Direct analysis of camptothecin from Nothapodytes nimmoniana by desorption electrospray ionization mass spectrometry (DESI-MS)

Desorption electrospray ionization was employed for fast and direct ambient detection of the anti-tumor drug, camptothecin, and its derivative, 9-methoxycamptothecin in Nothapodytes nimmoniana. Different parts of the plant such as leaves, stems and bark were examined. The ion intensities suggest that the concentration in bark is higher than that in the leaves and stems. The method does not require any sample preparation or preseparation. The identity of the alkaloids was further confirmed by tandem mass spectrometry

Centrosomes and associated proteins in pathogenesis and treatment of breast cancer

Breast cancer is the most prevalent malignancy among women worldwide. Despite significant advances in treatment, it remains one of the leading causes of female mortality. The inability to effectively treat advanced and/or treatment-resistant breast cancer demonstrates the need to develop novel treatment strategies and targeted therapies. Centrosomes and their associated proteins have been shown to play key roles in the pathogenesis of breast cancer and thus represent promising targets for drug and biomarker development. Centrosomes are fundamental cellular structures in the mammalian cell that are responsible for error-free execution of cell division. Centrosome amplification and aberrant expression of its associated proteins such as Polo-like kinases (PLKs), Aurora kinases (AURKs) and Cyclin-dependent kinases (CDKs) have been observed in various cancers, including breast cancer. These aberrations in breast cancer are thought to cause improper chromosomal segregation during mitosis, leading to chromosomal instability and uncontrolled cell division, allowing cancer cells to acquire new genetic changes that result in evasion of cell death and the promotion of tumor formation. Various chemical compounds developed against PLKs and AURKs have shown meaningful antitumorigenic effects in breast cancer cells in vitro and in vivo. The mechanism of action of these inhibitors is likely related to exacerbation of numerical genomic instability, such as aneuploidy or polyploidy. Furthermore, growing evidence demonstrates enhanced antitumorigenic effects when inhibitors specific to centrosome-associated proteins are used in combination with either radiation or chemotherapy drugs in breast cancer. This review focuses on the current knowledge regarding the roles of centrosome and centrosome-associated proteins in breast cancer pathogenesis and their utility as novel targets for breast cancer treatment

Long Non-Coding RNA H19 Acts as an Estrogen Receptor Modulator that is Required for Endocrine Therapy Resistance in ER+ Breast Cancer Cells

Background/Aims: Blocking estrogen signaling with endocrine therapies (Tamoxifen or Fulverstrant) is an effective treatment for Estrogen Receptor-α positive (ER+) breast cancer tumours. Unfortunately, development of endocrine therapy resistance (ETR) is a frequent event resulting in disease relapse and decreased overall patient survival. The long noncoding RNA, H19, was previously shown to play a significant role in estrogen-induced proliferation of both normal and malignant ER+ breast epithelial cells. We hypothesized that H19 expression is also important for the proliferation and survival of ETR cells. Methods: Here we utilized established ETR cell models; the Tamoxifen (Tam)-resistant LCC2 and the Fulvestrant and Tam cross-resistant LCC9 cells. Gain and loss of H19 function were achieved through lentiviral transduction as well as pharmacological inhibitors of the Notch and c-Met receptor signaling pathways. The effects of altered H19 expression on cell viability and ETR were assessed using three-dimensional (3D) organoid cultures and 2D co-cultures with low passage tumour-associated fbroblasts (TAFs). Results: Here we report that treating ETR cells with Tam or Fulvestrant increases H19 expression and that it’s decreased expression overcomes resistance to Tam and Fulvestrant in these cells. Interestingly, H19 expression is regulated by Notch and HGF signaling in the ETR cells and pharmacological inhibitors of Notch and c-MET signaling together significantly reverse resistance to Tam and Fulvestrant in an H19-dependent manner in these cells. Lastly, we demonstrate that H19 regulates ERα expression at the transcript and protein levels in the ETR cells and that H19 protects ERα against Fulvestrant-mediated downregulation of ERα protein. We also observed that blocking Notch and the c-MET receptor signaling also overcomes Fulvestrant and Tam resistance in 3D organoid cultures by decreasing ERα and H19 expression in the ETR cells. Conclusion: In endocrine therapy resistant breast cancer cells Fulvestrant is ineffective in decreasing ERα levels. Our data suggest that in the ETR cells, H19 expression acts as an ER modulator and that its levels and subsequently ERα levels can be substantially decreased by blocking Notch and c-MET receptor signaling. Consequently, treating ETR cells with these pharmacological inhibitors helps overcome resistance to Fulvestrant and Tamoxifen

HNbWO6 and HTaWO6: Novel layered oxides related to the rutile structure. Synthesis and investigation of ion-exchange and intercalation behaviour

New protonated layered oxides, HMWO6·1.5H2O (M=Nb or Ta), have been synthesized by topotactic exchange of lithium in trirutile LiMWO6 with protons by treatment with dilute HNO3. The tetragonal cell constants are a=4.71 (2) and c=25.70 (8)Å for HNbWO6·1.5H2O and a=4.70 (2) and c=25.75 (9) Å for HTaWO6·1.5H2O. Partially hydrated compounds, HMWO6·0.5H2O and anhydrous compounds, HMWO6 retain the layered structure. The structure of these oxides consists of MWO6 sheets built up of M/W-oxygen octahedra with rutile type corner- and edge-sharing. Interlayer protons in HMWO6 are exchanged with Li+, Na+, K+ and Tl+. HMWO6 exhibit Brønsted acidity intercalating n-alkylamines and pyridine

HNbWO<SUB>6</SUB> and HTaWO<SUB>6</SUB>: novel oxides related to ReO<SUB>3</SUB> formed by ion exchange of rutile-type LiNbWO<SUB>6</SUB> and LiTaWO<SUB>6</SUB>

Both LiNbWO6 and LiTaWO6 undergo ion exchange in hot aqueous H2SO4 yielding the hydrates HMWO6 &#183; H2O (M = Nb or Ta). The reaction is accompanied by a structural transformation from the rutile to the ReO3 structure. The cell constants are a = 3.783(3)&#197; for HNbWO6 &#183; H2O and a = 3.785(5)&#197; for HTaWO6 . H2O. The ReO3 structure is retained by the dehydration products HMWO6 and MWO5.5 as well. HMWO6 phases yield H1+xMWO6 hydrogen bronzes on exposure to hydrogen in the presence of platinum catalyst

Oxidative extraction and ion-exchange of lithium in Li<SUB>2</SUB>MoO<SUB>3</SUB>: synthesis of Li<SUB>2-x</SUB>MoO<SUB>3</SUB> (0 &lt; x &#8804; 2.0) and H<SUB>2</SUB>MoO<SUB>3</SUB>

It is shown that lithium can be oxidatively extracted from Li2MoO3 at room temperature using Br2 in CHCl3. The delithiated oxides, Li2-xMoO3 (0 &lt; x &#8804; 1.5) retain the parent ordered rocksalt structure. Complete removal of lithium from Li2MoO3 using Br2 in CH3CN results in a poorly crystalline MoO3 that transforms to the stable structure at 280&#176;C. Li2MoO3 undergoes topotactic ion-exchange in aqueous H2SO4 to yield a new protonated oxide, H2MoO3

Mechanism of protonic conduction in defect pyrochlore HNbWO6.xH(2)O using MAS NMR

We have carried out H-1 Magic Angle Spinning (MAS) NMR measurements at various spinning speeds (1-12 kHz) on HNbWO(6)xH(2)O (x = 0 and 1) defect pyrochlore systems. The variation of the line width with the spinning speed in the two systems points towards the presence of motions with different time scales. We conclude that the mechanism of conduction in both the compounds are similar except that the proton hopping in hydrated form is assisted by the water of hydration

A2Ln2Ti3O10A_2Ln_2Ti_3O_{10} (A = potassium or rubidium; Ln = lanthanum or rare earth): a new series of layered perovskites exhibiting ion exchange

Several layered perovskites $A_2Ln_2Ti_3O_{10}$ (A = K or Rb; Ln = rare earth) and their monohydrates, crystg. in tetragonal structures related to ${Sr_4Ti_3O_10}$, were prepd. The alkali ions in $K_2Ln_2Ti_3O_{10}$ are topochem. exchanged by protons in aq. acid or by other alkali ions in molten salts. $H_2Ln_2Ti_3O_{10}$ also adopt a tetragonal structure similar to the parent oxides. Dehydrated $H_2La_2Ti_3O_{10}$ crystallizes at 1000 giving a new defect perovskite, $La_2/3TiO_3$, possessing a tetragonal structure

A2Ln2Ti3O10 (A = potassium or rubidium; Ln = lanthanum or rare earth): a new series of layered perovskites exhibiting ion exchange

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