Because only a small fraction of asbestos-exposed individuals develop malignant mesothelioma, and because mesothelioma clustering is observed in some families, we searched for genetic predisposing ...factors. We discovered germline mutations in the gene encoding BRCA1 associated protein-1 (BAP1) in two families with a high incidence of mesothelioma, and we observed somatic alterations affecting BAP1 in familial mesotheliomas, indicating biallelic inactivation. In addition to mesothelioma, some BAP1 mutation carriers developed uveal melanoma. We also found germline BAP1 mutations in 2 of 26 sporadic mesotheliomas; both individuals with mutant BAP1 were previously diagnosed with uveal melanoma. We also observed somatic truncating BAP1 mutations and aberrant BAP1 expression in sporadic mesotheliomas without germline mutations. These results identify a BAP1-related cancer syndrome that is characterized by mesothelioma and uveal melanoma. We hypothesize that other cancers may also be involved and that mesothelioma predominates upon asbestos exposure. These findings will help to identify individuals at high risk of mesothelioma who could be targeted for early intervention.
Exposure to erionite, an asbestos-like mineral, causes unprecedented rates of malignant mesothelioma (MM) mortality in some Turkish villages. Erionite deposits are present in at least 12 US states. ...We investigated whether increased urban development has led to erionite exposure in the United States and after preliminary exploration, focused our studies on Dunn County, North Dakota (ND). In Dunn County, ND, we discovered that over the past three decades, more than 300 miles of roads were surfaced with erionite-containing gravel. To determine potential health implications, we compared erionite from the Turkish villages to that from ND. Our study evaluated airborne point exposure concentrations, examined the physical and chemical properties of erionite, and examined the hallmarks of mesothelial cell transformation in vitro and in vivo. Airborne erionite concentrations measured in ND along roadsides, indoors, and inside vehicles, including school buses, equaled or exceeded concentrations in Boyali, where 6.25% of all deaths are caused by MM. With the exception of outdoor samples along roadsides, ND concentrations were lower than those measured in Turkish villages with MM mortality ranging from 20 to 50%. The physical and chemical properties of erionite from Turkey and ND are very similar and they showed identical biological activities. Considering the known 30- to 60-y latency for MM development, there is reason for concern for increased risk in ND in the future. Our findings indicate that implementation of novel preventive and early detection programs in ND and other erionite-rich areas of the United States, similar to efforts currently being undertaken in Turkey, is warranted.
The hypothesis that most cancers are of monoclonal origin is often accepted as a fact in the scientific community. This dogma arose decades ago, primarily from the study of hematopoietic malignancies ...and sarcomas, which originate as monoclonal tumors. The possible clonal origin of malignant mesothelioma (MM) has not been investigated. Asbestos inhalation induces a chronic inflammatory response at sites of fiber deposition that may lead to malignant transformation after 30-50 years latency. As many mesothelial cells are simultaneously exposed to asbestos fibers and to asbestos-induced inflammation, it may be possible that more than one cell undergoes malignant transformation during the process that gives rise to MM, and result in a polyclonal malignancy.
To investigate the clonality patterns of MM, we used the HUMARA (Human Androgen Receptor) assay to examine 16 biopsies from 14 women MM patients. Out of 16 samples, one was non-informative due to skewed Lyonization in its normal adjacent tissue. Fourteen out of the 15 informative samples revealed two electrophoretically distinct methylated HUMARA alleles, the Corrected Allele Ratio (CR) calculated on the allele peak areas indicating polyclonal origin MM.
Our results show that MM originate as polyclonal tumors and suggest that the carcinogenic "field effect" of mineral fibers leads to several premalignant clones that give rise to these polyclonal malignancies.
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•Water soluble carbon dots (CDs) successfully synthesized from waste cotton linter.•The produced CDs gave maximum emission peak at 420 nm when excited at 376 nm.•The average particle ...diameter of the CDs was calculated as 10.14 nm.•Application as a fluorescent cell imaging were conducted.
The water dispersed-fluorescent carbon quantum dots (CDs) were synthesized using microwave-assisted hydrothermal process in the closed system from the waste cotton linter as a new carbon source. This method provided an ultra-fast, more effective, economical and easier synthesis for cancer-imaging applications compared to the other methods presented in literature. The morphological and optical properties of the hydrothermally produced carbon quantum dots were characterized by using FT-IR, transmission electron microscopy (TEM), SEM, EDX, UV–vis and fluorescent spectrophotometry techniques. An emission peak was observed at 420 nm when the CDs were excited at 376 nm. CDs were calculated to have an average particle diameter of 10.14 nm by TEM. In order to determine the usability of the CDs in cell imaging, two different concentrations (50 μL/mL and 100 μL/mL) of the CDs colloidal solution were applied to a human mesothelioma cell line, H2452, and human umbilical vein endothelial cells (HUVEC) for varying durations. While the fluorescent photos revealed that 2 h of exposure was sufficient for the cells to take the C-dots in and higher concentrations appeared brighter in the wavelengths studied (red channel (excitation/emission 586/646 nm), blue channel (390/446 nm) and the green channel (482/532 nm)), cell viability and proliferation assays indicated that the material was cytotoxic against the both cell lines and inhibited the cell growth in a time- and dose- dependent manner.
Mesothelioma is a highly lethal cancer developing in the lung, heart, and abdominal membranes. Zingerone, a capsaicin-like bioactive compound, has been shown to have anticancer properties. Transient ...Receptor Potential Vanilloid 1 (TRPV1) is an ion channel involving in the cytotoxicity of capsaicin. In the present study, we aimed at determining the cytotoxicity of zingerone on a mesothelioma cell line and to evaluate the role of TRPV1 in this effect. For this purpose, H2452 was used as the mesothelioma cell line and MTS was performed to calculate zingerone cytotoxicity. Moreover, TRPV1 was inhibited by capsazepeine while TRPV1 production was reduced through shRNA treatment. Besides, wound healing and clonogenic assays were performed to measure the migration and colony forming abilities, respectively. As a result, IC
50
value of zingerone was calculated as 11.49 mM. Capsazepine treatment or lowered TRPV1 gene expression did not appear to affect zingerone cytotoxicity (p > 0.05) even though the migration rate and colony forming abilities of the zingerone treated cells decreased significantly compared to the control (p < 0.05). Therefore, we concluded that zingerone was less cytotoxic to H2452 cells than the most cancer types and TRPV1 did not seem to have a role in its cytotoxicity.
Fritillaria imperialis needs 2-3 years to regenerate from seeds, which makes its production
quite challenging. In this study, effects of three concentrations of
6-Benzylaminopurine (BAP) (0.00, 0.10 ...and 0.15 mg/L) and three different
amounts (0.0, 3.0 and 3.5 g/L) of activated carbon (AC) on the growth of F.
imperialis plantlets in vitro were determined. The auxins were at
similar concentration (0.01 mg/L of NAA and 0.01 mg/L of IAA) for all
treatments. It has been found that the size and number of bulblets, as well as
root and shoot numbers in regenerated plantlets were increased significantly
(p<0.05) by adding 3.5 g/L of AC in culture medium supplemented with 0.10
mg/L of BAP. Moreover, addition of AC significantly reduced the length of roots
in all doses studied (p<0.05). The supreme concentration of BAP (0.15 mg/L)
decreased the bulblet number in all treatments, however, when supplemented with
3.5 g/L of AC, it was found to raise all the values measured (p<0.05).
Overall, the best growth of the plant parts from callus were achieved with the
highest concentration of AC and 1.5 mg/L of BAP.
Fritillaria imperialis türü bitkiler, tohumlarını
yenilemek için iki yıldan fazla bir süreye ihtiyacı duymakta ve bu durum
üretimlerini zorlaştırmaktadır. Bu çalışmada, üç farklı derişimdeki
6-Benzilaminopurinin (BAP) (0.00, 0.10 ve 0.15 mg/L) ve üç farklı miktardaki
(0.0, 3.0 ve 3.5 g/L) aktif karbonun (AC) F.
imperialis bitkilerinin büyümesine etkisi in vitro olarak
incelenmiştir. Tüm muamele grupları için benzer konsantrasyonda oksin (0.01
mg/L NAA ve 0.01 mg/L IAA) kullanılmıştır. 0.10 mg/L BAP ilave edilmiş kültür
ortamlarına 3.5 g/L AC eklenmesinin bitkilerin yumru çap uzunluğu ve sayısının
yanında kök ve sürgün sayılarını istatiksel olarak anlamlı bir şekilde (p<0.05) arttırdığı
gözlenmiştir. Dahası, AC eklenmesi, çalışılan tüm dozlarda kök uzunluklarını
önemli ölçüde azaltmıştır (p<0.05). Yüksek BAP konsantrasyonunun (0.15 mg/L)
çalışılan tüm grupların yumru sayılarını azalttığı, ancak 3.5 g/L AC ile
desteklendiğinde ölçülen tüm değerlerin artışını sağladığı bulunmuştur
(p<0.05). ).
Genel olarak, kallustan bitki kısımlarının en iyi şekilde büyümesi, en yüksek
konsantrasyonda AC ve >1.5 mg/L BAP ile elde
edilmiştir.
Chondrosarcoma is a common form of bone cancer which effects the fibrous connective tissue around a joint. It most commonly develops in legs, arms, shoulder blades, rib cage, and pelvis. Capsaicin is ...an active bitter compound found in red pepper, the fruit of the species Capsicum annuum, and it has been shown to have a lethal effect on different types of cancer. However, to date, investigation of its effect on human chondrosarcoma cells has remained limited. In the study presented here, we determined IC
values of capsaicin for chondrosarcoma and chondrocyte cells in both fetal bovine serum (FBS)-containing and FBS-deprived media, and no statistically significant difference was found between the cell types. Besides, when the cells were cultured with capsaicin at their determined IC
value for 24 h and their caspase-3 gene expression levels were detected by real-time polymerase chain reaction (RTPCR) and western blotting, it was demonstrated that the caspase-3 protein and mRNA levels were not altered in any cells upon capsaicin exposure, suggesting a caspase-independent pathway for cell death. Migration and invasion abilities of the cancerous cells, on the other hand, were observed to decrease dramatically when the cells were exposed to capsaicin (P < 0.05).
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•A new quinoline-Schiff base ligand (LTPP) containing the lipophilic triphenylphosphonium cation and its complexes Cu(II) and Zn(II) were synthesized and characterized.•DNA binding ...interactions of the ligand and its metal complexes were investigated by UV–vis absorption and fluorescence spectroscopies as well as viscosity measurements.•The DNA binding affinity (Kb) for the ligand and complexes Cu(LTPP)ClCl and Zn(LTPP)ClCl) obtained from absorption spectra were found as 4.33, 4.66 and 6.01 (×105 M−1), respectively.•The ligand and its complexes were screened for their cytotoxic properties towards malignant mesothelioma (H2452) and healthy human umbilical vein endothelial (HUVEC) cells.•In vitro antioxidant properties of the ligand and its metal complexes were also studied.
A new quinoline-Schiff base ligand (LTPP) containing the lipophilic triphenylphosphonium cation and its complexes Cu(LTPP)ClCl and Zn(LTPP)ClCl were synthesized and characterized. The structures of the ligand and metal complexes were characterized by FTIR, elemental analysis, NMR (for ligand), UV–Vis absorption and fluorescence spectroscopies. DNA binding interactions of the ligand and its metal complexes were investigated by UV–vis absorption and fluorescence spectroscopies as well as viscosity measurements. The DNA binding affinity (Kb) for the ligand and complexes Cu(LTPP)ClCl and Zn(LTPP)ClCl) obtained from absorption spectra were found as 4.33, 4.66 and 6.01 (×105 M−1), respectively. The ligand and its Cu(II) complex showed similar propensities to interact with DNA, yet the DNA binding affinity of the Zn(II) complex was relatively higher than free ligand and its Cu(II) complex. Docking studies were conducted in order to further investigate the DNA binding interactions. The ligand and its complexes were screened for their cytotoxic properties towards malignant mesothelioma (H2452) and healthy human umbilical vein endothelial (HUVEC) cells. The Cu(II) and Zn(II) complexes that were loaded into the cells (H2452) confirm their intracellular uptake by fluorescence-based cell imaging. Complex Zn(LTPP)ClCl emitted fluorescent light even after entering the cell suggesting that the compound can be used for cell tracking purposes. In order to find out whether the compounds we synthesized had the potency to enter human cells, we measured the florescent light emission of H2452 cells treated with the products at their IC50 concentration for 24 h. In vitro antioxidant properties of the ligand and its metal complexes were also studied.
Capsaicin is one of the most extensively studied phytochemicals and its cytotoxicity on various types of cancer has been demonstrated both in vitro and in vivo. The evaluation of its effect on ...mesothelioma, however, has remained quite limited. In this study, we investigated the anti-mesothelioma potential of capsaicin by observing its cytotoxicity on healthy, immortalized and cancerous cells of mesothelium in vitro and how this potential be affected by lowered Cyclin E levels, a key regulator of G1/S transition of cell cycle. For this purpose, we determined and compared the IC50 values of capsaicin in both FBS (Fetal Bovine Serum) containing and FBS-deprived medium of each cell population studied. Additionally, we examined the changes in both protein and mRNA levels of caspase-3 upon capsaicin exposure as well as conducted a series of experiments through which the relatively long term effect of capsaicin on the growth rate of the cells was assessed. As a result, the reduced Cyclin E obtained through the absence of FBS in growth medium was found not only to decrease IC50 values for all cell types dramatically (p<0.05) but also to cause a considerable difference between the values determined for cancerous and non-cancerous populations (p<0.05), which had not been observed in regular medium. Moreover, along with the fact that capsaicin exposure did not have an impact on the cell growth in long term in most cases, caspase-3 levels also remained the same when exposed to capsaicin, suggesting a mechanism of cell death independent of caspases.
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