OBJECTIVE: Patients with recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) have proven benefit from anti-programmed cell death 1 (anti-PD-1) monotherapy. Here, we retrospectively analyze the association of plasma Epstein-Barr virus (EBV) DNA load and tumor viral lytic genome with clinical outcome from 2 registered phase I trials.
METHODS: Patients with RM-NPC from Checkmate 077 (nivolumab phase I trial in China) and Camrelizumab phase I trial between March 2016 and January 2018 were enrolled. Baseline EBV DNA titers were tested in 68 patients and EBV assessment was performed in 60 patients who had at least 3 post-baseline timepoints of EBV data and at least 1 post-baseline timepoint of radiographic assessment. We defined \"EBV response\" as 3 consecutive timepoints of load below 50% of baseline, and \"EBV progression\" as 3 consecutive timepoints of load above 150% of baseline. Whole-exome sequencing was performed in 60 patients with available tumor samples.
RESULTS: We found that the baseline EBV DNA load was positively correlated with tumor size (spearman p < 0.001). Both partial response (PR) and stable disease (SD) patients had significantly lower EBV load than progression disease (PD) patients. EBV assessment was highly consistent with radiographic evaluation. Patients with EBV response had significantly improved overall survival (OS) than patients with EBV progression (log-rank p = 0.004, HR = 0.351 [95% CI: 0.171-0.720], median 22.5 vs. 11.9 months). The median time to initial EBV response and progression were 25 and 36 days prior to initial radiographic response and progression, respectively. Patients with high levels of EBV lytic genomes at baseline, including BKRF2, BKRF3 and BKRF4, had better progression-free survival (PFS) and OS.
CONCLUSIONS: In summary, early clearance of plasma EBV DNA load and high levels of lytic EBV genes were associated with better clinical outcome in patients with RM-NPC receiving anti-PD-1 monotherapy.

Genome organization can regulate gene expression and promote cell fate transitions. The differentiation of germline stem cells (GSCs) to oocytes in Drosophila involves changes in genome organization mediated by heterochromatin and the nuclear pore complex (NPC). Heterochromatin represses germ cell genes during differentiation, and NPCs anchor these silenced genes to the nuclear periphery, maintaining silencing to allow for oocyte development. Surprisingly, we found that genome organization also contributes to NPC formation, mediated by the transcription factor Stonewall (Stwl). As GSCs differentiate, Stwl accumulates at boundaries between silenced and active gene compartments. Stwl at these boundaries plays a pivotal role in transitioning germ cell genes into a silenced state and activating a group of oocyte genes and nucleoporins (Nups). The upregulation of these Nups during differentiation is crucial for NPC formation and further genome organization. Thus, cross-talk between genome architecture and NPCs is essential for successful cell fate transitions.

UNASSIGNED: The introduction of Highly Active Anti-Retroviral Therapy (HAART) has led to a dramatic decrease in Human Immune Deficiency Virus (HIV) related morbidity and mortality in the developed as well as developing world. Whilst HAART has been effective in reducing rapidly progressive retinopathies, there are other ocular manifestations of HIV which are yet to be determined, characterised and addressed. The aim of the study was to determine the effect of HAART on Accommodative-Convergence mechanism among HIV/AIDS patients in Northwestern, Nigeria.
UNASSIGNED: This was hospital-based cohort study carried out from April 2019 to November 2019. Participants that met the inclusion criteria were recruited and were separated into two groups A and B. Group A were those about to commence HAART referred to as HAART naive, while group B were subdivided into four groups; comprising of B1: those that had been on HAART for 0 - 2½ years, group B2: >2½ - 5 years, group B3: >5 - 7½ years, and group B4: >7½ - 10 years, termed as HAART experience. Information obtained from the patients included sex, age, marital status, Near Point of Convergence (NPC), Amplitude of Accommodation (AA), Presbyopic reading Addition (ADD), CD4+ T cell count, HAART regimen and duration on HAART therapy.
UNASSIGNED: There were 400 participants aged 25 - 55years with a mean age of 37.86 ± 7.5years. The participant\'s NPC mean was 6.4 ± 1.47cm with a range of 2 - 18cm. Most of the participants 336 (84.0%) had an abnormal Near Point of Convergence compared to 64 (16%) with normal NPC values. The mean AA was 4.18± 1.34DS, ranging from 0.75 to 10.0DS and about 273 (68.2%) of the participant\'s AA was within 3 to 5DS. The mean presbyopic addition was 1.39± 0.98 DS ranging from 1.00 to 3.50DS whilst majority of the participants, 305 (76.2%) had an abnormal Reading Addition.
UNASSIGNED: The study showed that the HIV/AIDS patients on HAART exhibit an abnormally low AA, receded NPC and High presbyopic reading addition as compared to age matched HAART naïve. There was a statistically significant association between AA and HAART (p = 0.002) and HAART duration (p = 0.00), but there was no association with their CD4+ T cell levels and HAART regimen (p = 0.12, p = 0.08). There was no statistically significant association between Abnormal reading addition and HAART (p= 0.46), CD4+4 T cell levels and HAART regimen (p=0.53 and p= 0.59), but there was a statistically significant association with HAART duration (p= 0.00).

In eukaryotic cells, the nuclear envelope (NE) is a membrane partition between the nucleus and the cytoplasm to compartmentalize nuclear contents. It plays an important role in facilitating nuclear functions including transcription, DNA replication and repair. In mammalian cells, the NE breaks down and then reforms during cell division, and in interphase it is restored shortly after the NE rupture induced by mechanical force. In this way, the partitioning effect is regulated through dynamic processes throughout the cell cycle. A failure in rebuilding the NE structure triggers the mixing of nuclear and cytoplasmic contents, leading to catastrophic consequences for the nuclear functions. Whereas the precise details of molecular mechanisms for NE reformation during cell division and NE restoration in interphase are still being investigated, here, we mostly focus on mammalian cells to describe key aspects that have been identified and to discuss the crosstalk between them.

Nephron progenitor cells (NPCs) self-renew and differentiate into nephrons, the functional units of the kidney. Here, manipulation of p38 and YAP activity allowed for long-term clonal expansion of primary mouse and human NPCs and induced NPCs (iNPCs) from human pluripotent stem cells (hPSCs). Molecular analyses demonstrated that cultured iNPCs closely resemble primary human NPCs. iNPCs generated nephron organoids with minimal off-target cell types and enhanced maturation of podocytes relative to published human kidney organoid protocols. Surprisingly, the NPC culture medium uncovered plasticity in human podocyte programs, enabling podocyte reprogramming to an NPC-like state. Scalability and ease of genome editing facilitated genome-wide CRISPR screening in NPC culture, uncovering genes associated with kidney development and disease. Further, NPC-directed modeling of autosomal-dominant polycystic kidney disease (ADPKD) identified a small-molecule inhibitor of cystogenesis. These findings highlight a broad application for the reported iNPC platform in the study of kidney development, disease, plasticity, and regeneration.

The pan-immune-inflammation-value (PIV) is a comprehensive biomarker that integrates different peripheral blood cell subsets. The present study aimed to evaluate the prognostic ability of PIV in patients with nasopharyngeal carcinoma (NPC) undergoing chemoradiotherapy. PIV was assessed using the following equation: (Neutrophil count × platelet count × monocyte count)/lymphocyte count. The Kaplan-Meier method and Cox hazards regression models were used for survival analyses. The optimal cut-off values for PIV and systemic immune-inflammation index (SII) were determined using receiver operating characteristic analysis to be 428.0 and 1032.7, respectively. A total of 319 patients were recruited. Patients with a low baseline PIV (≤428.0) accounted for 69.9% (n=223) and patients with a high baseline PIV (>428.0) accounted for 30.1% (n=96). Compared with patients with low PIV, patients with a high PIV had significantly worse 5-year progression-free survival [PFS; 66.8 vs. 77.1%; hazard ratio (HR), 1.97; 95% confidence interval (CI), 1.22-3.23); P=0.005] and 5-year overall survival (OS; 68.7 vs. 86.9%, HR, 2.71; 95% CI, 1.45-5.03; P=0.001). PIV was also a significant independent prognostic indicator for OS (HR, 2.19; 95% CI, 1.16-4.12; P=0.016) and PFS (HR, 1.86; 95% CI, 1.14-3.04; P=0.013) and outperformed the SII in multivariate analysis. In conclusion, the PIV was a powerful predictor of survival outcomes and outperformed the SII in patients with NPC treated with chemoradiotherapy. Prospective validation of the PIV should be performed to better stratify radical treatment of patients with NPC.

The present study aimed to investigate the value of intravoxel incoherent motion imaging (IVIM) and three-dimensional pulsed continuous arterial spin labeling (ASL) in assessing dynamic changes of the parotid gland in patients with nasopharyngeal carcinoma (NPC) following radiotherapy (RT). A total of 18 patients with NPC who underwent intensity-modulated RT were enrolled in the present study. All patients underwent conventional magnetic resonance imaging, plus IVIM and ASL imaging of the bilateral parotid glands within 2 weeks prior to RT, and 1 week (1W) and 3 months (3M) following RT. Pure diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction (F) and blood flow (BF) were analyzed. D and BF values were significantly increased from pre-RT to 1W post-RT [change rate: Median (IQR), ΔD1W%: 39.28% (38.23%) and ΔBF1W%: 60.84% (54.88%)] and continued to increase from 1W post-RT to 3M post-RT [55.44% (40.56%) and ΔBF%: 120.39% (128.74%)]. In addition, the F value was significantly increased from pre-RT to 1W post-RT, [change rate: Median (IQR), ΔF1W%: 28.13% (44.66%)], and this decreased significantly from 1W post-RT to 3M post-RT. However, no significant differences were observed between pre-RT and 3M post-RT. Results of the present study also demonstrated that the D* value was significantly decreased from pre-RT to 1W post-RT and 3M post-RT [change rate: Median (IQR), ΔD*1w%: -41.86% (51.71%) and ΔD*3M: -29.11% (42.67%)]. No significant difference was observed between the different time intervals post-RT. There was a significant positive correlation between percentage change in ΔBF1W and radiation dose (ρ=0.548, P=0.001). Thus, IVIM-diffusion-weighted imaging and ASL may aid in the detection and prediction of radiation-induced parotid damage in the early stages following RT. They may contribute to further understanding the potential association between damage to the parotid glands and patient-/treatment-related variables, through the assessment of individual microcapillary perfusion and tissue diffusivity.

Leptomeningeal metastasis is a rare in nasopharyngeal carcinoma, affecting less than 5% of patients with a poor prognosis. The aim of this case report was to present management of palliative radiotherapy in leptomeningeal metastasis of nasopharyngeal carcinoma patient. A 33-year-old female presented with nasopharyngeal carcinoma with stage III, T3N3M0, WHO type III. The patient has received chemoradiation with photon-based intensity-modulated radiotherapy (IMRT) technique at the dose of 70 Gy in 33 fractions and showed a satisfactory outcome in 12 months follow-up. Later, at 18 months after chemoradiation completion, the patient complained of worsening bilateral sciatic pain, particularly during coughing, with slight limitations in bilateral hip flexion observed during straight leg raises. The whole spine contrast-enhanced magnetic resonance imaging (MRI) examination showed nodular enhancement of leptomeningeal thickening at the T4 level of the spinal cord lower than S3. Palliative radiation therapy utilized a three-dimensional conformal radiation therapy (3D-CRT) technique producing 35 Gy in 14 fractions placed in a field spanning the T4-S3 vertebral bodies. Methotrexate was administered intravenously every two weeks for three cycles to ensure central nervous system penetration. After four months of follow-up, no evidence of disease was found at the primary site and metastatic areas on subsequent physical examination or imaging with MRI and there was satisfactory improvement in neurologic symptoms. In conclusion, leptomeningeal metastases with primary nasopharyngeal carcinoma are rare and typically cause neurological impairments in patients. Hematogenous or cerebrospinal fluid-mediated spread of the cancer is considered the most likely pathway for leptomeningeal dissemination. Strategic modalities, such as radiotherapy with chemotherapy, may improve outcomes in symptoms and quality of life.

Matrix stiffness potently promotes the malignant phenotype in various biological contexts. Therefore, identification of gene expression to participate in mechanical force signals transduced into downstream biochemical signaling will contribute substantially to the advances in nasopharyngeal carcinoma (NPC) treatment. In the present study, we detected that cortactin (CTTN) played an indispensable role in matrix stiffness-induced cell migration, invasion, and invadopodia formation. Advances in cancer research have highlighted that dysregulated alternative splicing contributes to cancer progression as an oncogenic driver. However, whether WT-CTTN or splice variants (SV1-CTTN or SV2-CTTN) regulate matrix stiffness-induced malignant phenotype is largely unknown. We proved that alteration of WT-CTTN expression modulated matrix stiffness-induced cell migration, invasion, and invadopodia formation. Considering that splicing factors might drive cancer progression through positive feedback loops, we analyzed and showed how the splicing factor PTBP2 and TIA1 modulated the production of WT-CTTN. Moreover, we determined that high stiffness activated PTBP2 expression. Taken together, our findings showed that the PTBP2-WT-CTTN level increases upon stiffening and then promotes cell migration, invasion, and invadopodia formation in NPC.

The present study aimed to investigate the association between the expression profiles of long non-coding RNAs (lncRNAs) and the clinical characteristics or prognosis of patients with nasopharyngeal carcinoma (NPC). The findings presented in the present review may provide novel strategies for the prevention and treatment of NPC. For the analyses, medical databases, including PubMed, Web of Science and Cochrane library were searched using specific search terms, search strategies and screening strategies. Endnote X9 document management software was then employed to extract documents from January, 2010 to May, 2023. Data were extracted following the prescribed standards. Review Manager 5.4 and STATA 12.0 data analysis software were used for data analysis. A total of 490 publications were analyzed for inclusion. In total, 29 publications, composed of 24 studies with upregulated lncRNAs and 5 studies with downregulated lncRNAs, were included in the final analysis. The analysis revealed that the upregulation of lncRNAs was significantly associated with T stage, N stage and clinical stage, as well as with the overall survival (OS) and disease-free survival (DFS) of patients with NPC (P<0.05). However, there was no significant association between the upregulated lncRNAs and sex, M stage or relapse-free survival (RFS) (P>0.05). On the other hand, the suppression of lncRNA expression was significantly associated with N stage, M stage, clinical stage and the OS of patients with NPC (P<0.05), but not with T stage and RFS (P>0.05). Taken together, the present review demonstrates that the up- and downregulation of different lncRNAs was associated with an advanced clinical stage and a shorter OS of patients with NPC. Therefore, lncRNAs may serve as potential prognostic factors in NPC.