The Notch and TGF-β Signaling Pathways Contribute to the Aggressiveness of Clear Cell Renal Cell Carcinoma

Despite recent progress, therapy for metastatic clear cell renal cell carcinoma (CCRCC) is still inadequate. Dysregulated Notch signaling in CCRCC contributes to tumor growth, but the full spectrum of downstream processes regulated by Notch in this tumor form is unknown

Black tea extract can modulate protein expression of H-ras, c-Myc, p53, and Bcl-2 genes during pulmonary hyperplasia, dysplasia, and carcinoma in situ

Lung cancer has emerged as one of the leading causes of cancer death in most developed and many developing countries of the world. In the absence of effective screening and early detection methods of lung cancer and overall poor prognosis, the 5-year survival following treatment has not improved significantly over the last two decades. It is hoped that the risk of the disease can be minimized by preventive measures. One aspect of lung cancer prevention emphasizes the cessation of tobacco smoking, and another strategy envisages reversal or restriction of the process of lung carcinogenesis by chemopreventive intervention. The latter strategy, however, demands a deeper understanding of the pathogenesis of the disease and the identification of the ideal point of intervention. In the present investigation, we assessed the role of the antioxidant tea components theaflavins (TF) and epigallocatechin gallate (EGCG) for their chemopreventive potential and molecular mechanism of action when administered at the post-initiation phase of lung carcinogenesis in an experimental mouse model. We serially examined the histopathological changes in the lung of mice administered benzo(a)pyrene and correlated them with the frequency of proliferative and apoptotic cells in situ as well as with the expression of H-ras, c-Myc, p53, and Bcl-2 genes, which play key roles in the histopathogenesis of neoplasia. Our findings indicate that both TF and EGCG can influence gene expression to modulate the process of carcinogenesis through the regulation of apoptosis. This results in a lowered incidence and delayed onset of preinvasive lung lesions

Black tea polyphenols restrict benzopyrene-induced mouse lung cancer progression through inhibition of Cox-2 and induction of caspase-3 expression

Lung cancer is one of the leading causes of cancer related death in most developed and many developing countries of the world. Due to lack of validated screening methods and poor prognosis, treatment of lung cancer has not improved significantly over the last two decades. Therefore the risk of the disease needs to be minimized by preventive measures. One approach for lung cancer prevention envisages reversal or restriction of precancerous lesions by chemopreventive intervention. It demands a deeper understanding of the pathogenesis of the disease and identification of the ideal point of intervention. In the present investigation, tea components, epigallocatechin gallate (EGCG) and theaflavins (TF) were assessed for their chemopreventive potential when administered in the post initiation phase of lung carcinogenesis in an experimental mouse model. Histopathological changes in lungs of mice administered benzo(a)pyrene (BP) were followed serially and correlated with the expression of Cox-2, caspase-3 and caspase-7, which play key roles in histopathogenesis of neoplasia. The observations strongly indicate that both EGCG and TF can influence the expression of these genes to modulate the process of carcinogenesis, resulting in delayed onset and lowered incidence of pre-invasive lung lesions

Differential alterations in metabolic pattern of the spliceosomal UsnRNAs during pre-malignant lung lesions induced by benzo(a)pyrene: modulation by tea polyphenols

The differential alterations of the spliceosomal UsnRNAs (U1, U2, U4, U5, and U6) were reported to be associated with cellular proliferation and development. The attempt was made in this study to analyze the metabolic pattern of the spliceosomal UsnRNAs during the development of pre-malignant lung lesions induced in experimental mice model system by benzo(a)pyrene (BP) and also to see how tea polyphenols, epigallocatechin gallate (EGCG) and epicatechin gallate (ECG), modulate the metabolism of these UsnRNAs during the lung carcinogenesis. No significant changes in the level of the UsnRNAs were seen in the inflammatory lung lesions at 9th week due to treatment of BP. However, there was significant increase in the level of U1 ( approximately 2.5 fold) and U5 ( approximately 47%) in the hyperplastic lung lesions at 17th week. But in the mild dysplastic lung lesions at 26th week, the level of UsnRNAs did not change significantly. Whereas, in the dysplastic lung lesions at 36th week there was significant increase in the level of the U2 ( approximately 2 fold), U4 ( approximately 2.5 fold) and U5 ( approximately 2 fold). Due to the EGCG and ECG treatment the lung lesions at 9th week appeared normal and in the 17th, 26th, and 36th week it appeared as hyperplasia. The level of the UsnRNAs was significantly low in the lung lesions at 9th week (only U2 and U4 by EGCG), at 17th week (only U1 by EGCG/ECG), at 26th week (U1 by ECG; U2, U4 and U5 by EGCG/ECG) and at 36th week (U1 by ECG, U2 and U4 by EGCG/ECG). Whereas, there was significant increase in the level of U5 (by EGCG/ECG) and U6 (by EGCG only) in the lung lesions at 36th and 26th week respectively. This indicates that the metabolism of the spliceosomal UsnRNAs differentially altered during the development of pre-malignant lung lesions by BP as well as during the modulation of the lung lesions by the tea polyphenols

Vegetation cover change analysis from multi-temporal satellite data in Jharkhali Island, Sundarbans, India

331-342Present study intends to quantify change of natural vegetation cover (mainly of mangrove forest) in Sundarbans Island between the time span of 2004-2010, when sustained efforts of a forestation and conservation has been in vogue. Vegetation indices like Normalized Difference Vegetation Index (NDVI), Global Environmental Monitoring Index (GEMI), Optimized Soil Adjusted Vegetation Index (OSAVI) and Transformed Difference Vegetation Index (TDVI) have been used to decipher the measure of vegetation cover in this island and its changes during the period. Radiometric normalization technique is used to nullify various imaging condition anomalies while comparing multi-temporal data for change detection analysis. TDVI has been found to be more effective in vegetation cover change detection in such deltaic environment. Present study shows an overall net increase of vegetation cover in the island as a result of sustained conservation and plantation efforts

Histone H3 Lysine 27 demethylases Jmjd3 and Utx are required for T-cell differentiation

International audienceAlthough histone H3 lysine 27 trimethylation (H3K27Me3) is associated with gene silencing, whether H3K27Me3 demethylation affects transcription and cell differentiation in vivo has remained elusive. To investigate this, we conditionally inactivated the two H3K27Me3 demethylases, Jmjd3 and Utx, in non-dividing intrathymic CD4+ T-cell precursors. Here we show that both enzymes redundantly promote H3K27Me3 removal at, and expression of, a specific subset of genes involved in terminal thymocyte differentiation, especially S1pr1, encoding a sphingosine-phosphate receptor required for thymocyte egress. Thymocyte expression of S1pr1 was not rescued in Jmjd3- and Utx-deficient male mice, which carry the catalytically inactive Utx homolog Uty, supporting the conclusion that it requires H3K27Me3 demethylase activity. These findings demonstrate that Jmjd3 and Utx are required for T-cell development, and point to a requirement for their H3K27Me3 demethylase activity in cell differentiation

Suppression of renal cell carcinoma growth by inhibition of Notch signaling in vitro and in vivo

Loss of the tumor suppressor gene von Hippel–Lindau (VHL) plays a key role in the oncogenesis of clear cell renal cell carcinoma (CCRCC). The loss leads to stabilization of the HIF transcription complex, which induces angiogenic and mitogenic pathways essential for tumor formation. Nonetheless, additional oncogenic events have been postulated to be required for the formation of CCRCC tumors. Here, we show that the Notch signaling cascade is constitutively active in human CCRCC cell lines independently of the VHL/HIF pathway. Blocking Notch signaling resulted in attenuation of proliferation and restrained anchorage-independent growth of CCRCC cell lines. Using siRNA targeting the different Notch receptors established that the growth-promoting effects of the Notch signaling pathway were attributable to Notch-1 and that Notch-1 knockdown was accompanied by elevated levels of the negative cell-cycle regulators p21Cip1 and/or p27Kip1. Treatment of nude mice with an inhibitor of Notch signaling potently inhibited growth of xenotransplanted CCRCC cells. Moreover, Notch-1 and the Notch ligand Jagged-1 were expressed at significantly higher levels in CCRCC tumors than in normal human renal tissue, and the growth of primary CCRCC cells was attenuated upon inhibition of Notch signaling. These findings indicate that the Notch cascade may represent a novel and therapeutically accessible pathway in CCRCC

Microphytoplankton species assemblages, species-specific carbon stock and nutrient stoichiometry in the shallow continental shelf of the northern Bay of Bengal during winter

1827-1835Microphytoplankton species composition, diversity, abundance and biomass (chlorophyll-a) was studied for the first time in the shallow continental shelf (Thalassionema frauenfeldii was the most abundant species, followed by Thalassionema nitzschioides and Coscinodiscus radiatus. Highest cell chlorophyll and carbon content was found in Coscinodiscus gigas. Dinoflagellate species were found to comprise 15.55% of the total taxa. Amongst the dinoflagellates, Ceratium furca had the highest abundance, whereas Ceratium symmetricum had the maximum species-specific chlorophyll and carbon stock. The nutrient stoichiometry was highly deviated from the standard Redfield ratio of Si: N: P (16:16:1)

Combined Experimental and Theoretical Investigation of Ligand and Anion Controlled Complex Formation with Unprecedented Structural Features and Photoluminescence Properties of Zinc(II) Complexes

By using two potential tridentate ligands, HL¹ [4-chloro-2-[(2-morpholin-4-yl-ethylimino)-methyl]-phenol] and HL² [4-chloro-2-[(3-morpholin-4-yl-propylimino)-methyl]-phenol], which differ by one methylene group in the alkyl chain, four new Zn^II complexes, namely, [Zn(L²H)₂](ClO₄)₂ (1), [Zn(L¹)(H₂O)₂][Zn(L¹)(SCN)₂] (2), [Zn(L¹)(dca)]n (3), and [Zn₂(L¹)₂(N₃)₂(H₂O)₂] (4) [where dca = dicyanamide anion] were synthesized and structurally characterized. The results indicate that the slight structural difference between the ligands, HL¹ and HL², because of the one methylene group connecting the nitrogen atoms provokes a chemical behavior completely different from what was expected. Any attempt to isolate the Zn(L²) complexes with thiocyanato, dicyanamido, and azide was unsuccessful, and perchlorate complex 1 was always obtained. In contrast, with HL¹ we obtained structural diversity on varying the anions, but we failed to isolate the analogous perchlorate complex of HL¹. Single-crystal X-ray analyses revealed that the morpholine nitrogen of ligand L² is protonated and thus does not take part in coordination with Zn^II in complex 1. On the other hand, the morpholine nitrogen of L¹ is coordinated to Zn^II in 2–4. Of these, 2 and 4 are rare examples of a cocrystallized cationic/anionic complex and of a dinuclear complex bridged by a single azide, respectively. Some of these unexpected findings and some interesting noncovalent interactions leading to the formation of dimeric entities in solid-state compound 4 were rationalized by a DFT approach. Photoluminescence properties of the complexes as well as the ligands were investigated in solution at ambient temperature and at 77 K. The very fast photoinduced electron transfer (PET) from the nitrogen lone pair to the conjugated phenolic moiety is responsible for very low quantum yield (Φ) exhibited by the ligands, whereas complexation prevents PET, thus enhancing the Φ in the complexes. The origin of the electronic and photoluminescence properties of the ligands and complexes was assessed in light of theoretical calculations