30 research outputs found
Role of dysfunctional HDL and oxidative stress in bladder cancer.
No full textIl cancro alla vescica urinaria (BC) è uno dei tumori più comuni alla vescica urinaria, sia per le donne che per gli uomini, nei Paesi occidentali. Studi in vitro e in vivo suggeriscono che alti livelli di specie reattive dell’ossigeno (ROS) e le specie reattive dell’azoto (RNS) e lo stress ossidativo hanno un ruolo cruciale nel cancro dell’uomo. Basse concentrazioni di ROS e di RNS sono indispensabili per la sopravvivenza e la proliferazione delle cellule. Comunque, alte concentrazioni di ROS e d RNS possono esercitare un effetto citotossico. Un aumento dello stress ossidativo è il risultato o di un aumento della produzione di ROS/RNS o una diminuzione del meccanismo di difesa antiossidante. Una ricerca letteraria è stata portata avanti su PubMed, Medline, e Google Scholar con articoli in inglese pubblicati fino a Maggio 2018 che usano le seguenti parole chiave: stress ossidativo, antiossidanti, specie reattive dell’ossigeno, perossidazione lipidica, paraoxonasi, cancro alla vescica urinaria, ossido di azoto. Dati letterari dimostrano che BC è associato allo stress ossidativo e con uno sbilancio trae enzimi ossidanti e antiossidanti. I marcatori della perossidazione lipidica, l’ossidazione delle proteine e degli acidi nucleici sono significativamente più alte nei tessuti di pazienti con il cancro alla vescica comparati a gruppi di controllo. Una diminuzione dell’attività di enzimi antiossidanti (superossido dismutasi, catalasi, glutatione, e paraoxonasi) è stata dimostrata. Lo sbilancio tra ossidanti e antiossidanti potrebbe avere un potenziale ruolo nell’eziologia e nella progressione del cancro alla vescica.Epidemiological studies suggest associations between type 2 diabetes mellitus and bladder cancer. Several potential mechanisms may explain the increased bladder cancer burden in DM patients. Hyperglycaemia is associated with dysregulation of cell intracellular metabolism and alterations of lipoprotein metabolism and oxidative stress. In fact, previous studies have shown that levels and functions of circulating lipoprotein are modified in DM patients. Dysfunctional HDL including glycated and oxidized HDL are described in patients with type 2 diabetes mellitus. We evaluated the effect of normal HDL and glycated HDL on cell proliferation and oxidative stress of J82 bladder cancer cells. We also studied the effect of HDL on cholesterol influx and efflux. In addition, the expression of proteins involved in cholesterol transport (ABCA1, SRB1, ABCG1) by western blot analysis was studied. Our results demonstrate that HDL incubated 7 days at 370C with increasing concentrations of glucose (30-100mM) have lower levels of free amino groups with respect to untreated HDL. The decrease realized at a higher extent using glucose 100 mM therefore this concentration was used to investigate the effect of glycated HDL on J82 cells. Levels of TBARS and conjugated dienes were higher in G-HDL compared with N-HDL. These results demonstrate that lipid peroxidation occurs during glycation treatment. The enzyme activity of paraoxonase (HDL-PON1) was significantly decreased in G-HDL . High markers of lipid peroxidation and a decrease of Paraoxonase activity are described in dysfunctional HDL.
The study of the effect of Normal HDL and glycated HDL (G-HDL) on J82 cells in culture has shown that both N-HDL and G-HDL promote cell proliferation and increase the levels of intracellular reactive oxygen species (ROS) during incubation with the oxidizing agent tert-butyl hydroperoxide. The increase of intracellular ROS was associated to higher levels of TBARS in cells incubated with G-HDL than N-HDL. The increase in oxidative stress in cells incubated with N-HDL was associated with alterations of cholesterol homeostasis. In detail Cholesterol efflux was increased, on the contrary cholesterol influx was significantly decreased in cells incubated with G-HDL. Expression of receptor protein SR-B1 and ABCG1 was increased. The higher expression of SR-B1 in cells incubated with G-HDL suggests that dysfunctional HDL could affect cholesterol homeostasis in J82 bladder cancer cells. These results suggest that HDL-based treatments should be considered for treatment of bladder cancer
Alterations of Antioxidant Enzymes and Biomarkers of Nitro-oxidative Stress in Tissues of Bladder Cancer
No full textBladder cancer (BC) is one of the most common tumors found in the urinary bladder for both male and female in western countries. In vitro and in vivo studies suggest that high levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) and oxidative stress play a crucial role in human cancer. Low concentration of ROS and RNS is indispensable for cell survival and proliferation. However, high concentration of ROS and RNS can exert a cytotoxic effect. Increased oxidative stress is a result of either increased ROS/RNS production or a decrease of antioxidant defense mechanisms. A literature search was carried out on PubMed, Medline, and Google Scholar for articles in English published up to May 2018 using the following keywords: oxidative stress, antioxidants, reactive oxygen species, lipid peroxidation, paraoxonase, urinary bladder cancer, and nitric oxide. Literature data demonstrate that BC is associated with oxidative stress and with an imbalance between oxidants and antioxidant enzymes. Markers of lipid peroxidation, protein and nucleic acid oxidation are significantly higher in tissues of patients with BC compared with control groups. A decrease of activity of antioxidant enzymes (superoxide dismutase, catalase, glutathione, and paraoxonase) has also been demonstrated. The imbalance between oxidants and antioxidants could have a potential role in the etiology and progression of bladder cancer
Effect of glycated HDL on oxidative stress and cholesterol homeostasis in a human bladder cancer cell line, J82
No full textEpidemiological studies suggest associations between diabetes mellitus (DM) andbladder cancer. Several potential mechanisms may explain the increased bladdercancer burden in DM patients. Hyperglycaemia is associated with dysregulation of cellintracellular metabolism and alterations of lipoprotein metabolism and oxidative stress. Dysfunctional HDL including glycated and oxidized HDL are described in DM. Weevaluated the effect of normal HDL (N-HDL) and glycated HDL (G-HDL) on cellproliferation and oxidative stress of J82 bladder cancer cells. We also studied the effectof HDL on cholesterol influx and efflux. In addition, the levels of proteins involvedin cholesterol transport (ABCA1, SRB1, ABCG1) by western blot analysis were studied.Our results demonstrate that N-HDL and G-HDL promote cell proliferation and increase intracellular reactive oxygen species (ROS) levels triggered by incubation of tert-butylhydroperoxide. The increase of intracellular ROS in cells preincubated with G-HDL was associated to higher levels of TBARS in cells compared to N-HDL. Cholesterol efflux wasincreased, on the contrary cholesterol influx was significantly decreased in cellsincubated with G-HDL with respect to cells incubated with N-HDL. Levels of SR-B1 and ABCG1 was increased in cells incubated with G-HDL, suggestingthat dysfunctional HDL could affect cholesterol homeostasis in J82 cells. These resultssuggest that HDL-based treatments should be considered for treatment of urinary bladder cancer
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Abstract 375: Smoking induces Wee1 expression through miRNA deregulation, promoting docetaxel resistance in esophageal adenocarcinoma
No full textAbstract Esophageal Adenocarcinoma (EAC) is the most common subtype of Esophageal Cancer in Western countries, and its incidence rate has increased over the past few decades. The overall five-year survival rate of EAC is less than 20%. Smoking is a major risk factor for EAC development. WEE1 kinase plays a crucial role in the cell cycle by regulating the G2/M checkpoint, providing a time frame for the cells to repair DNA damage. Thus, targeting WEE1 using an inhibitor could potentiate the effect of chemotherapeutic drugs. This study investigated how smoking induces WEE1 protein expression, promoting docetaxel resistance in EAC. IHC staining for WEE1 in the normal esophagus and EAC tissue sections revealed significant over-expression of WEE1 protein in EAC. Nicotine, Nicotine derived Nitrosamine Ketone (NNK), and 2% cigarette smoke extract (CSE) treatment induced WEE1 expression with a concomitant increase in CDC2 phosphorylation (p-CDC2, Y15), a well-established read-out of WEE1 activity in EAC cells. In addition, we found that smoking upregulates WEE1 expression by decreasing miR-195-5p expression levels in EAC. Based on the differential gene expression signatures in EAC cell lines FLO1 and OE33 following WEE1 knockdown, drug and small molecule induced gene expression signatures analysis, L1000 fireworks display (L1000FWD), predicted that docetaxel is one of the best drug candidates which can synergize with the WEE1 inhibitor MK1775. Smoking-induced docetaxel resistance in EAC cells measured by cell viability assay. Down-regulating WEE1 expression with siRNA or pharmacological inhibition using MK1775 significantly sensitized EAC cells to docetaxel treatment, as evidenced by a remarkable decrease in the IC50 value of docetaxel. Inhibition of WEE1 combined with docetaxel can be considered an ideal therapeutic strategy due to its superior anti-tumor efficacy compared to the standard single-agent treatment. In conclusion, our data provide a firm rationale for the clinical combination of docetaxel with MK1775 in EAC patients. Citation Format: Krishnapriya Thangaretnam, Islam MD Obaidul, Heng Lu, Dunfa Peng, Nadeem Sidiq Bhat, Mohammed Soutto, Zheng Chen. Smoking induces Wee1 expression through miRNA deregulation, promoting docetaxel resistance in esophageal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 375
NSECT PESTS OF LETTUCE AND THEIR BIORATIONAL MANAGEMENT
No full textA Thesis
Submitted to the Department of Entomology
Faculty of Agriculture,
Sher-e-Bangla Agricultural University, Dhaka,
in partial fulfillment of the requirements
for the degree of
MASTER OF SCIENCE (MS)
IN
ENTOMOLOGYThe experiment was conducted in the experimental field of Sher-e-Bangla Agricultural
University, Dhaka, Bangladesh during the period from 10 November, 2019 to 20 February, 2020
to record the insect pests of lettuce and to evaluate their biorational management practices. The
experiment was laid out in Randomized Complete Block Design (RCBD) with four replications.
There were six treatments viz.; T
1
= Abamectin @ 1.0 ml/L of water, T
2
= Bacillus thuringiensis
and abamectin @ 1.0 ml/L of water, T
3
= Spinosad @ 0.5 ml/L of water, T
4
= Azadirachtin @ 1.0
ml/L of water, T
5
= Potassium salt of fatty acid @ 1.0 ml/L of water and T
6
= untreated control
were used at 7 day interval. Flea beetle (Monolepta signata Olivier), Tobacco caterpillar
(Spdoptera litura Fabricius), Aphid (Lipaphis erysimi Kaltenbach), Jute hairy caterpillar
(Spilosoma obliqua Walker), Grasshopper (Oxya velox Fabricius) and Red pumpkin beetle
(Raphidopalpa foveicollis Lucas) were recorded. The lowest percent of leaf infestation (10.70,
4.67, 4.76, 5.07, 5.03 and 8.74% respectively) of Flea beetle, Tobacco caterpillar, Aphid, Jute
hairy caterpillar, Grasshopper and Red pumpkin beetle were observed in T
3
(Spinosad 45SC)
treatments as against the highest (26.93, 18.81, 18.22, 37.67, 24.70 and 26.93%) was observed in
T
6
treatment (untreated control). The highest single (0.91 kg plant
ii
-1
) and healthy plant weight
(0.76 kg plant
-1
) and highest yield (16.43 ton ha
-1
) were observed in the same treatment (T
3
). In
contrast, the highest leaf infestation (21.50%), the lowest single plant weight (0.24 kg), healthy
plant weight (0.29 kg plant
-1
) and lowest total yield (7.08 ton ha
-1
) were obtained from T
6
(untreated control). Spinosad 45SC @ 1.0 ml/L of water at 7 days interval gave the highest
performance against insect pests of lettuce compared to all other treatments and may be used for
the management insect pests of lettuce
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Abstract 4744: Overcoming MK1775 resistance in upper gastrointestinal cancers with combined WEE1 and CHK1 inhibition
No full textAbstract Background: Upper gastrointestinal cancers (UGC), encompassing esophageal and gastric cancers, rank among the top causes of cancer-related deaths globally, with esophageal cancer being the sixth and gastric cancer the fourth leading cause. Esophageal adenocarcinoma (EAC), predominant in the western world, shares histopathological and molecular characteristics with gastric cancer (GC). Despite these similarities, treatment challenges persist, exemplified by the limited efficacy of the WEE1 inhibitor MK1775 in clinical trials due to drug resistance. Our study investigates novel mechanisms underlying this resistance in UGC. Methods and results: RNA sequencing and immunohistochemistry staining demonstrated notable overexpression of WEE1 in over two hundred human EAC and GC samples compared to normal tissues. Concurrently, Western blot analysis revealed a positive correlation between WEE1 and CHK1 overexpression across 16 UGC cell lines. To categorize UGC cells based on their sensitivity to MK1775, we conducted ATP-glo cell viability assays, determining their half-maximal inhibitory concentration (IC50) values. Utilizing nuclear-cytosol separation, our data intriguingly uncovered, for the first time, that in MK1775-resistant cells, MK1775 treatment induces the abnormal translocation of phosphorylated CHK1 (p-CHK1) from the nucleus to the cytoplasm, a shift not observed in MK1775-sensitive cells. Further analysis through Western blot suggested that the cytoplasmic presence of p-CHK1 might trigger the activation of oncogenic STAT3 following MK1775 treatment. This activation appears to stimulate the expression of genes that promote cancer cell survival and drug resistance by enhancing cell survival and inhibiting apoptosis. Notably, combining the WEE1 inhibitor with the CHK1 inhibitor CHIR124 effectively inhibited CHK1 kinase activity and abrogated STAT3 phosphorylation, DNA binding, and transcriptional activity in UGC cells. Our findings strongly indicate that a combined therapy of WEE1 and CHK1 inhibitors could be a promising strategy to overcome MK1775 resistance in UGC cells. Our ongoing research will employ human-derived UGC organoids, patient-derived xenografts (PDXs), and human tissue samples to further validate these findings. Conclusions: Our study underscores the potential of combining WEE1 and CHK1 inhibitors to effectively combat MK1775 resistance in UGC, offering a promising direction for improved treatment strategies and patient outcomes in these challenging malignancies. Citation Format: Krishnapriya Thangaretnam, MD Obaidul Islam, Heng Lu, Dunfa Peng, Nadeem Sidiq Bhat, Mohammed Soutto, EL-Rifai Wael, Zheng Chen. Overcoming MK1775 resistance in upper gastrointestinal cancers with combined WEE1 and CHK1 inhibition [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4744
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Productivity and economic efficiency of sugarcane cultivation under intercropping system with potato and mungbean
No full textSugarcane is an important cash-cum-industrial crop of Bangladesh and mainly cultivated in north-western part of the country where different intercropping systems are available. The experiment was carried out at the Bangladesh Sugarcane Research Institute (BSRI) farm, Ishurdi, Pabna, Bangladesh in two successive years viz. 2008–2009 and 2009–2010 to investigate the profitability of sugarcane (cv. Isd 37) with potato (cv. Cardinal) and mungbean (cv. BINA mung5) as successive intercrops. Two factors included in the experiment viz. Factor A: Row to row distance of sugarcane such as 80 cm (S1), 100 cm (S2) and 120 cm (S3) where potato and Mungbean were intercropped. Factor B: Cutting of sugarcane leaf such as cutting of leaves (C1) and No cutting of leaves (C2). The experiment was laid out following randomize complete block design. For sugarcane cultivation BSRI technique and for intercropping the cultivation systems indicated by Bangladesh Agricultural Research Institute were followed. The cane yield and sugar yield were the highest at 100 cm row to row spacing (RRS) of sugarcane (non-leaf cutting = C0) intercropped with 2 rows (2R) of potato followed by 2R of mungbean (S2C0). The lowest yield of sugarcane was found at 80 RRS (C0) with one row (1R) of potato and 1R of mungbean (S1C0). The effect of light interception on growth and yield of first intercrop (potato) was insignificant but significant for second intercrop. The highest yield of potato tuber was 15.28 t ha–1 in S5 (sole potato) followed by 10.85 t ha–1 in S3C1 (sugarcane under leaf cutting at RRS 120 cm with 3R of potato followed by 3R of mungbean). For the yield of mungbean (2nd intercrop), light interception ratio (%) was significantly lowest in (S3C1) where sugarcane RRS was 120 cm with 3R of potato followed by 3R of mungbean under leaf non-cutting (C0) of sugarcane. The highest adjusted cane yield (170.66 t ha–1), benefit cost ratio (3.49) and LER (2.33) were observed in sugarcane at RRS 120 cm with 3R of potato followed by 3R of mungbean (S3C1). Results of both years indicated that intercrops gave higher land equivalent ratio and net return over sole sugarcane planted while sole sugarcane gave maximum benefit cost ratio compared with other intercrops. Finally, on the basis of results it may be concluded that sugarcane transplanted at RRS at 120 cm with 3R potato followed by 3R of mungbean can be grown as intercrops for higher economic return
Productivity and economic efficiency of sugarcane cultivation under intercropping system with potato and mungbean
No full textSugarcane is an important cash-cum-industrial crop of Bangladesh and mainly cultivated in north-western part of the country where different intercropping systems are available. The experiment was carried out at the Bangladesh Sugarcane Research Institute (BSRI) farm, Ishurdi, Pabna, Bangladesh in two successive years viz. 2008–2009 and 2009–2010 to investigate the profitability of sugarcane (cv. Isd 37) with potato (cv. Cardinal) and mungbean (cv. BINA mung5) as successive intercrops. Two factors included in the experiment viz. Factor A: Row to row distance of sugarcane such as 80 cm (S1), 100 cm (S2) and 120 cm (S3) where potato and Mungbean were intercropped. Factor B: Cutting of sugarcane leaf such as cutting of leaves (C1) and No cutting of leaves (C2). The experiment was laid out following randomize complete block design. For sugarcane cultivation BSRI technique and for intercropping the cultivation systems indicated by Bangladesh Agricultural Research Institute were followed. The cane yield and sugar yield were the highest at 100 cm row to row spacing (RRS) of sugarcane (non-leaf cutting = C0) intercropped with 2 rows (2R) of potato followed by 2R of mungbean (S2C0). The lowest yield of sugarcane was found at 80 RRS (C0) with one row (1R) of potato and 1R of mungbean (S1C0). The effect of light interception on growth and yield of first intercrop (potato) was insignificant but significant for second intercrop. The highest yield of potato tuber was 15.28 t ha–1 in S5 (sole potato) followed by 10.85 t ha–1 in S3C1 (sugarcane under leaf cutting at RRS 120 cm with 3R of potato followed by 3R of mungbean). For the yield of mungbean (2nd intercrop), light interception ratio (%) was significantly lowest in (S3C1) where sugarcane RRS was 120 cm with 3R of potato followed by 3R of mungbean under leaf non-cutting (C0) of sugarcane. The highest adjusted cane yield (170.66 t ha–1), benefit cost ratio (3.49) and LER (2.33) were observed in sugarcane at RRS 120 cm with 3R of potato followed by 3R of mungbean (S3C1). Results of both years indicated that intercrops gave higher land equivalent ratio and net return over sole sugarcane planted while sole sugarcane gave maximum benefit cost ratio compared with other intercrops. Finally, on the basis of results it may be concluded that sugarcane transplanted at RRS at 120 cm with 3R potato followed by 3R of mungbean can be grown as intercrops for higher economic return
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Abstract 5583: Helicobacter pylori induces the wee1, promoting immune suppressive in human gastric adenocarcinoma
No full textAbstract Background: Gastric cancer (GC) is the fourth most common cause of cancer-related death worldwide. GC has a dismal 5-year survival rate of about 32%. Helicobacter pylori (H. pylori) infection is the strongest risk factor for gastric carcinogenesis. 75-90% of gastric cancer patients exhibit positive H. pylori serology. WEE1 is a nuclear kinase that regulates cell cycle progression by inhibiting cyclin-dependent kinases. Methods & Results: Analysis of non-cancer normal stomach tissue (n=360) and human GC samples (n=1221) identified that WEE1 mRNA was significantly overexpressed in GC. Using immunohistochemistry (IHC) staining in 41 normal and 44 GC human samples, the data indicated that WEE1 protein was significantly overexpressed in GC. Western blot and immunofluorescence (IF) staining confirmed that H. pylori infection induces WEE1 overexpression in GC cells with an unexpected cytosolic localization of WEE1 in GC cells. Tff1 knockout GC mouse model (Tff1-/-) was infected with mouse-adapted H. pylori strain PMSS1. Western blot and immunohistochemistry data demonstrated that H. pylori infection induced WEE1 expression in Tff1 -/- HGD/cancer mouse gastric tissues compared to control Tff1 -/- mouse stomach. To study how H. pylori infection induces WEE1 in GC, analysis from miRTAR, Target Scan, and miRDB demonstrated that WEE1 is predicted to be targeted by miR-497-5p. Using qRT-PCR analysis, we assessed 30 normal and 30 GC human tissue samples, revealing a pronounced downregulation of miR-497-5p in GC specimens. Western blot analysis confirmed that the restoration of miR-497-5p in GC cells markedly reduced WEE1 protein expression. Interestingly, H. pylori infection further decreased miR-497-5p levels in GC cells, upregulating WEE1 protein expression. Since the miR-497-5P host gene promoter region contains CpG islands, we confirmed that treatment with 5 Azacytidine (demethylating agent) or DNMT1 knockdown induced expression of miR-497-5p with decreased WEE1 level in GC cells. Furthermore, our preliminary results indicate that aberrant WEE1 overexpression in GC demonstrates a significant positive correlation with immune-suppression gene signatures, underscoring its predictive value for unfavorable patient survival outcomes in GC. Using the TFF1 knockout mouse GC model, we found that WEE1 inhibition notably decreases the number and activation of CD4+ and CD8+ T cells in neoplastic gastric tissues. These findings also indicate a crucial relationship between WEE1 and the immunosuppressive microenvironment in GC, establishing WEE1 as a promising therapeutic target to enhance therapeutic efficacy and overcome immunotherapy resistance in GC. Conclusions: Our findings demonstrated a novel mechanism in which H. pylori activates the WEE1 in GC, promoting an immune suppressive microenvironment. WEE1 inhibition with immunotherapy could be a promising therapeutic method for GC patients. Citation Format: Md Obaidul Islam, Krishnapriya Thangaretnam, Heng Lu, Dunfa Peng, Nadeem Sidiq Bhat, Mohammed Soutto, Wael El-Rifai, Zheng Chen. Helicobacter pylori induces the wee1, promoting immune suppressive in human gastric adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5583
