BackgroundTriple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by high metastatic potential and resistance to conventional therapies, representing a significant clinical challenge. Although nano albumin-bound paclitaxel (nab-PTX) has demonstrated generally good treatment effect, the mechanisms underlying its enhanced therapeutic performance, particularly its potential immunomodulatory effects, remain unclear.MethodsUsing both in vitro and in vivo TNBC models, we investigated the immunomodulatory effects of nab-PTX. Specifically, we evaluated its ability to induce immunogenic cell death (ICD), activate dendritic cells (DCs) via the cGAS-STING signaling pathway, and influence CD8+ T cell recruitment and infiltration within the tumor microenvironment.ResultsTreatment with nab-PTX induced ICD in TNBC cells was associated with enhanced activation of DCs through the cGAS-STING pathway. This activation was accompanied by improved antigen presentation and a significant increase in intratumoral CD8+ T cell infiltration. Collectively, these immune alterations suggest that nab-PTX contributes to a more immunologically active tumor microenvironment, characterized by heightened T cell mediated immune engagement.ConclusionOur study indicate that, beyond its direct cytotoxic effects, nab-PTX may exert anti-tumor activity in TNBC through modulation of the tumor immune microenvironment. By inducing ICD and promoting DCs activation, nab-PTX appears to support CD8+ T cell recruitment, thereby potentially enhancing immune mediated tumor regression. This immunologically supportive role of nab-PTX highlights its potential value in strategies aimed at improving the efficacy of chemotherapy based or immunotherapy combined treatments in TNBC.

TPS6137 Background: Radiotherapy is the primary treatment for nasopharyngeal carcinoma (NPC). Currently, induction chemotherapy combined with concurrent chemoradiotherapy has become a Category I recommendation for NPC treatment. Studies show that the GP regimen is one of the most effective induction chemotherapy protocols for locally advanced NPC. However, the incidence of grade 3-4 acute toxicities with the GP regimen is as high as 75.7%, severely affecting patient treatment compliance. To reduce toxicity while maintaining efficacy, this study focuses on a "chronomodulated chemotherapy" strategy, which adjusts drug administration timing based on biological rhythms to minimize damage to normal tissues. Methods: Clinical Data: 1. Sample Size Calculation: This study is a randomized controlled trial with a non-inferiority design. Based on a 3-year recurrence-free survival rate of 85.3% in the conventional group, a non-inferiority margin (δ) of 10%, a one-sided α of 0.025, a power (1-β) of 0.8, equal group sizes, and accounting for a 10% dropout rate, the calculated total sample size is 434 subjects. 2. Inclusion Criteria: Treatment-naïve patients with Stage III or IVa non-keratinizing nasopharyngeal carcinoma (UICC/AJCC 8th edition). 3. Exclusion Criteria: History of prior malignancy, prior radiotherapy, or presence of other severe diseases. 4. Withdrawal Criteria: Occurrence of severe adverse events or intolerable toxicities during the study. Treatment Protocol: 1. Induction Chemotherapy Phase: Experimental Group: Gemcitabine 1000 mg/m², IV infusion over 30 min on days 1 & 8, administered between 08:00-09:30; Cisplatin 80 mg/m², continuous IV infusion (civ) on day 1, delivered evenly over 12 h from 10:00 to 22:00. Repeated every 3 weeks (Q3W) for 3 cycles. Control Group: Gemcitabine 1000 mg/m², IV infusion over 30 min on days 1 & 8; Cisplatin 80 mg/m², IV infusion over 2-3 h on day 1. Q3W for 3 cycles. 2. Concurrent Chemoradiotherapy Phase: Concurrent Cisplatin Regimen: Experimental Group: Cisplatin 100 mg/m², civ on day 1, delivered evenly over 12 h from 10:00 to 22:00. Q3W for 3 courses. Control Group: Cisplatin 100 mg/m², IV infusion over 2-3 h on day 1. Q3W for 3 courses. 3. Radiotherapy: Intensity-Modulated Radiation Therapy (IMRT) was used, with a total dose of 69.96-72.6 Gy delivered in 33 fractions. Innovation: Therapeutic efficacy for nasopharyngeal carcinoma has reached a plateau, making “toxicity reduction” a key research focus. The toxicity-reducing approach of chronomodulated chemotherapy holds promising application prospects for locally advanced nasopharyngeal carcinoma. Current Status: To date, 122 patients have been enrolled. Clinical trial information: ChiCTR2400086032.

PURPOSE:The efficacy and safety of TPF-induced chemotherapy(IC) combined with concurrent chemoradiotherapy(CCRT) compared to CCRT and sequential PF-adjuvant chemotherapy(AC) lack phase III randomized controlled clinical trials for evaluation, so the comparative efficacy and safety between the two approaches remain unclear. METHODS AND MATERIALS:This randomized clinical phase III trial recruited patients from May 2018 to July 2021,at 4 institutions in China(NCT03574324), 266 patients were enrolled and randomly assigned to either the IC or AC groups. The IC group received TPF followed by CCRT, while the AC group received CCRT followed by PF. We are reporting on the primary outcome of progression-free survival (PFS) and secondary endpoints of overall survival(OS), locoregional relapse-free survival(LRFS), distant metastasis-free survival(DMFS), and toxicity profile. RESULTS:The 3-year PFS was similar between the two groups, with 79 % for the IC group and 74.5 % for the AC group (P = 0.454) at a median follow-up of 39 months. Similar findings were observed, with no significant disparities in OS, LRFS, and DMFS between the two treatment cohorts. Both groups had similar compliance rates for radiotherapy and chemotherapy. However, the IC group experienced fewer grade toxic effects during CCRT, such as nausea/vomiting, swallowing, and dryness (101[77.10 %] vs. 114[89.06 %] patients,40 [30.53 %]vs56 [43.75 %] patients and 58 [44.27 %]vs86 [67.19 %] patients, respectively). However,3-4 grade leukopenia and neutrophilia patients were increased(58 [44.27 %]vs28 [21.88 %] patients and 78 [59.54 %]vs24 [18.75 %]) in the IC group. CONCLUSIONS:In this randomized clinical trial, IC did not improve 3-year PFS for LA-NPC patients and increased hematological toxicity. Still, the advantage of it is that it did reduce the incidence rates of nausea/vomiting, swallowing, and dry mouth during radiotherapy.

6113 Background: Induction chemotherapy followed by radiotherapy with concurrent cisplatin is a standard treatment for locoregionally advanced nasopharyngeal carcinoma (LA-NPC). The TPF induction regimen combined with intensity-modulated radiation therapy (IMRT) improves tumor control but causes substantial toxicity. Circadian rhythms regulate tumor biology and drug metabolism. Docetaxel, cisplatin, and 5-fluorouracil show circadian-dependent pharmacologic properties. Chrono-chemotherapy aligns drug administration with circadian rhythms and may reduce toxicity. This study compared long-term outcomes and late adverse events between chrono-chemotherapy and conventional chemotherapy combined with IMRT in LA-NPC. Methods: This single-center, prospective, randomized clinical trial was registered at ClinicalTrials.gov (NCT03196869). Between April 2017 and May 2018, 128 patients with newly diagnosed stage III–IVa nasopharyngeal carcinoma were randomly assigned to chrono-chemotherapy or conventional chemotherapy. All patients received three cycles of TPF induction chemotherapy, followed by IMRT with two cycles of concurrent cisplatin chemotherapy. Survival outcomes were analyzed using the Kaplan–Meier method and compared by log-rank test. Late toxicities were graded using CTCAE v5.0. Quality of life was assessed with the EORTC QLQ-C30 questionnaire. Results: A total of 124 patients were included in the survival analysis. No significant differences were observed between groups in 5-year overall survival (P=0.709), progression-free survival (P=0.492), distant metastasis-free survival (P=0.467), or locoregional recurrence-free survival (P=0.697). The chrono-chemotherapy group showed lower rates of xerostomia (P=0.034) and dysphagia (P=0.019). No grade ≥4 late toxicities were observed. Global health status scores were higher in the chrono-chemotherapy group (P=0.043). Conclusions: Chrono-chemotherapy combined with IMRT achieved long-term survival outcomes comparable to conventional chemotherapy in LA-NPC. This approach reduced selected late toxicities and improved overall health status. Chrono-chemotherapy may represent a toxicity-sparing treatment option. Clinical trial information: NCT03196869 . Late toxicities and quality of life. Outcome Conventional Chemotherapy Chrono-chemotherapy P value Xerostomia, n (%) 24/36 (66.7) 16/38 (42.1) 0.034 Dysphagia, n (%) 24/36 (66.7) 15/38 (39.5) 0.019 Global health status score* 58.33 (50.00–72.92) 75.00 (50.00–83.33) 0.043 *Scores derived from the EORTC QLQ-C30 questionnaire; values are presented as median (interquartile range).

e18034 Background: To research whether TPF (Docetaxel plus Fluorouracil plus Cisplatin) chrono-chemotherapy combined with cisplatin concurrent chemoradiotherapy can reduce long-term toxicity without affecting the survival of patients with de novo metastatic nasopharyngeal carcinoma (mNPC) compared with conventional chemotherapy combined with cisplatin concurrent chemoradiotherapy. Methods: A retrospective analysis of the clinical data of 121 de novo mNPC patients who treated with TPF chemotherapy at our hospital from January 1, 2012, to December 31, 2018. Among them, 79 patients were treated with chrono-chemotherapy and 42 patients were treated with conventional chemotherapy. The specific chemotherapy regimen for chrono-chemotherapy group:TPF induction chemotherapy for 2-4 cycles, docetaxel: 75mg/m2, ivgtt, d1; Cisplatin: 75mg/m2, civ, d1-5, 60h (10Am—10Pm); 5-Fluorouracil: 750mg/m2/d, civ, administered by intravenous infusion of electronic chemotherapy automatic injection pump d1-5, 60 hours (10 Pm-10 Am), 21 days/cycle. The evaluation of therapeutic efficacy after induction should involve intensity-modulated radiotherapy for at least patients with stable disease, during which concurrent cisplatin chemotherapy is administered. Two cycles of adjuvant chemotherapy were administered 1 month after radiotherapy with the same regimen as induction chemotherapy. The total chemotherapy cycle was 4-6 cycles. The Kaplan-Meier method and log-rank test were used to estimate overall survival (OS) and progression-free survival (PFS), while the COX proportional hazards model was employed for multivariate analysis. Long-term toxic side effects between the two groups were assessed using the chi-square test or Mann-Whitney U test. Propensity score matching was utilized to address confounding factors. Results: At a median follow-up of 104 months, 69.6% of patients died in the chrono-chemotherapy group and 73.8% in the conventional chemotherapy group, and the median OS and PFS in the chrono-chemotherapy group and conventional chemotherapy group were 40 vs 32 months (P=0.636) and 30 vs 19 months, respectively (P=0. 975), there were no statistically significant differences in OS rates and PFS rates at 3, 5, and 7 years between the two groups before and after matching. The incidence of xerostomia, dysphagia, and trismus in the chrono-chemotherapy group matched for timing was significantly lower than that in the conventional chemotherapy group, with a statistically significant difference. (P<0.05). Conclusions: The TPF chrono-chemotherapy combined with cisplatin concurrent chemoradiotherapy reduces the incidence of toxic side effects while ensuring survival, which can benefit patients.

6100 Background: To investigate whether TPF induction chemotherapy combined with concurrent chemoradiotherapy (CCRT) can provide greater survival benefits compared to CCRT followed by PF adjuvant chemotherapy. Methods: Patients with newly diagnosed locally advanced (Stage III–IVA) nasopharyngeal carcinoma (NPC) treated at the Affiliated Tumor Hospital of Guizhou Medical University, the Second Affiliated Hospital of Guizhou Medical University, the Second Affiliated Hospital of Zunyi Medical University, and Guiyang Hospital of Guizhou Aviation from May 2018 to July 2021 were enrolled. Each group included 133 patients. The experimental group received 3 cycles of TPF induction chemotherapy (docetaxel 75mg/m²,intravenous infusion, Day 1; cisplatin 75mg/m²,continuous intravenous infusion over 5 days,10:00–22:00 daily; fluorouracil 750mg/m²/day, continuous intravenous infusion over 5 days, 22:00–10:00 daily) followed by 2–3 cycles of concurrent chemotherapy (cisplatin 100mg/m², continuous intravenous infusion over 2 days, 10:00–22:00 daily). The control group received PF adjuvant chemotherapy (cisplatin 80mg/m², continuous intravenous infusion over 5 days,10:00–22:00 daily; fluorouracil 800mg/m²/day, continuous intravenous infusion over 5 days, 22:00–10:00 daily) combined with 2–3 cycles of concurrent chemotherapy (same as induction chemotherapy).Both groups underwent intensity-modulated radiotherapy (IMRT),with total doses of 69.96 Gy for T1–T2 primary lesions, 72.6 Gy for T3–T4 lesions, and 69.96 Gy for positive lymph nodes. Data were analyzed using SPSS 26.0.Differences in 5-year PFS, OS, LRFS, DMFS, and adverse events were compared between the two groups. Results: No significant differences were observed between the two groups in age, sex, Karnofsky Performance Status (KPS) score, T stage, N stage, or overall stage ( P > 0.05).At a median follow-up of 58 months, the 5-year PFS in both the intention-to-treat and per-protocol populations was similar between the induction chemotherapy (IC) and adjuvant chemotherapy (AC) groups (66.6% vs 66.0%, P = 0.589; 75.3% vs 69.9%, P =0.471). The 5-year OS, LRFS, and DMFS rates were 73.0% vs 71.3% ( P =0.582), 87.4% vs 90.8% ( P =0.508), and 76.9% vs 72.6% ( P =0.267), respectively, with no significant differences. Conclusions: Both groups had similar 5-year PFS, OS, LRFS, DMFS, and long-term toxicity profiles. Clinical trial information: NCT03574324 . 5-year observation indicators for two groups. Observation indicators IC+CCRT CCRT+AC P value Risk ratio(95% CI) PFS ITT Population 66.6% 66.0% 0.589 0.89（0.58-1.36） PP Population 75.3% 69.9% 0.471 0.85（0.55-1.33） OS 73.0% 71.3% 0.582 0.88（0.55-1.39） LRFS 87.4% 90.8% 0.508 1.30（0.60-2.80） DMFS 76.9% 72.6% 0.267 0.75（0.45-1.25） OS, LRFS, and DMFS were all calculated in the ITT population.

e18036 Background: To investigate the dynamic changes of peripheral blood immune-related indicators and their association with therapeutic efficacy in patients with recurrent/metastatic nasopharyngeal carcinoma (NPC) treated with PD-1 inhibitors combined with the GP regimen. Methods: A retrospective analysis was conducted on 46 patients with recurrent/metastatic NPC. All patients received at least one PD-1 antibody inhibitor (camrelizumab/toripalimab/sintilimab/tislelizumab) combined with GP (gemcitabine + cisplatin) chemotherapy. Peripheral blood samples were collected at baseline and after three treatment cycles to measure immune-related indicators, including PD-1, CTLA-4, and Treg cells. The expression differences of these indicators at baseline between the objective response group (PR+CR) and the poor-response group (SD+PD), as well as their dynamic percentage changes during treatment, were compared. Univariate and multivariate logistic regression analyses were further performed to determine whether PD-1, CTLA-4, Treg, CD4+/CD8+ ratio, CD3+, CD4+, CD16+, PDC, and MDC were independent factors influencing treatment efficacy. Results: Baseline peripheral blood PD-1 expression was significantly lower in the objective response group (PR+CR) compared to the poor-response group (SD+PD) (p<0.05). Trends of decrease were observed in Treg, CD16+, CD4+, and CD4+/CD8+ ratio in the objective response group (p>0.05), while trends of increase were noted for CTLA-4, CD3+, MDC, and PDC (p>0.05). After treatment, levels of PD-1 and CD16+ decreased significantly compared to baseline (p<0.05). Although CTLA-4, Treg, CD3+, CD4+, CD4+/CD8+ ratio, MDC, and PDC showed decreasing trends post-treatment, the differences were not statistically significant (p>0.05). Multivariate logistic regression analysis indicated that PD-1 was an independent factor influencing treatment efficacy in patients with recurrent/metastatic NPC (p<0.05). Conclusions: PD-1 inhibitor combined with GP regimen chemotherapy demonstrates favorable efficacy in recurrent/metastatic NPC. Low baseline PD-1 expression may be associated with better therapeutic outcomes. The significant post-treatment decrease in PD-1 and CD16+ expression may suggest immune cell activation and migration to tumor sites following treatment.

Dendritic cell (DC)-based immunotherapy shows limited efficacy against hepatic fibrosis, and the underlying mechanometabolic crosstalk remains unclear. Here, from a mechanobiological perspective, we demonstrate that increased extracellular matrix (ECM) stiffness in fibrotic liver triggered antigen-independent abnormal DC maturation, characterized by elevated co-stimulatory molecules, impaired phagocytic capacity, reduced IL-10 secretion, and suppressed regulatory T cell (Treg) differentiation. Mechanistically, stiff ECM inhibited the AMPK-LXRα-ABCG1 signaling axis in DCs, reducing cholesterol efflux and promoting intracellular cholesterol accumulation. Cholesterol depletion or AMPK activation reversed stiffness-induced abnormal DC maturation. In mouse models, combined treatment with pirfenidone and simvastatin reduced liver stiffness, collagen deposition, and restored immune tolerance by correcting DC cholesterol metabolism. Our study identified a mechanometabolic pathway linking matrix stiffness to DC dysfunction, providing a promising immunometabolic strategy for antifibrotic therapy.

Intracranial neuroendocrine carcinoma (NEC) is a highly uncommon malignancy, accounting for approximately 0.74% of cases. It is characterized by rapid infiltration and poor survival rates. This case report details a 51-year-old woman who presented with headaches. Magnetic resonance imaging (MRI) identified an enhancing lesion in the right temporal lobe, and the diagnosis was confirmed by immunohistochemical (IHC) analysis. The patient underwent surgical resection, followed by chemoradiotherapy for recurrence, and subsequent Gamma Knife radiosurgery combined with bevacizumab. Notably, she has achieved a postoperative survival exceeding four years to date. This report comprehensively describes the clinical presentation, diagnostic workup, multidisciplinary treatment course, and favorable outcome, highlighting the potential for prolonged survival with aggressive, multimodal management.

Aim and backgroundDue to the radiosensitivity and deep anatomical location of nasopharyngeal carcinoma (NPC), radiotherapy serves as the cornerstone of standardized treatment for this malignancy. Beyond its cytotoxic effects, radiotherapy can serve as an immunological adjuvant by inducing immunogenic cell death (ICD). Dendritic cells (DCs), as potent antigen-presenting cells, play a critical role in tumor immunotherapy, but their exact role in the ICD process of NPC remains unclear. The effects of high-dose radiation (≥2 Gy) on DCs and the type of immune response it elicits in NPC have not been fully elucidated.MethodsAn in vitro study was conducted to assess whether ICD of NPC 5-8F cells induced by high-dose radiation could regulate the immune response of DCs. Specifically, the maturation and antigen-presenting capacity of DCs were evaluated following co-culture with NPC cells exposed to high-dose radiation.ResultsHigh-dose radiation was found to induce ICD in NPC 5-8F cells, as evidenced by increased pro-inflammatory factor levels and reduced anti-inflammatory factor levels in the cell culture supernatant. Co-culture with NPC cells exposed to high-dose radiation for 15 minutes significantly enhanced the expression of surface molecules on DCs, promoting their immune sensitization.ConclusionHigh-dose radiation-induced apoptosis of NPC 5-8F cells is a form of ICD, which plays an important role in regulating DC immune function. These findings provide insight into the immunomodulatory effects of radiotherapy in NPC and its potential to enhance tumor immunotherapy through DC activation.

BACKGROUND AND PURPOSE:Radiotherapy (RT) is the most commonly-used treatment for nasopharyngeal carcinoma (NPC). Ferroptosis is a type of regulated cell death that is associated with cancer development. This study aims to investigate the relationship between RT and iron metabolism in NPC patients, as well as the effects of different doses of ionizing radiation (IR) on NPC cells and the role played by ferroptosis METHODS AND MATERIALS: A retrospective analysis was conducted on changes in iron metabolism markers-serum iron, hemoglobin, TIBC, UIBC, and transferrin saturation-before and after radiotherapy in 73 participants. CCK-8 assay was used to assess the effects of varying radiation doses on the viability of 5-8F cells, determining the radiation dose applied in this study. Real-time quantitative PCR (RT-qPCR) was performed to examine how different radiation doses affect the expression of ferroptosis-related genes (FRGs), including ACSL4, ATP5G3, PTGS2, and IREB2. Western blot analysis was employed to measure the protein expression levels of GPX4 under varying radiation doses. The contents of lactate dehydrogenase (LDH), reactive oxygen species (ROS), malonaldehyde (MDA), [Fe2+], adenosine triphosphate (ATP), and glutathione (GSH) were assessed to evaluate the induction of ferroptosis. In addition, flow cytometry was used to analyze cell cycle distribution in NPC cells following various doses of IR. FRGs expression was assessed in NPC cell lines with varying radiosensitivity RESULTS: Compared to pre-radiotherapy levels, serum iron and transferrin saturation significantly increased after treatment, while hemoglobin and UIBC showed marked reductions. The CCK8 results indicated that after exposure to 2-18 Gy of radiation, the viability of 5-8F cells was lowest at a dose of 10 Gy. In irradiated NPC cells, mRNA expression of pro-ferroptosis factors such as ACSL4, PTGS2, and IREB2 was generally upregulated, whereas protein levels of the anti-ferroptosis factor GPX4 were downregulated. As the IR dose increased, the contents of LDH, ROS, and MDA were upregulated, while ATP and GSH levels were downregulated. In addition, high-dose IR exposure can block NPC cells in the G2/M phase. Moreover, we found that the expression levels of three ferroptosis driver genes were lower in radioresistant NPC cell line CONCLUSIONS: High dose IR can induce ferroptosis in NPC cells, highlighting the potential for developing novel ferroptosis-based targets and overcoming radioresistance in clinical NPC treatments.

Radiotherapy is a commonly used method in the treatment of bladder cancers (BC). Radiation-induced immunogenic cell death (ICD) is related to the immune response against cancers and their prognoses. Even though dendritic cells (DC) act as powerful antigen-presenting cells in the body, their precise role in this ICD process remains unclear. Accordingly, an in vitro study was undertaken to ascertain whether high-dose radiation-induced ICD of BC cells could regulate the immune response of DC. The results indicated that high-dose radiation treatments of BC cells significantly increased their levels of apoptosis, blocked their cell cycle in the G2/M phase, increased their expression of ICD-related proteins, and upregulated their secretion of CCL5 and CCL21 which control the directed migration of DC. It was also noted that expression of CD80, CD86, CCR5, and CCR7 on DC was upregulated in the medium containing the irradiated cells. In conclusion, the present findings illustrate that high-dose radiation can induce the occurrence of ICD within BC cells, concomitantly resulting in the activation of DC. Such findings could be of great significance in increasing the understanding how radiotherapy of BC may work to bring about reductions in cell activity and how these processes in turn lead to immunoregulation of the function of DC.

Nasopharyngeal carcinoma (NPC) still recurs or leads to distant metastasis in 10%-30% patients after standardized treatment, which increases the serious toxic side effects and treatment difficulty with recourse therapy. In this study, we found that the biological clock gene Period1(PER1) was expressed at low levels in human nasopharyngeal carcinoma cell (CNE2)and NPC tissues, and overexpression of PER1 decreased the invasion and migration ability of NPC cells and increased the expression of lipid peroxidation (LPO), Fe2+ and glutathione (GSH). The expression of glutathione peroxidase (GPX4) and solute carrier family 7 member 11 (SLC7A11) was found to be decreased in CNE2 cells and tissues of NPC. Our results suggest that PER1 may induce ferroptosis in CNE2 by inhibiting the expression of GPX4 and SLC7A11, thereby causing LPO and Fe2+ accumulation in CNE2 and finally inducing ferroptosis in CNE2. This novel mechanism may provide a new direction for the treatment of NPC.

Distal metastasis is the main cause of clinical treatment failure in patients with colon cancer. It is now known that the invasion and metastasis of cancer cells is precisely regulated by chemical and physical factors in vivo. However, the role of extracellular matrix (ECM) stiffness in colon cancer cell (CCCs) invasion and metastasis remains unclear. Here, bioinformatical analysis suggested that a high expression level of yes associated protein1 (YAP1) was significantly associated with metastasis and poor prognosis in colon cancer patients. We further investigated the effects of polyacrylamide hydrogels with different stiffnesses (3, 20, and 38 kPa), which were simulated as ECM, on the mechanophenotype (F-actin cytoskeleton organization, electrophoretic rate, membrane fluidity, and Young's modulus) of CCCs. The results showed that a stiffer ECM could induce the maturation of focal adhesions and formation of stress fibers in CCCs, regulate their mechanophenotypes, and promote cell motility. We also demonstrated that the expression levels of YAP1 and paxillin were positively correlated in patients with colon cancer. YAP1 knockdown reduces paxillin clustering and cell motility and alters the cellular mechanophenotypes of CCCs. This is of great significance for an in-depth understanding of the invasion and metastatic mechanisms of colon cancer and for the optimization of clinical therapy from the perspective of mechanobiology.

Tumor vascular normalization (TVN) is associated with antitumor therapeutic efficacy in nasopharyngeal carcinoma (NPC). However, the short time window of TVN is the biggest hindrance to its wide clinical application. We investigated whether targeting transforming growth factor beta can enhance the TVN effect of bevacizumab (BEV)-induced patient-derived xenograft (PDX) models of NPC. We constructed mouse subcutaneous PDX models of NPC and classified the mice into four drug-treatment groups, namely placebo control, galunisertib, BEV, and galunisertib + BEV. We performed MRI multi-parameter examinations at different time points and evaluated the vascular density, vascular structure, and tumor hypoxia microenvironment by histopathology. The efficacy of chemotherapy and drug delivery was evaluated by administering cisplatin. We found that combined therapy with galunisertib and BEV significantly delayed tumor growth, enhanced the TVN effect, and improved chemotherapeutic efficacy compared with monotherapy. Mechanistically, galunisertib reversed the epithelial-mesenchymal transition process and inhibited the expression of hypoxia-inducible factor 1α and vascular endothelial growth factor by downregulating LAMC2. Correlation analysis of MRI data and pathological indicators showed that there was a good correlation between them.

PurposeThis study aimed to evaluate 5-year outcomes and the late toxicity profile of chrono-chemotherapy with different infusion rates in patients with locally advanced nasopharyngeal carcinoma (NPC).Methods and materialsOur retrospective analysis included 70 patients with locally advanced NPC stages III and IVB (according to the 2010 American Joint Committee on Cancer staging system). Patients were treated with two cycles of induction chemotherapy (IC) before concurrent chemoradiotherapy (CCRT) at Guizhou Cancer Hospital. The IC with docetaxel, cisplatin (DDP) and fluorouracil regimen. Patients were divided into two groups during CCRT. Using a “MELODIE” multi-channel programmed pump, DDP (100 mg/m2) was administered for 12 hours from 10:00 am to 10:00 pm and repeated every 3 weeks for 2-3 cycles. DDP was administered at the peak period of 4:00 pm in the sinusoidal chrono-modulated infusion group (Arm A, n=35). The patients in Arm B received a constant rate of infusion. Both arms received radiotherapy through the same technique and dose fraction. The long-term survival and disease progression were observed.ResultsAfter a median follow-up of 82.8 months, the 5-year progression-free survival rate was 81.3% in Arm A and 79.6% in Arm B (P = 0.85). The 5-year overall survival rate was not significantly different between Arm A and Arm B (79.6% vs 85.3%, P = 0.79). The 5-year distant metastasis-free survival rate was 83.6% in Arm A and 84.6% in Arm B (P = 0.75). The 5-year local recurrence-free survival rate was 88.2% in Arm A and 85.3% in Arm B (P = 0.16). There were no late toxicities of grade 3-4 in either group. Both groups had grade 1-2 late toxicities. Dry mouth was the most common late toxic side effect, followed by hearing loss and difficulty in swallowing. There was no statistically significant difference between Arm A and Arm B in terms of side effects.ConclusionLong-term analysis confirmed that in CCRT, cisplatin administration with sinusoidal chrono-modulated infusion was not superior to the constant infusion rate in terms of long-term toxicity and prognosis.