• The Korean Journal of Physiology and Pharmacology
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• v.23 no.5
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• pp.393-402
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• 2019

Aurora kinases inhibitors, including ZM447439 (ZM), which suppress cell division, have attracted a great deal of attention as potential novel anti-cancer drugs. Several recent studies have confirmed the anti-cancer effects of ZM in various cancer cell lines. However, there have been no studies regarding the cardiac safety of this agent. We performed several cytotoxicity, invasion and migration assays to examine the anti-cancer effects of ZM. To evaluate the potential effects of ZM on cardiac repolarisation, whole-cell patch-clamp experiments were performed with human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and cells with heterogeneous cardiac ion channel expression. We also conducted a contractility assay with rat ventricular myocytes to determine the effects of ZM on myocardial contraction and/or relaxation. In tests to determine in vitro efficacy, ZM inhibited the proliferation of A549, H1299 (lung cancer), MCF-7 (breast cancer) and HepG2 (hepatoma) cell lines with $IC_{50}$ in the submicromolar range, and attenuated the invasive and metastatic capacity of A549 cells. In cardiac toxicity testing, ZM did not significantly affect $I_{Na}$, $I_{Ks}$ or $I_{K1}$, but decreased $I_{hERG}$ in a dose-dependent manner ($IC_{50}$: $6.53{\mu}M$). In action potential (AP) assay using hiPSC-CMs, ZM did not induce any changes in AP parameters up to $3{\mu}M$, but it at $10{\mu}M$ induced prolongation of AP duration. In summary, ZM showed potent broad-spectrum anti-tumor activity, but relatively low levels of cardiac side effects compared to the effective doses to tumor. Therefore, ZM has a potential to be a candidate as an anti-cancer with low cardiac toxicity.

• Progress in Medical Physics
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• v.34 no.1
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• pp.10-13
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• 2023

Patients with breast cancer can be positioned with their head turned to the contra lateral side or with their head straight during the radiation therapy treatment set-up. In our hospital, patients with locally advanced breast cancer who were receiving radiation therapy have experienced swallowing difficulty after 2 weeks of irradiation. In this pilot study, the impact of head position on reducing dysphagia occurrence was dosimetrically evaluated. Patients were divided into two groups viz., HT (head turned to the contra lateral side of the breast) and HS (head straight) with 10 members in each. Treatment planning was performed, and the dosimetric parameters such as Dmin, Dmax, Dmean, V₅, V₁₀, V₂₀, V₃₀, V₄₀, and V₅₀ of both groups were extracted from the dose volume histogram (DVH) of esophagus. The target coverage in the supraclavicular fossa (SCF) region was analyzed using D₉₅ and D₉₈; moreover, the dose heterogeneity was assessed with D₂ from the DVHs. The average values of the dose volume parameters were 27.6%, 58.6%, 35.4%, 19%, 13.8%, 14.1%, 11.8%, 8.4%, and 8.1% higher in the HT group compared with those in the HS group. Furthermore, for the SCF, the mean values of D₉₈, D₉₅, and D₂ were 42.4, 47.5, and 54 Gy, respectively, in the HS group and 38.9, 45.35, and 55.5 Gy, respectively, in the HT group. This pilot study attempts to give a solution for the poor quality of life of patients after breast radiotherapy due to dysphagia. The findings confirm that the head position could play a significant role in alleviating esophageal toxicity without compromising tumor control.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4369-4371
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• 2012

Aim: Metastatic tumor of bone is the most common malignancy involving bone and is an important predictor of prognosis in advanced cancers. The prognosis depends upon the primary site of origin and the extent of disease. In current study, we present the pattern and distribution of metastatic bone disease seen in the leading cancer care center of Pakistan, Shaukat Khanum Cancer Hospital & Research Center (SKMCH & RC), Lahore. Materials & Methods: All cases of bony metastatic disease were included that presented in the Pathology Department, from Jan 2005 to July 2011. Patients of all ages and both sexes were included. Primary bone tumors, lymphomas, sarcomas and other malignancies were excluded. The data were recorded and analyzed with SPSS 16.0. Results: A total of 146 cases of metastatic bone disease were included in the study. Out of the total cases, 79 were male and 67 were female. Age range 25-82 years (median 52). Hip bone was the most frequent bone involved, with femur and vertebrae as second and third in the list. The commonest bone involved in males was vertebrae with 23 cases and in females was hip bone with 22 cases. Regarding primary site, cancers of breast, prostate and gastrointestinal tract were at the top of the list with prostate and breast being the most frequent primary sites of metastasis in males and females respectively. Conclusion: Bone metastasis is an important entity to consider in the differential diagnosis whenever a bony tumor especially carcinoma present in older age. Our data are comparable with international findings and the literature available regarding the site and distribution of skeletal metastatic lesions. A slight deviation noted was more common bony metastatic lesions with ovarian primaries in females and gastrointestinal tract cancers in males in our study.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.24
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• pp.10659-10663
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• 2015

Background: Rapamycin is an effective anti-angiogenic drug. However, the mode of its action remains unclear. Therefore, in this study, we aimed to elucidate the antitumor mechanism of rapamycin, hypothetically via apoptotic promotion, using MCF-7 breast cancer cells. Materials and Methods: MCF-7 cells were plated at a density of $1{\times}10^5$ cells/well in 6-well plates. After 24h, cells were treated with a series of concentrations of rapamycin while only adding DMEM medium with PEG for the control regiment and grown at $37^{\circ}C$, 5% $CO_2$ and 95% air for 72h. Trypan blue was used to determine the cell viability and proliferation. Untreated and rapamycin-treated MCF-7 cells were also examined for morphological changes with an inverted-phase contrast microscope. Alteration in cell morphology was ascertained, along with a stage in the cell cycle and proliferation. In addition, cytotoxicity testing was performed using normal mouse breast mammary pads. Results: Our results clearly showed that rapamycin exhibited inhibitory activity on MCF-7 cell lines. The $IC_{50}$ value of rapamycin on the MCF-7 cells was determined as $0.4{\mu}g/ml$ (p<0.05). Direct observation by inverted microscopy demonstrated that the MCF-7 cells treated with rapamycin showed characteristic features of apoptosis including cell shrinkage, vascularization and autophagy. Cells underwent early apoptosis up to 24% after 72h. Analysis of the cell cycle showed an increase in the G0G1 phase cell population and a corresponding decrease in the S and G2M phase populations, from 81.5% to 91.3% and 17.3% to 7.9%, respectively. Conclusions: This study demonstrated that rapamycin may potentially act as an anti-cancer agent via the inhibition of growth with some morphological changes of the MCF-7 cancer cells, arrest cell cycle progression at G0/G1 phase and induction of apoptosis in late stage of apoptosis. Further studies are needed to further characterize the mode of action of rapamycin as an anti-cancer agent.

• Interdisciplinary Bio Central
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• v.4 no.4
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• pp.13.1-13.6
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• 2012

The advanced glycation endproducts receptor (AGER) is a multiligand signal transduction receptor. One of its ligands, S100b molecules activates vascular smooth muscle cells and endothelial cells via its receptor, thus triggering activation of signaling cascades and generation of cytokines and proinflammatory molecules. Ubiquitin-conjugating enzyme Ubc9 is an E2 conjugating enzyme that transfers the activated small ubiquitin-related modifier to protein substrates, and thus it plays a critical role in SUR-Mylation-mediated cellular pathways. Previous studies have shown that both AGE-R and Ubc9 play roles in diverse cellular signaling pathways. However, until recently, little attention has been paid to interactions between AGE-R and Ubc9. In this study, sequence database searches allowed us to identify a potential interaction motif between AGE-R and Ubc9. The subsequent biochemical and molecular biological analysis suggested that there may be specificity in AGE-R and Ubc9 complex signaling in atherosclerosis and cancer cells in a cell-type specific manner. Although the determinant for specificity in AGE-R and Ubc9 complex signaling in cancer cells and atherosclerosis is yet to be determined, this study provides the basis to develop a specific therapeutic application of AGE-R, SURM (small ubiquitin-related modifier)-1, and Ubc9 complex activation pathways in atherosclerosis, diabetes, cancer and inflammatory diseases.

• The Journal of Internal Korean Medicine
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• v.31 no.1
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• pp.102-112
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• 2010

Objective : This study was aimed to obtain epidemiological information of cancer patients treated with Oriental medicine. Methods :The medical records of 899 cancer patients treated at the East-West Cancer Center of Dunsan Oriental Hospital from January to December 2008 were analyzed. Careful investigations were done by categorizing these patients by their sex, origin, stage, treatment duration, conventional treatment type, etc. Results : 61.7% of the patients had stage IV tumor. 53.1% of patients visited Oriental hospital for combination treatment with conventional medicine. In the tumor origin, lung cancer showed the largest proportion (21.6%). Of the two genders, lung cancer was the most frequent cause (31%) in male patients, and breast cancer in females (21.2%). In inpatients, thyroid cancer resulted in the highest percentage (24.0%). Lung, colon, stomach cancer patients were mostly in stage III or IV. Thyroid cancer patients were mostly in stage I. Conclusions : This study presented the characteristics of cancer patients treated by Oriental medicine. Based on this study, further advanced study of Oriental medical cancer treatments is needed.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7819-7824
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• 2015

Purpose: To subtype breast cancer (BC) in Saudi women according to the recent molecular classification and to correlate these subtypes with available clinicopathological parameters. Materials and Methods: Estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor (Her2/neu) immunostaining was semi-quantitatively assessed to define molecular subtypes of luminal A and B, HER-2 and triple negative (basal-like) in BC paraffin embedded sections from 115 Saudi female patients diagnosed between 2005 to 2015 at the Department of Pathology, King Fahd Hospital, Almadinah, Saudi Arabia. Results: The most common subtypes were luminal A (47%), followed by luminal B (27.8%) and basal like subtypes (18.3%), whereas HER-2 was the least common subtype (6.9%). Luminal A was predominantly found in the old age group, with low tumor grade (p<0.001) and small tumor size, whereas HER-2 and basal-like subtypes were significantly associated with young age, high tumor grade, lymph node metastasis and lymphovascular invasion (p<0.03, 0.004, 0.05 and 0.04 respectively). All subtypes showed advanced clinical stage at the time of presentation. Conclusions: Molecular subtypes of Saudi BC patients in Almadinah region are consistent with most of the worldwide subtyping. The biological behaviour of each molecular subtype could be expected based on its characteristic clinicopathological features. Along with other prognostic indicators, molecular subtyping would be helpful in predicting prognosis and management of our BC patients. We recommend screening and early diagnosis of BC in our population.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.9033-9038
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• 2014

Background: The purpose of this study was to assess the feasibility of deep inspiration breath-hold (DIBH) based volumetric modulated arc therapy (VMAT) for locally advanced left sided breast cancer patients undergoing radical mastectomy. DIBH immobilizes the tumor bed providing dosimetric benefits over free breathing (FB). Materials and Methods: Ten left sided post mastectomy patients were immobilized in a supine position with both the arms lifted above the head on a hemi-body vaclock. Two thermoplastic masks were prepared for each patient, one for normal free breathing and a second made with breath-hold to maintain reproducibility. DIBH CT scans were performed in the prospective mode of the Varian real time position management (RPM) system. The planning target volume (PTV) included the left chest wall and supraclavicular nodes and PTV prescription dose was 5000cGy in 25 fractions. DIBH-3DCRT planning was performed with the single iso-centre technique using a 6MV photon beam and the field-in-field technique. VMAT plans for FB and DIBH contained two partial arcs ($179^{\circ}-300^{\circ}CCW/CW$). Dose volume histograms of PTV and OAR's were analyzed for DIBH-VMAT, FB-VMAT and DIBH-3DCRT. In DIBH mode daily orthogonal ($0^{\circ}$ and $90^{\circ}$) KV images were taken to determine the setup variability and weekly twice CBCT to verify gating threshold level reproducibility. Results: DIBH-VMAT reduced the lung and heart dose compared to FB-VMAT, while maintaining similar PTV coverage. The mean heart $V_{30Gy}$ was $2.3%{\pm}2.7$, $5.1%{\pm}3.2$ and $3.3%{\pm}7.2$ and for left lung $V_{20Gy}$ was $18.57%{\pm}2.9$, $21.7%{\pm}3.9$ and $23.5%{\pm}5.1$ for DIBH-VMAT, FB-VMAT and DIBH-3DCRT respectively. Conclusions: DIBH-VMAT significantly reduced the heart and lung dose for left side chest wall patients compared to FB-VMAT. PTV conformity index, homogeneity index, ipsilateral lung dose and heart dose were better for DIBH-VMAT compared to DIBH-3DCRT. However, contralateral lung and breast volumes exposed to low doses were increased with DIBH-VMAT.

• Journal of Korean Traditional Oncology
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• v.26 no.1
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• pp.17-27
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• 2021

Objective: This study aimed to evaluate which information of cancer patients should be collected for the Korean medicine cancer registry in order to assess the efficacy and safety of Korean medicine (KM) treatment and to identify Korean medical prognostic predictors. Methods: A total of fifteen Korean medical specialists completed an online survey questionnaire including items about general characteristics of cancer patients and clinical practice patterns. Results: The four main types of cancer at Korean medical hospitals were breast, lung, stomach, and colorectal cancer. The majority of patients with cancer at Korean medical hospitals were in the advanced or metastatic stage (50.0%). The prominent purposes of KM treatment were to alleviate cancer-related symptoms, reduce the side effects of conventional therapy, and improve quality of life. The major options for treatment were traditional herbal medicine (THM), acupuncture, moxibustion, thermotherapy, pharmacoacupuncture, and meditation, with THM being the most frequently used (35.7%). Almost all Korean medical specialists (93.9%) used syndrome differentiation in clinical practice and identified over half the cancer patients as deficiency syndrome (57.2%). Conclusion: Physicians considered the primary goal of KM treatment for cancer patients to be symptom management since advanced or metastatic stage patients were the majority at Korean medical hospitals. THM were the most common treatment option and syndrome differentiation was used by almost all physicians. Further research is needed to monitor and ensure optimal KM treatment for patients with cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.4119-4123
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• 2012

Background: Neoadjuvant systemic chemotherapy is the accepted approach for women with locally advanced breast cancer. Anthracycline- and taxane-based regimens have been extensively studied in clinical trials and consequently are widely used. In this study aimed to research the complete response (pCR) rates in different regimens for neoadjuvant setting and determine associated clinical and biological factors. Methods: This study included 63 patients diagnosed with breast carcinoma among 95 patients that had been treated with neoadjuvant chemotherapy between 2007 and 2010. TNM staging system was used for staging. The histologic response to neoadjuvant chemotherapy was characterized as a pCR when there was no evidence of residual invasive tumor in the breast or axillary lymph nodes. Biologic subclassification using estrogen receptor (ER), progesterone receptor (PR), HER2 were performed. Luminal A was defined as ER+, PR+, HER2-; Luminal B tumor was defined as ER+, PR-, HER2-; ER+, PR-, HER2+; ER-, PR+, HER2-; ER+, PR+, HER2+; HER2 like tumor ER-, PR+, HER2+; and triple negative tumor ER, PR, HER2 negative. Results: Patients median age was 54.14 (min-max: 30-75). Thirty-two patients (50.8%) were premenapousal and 31 (49.2%) were postmenapousal. Staging was performed postoperatively based on the pathology report and appropriated imaging modalities The TNM (tumor, lymph node, metastasis) system was used for clinical and pathological staging. Fifty-seven (90.5%) were invasive ductal carcinomas, 6 (9.5%) were other subtypes. Thirty nine (61.9%) were grade II and 24 (38.1%) were grade III. Seven (11.1%) patients were stage II and 56 (88.9) patients were stage III. The patients were classified for ER, PR receptor and HER2 positivity. Seventeen patients had complete response to chemotherapy. Forty patients (63.5%) were treated with dose dense regimen (cyclophosphamide 600 mg/m2 and doxorubicine 60 mg/m every two weeks than paclitaxel 175 mg/m2 every two weeks with filgrastim support) 40 patients (48%) were treated anthracycline and taxane containing regimens. Thirteen patients (76%) from 17 patients with pCR were treated with the dose dense regimen but without statistical significance (p=0.06). pCR was higher in HER2(-), ER(-), grade III, premenopausal patients. Conclusion: pCR rate was higher in the group that treated with dose dense regimen, which should thus be the selected regimen in neoadjuvant setting. Some other factors can predict pCR in Turkish patients, like grade, menopausal status, triple negativity, percentage of ER positivity, and HER2 expression.