• Asian Pacific Journal of Cancer Prevention
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• v.15 no.19
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• pp.8377-8382
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• 2014

Background: Oral squamous cell carcinoma (OSCC) is the sixth most common malignancy worldwide. Cancer development and progression require inactivation of tumor suppressor genes and activation of proto-oncogenes. The well recognized mechanism of action demonstrated for chemotherapeutic agents is induction of apoptosis via reactivation of p53. In this context, we evaluate the efficacy of IV and oral routes of our novel PH and temperature sensitive doxorubicin-methotrexate-loaded nanoparticles (DOX-MTX NP) in affecting p53 profile in an OSCC rat model. Methods: In this study, 120 male rats were divided into 8 groups of 15 animals each. The new formulated DOX-MTX NP and free doxorubicin were IV and orally given to rats with 4-nitroquinoline-1-oxide induced OSCC. Results: Results showed that both DOX and DOX-MTX-NP caused significant increase in mRNA levels of P53 compared to the untreated group (p<0.000). With both DOX and DOX-MTX NP, the IV mode was more effective than the oral (gavage) route (p<0.000). Surprisingly, in oral mode, p53 mRNA was not affected in DOX treated groups (p>0.05), Nonetheless, both IV and oral administration of MTX-DOX NP showed superior activity (~3 fold) over free DOX in reactivation of p53 in OSCC (p<0.000). The effectiveness of oral route in group treated with nanodrug accounts for the enhanced bioavailability of nanoparticulated DOX-MTX compared to free DOX. Moreover, in treated groups, tumor stage was markedly related to the amount of p53 mRNA (p<0.05). Conclusion: Both oral and IV application of our novel nanodrug possesses superior activity over free DOX-in up-regulation of p53 in a OSCC model and this increase in p53 level associated with less aggressive tumors in our study. Although, impressive results obtained with IV form of nanodrug (-21 fold increase in p53 mRNA level) but both forms of nanodrug are effective in OSCC, with less toxicity normal cells.

• Asian-Australasian Journal of Animal Sciences
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• v.25 no.12
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• pp.1681-1690
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• 2012

The aim of this study was to investigate the impact of a reported p53 inhibitor, pifithrin-${\alpha}$ (PFT-${\alpha}$), on preimplantation porcine in vitro fertilized (IVF) embryo development in culture. Treatment of PFT-${\alpha}$ was administered at both early (0 to 48 hpi), and later stages (48 to 168 hpi) of preimplantation development, and its impact upon the expression of five genes related to apoptosis (p53, bak, bcl-xL, p66Shc and caspase3), was assessed in resulting d 7 blastocysts, using real-time quantitative PCR. Total cell numbers, along with the number of apoptotic nuclei, as detected by the in situ cell death detection assay, were also calculated on d 7 in treated and non-treated control embryos. The results indicate that PFT-${\alpha}$, when administered at both early and later stages of porcine IVF embryo development, increases the incidence of apoptosis in resulting blastocysts. When administered at early cleavage stages, PFT-${\alpha}$ treatment was shown to reduce the developmental competence of porcine IVF embryos, as well as reducing the quality of resulting blastocysts in terms of overall cell numbers. In contrast, at later stages, PFT-${\alpha}$ administration resulted in marginally increased blastocyst development rates amongst treated embryos, but did not affect cell numbers. However, PFT-${\alpha}$ treatment induced apoptosis and apoptotic related gene expression, in all treated embryos, irrespective of the timing of treatment. Our results indicate that PFT-${\alpha}$ may severely compromise the developmental potential of porcine IVF embryos, and is a potent apoptotic agent when placed into porcine embryo culture media. Thus, caution should be exercised when using PFT-${\alpha}$ as a specific inhibitor of p53 mediated apoptosis, in the context of porcine IVF embryo culture systems.

• Asian-Australasian Journal of Animal Sciences
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• v.25 no.1
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• pp.122-142
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• 2012

The importance of rainfed areas and animal agriculture on productivity enhancement and food security for economic rural growth in Asia is discussed in the context of opportunities for increasing potential contribution from them. The extent of the rainfed area of about 223 million hectares and the biophysical attributes are described. They have been variously referred to inter alia as fragile, marginal, dry, waste, problem, threatened, range, less favoured, low potential lands, forests and woodlands, including lowlands and uplands. Of these, the terms less favoured areas (LFAs), and low or high potential are quite widely used. The LFAs are characterised by four key features: i) very variable biophysical elements, notably poor soil quality, rainfall, length of growing season and dry periods, ii) extreme poverty and very poor people who continuously face hunger and vulnerability, iii) presence of large populations of ruminant animals (buffaloes, cattle, goats and sheep), and iv) have had minimum development attention and an unfinished wanting agenda. The rainfed humid/sub-humid areas found mainly in South East Asia (99 million ha), and arid/semi-arid tropical systems found in South Asia (116 million ha) are priority agro-ecological zones (AEZs). In India for example, the ecosystem occupies 68% of the total cultivated area and supports 40% of the human and 65% of the livestock populations. The area also produces 4% of food requirements. The biophysical and typical household characteristics, agricultural diversification, patterns of mixed farming and cropping systems are also described. Concerning animals, their role and economic importance, relevance of ownership, nomadic movements, and more importantly their potential value as the entry point for the development of LFAs is discussed. Two examples of demonstrated success concern increasing buffalo production for milk and their expanded use in semi-arid AEZs in India, and the integration of cattle and goats with oil palm in Malaysia. Revitalised development of the LFAs is justified by the demand for agricultural land to meet human needs e.g. housing, recreation and industrialisation; use of arable land to expand crop production to ceiling levels; increasing and very high animal densities; increased urbanisation and pressure on the use of available land; growing environmental concerns of very intensive crop production e.g. acidification and salinisation with rice cultivation; and human health risks due to expanding peri-urban poultry and pig production. The strategies for promoting productivity growth will require concerted R and D on improved use of LFAs, application of systems perspectives for technology delivery, increased investments, a policy framework and improved farmer-researcher-extension linkages. These challenges and their resolution in rainfed areas can forcefully impact on increased productivity, improved livelihoods and human welfare, and environmental sustainability in the future.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1061-1075
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• 2016

Context: There are no recent authoritative data about incidence and prevalence of various types of cancers in Pakistan. Aim: To determine the frequency of malignant tumors seen in our practice and provide a foundation for building a comprehensive cancer care strategy. Materials and Methods: 10,000 successive cases of solid malignant tumors reported in 2014 were included. All cases had formalin fixed, paraffin embedded specimens available and diagnosis was based on histological examination of H&E stained slides plus ancillary studies at the Section of Histopathology, Department of Pathology and Laboratory Medicine, Aga Khan University Hospital, Karachi. The latest WHO classifications were used along with the latest CAP protocols for reporting and the most updated TNM staging. Results: There were 9,492 (94.9%) primary tumors while 508 (5.1%) were metastatic. Some 5,153 (51.5%) were diagnosed in females and 4,847 (48.5%) in males. The commonest malignant tumors in females were breast (32%), esophagus (7%), lymphomas (6.8%), oral cavity (6.7%) and ovary (4.8%), while in males they were oral cavity (13.9%), lymphomas (12.8%), colorectum (7.9%), stomach (6.9%) and esophagus (6.6%). Malignant tumors were most common in the 5th, 6th and 7th decades. About 8% were seen under 20 years of age. Conclusions: Oral cavity and gastrointestinal cancers continue to be extremely common in both genders. Breast and esophageal cancers are prevalent in females. Lung and prostate cancer are less common than in the west. Ovarian cancer was very common but cervix cancer was less so.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6883-6888
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• 2013

Background: Platinum based concurrent chemo-radiation is the de-facto standard of care in the non-surgical management of locally-advanced head and neck cancer of squamous origin. Three-weekly single agent cisplatin at 100 $mg/m^2$ concurrent with radical radiotherapy has demonstrated consistent improvement in loco-regional control and survival. This improvement is however at the cost of considerable hematologic toxicity and poor overall compliance. The routine use of this regime is improbable in developing countries with limited resources. We therefore aimed to determine the safety and efficacy of an alternative regime of weekly cisplatin and concurrent radiotherapy in such patients. Materials and Methods: January-05 and April-12, 188 patients of locally-advanced head and neck cancer of squamous origin were treated with concurrent weekly-cisplatin at $35mg/m^2$ and conventional radiotherapy 60-66Gy/30-33 fractions/5days per week. Results: Overall, 95% patients received planned doses of RT while 74% completed within the stipulated overall treatment time of <50 days. Eighty-two percent received at-least 5 weekly cycles. Grade-III/IV mucositis was seen in 58%/9% respectively, which resulted in mean weight loss of 9.2% from a pre-treatment mean of 54.5 kg. Grade-III hematologic toxicity-0.5%; grade II nephrotoxicity-2.5% and grade III emesis-3% were also seen. Grade-III/IV subcutaneous toxicity-10%/1% and grade-III/IV xerostomia-10%/0% were observed. Complete responses at the primary site, regional nodes and overall disease were seen in 86%, 89% and 83% patients respectively. The median and 5-years disease-free survival were 26 months and 39.4% respectively, while the median and overall survival were 27 months and 41.8% respectively. Conclusions: Weekly-cisplatin at 35 $mg/m^2$ when delivered concurrently with conventional radical RT (at-least 66y/33 fractions) in locally-advanced head and neck cancer is well tolerated with minimal hematologic and neprologic toxicity and can be routinely delivered on an out-patient basis. It is an effective alternative to the standard 3-weekly cisplatin especially in the context of developing countries.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.8
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• pp.3403-3410
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• 2014

Context: Interest exits in whether TNF-alpha antagonists increase the risk of breast cancer and total malignancies in patients with rheumatoid arthritis (RA). Objectives: To analyze the risk of malignancies, especially breast cancer, in patients with RA enrolled in randomized control trials (RCTs). Methods: A systematic literature search for RCTs from 1 January 1998 to 1 July 2013 from online databases, such as PubMed, WILEY, EMBASE, ISI web of knowledge and Cochrane Library was conducted. Studies included RCTs that compared the safety of at least one dose of the five TNF-${\alpha}$ antagonists with placebo or methotrexate (MTX) (or TNF-${\alpha}$ antagonists plus MTX vs placebo plus MTX) in RA patients for more than 24 weeks and imported all the references into document management software EndNote${\times}6$. Two independent reviewers selected studies and extracted the data about study design, patients' characteristics and the type, number of all malignancies. Results: 28 RCTs from 34 records with 11,741 patients were analyzed. Of the total, 97 developed at least one malignancy during the double-blind trials, and breast cancer was observed in 17 patients (17.5% of total malignancies). However, there was no statistically significant increased risk observed in either the per protocol (PP) model (OR 0.65, 95%CI [0.22, 1.93]) or the modified intention to treat (mITT) model (OR 0.75, 95%CI [0.25, 2.21]). There were also no significant trend for increased risk of total malignancies on anti-TNF-${\alpha}$ therapy administered at approved doses in either model (OR, 1.06, 95%CI [0.64, 1.75], and OR, 1.30, 95%CI [0.80, 2.14], respectively). As to the two models, modified intention to treat model analysis led to higher estimation than per protocol model analysis. Conclusions: This study did not find a significantly increased risk of breast cancer and total malignancies in adults RA patients treated with TNF-${\alpha}$ antagonists at approved doses. However, it cannot be ignored that more patients developed malignancies with TNF-${\alpha}$ antagonists therapy compared with patients with placebo or MTX, in spite of the lack of statistical significance, so that more strict clinical trials and long-term follow-up are needed, and both mITT and PP analyses should be used in such safety analyses.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.sup3
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• pp.191-195
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• 2016

Breast cancer is the most frequent cancer in females. Its incidence is higher in developed countries than in developing ones partly due to variation in risk exposure and partly due to better detection methods. Scattered evidence in Basrah, Iraq, suggests that breast cancer has been increasing at a significant pace in recent years. This study aimed to measure the current level of risk of breast cancer among females in Basrah and to describe the time trend over almost a decade of years. Data on breast cancer cases from all sources of cancer registration in Basrah governorate were compiled for the years 2005-2012. The data for each year were first checked separately for duplicate reporting of cases among various sources. Then the eight files were pooled together and checked again for any duplicate cases among years of registration. The final set of data contained 2,284 cases of breast cancer (2,213 female cases and 71 male cases). All patients were inhabitants of Basrah governorate at the time of diagnosis. Figures on the Basrah population were obtained from various sources including the Ministry of Health, Ministry of Planning and Developmental Collaboration and local household surveys. It was possible to have total population estimates for each year and by age and sex. The data were imported into SPSS (version 17) software. Age specific and year specific incidence rates were calculated. The age standardized incidence rate was also calculated using world population as the standard population to be 34.9 per 100,000 females. Age-wise, no case was reported among children aged less than 15 years and the incidence increased with advancing age reaching a peak of 123.8/100,000 females at the age range of 50-54 years. The time trend of the crude incidence rate showed only modest increased risk with passage of years and no age shift could be documented in this study. Breast cancer in females in Basrah is a significant health problem. The current incidence rate (crude, 23.7/100,000, age-standardized, 34.9/100,000) is high and justifies intensive efforts to improve early detection of cases, provide better treatment amenities and introduce long term preventive measures. Using the age standardized incidence rate as reported in this paper, it is possible to put the risk in Basrah within a regional and international context.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.1861-1864
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• 2016

Although early diagnosis of thyroid nodule type is very important, the diagnostic accuracy of standard tests is a challenging issue. We here aimed to find an optimal combination of factors to improve diagnostic accuracy for distinguishing malignant from benign thyroid nodules before surgery. In a prospective study from 2008 to 2012, 345 patients referred for thyroidectomy were enrolled. The sample size was split into a training set and testing set as a ratio of 7:3. The former was used for estimation and variable selection and obtaining a linear combination of factors. We utilized smoothly clipped absolute deviation (SCAD) logistic regression to achieve the sparse optimal combination of factors. To evaluate the performance of the estimated model in the testing set, a receiver operating characteristic (ROC) curve was utilized. The mean age of the examined patients (66 male and 279 female) was $40.9{\pm}13.4years$ (range 15- 90 years). Some 54.8% of the patients (24.3% male and 75.7% female) had benign and 45.2% (14% male and 86% female) malignant thyroid nodules. In addition to maximum diameters of nodules and lobes, their volumes were considered as related factors for malignancy prediction (a total of 16 factors). However, the SCAD method estimated the coefficients of 8 factors to be zero and eliminated them from the model. Hence a sparse model which combined the effects of 8 factors to distinguish malignant from benign thyroid nodules was generated. An optimal cut off point of the ROC curve for our estimated model was obtained (p=0.44) and the area under the curve (AUC) was equal to 77% (95% CI: 68%-85%). Sensitivity, specificity, positive predictive value and negative predictive values for this model were 70%, 72%, 71% and 76%, respectively. An increase of 10 percent and a greater accuracy rate in early diagnosis of thyroid nodule type by statistical methods (SCAD and ANN methods) compared with the results of FNA testing revealed that the statistical modeling methods are helpful in disease diagnosis. In addition, the factor ranking offered by these methods is valuable in the clinical context.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.3131-3137
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• 2013

Background: Visual inspection of cervix with acetic acid (VIA) is offered at 252 centers in 64 districts of Bangladesh. VIA+ve women are managed at colposcopy clinics of Bangabandhu Sheikh Mujib Medical University (BSMMU) and 14 Medical College Hospitals (MCHs). This research work has been supported by 'UICC Cancer Prevention Campaign' programme. Objectives: This study explored the role of print materials and electronic media to improve cervical cancer screening in the present socio-cultural context of Bangladesh. Methods: This study was performed from January to August 2011 at two upazilas of Bangladesh (Singair with screening facility and Sonargaon without screening facility). Data were collected by focus group discussion (FGD) with women, husbands and community people before and after intervention. Information on cervical cancer screening and VIA camps was disseminated using advertisement through local cable line of the television, microphone announcement, service providers and leaflet throughout the week prior to a VIA camp. Three-day VIA camps were organized at the upazila health complex (UHC) of both upazilas. Quantitative data was gathered from women at the camps on source of information on VIA and the best method of awareness creation. Results: The population was aware of "cancer" and a notable number knew about cervical cancer. Baseline awareness on prevention and VIA was low and it was negligible where screening services were unavailable. Awareness was increased fourfold in both upazilas after interventions and half of the women and the majority of the community people became aware of screening and available facilities. Cable line advertisement (25.5%), microphone announcement (21.4%), and discussion sessions (20.4%) were effective for awareness creation on VIA. Television was mentioned as the best method (37.4%) of awareness creation. Conclusion: Television should be used for nation-wide awareness creation. For local awareness creation, cable line advertisement, microphone announcements and health education at Uthan Baithaks/ EPI sessions can easily be adopted by the government.

• Asian-Australasian Journal of Animal Sciences
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• v.23 no.5
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• pp.573-579
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• 2010

This study was conducted to determine the effects of different copper (inorganic and organic) and energy (tallow and glycerol) sources on growth performance, nutrient digestibility, gas emission, diarrhea incidence, and fecal copper concentration in growing pigs by using a 2${\times}$2 factorial design. In this trial, 96 pigs (63 d of age) were employed, with an average initial weight of 28.36${\pm}$1.14 kg. The dietary treatments were i) basal diet with 134 ppm copper (Korea recommendation) as $CuSO_4$+tallow; ii) basal diet with 134 ppm Cu as $CuSO_4$+glycerol; iii) basal diet with 134 ppm copper as CuMet+tallow; and iv) basal diet with 134 ppm copper as CuMet+ glycerol. Throughout the entire experimental period, no differences were noted among treatment groups with regard to the magnitude of improvement in ADG (average daily gain), ADFI (average daily feed intake) and G/F (gain:feed) ratios. The nitrogen (N) digestibility of pigs fed on diets containing organic copper was improved as compared with that observed in pigs fed on diets containing inorganic copper (p<0.05). An interaction of copper${\times}$energy was observed in the context of both nitrogen (p<0.05) and energy (p<0.01) digestibility. Ammonia emissions were significantly lower in the organic copper-added treatment groups than in the inorganic copperadded treatment groups (p<0.05). Mercaptan and hydrogen sulfide emissions were reduced via the addition of glycerol (p<0.05). No significant effects of copper or energy source, or their interaction, were observed in reference to diarrhea appearance and incidence throughout the entirety of the experimental period. The copper concentration in the feces was significantly lower in the organic copper source treatment group than was observed in the inorganic copper source treatment group (p<0.05). The results of this experiment show that organic copper substituted for inorganic copper in the diet results in a decreased fecal copper excretion, but exerts no effect on performance. The different energy (tallow and glycerol) sources interact with different copper sources and thus influence nutrient digestibility. Glycerol supplementation may reduce the concentrations of odorous sulfuric compounds with different Cu sources.