Genomic Deregulation of the E2F/Rb Pathway Leads to Activation of the Oncogene EZH2 in Small Cell Lung Cancer

Small cell lung cancer (SCLC) is a highly aggressive lung neoplasm with extremely poor clinical outcomes and no approved targeted treatments. To elucidate the mechanisms responsible for driving the SCLC phenotype in hopes of revealing novel therapeutic targets, we studied copy number and methylation profiles of SCLC. We found disruption of the E2F/Rb pathway was a prominent feature deregulated in 96% of the SCLC samples investigated and was strongly associated with increased expression of EZH2, an oncogene and core member of the polycomb repressive complex 2 (PRC2). Through its catalytic role in the PRC2 complex, EZH2 normally functions to epigenetically silence genes during development, however, it aberrantly silences genes in human cancers. We provide evidence to support that EZH2 is functionally active in SCLC tumours, exerts pro-tumourigenic functions in vitro, and is associated with aberrant methylation profiles of PRC2 target genes indicative of a “stem-cell like” hypermethylator profile in SCLC tumours. Furthermore, lentiviral-mediated knockdown of EZH2 demonstrated a significant reduction in the growth of SCLC cell lines, suggesting EZH2 has a key role in driving SCLC biology. In conclusion, our data confirm the role of EZH2 as a critical oncogene in SCLC, and lend support to the prioritization of EZH2 as a potential therapeutic target in clinical disease.     

Fine-Resolution Mapping of TF Binding and Chromatin Interactions

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ICAMs Are Not Obligatory for Functional Immune Synapses between Naive CD4 T Cells and Lymph Node DCs

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Swidden, Sawah, and In-Between: Agricultural Transformation in Borneo

The change from swidden to sawah cultivation in Tara'n Dayak villages in West Kalimantan, Indonesia, is presented as a long-term, complex incremental process in which distinct, unstable, and often confusing production technologies figure as transitional forms. The transitional phases are discussed in terms of their efficiency and sustainability. It is argued that the failure to perceive and understand long-term processes of agricultural change may result in both misinterpretation of technological patterns and environmental variables, as well as of rules of labor and resource sharing.     

Lymph node metastasis of soft tissue tumors: a cytomorphologic study

OBJECTIVE: To study the frequency of regional lymph node metastasis of soft tissue tumors (STT) and to evaluate the utility of fine needle aspiration cytology (FNAC) as an initial investigative modality. STUDY DESIGN: A prospective and retrospective study of over 6 years (1998-2004) was performed to look for frequency of STT metastasizing to lymph nodes. FNAC of enlarged nodes was performed as a routine outpatient procedure after obtaining complete clinical details. Histopathology and immunohistochemistry were correlated where available. RESULTS: Lymph node enlargement was seen in 23 of 241 patients with STTs, of which 19 cases showed involvement (7.88%), synchronous with primary in 12 cases and metachronous in 7 cases. The most common sites of primary tumor were the lower extremity and head and neck region with involved regional lymph nodes. STTs commonly involving lymph nodes were rhabdomyosarcoma and extraskeletal Ewing's/primitive neuroectodermal tumor (PNET); other rare tumors included malignant granular cell tumor, epithelioid hemangioendothelioma, mediastinal ganglioneuroblastoma, angiosarcoma and epithelioid sarcoma. CONCLUSION: Lymph node aspirates should be examined for alien cells, particularly smears that are paucicellular and demonstrate cystic change. Lymph node metastasis of STT is rare and influences staging, treatment and prognosis. Enlarged regional nodes should be examined with FNAC.     

New structural–optical effect in LiF–Li2B4O7 thin-film structures in the crystallization

The effect of optical radiation during the phase transition from the amorphous to the crystalline state of matter was investigated for the first time. The results were obtained on nanoscale films of (LiF)_x(Li₂B₄O₇)_1-x compositions by sputtering on cold Ni substrates. The starting materials for films were chosen due to their wide use for tissue-equivalent ionizing radiation dosimetry. It is shown that the detected thermoluminescence effect is sensitive to the thickness of the films. The paper compares the results of these studies with the study of the thermoluminescence characteristics of films irradiated by an M-30 microtron with bremsstrahlung radiation with a maximum energy of 6 MeV. The absorbed radiation dose was 1 kGy. Differences in the luminescence characteristics of irradiated and nonirradiated films were revealed. The nature of the demonstrated structural–optical effect is discussed.     

Role of endoscopic ultrasound‐guided‐fine needle aspiration biopsy in the diagnosis of lymphoma of the pancreas: A clinicopathological study of nine cases

Objective

Endoscopic ultrasound‐guided‐fine needle aspiration (EUS‐FNA) is an established first‐line procedure in the management of solid and cystic pancreatic masses. Lymphoma is an uncommon diagnosis in EUS‐FNA of the pancreas, and it is more common for such a diagnosis to be because of secondary involvement of the pancreas by a lymphoproliferative disorder than for this to represent isolated primary pancreatic lymphoma (PPL). We present the clinical, EUS and cytological features of these lesions.

Material and methods

After obtaining approval from our Institutional Review Board (IRB), nine cases of lymphoma diagnosed on EUS‐FNA at a tertiary care cancer centre over a period of 8 years from 2008 to 2016 were retrieved from our endoscopy and pathology archives. Rapid onsite evaluation (ROSE) was carried out by a trained cytopathologist in all these cases. Cell blocks were available in seven cases, and immunophenotyping was performed on cell blocks using the immunoperoxidase method. Flow cytometry was performed in two cases.

Results

The most frequent site of involvement was the head of the pancreas (n=5, 55.6%). Four out of nine cases were diagnosed as PPL (44.4%). Five cases were diagnosed as lymphoma secondarily involving the pancreas (55.6%). The most frequent diagnosis was diffuse large B‐cell lymphoma (n=6, 66.7%), followed by Hodgkin's lymphoma (n=2, 22.2%) and peripheral T‐cell lymphoma (n=1, 11.1%).

Conclusion

EUS‐FNA in experienced hands is a valuable diagnostic modality, in conjunction with ROSE, immunohistochemistry and flow cytometry, in the diagnosis and sub‐typing of both primary and secondary pancreatic lymphoma.     

The transition from day-to-night activity is a risk factor for the development of CNS oxygen toxicity in the diurnal fat sand rat (Psammomys obesus)

Performance and safety are impaired in employees engaged in shift work. Combat divers who use closed-circuit oxygen diving apparatus undergo part of their training during the night hours. The greatest risk involved in diving with such apparatus is the development of central nervous system oxygen toxicity (CNS-OT). We investigated whether the switch from day-to-night activity may be a risk factor for the development of CNS-OT using a diurnal animal model, the fat sand rat (Psammomys obesus). Animals were kept on a 12:12 light–dark schedule (6 a.m. to 6 p.m. at 500?lx). The study included two groups: (1) Control group: animals were kept awake and active during the day, between 09:00 and 15:00. (2) Experimental group: animals were kept awake and active during the night, between 21:00 and 03:00, when they were exposed to dim light in order to simulate the conditions prevalent during combat diver training. This continued for a period of 3?weeks, 5?days a week. On completion of this phase, 6-sulphatoxymelatonin (6-SMT) levels in urine were determined over a period of 24?h. Animals were then exposed to hyperbaric oxygen (HBO). To investigate the effect of acute melatonin administration, melatonin (50?mg/kg) or its vehicle was administered to the animals in both groups 20?min prior to HBO exposure. After the exposure, the activity of superoxide dismutase, catalase and glutathione peroxidase was measured, as were the levels of neuronal nitric oxide synthase (nNOS) and overall nitrotyrosylation in the cortex and hippocampus. Latency to CNS-OT was significantly reduced after the transition from day-to-night activity. This was associated with alterations in the level of melatonin metabolites secreted in the urine. Acute melatonin administration had no effect on latency to CNS-OT in either of the groups. Nevertheless, the activity of superoxide dismutase and catalase, as well as nitrotyrosine and nNOS levels, were altered in the hippocampus following melatonin administration. On the basis of these results, we suggest that a switch from diurnal to nocturnal activity may represent an additional risk factor for the development of CNS-OT. Utilizing a diurnal animal model may contribute to our understanding of the heightened risk of developing CNS-OT when diving with closed-circuit oxygen apparatus at night.