Abrupt elevation of tumor marker levels in a huge splenic epidermoid cyst, a case report.

Epidermoid cyst of the spleen is a rare disease, and relatively few cases were reported by literatures. Most published case reports provided inadequate information on the impact of splenic epidermoid cyst on tumor markers. A 32-year-old woman with a giant splenic epidermoid cyst was reported, for whom the serum concentration of a collection of tumor markers (CA19-9, CEA, CA125, CA242, and CA50) increased abruptly accompanied by left upper abdominal pain for 5 days. After comprehensive preoperative examination and multidisciplinary team discussion, we ruled out any concurrent malignancy and a laparoscopic total splenectomy was performed, during which the splenic cyst spontaneously ruptured unexpectedly. After surgery, the elevated serum tumor marker levels decreased sharply until reaching normal range 3 months later. Learning from the case, we conclude that interval monitoring of serum tumor markers is of critical value for patients with splenic epidermoid cyst. Abrupt elevation of tumor marker levels and abdominal pain may serve as signs of cyst rupture, which is strongly indicative of surgical intervention as soon as possible. Total removal of the splenic cyst is strongly suggested considering the recurrence and malignant potential of the splenic epidermoid cyst.

Successfully treated with siltuximab and prednisone in a 7-year-old girl with DOCK8-deficiency presenting as recurrent wart-like lesions: a case report.

Dedicator of cytokinesis 8 (DOCK8) deficiency represents a primary immunodeficiency with a wide range of clinical symptoms, including recurrent infections, atopy, and increased malignancy risk. This study presents a case of a 6-year-old girl with DOCK8 deficiency, characterized by severe, treatment-resistant herpetic infections who was successfully treated with siltuximab and glucocorticoids. The successful use of siltuximab in achieving remission highlights the pivotal role of interleukin-6 (IL-6) in DOCK8 deficiency pathogenesis and suggests that IL-6 modulation can be critical in managing DOCK8 deficiency-related viral infections, which may inform future therapeutic strategies for DOCK8 deficiency and similar immunodeficiencies.

Few-Shot Object Detection in Remote Sensing Images via Data Clearing and Stationary Meta-Learning.

Nowadays, the focus on few-shot object detection (FSOD) is fueled by limited remote sensing data availability. In view of various challenges posed by remote sensing images (RSIs) and FSOD, we propose a meta-learning-based Balanced Few-Shot Object Detector (B-FSDet), built upon YOLOv9 (GELAN-C version). Firstly, addressing the problem of incompletely annotated objects that potentially breaks the balance of the few-shot principle, we propose a straightforward yet efficient data clearing strategy, which ensures balanced input of each category. Additionally, considering the significant variance fluctuations in output feature vectors from the support set that lead to reduced effectiveness in accurately representing object information for each class, we propose a stationary feature extraction module and corresponding stationary and fast prediction method, forming a stationary meta-learning mode. In the end, in consideration of the issue of minimal inter-class differences in RSIs, we propose inter-class discrimination support loss based on the stationary meta-learning mode to ensure the information provided for each class from the support set is balanced and easier to distinguish. Our proposed detector's performance is evaluated on the DIOR and NWPU VHR-10.v2 datasets, and comparative analysis with state-of-the-art detectors reveals promising performance.

Phylogenetic conservatism and coordination in traits of Chinese woody endemic flora.

Range-limited endemic species, often labeled as endangered due to their low adaptability to climate change, exhibit unclear evolutionary mechanisms influencing their distribution. This study explores the relationship between leaf length, maximum height, and seed diameter and their linkage to phylogeny and climate in the macroecology of 1,370 woody endemics. Using Bayesian analytical method that allows partitioning phylogenetic and environmental variances and covariance, we revealed moderate to high phylogenetic signals in these traits, indicating evolutionary constraints potentially impacting climate change adaptability. The study uncovered a phylogenetically conserved coordination between height and leaf length which showed to be independent of macroecological patterns of temperature and precipitation. These findings emphasize the role of phylogenetic ancestry in shaping the distribution of woody endemics, highlighting the need for prioritized in-situ conservation and providing insights for ex situ conservation strategies.

Desmoplastic fibroma of the pediatric cranium with CTNNB1 mutation: case report and literature review.

PURPOSE: Desmoplastic fibroma (DF) is an uncommon intermediate bone tumor rarely involving the skull with unidentified pathogenesis. We report the first case of pediatric temporoparietal cranial desmoplastic fibroma (DF) with a CTNNB1 gene mutation and review the previous literature. CASE PRESENTATION: A 3-year-old boy had a firm, painless mass on the right temporoparietal region for 22 months. The cranial CT scan showed isolated osteolytic destruction in the outer plate and diploe of the right temporoparietal bone. Gross total resection of the lesion and cranioplasty were performed. After that, a growing epidural hematoma was observed so another operation was performed to remove the artificial titanium plate. Postoperative pathology indicated a DF diagnosis and molecular pathology suggested a missense mutation in exon 3 of the CTNNB1 gene (c.100G > A,p.Gly34Arg). CONCLUSION: Pediatric cranial DF is rare and easy to be misdiagnosed before operation. For cranial DF, lesion resection can be performed and perioperative management should be strengthened. Mutations in the CTNNB1 gene might be one of the molecular pathologic features of DF.

Fibrous dysplasia with aneurysmal bone cyst-like change occurring in pediatric orbit: case report and literature review.

PURPOSE: We report a case of fibrous dysplasia (FD) with aneurysmal bone cyst (ABC)-like change in a child with orbital involvement, review the related cases, and discuss clinical features, therapy, and prognosis of this disease. CASE PRESENTATION: A 10-year-old girl had right proptosis (degree of exophthalmos: OD 16 mm, OS 13 mm) and limited vision (visual acuity: OD 1.0, OS 0.8) without trauma. Preoperative CT showed a 5.0*4.3 cm right-sided crania-orbital communicating tumor. MRI indicated a well-defined multicystic mass with scattered fluid levels and soap bubble-like alterations. The child underwent total tumor resection and orbital parietal titanium mesh reconstruction. At 20 months of follow-up, the child has recovered from ocular problems, and the tumor has not recurred. CONCLUSION: FD combined with ABC rarely occurs in orbit and generally begins with ocular symptoms. The etiology is uncertain. Early diagnosis and surgery are essential. Complete resection is suggested whenever possible because residual lesions may recur.

Novel model of pyroptosis-related molecular signatures for prognosis prediction of clear cell renal cell carcinoma patients.

Background: Pyroptosis is a programmed death mode of inflammatory cells, which is closely related to tumor progression and tumor immunity. Clear cell renal cell carcinoma (ccRCC) is the major pathological type of renal cell carcinoma (RCC) with poor prognosis. Many theories have tried to clarify the mechanism in the development of ccRCC, but the role of pyroptosis in ccRCC has not been well described. The main purpose of this study is to explore the role of pyroptosis in ccRCC and establish a novel prognosis prediction model of pyroptosis-related molecular signatures for ccRCC. Methods: In the present study, we made a systematical analysis of the association between ccRCC RNA transcriptome sequencing data from The Cancer Genome Atlas (TCGA) database [which included 529 ccRCC patients who were randomized in a training cohort (n=265) and an internal validation cohort (n=264)] and 40 pyroptosis-related genes (PRGs), from which four genes (CASP9, GSDME, IL1B and TIRAP) were selected to construct a molecular prediction model of PRGs for ccRCC. In addition, a cohort of 114 ccRCC patients from Shanghai Eastern Hepatobiliary Surgery Hospital (EHSH) was used as external data to verify the effectiveness of the model by immunohistochemistry. Moreover, the biological functions of the four PRGs were also verified in ccRCC 786-O and 769-P cells by Western blot (WB), CCK-8 cell proliferation, and Transwell invasion assays. Results: The model was able to differentiate high-risk patients from low-risk patients, and this differentiation was consistent with their clinical survival outcomes. In addition, the four PRGs also affected the ability of cell proliferation and invasion in ccRCC. Conclusion: The prediction model of pyroptosis-related molecular markers developed in this study may prove to be a novel understanding for ccRCC.

Liver transplantation for advanced-stage primary hepatic yolk sac tumor: A case report and literature review.

RATIONALE: Primary hepatic yolk sac tumors (YSTs) are rare in adults. Liver resection is an acknowledged treatment modality for primary hepatic YST. Liver transplantation may offer a possible cure for unresectable cases. PATIENT CONCERNS: We present a case of a 31-year-old woman with an abdominal mass who had abnormally elevated alpha-fetoprotein (AFP) levels (31,132 ng/mL; normal: 0-7 ng/mL). Contrast-enhanced computed tomography (CT) revealed large tumors located in both lobes of the liver, with arterial enhancement and venous washout. Fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/CT indicated increased 18F-FDG uptake (maximum standardized uptake value, 24.4) in the liver tumors and left middle intra-abdominal nodule. DIAGNOSES: The diagnosis was primary hepatic YST with metastasis to the greater omentum. INTERVENTIONS: The patient underwent orthotopic liver transplantation and intra-abdominal nodule resection after transarterial chemoembolization (TACE) as a bridge. Intraoperatively, an intra-abdominal nodule was confirmed in the greater omentum. Histopathological examination of the liver tumors revealed Schiller-Duval bodies. The tropomyosin receptor kinase (TRK) inhibitor larotrectinib was administered, followed by four cycles of chemotherapy with bleomycin, etoposide, and cisplatin based on the next-generation sequencing results. OUTCOMES: The AFP level decreased to within the normal range. No evidence of tumor collapse was observed during the 34-month follow-up period. LESSONS: This case suggests that multimodal therapy dominated by liver transplantation, including preoperative TACE, postoperative adjuvant chemotherapy, and TRK inhibitors, is an effective treatment modality for unresectable primary hepatic YST.

Molecular subtyping and characterization of clear cell renal cell carcinoma by tumor differentiation trajectories.

Previous bulk RNA sequencing or whole genome sequencing on clear cell renal cell carcinoma (ccRCC) subtyping mainly focused on ccRCC cell origin or the complex tumor microenvironment (TME). Based on the single-cell RNA sequencing (scRNA-seq) data of 11 primary ccRCC specimens, cancer stem-cell-like subsets could be differentiated into five trajectories, whereby we further classified ccRCC cells into three groups with diverse molecular features. These three ccRCC subgroups showed significantly different outcomes and potential targets to tyrosine kinase inhibitors (TKIs) or immune checkpoint inhibitors (ICIs). Tumor cells in three differentiation directions exhibited distinct interactions with other subsets in the ccRCC niches. The subtyping model was examined through immunohistochemistry staining in our ccRCC cohort and validated the same classification effect as the public patients. All these findings help gain a deeper understanding about the pathogenesis of ccRCC and provide useful clues for optimizing therapeutic schemes based on the molecular subtype analysis.

Targeting Bcl-xL is a potential therapeutic strategy for extranodal NK/T cell lymphoma.

Extranodal natural killer/T cell lymphoma, nasal type (ENKTL) is an aggressive lymphoid malignancy with a poor prognosis and lacks standard treatment. Targeted therapies are urgently needed. Here we systematically investigated the druggable mechanisms through chemogenomic screening and identified that Bcl-xL-specific BH3 mimetics effectively induced ENKTL cell apoptosis. Notably, the specific accumulation of Bcl-xL, but not other Bcl-2 family members, was verified in ENKTL cell lines and patient tissues. Furthermore, Bcl-xL high expression was shown to be closely associated with worse patient survival. The critical role of Bcl-xL in ENKTL cell survival was demonstrated utilizing selective inhibitors, genetic silencing, and a specific degrader. Additionally, the IL2-JAK1/3-STAT5 signaling was implicated in Bcl-xL dysregulation. In vivo, Bcl-xL inhibition reduced tumor burden, increased apoptosis, and prolonged survival in ENKTL cell line xenograft and patient-derived xenograft models. Our study indicates Bcl-xL as a promising therapeutic target for ENKTL, warranting monitoring in ongoing clinical trials by targeting Bcl-xL.

Yeast UPS1 deficiency leads to UVC radiation sensitivity and shortened lifespan.

UPS1/YLR193C of Saccharomyces cerevisiae (S. cerevisiae) encodes a mitochondrial intermembrane space protein. A previous study found that Ups1p is needed for normal mitochondrial morphology and that UPS1 deficiency disrupts the intramitochondrial transport of phosphatidic acid in yeast cells and leads to an altered unfolded protein response and mTORC1 signaling activation. In this paper, we first provide evidence showing that the UPS1 gene is involved in the UVC-induced DNA damage response and aging. We show that UPS1 deficiency leads to sensitivity to ultraviolet C (UVC) radiation and that this effect is accompanied by elevated DNA damage, increased intracellular ROS levels, abnormal mitochondrial respiratory function, an increased early apoptosis rate, and shortened replicative lifespan and chronological lifespan. Moreover, we show that overexpression of the DNA damage-induced checkpoint gene RAD9 effectively eliminates the senescence-related defects observed in the UPS1-deficient strain. Collectively, these results suggest a novel role for UPS1 in the UVC-induced DNA damage response and aging.

Histopathology of Ganglion Cells in the Proximal Resected Bowel Correlates With the Clinical Outcome in Hirschsprung Disease: A Pilot Study.

INTRODUCTION: Intraoperative leveling biopsy by identifying ganglion cells is crucial to determine surgical margin during surgery for Hirschsprung disease (HSCR). The anastomosis should be performed at least 5 cm proximal to the ganglionic segment to prevent transition zone pull-through. However, the length of the transition zone could be much longer than expected and the histological evaluation of the entire circumference of the proximal margin is recommended, which is time-consuming and not applicable for leveling biopsy. We found that the histopathologic features of ganglion cells varied in the examined bowel specimens and demonstrated a pattern similar to immature and degenerated neuron cells. We assumed that the histopathologic features of ganglion cells in the proximal resected bowel were associated with the clinical outcome and might guide the leveling biopsy. In this study, we described a histopathologic grade of ganglion cells based on the degree of maturity and degeneration. We assessed the correlation between the histopathological grade of ganglion cells in the proximal surgical margin and clinical outcome. METHODS: Three hundred fifty seven patients with HSCR treated between 2013 and 2020 were included. The ganglion cells were divided into six grades based on the histopathologic features in frozen sections. Medical records and detailed histopathologic results of intraoperative frozen sections were reviewed. Follow-up data were collected to evaluate clinical outcomes. The pediatric incontinence and constipation scoring system was used to predict bowel function. RESULTS: The histopathologic results of proximal resected bowel from 357 HSCR patients were presented as follows: Grade I in 52 patients (14.6%), Grade II in 186 patients (52.1%), Grade III in 107 patients (30.0%), and Grade IV in 12 patients (3.4%). The median follow-up time was 46.8 mo (13.0-97.6 mo). The histopathologic grade of ganglion cells from the proximal resected margin was significantly related to postoperative constipation problems and the incidence of Hirschsprung-associated enterocolitis. The results from the pediatric incontinence and constipation scoring system indicated a positive correlation between better postoperative bowel function and lower histopathologic grade of ganglion cells. CONCLUSIONS: This pilot study showed an association between the histopathologic features of ganglion cells in the proximal surgical margin and the clinical outcome. It may provide additional information for intraoperative pathologic consultation in leveling biopsy to prevent insufficient resection of the affected colon. A prospective study is warranted to validate these findings before clinical application.

Breast Cancer Growth on Serial MRI: Volume Doubling Time Based on 3-Dimensional Tumor Volume Assessment.

BACKGROUND: The volume doubling time (VDT) of breast cancer was most frequently calculated using the two-dimensional (2D) diameter, which is not reliable for irregular tumors. It was rarely investigated using three-dimensional (3D) imaging with tumor volume on serial magnetic resonance imaging (MRI). PURPOSE: To investigate the VDT of breast cancer using 3D tumor volume assessment on serial breast MRIs. STUDY TYPE: Retrospective. SUBJECTS: Sixty women (age at diagnosis: 57 ± 10 years) with breast cancer, assessed by two or more breast MRI examinations. The median interval time was 791 days (range: 70-3654 days). FIELD STRENGTH/SEQUENCE: 3-T, fast spin-echo T2-weighted imaging (T2WI), single-shot echo-planar diffusion-weighted imaging (DWI), and gradient echo dynamic contrast-enhanced imaging. ASSESSMENT: Three radiologists independently reviewed the morphological, DWI, and T2WI features of lesions. The whole tumor was segmented to measure the volume on contrast-enhanced images. The exponential growth model was fitted in the 11 patients with at least three MRI examinations. The VDT of breast cancer was calculated using the modified Schwartz equation. STATISTICAL TESTS: Mann-Whitney U test, Kruskal-Wallis test, Chi-squared test, intraclass correlation coefficients, and Fleiss kappa coefficients. A P-value <0.05 was considered statistically significant. The exponential growth model was evaluated using the adjusted R2 and root mean square error (RMSE). RESULTS: The median tumor diameter was 9.7 mm and 15.2 mm on the initial and final MRI, respectively. The median adjusted R2 and RMSE of the 11 exponential models were 0.97 and 15.8, respectively. The median VDT was 540 days (range: 68-2424 days). For invasive ductal carcinoma (N = 33), the median VDT of the non-luminal type was shorter than that of the luminal type (178 days vs. 478 days). On initial MRI, breast cancer manifesting as a focus or mass lesion showed a shorter VDT than that of a non-mass enhancement (NME) lesion (median VDT: 426 days vs. 665 days). DATA CONCLUSION: A shorter VDT was observed in breast cancer manifesting as focus or mass as compared to an NME lesion. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Differential gene expression and potential regulatory network of fatty acid biosynthesis during fruit and leaf development in yellowhorn (Xanthoceras sorbifolium), an oil-producing tree with significant deployment values.

Xanthoceras sorbifolium (yellowhorn) is a woody oil plant with super stress resistance and excellent oil characteristics. The yellowhorn oil can be used as biofuel and edible oil with high nutritional and medicinal value. However, genetic studies on yellowhorn are just in the beginning, and fundamental biological questions regarding its very long-chain fatty acid (VLCFA) biosynthesis pathway remain largely unknown. In this study, we reconstructed the VLCFA biosynthesis pathway and annotated 137 genes encoding relevant enzymes. We identified four oleosin genes that package triacylglycerols (TAGs) and are specifically expressed in fruits, likely playing key roles in yellowhorn oil production. Especially, by examining time-ordered gene co-expression network (TO-GCN) constructed from fruit and leaf developments, we identified key enzymatic genes and potential regulatory transcription factors involved in VLCFA synthesis. In fruits, we further inferred a hierarchical regulatory network with MYB-related (XS03G0296800) and B3 (XS02G0057600) transcription factors as top-tier regulators, providing clues into factors controlling carbon flux into fatty acids. Our results offer new insights into key genes and transcriptional regulators governing fatty acid production in yellowhorn, laying the foundation for efforts to optimize oil content and fatty acid composition. Moreover, the gene expression patterns and putative regulatory relationships identified here will inform metabolic engineering and molecular breeding approaches tailored to meet biofuel and bioproduct demands.

A novel CLCN5 frame shift mutation responsible for Dent disease 1: Case report.

Background: Dent disease is a group of inherited X-linked recessive renal tubular disorders. This group of disorders is characterized by low molecular weight proteinuria (LMWP), nephrocalcinosis, hypercalciuria and renal failure. Case presentation: Here we report one 11-year-old Chinese boy (proband) and one 13-year-old Chinese boy who was proband's cousin, both presented with massive proteinuria. Further laboratory examinations revealed a lack of nephrocalcinosis, nor any other signs of tubular dysfunction, but only LMWP and hypercalciuria. There was no abnormality in growth, renal function or mineral density of the bones. A novel deletion (c.1448delG) in the CLCN5 gene was identified, resulting in a frame shift mutation (p.Gly483fs). The proband's and his cousin's mothers were found to be the carrier of this mutation. Conclusions: In this study, we have found a novel frameshift mutation (c. 1448delG) at exon 11 of the CLCN5 gene which leads to Dent disease 1, expanding the spectrum of CLCN5 mutations.

Axillary lymph node dissection combined with radiotherapy for trichilemmal carcinoma with giant lymph node metastasis: A case report.

Background: Trichilemmal carcinoma (TC) is a rare malignancy with a poor outcome if local recurrence and distant metastasis occur. There is no treatment strategy for such a disease. Case presentation: We reported a complicated case of TC in the right lower abdomen with ipsilateral axillary and inguinal lymph node metastases. After surgery and radiotherapy, there has been no recurrence or metastasis in the follow-up to date. Conclusion: We believe that even though considered a tumor of low malignant potential, TC still has the risk of recurrence and metastasis, and the lymph node status should be identified if a high suspicion or diagnosis is made. Regional lymph node dissection followed by local radiotherapy is recommended as the optimal treatment strategy for patients with lymph node metastases of TC. Screening for metastasis and close follow-up are indispensable for improving prognosis.

Embryonal tumors with multilayered rosettes, C19MC-altered or not elsewhere classified: Clinicopathological characteristics, prognostic factors, and outcomes of 17 children from 2018 to 2022.

Objective: Embryonal tumors with multilayered rosettes (ETMRs) are a histologically heterogeneous entity and gather embryonal tumors with abundant neuropil and true rosettes (ETANTRs), ependymoblastoma, and medulloepithelioma. ETMRs are highly aggressive and associated with poorer clinical courses. However, cases of this entity are rare, and advances in molecular genetics and therapy are minor. The purpose of our study was to retrospectively analyze the clinical, pathological features, and prognostic factors of ETMRs. Methods: Our cohort consisted of 17 patients diagnosed with ETMRs in our hospital from 2018 to 2022, and two of them were lost to follow-up. Clinical data were retrieved, and immunohistochemistry and genetic analyses were performed. Results: Among 17 cases, 16 were ETANTRs, and one was medulloepithelioma. Morphologically, tumor cells of ETANTRs could transform into anaplasia and lose the biphasic architecture during tumor progression. Immunohistochemistry of LIN28A revealed positive expression in 17 cases, and the expression of LIN28A was more intense and diffuse in the recurrent lesions than in primaries. The increased N-MYC copy numbers were detected in the primary tumor and recurrence of patient 8. Moreover, the incidence of metastatic disease was 100% in patients aged > 4 years and 18% in the younger group. For patients receiving chemotherapy, the median overall survival time was 7.4 months, while that of those who didn't receive it was 1.2 months. Nevertheless, surgical approaches, radiotherapy, age at presentation, gender, tumor location, and metastatic status were not associated with independent prognosis. Conclusion: ETANTR might not present as the typical morphologies during tumor progression, so analyses of C19MC amplification and Lin28A antibody are indispensable for diagnosing ETMRs accurately. Children aged > 4 years tend to have a higher rate of metastasis in ETMRs. Chemotherapy is the only prognostic factor for ETMRs patients with a favorable prognosis. The biological nature and clinical patterns for recurrent diseases need to be further demonstrated to predict prognosis and guide treatment.

GBP2 serves as a novel prognostic biomarker and potential immune microenvironment indicator in renal cell carcinoma.

Since the application of immune checkpoint therapy (ICT) has gradually become a new strategy for clear cell renal cell carcinoma (ccRCC) treatment, biomarkers that predict the individual response to ICT is needed. This study aimed to identify a new clinical indicator for postoperative surveillance of ccRCC and prediction of ICT response. We investigated the GBP2 expression and its relation with immune cell infiltration in tumor microenvironment using public databases, clinical specimens and ccRCC cell lines. Bioinformatic analysis using public database revealed that GBP2 expression is higher in cancer tissues than in adherent normal tissues among different cancer types including ccRCC, and the same results were acquired from clinical tissue samples tested by Western Blot and PCR. In ccRCC cell lines, CCk-8 proliferation assay and apoptosis assessment suggested GBP2 facilitates the malignancy of ccRCC. 286 ccRCC patients were randomly divided into a training or validation cohort, and immunohistochemistry (IHC) and Kaplan-Meier analysis revealed that higher GBP2 expression is related to worse prognosis. C-index analysis implied that integrating GBP2 expression with TNM stage improved the accuracy in predicting prognosis of ccRCC patients compared to the solitary use of either. Bioinformatic analysis implied a relation between GBP2 and immunity, and GBP2 expression is positively related with suppressive immune markers in ccRCC microenvironment. Taken together, our study demonstrated the potential of GBP2 to sever as a prognostic predictor of ccRCC, and an association between GBP2 and tumor-infiltrating lymphocytes in ccRCC was observed, making it a promising indicator of ICT response.

Bilateral Thalamic Gliomas Harboring Alterations of EGFR and H3K27M: An Integrated Clinicopathological Characteristics Case Series.

BACKGROUND: Bilateral thalamic gliomas (BTGs) are rare central nervous system tumors, and the outcome is usually dismal. BTG often harbors an EGFR mutation; however, a mutation in H3K27M is rare. We described 5 cases of BTGs harboring concomitant alterations of EGFR and H3K27M and retrospectively analyzed the clinicopathological features and prognosis of this rare entity. METHODS: Clinical data of patients were retrieved, and immunohistochemistry and molecular analyses were performed. In addition, a systematic review of literature was conducted using PubMed. RESULTS: Median patient age was 6 years (range, 3-9 years). The male-to-female ratio was 3:2. Tremors and disturbed speech were the main clinical manifestations. All lesions were located at bilateral thalami, and in 3 of 4 patients, the more significant thalamic lesion was on the left. Two patients harbored insertion mutations in exon 20 of EGFR, 1 missense mutation in exon 7 of EGFR, and 2 EGFR amplifications. After a median overall survival of 8 months, 3 patients died as a result of tumor progression. CONCLUSIONS: Concomitant alterations of EGFR and H3K27M might indicate a new subtype of diffuse midline glioma, H3K27M-altered. In addition, EGFR alterations could provide potential molecular therapeutic strategies to improve the dismal prognosis of BTGs. Due to the rarity of these tumors, more cases must be collected to study the pathogenesis, treatment, and clinical outcomes of BTGs with double alteration phenotypes.

Cancer-associated fibroblasts subtypes and role in invasion and metastasis of gastric cancer.

Gastric cancer (GC) is the fifth most common malignancy and the fourth leading cause of cancer-related death worldwide. Cancer-associated fibroblasts (CAFs), an important cell type in the tumor microenvironment, play an important role in GC development. In this review, we describe the current knowledge of CAFs' heterogeneity and their role in GC invasion and metastasis. Currently, CAF-targeted cancer therapies are being rapidly explored and developed. However, the heterogeneity of CAFs limits the application of this therapy, so it is urgent to find specific markers and divide them into different subpopulations. With the development of single-cell RNA sequencing technology, researchers have used this technology to classify CAFs in many tumors, but whether it is applicable to GC and other tumors needs further study. And we believe that this technology will be in the near future utilized to sort CAFs on the basis of different cell markers and functions, so as to target tumor-promoting CAFs and inhibit tumor progression. Targeting CAFs by cell surface markers or normalizing the activated CAFs subsets may be an effective therapy, alone or in combination with other therapeutic approaches for GC treatment. Therefore, in the coming decades, the interaction between CAFs and GC cells will be still the focus of our research.