Atmospheric Nanoparticles in Photocatalytic and Thermal Production of Atmospheric Pollutants

Atmospheric aerosols which occur above heavily polluted areas such as Mexico City, are characterized and found to be complex materials that have the potential to accelerate important ozone-forming reactions photocatalytically and thermocatalytically. In addition, because the particles are respirable, they may represent a considerable health hazard. The aerosols consist of two intermixed components. The first component consists of amorphous carbonaceous materials of variable composition with fullerene like materials dispersed throughout. The second component is an inorganic material consisting of nanoparticles of oxides and sulfides supported on clay minerals. This inorganic component has all of the characteristics of an airborne photocatalyst. Nanoparticles of Fe2O3, MnO2 and FeS2 have demonstrated catalytic properties, particularly when they occur in the nanoparticle range, as they do in the subject aerosol materials. These materials have band-gaps that occur in the broad solar spectrum enhancing the photocatalytic adsorption of solar radiation beyond that of the wider band-gap aluminosilicate and titanate materials, which also occur in aerosols. In addition, the materials are acidic and probably are coated with moisture when suspended in air, further enhancing their catalytic ability to crack hydrocarbons and create free radicals

Characteristics and survival of patients with advanced cancer and p53 mutations.

P53 mutations are associated with invasive tumors in mouse models. We assessed the p53mutations and survival in patients with advanced cancer treated in the Phase I Program. Of 691 tested patients, 273 (39.5%) had p53 mutations. Patients with p53 mutations were older (p<.0001) and had higher numbers of liver metastases (p=.005). P53 mutations were associated with higher numbers of other aberrations; PTEN (p=.0005) and HER2 (p=.003)aberrations were more common in the p53 mutation group. No survival difference was observed between patients with p53 mutations and those with wild-type p53. In patients with wild-type p53 and other aberrations, patients treated with matched-therapy against the additional aberrations had longer survival compared to those treated with non-matched-therapy or those who received no therapy (median survival, 26.0 vs. 11.8 vs. 9.8 months, respectively; p= .0007). Results were confirmed in a multivariate analysis (p= .0002). In the p53 mutation group with additional aberrations, those who received matched-therapy against the additional aberrations had survival similar to those treated with non-matched-therapy or those who received no therapy (p=.15). In conclusion, our results demonstrated resistance to matched-targeted therapy to the other aberrations in patients with p53 mutations and emphasize the need to overcome this resistance

Malignant melanotic nerve sheath tumor with PRKAR1A, KMT2C and GNAQ mutations

Malignant melanotic nerve sheath tumor (MMNST) is a rare and potentially aggressive lesion defined in the 2021 WHO Classification of Tumors of the Central Nervous System. MMNST demonstrate overlapping histologic and clinical features of schwannoma and melanoma. MMNST often harbor PRKAR1A mutations, especially within the Carney Complex. We present a case of aggressive MMNST of the sacral region in a 48-year-old woman. The tumor contained PRKAR1A frameshift pR352Hfs*89, KMT2C splice site c.7443-1G>T and GNAQ p.R183L missense mutations, as well as BRAF and MYC gains. Genomic DNA methylation analysis using the Illumina 850K EpicBead chip revealed that the lesion did not match an established methylation class; however, uniform manifold approximation and projection (UMAP) placed the tumor very near, or with, schwannomas. The tumor expressed PD-L1, and the patient was treated with radiation and immune checkpoint inhibitors following en bloc resection. Although she had symptomatic improvement, she suffered early disease progression with local recurrence, and distant metastases, and died 18 months after resection. It has been suggested that the presence of GNAQ mutations can differentiate leptomeningeal melanocytic neoplasms and uveal melanoma from MMNST. This case and others demonstrate that GNAQ mutations may exist in malignant nerve sheath tumors; that GNAQ and PRKAR1A mutations are not always mutually exclusive and that neither can be used to differentiate MMNST or MPNST from all melanocytic lesions

Reference on copy number variations in pleomorphic xanthoastrocytoma: Implications for diagnostic approach

Pleomorphic xanthoastrocytoma (PXA) poses a diagnostic challenge. The present study relies on methylation-based predictions and focuses on copy number variations (CNV) in PXA. We identified 551 tumors from patients having received the histologic diagnosis or differential diagnosis pleomorphic xanthoastrocytoma (PXA) uploaded to the web page www.molecularneuropathology.org. Of these 551 tumors, 165 received the prediction “methylation class (anaplastic) pleomorphic xanthoastrocytoma” with a calibrated score >=0.9 by the brain tumor classifier version v12.8 and, therefore, were defined the PXA reference set designated mcPXAref. In addition to these 165 mcPXAref, 767 other tumors received the prediction mcPXA with a calibrated score >=0.9 but without a histological PXA diagnosis. The total number of individual tumors predicted by histology and/or by methylome based classification as PXA, mcPXA or both was 1318, and these were designated the study cohort. The selection of a control cohort was guided by methylation-based predictions recurrently observed for the other 386/551 tumors diagnosed as histologic PXA. 131/386 received predictions for another entity besides PXA with a score >=0.9. Control tumors corresponding to the 11 most common other predictions were selected, adding up to 1100 reference cases. CNV profiles were calculated from all methylation datasets of the study and control cohorts. Special attention was given to the 7/10 signature, gene amplifications and homozygous deletion of CDKN2A/B. Comparison of CNV in the subsets of the study cohort and the control cohort were used to establish relations independent of histological diagnoses. Tumors in mcPXA were highly homogenous in regard to CNV alterations, irrespective of the histological diagnoses. The 7/10 signature commonly present in glioblastoma, IDH-wildtype, was present in 15-20% of mcPXA, whereas amplification of oncogenes (likewise common in glioblastoma) was very rare in mcPXA (<1%). In contrast, the histology-based PXA group exhibited high variance in regard to methylation classes as well as to CNVs. Our data add to the notion, that histologically defined PXA likely only represent a subset of the biological disease

Reversing HOXA9 oncogene activation by PI3K inhibition: epigenetic mechanism and prognostic significance in human glioblastoma

HOXA genes encode critical transcriptional regulators of embryonic development that have been implicated in cancer. In this study, we documented functional relevance and mechanism of activation of HOXA9 in glioblastoma (GBM), the most common malignant brain tumor. Expression of HOXA genes was investigated using reverse transcription-PCR in primary gliomas and glioblastoma cell lines and was validated in two sets of expression array data. In a subset of GBM, HOXA genes are aberrently activated within confined chromosomal domains. Transcriptional activation of the HOXA cluster was reversible by a phosphoinostide 3-kinase (PI3K) inhibitor through an epigenetic mechanism involving histone H3K27 trimethylation. Functional studies of HOXA9 showed its capacity to decrease apoptosis and increase cellular proliferation along with tumor necrosis factor-related apoptosis-including ligand resistance. Notably, aberrant expression of HOXA9 was independently predictive of shorter overall and progression-free survival in two GBM patient sets and improved survival prediction by MGMT promoter methylation. Thus, HOXA9 activation is a novel, independent, and negative prognostic marker in GBM that is reversible through a PI3K-associated epigenetic mechanism. Our findings suggest a transcriptional pathway through which PI3K activates oncogenic HOXA expression with implications for mTOR or PI3K targeted therapies.NIH grants NIH CA094971 (J.F. Costello) and NIH/NCI F32 CA113039-01 (J.S. Smith); Karen Osney Brownstein Endowed Chair (J.F. Costello); UC Discovery grant Bio05-10501 (J.F. Costello and H.S. Phillips); Portuguese Science and Technology Foundation SFRH/BD/15258/2004 (B.M. Costa); and Luso-American Development Foundation, Portugal 186/06 (B.M. Costa

In vitro test of external Qigong

BACKGROUND: Practitioners of the alternative medical practice 'external Qigong' generally claim the ability to emit or direct "healing energy" to treat patients. We investigated the ability of experienced Qigong practitioners to enhance the healthy growth of cultured human cells in a series of studies, each following a rigorously designed protocol with randomization, blinding and controls for variability. METHODS: Qigong practitioners directed healing intentionality toward normal brain cell cultures in a basic science laboratory. Qigong treatments were delivered for 20 minutes from a minimum distance of 10 centimeters. Cell proliferation was measured by a standard colony-forming efficiency (CFE) assay and a CFE ratio (CFE for treated samples/CFE for sham samples) was the dependent measure for each experiment. RESULTS: During a pilot study (8 experiments), a trend of increased cell proliferation in Qigong-treated samples (CFE Qigong/sham ratios > 1.0) was observed (P = 0.162). In a formal study (28 experiments), a similar trend was observed, with Qigong-treated samples showing on average more colony formation than sham samples (P = 0.036). In a replication study (60 experiments), no significant difference between Qigong-treated samples and sham samples was observed (P = 0.465). CONCLUSION: We observed an apparent increase in the proliferation of cultured cells following external Qigong treatment by practitioners under strictly controlled conditions, but we did not observe this effect in a replication study. These results suggest the need for more controlled and thorough investigation of external Qigong before scientific validation is claimed