PUMC-MB1 is a novel group 3 medulloblastoma preclinical model, sensitive to PI3K/mTOR dual inhibitor.

PURPOSE: Medulloblastoma (MB), a common and heterogeneous posterior fossa tumor in pediatric patients, presents diverse prognostic outcomes. To advance our understanding of MB's intricate biology, the development of novel patient tumor-derived culture MB models with necessary data is still an essential requirement. METHODS: We continuously passaged PUMC-MB1 in vitro in order to establish a continuous cell line. We examined the in vitro growth using Cell Counting Kit-8 (CCK-8) and in vivo growth with subcutaneous and intracranial xenograft models. The xenografts were investigated histopathologically with Hematoxylin and Eosin (HE) staining and immunohistochemistry (IHC). Concurrently, we explored its molecular features using Whole Genome Sequencing (WGS), targeted sequencing, and RNA sequecing. Guided by bioinformatics analysis, we validated PUMC-MB1's drug sensitivity in vitro and in vivo. RESULTS: PUMC-MB1, derived from a high-risk MB patient, displayed a population doubling time (PDT) of 48.18 h and achieved 100% tumor growth in SCID mice within 20 days. HE and Immunohistochemical examination of the original tumor and xenografts confirmed the classification of PUMC-MB1 as a classic MB. Genomic analysis via WGS revealed concurrent MYC and OTX2 amplifications. The RNA-seq data classified it within the Group 3 MB subgroup, while according to the WHO classification, it fell under the Non-WNT/Non-SHH MB. Comparative analysis with D283 and D341med identified 4065 differentially expressed genes, with notable enrichment in the PI3K-AKT pathway. Cisplatin, 4-hydroperoxy cyclophosphamide/cyclophosphamide, vincristine, and dactolisib (a selective PI3K/mTOR dual inhibitor) significantly inhibited PUMC-MB1 proliferation in vitro and in vivo. CONCLUSIONS: PUMC-MB1, a novel Group 3 (Non-WNT/Non-SHH) MB cell line, is comprehensively characterized for its growth, pathology, and molecular characteristics. Notably, dactolisib demonstrated potent anti-proliferative effects with minimal toxicity, promising a potential therapeutic avenue. PUMC-MB1 could serve as a valuable tool for unraveling MB mechanisms and innovative treatment strategies.

Establishment and characterization of a new human colon cancer cell line, PUMC-CRC1.

Colorectal cancer (CRC) is one of the most common and fatal gastrointestinal cancers worldwide. Considering their diversity, the establishment of new continuous CRC cell lines with clear genetic backgrounds will provide useful tools for exploring molecular mechanisms, screening and evaluating antitumor drugs in CRC studies. Our de novo CRC cell line, PUMC-CRC1 (Peking Union Medical College Colorectal Cancer 1) was derived from a 47-year-old Chinese female patient diagnosed with moderately to poorly differentiated colon adenocarcinoma. Multiple experiments were used for full characterization. The new cell line was epithelial-like and was passaged for more than 40 times, with a population doubling time of 44 h in vitro, detected by cell counts. The cells exhibited complicated chromosomal abnormalities. The tumor formation rate in SCID mice was 100%. The xenograft tumor was adenocarcinoma with poor to moderate differentiation by Haematoxylin and Eosin staining (H&E) sections. Immunohistochemistry (IHC) analysis and next-generation sequencing (NGS) revealed microsatellite stable (MSS), APC (p.T1493fs) inactivation, KRAS (p.G12V) activation, and SMAD4 (p.V506A) mutation. Quality control of the cell line proved mycoplasma negative and identical STR profile with that of the original tissue, and no interspecific or intraspecific cross contamination was detected. In conclusion, PUMC-CRC1 was a newly established and well characterized human colon cancer cell line, which might be a good model for both in vitro and in vivo studies of the mechanism of colon cancer progression and the treatment strategies for MSS CRC.

[Study of transcranial magnetic stimulation on diaphragm in patients with obstructive sleep apnea-hypopnea syndrome].

OBJECTIVE: To investigate the changes and possible mechanisms of diaphragm motor evoked potential (MEP) elicited by transcranial magnetic stimulation (TMS) in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). METHODS: Sixteen healthy volunteers (control group), 7 primary snorers (snore group), 13 mild-moderate OSAHS patients (mild-moderate group) and 16 severe OSAHS patients (severe group) were recruited for the study from June in 2005 to June in 2006. Esophageal electrodes combined with TMS and cervical magnetic stimulation (CMS) were used to measure the latency and amplitude of right diaphragm MEP, as well as central motor conduction time (CMCT). The study was repeated in 5 OSAHS patients after effective nasal continuous positive airway pressure (nCPAP) treatment for at least 2 months. RESULTS: The amplitude of right MEP in severe OSAHS group was (152 +/- 116) microV, which was significantly lower than that in the control group (414 +/- 201) microV, the snore group (352 +/- 99) microV and the mild-moderate group (372 +/- 206) microV. The latency and CMCT in the severe OSAHS group were (18.1 +/- 1.8), (10.6 +/- 1.8) ms respectively, which were significantly longer than those in the control group (13.9 +/- 1.6), (7.7 +/- 1.7) ms, the snore group (14.6 +/- 1.6), (8.1 +/- 1.6) ms, and the mild-moderate group (15.4 +/- 2.7) , (9.0 +/- 2.2) ms. The latency and amplitude of diaphragm MEP as well as CMCT correlated significantly with arousal index, longest apnea duration, minimum pulse oxygen saturation (SpO2), oxygen desaturation index, the percentage of total sleep time with SpO2 below 90% and apnea-hypoxia index (AHI). The latency became significantly shorter after effective nCPAP treatment for more than 2 months, which was (17.5 +/- 0.6) and (15.5 +/- 0.7) ms respectively. CONCLUSIONS: The latency of MEP and CMCT in OSAHS patients prolonged significantly, while the amplitude of MEP lowered, which may be due to repeated hypoxia, carbon dioxide retention and disorder of sleep structure at night.

[Phrenic nerve conduction of obstructive sleep apnea-hypopnea syndrome patients].

OBJECTIVE: To investigate the significance of phrenic nerve conduction time (PNCT) and diaphragm compound muscle action potential (CMAP) detection in the assessment of severity and response to treatment in obstructive sleep apnea-hypopnea syndrome (OSAHS) patients. METHODS: Sixteen healthy volunteers (control group), 8 primary snorers (snorer group), 14 mild-moderate OSAHS patients (mild-moderate group) and 18 severe OSAHS patients (severe group) were recruited for the study from January to July in 2005. Multi-pair esophageal electrodes were used to measure PNCT and CMAP of diaphragm in response to unilateral magnetic stimulation. The study was repeated in 5 OSAHS patients after effective nCPAP treatment for at least 2 months. RESULTS: The PNCT in severe OSAHS group was (8.9 +/- 1.2), (7.9 +/- 1.5) ms respectively, which was significantly longer than those in the control group (6.5 +/- 0.7), (6.0 +/- 0.5) ms, snorer group (6.5 +/- 1.2), (6.0 +/- 0.8) ms and mild-moderate group (7.3 +/- 1.0), (6.3 +/- 0.7) ms. The amplitude of diaphragm CMAP was (1.4 +/- 0.4), (1.4 +/- 0.3) mV in mild-moderate group and (0.9 +/- 0.4), (1.1 +/- 0.6) mV in severe group, which was significantly lower than those in the control group (2.3 +/- 0.9), (2.1 +/- 0.9) mV and snorer group (1.9 +/- 0.5), (2.1 +/- 0.7) mV, and severe patients have significantly lower CMAP than mild-moderate patients. The PNCT and CMAP of both sides for all subjects correlated significantly with oxygen desaturation index and apnea-hypopnea index. The PNCT shortened significantly after effective nCPAP treatment, which was (8.6 +/- 0.6) ms, (7.4 +/- 0.5) ms for left side and (7.8 +/- 0.6) ms, (6.5 +/- 0.5) ms for right side. CONCLUSION: PNCT and CMAP detection with multi-pair esophageal electrodes in response to unilateral magnetic stimulation may be useful for the severity assessment and evaluation of response to effective treatment in OSAHS patients.

Correlation between EGFR mutations and serum tumor markers in lung adenocarcinoma patients.

BACKGROUND: Mutations affecting the epidermal growth factor receptor (EGFR) are good predictors of clinical efficacy of EGFR tyrosine kinase inhibitors (TKI) in patients with non-small cell lung cancer. Serum carcinoembryonic antigen (CEA) levels are also regarded as predictive for the efficacy of EGFR-TKI and EGFR gene mutations. This study analyzed the association between EGFR gene mutations and clinical features, including serum tumor marker levels in lung adenocarcinomas patients. PATIENTS AND METHODS: A total of 70 lung adenocarcinoma patients with complete clinical data and pathological specimens were investigated. EGFR gene mutations at exons 19 and 21 were assessed. Serum tumor markers were detected by protein chip- chemiluminescence at the corresponding time, and correlations were analyzed. RESULTS: Mutations of the EGFR gene were detected in 27 of the 70 patients and the serum CEA and CA242 concentrations were found to be significantly associated with the incidence of EGFR gene mutations (P<0.05). The AUCs for CEA and CA242 were 0.724 (95% CI: 0.598~0.850, P<0.05) and 0.769 (95% CI: 0.523~0.800, P<0.05) respectively. CONCLUSIONS: Serum CEA and CA242 levels are associated with mutations of the EGFR gene in patients with lung adenocarcinomas.

[Dynamic characteristics of leaf area index and allocation characters of ecological resources for different yielding spring maize populations].

By using 3-year field experimental results and related meteorological observation data, the dynamic characteristics of leaf area index (LAI) and the allocation characters of ecological resources for different yielding spring maize (Zea Mays L.) population in Huadian of Jilin Province were studied. The results showed that the dynamic characteristics of relative LAI, with the relative growth days of test population, relative effective accumulated temperature, relative sunshine hours and relative rainfall as independent variables, fitted rational formula y = (a + bx) /(1 + cx + dx2), and the regression equation of maize yield with the ratios of growth days before and after silking (x1), effective accumulated temperature before and after silking (x2), rainfall before and after silking (x3), and sunshine hours before and after silking (x4) was y = 5465.19 + 17810.64x(1) - 23236.14x(2) + 4093.41x(3) + 6287.37x(4) (R2 = 0. 8187, P < 0.01), with the effects of these ecological factors on yield being in the sequence of x1 > x2 > x3 > x4 according to the absolute values of partial regression coefficients. In super high yielding (15499.86 kg x hm(-2)) spring maize population, the allocation ratios of x1, x2, x3, and x4 were 1.43, 1.41, 1.44, and 1.40, respectively. Therefore, in Northeast China, appropriate early sowing of spring maize to prolong its growth days with more rainfall and sunshine hours before silking could attain high yielding, and high or super high yield could be achieved when the allocation ratios of x1, x2, x3, and x4 were all about 1.4.