c-Jun-mediated JMJD6 restoration enhances resistance of liver cancer to radiotherapy through the IL-4-activated ERK pathway.

Radiotherapy is widely used in the treatment of liver cancer, but the efficacy can be limited by radioresistance. In this study, we attempt to delineate the possible molecular mechanism of c-Jun-regulated Jumonji domain-containing protein 6/interleukin 4/extracellular signal-regulated kinase (JMJD6/IL-4/ERK) axis in radioresistance of liver cancer. The expression of c-Jun was quantified in liver cancer tissues and cell lines, and the results indicated that c-Jun was upregulated in liver cancer tissues and cells. We further illustrated the role of c-Jun following gain- and loss-of-function strategies in malignant phenotypes of liver cancer cells. It was established that c-Jun elevated JMJD6 expression and augmented the malignancy and aggressiveness of liver cancer cells. The in vivo effects of c-Jun on radioresistance in liver cancer were validated in nude mice, in response to IL-4 knockdown or the ERK pathway inhibitor, PD98059. In the presence of JMJD6 upregulation, the expression of IL-4 was elevated in mice with liver cancer, which enhanced the radiation resistance. Moreover, knockdown of IL-4 inactivated the ERK pathway, thereby reversing the radiation resistance caused by overexpressed JMJD6 in tumor-bearing mice. Taken together, c-Jun augments the radiation resistance in liver cancer by activating the ERK pathway through JMJD6-upregulated IL-4 transcription.

Dimethylation of histone H3 lysine 36 (H3K36me2) as a potential biomarker for glioma diagnosis, grading, and prognosis.

Abnormal histone methylation plays a key role in glioma development but the clinical value of specific alterations is still unclear. Here, the potential significance of histone H3 lysine 36 dimethylation (H3K36me2) was investigated as a biomarker for glioma. Seventy-three glioma patients were included in the study and the level of H3K36me2 in the tumor tissues was determined by immunohistochemistry. The χ2 test was used to explore the influence of clinical and pathological characteristics on H3K36me2 levels. The Kaplan-Meier method was used to estimate progression-free survival (PFS) and overall survival (OS). COX regression was used to explore the relationship between H3K36me2 levels and glioma prognosis. The results indicated that the H3K36me2 level increases with glioma grade. The proportion of high H3K36me2 levels was lower in glioma patients under the age of 52 years. H3K36me2 levels were negatively correlated with IDH1 mutation and MGMT promoter methylation, and positively correlated with p53 expression. Thus, high H3K36me2 levels positively correlated with poor prognosis of gliomas. In conclusion, H3K36me2 may be considered as a potential biomarker for glioma diagnosis, grading, and prognosis, but the overall clinical value of H3K36me2 determination deserves further investigation. These results may have important implications for accurate diagnosis and future precision treatment of gliomas.

The Interaction of the IFNγ/JAK/STAT1 and JAK/STAT3 Signalling Pathways in EGFR-Mutated Lung Adenocarcinoma Cells.

Purpose: It was reported that the EGFR (epidermal growth factor receptor) mutation status was related to primary immune resistance in NSCLC (non-small-cell lung cancer). ICIs (immune checkpoint inhibitors) have poor efficacy and large side effects for people with EGFR mutation. EGFR mutation was considered as a sign of immune therapeutic resistance, but its underlying mechanism is difficult to be determined. Combined with our research basis, we tried to explore the possible mechanism of primary drug resistance in EFGR mutant lung adenocarcinoma through the interaction between the JAK/STAT1 and JAK/STAT3 pathway. Materials and Methods: Cell apoptosis and viability test were used to study the role of the JAK/STAT signalling pathway in lung adenocarcinoma cell survival. Western blot, RT-PCR, and flow cytometry were employed to explore the changes of expression in JAK1/2, STAT1/3, PD-L1, and related signal molecules in the case of activation or inhibition of the JAK/STAT3 signalling pathway. Results: With inhibition of inhibiting the JAK/STAT3 signalling pathway by STAT3 inhibitors, we found IFNγ-JAK-STAT1 pathway activation by IFNγ could further keep lung adenocarcinoma cells from proliferation and promote its apoptosis. The inhibition of the JAK/STAT3 pathway results in the upregulation of JAK1/2, STAT1, IRF1, IRF9, and PD-L1 and downregulation of STAT3 and SOCS1. Conclusions: The absence of the IFNγ-JAK-STAT1 signal pathway is one of the main mechanisms for the ICI endogenous resistance. The abnormal activation of the downstream JAK/STAT3 pathway in cells with EGFR mutation may have antagonistic effects on the STAT1 induced antitumor immune response, which may cause the IFNγ-JAK-STAT1 pathway to lose its function. The mechanism may result in production of the immune tolerance of the EGFR mutant, which promotes immune escape.

hsa_circ_0000518 Facilitates Non-Small-Cell Lung Cancer Progression via Moderating miR-330-3p and Positively Regulating SLC1A5.

Background/Aim: Non-small-cell lung cancer (NSCLC) is the principal agent of cancer deaths globally. The goal of this study was to determine how circular RNA_0000518 (circ_0000518) regulates tumor progression. Materials/Methods. circ_0000518 was selected as a study target involved in NSCLC from GEO (Gene Expression Omnibus) database. circ_0000518 level was gauged by qRT-PCR. It was confirmed as circRNA by actinomycin D inhibition and RNase R assay. Subcellular localization of circ_0000518 was identified by FISH. Cell function was determined by CCK-8, Transwell, and western blot. Glutamine metabolic factors were detected by ELISA. The target regulation relationship between genes was clarified by dual-luciferase reporter assay. In vivo models were established to evaluate the impact of circ_0000518 on tumor growth. Immunohistochemical staining for Ki67, vimentin, and E-cadherin was used to detect cell proliferation and metastasis, respectively. Results: circ_0000518 expression was enhanced in NSCLC. si-circ_0000518 inhibited cell proliferation, invasion, and glutamine metabolism. circ_0000518 functioned as a molecular sponge for miR-330-3p, and inhibition of miR-330-3p in cells markedly reversed circ_0000518 interference-mediated antitumor effects. miR-330-3p interacted with 3'-UTR of SLC1A5. miR-330-3p inhibitor-mediated protumor effect was remarkably reversed in cells after the knockdown of SLC1A5. circ_0000518 knockdown reduced glutamine, glutamate, and α-KG by targeting miR-330-3p. Intertumoral injection of circ_0000518 shRNA adeno-associated virus effectively halted xenograft tumor growth. Conclusion: The current study revealed that circ_0000518 may have a prooncogenic function in the formation and progression of NSCLC, which might be achieved through moderating the miR-330-3p/SLC1A5 axis.

Prognosis of Patients With Brainstem Glioblastoma Based on "age, surgery and radiotherapy": A SEER Database Analysis.

Introduction: Primary brainstem glioma is a rare tumor with a dismal prognosis that poses significant treatment challenges. The purpose of the current study is to identify and determine prognostic factors associated with survival in high-grade brainstem glioma patients. Methods: We gathered the data from the SEER database for the duration of years from 1973 to 2016 to examine the survival of patients particularly reported with the high-grade brainstem glioma and subsequently ascertained the potential impact of demographic features, tumor, and clinical characteristics on the overall survival of these patients. The survival patterns were assessed using Kaplan-Meier curves and Cox proportional hazards models. Propensity score matching (PSM) analysis was performed between patients with or without radiation therapy based on age and surgical resection to investigate the effect of radiotherapy on overall survival (OS). Results: A total 232 patient's data were obtained from the SEER database and included in this study. The median overall survival was 8 months. Kaplan-Meier survival analysis delineated that the patients who were in younger age (P = .001) and underwent surgery (P = .001) exhibited typically a better prognosis. Among 232 patients, a total of 204 patients were categorized as radiotherapy group (RG) received radiation therapy whereas 28 patients were considered as nonradiotherapy group (NRG), who were not receiving radiotherapy. Radiotherapy was associated with an improvement in the overall survival without statistical significance (P = .104). PSM was performed between RG and NRG based on age and surgical resection. After the PSM, 56 patients were included. Overall Survival was significantly different between both groups (P = .038). Conclusion: Furthermore, the patients with high-grade brain glioma who received "both radiotherapy and chemotherapy" exhibited significantly longer survival compared to the patients who received chemotherapy alone. Multivariate analysis showed that treatment with surgery and radiotherapy were considered as the independent prognostic factors (P < .05).

125I Seed Brachytherapy for Refractory Loco-Regional Recurrence of Non-Anaplastic Thyroid Cancer.

PURPOSE: The purpose of this research was to evaluate the feasibility and efficacy of 125I seed brachytherapy as salvage treatment for recurrence from non-anaplastic thyroid cancer refractory to other modalities. METHODS: Between June 2006 and September 2019, fifteen patients with recurrent non-anaplastic thyroid cancer were treated with 125I seed brachytherapy. 125I seeds were implanted into the tumor under the guidance of CT and/or ultrasound images with the median prescription dose of 120 Gy (range, 100-140 Gy). The median seed number was 80 (range 10-214). Clinical efficacy was evaluated with Response Evaluation Criteria in Solid Tumors. FINDINGS: Fifteen patients were selected, eleven of whom had papillary carcinoma, two suffered from follicular carcinoma, and two were diagnosed with medullary carcinoma. These patients had twenty-four nodes in total. After they received salvage surgery and/or radioactive iodine (RAI) therapy, local recurrence was detected in all of them. No less than one node was observed in everyone's cervical or supraclavicular areas, and four patients had lung metastatic. The median follow-up period lasted 48 months (range, 5-93 months). All patients did not develop locoregional recurrence after experiencing 125I seed brachytherapy. Only three of them formed new metastases in nontarget regional nodes after brachytherapy, and additional brachytherapy can solve all regional failure problems. No significant adverse events were observed in any patient. IMPLICATIONS: For the chosen patients, 125I seed brachytherapy is feasible for treating refractory local recurrence from non-anaplastic thyroid cancer. Further studies are required to determine the role of 125I seed brachytherapy in the treatment of thyroid cancer.

Deciphering the roles of miR-16-5p in malignant solid tumors.

MiR-16-5p, a member of the miR-16 family, has been reported to be abnormal expression in tumor tissues and blood of tumor patients, and also downregulated in most cancer cell lines. Aberrant expression of miR-16-5p promotes tumor cell proliferation, invasion, metastasis, angiogenesis, and can also affect the treatment sensitivity, such as radiotherapy and chemotherapy. Generally, miR-16-5p plays an anti-tumor role and these diverse functions of miR-16-5p in tumors collectively indicate that miR-16-5p may become an attractive target for novel anticancer therapies and a powerful diagnostic and prognostic biomarker for early tumor detection and population risk screening. Herein we review the role and utilization of miR-16-5p in malignant tumor in detail.

The Epigenetic Regulation of OLIG2 by Histone Demethylase KDM6B in Glioma Cells.

Gliomas are common tumors that occur in the brain, accounting for 80% of all malignant brain tumors. Oligodendrocyte transcription factor 2 (OLIG2) is a key transcription factor and strongly expressed in gliomas, which drives proliferation and invasion of glioma cells. Our previous studies have shown that histone lysine (K) demethylase 6B (KDM6B) promotes glioma development. The data also showed that OLIG2 content was positively correlated with KDM6B. Based on this, we proposed that KDM6B may play biological roles by regulating OLIG2 expression. Subsequently, many experiments were performed including specific inhibitor treatment, gene knockdown, and chromatin immunoprecipitation (ChIP) array. These results indicated that inhibition of KDM6B enzymatic activity with GSK-J4 reduces OLIG2 gene expression and protein content. The KDM6B knockdown experiment yielded similar results, that is, it reduces the mRNA and protein level of OLIG2 in glioma cells. ChIP assay showed that the promoter of OLIG2 can be bound by KDM6B, which catalyzes the demethylation of H3K27me3 and increases the expression of OLIG2. This study reveals a new regulatory mechanism of OLIG2 by KDM6B, which has important implications for the future development of drugs for gliomas and other neurological diseases.

3D-Printed Template-Guided 125I Seed Brachytherapy: A Salvage Approach for Locoregional Refractory Recurrence of Papillary Thyroid Cancer.

BACKGROUND: Papillary thyroid carcinoma (PTC) is typically treated with surgical resection, even in recurrent cases. However, some cases of recurrent PTC are refractory to the conventionally used locoregional radiotherapy and resection methods. 125I seed permanent brachytherapy has emerged as a promising alternative for such PTCs, but no effective brachytherapy protocol has been reported for tumors with a huge volume, liquefaction, necrosis, and skin invasion. CASE PRESENTATION: A 47-year-old man presented with recurrence 8 years after 2 thyroidectomy procedures for PTC and recurrent PTC. The tumor measured 6 × 7 × 8 cm3 and exhibited liquefaction, necrosis, and skin invasion. The patient was treated at our hospital from December 2017 to November 2018. He received one round of 125I seed temporary brachytherapy and 4 rounds of 125I seed permanent implantation. The activity of the seeds was 0.3-3.0 mCi, and the total dose delivered to the tumor was 145 Gy. The recurrent tumor was successfully removed by 125I seed brachytherapy guided with a 3D-printed template and ultrasound and CT scanning. The refractory tumor healed uneventfully after 125I seed brachytherapy without recurrence over the 25-month follow-up. CONCLUSIONS: To the best of our knowledge, this is the first reported case of a large thyroid carcinoma that was effectively treated by 3D-printed template-guided 125I seed brachytherapy.

BRAF V600E mutation as a novel mechanism of acquired resistance to ALK inhibition in ALK-rearranged lung adenocarcinoma: A case report.

RATIONALE: Patients with lung adenocarcinoma harboring EML4-ALK rearrangements respond well to multiple ALK tyrosine kinase inhibitors (TKIs). However, the tumor will invariably progress due to acquired resistance. Comprehensive genomic profiling appears to be a promising strategy to reveal the underlying molecular mechanisms of ALK-TKIs resistance. PATIENT CONCERNS: A patient with right lung adenocarcinoma harboring an ALK rearrangement received targeted therapy with multiple ALK-TKIs. He sought for follow-up treatment after his disease progressed again. DIAGNOSIS: The patient had a tumor diagnosed with stage I (T1bN0M0) lung adenocarcinoma. INTERVENTIONS: Due to the surgical contraindication, the patient did not undergo surgical resection. Instead, he received crizotinib as the first-line therapy with the progression-free survival of 20 months. Then he switched to alectinib treatment, however the disease rapidly progressed again. OUTCOMES: Next-generation sequencing was performed and revealed that 7 somatic mutations were identified. Among them, 2 mutations, ALK I1171T and BRAF V600E, may be responsible for the resistance of this patient to ALK-TKIs. BRAF V600E mutation may explain the patient's resistance to lorlatinib. LESSONS: We present a case of ALK-rearranged lung adenocarcinoma with acquired resistance to ALK inhibition, in which the BRAF V600E mutation is a novel resistance mechanism. This provides evidence that BRAF V600E mutation is one mechanism of ALK-TKI resistance.

Clinical Application of Iodine-125 Seed Brachytherapy Combined with Anti-PD-1 Antibodies in the Treatment of Lung Cancer.

PURPOSE: The purpose of this case report was to investigate the clinical efficacy and tolerability of anti-programmed cell death protein (PD)-1 antibody combined with iodine (I)-125 seed brachytherapy in lung cancer treatment. METHODS: Three patients with advanced PD-L1-positive non-small-cell lung cancer were treated first with I-125 seed brachytherapy and then with anti-PD-1 antibody. Clinical efficacy was evaluated with Response Evaluation Criteria in Solid Tumors. FINDINGS: All 3 patients had complete response or partial response. None of the 3 patients had reported obvious adverse events. IMPLICATIONS: Encouraging preliminary results provide important support for further clinical treatment of lung cancer using anti-PD-1 antibody combined with I-125 seed brachytherapy.

Efficacy and safety of CT-guided 125I brachytherapy in elderly patients with non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) has become the most common cancer type and the leading cause of cancer-associated mortality worldwide. The aim of the present retrospective study was to evaluate the efficacy and safety of computed tomography (CT)-guided 125I brachytherapy alone in elderly patients with NSCLC. A total of 26 elderly patients with NSCLC stage I-III who had an inoperable lesion or progressive disease following radio-chemotherapy were treated with CT-guided 125I seed implantation for lung lesions and included in the present study. The prescribed dose of 125I brachytherapy was 80-140 Gy, and dosimetric verification was performed immediately after the procedure. The response rate (RR) and local control rate (LCR) were analyzed according to the Response Evaluation Criteria in Solid Tumors (version 1.1). Survival was estimated using the Kaplan-Meier method. Safety and complications were also documented. All patients were aged 65-85 years (median age, 77 years) and successfully completed the procedure, and the median follow-up time was 9.4 months (range, 3-31 months). After a 6-month follow-up, for pulmonary lesions, complete response (CR) was achieved in 11 (42.3%) cases, partial response in 9 (34.6%) cases, stable disease in 4 (15.4%) cases and progressive disease in 2 (7.7%) cases. The 6-month RR and LCR were 76.9 (20/26) and 92.3% (24/26), respectively. The mean overall survival (OS) time was 11.7±7.6 months and the 0.5- and 1-year OS rates were 90.1 and 73.3%, respectively. Tumor-related symptoms in patients were significantly alleviated following the procedure. No severe complications occurred during and after the procedure of 125I seed implantation. In conclusion, CT-guided 125I brachytherapy is a feasible, effective and safe therapy and may be considered as an alternative option to surgery and radiotherapy for elderly patients with NSCLC.

125I brachytherapy seeds implantation for an inoperable large retroperitoneal leiomyosarcoma.

Retroperitoneal leiomyosarcoma is relatively uncommon. Leiomyosarcoma has accounted for about 5%-10% of soft-tissue sarcoma, and 1/2-2/3 of the primary lesions were retroperitoneal, with a cumulative 5-year survival rate of only 35%.Leiomyosarcoma is one kind of soft-tissue sarcoma with the lowest survival rates due to the invasive growth, difficult treatment, and poor prognosis.The present study reported a case of a 78-year-old male diagnosed as left retroperitoneal leiomyosarcoma, who had received three operations. Computed tomography (CT) demonstrated a mass of approximately 12.9 cm × 6.9 cm × 6.6 cm in his retroperitoneal region. The Eastern cooperative oncology group and numerical rating scale scores of pain were 1 and 5, respectively. Multiple treatment strategies were administered, including the application of drainage and125I seed implantation. A total of 90125I seeds were implanted into the tumor through repetitious operations, with 30 seeds each time. Treatment planning system was involved to calculate the source distribution.125I seeds with the activity of 0.5 mCi were implanted under the guidance of CT, and dosimetric verification was performed after the operation. D90 (90% minimum prescription dose received by target volume) was 40 Gy. Follow-up was performed after 6 months, and complete response was achieved in the local lesions. However, there was no evidence-based treatment currently and the majority of our knowledge was based on results from case reports, thus further studies would be required.

Prognostic impact of neutrophil-to-lymphocyte ratio in gliomas: a systematic review and meta-analysis.

BACKGROUND: In some malignant tumors, a high neutrophil-to-lymphocyte ratio (NLR) is connected with unfavorable prognosis. Nevertheless, the prognostic value of the NLR in gliomas remains disputed. The clinical significance of the NLR in gliomas was investigated in our study. METHODS: The databases, PubMed, Embase, and the Cochrane Library, were searched using words like "glioma," "glioblastoma," "neutrophil-to-lymphocyte ratio," and others through May 2019. We evaluated the significance of NLR on overall survival (OS) of patients with gliomas in our study. RESULTS: Finally, 16 cohorts with 2275 patients were analyzed. The pooled analysis revealed that an elevated NLR was connected with unfavorable OS (hazards ratio (HR): 1.43, 95% confidence interval (CI): 1.27-1.62) outcomes of patients with gliomas. CONCLUSION: A high NLR can be considered a high-risk prognostic factor in gliomas, and more adjuvant chemotherapy should be recommended for high-risk patients.

Feasibility of three-dimensional-printed template-guided 125I seed brachytherapy and dosimetric evaluation in patients with malignant tumor.

OBJECTIVE: The objective of the study is to test whether three-dimensional (3D)-printed template can be used reproducibly for guiding malignant tumors brachytherapy and study the dosimetric consistency and adequacy between pre- and post-plan. MATERIALS AND METHODS: Between January and December 2016 in our hospital, a total of 14 patients underwent 3D-printed template-guided brachytherapy. All the patients were fixed into position using a vacuum cushion before undertaking a computed tomography (CT) scan. After the preplan was designed, the templates were printed. The tumors were punctured through predesigned needle holes. Following this, another CT scan was used to confirm the locations of needles, and then the 125 I radioactive seeds were implanted into the tumor according to the preplan. Postplan was performed after the operation. Data of the D90 (minimum absorbed dose of 90% target volume), V90 (90% prescription dose coverage volume percentage of target volume), V100, V150, and seed number pre- and post-operation were collected and compared. RESULTS: The mean D90, V90, V100, V150, and seed number preoperation were 94.96 ± 16.43 Gy, 94.64% ± 1.43%, 91.21% ± 1.59%, 65.01% ± 5.78%, and 46.67 ± 21.87, respectively. The mean D90, V90, V100, V150, and seed number postoperation were 91.97 ± 17.54 Gy, 93.35% ± 2.45%, 89.35% ± 3.21%, 63.40% ± 6.36%, and 46.60 ± 22.85, respectively. No significant difference between pre- and post-operation was observed across the data (P >0.05). CONCLUSION: For immobilized malignant tumors, 3D-printed template can be used reproducibly. The dose parameters in preplan can be achieved easily and satisfactorily by 3D-printed template guided brachytherapy, and it may become an easily reproducible standardized procedure in the future.

Preliminary investigation of computed tomography-guided iodine-125 seed implantation treatment efficacy in patients with iliac lymph nodes metastases.

OBJECTIVES: The objective of this study is to assess the technical feasibility, safety, and efficacy of computed tomography (CT)-guided iodine-125 (125 I) seed implantation to treat malignant iliac lymph node metastases. MATERIALS AND METHODS: In this retrospective study, 11 patients with a total of 11 iliac lymph node metastases were implanted with 125 I seeds (14.8-25.9 MBq) under CT-guidance, both the seed quantity and distribution were measured with a computerized treatment planning system. Treatment effects and adverse events were evaluated. RESULTS: 125 I seeds were successfully implanted in all patients, and the minimum peripheral dose of seeds was ranged from 30 to 110 Gy (median of 75 Gy). The median follow-up period was 11 months (ranged 3-39 months). Follow-up at 2 months after implantation revealed partial response in eight patients, stable disease in two patients, and progressive disease in one patient. The overall response rate and the local tumor control rate at 2 months were 72.73% and 90.91%, respectively. The rates of refractory pain and leg edema relief were 100% and 50% within 2 weeks after treatment, respectively. Survival rate at 1 year was 45.45%. No peri-interventional mortality or major complication was observed. CONCLUSION: 125 I seed implantation was a safe and effective technique for minimally invasive treatment for iliac lymph node malignant metastasis.

Precision dose measurement of 125I seed in solid water through SPECT/CT detecting.

PURPOSE: The aim of the study is to study the feasibility of gamma-ray-detection-based precision dose measurement of 125I seed brachytherapy in solid water. MATERIALS AND METHODS: Seven group 125I seeds with different activities were put into a hole in the center of solid water individually. Each group had ten seeds, and the seed activity ranged from 1.48 × 107 Bq to 3.7 × 107 Bq. Single-photon emission computed tomography/computed tomography (SPECT/CT) was used to scan the seeds perpendicular to the long axis of the seed, with a slice thickness of 3.75 mm. The radioactive count values (x) of the radioactive concentration around the seeds were collected at a distance of 1-15 mm from the center of the seeds, while the corresponding doses (Y) (Gy) were calculated. SPSS 18.0 was used to analyze the relationship between the count value and the dose. RESULTS: With the same seed activity, the count values became smaller according to the distance from the center of the seeds. The count values at the same point had an increasing trend according to the activity. This is similar to the doses calculated at the same point. There was an exponential relationship between the dose around the 125I seeds, and the radioactive count value detected by SPECT/CT. Correlative curves between the dose and radioactive count value detected by SPECT/CT of different-activity 125I seeds were fitted. The formulas of the dose and radioactive count with different seed activity were in the form of Y = b0 (b1)x. The constant b0 ranged from 1.48 to 3.93, according to the seed activity, while b1 was 1.006 for every seed's activity. CONCLUSION: The count value around the 125I seed can be detected accurately by SPECT/CT, and then can be quantified. This study provided useful experiment data for the precision measurement of 125I seed implantation. Radiation detection-based dose measurement may become a new noninvasive technology for the dynamic dosimetry verification method after brachytherapy.

Histone demethylase KDM6B regulates 1,25-dihydroxyvitamin D3-induced senescence in glioma cells.

Vitamin D is a fat-soluble vitamin and plays an important role in calcium absorption and bone development, whose lack can cause a variety of diseases, including cancer. Human epidemiological studies suggested that vitamin D3 deficiency might increase glioma incidence, but molecular mechanism is less understood. In this study, we show that 1,25-dihydroxyvitamin D3 (the active form of vitamin D3) induces senescence of glioma cells and increases the expression of senescence markers, INK4A and cyclin-dependent kinase inhibitor 1A (CDKN1A). 1,25-Dihydroxyvitamin D3 also upregulates the expression of histone demethylase, KDM6B. Knockdown of KDM6B attenuates 1,25-dihydroxyvitamin D3-induced senescence and upregulation of INK4A and CDKN1A. KDM6B promotes the transcription of INK4A by eliminating the trimethylation of repressive marker H3K27me3 near its promoter. This study reveals a new regulatory mechanism involved in vitamin D3 inhibition on gliomas, which is beneficial to prevention and adjuvant therapy of glioma.

The histone H3 Lys 27 demethylase KDM6B promotes migration and invasion of glioma cells partly by regulating the expression of SNAI1.

The histone demethylase KDM6B, also known as jumonji domain-containing protein 3 (JMJD3), is an epigenetic regulator which plays important roles in immune activation, tissue regeneration, cellular senescence and cancer metastasis. But, the role of KDM6B in glioma metastasis is poorly understood. In this study, we achieved transcriptional regulation of KDM6B in glioma cells using CRISPR interference (CRISPRi) and CRISPR activation (CRISPRa). Our results showed that KDM6B promotes the proliferation, migration and invasion of human glioblastoma cells U87 and U251 using CCK8, scratch and transwell assays. Further results indicated that KDM6B increases the expression of SNAI1, a key factor of epithelial-mesenchymal transition (EMT). KDM6B catalyzes the demethylation of histone H3 Lys 27 trimethylation (H3K27me3) in the promoter of SNAI1, which is important for SNAI1 upregulation. Taken together, these findings provide new insight into the mechanism by which KDM6B promotes glioma metastasis.

125I seeds implantation for an elderly patient of skin squamous cell carcinomas with ulcer guided by ultrasound.

The skin squamous cell carcinoma (SCC) is a kind of malignancy of keratinocytes. SCC was originated within the epidermis or relevant appendages, which commonly occurred on sunlight exposure sites, such as the head and neck. This case report described an 85-year-old female patient with skin SCC at the right frontal, accompanied with skin ulcer. This patient suffered from indications that were not suitable for surgical resection, including old age, Alzheimer's disease (AD), lacunar infarction, hydropericardium, and some other concomitant diseases. In addition, the external beam radiotherapy was rejected by the relatives of this patient. Then, the patient received 125I seeds interstitial brachytherapy guided by bedside ultrasound. The tumor response was evaluated based on the response evaluation criteria in solid tumors version 1.1 criteria. Complete response was achieved 4 months after brachytherapy. No complications and recurrence were observed during 8-month follow-up. As the sole modality, the 125I seeds implantation could be a reasonable and safe alternative for treating skin SCC with ulcer, especially for the elderly patients.