• Asian Pacific Journal of Cancer Prevention
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• 제14권8호
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• pp.4801-4804
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• 2013

Purpose: To investigate short-term response rate, quality of life and toxicities of mannan peptide combined with TP regimen in treating patients with non-small cell lung cancer (NSCLC). Patients and Methods: Forty one patients with NSCLC were divided into an experimental group treated with TP regimen combined with mannan peptide (21 patients) and a control group treated with TP alone (20 patients). Results: Response rates were 61.9% (13/21) for the experimental and 60% (12/20) for the control group (p>0.05). Regarding toxicity, white blood cell decreased more frequently in the control group (65%, 13/20) than in the experimental group (33.3%, 7/21) (p<0.05); nausea and vomiting also occurred more frequently in the control group (55%, 11/20 vs 23.8%, 5/21) (p<0.05). In terms of quality of life, this index was improved by 57.1% (12/21) and 25% (5/20) in experimental and control groups, respectively (p<0.05). Conclusions: Response rate of TP after combined with mannan peptide is mildly increased, while this combination alleviates bone marrow suppression as well as nausea and vomiting of TP, and improves quality of life when treating patients with NSCLC. However, this conclusion should be confirmed by randomized clinical trails.

• Molecules and Cells
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• 제25권4호
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• pp.457-461
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• 2008

DNA damage checkpoint is an important self-defense mechanism for the maintenance of genome stability. Defects in DNA damage signaling and repair lead to various disorders and increase tumor incidence in humans. In the past 10 years, we have identified many components involved in the DNA damage-signaling pathway, including the product of breast cancer susceptibility gene 1 (BRCA1). Mutations in BRCA1 are associated with increased risk of breast and ovarian cancers, highlighting the importance of this DNA damage-signaling pathway in tumor suppression. While it becomes clear that BRCA1 plays a crucial role in the DNA damage responsive pathway, exactly how BRCA1 receives DNA damage signals and exerts its checkpoint function has not been fully addressed. A series of recent studies reported the discovery of many novel components involved in DNA damage-signaling pathway. These newly identified checkpoint proteins, including RNF8, RAP80 and CCDC98, work in concern in recruiting BRCA1 to DNA damage sites and thus regulate BRCA1 function in G2/M checkpoint control. This review will summarize these recent findings and provide an updated view of the regulation of BRCA1 in response to DNA damage.

• Archives of Pharmacal Research
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• 제25권4호
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• pp.475-479
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• 2002

Capsaicin, a major pungent constituent of red pepper (Capsicum annuum L.) possesses a vast variety of pharmacologic and physiologic activities. Despite its irritant properties, the compound exerts anti-inflammatory and anti-nociceptive effects. Previous studies from this laboratory revealed that capsaicin, when topically applied onto dorsal skin of female ICR mice, strongly attenuated activation of NF-kB and AP-1 induced by the typical tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), which may account for its anti-tumor promoting activity in mouse skin. In the present work, we have found that capsaicin suppresses TPA-stimulated activation of NF-kB through inhibition of $IkB{\alpha}$ degradation and blockade of subsequent nuclear translocation of p65 in human pro myelocytic leukemia HL-60 cells. Methylation of the phenolic hydroxyl group of capsaicin abolished its inhibitory effect on NF-kB DNA binding. Likewise, TPA-induced activation of AP-1 was mitigated by capsaicin treatment.

• 한국임상수의학회지
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• 제36권1호
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• pp.30-37
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• 2019

The purpose of this present study was to objectively evaluate gastrointestinal and bone marrow AEs after administration of various chemotherapeutic agents in canines with malignant tumors, using the Veterinary Cooperative Oncology Group-Common Terminology Criteria for Adverse Events (VCOG-CTCAE), which includes descriptive terminology used for adverse events (AEs) reported in dogs and cats. The medical records of 42 dogs with malignant tumor that underwent chemotherapy were reviewed retrospectively. There were no significant differences in the prevalence of gastrointestinal AEs among the 5 chemotherapeutic agents (vincristine, cyclophosphamide, doxorubicin, lomistine, and carboplatin). The prevalence of bone marrow AEs was significantly higher after administration of lomustine than after administration of vincristine or doxorubicin. Grade 1 AEs of the gastrointestinal tract and bone marrow were most often observed after administration of various chemotherapeutic agents. Delayed and cumulative myelosuppression of lomustine in some dogs receiving regular blood examination were identified. The findings of this study will help predict possible gastrointestinal and bone marrow AEs due to the use of chemotherapeutic agents to treat canines with malignant tumors.

• Molecules and Cells
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• 제38권6호
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• pp.548-561
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• 2015

By combining conventional single cell analysis with flow cytometry and public database searches with bioinformatics tools, we extended the expression profiling of thymic stromal cotransporter (TSCOT), Slc46A2/Ly110, that was shown to be expressed in bipotent precursor and cortical thymic epithelial cells. Genome scale analysis verified TSCOT expression in thymic tissue- and cell type- specific fashion and is also expressed in some other epithelial tissues including skin and lung. Coexpression profiling with genes, Foxn1 and Hoxa3, revealed the role of TSCOT during the organogenesis. TSCOT expression was detected in all thymic epithelial cells (TECs), but not in the $CD31^+$endothelial cell lineage in fetal thymus. In addition, ABC transporter-dependent side population and Sca-$1^+$ fetal TEC populations both contain TSCOT-expressing cells, indicating TEC stem cells express TSCOT. TSCOT expression was identified as early as in differentiating embryonic stem cells. TSCOT expression is not under the control of Foxn1 since TSCOT is present in the thymic rudiment of nude mice. By searching variations in the expression levels, TSCOT is positively associated with Grhl3 and Irf6. Cytokines such as IL1b, IL22 and IL24 are the potential regulators of the TSCOT expression. Surprisingly, we found TSCOT expression in the lung is diminished in lung cancers, suggesting TSCOT may be involved in the suppression of lung tumor development. Based on these results, a model for TEC differentiation from the stem cells was proposed in context of multiple epithelial organ formation.

• Asian Pacific Journal of Cancer Prevention
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• 제16권6호
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• pp.2397-2402
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• 2015

Previous studies have shown that miR-454 plays an important role in a variety of biological processes in various human cancer cells. However, the underlying mechanisms of this microRNA in colorectal cancer (CRC) cells remain largely unknown. In the present study, we investigated the miR-454 role in CRC cell proliferation. We found that miR-454 expression is markedly upregulated in CRC tissues and CRC cells compared with the matched tumor adjacent tissues and the FHC normal colonic cell line. Ectopic expression of miR-454 promoted the proliferation and anchorage-independent growth of CRC cells, whereas inhibition of miR-454 reduced this effect. Bioinformatics analysis further revealed cylindromatosis (CYLD), a putative tumor suppressor as a potential target of miR-454. Data from luciferase reporter assays showed that miR-454 directly binds to the 3'-untranslated region (3'-UTR) of CYLD mRNA and repressed expression at both transcriptional and translational levels. In functional assays, CYLD-silenced in miR-454-in-transfected SW480 cells have positive effect to promote cell proliferation, suggesting that direct CYLD downregulation is required for miR-454-induced CRC cell proliferation. In sum, our data provide compelling evidence that miR-454 functions as an onco-miRNA, playing a crucial role in the promoting cell proliferation in CRC, and its oncogenic effect is mediated chiefly through direct suppression of CYLD expression.

• Journal of Microbiology and Biotechnology
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• 제23권9호
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• pp.1327-1338
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• 2013

The humanized anti-hepatocyte growth factor (HGF) monoclonal antibody (mAb) YYB-101 is a promising therapeutic candidate for treating various cancers. In this study, we developed a bioprocess for large-scale production of YYB-101 and evaluated its therapeutic potential for tumor treatment using a xenograft mouse model. By screening diverse chemically defined basal media formulations and by assessing the effects of various feed supplements and feeding schedules on cell growth and antibody production, we established an optimal medium and feeding method to produce 757 mg/l of YYB-101 in flask cultures, representing a 7.5-fold increase in titer compared with that obtained under non-optimized conditions. The optimal dissolved oxygen concentration for antibody production was 70% $pO_2$. A pH shift from 7.2 to 7.0, rather than controlled pH of either 7.0 or 7.2, resulted in productivity improvement in 5 L and 200 L bioreactors, yielding 737 and 830 mg/ml of YYB-101, respectively. The YYB-101 mAb highly purified by affinity chromatography using a Protein A column and two-step ion exchange chromatography effectively neutralized HGF in a cell-based assay and showed potent tumor suppression activity in a mouse xenograft model established with human glioblastoma cells.

• Biomolecules & Therapeutics
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• 제25권4호
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• pp.411-416
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• 2017

Paclitaxel (PTX) is a effectively chemotherapeutic agent which is extensively able to treat the non-small cell lung, pancreatic, breast and other cancers. But it is a practically insoluble drug with water solubility less than $1{\mu}g/mL$, which restricts its therapeutic application. To overcome the problem, hyaluronic acid-complexed paclitaxel nanoemulsions (HPNs) were prepared by ionic complexation of paclitaxel (PTX) nanoemulsions and hyaluronic acid (HA) to specifically target non-small cell lung cancer. HPNs were composed of ${\small{DL}}-{\alpha}$-tocopheryl acetate, soybean oil, polysorbate 80, ferric chloride, and HA and fabricated by high-pressure homogenization. The HPNs were $85.2{\pm}7.55nm$ in diameter and had a zeta potential of $-35.7{\pm}0.25mV$. The encapsulation efficiency was almost 100%, and the PTX content was 3.0 mg/mL. We assessed the in vivo antitumor efficacy of the HPNs by measuring changes in tumor volume and body weight in nude mice transplanted with CD44-overexpressing NCI-H460 xenografts and treated with a bolus dose of saline, $Taxol^{(R)}$, PTX nanoemulsions (PNs), or HPNs at a dose of 25 mg/kg. Suppression of cancer cell growth was higher in the PN- and HPN-treated groups than in the $Taxol^{(R)}$ group. In particular, HPN treatment dramatically inhibited tumor growth, likely because of the specific tumor-targeting affinity of HA for CD44-overexpressed cancer cells. The loss of body weight and organ weight did not vary significantly between the groups. It is suggest that HPNs should be used to effective nanocarrier system for targeting delivery of non-small cell lung cancer overexpressing CD44 and high solubilization of poorly soluble drug.

• Asian Pacific Journal of Cancer Prevention
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• 제15권17호
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• pp.7413-7417
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• 2014

Background: Development of gastric cancer (GC) is a multistep process that requires alterations in the expression of oncogenes and tumor suppressor genes, occurring over several decades. The p53 tumor suppressor protein is involved in cell-cycle control, apoptosis and DNA repair. One of the most important regulators of p53 is MDM2, which acts as a negative regulator in the p53 pathway. Based on the key role of p53 and MDM2 in tumor suppression, polymorphisms that cause change in their function might affect cancer risk. We therefore elevated associations of the polymorphisms of p53 (R72P) and MDM2 (SNP309) with GC in Iran. Materials and Methods: A total of 104 patients with gastric cancer and 100 controls were recruited. Genomic DNA was extracted from fresh gastric samples. Genotyping of the p53 and MDM2 genes was performed using allele specific PCR (AS-PCR). Results: There was no significant difference between the p53 codon 72 polymorphism distribution in control and patient groups (p=0.54), but the G allele of MDM2 was found to be over-represented in patients (p=0. 01, Odds Ratio=2. 08, 95% Confidence Interval= 1.37-4.34). Conclusions: The p53 R72P seems not to be a potential risk factor for development of GC among Iranian patients, but our data suggest that MDM2 SNP309 might modify the risk related to GC.

• Asian Pacific Journal of Cancer Prevention
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• 제16권13호
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• pp.5359-5364
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• 2015

Background: Multiple complex pathways are operable in the evolution of cutaneous T cell lymphomas (CTCLs). These pathways involve interaction between neoplastic T cells and cells of the immune system (especially dendritic cells and the non-malignant T cells). Granulysin is a proinflammatory antimicrobial peptide which has an immune alarmin function, activating dendritic cells, as well as an active role in tumor immunology and prognosis. FOXP3+ regulatory T cells Tregs are an important player in the immune system. Much controversy is found in the literature about the role of Tregs in CTCL. Aim: The present study aimed to investigate the expression of granulysin and FOXP3 in mycosis fungoides (MF), its precursor lesion large plaque parapsoriasis and its leukemic form ;$s\acute{e}ezary$ syndrome (SS). Materials and Methods: Immunohistochemical expression of granulysin and FOXP3 were assessed in lesional skin biopsies taken from 58 patients (4 large plaque parapsoriasis, 48 MF and 6 SS). Results: Granulysin positivity was cytoplasmic and higher in MF than in parapsoriasis en plaque and higher in the more advanced stages of MF (p<0.001). All groups showed significant differences between each other except between MF tumor stage and SS. FOXP3 positivity was nuclear and higher in early stage MF (plaque and patch stages) than in tumor stages and SS (p<0.001). However the FOXP3 count was lower in parapsoriasis en plaque than in other stages of MF. All the groups showed significant differences between each other except between parapsoriasis and SS and between patch and plaque stages of MF. Conclusions: The present study supports a role for granulysin in MF progression and proposes a novel hypothesis about the effect of FOXP3 +veTregs in the suppression of the activity of the neoplastic cells in MF.