• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6359-6364
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• 2015

Background: Preclinical studies have shown that the combination of an aromatase inhibitor (AI) and capecitabine in estrogen receptor (ER)- positive cell lines enhance antitumor efficacy. This retrospective analysis of a group of patients with metastatic breast cancer (MBC) evaluated the efficacy and safety of combined AI with capecitabine. Materials and Methods: Patients with hormone receptor-positive metastatic breast cancer treated between 1st January 2005 and 31st December 2010 with a combination of capecitabine and AI were evaluated and outcomes were compared with those of women treated with capecitabine in conventional dose or AI as a monotherapy. Results: Of 72 patients evaluated, 31 received the combination treatment, 22 AI and 19 capecitabine. The combination was used in 20 patients as first-line and 11 as second-line treatment. Mean age was 46.2 years with a range of 28-72 years. At the time of progression, 97% had a performance status of <2 and 55% had visceral disease. No significant difference was observed between the three groups according to clinical and pathological features. Mean follow up was 38 months with a range of 16-66 months. The median PFS of first-line treatment was significantly better for the combination (PFS 21 months vs 8.0 months for capecitabine and 15.0 months for AI). For second-line treatment, the PFS was longer in the combination compared with capecitabine and Al groups (18 months vs. 5.0 months vs. 11.0 months, respectively). Median 2 year and 5 year survival did not show any significant differences among combination and monotherapy groups. The most common adverse events for the combination group were grade 1 and 2 hand-for syndrome (69%), grade 1 fatigue (64%) and grade 1 diarrhoea (29%). Three grade 3 hand-foot syndrome events were reported. Conclusions: Combination treatment with capecitabine and AI used as a first line or second line treatment was safe with much lowered toxicity. Prospective randomized clinical trials should evaluate the use of combination therapy in advanced breast cancer to confirm these findings.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.19
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• pp.8371-8376
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• 2014

Background: The use of statistical methods has become an imperative tool in breast cancer survival data analysis. The purpose of this study was to develop the best statistical probability model using the Bayesian method to predict future survival times for the black non-Hispanic female breast cancer patients diagnosed during 1973-2009 in the U.S. Materials and Methods: We used a stratified random sample of black non-Hispanic female breast cancer patient data from the Surveillance Epidemiology and End Results (SEER) database. Survival analysis was performed using Kaplan-Meier and Cox proportional regression methods. Four advanced types of statistical models, Exponentiated Exponential (EE), Beta Generalized Exponential (BGE), Exponentiated Weibull (EW), and Beta Inverse Weibull (BIW) were utilized for data analysis. The statistical model building criteria, Akaike Information Criteria (AIC), Bayesian Information Criteria (BIC), and Deviance Information Criteria (DIC) were used to measure the goodness of fit tests. Furthermore, we used the Bayesian approach to obtain the predictive survival inferences from the best-fit data based on the exponentiated Weibull model. Results: We identified the highest number of black non-Hispanic female breast cancer patients in Michigan and the lowest in Hawaii. The mean (SD), of age at diagnosis (years) was 58.3 (14.43). The mean (SD), of survival time (months) for black non-Hispanic females was 66.8 (30.20). Non-Hispanic blacks had a significantly increased risk of death compared to Black Hispanics (Hazard ratio: 1.96, 95%CI: 1.51-2.54). Compared to other statistical probability models, we found that the exponentiated Weibull model better fits for the survival times. By making use of the Bayesian method predictive inferences for future survival times were obtained. Conclusions: These findings will be of great significance in determining appropriate treatment plans and health-care cost allocation. Furthermore, the same approach should contribute to build future predictive models for any health related diseases.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.6963-6966
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• 2015

Background: During the past few years, Hesa-A, a herbal-marine mixture, has been used to treat cancer as an alternative medicine in Iran. Based on a series of studies, it is speculated that Hesa-A possesses special cytotoxic effects on invasive tumors. To test this hypothesis, we investigated the selective anticancer effects of Hesa-A on several cancer cell lines with different metastatic potential. Materials and Methods: Hesa-A was prepared in normal saline as a stock solution of 10 mg/ml and further diluted to final concentrations of $100{\mu}/ml$, $200{\mu}g/ml$, $300{\mu}g/ml$ and $400{\mu}g/ml$. MTT-based cytotoxicity assays were performed with A549 (lung non small cancer), MCF-7 (breast adenocarcinoma), SKOV3 (ovarian cancer), and PC-3 (prostate adenocarcinoma) cells. Results: All treated cancer cells showed significant (P<0.01) or very significant (P<0.0001) differences in comparison to negative control at almost all of the tested doses ($100-400{\mu}g/ml$). At the lower dose ($100{\mu}g/ml$), Hesa-A reduced cell viability to 66%, 45.3%, 35.5%, 33.2% in SKOV3, A549, PC-3 and MCF-7 cells, respectively. Moreover, at the highest dose ($400{\mu}g/ml$), Hesa-A resulted in 88.5%, 86.6%, 84.9% and 79.3% growth inhibition in A549, MCF-7, PC-3 and SKOV3 cells, respectively. Conclusions: Hesa-A exert potent cytotoxic effects on different human cancer cells, especially those with a high metastatic potential.

• Korean Journal of Radiology
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• v.22 no.5
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• pp.677-687
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• 2021

Microvascular ultrasound (US) techniques are advanced Doppler techniques that provide high sensitivity and spatial resolution for detailed visualization of low-flow vessels. Microvascular US imaging can be applied to breast lesion evaluation with or without US contrast agents. Microvascular US imaging without a contrast agent uses a sophisticated wall filtering system to selectively obtain low-flow Doppler signals from overlapped artifacts. Microvascular US imaging with second-generation contrast agents amplifies flow signals and makes them last longer, which facilitates hemodynamic evaluation of breast lesions. In this review article, we will introduce various microvascular US techniques, explain their clinical applications in breast cancer diagnosis and radiologic-histopathologic correlation, and provide a summary of a recent radiogenomic study using microvascular US.

• Biomolecules & Therapeutics
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• v.30 no.4
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• pp.340-347
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• 2022

Advanced or metastatic breast cancer affects multiple organs and is a leading cause of cancer-related death. Cancer metastasis is associated with epithelial-mesenchymal metastasis (EMT). However, the specific signals that induce and regulate EMT in carcinoma cells remain unclear. PRR16/Largen is a cell size regulator that is independent of mTOR and Hippo signalling pathways. However, little is known about the role PRR16 plays in the EMT process. We found that the expression of PRR16 was increased in mesenchymal breast cancer cell lines. PRR16 overexpression induced EMT in MCF7 breast cancer cells and enhances migration and invasion. To determine how PRR16 induces EMT, the binding proteins for PRR16 were screened, revealing that PRR16 binds to Abl interactor 2 (ABI2). We then investigated whether ABI2 is involved in EMT. Gene silencing of ABI2 induces EMT, leading to enhanced migration and invasion. ABI2 is a gene that codes for a protein that interacts with ABL proto-oncogene 1 (ABL1) kinase. Therefore, we investigated whether the change in ABI2 expression affected the activation of ABL1 kinase. The knockdown of ABI2 and PRR16 overexpression increased the phosphorylation of Y412 in ABL1 kinase. Our results suggest that PRR16 may be involved in EMT by binding to ABI2 and interfering with its inhibition of ABL1 kinase. This indicates that ABL1 kinase inhibitors may be potential therapeutic agents for the treatment of PRR16-related breast cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6949-6953
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• 2013

Background: Nowadays, the encapsulation of cytotoxic chemotherapeutic agents is attracting interest as a method for drug delivery. We hypothesized that the efficiency of helenalin might be maximized by encapsulation in ${\beta}$-cyclodextrin nanoparticles. Helenalin, with a hydrophobic structure obtained from flowers of Arnica chamissonis and Arnica Montana, has anti-cancer and anti-inflammatory activity but low water solubility and bioavailability. ${\beta}$-Cyclodextrin (${\beta}$-CD) is a cyclic oligosaccharide comprising seven D-glucopyranoside units, linked through 1,4-glycosidic bonds. Materials and Methods: To test our hypothesis, we prepared ${\beta}$-cyclodextrin-helenalin complexes to determine their inhibitory effects on telomerase gene expression by real-time polymerase chain reaction (q-PCR) and cytotoxic effects by colorimetric cell viability (MTT) assay. Results: MTT assay showed that not only ${\beta}$-cyclodextrin has no cytotoxic effect on its own but also it demonstrated that ${\beta}$-cyclodextrin-helenalin complexes inhibited the growth of the T47D breast cancer cell line in a time and dose-dependent manner. Our q-PCR results showed that the expression of telomerase gene was effectively reduced as the concentration of ${\beta}$-cyclodextrin-helenalin complexes increased. Conclusions: ${\beta}$-Cyclodextrin-helenalin complexes exerted cytotoxic effects on T47D cells through down-regulation of telomerase expression and by enhancing Helenalin uptake by cells. Therefore, ${\beta}$-cyclodextrin could be superior carrier for this kind of hydrophobic agent.

• Korean Journal of Clinical Pharmacy
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• v.30 no.1
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• pp.1-10
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• 2020

Objective: The aim of the study was to perform a meta-analysis of randomized clinical trials to compare the clinical efficacy and safety between combination of cyclin-dependent kinase (CDK) 4/6 inhibitors with aromatase inhibitors (AIs) and AIs alone in patients with hormone receptor+/human epidermal growth factor receptor type2-(HR+/HER2-) advanced breast cancer. Methods: Published clinical studies were identified through electronic database searches until February 2019. Literature qualities were assessed by the Scottish Intercollegiate Guidelines Network Checklist. Key endpoints of efficacy were progression-free survival (PFS), objective response rate (ORR), and clinical benefit (CB). Endpoints of safety were adverse events (AEs) (neutropenia, leukopenia, any grade 3/4 AEs, and serious AEs) and on-treatment death. Meta-analysis was performed using the RevMan 5.3 software. Results: The selected five studies were evaluated as "good" in quality assessment. Compared to AIs alone, the combination therapy significantly improved PFS (pooled hazard ratio=0.55; 95% confidence interval (CI) 0.49-0.62), ORR (odds ratio=1.78; 95% CI=1.49-2.13), and CB (odds ratio=1.86; 95% CI=1.51-2.28). The prevalence of AEs was significantly higher in the combination group than in the AIs alone group. On-treatment death was greater in the combination group than in the AIs alone group, although insignificant. Conclusion: The combination therapy of CDK4/6 inhibitors with AIs was more effective for the treatment of HR+/HER2- advanced breast cancer, but less safe than AIs alone. The combination therapy should be effectively managed through patient monitoring, and further studies are needed to reduce AEs in the combination therapy of CDK4/6 inhibitors with AIs.

• Journal of the Korean Chemical Society
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• v.68 no.3
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• pp.151-159
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• 2024

Indian spices are well known for their numerous health benefits, flavour, taste, and colour. Recent Advancements in chemical technology have led to better extraction and identification of bioactive molecules (phytochemicals) from spices. The therapeutic effects of spices against diabetes, cardiac problems, and various cancers has been well established. The present in silico study aims to investigate the binding affinity of 29 phytochemicals from 11 Indian spices with two prominent proteins, BCL3 and CXCL10 involved in invasiveness and bone metastasis of breast cancer. The three-dimensional structures of 29 phytochemicals were extracted from PubChem database. Protein Data Bank was used to retrieve the 3D structures of BCL3 and CXCL10 proteins. The drug-likeness and other properties of compounds were analysed by ADME and Lipinski rule of five (RO5). All computational simulations were carried out using Autodock 4.0 on Windows platform. The proteins were set to be rigid and compounds were kept free to rotate. In-silico study demonstrated a strong complex formation (positive binding constants and negative binding energy ΔG) between all phytochemicals and target proteins. However, piperine and sesamolin demonstrated high binding constants with BCL3 (50.681 × 10³ mol^-1, 137.76 × 10³ mol^-1) and CXCL10 (98.71 × 10³ mol^-1, 861.7 × 10³ mol^-1), respectively. The potential of these two phytochemicals as a drug candidate was highlighted by their binding energy of -6.5 kcal mol^-1, -7.1 kcal mol^-1 with BCL3 and -6.9 kcal mol^-1, -8.2 kcal mol^-1 with CXCL10, respectively coupled with their favourable drug likeliness and pharmacokinetics properties. These findings underscore the potential of piperine and sesamolin as drug candidates for inhibiting invasiveness and regulating breast cancer metastasis. However, further validation through in vitro and in vivo studies is necessary to confirm the in silico results and evaluate their clinical potential.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.6
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• pp.2607-2612
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• 2014

Background: Cancer screening rates in Japan are much lower than those in Western countries. This study evaluated the relationship between cancer screening rates and strategies used to improve screening rates, and determined which strategy is the most effective. Materials and Methods: All municipalities are responsible for conducting gastric, lung, colorectal, cervical, and breast cancer screenings in Japan. Of the 1,746 municipalities in total, 92-99% were included in the analyses for each cancer screening. Using national data in 2009, the correlations between cancer screening rates and strategies for improving screening rates of all municipalities, both large (populations of over 30,000) and small (populations of under 30,000), were determined. The strategies used were as follows: sending personal invitation letters, personal visits by community health workers, use of a clinical setting for screening, and free screening. Results: Of all four strategies used to improve cancer screening rates, sending personal invitation letters had the highest correlations with all screening rates, with the exception of breast cancer screening. The partial correlation coefficients linking this strategy with the screening rates in all municipalities were 0.28, 0.32, 0.30, and 0.26 for gastric, lung, colorectal, and cervical cancer screening, respectively. In large municipalities, the correlations between the number of examinees in a clinical setting and the screening rates were also relatively high, particularly for cervical cancer screening (r=0.41). Conclusions: Sending personal invitation letters appears to be particularly effective in improving cancer screening rates in all municipalities. All municipalities should implement a system that sends personal invitation letters for cancer screening. In large municipalities, increasing the availability of screening in a clinical setting is also effective in improving cancer screening rates.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3767-3772
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• 2012

Objective: We estimated the total medical costs incurred during the 5 years following a cancer diagnosis and annual medical use status for the six most prevalent cancers in Korea. Methods: From January 1 to December 31, 2006, new patients registered with the six most prevalent cancers (stomach, liver, lung, breast, colon, and thyroid) were randomly selected from the Korea Central Cancer Registry, with 30% of patients being drawn from each cancer group. For the selected patients, cost data were generated using National Health Insurance claims data from the time of cancer diagnosis in 2006 to December 31, 2010. The total number of patients selected was 28,509. Five-year total medical costs by tumor site and Surveillance, Epidemiology, and End Results (SEER) stage at the time of diagnosis, and annual total medical costs from diagnosis, were estimated. All costs were calculated as per-patient net costs. Results: Mean 5-year net costs per patient varied widely, from $5,647 for thyroid cancer to $20,217 for lung cancer. Advanced stage at diagnosis was associated with a 1.8-2.5-fold higher total cost, and the total medical cost was highest during the first year following diagnosis and decreased by the third or fourth year. Conclusions: The costs of cancer care were substantial and varied by tumor site, annual phase, and stage at diagnosis. This indicates the need for increased prevention, earlier diagnosis, and new therapies that may assist in reducing medical costs.