• Biomolecules & Therapeutics
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• v.22 no.6
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• pp.540-546
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• 2014

The high mortality rates associated with cancer reflect the metastatic spread of tumor cells from the site of their origin. Metastasis, in fact, is the cause of 90% of cancer deaths. Therefore, considerable effort is being made to inhibit metastasis. In the present study, we screened ketotifen for anti-migratory and anti-invasive activities against MDA-MB-231 breast cancer and HT-1080 fibrosarcoma cancer cells. Cancer cell migration and invasion were measured using multi-well chambers. Additionally, western blots were used to examine the effects of ketotifen on the expressions of CDC42, Rho, Rac, and matrix metalloproteinase 9 (MMP-9). The results showed that ketotifen dose-dependently suppressed the migration and invasion of MDA-MB-231 and HT-1080 cells. Ketotifen also suppressed the expressions of CDC42, Rac, and Rho, which, significantly, are involved in MDA-MB-231 and HT-1080 cancer cell migration. Moreover, ketotifen suppressed the expression and activity of MMP-9, which is involved in degradation of the extracellular matrix leading to invasion. The overall data suggested that ketotifen suppresses the migration and invasion of MDA-MB-231 and HT-1080 cancer cells via inhibition of CDC42, Rac, Rho, and MMP-9 expression.

• Journal of the Korean Society of Radiology
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• v.82 no.2
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• pp.423-428
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• 2021

Progressive transformation of germinal centers (PTGC) is a rarely diagnosed, benign disease of the lymph nodes that commonly manifests as chronic lymphadenopathy. PTGC may be characterized by single or multiple non-tender lymph nodes, and it commonly involves the cervical, axillary, and inguinal areas. Although PTGC is identified with concurrent lymphoma in some patients, it is not considered as a premalignant entity. Histopathologic diagnosis of PTGC is rarely made, and imaging findings have been reported in very few studies. We present a case of PTGC that occurred at the contralateral axillary lymph nodes and mimicked metastatic lymphadenopathy after breast cancer surgery. We also discuss its imaging findings.

• Journal of Applied Biological Chemistry
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• v.58 no.3
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• pp.219-226
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• 2015

The anticancer activity of a methanolic extract from lemon leaves (MLL) was assessed in MCF-7-SC human breast cancer stem cells. MLL induced apoptosis in MCF-7-SC, as evidenced by increased apoptotic body formation, sub-G1 cell population, annexin V-positive cells, Bax/Bcl-2 ratio, as well as proteolytic activation of caspase-9 and caspase-3, and degradation of poly (ADP-ribose) polymerase (PARP) protein. Concomitantly, MLL induced the formation of acidic vesicular organelles, increased LC3-II accumulation, and reduced the activation of Akt, mTOR, and p70S6K, suggesting that MLL initiates an autophagic progression in MCF-7-SC via the Akt/mTOR pathway. Epithelial-mesenchymal transition (EMT), a critical step in the acquisition of the metastatic state, is an attractive target for therapeutic interventions directed against tumor metastasis. At low concentrations, MLL induced anti-metastatic effects on MCF-7-SC by inhibiting the EMT process. Exposure to MLL also led to an increase in the epithelial marker E-cadherin, but decreased protein levels of the mesenchymal markers Snail and Slug. Collectively, this study provides evidence that lemon leaves possess cytotoxicity and anti-metastatic properties. Therefore, MLL may prove to be beneficial as a medicinal plant for alternative novel anticancer drugs and nutraceutical products.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.27 no.6
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• pp.483-490
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• 2001

There were many controversies in the cause and progress of tumorigenesis. Recently, studies on the mutation of genes related to the tumor have extensively been performed due to development of molecular biology. Structural and morphological changes of chromosomes, which are related to the abnormal activation of oncogenes or inactivation of tumor suppression genes, transform the normal cells into the tumor cells. p53 and Rb are well known tumor suppressor genes, while oncogenes include c-myc, bcl-2 and ras, etc. When exposed to cell damaging agents, p53 inhibits cell growth by inducing transcription of p21. Especially p73, which is homo-logy of p53, frequently deleted in melanoma, neuroblastoma, colon cancer, and breast cancer, when over produced, p73 activates the transcription of p21, bax-1 and inhibits cell growth by inducing apoptosis. For study on mRNA expression of p21 and p73, normal oral keratinocytes, and cell lines of primary and metastatic oral squamous cell carcinoma were cultured and then electrophoresis and RT-PCR(reverse transcription-polymerase chain reaction) were performed. 1. The mRNA of p21 and p73 in normal oral keratinocyte expressed lower than that of primary squamous cell carcinoma. 2. The mRNA of p21 in metastatic oral squamous carcinoma cell lines was expressed as various patterns compared with that of normal oral keratinocyte. 3. In the metastatic oral squamous cell lines, the mRNA of HN8 expressed higher than that of HN12 or HN19. 4. The mRNA of p73 in primary oral squamous cell lines expressed 4-5 times higher than that of normal keratinocyte. 5. In metastatic oral squamous cell lines, there was no significant expression of p73 mRNA compared with that of normal oral keratinocyte. From the results obtained in this study, mRNA expression of p73 in primary oral squamous cell lines was remarkable, while mRNA expression of p21 and p73 in metastatic oral squamous cell lines were statistically insignificant.

• The Korean Journal of Nuclear Medicine
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• v.34 no.3
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• pp.234-242
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• 2000

Purpose: Tc-99m MIBI scintimammography has been validated as an useful non-invasive diagnostic tool for the primary breast cancer. But most studies have included small population of patients. We have experienced a large study population and investigated the diagnostic usefulness of Tc-99m MIBI scintimammography in detection of primary breast cancer and axillary lymph node metastasis. Materials and Methods: This study included 305 patients who underwent scintimammogtaphy for palpable breast masses or abnormal radiologic findings. Tc-99m MIBI scintimammography was performed 10 minutes after intravenous injection of 925 MBq of Tc-99m MIBI. If the early image revealed abnormal finding, 3 hour delayed image was also acquired. We calculated early and delayed lesion to non-lesion ratios (L/N). The pathologic diagnosis was obtained from surgical operation or FNAB and compared with the results of Tc-99m MIBI scintimammography. Results: Malignant breast diseases were 155 and benign ones were 150. Tc-99m MIBI scintimammography revealed 132 true positive, 23 false negative, 10 false positive, and 140 true negative cases. The sensitivity, specificity, positive predictive value and negative predictive value for the primary breast cancer detection were 85.2%, 93.4%, 92.9%, and 85.9%, respectively. The sensitivity, specificity, positive predictive and negative predictive values of Tc-99m MIBI scintimammography in detecting metastatic axillary lymph node involvement were 22%, 90.4%, 61.9% and 62.3%, respectively. Early L/N of malignant breast disease was significantly higher than that of benign one ($2.44{\pm}0.97\;vs\;1.94{\pm}0.78$, p=0.01). Delayed L/N had no significant difference between malignant and benign breast diseases ($1.94{\pm}0.52\;vs\;1.91{\pm}0.73$, p=0.43). Conclusion: Our study revealed that Tc-99m MIBI scintimammography was an useful diagnostic tool for the diagnosis of breast cancer. And early L/N ratio might provide complementary role in the detection of breast cancer. But the Tc-99m MIBI scintimammography had limited value in the detection of small breast cancer (less than 1 cm) and axillary lymph node metastasis.

• The Korean Journal of Pain
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• v.10 no.1
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• pp.117-120
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• 1997

Cancer is a devastating disease, and the treatment of related pain is an extremely challenging task. Providing adequate analgesia while avoiding unnecessary drug effects often requires a polypharmacologic approach in cancer pain management. A 36-year old woman with breast cancer metastatic to the axial skeleton and bilateral hip joints was admitted to hemato-oncology service with complaints of intractable abdominal and hip pain. Despite rapidly increasing doses of intravenous morphine up to 350 mg per day; transdermal fentanyl; midazolam; ketorolac; lorazepam; dexamethasone, the patient continued to describe her pain as 10 of 10, refusing all surgical/diagnostic interventions not directly related to pain control. She did, however, consent to lumbar epidural catheter placement. The patient was sedated with titrating doses of propofol to assist with positioning. Even though the procedure was not successful due to significant thoracolumbar scoliosis, the patient admitted feeling better than she has in months during attempted placement. After continuous infusion of propofol was initiated at subhypnotic dose, the patient's analgesic demand was drastically reduced and described her pain as "1 to 3" of "10". Approximately 96 hours after the propofol infusion was started, the patient expired comfortably. There had been no change in her medical regimen during fecal 48 hours. In the case described, propofol was extremely advantageous as an adjuvant in the management of cancer related pain.

• Journal of Biomedical Engineering Research
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• v.30 no.5
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• pp.444-451
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• 2009

Purpose: The aim of present study is to detect longitudinal alterations of mechanical characteristic determined by bone quality (microarchitecture and degree of mineralization) on femur trabecular bone due to metastatic bone tumor Materials and Methods: Each 6 female SD rats (12 weeks old, approximate 250g) were allocated in SHAM and TUMOR Group. W256 (Walker carcinosarcoma 256 malignant breast cancer cell) was injected into the right femur (intraosseous injection) in TUMOR Group, whereas 0.9% NaCl (saline solution) was injected in SHAM Group. The right hind limbs of all rats were scanned by in-vivo micro-CT to acquire structural parameters, bone mineral density, X-ray attenuation and bone mineralization distribution at 0 week and 4 weeks after surgery. Results: BMD, BV/TV and Tb.N of trabecular bone in TUMOR group were markedly decreased (26%, 11% and 23%) while those in SHAM group were significantly increased (34%, 48% and 11%) (p<0.05). BS/BV, Tb.Sp and SMI in TUMOR group were significantly increased (-16%, 38% and 2%) compared with those in SHAM group (-33%, 12% and -16%) (p<0.05). Additionally, bone mineralization in TUMOR group significantly decreased while those in SHAM group was significantly increased (p<0.05). Conclusion: It is identified that how much bone microarchitecture and mineralization are diminished due to the metastatic bone tumor. The results may be helpful to prediction of fracture risk by metastatic bone tumor.

• Journal of the Korean Society of Radiology
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• v.83 no.3
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• pp.620-631
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• 2022

Purpose This study aimed to investigate the diagnostic performance of features suggestive of nodal metastasis on preoperative MRI in patients with invasive breast cancer. Materials and Methods We retrospectively reviewed the preoperative breast MRI of 192 consecutive patients with surgically proven invasive breast cancer. We analyzed MRI findings of axillary lymph nodes with regard to the size, long/short ratio, cortical thickness, shape and margin of the cortex, loss of hilum, asymmetry, signal intensity (SI) on T2-weighted images (T2WI), degree of enhancement in the early phase, and enhancement kinetics. Receiver operating characteristic (ROC) analysis, chi-square test, t test, and McNemar's test were used for statistical analysis. Results Increased shorter diameter, uneven cortical shape, increased cortical thickness, loss of hilum, asymmetry, irregular cortical margin, and low SI on T2WI were significantly suggestive of metastasis. ROC analysis revealed the cutoff value for the shorter diameter and cortical thickness as 8.05 mm and 2.75 mm, respectively. Increased cortical thickness (> 2.75 mm) and uneven cortical shape showed significantly higher sensitivity than other findings in McNemar's test. Irregular cortical margins showed the highest specificity (100%). Conclusion Cortical thickness > 2.75 mm and uneven cortical shape are more sensitive parameters than other findings, and an irregular cortical margin is the most specific parameter for predicting axillary metastasis in patients with invasive breast cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.43-45
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• 2013

Background: The aim of this epidemiological study was to establish the laterality of breast cancer (BC) and its association with size, receptor status of the primary tumor and bone metastasis (BM) in a local population. Materials and Methods: This retrospective study included cases of BC from Jan-2009 to Dec-2011 who were referred for metastatic work up or follow up survey with Technetium-99m MDP bone scan (BS) to the Nuclear Medicine Department of Karachi Institute of Radiotherapy and Nuclear Medicine (KIRAN). A total of 384 patients out of 521 were included and all reviewed for age, primary tumor size (PTS), laterality, receptor status like estrogen receptor (ER) progesterone receptor (PR) and Her-2-Neu receptor, presence or absence of BM with sites of involvement and time interval between diagnosis of BC and appearance of BM. Results: The left to right sided BC proportion was significantly higher than unity (59%:41%; p<0.001). The right sided BC was observed in younger age group (46:52 years; p<0.0001) and with a smaller PTS than the left sided (3.43:4.15 cm; p<0.0001). The patients with BM had relatively higher negative receptor status with a significant predominance of right sided BC. The overall incidence of BM on BS was 28% and relatively higher in right than left breast (33%:24% p=0.068). The average number of BM sites was also significantly greater for the right side (6:4, P<0.0001). The % cumulative risk of BM in right breast was noted at significantly smaller PTS than left side with log rank value of 5.579; p<0.05. The Kaplan Meier survival plot for event free survival of BM in left sided BC was significantly higher than for the right side (log rank value=4.155, p<0.05), with an earlier appearance of BM in right BC. Conclusions: 1) A left sided predominance of BC was seen in local population; 2) right sided BC had a more aggressive behavior with extensive and earlier appearance of BM at relatively younger age, smaller PTS and receptor (s) negativity.

• Natural Product Sciences
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• v.28 no.3
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• pp.115-120
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• 2022

Ten compounds, consisting of neoflavonoids (1-5), isoflavonoids (6 and 7), flavanone (8), and chalcones (9 and 10) were isolated from the ethyl acetate and n-butanol-soluble fractions of the heartwood of Dalbergia melanoxylon. The chemical structures were identified on the basis of spectroscopic evidence and compared to previously reported spectra. Compounds 1-10 were evaluated for cytotoxicity against HCT116 human colorectal cancer, MDA-MB-231 human metastatic breast cancer, and A2058 human melanoma cell lines. Among them, compounds 3 and 10 showed the strongest cytotoxic activity with IC₅₀ values of 11.92±1.07 μM, 10.83±1.02 μM, and 14.37±1.02 μM, 13.62±1.09 μM against HCT116 and MDA-MB-231 cell lines, respectively. Compounds 9 and 10 also had cytotoxic activity with IC₅₀ values of 13.49±1.18 μM and 9.82±0.91 μM against A2058 cell lines, respectively. To the best our knowledge, compounds 2 and 5-10 were isolated from this source for the first time.