• Journal of Digestive Cancer Research
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• v.6 no.2
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• pp.59-63
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• 2018

Over the past decade, circulating tumor cell have received tremendous attention as new biomarkers and basic research subjects.In recent years, research on circulating tumor DNA, exosomes and microRNAs has also been actively conducted.These circulating tumor markers have the potential to become the basis of precision medicine, such as determining the genome / immune profile, monitoring response and tolerance, and selecting therapeutic agents beyond the early diagnosis and prognosis prediction.In this article, we introduce the diagnostic methods, efficacy, meaning, and applicability of various circulating tumor markers.

• Annals of Surgical Treatment and Research
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• v.95 no.6
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• pp.303-311
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• 2018

Purpose: OncoHepa test is a multigene expression profile test developed for assessment of hepatocellular carcinoma (HCC) prognosis. Multiplication of ${\alpha}$-FP, des-${\gamma}$-carboxy prothrombin (DCP) and tumor volume (TV) gives the ${\alpha}$-FP-DCP-volume (ADV) score, which is also developed for assessment of HCC prognosis. Methods: The predictive powers of OncoHepa test and ADV score were validated in 35 patients who underwent curative hepatic resection for naïve solitary HCCs ${\leq}5cm$. Results: Median tumor diameter was 3.0 cm. Tumor recurrence and patient survival rates were 28.6% and 100% at 1 year, 48.6% and 82.9% at 3 years, and 54.3% and 71.4% at 5 years, respectively. The site of first tumor recurrence was the remnant liver in 18, lung in 1, and the peritoneum in 1. All patients with HCC recurrence received locoregional treatment. OncoHepa test showed marginal prognostic significance for tumor recurrence and patient survival. ADV score at 4log also showed marginal prognostic difference with respect to tumor recurrence and patient survival. Combination of these 2 tests resulted in greater prognostic significance for both tumor recurrence (P = 0.046) and patient survival (P = 0.048). Conclusion: Both OncoHepa test and ADV score have considerably strong prognostic power, thus individual and combined findings of OncoHepa test and ADV score will be helpful to guide postresection surveillance in patients with solitary HCCs ${\leq}5cm$.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.8
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• pp.3659-3665
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• 2014

To assess inhibition mechanisms of a Phellinus igniarius (PI) extract on cancer, C57BL/6 mice were orally treated with PI extractive after or before implanting H22 (hepatocellular carcinoma ) or B16 (melanoma) cells. Mice were orally gavaged with different doses of PI for 36 days 24h after introduction of H22 or B16 cells. Mice in another group were orally treated as above daily for 42 days and implanted with H22 cells on day 7. Then the T lymphocyte, antibody, cytokine, LAK, NK cell activity in spleen, tumor cell apoptosis status and tumor inhibition in related organs, as well as the expression of iNOS and PCNA in tumor tissue were examined. The PI extract could improve animal immunity as well as inhibit cancer cell growth and metastasis with a dose-response relationship. Notably, PI's regulation with the two kinds of tumor appeared to occur in different ways, since the antibody profile and tumor metastasis demonstrated variation between animals implanted with hepatocellular carcinoma and melanoma cells.

• IMMUNE NETWORK
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• v.4 no.3
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• pp.184-189
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• 2004

Background: Hu syndrome, a neurological disorder, is characterized by the remote effect of small cell lung cancer on the neural degeneration. The suspicious effectors for this disease are anti-Hu autoantibodies or Hu-related CD8+ T lymphocytes. Interestingly, the same effectors have been suggested to act against tumor growth and this phenomenon may represent natural tumor immunity. For these diagnostic and therapeutic reasons, the demand for antibodies against Hu protein is rapidly growing. Methods: Polyclonal and monoclonal antibodies were generated using recombinant HuR protein. Western blot analyses were performed to check the specificity of generated antibodies using various recombinant proteins and cell lysates. Extracellular stimuli for HuR expression had been searched and HuR-associated proteins were isolated from polysome lysates and then separated in a 2-dimensional gel. Results: Polyclonal and monoclonal antibodies against HuR protein were generated and these antibodies showed HuR specificity. Antibodies were also useful to detect and immunoprecipitate endogenous HuR protein in Jurkat and BJAB. This report also revealed that TNF-${\alpha}$ treatment in BJAB up-regulated HuR expression. Lastly, protein profile in HuR-associated mRNAprotein complexes was mapped by 2-dimensional gel electrophoresis. Conclusion: This study reported that new antibodies against HuR protein were successfully generated. Currently, project to develop a diagnostic kit is in process. Also, this report showed that TNF-${\alpha}$ up-regulated HuR expression in BJAB and protein profile associated with HuR protein was mapped.

• Nutritional Sciences
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• v.8 no.1
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• pp.23-27
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• 2005

The major garlic component, Allicin [diallylthiosulfinate, or (R, S)-diallyldissulfid-S-oxide] is known for its medicinal effects, such as antihypertensive activity, microbicidal activity, and antitumor activity. Allicin and diallyldisulfide, which is a converted form of allicin, inhibited the cholesterol level in hepatocytes, in vivo and in vitro. The metabolism of allicin reportedly occurs in the microsomes of hepatocytes, predominantly with the contribution of cytochrome P-450. However, little is known about how allicin affects the genes involved in the activity of hepatocytes in vivo. In the present study, we used the short-term intravenous injection of allicin to examine the in vivo genetic profile of hepatocytes. Allicin up-regulate ten genes in the hepatocytes. For example, the interferon regulator 1 (IRF-I), the wingless-related MMTV (mouse mammary tumor virus) integration site 4 (wnt-4), and the fatty acid binding protein 1. However, allicin down-regulated three genes: namely, glutathione S-transferase mu6, a-2-HS glycoprotein, and the corticosteroid binding globulin of hepatocytes. The up-regulated wnt-4, IRF-1, and mannose binding lectin genes can enhance the growth factors, cytokines, transcription activators and repressors that are involved in the immune defense mechanism. These primary data, which were generated with the aid of the Atlas Plastic Mouse 5 K Microarray, help to explain the mechanism which enables allicin to act as a therapeutic agent, to enhance immunity, and to prevent cancer. The data suggest that these benefits of allicin are partly caused by the up-regulated or down-regulated gene profiles of hepatocytes. To evaluate the genetic profile in more detail, we need to use a more extensive mouse genome array.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.2195-2198
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• 2016

Background: Breast cancer is the most prevalent malignancy among women with wide differences in clinical profile from region to region. The present study aimed to describe the profile of breast cancer patients attending a tertiary care hospital in Marathwada region of Western India. Materials and Methods: In this descriptive retrospective study, we reviewed records of pathologically diagnosed patients of breast cancer managed at our center from years 2009 to 2015. Data with respect to demographic status, detailed past, medical, familial and personal history, findings of clinical examination and histological features were obtained. Patients were staged according to the Tumor Node Metastasis (TNM) system. Results: Among 260 cases, mean age of presentation was 52.6, with average age of menarche of 11.3 and menopause of 52.6 years. The majority of patients were from urban regions and were postmenopausal (64.3%). Main clinical features presentation were breast lumps. Most patients were in stage II and had infiltrating duct carcinomas. Conclusions: Most common risk factors for breast cancer observed are increasing age, low parity and obesity. Breast cancer was more prevalent among postmenopausal women presenting in stage II with infiltating duct carcinoma in our region of India.

• Molecular & Cellular Toxicology
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• v.2 no.4
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• pp.273-278
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• 2006

95 squamous cell lung carcinoma samples (normal tissue: 40 samples, tumor: 55 samples) were analyzed with 8 K cDNA microarray. 1-way ANOVA test was employed to select differentially expressed genes in tumor with FDR<0.01. Among the selected 1,655 genes, final 212 genes were chosen according to the expression fold change and used for following analysis. The expression of up-regulated 64 genes was verified with Reverse Transcription PCR and 10 genes were identified as candidates for SCC markers. In our opinion, those candidates can be exploited as diagnostic or therapeutic purposes. Gene Ontology (GO) based analysis was performed using those 212 genes, and following categories were revealed as significant biological processes: Immune response (GO: 0006955), antigen processing (GO: 0030333), inflammatory response (GO: 0006954), Cell adhesion (GO: 0007155), and Epidermis differentiation (GO: 0008544). Gene set enrichment analysis (GSEA) also carried out on overall gene expression profile with 522 functional gene sets. Glycolysis, cell cycle, K-ras and amino acid biosynthesis related gene sets were most distinguished. These results are consistent with the known characteristics of SCC and may be interconnected to rapid cell proliferation. However, the unexpected results from ERK activation in squamous cell carcinoma gripped our attention, and further studies are under progress.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7187-7191
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• 2013

Most of the exogenous and endogenous chemical compounds are metabolized by enzymes of xenobiotic processing pathways, including the phase I cytochrome p450 species. Carcinogens and their metabolites are generally detoxified by phase II enzymes like glutathione-S-transferases (GST). The balance of enzymes determines whether metabolic activation of pro-carcinogens or inactivation of carcinogens occurs. Under certain conditions, deregulated expression of xenobiotic enzymes may also convert endogenous substrates to metabolites that can facilitate DNA adduct formation and ultimately lead to cancer development. In this study, we aimed to test the association between deregulation of metabolizing genes and brain tumorigenesis. The expression profile of metabolizing genes CYP1A1 and GSTP1 was therefore studied in a cohort of 36 brain tumor patients and controls using Western blotting. In a second part of the study we analyzed protein expression of GSTs in the same study cohort by ELISA. CYP1A1 expression was found to be significantly high (p<0.001) in brain tumor as compared to the normal tissues, with ~4 fold (OR=4, 95%CI=0.43-37) increase in some cases. In contrast, the expression of GSTP1 was found to be significantly low in brain tumor tissues as compared to the controls (p<0.02). This down regulation was significantly higher (OR=0.05, 95%CI=0.006-0.51; p<0.007) in certain grades of lesions. Furthermore, GSTs levels were significantly down-regulated (p<0.014) in brain tumor patients compared to controls. Statistically significant decrease in GST levels was observed in the more advanced lesions (III-IV, p<0.005) as compared to the early tissue grades (I-II). Thus, altered expression of these xenobiotic metabolizing genes may be involved in brain tumor development in Pakistani population. Investigation of expression of these genes may provide information not only for the prediction of individual cancer risk but also for the prevention of cancer.

• Nuclear Engineering and Technology
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• v.54 no.8
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• pp.3006-3016
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• 2022

In this study, the images of specific prompt gamma (PG)-rays of 719 keV emitted from proton-boron reactions were analyzed using single-photon emission computed tomography (SPECT). Quantitative evaluation of the images verified the detection of anatomical changes in tumors, one of the important factors in daily adaptive proton therapy (DAPT) and verified the possibility of application of the PG-ray images to DAPT. Six scenarios were considered based on various sizes and locations compared to the reference virtual tumor to observe the anatomical alterations in the virtual tumor. Subsequently, PG-rays SPECT images were acquired using the modified ordered subset expectation-maximization algorithm, and these were evaluated using quantitative analysis methods. The results confirmed that the pixel range and location of the highest value of the normalized pixel in the PG-rays SPECT image profile changed according to the size and location of the virtual tumor. Moreover, the alterations in the virtual tumor size and location in the PG-rays SPECT images were similar to the true size and location alterations set in the phantom. Based on the above results, the tumor anatomical alterations in DAPT could be adequately detected and verified through SPECT imaging using the 719 keV PG-rays acquired during treatment.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.7 no.2
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• pp.79-84
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• 2021

Radiopharmaceuticals are important for tumor diagnosis and therapy. To deliver a radiotracer at the desired target excluding non-targeted tissues is difficult The development of a targeted tracer that has a good clearance profile while maintaining high biostability and biocompatibility is key to optimizing its biodistribution and transport across biological barriers. Improving the hydrophilicity of radiotracers by PEGylation can reduce serum binding, allowing the tracer to circulate without retention and reducing its affinity for non-targeted tissues. In this study, we synthesized a new benzamido tracer (SnBz-PEG₃₆) with the introduction of a low molecular weight polyethylene glycol unit (PEG₃₆, ~2,100 Da). The tumor targeting efficiency and biodistribution of [¹³¹I]-Bz-PEG₃₆ or radiotracer-loaded liposomes were evaluated after their administration to normal mice or mouse tumor models including CT26 (xenograft) and 4T1 (xenograft and orthotopic). Most of the radiotracer was cleared out rapidly (1-24 h post-administration) through the kidney and there was little tumor uptake.