The most severe form of brain glioma, glioblastoma (GBM), is highly malignant and usually resistant to chemotherapy. Therefore, discovery of new targets for gene therapy is important. Using subtraction cloning, we identified the human N‐Myc downstream‐regulated gene 2 (hNDRG2), located at chromosome 14q11.2, as a gene that is significantly suppressed in GBM tissues. Semiquantitative RT‐PCR showed that the hNDRG2 gene transcript is expressed in normal brain tissue and low‐grade gliomas but is present at low levels in 15 of 27 (56%) human GBM tissues and all of the 6 human glioblastoma cell lines examined. Furthermore, transfection of human glioblastoma U373 and U138 cells with a cDNA encoding hNDRG2 markedly reduced the cell proliferation. Our findings provide the first evidence to suggest that hNDRG2 may play a role in glioblastoma carcinogenesis.

Glioblastoma multiform (GBM) is recognized as the most malignant brain tumor with a high level of hypoxia, containing a small population of glioblastoma stem like cells (GSCs). These GSCs have the capacity of self-renewal, proliferation, invasion and recapitulating the parent tumor, and are major causes of radio-and chemoresistance of GBM. Upregulated expression of hypoxia inducible factors (HIFs) in hypoxia fundamentally contributes to maintenance and progression of GSCs. Therefore, we thoroughly reviewed the currently acknowledged roles of hypoxia-associated GSCs in development of GBM. In detail, we recapitulated general features of GBM, especially GSC-related features, and delineated essential responses resulted from interactions between GSC and hypoxia, including hypoxia-induced signatures, genes and pathways, and hypoxia-regulated metabolic alterations. Five hypothesized GSC niches are discussed and integrated into one comprehensive concept: hypoxic peri-arteriolar niche of GSCs. Autophagy, another protective mechanism against chemotherapy, is also closely related to hypoxia and is a potential therapeutic target for GBM. In addition, potential causes of therapeutic resistance (chemo-, radio-, surgical-, immuno-), and chemotherapeutic agents which can improve the therapeutic effects of chemo-, radio-, or immunotherapy are introduced and discussed. At last, as a potential approach to reverse the hypoxic microenvironment in GBM, hyperbaric oxygen therapy (HBOT) might be an adjuvant therapy to chemo-and radiotherapy after surgery. In conclusion, we focus on demonstrating the important role of hypoxia on development of GBM, especially by affecting the function of GSCs. Important advantages have been made to understand the complicated responses induced by hypoxia in GBM. Further exploration of targeting hypoxia and GSCs can help to develop novel therapeutic strategies to improve the survival of GBM patients.

Background: Current clinical guidelines recommend the removal of at least 12 lymph nodes (LNs) in resectable colorectal cancer (CRC). With advancements in lymphadenectomy technologies, the number of retrieved lymph nodes (rLNs) has markedly increased. This study aimed to investigate the lowest number of rLNs in node-negative patients. Materials and Methods: A total of 1103 N0 and 208 N1a stage patients were enrolled in our cohort, while 8503 N0 and 1276 N1a patients from the Surveillance, Epidemiology, and End Results CRC database were included. Propensity score matching and multivariate Cox regression analyses were performed to mitigate the influence of selection bias and control for potential confounding variables. Results: The median number of rLNs in N0 patients increased from 13.5 (interquartile range [IQR]: 9–18) in 2013 to 17 (IQR: 15–20) in 2019. The restrictive cubic spline illustrated a nonlinear relationship between rLNs and prognosis (nonlinearity, P=0.009), with a threshold (N=16) influencing clinical outcomes. Patients at either N0 or N1a stage with sufficient rLNs (≥16) demonstrated superior prognoses to those with a limited rLNs (<16). After adjusting for clinical confounders, similar prognoses were observed in N0 limited and N1a adequate populations. Furthermore, Kaplan–Meier curves revealed that N0 limited patients who received chemotherapy exhibited better outcomes than those who did not. Conclusions: Among patients with node-negative CRC, it is crucial to remove 16 or more LNs effectively. Fewer than 16 rLNs should be regarded as an independent risk factor, implying the need for adjuvant chemotherapy.

Background: Gastric cancer (GC) is a globally prevalent cancer, ranking fifth for incidence and fourth for mortality worldwide. The N6-methyladenosine (m⁶A) related long noncoding RNAs (lncRNAs) were widely investigated in recent studies. Nevertheless, the underlying prognostic implication and tumor immune mechanism of m⁶A-related lncRNA in GC remain unknown. Methods: We systematically assessed the m⁶A modification expression of 407 GC clinical samples based on 23 m⁶A regulators and comprehensively associated these genes with lncRNAs. Then, we constructed a m⁶A-related lncRNA prognostic signature (m⁶A-LPS) to evaluate both status and prognosis of the disease. Immune-related mechanisms were explored via dissecting tumor-infiltrating cells as well as applying tumor immune dysfunction and the exclusion algorithm. Furthermore, we validated the latent regulative mechanism of m⁶A-related lncRNA in GC cell lines. Results: The m⁶A-LPS containing nine hub lncRNAs was built, which possessed a superior capability to predict the outcomes of GC patients. Meanwhile, we found an intimate correlation between the m⁶A-LPS and tumor infiltrating cells, and that the low-risk group had a higher expression of immune checkpoints and responsed more to immunotherapy than the high-risk group. Clinically, these crucial lncRNAs expression levels were verified in ten pairs of GC samples. In in vitro experiments, the abilities of migration and proliferation were significantly enhanced via downregulating the lncRNA AC026691.1. Both migrative and proliferative capabilities of tumor cells were significantly enhanced via downregulating the lncRNA AC026691.1. in vitro. Conclusions: Collectively, the m⁶A-LPS could provide a novel prediction insight into the prognosis of GC patients and serve as an independent clinical factor for GC. These m⁶A-related lncRNAs might remodel the tumor microenvironment and affect the anti-cancer ability of immune checkpoint blockers. Importantly, lncRNA AC026691.1 could inhibit both migration and proliferation of GC by means of FTO regulation.

MSP58, a 58‐kD nuclear microspherule protein, is an evolutionarily conserved nuclear protein implicated in the regulation of gene transcription as well as in malignant transformation. An analysis of mRNA expression by real‐time PCR revealed that MSP58 was significantly up‐regulated in 29% of high‐grade glioblastoma tissues as well as in four glioblastoma cell lines. In the present study, we further evaluated the biological functions of MSP58 in U251 glioma cell proliferation, migration, invasion and tumour growth in vivo by specific MSP58 knockdown using short hairpin RNA (shRNA). We found that MSP58 depletion inhibited glioma cell growth, primarily by inducing cell cycle arrest rather than apoptosis. MSP58 depletion also decreased the invasive capability of glioma cells and anchorage‐independent colony formation in soft agar. Moreover, suppression of MSP58 expression significantly impaired the growth of glioma xenografts in nude mice. Finally, a cell cycle‐associated gene array revealed potential molecular mechanisms contributing to cell cycle arrest in MSP58‐depleted glioma cells. In summary, our data highlight the importance of MSP58 in glioma progression and provided a biological basis for MSP58 as a novel candidate target for treatment of glioma.

Background: Gastric cancer (GC) patients frequently face the debilitating comorbidity of malignant cachexia, a condition that consistently forecasts a dismal prognosis. Early diagnosis of cachexia and timely prediction of survival outcomes are essential for them. Here, we aimed to construct an immune-inflammatory-nutritional-tumor-marker (IINTM) prognostic score for GC, and further scrutinize its clinical relevance in early forecasting the cachexia.Method: A total of 1,101 GC patients underwent curative surgical were incorporated in our study, and they were evaluated by the Computed Tomography (CT) of skeletal muscle mass at third lumbar spine plane levels (SMI-L3). Using restricted cubic spline (RCS) analysis, we examined associations between prognosis and nutritional indices, including the Prognostic Nutritional Index (PNI) and Systemic Immune-Inflammation Index (SII). The IINTM score was constructed by the multivariate Cox analysis and evaluated by the Receiver Operating Characteristic (ROC) and area under the ROC (AUC).Results: We identified striking discrepancies in immunonutrition profiles and prognoses between cachexia and non-cachexia GC patients. Patients with cachexia had worse prognosis and lower SMI-L3 scores than those without cachexia. The IINTM score, incorporating PNI, SII, body mass index (BMI), NRS2002, serum albumin, platelet, D-dimer, CEA, and CA199, exhibited a high concordance index (C-index) of 0.784, underscoring its robust predictive efficacy. Most crucially, IINTM score demonstrated substantial diagnostic value for cachexia, with an AUC of 0.858, denoting its high degree of accuracy.Conclusion: The IINTM score could be a reliable tool and precisely predict the cachexia and prognosis for GC patients. Our findings provide novel insights into the role of immune-inflammatory-nutrition, tumor marker and cachexia in GC patients.