• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8431-8438
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• 2016

Doxorubicin (DOX) was introduced as an effective chemotherapeutic for a wide range of cancers but with some severe side effects especially on myocardia. 2-Deoxy-D-glucose (2DG) enhances the damage caused by chemotherapeutics and ionizing radiation (IR) selectively in cancer cells. We have studied the effects of $1{\mu}M$ DOX and $500{\mu}M$ 2DG on radiation induced cell death, apoptosis and also on the expression levels of p53 and PTEN genes in T47D and SKBR3 breast cancer cells irradiated with 100, 150 and 200 cGy x-rays. DOX and 2DG treatments resulted in altered radiation-induced expression levels of p53 and PTEN genes in T47D as well as SKBR3 cells. In addition, the combination along with IR decreased the viability of both cell lines. The radiobiological parameter (D0) of T47D cells treated with 2DG/DOX and IR was 140 cGy compared to 160 cGy obtained with IR alone. The same parameters for SKBR3 cell lines were calculated as 120 and 140 cGy, respectively. The sensitivity enhancement ratios (SERs) for the combined chemo-radiotherapy on T47D and SKBR3 cell lines were 1.14 and 1.16, respectively. According to the obtained results, the combination treatment may use as an effective targeted treatment of breast cancer either by reducing the single modality treatment side effects.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.8
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• pp.3855-3859
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• 2016

Colorectal cancer (CRC) is reproted to be the third most common cancer worldwide and the fourth most common cause of cancer related deaths. CRC is considered to be a multifactorial disease whose risk varies due to the complex interaction between individual genetic basis and disposure to multiple endogenous factors. Glutathione S-transferases are pro-carcinogenic in CRC and are required for the conjugation between chemotherapeutics and broad spectrum xenobiotics. One hundred and eleven patients with CRC and 128 control subjects without any cancer history were enrolled in this study. Multiplex PCR was applied to determine polymorphisms for the GSTT1 and M1 genes, and PCR-RFLP was applied for the GSTP1 (Ile105Val) gene polymorphism. Values p<0.05 were defined as statistically significant. We detected a significant high correlation between predisposition for CRC and presence of the Ile/Ile genotype of the GSTP1 (IIe105Val) gene polymorphism, but we did not find a significant relationship between predisposition for CRC and GSTT1 and M1 deletion polymorphisms. In addition, we did not determine a relationship between GSTT1, M1 and P1 gene polymorphisms and any clinicopathological features of CRC. GSTT1 null/GSTM1 positive and GSTT1 null/GSTM1 positive/GSTP1 Ile/Ile genotypes were significantly higher in the patient group. Our results revealed that there is no relationship among CRC, its clinicopathologic features, and GSTT1 M1 gene polymorphisms. However, there was a significant correlation between CRC and the GSTP1 Ile/Ile genotype. Further studies with larger patient groups are required to delineate the relationships between GST gene polymorphisms and the clinicopathologic features of CRC in Turkey.

• Korean Journal of Clinical Pharmacy
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• v.27 no.3
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• pp.150-160
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• 2017

Background: Recently, a fixed combination of grazoprevir and elbasvir (GE) has been introduced to the arsenal of chemotherapeutics to fight against this virus. The study aimed to provide information on the efficacy and safety of GE for the treatment of HCV infection by performing a meta-analysis of literature data. Methods: PubMed and EMBASE database searches were conducted. Among the literature retrieved, pivotal Phase III clinical studies were analyzed. Statistical analysis of the data was performed by RevMan. Results: Four pivotal Phase III clinical studies compared the efficacy and safety of GE. When HCV patients were treated with GE for 12 weeks, the sustained virologic response, defined as the viral RNA level below the lower limit of quantification at 12 weeks after the cessation of therapy (SVR12), was 94.7%. The clinical advantage of GE involves its use by patients with cirrhosis and/or renal failure without dose adjustment. If the genotype (GT) of the causative virus was GT1a with NS5A polymorphism or GT4 with resistance to peginterferon/ribavirin, treatment with GE plus ribavirin for 16 weeks resulted in a better outcome compared to treatment with GE alone for 12 weeks. Adverse events reported during the four clinical studies were 71.09% in the GE arms and it was 76.61% in the non-GE arms, with the most frequent events being mild central nervous system symptoms. Conclusion: GE was generally safe and effective for the treatment of HCV infection. However, since HCV mutates very rapidly and becomes resistant to antiviral agents, long-term monitoring should be mandatory.

• Parasites, Hosts and Diseases
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• v.42 no.2
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• pp.61-66
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• 2004

The plasmepsins are the aspartic proteases of malaria parasites. Treatment of aspartic protease inhibitor inhibits hemoglobin hydrolysis and blocks the parasite development in vitro suggesting that these proteases might be exploited their potentials as antimalarial drug targets. In this study, we determined the genetic variations of the aspartic proteases of Plasmodium vivax (PvPMs) of wild isolates. Two plasmepsins (PvPM4 and PvPM5) were cloned and sequenced from 20 P. vivax Korean isolates and two imported isolates. The sequences of the enzymes were highly conserved except a small number of amino acid substitutions did not modify key residues for the function or the structure of the enzymes. The high sequence conservations between the plasmepsins from the isolates support the notion that the enzymes could be reliable targets for new antimalarial chemotherapeutics.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.6109-6114
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• 2013

Aim: To determine whether beta-blockers (BBs) improve the overall survival (OS) of patients with metastatic non-small cell lung cancer (NSCLC). Materials and Methods: The medical charts of 107 patients with metastatic NSCLC were retrospectively assessed. Thirty-five patients (BB group) using BBs during chemotherapy (CT) were compared with 72 controls [control=(C) group] who did not use BBs following the diagnosis of NSCLC. The histological tumor subtype, performance status (ECOG), age, gender, smoking status, comorbidities, other medications and chemotherapeutics that were received in any line of treatment were recorded. We compared the overall survival (OS) of the patients in the BB and C groups. Results: The mean age of the patients was 61 years (range 42-81 years) and all patients were administered CT. The BB group was more likely to have HT and IHD and was more likely to use RAS blockers (p<0.01 for all) compared with the C group, as expected. The mean follow-up time was 17.8 months (range 1-102 months) for the entire group. The most commonly prescribed BB agent was metoprolol (80% of cases). At the time of the analysis, 74 (69%) of all patients had died. In the univariate analysis the median overall survival (OS) was 19.25 (${\pm}2.87$) months (95%CI: 13.62-24.88) in the BB group and 13.20 (${\pm}2.37$) months (95%CI: 8.55-17.85) in the C group (p=0.017). However, the benefit of BBs on survival disappeared in the multivariate analysis. Conclusions: The use of BBs during CT may be associated with an improved OS for patients with metastatic NSCLC.

• Clinical and Experimental Pediatrics
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• v.50 no.7
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• pp.606-612
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• 2007

Since the introduction of chemotherapy for the treatment of childhood leukemia more than 50 years ago, the results of childhood cancer have improved dramatically. The 5-year survival rate of disease, many of which were uniformly fatal in the prechemotherapy era, reached to more than 75%. This remarkable improvement in survival is a direct result of the incorporation of chemotherapeutics into treatment regimens that previously relied only on surgery or radiotherapy for the primary tumor. The multimodality approach, which integrates surgery and radiotherapy to control local disease with chemotherapy to eradicate systemic or metastatic disease, has become the standard approach to treating most childhood cancers. The overall improvement in outcomes in childhood solid tumors has been related to the development of multidisplinary cooperative studies that has permitted the development of well-designed tumor treatment protocols characterized by uniform staging criteria, sharing informations in pathologic classification, uniform methods for tumor markers, oncogenes, and other biologic and genetic factors. Important advances in the biologic study of cancer and its genetic basis led to a number of observations that impact directly on the management of childhood solid tumors. Identification of specific genes, oncogenes, tumor markers, and other biologic and pathologic factors plays an important role in both staging and clarifying the risk categorization of individual patients. Treatment of the patient is influenced by the recognition of specific risk factors. This knowledge has resulted in a change in the approach to care based not only on staging criteria, but also on risk-based management. This concept uses various risk factors of outcomes. Risk-based management allows for each patient to maximize survival, minimize long-term morbidity and improve the quality of life, especially for children's growth and development.

• Molecules and Cells
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• v.38 no.5
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• pp.416-425
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• 2015

NF-E2-related factor 2 (Nrf2), a basic leucine zipper transcription factor, has recently received a great deal of attention as an important molecule that enhances antioxidative defenses and induces resistance to chemotherapy or radiotherapy. In this study, we investigated the apoptosis-inducing and Nrf2- upregulating effects of quercetin on malignant mesothelioma (MM) MSTO-211H and H2452 cells. Quercetin treatment inhibited cell growth and led to upregulation of Nrf2 at both the mRNA and protein levels without altering the ubiquitination and extending the half-life of the Nrf2 protein. Following treatment with quercetin, analyses of the nuclear level of Nrf2, Nrf2 antioxidant response element-binding assay, Nrf2 promoter-luc assay, and RT-PCR toward the Nrf2-regulated gene, heme oxygenase-1, demonstrated that the induced Nrf2 is transcriptionally active. Knockdown of Nrf2 expression with siRNA enhanced cytotoxicity due to the induction of apoptosis, as evidenced by an increase in the level of proapoptotic Bax, a decrease in the level of antiapoptotic Bcl-2 with enhanced cleavage of caspase-3 and PARP proteins, the appearance of a sub-$G_0/G_1$ peak in the flow cytometric assay, and increased percentage of apoptotic propensities in the annexin V binding assay. Effective reversal of apoptosis was observed following pretreatment with the pan-caspase inhibitor Z-VAD. Moreover, Nrf2 knockdown exhibited increased sensitivity to the anticancer drug, cisplatin, presumably by potentiating the oxidative stress induced by cisplatin. Collectively, our data demonstrate the importance of Nrf2 in cytoprotection, survival, and drug resistance with implications for the potential significance of targeting Nrf2 as a promising strategy for overcoming resistance to chemotherapeutics in MM.

• Journal of Veterinary Clinics
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• v.27 no.5
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• pp.565-568
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• 2010

Sulfaquinoxaline (SQX) and trimethoprim (TMP) are chemotherapeutics that are extensively used in various animal species for the treatment or prevention of coccidia and coccidia-like parasites. Little information about the depletion kinetics of these compounds in chickens exists in the literature. In this study, a new commercial liquid concentrate of SQX in combination with TMP (100 g/l of SQX and 33.4 g/l of TMP) was administered with drinking water at a dose of 0.75 ml/l or 1.5 ml/l. The edible tissue concentrations of the drugs were determined by the validated high-performance liquid chromatography/mass spectrometric method. Residue concentrations of SQX and TMP were lower than their maximum residual limits (MRLs) in all tissues from both dose groups at 5 days after the treatment. The optimal withdrawal time of SQX/TMP combination was suggested to be over 5 days after cessation of medication in broilers.

• Journal of Plant Biotechnology
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• v.48 no.2
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• pp.115-122
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• 2021

Aspilia africana (Pers) C.D.Adams, a plant used for centuries in many African countries to treat diseases such as osteoporosis, malaria, tuberculosis, and diabetes, is of great pharmaceutical interest, yet there is limited scientific literature on its germination and growth. This research paper describes the effects of different commercial soils on the germination, growth, and chlorophyll content of A. africana. The germination parameters assessed included final germination percentage (FGP), mean germination time (MGT), and germination index (GI). Shoot length, leaf number, and fresh and dry weights were some of the parameters used to assess A. africana growth. The FGP was low and did not vary significantly; the MGT was 7 ~ 10 days; and the GI was significantly higher in PPS soil at 4.61 ± 0.332 days. Aspilia africana plants in HS:PPS soil showed the best overall growth, producing the highest mean leaf number (18.00 ± 1.129), longest mean shoot length (202.43 ± 13.451 mm), and highest mean fresh and dry weights (7.08 ± 1.061 g and 0.629 ± 0.112 g, respectively). The highest chlorophyll content in leaves of A. africana under HS:PPS conditions suggested a higher photosynthetic potential of plants in this soil. The best growth performance of A. africana in the HS:PPS soil could be attributed to a higher amount of certain mineral nutrients such as nitrogen, potassium, and phosphorus in the HS:PPS soil compared to the other soil categories. It is unclear why the FGP of A. africana was low and we recommend an exclusive study to investigate this further.

• Biomolecules & Therapeutics
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• v.30 no.3
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• pp.284-290
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• 2022

Oral squamous cell carcinoma (OSCC) is mostly diagnosed at an advanced stage, with local and/or distal metastasis. Thus, locoregional and/or local control of the primary tumor is crucial for a better prognosis in patients with OSCC. Platelets have long been considered major players in cancer metastasis. Traditional antiplatelet agents, such as aspirin, are thought to be potential chemotherapeutics, but they need to be used with caution because of the increased bleeding risk. Podoplanin (PDPN)-expressing cancer cells can activate platelets and promote OSCC metastasis. However, the reciprocal effect of platelets on PDPN expression in OSCC has not been investigated. In this study, we found that direct contact with platelets upregulated PDPN and integrin β1 at the protein level and promoted invasiveness of human OSCC Ca9.22 cells that express low levels of PDPN. In another human OSCC HSC3 cell line that express PDPN at an abundant level, silencing of the PDPN gene reduced cell invasiveness. Analysis of the public database further supported the co-expression of PDPN and integrin β1 and their increased expression in metastatic tissues compared to normal and tumor tissues of the oral cavity. Taken together, these data suggest that PDPN is a potential target to regulate platelet-tumor interaction and metastasis for OSCC treatment, which can overcome the limitations of traditional antiplatelet drugs.