Cancer Management and Research最新文献

Introduction: The aim of this study was to clarify the genome of ferroptosis in the genes involved in radiotherapy resistance and regulation of tumor immune microenvironment by multigene analysis of cervical cancer (CC) patients.

Methods: Different radiation sensitivity samples from CC patients were collected for RNA sequencing. Differentially expressed genes (DEGs) between the RNA dataset and the GSE9750 dataset were considered as radiotherapy-DEGs. The intersection genes of radiotherapy-DEGs with ferroptosis-related genes (FRGs) and the intersection genes of radiotherapy-DEGs with immune-related genes (IRGs) were labeled as FRGs-IRGs-DEGs (FIGs). A risk model was established by prognostic genes selected from FIGs by univariate Cox analysis and least absolute shrinkage and selection operator (LASSO) analysis. The results were further validated using samples from CC tissue samples.

Results: The 329 DEGs related to CC radiotherapy were identified. LSAAO analysis was utilized to identify five prognostic genes (CALCRL, UCHL1, GNRH1, ACVRL1, and MUC1) from six candidate prognosis genes and construct a risk model. The risk model demonstrated favorable effectiveness in predicting outcomes at 1, 3, and 5 years, as evidenced by ROC curves. Univariate and multivariate Cox regression analysis demonstrated that CALCRL, GNRH1, and MUC1 were independent prognostic factors. The results of functional similarity analysis showed that CALCRL, UCHL1, ACVRL1 and MUC1 had high average functional similarity. The results of PCR and IHC showed the same trend with the results above.

Discussion: A novel prognostic model related to ferroptosis and immune microenvironment in CC radiotherapy was developed and validated, providing valuable guidance for personalized anti-cancer therapy.

Background: Iron oxide nanoparticles coated with paclitaxel (IONP@PTX) are frequently applied to various tumor types. However, inhibitory effect and possible mechanism of IONP@ PTX on non-small-cell lung cancer (NSCLC) remain unclear.

Objective: This work aimed to assess inhibitory effects and potential mechanisms of IONP@PTX on lung cancer A549 cells and further explore the nanomedicine delivery systems for applications in cancer therapies.

Methods: Morphology features and qualities of IONP@PTX were directly assessed. After treatment of A549 cells with either PTX or IONP@PTX, cell viability and apoptosis were separately detected by CCK‑8 assay and flow cytometry. In addition, intracellular iron ion, lipid peroxidation (LPD) and reactive oxygen species (ROS) were identified by using an iron colorimetric assay kit, DCFH-DA and C11-BODIPY fluorescent probe, respectively. Moreover, the expression levels of autophagy-, ferroptosis-, and apoptosis-related proteins were measured by Western blot.

Results: The synthesized IONP@PTX had a core particle size of about 10 nm and a hydrated particle size of 31.01±2.47 nm. In comparison with PTX, IONP@PTX had a stronger anti-tumor effect on A549 cells, with considerably higher levels of ROS, LPD, and total iron ion concentration (P<0.05). Likewise, IONP@PTX markedly reduced the expression levels of GPX4, FTH, and SLC7A11 proteins whereas obviously increased the expression levels of LC3II/I and ACSL4 proteins (P<0.05). Furthermore, the inhibitory effects of both PTX and IONP@PTX on A549 cells could be evidently reversed by additional 3-methyladenine (3-MA) or ferrostatin-1. Interestingly, the apoptosis rates of A549 cells, together with the expression level of pro-apoptotic protein Cleaved caspase-3, were significantly higher in the IONP@PTX group than those in the control and PTX groups (P<0.05).

Conclusion: IONP@PTX inhibits the proliferation of human lung cancer A549 cells by enhancing autophagy-dependent ferroptosis and apoptosis pathways.

Objective: To evaluate the clinical value of serum soluble T cell immunoglobulin 3 (sTim-3) on postoperative recurrence of breast cancer (BC).

Methods: A highly sensitive time-resolved fluorescence immunoassay (TRFIA) was employed to measure sTim-3. Quantification of serum sTim-3 in 172 BC patients more than one-year postoperative (96 patients with stage I + II, 76 patients with stage III + IV; 31 patients with postoperative recurrence, and 141 patients with postoperative non-recurrence) and 51 healthy controls (HC). To evaluate the difference of serum sTim-3 in different stages of BC and its clinical value for postoperative recurrence of BC.

Results: The serum sTim-3 level of BC patients with stage III + IV (21.62 (17.27, 29.78)) were significantly higher than HC (4.49 (3.30, 7.60)), patients with stage I + II (14.96 + 4.94) (P < 0.0001). Serum sTim-3 level of BC patients with postoperative recurrence (21.8(12.40,34.20) were significantly higher than those without recurrence (17.13 ± 6.44) (P = 0.0130). When the serum sTim-3 level was below 11.8 ng/mL, the negative predictive values of sTim-3, CEA and CA15-3 were 90.9%, 68.0% and 67.1%, respectively, and the negative likelihood ratios were 0.16, 0.77 and 0.81, respectively. The positive rate of combined detection of sTim-3, CEA and CA15-3 was 58.1%, higher than single detection of CEA (22.6%) and CA15-3 (19.4%).

Conclusion: Serum sTim-3 levels may assist in the staging of BC. Combined detection of sTim-3, CEA, and CA15-3 can be used to routinely monitor the progression of BC and indicate the risk of postoperative BC recurrence.

Background: The neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) have been confirmed to be related to the clinicopathological features and prognosis of colorectal cancer (CRC) patients. However, the results have been inconsistent, and few studies have focused on a specific point in time during surgery and dynamic changes prior to and after surgery.

Methods: We conducted a retrospective analysis of 349 CRC patients and explored the value of NLR, PLR and their dynamic changes in predicting clinicopathological variables and prognosis in CRC.

Results: Preoperative NLR (Pre-NLR) was correlated with CEA, CA199 levels, tumor location and tumor stage (P=0.041, P=0.002, P=0.001 and P=0.012, respectively), whereas postoperative NLR (post-NLR) was relevant to age, sex, CA125 levels and T stage significantly (P=0.032, P=0.002, P=0.026, P=0.019, respectively). When comparing post- and pre-NLR values, there was a positive connection between increases in NLR and BMI, tumor location, T stage, and tumor stage (P=0.034, P=0.005, P=0.023, P=0.023, respectively). In addition, Preoperative PLR (pre-PLR) was correlated with sex, smoke and drink history, CEA and CA199 levels, tumor location, T stage and tumor stage (P=0.006, P=0.037, P=0.040, P=0.006, P=0.005, P<0.001, P=0.007, P=0.003 respectively), while postoperativePLR (post-PLR) was only associated with tumor location (P=0.010). Increases in PLR were significantly related to sex, smoking history, tumor location and differentiation (P=0.001, P=0.002, P<0.001, P=0.034, respectively). Patients with CRC who had a high post-PLR experienced significantly shorter relapse-free survival (RFS) compared to other patients (HR 0.607 (0.381-0.968), P=0.036). Furthermore, this high post-PLR has tendency association with shorter overall survival (OS) (HR 0.596 (0.338-1.050), P=0.076).

Conclusion: These findings suggest that levels and changes in NLR/PLR are associated with several unfavorable clinicopathological features in CRC patients. Furthermore, patients with high levels of post-PLR exhibit a worse prognosis.

Basal cell carcinoma (BCC) is the most common type of malignant skin tumour. This skin cancer is further divided into pigmented, morpheaform, superficial, and nodular BCC (nBCC), as well as fibroepithelioma of Pinkus. Despite its slow growth and very rare metastases, BCC might cause morbidity due to its tendency to relapse as well as its locally invasive nature, especially when located on the face. Wide local excision might be an effective treatment option for BCC and is usually followed by a surgical defect reconstruction procedure. We report a case of 61-year-old woman who presented with a superficially ulcerated, well-defined, hyperpigmented nodule with a rolled edge and frequent episodes of bleeding, as well as suppuration on the right mid-cheek in the past year before the consultation. The lesion was excised and the sample was sent for histopathological examination, revealing tumour mass in a palisading arrangement at the edges, forming solid islands, which is consistent with the diagnosis of nBCC with tumour-free edges. Defect closure with the mini cheek advancement flap (mini-CAF) technique yielded good results after eight months without any recurrence in one year. Skin flap techniques vary widely, among them is the cheek advancement flap technique which might be used for reconstructing defects on the mid-cheek. This flap technique can be modified as mini-CAF by placing a flap incision on the natural creases of the mid-cheek, namely the palpebromalar and nasojugal creases. Mini-CAF offer the advantage as its ability to camouflage the excision line by utilising the natural creases of the face, thus resulting in an aesthetically and functionally favourable result.

Background and aim: Ovarian metastasis occurs in 3-5% of patients with CRC. Ovaries are considered sanctuary sites and typically do not respond effectively to chemotherapy. Patients with KRAS mutation generally have a worse prognosis compared to those with KRAS wild type. This study will discuss the effect of palliative oophorectomy on survival rates for those patients compared to chemotherapy alone.

Methods: This is a retrospective study; we reviewed the charts of patients diagnosed with metastatic colorectal cancer at KHCC between January 2015 and December 2022. Out of 862 patients, 50 patients were eligible for the study; Patients were divided into two groups based on their treatment type, the palliative oophorectomy group and the chemotherapy alone group. The primary endpoint was a three-year median overall survival rate between the two groups. The secondary endpoints included three-year median progression-free survival and the difference in survival rate between the groups based on KRAS and BRAF mutation status.

Results: In the oophorectomy group, the median overall survival (OS) was 19.3 months compared to 10.3 months in the chemotherapy alone group, with a P value of 0.05. Median progression-free survival (PFS) was also better in the oophorectomy group at 14.6 months compared to 9.4 months, with a P value of 0.59. For patients with KRAS mutation who underwent oophorectomy, the median OS was significantly better at 29.1 months compared to 10.3 months in the chemotherapy alone group, P value of 0.03.

Conclusion: Our study indicates that palliative oophorectomy in metastatic CRC is associated with better survival. Even patients who harbor mutated KRAS, which typically have more aggressive disease behavior, showed better survival outcomes with oophorectomy compared to systemic chemotherapy alone.

Purpose: To evaluate the survival outcomes of patients with intermediate to advanced hepatocellular carcinoma (HCC), patients who underwent transarterial chemoembolization (TACE) alone were compared with those who underwent a combination of TACE and ablation therapy.

Patients and methods: This study retrospectively evaluated 536 HCC patients in our hospital from July 2016 to November 2022. All patients underwent TACE, with a subset also receiving ablation therapy. To ensure comparability, propensity score matching (PSM) was performed. We then compared overall survival (OS) and progression-free survival (PFS) between these two groups. Survival outcomes were analyzed utilizing Kaplan-Meier curves and compared via the Cox regression.

Results: 200 among these 536 HCC patients received TACE combined with ablation whereas the remaining 336 received TACE alone. With PFS analysis, the numbers were reduced to 176 in combination therapy group and 250 in TACE alone group. With and without PSM, the OS and PFS were consistently and significantly better in the former than the latter group. In patients with Barcelona Clinic Liver Cancer (BCLC) stage B or C, those who received combination therapy demonstrated significantly higher OS compared to those treated with TACE alone. For stage B patients, PFS was also significantly longer in the combination therapy group, before and after PSM [hazard ratio (HR), 0.563; 95% CI: 0.360-0.879; P = 0.012, HR, 0.613; 95% CI: 0.382-0.985; P = 0.043]. However, after PSM, no statistical difference in survival outcomes was observed between the two groups for stage C patients (HR, 0.673; 95% CI: 0.395-1.146; P = 0.145).

Conclusion: Our data suggested that for OS, the combination therapy has sustained benefits for both patients with stage B and C, But for PFS, the benefits of the combination therapy among the stage C patients, could not be persistently demonstrated by the current datasets.

Purpose: To explore the efficacy and safety of pyrotinib in a real-world setting in a population with HER2-positive advanced breast cancer, subgroup analysis was conducted based on different clinicopathological features to further explore the general characteristics of patients, tumor nature, and the effect of various lines of treatment before patients started pyrotinib on the efficacy of pyrotinib in the real-world study.

Methods: The clinical pathological characteristics, drug efficacy and related adverse reactions of HER2-positive MBC patients treated with pyrotinib in six hospitals in Southeast Zhejiang Province from February 2018 to December 2023 were collected and analyzed retrospectively.

Results: A total of 342 patients with HER2-positive MBC were enrolled. The median follow-up time of 42.0 months. The median age of the overall population was 52 years (range from 25-90 year old). Median progression-free survival in the total population was 10.0 months, the median overall survival was 29.0 months. The (objective response rate, ORR) was 40.35% and the (disease control rate, DCR) was 83.92%. The median progression-free survival (PFS) in the total population was 10.0 months, the median overall survival was 29.0 months. And pyrotinib had better mPFS for advanced first-line treatment than for second-third-line and beyond(14.0 months vs.10.0 months vs.6.0 months, P<0.001). Multivariate Cox regression analysis showed that ECOG, HER2 status, brain metastasis, liver metastasis, number of pyrotinib treatment lines, previous lapatinib treatment, combined capecitabine therapy and trastuzumab resistance were independent prognostic factors for PFS. Diarrhea was the most common adverse reaction (ADR) in 205 patients (59.94%), which could be controlled by antidiarrheal drugs.

Conclusion: This multicenter study suggested that the use of pyrotinib for HER2 positive MBC had a relatively good efficacy, especially for those who received first-line pyrotinib treatment and those who were sensitive to previous trastuzumab treatment. Patients with brain metastasis and liver metastases also benefit from pyrotinib treatment, especially for patients treated with brain radiotherapy and/or surgery. ECOG, HER2 status, brain metastasis, liver metastasis, number of pyrotinib treatment lines, previous lapatinib treatment, combined capecitabine therapy and trastuzumab resistance were independent prognostic factors for PFS in HER2 Positive MBC patients treated with pyrotinib. The most common adverse reaction associated with pyrotinib is diarrhea, which can be well controlled through antidiarrheal treatment. Pyrotinib combined with vinorelbine has similar efficacy to pyrotinib combined with capecitabine and has fewer side effects, and can be used as an alternative to capecitabine.

Lung cancer is one of the most lethal malignancies worldwide, making early diagnosis and targeted treatment crucial for improving patient outcomes. Liquid biopsy, a rapidly advancing non-invasive diagnostic tool, has shown significant potential in lung cancer management through dynamic monitoring. This review explores the integration of liquid biopsy with traditional diagnostic techniques in lung cancer management. We first discuss the essential roles of traditional approaches, such as imaging and tissue biopsy, and then examine the concepts of liquid biopsy, emphasizing its unique advantages in early detection, treatment monitoring, and prognosis. Finally, we propose strategies for integrating liquid biopsy with traditional diagnostics, offering multimodal framework to enhance precision medicine in lung cancer.

Pancreatic cancer (PC) remains one of the most challenging malignancies to treat. Current therapeutic options are unsatisfactory, and there is an urgent need for more effective and less toxic drugs to improve the dismal prognosis of PC. In recent years, drug repurposing (DR) has emerged as an attractive strategy to identify novel treatments for PC by leveraging existing drugs approved for other indications. Through the use of electronic medical records, Artificial Intelligence, study of metabolic pathways, signalling pathways, and many other approaches, it has become much easier in recent years to identify potential novel uses for old drugs. Although policy, funding and research attention in this area are steadily growing, major challenges to efficient and effective patient-centric DR in PC need to be addressed. These include but are not limited to regulatory, financial and funding barriers and the lack of coordination and collaboration among several sectors and stakeholders. To explore the opportunities and challenges associated with DR in PC, a one-day multi-stakeholder meeting was held on 14^th of November 2024 in Brussels, Belgium as part of the REMEDi4ALL project. This meeting provided a platform for researchers, clinicians, industry representatives, funders, regulatory experts, and patient advocates to discuss and propose actions to optimize and accelerate DR in PC. Insights from this meeting support the potential of DR to enhance PC treatment options while highlighting the importance of systemic and supportive changes in the regulatory, policy and funding landscapes, interdisciplinary collaboration, data sharing, and patient involvement in driving therapeutic innovation. This summary highlights key outcomes and recommendations from the meeting in informing future efforts to advance DR initiatives in the context of PC.