-foot syndrome (27.3% vs 10.5%, P = 0.001), gingival bleeding/hemoptysis (18.5% vs 4.8%, P = 0.015) and rash (33.3% vs 4.8%, P < 0.001) in the anlotinib group than in the observation group.

Conclusion: Maintenance therapy with anlotinib improved the survival of patients with ES-SCLC after first-line chemotherapy and CTRT. Owing to the small sample size of the real-world trial, the reliability of our study needs to be confirmed in more studies.

MR-guided radiotherapy (MRgRT) is novel treatment modality in Radiation Oncology that could allow a higher precision and tolerability of Radiation Treatments. This modality is possible due to dedicated systems consisting of a MR scanner mounted on a conventional linac and software that permit daily online treatment plan adaptation. Prostate cancer (PC) is one of the most common malignancies in RO clinical practice and currently under investigation with this new technology. The focus of this review is to describe the current state of the art and clinical results of MRgRT in the treatment of PC. The available technology are briefly described, as well as the published literature and possible future applications.

Primary central nervous system lymphoma (PCNSL) is a very rare extranodal non-Hodgkin's lymphoma confined to the brain, eyes, spinal cord, and cerebrospinal fluid (CSF). This disease is highly aggressive. For decades, high-dose methotrexate-based induction regimens have been the standard treatment for PCNSL and have significantly improved patient overall survival (OS). However, some patients still experience disease recurrence or develop drug resistance. With a deeper understanding of the pathophysiology of PCNSL, various therapies, including CD20 monoclonal antibodies, Bruton's tyrosine kinase (BTK) inhibitors, immunomodulatory drugs, immune checkpoint inhibitors, phosphoinositide 3-kinase (PI3 K)/mammalian target of rapamycin(mTOR) inhibitors, and chimeric antigen receptor (CAR) -T cells are increasingly being applied and have demonstrated considerable efficacy. These therapies have paved the way for novel treatment strategies in PCNSL, representing a highly promising field. Investigating the mechanisms, specific targets, and signaling pathways, as well as interactions with the tumor microenvironment (TME), can provide a solid foundation for further exploration and potentially enhance the optimization of treatment approaches for PCNSL. This review seeks to explore the characteristics of the TME in PCNSL, elucidate the molecular mechanisms of various immunotherapies and targeted therapies, examine their interactions with the TME, and summarize the advancements in the research of PCNSL immunotherapy and targeted therapy.

Introduction: 3-dimensional (3D) printing and augmented reality (AR) are emerging technologies that are used in a wide variety of scientific fields. Among them, medicine is one of the most promising fields of application since these technologies can benefit not only surgeons, but also medical/surgical trainees, patients and can potentially benefit health care systems with better educated staff working on personalized solutions for the patients. Thus, potentially reducing intra-operative and post operative complications and overall costs for the health care systems. Hepatic malignancy surgeries are some of the most demanding surgeries that could a general surgeon perform. The intra-operative and post-operative risks and complications render them demanding. In literature there are cases of research studies including applications of 3D printing and augmented reality in hepatic malignancies. Methods: For this, a comprehensive literature search was conducted on Scopus and Pubmed databases (latest search September 5, 2024). Research studies that included applications of 3D printing and AR in hepatic malignancies were eligible for the review. Results: Herein, twelve papers have been included and presented, which either include the use of 3D printing or the use of AR. There are some cases where both technologies were used simultaneously. 3D printing technology and AR can be used alone or in combination together to aid in the management of hepatic malignancies. Conclusion: Encouraging results (eg, efforts to reduce cost of 3D printing, proper surgical pre-planning, usefulness in education of medical personnel and patients) from the use of these technologies, not only qualitatively but also quantitatively, show that the medical staff can help patients and improve their part of the health system. Yet much more studies need to validate whether the use of these two technologies provides positive results on the surgeries or not.

The management of early-stage colon cancer involves surgical resection of the primary tumor with or without chemotherapy, depending on pathological staging. The benefit of adjuvant chemotherapy for stage II and III colon cancer is approximately 5% and 15%, indicating the need for optimization for risk stratification and patient selection. Several studies have revealed that current clinicopathological factors lack precision. Circulating tumor DNA (ctDNA) is cell-free DNA originating from cancer cells and can be detected even in the absence of radiologically detectable disease among patients with colon cancer. Recent cohort studies revealed that ctDNA is one of the most significant prognostic factors for patients with early-stage colon cancer, surpassing pathological and clinical risk factors. Prospective cohort studies also suggest there may be a predictive role for ctDNA on the decision for consideration of adjuvant therapy. Currently, randomized clinical trials are enrolling to better define this role. In this review article, we review recent literature on ctDNA and its role in patients with colon cancer. We also elaborate on the future clinical utility of ctDNA in clinical practice and the unmet need for research to optimize currently available ctDNA assays.