• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7029-7035
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• 2014

Certain types of human papillomaviruses (HPVs) are undoubtedly involved in genesis of human malignancies. HPV plays an etiological role in cervical cancer, but also in many vaginal, vulvar, anal and penile cancers, as well as head and neck cancers. In addition, a number of non-malignant diseases such as genital warts and recurrent respiratory papillomatosis are attributable to HPV. Moreover, HPV forms have detected in several other cancers including esophageal squamous cell carcinoma, lung, prostate, ovarian, breast, skin, colorectal and urinary tract cancers, but associations with etiology in these cases is controversial. The aim of this systematic assessment was to estimate the prevalence of HPV infection and HPV types in HPV-associated cancers, HPV-related non-malignant diseases and in cancers that may be associated with HPV in Iran. The present investiagtion covered 61 studies on a variety of cancers in Iranian populations. HPV prevalence was 77.5 % and 32.4% in cervical cancer and head and neck cancers, respectively. HPV was detected in 23.1%, 22.2%, 10.4%, 30.9%, 14% and 25.2% of esophageal squamous cell, lung, prostate, urinary tract cancers, breast and skin cancers, respectively. HPV16 and 18 were the most frequent HPV types in all cancers. The findings of present study imply that current HPV vaccines for cervical cancer may decrease the burden of other cancers if they are really related to HPV.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.8
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• pp.3443-3446
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• 2014

The aim of this study was to determine predictive factors for neutropenia after docetaxel-based systemic chemotherapy in patients with castration-resistant prostate cancer (CRPC). The study included 40 Korean CRPC patients who were treated with several cycles of docetaxel plus prednisolone from May 2005 to May 2012. Patients were evaluated for neutropenia risk factors and for the incidence of neutropenia. In this study, nine out of forty patients (22.5%) developed neutropenia during the first cycle of docetaxel-based systemic chemotherapy. Four experienced grade 2, three grade 3, and one grade 4 neutropenia. Multivariate analysis showed that pretreatment white blood cell (WBC) count (p=0.042), pretreatment neutrophil count (p=0.015), pretreatment serum creatinine level (p=0.027), and pretreatment serum albumin level (p=0.017) were significant predictive factors for neutropenia. In conclusion, pretreatment WBC counts, neutrophil counts, serum creatinine levels, and serum albumin levels proved to be significant independent risk factors for the development of neutropenia induced by docetaxel-based systemic chemotherapy in patients with CRPC.

• Biomolecules & Therapeutics
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• v.22 no.4
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• pp.355-362
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• 2014

We have developed a fully automated high throughput drug screening (HTDS) system based on the microfluidic cell culture array to perform combinational chemotherapy. This system has 64 individually addressable cell culture chambers where the sequential combinatorial concentrations of two different drugs can be generated by two microfluidic diffusive mixers. Each diffusive mixer has two integrated micropumps connected to the media and the drug reservoirs respectively for generating the desired combination without the need for any extra equipment to perfuse the solution such as syringe pumps. The cell array is periodically exposed to the drug combination with the programmed LabVIEW system during a couple of days without extra handling after seeding the cells into the microfluidic device and also, this device does not require the continuous generation of solutions compared to the previous systems. Therefore, the total amount of drug being consumed per experiment is less than a few hundred micro liters in each reservoir. The utility of this system is demonstrated through investigating the viability of the prostate cancer PC3 cell line with the combinational treatments of curcumin and tumor necrosis factor-alpha related apoptosis inducing ligand (TRAIL). Our results suggest that the system can be used for screening and optimizing drug combination with a small amount of reagent for combinatorial chemotherapy against cancer cells.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3437-3445
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• 2016

Background: There is an increasing concern in the role of microRNA (miRNA) in the pathogenesis of bone metastasis (BM) secondary to prostate cancer (CaP). In this exploratory study, we hypothesized that the expression of vinculin (VCL) and chemokine X3C ligand 1 (CX3CL1) might be down-regulated in clinical samples, most likely due to the post-transcriptional modification by microRNAs. Targeted genes would be up-regulated upon transfection of the bone metastatic prostate cancer cell line, PC3, with specific microRNA inhibitors. Materials and Methods: MicroRNA software predicted that miR-21 targets VCL while miR-29a targets CX3CL1. Twenty benign prostatic hyperplasia (BPH) and 16 high grade CaP formalin-fixed paraffin embedded (FFPE) specimens were analysed. From the bone scan results, high grade CaP samples were further classified into CaP with no BM and CaP with BM. Transient transfection with respective microRNA inhibitors was done in both RWPE-1 (normal) and PC3 cell lines. QPCR was performed in all FFPE samples and transfected cell lines to measure VCL and CX3CL1 levels. Results: QPCR confirmed that VCL messenger RNA (mRNA) was significantly down-regulated while CX3CL1 was up-regulated in all FFPE specimens. Transient transfection with microRNA inhibitors in PC3 cells followed by qPCR of the targeted genes showed that VCL mRNA was significantly upregulated while CX3CL1 mRNA was significantly down-regulated compared to the RWPE-1 case. Conclusions: The down-regulation of VCL in FFPE specimens is most likely regulated by miR-21 based on the in vitro evidence but the exact mechanism of how miR-21 can regulate VCL is unclear. Up-regulated in CaP, CX3CL1 was found not regulated by miR-29a. More microRNA screening is required to understand the regulation of this chemokine in CaP with bone metastasis. Understanding miRNA-mRNA interactions may provide additional knowledge for individualized study of cancers.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.4 no.2
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• pp.65-72
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• 2018

Prostate specific membrane antigen (PSMA) is a cell surface membrane protein, which is overexpressed in most prostate cancer. Recently, PET imaging with $[^{68}Ga]$PSMA-HBED-CC has been widely used for the diagnosis of recurrent prostate cancer and the studies on the diagnostic potential of $^{64}Cu$-labeled PSMA ligands reported actively. In this study, we monitored with biological evaluation in vivo and PET imaging of $^{64}Cu$-labeled PSMA ligand ($[^{64}Cu]$PSMA-617). The radiolabelling efficiency and stability of $[^{64}Cu]$PSMA-617 were confirmed by radio-thin layer chromatography. The radiolabeling efficiency of $[^{64}Cu]$PSMA-617 showed over 95%, and stabilities of intact remained over 98% in both human and mouse serum for 48 h. In normal male mice, in vivo uptake of $[^{64}Cu]$PSMA-617 in several organs was measured at 2, 4, 6, 24, 48 h after injection. Rapid blood clearance was observed for $[^{64}Cu]$PSMA-617. The high uptake was observed in the lung, liver, intestines and kidneys at 2 h postinjection, but was low in the other organs (1-2 %ID/g) at 4 h. The dynamic PET/CT images of 22RV1 tumor-bearing nude mice were acquired during 60 min and additionally acquired 24 h and 48 h after injection. In dynamic PET images, $[^{64}Cu]$PSMA-617 uptake ratio in tumors versus muscle was increased as time elaplsed until 60 minutes and remained in tumors at 48 h. In these results, the PET/CT imaging using $[^{64}Cu]$PSMA-617 in prostate cancer is expected to be useful for the diagnosis and treatment of prostate cancer patients.

• Journal of the Korean Chemical Society
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• v.63 no.2
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• pp.85-93
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• 2019

A panel of chalcone-sulphonamide hybrids has been designed by tethering appropriate sulphonamide scaffold with substituted chalcones as a multi-target drug for anticancer screening. Chalcones were prepared by Claisen-Schmidt condensation reaction of a substituted aldehyde with para aminoacetophenone. All the synthesized compounds were evaluated against selected five cancer cell lines, MCF-7 (Breast cancer), DU-145 (Human prostate Carcinoma), HCT-15 (Colon cancer), NCIH-522 (stage 2, adenocarcinoma; non-small cell lung cancer) and HT-3 (Human cervical cancer). Most of the synthesized chalcone-sulphonamide hybrids showed amended cytotoxic activity against various cancer cell lines which may be attributed to the linkage of sulphonamide with chalcone skeleton. The synthesized compounds were characterized by FT-IR, $^1H$ NMR, $^{13}C$ NMR and HR-LCMS and spectral study assert the structures of synthesized sulphonamide-chalcone hybrids.

• The Journal of Internal Korean Medicine
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• v.28 no.3
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• pp.409-420
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• 2007

Objectives : The purpose of this study was to identify the anti-tumor effects of realgar on various cancer cells through molecular biologic and cellular biologic methods. Materials & Methods : We used 5 kinds of cancer cell lines:stomach cancer cell (AGS), glioma cells (T98G, A172, SNU-489) and prostate cancer cells (LNCaP). We injected the boiled extract of realgar. $50{\mu}$g/ml and $100{\mu}$g/ml to culture media (ml) for 24 hours. We examined the morphological changes under an inverted microscope and a fluorescence microscope. We measured the suppressive effect on viability of 5 kinds of cancer cells via XTT assay. We examined the effect on the revelation of PARP cleavage, Bcl-2 protein and Bax protein by western blot analysis. Results : The extract of realgar caused markedly morphological changes on AGS, T98G, SNU-489, and LNCaP. All of them showed withdrawn and floating appearance. The suppressive effect on viability of AGS, T98G, A172, SNU-489, and LNCaP showed that each test group had more suppressive effect on viability of AGS, T98G, A172, SNU-489, and LNCaP than the control group, which was statistically significantly (p<0.01). The extract of realgar did not induce PARP cleavage in AGS, T98G, A 172, SNU-489, or LNCaP. In the revelation of protein related to apoptosis, the protein levels of Bcl-2 decreased and the protein levels of Bax increased in AGS, T98G, SNU-489, and LNCaP treated with realgar. The protein levels of Bcl-2 decreased and the protein levels of Bax did not change in A172 treated with realgar. Conclusions : This experiment showed that realgar has anti-tumor effect on stomach cancer cells (AGS), glioma cells (T98G, SNU-489L and prostate cancer cells (LNCaP)

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6369-6374
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• 2012

Vitexicarpin (3', 5-dihydroxy-3, 4', 6, 7-tetramethoxyflavone), a polymethoxyflavone isolated from Viticis Fructus (Vitex rotundifolia Linne fil.), has long been used as an anti-inflammatory herb in traditional Chinese medicine. It has also been reported that vitexicarpin can inhibit the growth of various cancer cells. However, there is no report elucidating its effect on human prostate carcinoma cells. The aim of the present study was to examine the apoptotic induction activity of vitexicarpin on PC-3 cells and molecular mechanisms involved. MTT studies showed that vitexicarpin dose-dependently inhibited growth of PC-3 cells with an $IC_{50}{\sim}28.8{\mu}M$. Hoechst 33258 staining further revealed that vitexicarpin induced apoptotic cell death. The effect of vitexicarpin on PC-3 cells apoptosis was tested using prodium iodide (PI)/Annexin V-FITC double staining and flow cytometry. The results indicated that vitexicarpin induction of apoptotic cell death in PC-3 cells was accompanied by cell cycle arrest in the G2/M phase. Furthermore, our study demonstrated that vitexicarpin induction of PC-3 cell apoptosis was associated with upregulation of the proapoptotic protein Bax, and downregulation of antiapoptotic protein Bcl-2, release of Cytochrome c from mitochondria and decrease in mitochondrial membrane potential. Our findings suggested that vitexicarpin may become a potential leading drug in the therapy of prostate carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.1739-1744
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• 2016

We report herein an in vitro anticancer evaluation of a series of seven curcumin analogues (3a-g). The National Cancer Institute (NCI US) Protocol was followed and all the compounds were evaluated for their anticancer activity on nine different panels (leukemia, non small cell lung cancer, colon cancer, CNS cancer, melanoma, ovarian cancer, renal cancer, prostate cancer and breast cancer) represented by 60 NCI human cancer cell lines. All the compounds showed significant anticancer activity in one dose assay (drug concentration $10{\mu}M$) and hence were evaluated further in five dose assays (0.01, 0.1, 1, 10 and $100{\mu}M$) and three dose related parameters $GI_{50}$, TGI and $LC_{50}$ were calculated for each (3a-g) in micro molar drug concentrations (${\mu}M$). The compound 3d (NSC 757927) showed maximum mean percent growth inhibition (PGI) of 112.2%, while compound 3g (NSC 763374) showed less mean PGI of 40.1% in the one dose assay. The maximum anticancer activity was observed with the SR (leukemia) cell line with a $GI_{50}$ of $0.03{\mu}M$. The calculated average sensitivity of all cell lines of a particular subpanel toward the test agent showed that all the curcumin analogues showed maximum activity on leukemia cell lines with $GI_{50}$ values between 0.23 and $2.67{\mu}M$.

• Journal of Life Science
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• v.26 no.4
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• pp.398-405
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• 2016

Statins, the inhibitors of 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase, are widely used in treatments of hypercholesterolemia and newly known as anti-cancer effect of various cancer cells. Recently, several studies suggested that reactive oxygen species (ROS) play a critical role on cell death signaling. However, mechanism of ROS by rosuvastatin is currently unclear. This study aimed to explore the molecular mechanism of apoptosis by rosuvastatin in human prostate cancer PC-3 cells. Cell viability and apoptosis-related protein expression were measured by MTT assay and western blotting, respectively. In addition, the levels of apoptosis and ROS were analyzed. The results showed that rosuvastatin dramatically reduced cell viability in a dose- and time-dependent manner. We confirmed that rosuvastatin induced apoptosis through reduction of procaspase-3 and cleavage of poly (ADP-ribose) polymerase (PARP) in PC-3 cells. In addition, rosuvastatin stimulated ROS production in a dose-dependent manner and pre-treatment with N-acetylcysteine (NAC), a ROS scavenger, significantly recovered rosuvastatin-induced ROS and apoptosis. Thus, we concluded that rosuvastain induces apoptosis through generation of ROS in human prostate cancer PC-3 cells and provides a promising approach to improve the efficacy of cancer therapy.