• Radiation Oncology Journal
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• v.25 no.4
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• pp.268-277
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• 2007

Purpose: Respiratory motion is a considerable inhibiting factor for precise treatment with stereotactic radiosurgery using the CyberKnife (CK). In this study, we developed a moving phantom to simulate three-dimensional breathing movement and investigated the distortion of dose profiles between the use of a moving phantom and a static phantom. Materials and Methods: The phantom consisted of four pieces of polyethylene; two sheets of Gafchromic film were inserted for dosimetry. Treatment was planned to deliver 30 Gy to virtual tumors of 20, 30, 40, and 50 mm diameters using 104 beams and a single center mode. A specially designed robot produced three-dimensional motion in the right-left, anterior-posterior, and craniocaudal directions of 5, 10 and 20 mm, respectively. Using the optical density of the films as a function of dose, the dose profiles of both static and moving phantoms were measured. Results: The prescribed isodose to cover the virtual tumors on the static phantom were 80% for 20 mm, 84% for 30 mm, 83% for 40 mm and 80% for 50 mm tumors. However, to compensate for the respiratory motion, the minimum isodose levels to cover the moving target were 70% for the $30{\sim}50$ mm diameter tumors and 60% for a 20 mm tumor. For the 20 mm tumor, the gaps between the isodose curves for the static and moving phantoms were 3.2, 3.3, 3.5 and 1.1 mm for the cranial, caudal, right, and left direction, respectively. In the case of the 30 mm tumor, the gaps were 3.9, 4.2, 2.8, 0 mm, respectively. In the case of the 40 mm tumor, the gaps were 4.0, 4.8, 1.1, and 0 mm, respectively. In the case of the 50 mm diameter tumor, the gaps were 3.9, 3.9, 0 and 0 mm, respectively. Conclusion: For a tumor of a 20 mm diameter, the 80% isodose curve can be planned to cover the tumor; a 60% isodose curve will have to be chosen due to the tumor motion. The gap between these 80% and 60% curves is 5 mm. In tumors with diameters of 30, 40 and 50 mm, the whole tumor will be covered if an isodose curve of about 70% is selected, equivalent of placing a respiratory margin of below 5 mm. It was confirmed that during CK treatment for a moving tumor, the range of distortion produced by motion was less than the range of motion itself.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.2
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• pp.759-765
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• 2016

Background: Breast cancer is the most frequent cancer of women in Pakistan with the majority presenting with stage III or IV lesionsat initial diagnosis. Patient and health system related factors are well known determinants of delay in presentation and diagnosis. Additionally, breast cancer being a heterogeneous disease, the various molecular subtypes featuring different aggressiveness also need to be considered. The present study evaluated the association of stage at initial diagnosis of breast cancer with these two factors in local women at a tertiary level health care facility in Lahore, Pakistan. Materials and Methods: Patient and tumor features were recorded separately during diagnostic workup in Breast Clinics at INMOL and at Services Hospital, Lahore. Data were entered in MS Excel and analyzed by descriptive statistics and Chi-Square test. Results: Among the 261 patients, 64% were staged as late breast cancer (LBC), the mean age was 46.8 with standard deviation of 13 years. Some 92% had invasive ductal carcinoma (IDC), 61% had luminal types (LT) of non-aggressive tumor while 39% had the non-luminal types (NLT) of of HER2-enriched or basal aggressive tumors. While 70% of patients presented within one year of symptomatic disease (early report group "ERG"), 30% reported after a mean delay of 4 years with a standard deviation of 3.75 years. The stage distribution among ERG patients was not statistically different from those reporting late (P=0.123). Statistically larger proportion of patients with NLT presented as LBC as compared to the LT (P =0.034). Among the ERG, statistically different stage distribution of disease was observed for the NLT versus LT (P=0.047). Among those presenting late, this difference was insignificant (P=0.416). Conclusions: Breast cancer is a distinct disease in Pakistan with a high frequency of aggressive molecular types affecting younger women, with the majority presenting as LBC. Association of NLT with higher stage at diagnosis is statistically significant whereas time delay in diagnosis is not. Further research is required to define the risk profile and features in local patients. The burden of LBC can be reduced by promoting breast health awareness and by establishing easily accessible dedicated breast care set ups in the hospitals.

• Molecular & Cellular Toxicology
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• v.3 no.3
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• pp.198-207
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• 2007

[ $^{18}F$ ]-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) scan has been found to reflect tumor aggressiveness and prognosis in various types of cancer. In this study, the gene expression profiles of glial tumors were evaluated to determine whether glial tumors with high $^{18}F$-FDG uptake have more aggressive biological potential than with low uptake. Surgical specimens were obtained from the 12 patients with glial tumors (4 males and 8 females, age range 42-68 years). The tumor samples were divided into two groups based on the $^{18}F$-FDG uptake PET scan findings: high $^{18}F$-FDG uptake (n=4) and low $^{18}F$-FDG uptake (n=8). The pathological tumor grade was closely correlated with the $^{18}F$-FDG uptake pattern: Glial tumors with high $^{18}F$-FDG uptake were pathologically Edmondson-Steiner grade III, while those with low uptake were grade II. The total RNA was extracted from the frozen tissues of all glial tumors (n=12), and adjacent non-cancerous tissue (n=3). The gene expression profiles were evaluated using cDNA microarray. The glial tumors with high $^{18}F$-FDG uptake showed increase expression of 15 genes compared to those with low uptake (P<0.005). Nine genes were down-regulated. Gene expression is closely related to cell survival, cell-to-cell adhesion or cell spreading; therefore, glial tumors with high $^{18}F$-FDG uptake appear to have more aggressive biological properties than those with low uptake.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.12
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• pp.4959-4964
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• 2015

Background: To assess the immunohistochemical expression of estrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor receptor-2 (HER2) neu receptor in breast cancer and their associations with various clinicopathological characteristics. Materials and Methods: This is a retrospective analysis of women who presented with primary, unilateral breast cancer in the Department of Medical Oncology at Rajiv Gandhi Cancer Institute and Research Centre, Delhi, India during the period from January 2008 to December 2011. Data were retrieved from the medical records of the hospital including both early and locally advanced cancer cases. ER, PgR and HER2neu expression in these patients was assessed and triple negative patients were identified. Associations of triple negative and non-triple negative groups with clinicopathological characteristics were also evaluated. Results: A total of 1,284 women (mean age 52.1 years, 41.9% premenopausal) were included in the analysis. Hormone receptor positivity (ER and/or PgR) was seen in 63.4% patients, while 23.8% of tumors were triple negative. Only 23.0% were HER2 positive. Around 10.0% of tumors were both ER and HER2 positive. ER and PgR positivity was significantly associated with negative HER2 status (p-value <0.0001). Younger age, premenopausal status, higher tumor grade, lymph node negativity, advanced cancer stage, and type of tumor were strongly associated with triple negativity. Significantly, a smaller proportion of women had ductal carcinoma in situ in the triple negative group compared with the non-triple negative group (35.6% versus 60.8%, p-value<0.01). Conclusions: The present analysis is one of the largest studies from India. The majority of the Indian breast cancer patients seen in our hospital present with ER and PgR positive tumors. The triple negative patients tended to be younger, premenopausal, and were associated with higher tumor grades, negative lymph nodes status and lower frequency of ductal carcinoma in situ.

• Radiation Oncology Journal
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• v.38 no.1
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• pp.35-43
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• 2020

Purpose: This retrospective study compares higher-dose whole-brain radiotherapy (hdWBRT) with reduced-dose WBRT (rdWBRT) in terms of clinical efficacy and toxicity profile in patients treated for primary central nervous system lymphoma (PCNSL). Materials and Methods: Radiotherapy followed by high-dose methotrexate (HD-MTX)-based chemotherapy was administered to immunocompetent patients with histologically confirmed PCNSL between 2000 and 2016. Response to chemotherapy was taken into account when prescribing the radiation dose to the whole brain and primary tumor bed. The whole brain dose was ≤23.4 Gy for rdWBRT (n = 20) and >23.4 Gy for hdWBRT (n = 68). Patients manifesting cognitive disturbance, memory impairment and dysarthria were considered to have neurotoxicity. A median follow-up was 3.62 years. Results: The 3-year overall survival (OS) and progression-free survival (PFS) were 70.0% and 48.9% with rdWBRT, and 63.2% and 43.2% with hdWBRT. The 3-year OS and PFS among patients with partial response (n = 45) after chemotherapy were 77.8% and 53.3% with rdWBRT, and 58.3% and 45.8% with hdWBRT (p > 0.05). Among patients with complete response achieved during follow-up, the 3-year freedom from neurotoxicity (FFNT) rate was 94.1% with rdWBRT and 62.4% with hdWBRT. Among patients aged ≥60 years, the 3-year FFNT rate was 87.5% with rdWBRT and 39.1% with hdWBRT (p = 0.49). Neurotoxicity was not observed after rdWBRT in patients aged below 60 years. Conclusion: rdWBRT with tumor bed boost combined with upfront HD-MTX is less neurotoxic and results in effective survival as higher-dose radiotherapy even in partial response after chemotherapy.

• Animal Bioscience
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• v.34 no.6
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• pp.1078-1087
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• 2021

Objective: Skeletal muscle satellite cells (SMSCs) are significant for the growth, regeneration, and maintenance of skeletal muscle after birth. However, currently, few studies have been performed on the isolation, culture and inducing differentiation of goose muscle satellite cells. Previous studies have shown that C1q and tumor necrosis factor-related protein 3 (CTRP3) participated in the process of muscle growth and development, but its role in the goose skeletal muscle development is not yet clear. This study aimed to isolate, culture, and identify the goose SMSCs in vitro. Additionally, to explore the function of CTRP3 in goose SMSCs. Methods: Goose SMSCs were isolated using 0.25% trypsin from leg muscle (LM) of 15 to 20 day fertilized goose eggs. Cell differentiation was induced by transferring the cells to differentiation medium with 2% horse serum and 1% penicillin streptomycin. Immunofluorescence staining of Desmin and Pax7 was used to identify goose SMSCs. Quantitative realtime polymerase chain reaction and western blot were applied to explore developmental expression profile of CTRP3 in LM and the regulation of CTRP3 on myosin heavy chains (MyHC), myogenin (MyoG) expression and Notch signaling pathway related genes expression. Results: The goose SMSCs were successfully isolated and cultured. The expression of Pax7 and Desmin were observed in the isolated cells. The expression of CTRP3 decreased significantly during leg muscle development. Overexpression of CTRP3 could enhance the expression of two myogenic differentiation marker genes, MyHC and MyoG. But knockdown of CTRP3 suppressed their expression. Furthermore, CTRP3 could repress the mRNA level of Notch signaling pathway-related genes, notch receptor 1, notch receptor 2 and hairy/enhancer-of-split related with YRPW motif 1, which previously showed a negative regulation in myoblast differentiation. Conclusion: These findings provide a useful cell model for the future research on goose muscle development and suggest that CTRP3 may play an essential role in skeletal muscle growth of goose.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4639-4643
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• 2012

The burden of lung cancer in terms of mortality is the highest among all types of cancers globally. The present study aimed to evaluate lifestyle related habits, clinico-pathological profile and treatment details of lung cancer patients who were registered at Malabar Cancer Centre (MCC), Kerala, during the calendar year 2010. A retrospective evaluation was made from medical records to gather data from 281 registered lung cancer cases in 241 males and 40 females, with a male to female ratio of 6.03: 1. Approximately 89% of the cases were above 50 years of age. Among males about 91% of the cases were smokers and 62% of them had a chronic smoking habit. Adenocarcinomas, squamous cell carcinomas, non-small cell carcinomas and small cell cancers accounted for 10.7, 13.9, 17.0 and 5.7% respectively. Out of 281 cases around 67% were diagnosed with distant metastasis and the remainder had regional lymph node involvement. However, no statistically significant difference was observed for secondary site of tumor according to gender. As majority of the cases reported at MCC were in an advanced stage of the disease, histology of the secondary site from supraclavicular lymph nodes or liver was taken for diagnosis. Initiation of population based screening for early detection of cancer, and primary and secondary prevention strategies for reducing the prevalence of tobacco consumption are high priorities to reduce the lung cancer burden in Kerala.

• Proceedings of the Korean Society of Plant Pathology Conference
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• 2003.10a
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• pp.126-126
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• 2003

Incidence of crown gall on lower stem of chrysanthemum, Chrysanthemum morifolium Ramat., was first observed at Hwasung, Gyeonggi, Korea in 2001, Tumors on the stem were 1.5-2 cm in size and semi-round with rough surface texture of dark brown color. Four strains of bacteria isolated from the tumor tissues were characterized. Their colonies were convex, glistening, circular with an entire edge, and white to tannish-cream in color on PDA plus CaCO$_3$. They were gram negative, oxidase positive, and growing on DIM agar. The bacterial isolates inducing gall formation in chrysanthemum were identified as Agrobacterium tumefaciens based on biochemical and physiological characteristics, fatty acid profile using Sherlock Microbial Identification System, and substrate utilization patterns using Biolog Identification System. Young chrysanthemum plants inoculated with the bacteria developed typical galls within two to three weeks. Seedlings of tomato and slices of carrot roots also produced typical galls two to three weeks after inoculation. This is the first report on crown gall of chrysanthemum in Korea.

• Korean Journal of Oriental Medicine
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• v.14 no.1
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• pp.145-160
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• 2008

Nelumbinis Semen(NS) has been used in traditional medicine to treat diseases such as depression and diarrhea. In inflammatory responses, microglia produces molecules which are known to play roles in the central nervous system. And we previously studied NS inhibited nitric oxide synthase and secretion of tumor necrosis factor alpha. To explore the global gene expression profiles in BV-2 microglial cell line treated with NS, microarray analysis was performed. The cells were treated with LPS or NS plus LPS for 30min, Ih, 3h, and 6h, respectively. Of 45,101 known genes, with cutoff value of 3-fold change in the expression, 340, 644, 280 and 219 genes were upregulated and 503, 570, 694 and 484 were downregulated in NS treated cells at each time point. The results of the present study shows that treatment of NS reversed the LPS-induced upregulation of such genes as Ecoxsackievirus and adenovirus receptor(CAR), pellino 1, and S100P binding protein. It is thought that microarrays will play an ever-growing role in the advance of our understanding of the pharmacologic actions NS.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.6129-6133
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• 2015

miR-129-2 is frequently downregulated in multiple cancers. However, how it is silenced in cancers remains unclear. Here we investigated the expression profile and potential biological function of miR-129-2 in glioblastoma (GBM), the most common and lethal form of brain tumors in adults. We showed that miR-129-2 is lost in GBM patient specimens and cultured cell lines. miR-129-2 expression could be restored upon treatment with a histone deadetylase inhibitor (trichostatin A) but not a DNA methylation inhibitor (5-Aza-2'-deoxycytidine), and more profound effect was observed with the treatment of these two drugs in combination. Furthermore, forced expression of miR-129-2 repressed the expression of major oncogenic genes such as PDGFRa and Foxp1 in GBMs. Consistently, expression of miR-129-2 significantly inhibits GBM cell proliferation in vitro. These results reveal that miR-129-2 is epigenetically regulated and functions as a tumor suppressor gene in GBMs, suggesting it may serve as a potential therapeutic target for GBM treatment.