• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.2157-2162
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• 2012

Objective: The PI3K/PTEN/AKT/mTOR signaling pathway has been implicated in resistance to cisplatin. In the current study, we determined whether common genetic variations in this pathway are associated with platinum-based chemotherapy response and clinical outcome in advanced non-small cell lung cancer (NSCLC) patients. Methods: Seven common single nucleotide polymorphisms (SNPs) in core genes of this pathway were genotyped in 199 patients and analyzed for associations with chemotherapy response, progression-free survival (PFS) and overall survival (OS). Results: Logistic regression analysis revealed an association between AKT1 rs2494752 and response to treatment. Patients carrying heterozygous AG had an increased risk of disease progression after two cycles of platinum-based chemotherapy compared to those with AA genotype (Adjusted odds ratio (OR)=2.18, 95% confidence interval (CI): 1.00-4.77, which remained significant in the stratified analyses). However, log-rank test and cox regression detected no association between these polymorphisms in the PI3K pathway genes and survival in advanced NSCLC patients. Conclusions: Our findings suggest that genetic variants in the PI3K/PTEN/AKT/mTOR pathway may predict platinum-based chemotherapy response in advanced NSCLC patients in a Chinese population.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.24
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• pp.10831-10836
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• 2015

This study was conducted to establish whether the preoperative platelet to lymphocyte ratio (PLR) is predictive of survival of women with ovarian clear cell carcinoma (OCCC). A PLR > 300 was deemed elevated. Progression-free survival (PFS) was estimated using the Kaplan-Meier method. Cox proportional hazard analysis was used to determine the independent effect of PLR. Thirty-six patients were reviewed. Elevated PLRs were more commonly noted in patients with an advanced vs an early stage of disease (88.9% vs 11.1%). Women with elevated PLR carried a higher rate of disease progression during primary therapy than that those in the normal PLR group (44.4 vs 22.2%). The median PFS for patients with elevated PLR was notably worse than that for patients with normal PLR (10 vs 34 months). Despite the impact of elevated PLR on PFS, it was found to be marginally significant when controlling for commonly applied prognostic markers. It, however, trended toward significance (HR=4.76; 95%CI, 0.95-23.8). In conclusion, an elevated PLR appears to be directly associated with adverse survival rather than being a surrogate for other indicators of a poor prognosis. PLR may be a useful biomarker for predicting survival of women with OCCC and merits further large-scale studies.

• Nutrition Research and Practice
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• v.1 no.3
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• pp.195-199
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• 2007

Inositol hexaphosphate ($IP_6$) is a major constituent of most cereals, legumes, nuts, oil seeds and soybean. Previous studies reported the anticancer effect of $IP_6$ and suggested that co-treatment of $IP_6$ with inositol may enhance anticancer effect of $IP_6$. Although the anticancer effect of $IP_6$ has been intensively studied, the combinational effect of $IP_6$ and inositol and involved mechanisms are not well understood so far. In the present study, we investigated the effect of $IP_6$ and myo-inositol (MI) on cell cycle regulation and apoptosis using PC3 prostate cancer cell lines. When cell, were co-treated with $IP_6$ and MI, the extent of cell growth inhibition was significantly increased than that by $IP_6$ alone. To identify the effect of $IP_6$ and MI on apoptosis, the activity of caspase-3 was measured. The caspase-3 activity was significantly increased when cells were treated with either $IP_6$ alone or both $IP_6$ and MI, with no significant enhancement by co-treatment. To investigate the effect of $IP_6$ and MI of cell cycle arrest, we measured p21 mRNA expression in PC3 cells and observed significant increase in p21 mRNA by $IP_6$. But synergistic regulation by co-treatment with $IP_6$ and MI was not observed. In addition, there was no significant effect by co-treatment compared to $IP_6$ treatment on the regulation of cell cycle progression although $IP_6$ significantly changed cell cycle distribution in the presence of MI or not. Therefore, these findings support that $IP_6$ has anticancer function by induction of apoptosis and regulation of cell cycle. However, synergistic effect by MI on cell cycle regulation and apoptosis was not observed in PC3 prostate cancer cells.

• Endocrinology and Metabolism
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• v.33 no.4
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• pp.473-484
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• 2018

Background: Epidemiological studies have suggested an association between Hashimoto thyroiditis (HT) and papillary thyroid cancer (PTC) development. Other studies, however, have reported a protective role of HT against PTC progression. Through this updated meta-analysis, we aimed to clarify the effects of HT on the progression of PTC. Methods: We searched citation databases, including PubMed and Embase, for relevant studies from inception to September 2017. From these studies, we calculated the pooled odds ratios (ORs) of clinicopathologic features and the relative risk (RR) of PTC recurrence with 95% confidence intervals (CIs) using the Mantel-Haenszel method. Additionally, the Higgins $I^2$ statistic was used to test for heterogeneity. Results: The meta-analysis included 71 published studies with 44,034 participants, among whom 11,132 had HT. We observed negative associations between PTC with comorbid HT and extrathyroidal extension (OR, 0.74; 95% CI, 0.68 to 0.81), lymph node metastasis (OR, 0.82; 95% CI, 0.72 to 0.94), distant metastasis (OR, 0.49; 95% CI, 0.32 to 0.76), and recurrence (RR, 0.50; 95% CI, 0.41 to 0.61). Conclusion: In this meta-analysis, PTC patients with HT appeared to exhibit more favorable clinicopathologic characteristics and a better prognosis than those without HT.

• Radiation Oncology Journal
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• v.32 no.4
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• pp.266-271
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• 2014

In the clinical state of oligometastases or oligorecurrence, a transitional state between localized and widespread systemic disease, local control of the disease may yield improved systemic control. Radiotherapy may be a good means for controlling oligometastatic tumors, particularly in very old patients for whom surgery may be infeasible. A combination of systemic therapy and local therapy is necessary to prevent systemic progression. Some kinds of cancers found in the elderly are known to be somewhat indolent for systemic progression. So, for very old patients who refuse or cannot tolerate chemotherapy, the use of radical radiotherapy alone to treat oligorecurrences may be very helpful. We successfully treated an 87-year-old patient who had been diagnosed with oligorecurrences three times over six years with radiotherapy alone. The patient is now, about four years after his first radiotherapy for liver metastasis, alive without any evidence of cancer and with fully active performance status.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.2
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• pp.479-482
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• 2012

Aim: Soy foods are the major source of isoflavones, which are believed to play important roles in genesis of breast cancer and its progression. We here conducted a prospective study to evaluate the association of soy isoflavone food consumption with breast cancer prognosis. Methods: A prospective study was performed from January 2004 and January 2006 in China. Trained interviewers conducted face-to-face interviews using a structured questionnaire to collect information on dietary habits and potential confounding factors. The relative risk [hazard ratio (HR)] and 95% CI were calculated from the Cox regression model for all significant predictors from cancer diagnosis to the endpoint of the study (event). Results: After a median follow up of 52.1 months (range, 9-60 months), a total of 79 breast cancer related deaths were recorded in our study, risk being inversely associated with a high intake of soy isoflavone. With an average intake of soy isoflavone above 17.3 mg/day, the mortality of breast cancer can be reduced by about 38-36%. We also found the decreased breast cancer death with high soy protein intake, with a HR (95% CI) of 0.71 (0.52-0.98). Stratified analysis with reference to the ER status, further demonstrated a better prognosis of ER positive breast cancer with a high intake of soy isoflavone (HR 0.59, 0.40-0.93). Conclusion: Our study shows the soy food intake is associated with longer survival and low recurrence among breast cancer patients. A cohort study with a larger sample size and long term follow-up is now needed.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.5
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• pp.2655-2660
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• 2016

Background: Prostate cancer is the second most common male cancer and remains a leading cause of cancer death worldwide. Heterogeneity regarding recurrence, tumor progression and therapeutic response reflects the inadequacy of traditional prognostic factors and underlies interest in new genetic and molecular markers. In this work, we studied the prognostic value of the expression of 9 proteins, Ki-67, p53, Bcl-2, PSA, HER2, E-cadherin, $p21^{WAF1/Cip1}$, $p27^{Kip1}$ and $p16^{ink4a}$ in prostate cancer. Materials and Methods: We conducted a retrospective study of 50 prostate cancers diagnosed in Pathology Department of Farhet Hached Hospital, Sousse, Tunisia, during a period of 12 months. Clinico-pathological data and survival were investigated. Protein expression was analyzed by immunohistochemistry on archived material. Results: Expression or over-expression of Ki-67, p53, Bcl-2, PSA, HER2, E-Cadherin, $p21^{WAF1/Cip1}$, $p27^{Kip1}$ and $p16^{ink4a}$ was observed in 68%, 24%, 32%, 78%, 12%, 90%, 20%, 44% and 56% of cases, respectively. Overall five-year survival was 68%. A statistically significant correlation was observed between death occurrence and advanced age (p=0.018), degree of tumor differentiation (p=0.0001), perineural invasion (p=0.016) and metastasis occurrence (p=0.05). Death occurrence was significantly correlated with the expression of p53 (p=0.007), Bcl-2 (p=0.02), Ki-67 (p=0.05) and $p27^{Kip1}$ (p=0.04). Conclusions: The p53, Bcl-2, Ki-67 and $p27^{Kip1}$ proteins may be useful additional prognostic markers for prostate cancer. The use of these proteins in clinical practice can improve prognosis prediction, disease screening and treatment response of prostatic cancer.

• BMB Reports
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• v.36 no.1
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• pp.78-81
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• 2003

The prevention of cancer is one of the most important public health and medical practices of the $21^{st}$ century. We have made much progress in this new emerging field, but so much remains to be accomplished before widespread use and practice become common place. Cancer chemoprevention encompasses the concepts of inhibition, reversal, and retardation of the cancer process. This process, called carcinogenesis, requires 20-40 years to reach the endpoint called invasive cancer. It typically follows multiple, diverse and complex pathways in a stochastic process of clonal evolution. These pathways appear amenable to inhibition, reversal or retardation at various points. We must therefore identify key pathways in the evolution of the cancer cell that can be exploited to prevent this carcinogenesis process. Basic research is identifying many genetic lesions and epigenetic processes associated with the progression of precancer to invasive disease. Many of these early precancerous lesions favor cell division over quiescence and protect cells against apoptosis when signals are present. Many oncogenes are active during early development and are reactivated in adulthood by aberrant gene promoting errors. Normal regulatory genes are mutated, making them insensitive to normal regulatory signals. Tumor suppressor genes are deleted or mutated rendering them inactive. Thus there is a wide range of defects in cellular machinery which can lead to evolution of the cancer phenotype. Mistakes may not have to appear in a certain order for cells to progress along the cancer pathway. To conquer this diverse disease, we must attack multiple key pathways at once for a predetermined period of time. Thus, agent combination prevention strategies are essential to decrease cancer morbidity. Furthermore, each cancer type may require custom combination of prevention strategies to be successful.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.341-346
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• 2013

The risk of cervical cancer development in women infected with HPV varies in relation to the individual host's genetic makeup. Many studies on polymorphisms as genetic factors have been aimed at analyzing associations with cervical cancer. In this study, single nucleotide polymorphisms (SNPs) in 3 genes were investigated in relation to cervical cancer progression in HPV16 infected women with lesions. Two thousand cervical specimens were typed by PCR sequencing methods for TP53 (rs1042522), p16 (rs11515 and rs3088440) and NQO1 (rs1800566). Ninety two HPV16 positive cases and thirty two normal cases were randomly selected. Analysis of TP53 (rs1042522) showed a significantly higher frequency in cancer samples (OR=1.22, 95%CI=1.004-1.481, p-value=0.016) while differences in frequency were not significant within each group (p-value=0.070). The genotype distributions of p16 (rs11515 and rs3088440) and NQO1 (rs1800566) did not show any significantly higher frequency in cancer samples (p-value=0.106, 0.675 and 0.132, respectively) or within each group (p-value=0.347, 0.939 and 0.111, respectively). The results indicated that the polymorphism in TP53 (rs1042522) might be associated with risk of cervical cancer development in HPV16 infected women. Further studies of possible mechanisms of influence on cervical cancer development would be useful to manage HPV infected patients.

• Journal of Korean Traditional Oncology
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• v.16 no.1
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• pp.33-39
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• 2011

Objective : To investigate the anti-metastasis and preventing relapses of HangAm-Plus (HAP) on pancreatic cancer patient. Methods : A 49 year old male patient diagnosed with pancreatic cancer (T3N0M0) was admitted to EWCC (East-West Cancer Center) on Jul. 21st 2008. He had operated pylorus preserving pancreatoduodenectomy (PPPD) and came to the anti-metastasis and preventing relapses on pancreatic cancer patient. The patient was treated with HangAm-Plus (HAP) (3,000 mg/day) for the period of 33 months from Jul. 21st, 2008 to Apr. 7th, 2011. Tumor markers (CEA and CA19-9) were used to evaluate the disease progression of the patient. Positron Emission Tomography (PET) and Computed Tomography (CT) were also followed up. Results : HAP treatment was well tolerated by the patient. Patient has shown 33 months of disease free survival until now. Conclusion : This case study supports HAP's potential efficacy in the anti-metastasis and preventing relapses of pancreatic cancer patient.