• Journal of Gastric Cancer
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• v.3 no.4
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• pp.206-213
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• 2003

Purpose: The clinical implication of p53 mutation in gastric cancer is still unclear, as shown by the discordant results that continue to be reported in the literature. Materials and Methods: To assess p53 gene mutation, tumor p53 overexpression, and serum anti-p53 antibody, we employed a polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis, an immunohistochemistry using monoclonal antibody DO-7, and an enzymelinked immunosorbent assay (ELISA), respectively. Results: Of 169 surgical specimens of gastric cancer, mutation at exon $5\∼8$ of the p53 was identified in 33 ($19.5\%$) and was significantly correlated with lymph node metastasis. Overexpression of p53 was found in 62 specimens ($36.7\%$) and had a significant correlation with tumor differentiation. Serum anti-p53 antibody was positive in 18 patients ($10.7\%$). Twenty-three of the mutated tumors ($69.7\%$) and 39 of the non-mutated tumors ($28.7\%$) displayed immunoreactivity. Twelve of the immunopositive tumors ($19.4\%$) and 6 of the immunonegative tumors produced anti-p53 antibody. These differences were statistically significant (P<0.001 and P=0.005, respectively). There was no significant difference in survival according to the mutation of p53. Conclusion: Mutation and overexpression of p53 can be easily detected by immunohistochemistry. However, standardization of the immunohistochemical staining method, as well as guidelines for interpreting the stained result, will produce concordant results and thereby improve clinical application.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.8753-8757
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• 2014

Background: Glioma is a heterogeneous central nervous system (CNS) tumor group that encompasses different histological subtypes with high variability in prognosis. The lesions account for almost 80% of primary malignant brain tumors. The aim of this study is to extend our understanding of the glioma epidemiology in the central Tunisian region. Materials and Methods: We analyzed 393 gliomas recorded in cancer registry of central Tunisia from 1993 to 2012. Crude incidence rates (CR) and world age-standardized rates (ASR) were estimated using annual population data size and age structure. Statistic correlations were established using Chi-square and Kaplan-Meier test. Results: Tunisian glioma patients were identified with a mean age at diagnosis of 48 years and 1.5 sex ratio (male/female). During the 19 years period of study the highest incidence value was observed in male group between 1998 and 2002 (CR: 0.28, ASR: 0.3). Incidence results underline increasing high grade glioma occurring in the adulthood in the last period (2007-2012). Median survival was 27 months, with 1-, 2- and 5-year survival rates of 42%, 30% and 26%, respectively. Survival was greater in patients with younger age, lower tumor grade, infratentrial tumor location and undergoing a palliative treatment. Conclusions: This central Tunisia gliomas registry study provides important information that could improve glioma management and healthcare practice.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.15
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• pp.5977-5982
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• 2014

Research over the years has progressively shown substantial broadening of the tumor necrosis factor alpha-related apoptosis-inducing ligand (TRAIL)-mediated signaling landscape. Increasingly it is being realized that pancreatic cancer is a multifaceted and genomically complex disease. Suppression of tumor suppressors, overexpression of oncogenes, epigenetic silencing, and loss of apoptosis are some of the extensively studied underlying mechanisms. Rapidly accumulating in vitro and in vivo evidence has started to shed light on the resistance mechanisms in pancreatic cancer cells. More interestingly a recent research has opened new horizons of miRNA regulation by DR5 in pancreatic cancer cells. It has been shown that DR5 interacts with the core microprocessor components Drosha and DGCR8, thus impairing processing of primary let-7. Xenografting DR5 silenced pancreatic cancer cells in SCID-mice indicated that there was notable suppression of tumor growth. There is a paradigm shift in our current understanding of TRAIL mediated signaling in pancreatic cancer cells that is now adding new layers of concepts into the existing scientific evidence. In this review we have attempted to provide an overview of recent advances in TRAIL mediated signaling in pancreatic cancer as evidenced by findings of in vitro and in vivo analyses. Furthermore, we discuss nanotechnological advances with emphasis on PEG-TRAIL and four-arm PEG cross-linked hyaluronic acid (HA) hydrogels to improve availability of TRAIL at target sites.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.1101-1106
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• 2013

Background: Osteosarcoma is the most common primary bone tumor in childhood and adolescence. Carboplatin, a platinum-derived agent, is used as neoadjuvant chemotherapy for pediatric osteosarcoma because of its anti-tumor activity and had low toxicity as compared to cisplatin. Objective: To determine demographic data, prognostic factors and outcome of childhood osteosarcoma treated with a carboplatin-based chemotherapeutic protocol at Chiang Mai University. Method: A retrospective analysis was conducted on 34 osteosarcoma patients aged less than 18 years and treated between 2003 and 2011. Results: Overall limb-salvage and amputation rates were 23.5% and 70.6%, respectively. With the mean follow-up time of 29.5 months (1.5-108.9), the Kaplan-Meier analysis for 3-year disease-free survival (DFS) and 3-year overall survival (OS) were $20.2{\pm}7.7%$ and $47.1{\pm}9.5%$ respectively. Patients who had initial pulmonary metastasis were at significantly greater risk for developing recurrence (p=0.02, OR=7; 1.2-40.1) and had a tendency to have lower 3-year OS compared to those without initial pulmonary metastasis ($28.1{\pm}13%$, $63.1{\pm}12.3%$, respectively, p=0.202). On univariate analysis, age at diagnosis >14 years and patients who were declined surgery were significantly associated with lower 3-year OS (p=0.008 and <0.05, respectively). However, age at diagnosis, sex, tumor size and histological subtypes were not found to significantly affect recurrence or survival. Conclusions: In our study, the survival rate was far lower than those reported from developed countries. These might indicate the ineffectiveness of carboplatin in combination with doxorubicin as frontline treatment of pediatric osteosarcoma, especially in those with initial pulmonary metastasis. Refinement in risk and treatment stratification and dose intensification for pediatric osteosarcoma constitutes a future challenge to improve outcomes, especially in metastatic patients who may need a more intensive regimen.

• Clinical and Experimental Reproductive Medicine
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• v.38 no.2
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• pp.98-102
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• 2011

Objective: To investigate the effects of pioglitazone on controlled ovarian stimulation (COS), IVF outcomes, and follicular fluid (FF) cytokine concentrations in patients with polycystic ovary syndrome (PCOS). Methods: Eighty-six infertile patients with PCOS resistant to clomiphene citrate were randomized to receive pioglitazone (30 mg/day) or placebo on the starting day of oral contraceptive (OC) pretreatment, followed by an IVF protocol using a GnRH antagonist. Pioglitazone or placebo was administered once daily from the starting day of OC to the day of hCG injection. Results: Total dose and days of recombinant follicle-stimulating hormone administered, and the numbers of retrieved and mature oocytes, were significantly lower in the pioglitazone group than in the control group. FF tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and interleukin-6 (IL-6) concentrations at oocyte retrieval were also significantly lower in the pioglitazone group. The clinical pregnancy rate was higher and the incidence of severe ovarian hyperstimulation syndrome was lower in the pioglitazone group, but the differences were not statistically significant. Conclusion: Pioglitazone reduces FF TNF-${\alpha}$ and IL-6 levels, and may improve ovarian response to COS in patients with PCOS.

• Journal of Veterinary Clinics
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• v.33 no.6
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• pp.395-399
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• 2016

In the present case, the effect and toxicity of carboplatin and cyclophosphamide chemotherapy combined with surgery of mammary tumors in a dog were examined. An 8-year old spayed female Beagle presented with a mammary tumor. Physical examination, radiography, ultrasonography, computed tomography (CT), and laboratory examination were performed. Metastasis of the mammary tumor was confirmed by CT scan. Chemotherapy using a combination of carboplatin and cyclophosphamide was initiated following surgery. The first cycle of chemotherapy was planned to last for 6 weeks; it was planned that carboplatin would be intravenously administered for the first week (1 day) and cyclophosphamide would be intravenously administered for the next 3 weeks (22 days). Between the end of cycle 1 and the beginning of cycle 2, based on CT, it was confirmed that the number and size of tumors were unchanged and the tumors had not spread to other organs. However, at the end of cycle 2 and the beginning of cycle 3, CT revealed an increase in the number and size of mass in the lung. Chemotherapy was associated with adverse effects such as lethargy, anorexia, leukopenia, and hair loss. In conclusion, this case showed that a combination of carboplatin and cyclophosphamide suppressed the development of new neoplasms as well as metastasis for a certain period of time but did not improve the survival time. Although more cases are required, this chemotherapeutic procedure remains challenging.

• Brain Tumor Research and Treatment
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• v.6 no.2
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• pp.54-59
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• 2018

Background Leptomeningeal metastasis (LM) is an uncommon, but devastating complication of advanced cancer and has no standard treatment. Herein, we analyzed the clinical characteristics and outcomes of patients with solid tumors who were diagnosed with LM. Methods Between January 2007 and December 2017, we retrospectively analyzed the medical records of patients with solid tumors who were diagnosed with LM. Results A total of 58 patients were enrolled in this study. The median age of patients was 51 years (range, 27-72 years), and 62.1% had a poor Eastern Cooperative Oncology Group (ECOG) performance status (PS) (>2). The common types of primary tumor were breast cancer (39.7%), gastric cancer (25.9%), and non-small cell lung cancer (20.7%). Forty-two patients (72.4%) were diagnosed with LM by MRI of the brain and/or spine and cerebrospinal fluid (CSF) analysis, 14 were diagnosed by CSF analysis alone, and 2 were diagnosed by MRI alone. Treatments for LM were performed in 53 patients (91.4%), and best supportive care was provided for 5 patients (8.6%). Intrathecal chemotherapy, radiotherapy, and systemic chemotherapy were administered in 43 (74.1%), 17 (29.3%), and 24 (41.4%) patients, respectively. The median overall survival of the entire cohort was 2.4 months (95% confidence interval, 1.0-3.7). In the analysis of prognostic factors for survival, a good ECOG PS (${\leq}2$), administration of systemic chemotherapy after LM diagnosis, and a prior history of brain radiation were associated with prolonged survival. Conclusion Although the prognosis of LM in patients with solid tumors is poor, systemic chemotherapy might improve survival in selected patients with a good PS.

• The Journal of Internal Korean Medicine
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• v.43 no.4
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• pp.751-760
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• 2022

Objective: To show a decrease in tumor recurrence and improvement in quality of life in patients with recurrent cervical cancer. Method: A 58-year-old female patient diagnosed with recurrent cervical cancer in February 2021 was treated for 14 months with integrative cancer treatment (ICT) to decrease the tumor size and improve chemotherapy-induced peripheral neuropathy (CIPN) and nausea. The patient underwent chemotherapy or concomitant chemoradiation therapy (CCRT) with ICT. Radiologic outcomes were assessed by abdomen & pelvis computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography-computed tomography (PET-CT) based on the Response Evaluation Criteria in Solid Tumors (RECIST) protocol. Clinical outcomes were assessed by the National Cancer Institute Common Terminology Criteria for Adverse Event (NCI-CTCAE), Eastern Cooperative Oncology Group (ECOG), and a numeric rating scale (NRS). Result: During the 14 months of treatment, the size and metabolic activity of the recurrent tumor decreased and underwent partial remission based on RECIST. The NRS scores for CIPN and nausea were improved, and the ECOG score improved from grade 2 to 1. No serious side effects of grade 3 or higher were noted on the NCI-CTCAE test. Conclusion: This case suggests that ICT may have a synergetic effect with chemotherapy or radiotherapy for recurrent cervical cancer.

• The Journal of Internal Korean Medicine
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• v.44 no.3
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• pp.594-601
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• 2023

Objective: To demonstrate an improvement in metastatic cancer pain and a decrease in tumor size in a patient with non-small cell lung cancer. Method: A 53-year-old female patient diagnosed with metastatic non-small cell lung cancer in August 2022 underwent integrative cancer treatment (ICT) for two months to decrease the tumor size and improve back pain from bone metastasis. The patient underwent chemotherapy with ICT. Radiologic outcomes were assessed by chest, abdomen, and pelvis computed tomography based on the Response Evaluation Criteria in Solid Tumors (RECIST) protocol. Clinical outcomes were assessed using National Cancer Institute Common Terminology Criteria for Adverse Event (NCI-CTCAE), Eastern Cooperative Oncology Group (ECOG), and a numeric rating scale (NRS). Result: During the two months of treatment, the NRS scores for back pain were improved, and the ECOG score improved from grade 2 to 1. The size and metabolic activity of the primary lung tumor decreased and underwent partial remission based on RECIST. No serious side effects of grade 3 or higher were noted on the NCI-CTCAE test. Conclusion: This case suggests that ICT may have a therapeutic effect for cancer pain and a synergetic effect with chemotherapy for metastatic non-small cell lung cancer.

• Journal of Digestive Cancer Research
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• v.4 no.1
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• pp.1-9
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• 2016

The abundance of multi-drug resistance ATPase binding cassette and deranged self-renewal pathways shown in cancer stem cells (CSCs) played a crucial role in tumorigenesis, tumor resistance, tumor recurrence, and tumor metastasis. Therefore, elucidation of CSCs biology can improve diagnosis, enable targeted treatment, and guide the follow up of GI cancer patients. In order to achieve chemoquiescence, seizing cancer through complete ablation of CSCs, CSCs are rational targets for the design of interventions that will enhance responsiveness to traditional therapeutic strategies and contribute in the prevention of local recurrence as well as metastasis. However, current cancer treatment strategies fail to either detect or differentiate the CSCs from their non-tumorigenic progenies mostly due to the absence of specific biomarkers and potent agents to kill CSCs. Recent advances in knowledge of CSCs enable to produce several candidates to ablate CSCs in gastrointestinal (GI) cancers, especially cancers originated from inflammation-driven mutagenesis such as Barrett's esophagus (BE), Helicobacter pylori-associated gastric cancer, and colitis-associated cancer (CAC). Our research teams elucidated through revisiting old drugs that proton pump inhibitor (PPI) and potassium competitive acid blocker (p-CAB) beyond authentic acid suppression, chloroquine for autophage inhibition, sonic hedgehog (SHH) inhibitors, and Wnt/β-catenin/NOTCH inhibitor can ablate CSCs specifically and efficiently. Furthermore, nanoformulations of these molecules could provide an additional advantage for more selective targeting of the pathways existing in CSCs just like current molecular targeted therapeutics and sustained action, while normal stem cells intact. In this review article, the novel approach specifically to ablate CSCs existing in GI cancers will be introduced with the introduction of explored mode of action.