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2. A Systematic Review of Chronic Diseases and Their Prevalence Among the Population of Northern Borders Province (NBP) in Saudi Arabia

Author

Alenzi EO, Fatima W, Amara A, Imran M, Shah SSH, Elbilgahy AA, Fawzy MS, Abu-Negm LM, Mujtaba MA, Jacinto-Caspillo I, and Al-Hazimi AM

Subjects
chronic diseases, medical healthcare, northern borders province, systematic review, Medicine (General), R5-920
Abstract

Ebtihag O Alenzi,1– 3 Waseem Fatima,3,4 Abdelbasset Amara,3,5 Mohd Imran,3,6 Syed Sajid Hussain Shah,3,7 Amal Ahmed Elbilgahy,3,8,9 Manal S Fawzy,3,10,11 Lobna M Abu-Negm,3,12,13 Md Ali Mujtaba,3,14 Ingrid Jacinto-Caspillo,3,15 Awdah M Al-Hazimi3,16 1Department of Family and Community Medicine, Faculty of Medicine, Northern Border University, Arar, Saudi Arabia; 2Clinical Sciences Department, College of Medicine, Princess Nourah bint Abdul Rahman University, Riyadh, Saudi Arabia; 3Health & Medical Research Unit, Deanship of Scientific Research, Northern Border University, Arar, Saudi Arabia; 4Department of Clinical Nutrition, Faculty of Applied Medical Sciences, Northern Border University, Arar, Saudi Arabia; 5Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, Northern Border University, Arar, Saudi Arabia; 6Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Northern Border University, Rafha, Saudi Arabia; 7Department of Pathology, Faculty of Medicine, Northern Border University, Arar, Saudi Arabia; 8Maternal and Child Health Nursing Department, Faculty of Nursing, Northern Border University, Arar, Saudi Arabia; 9Pediatric Nursing, Faculty of Nursing, Mansoura University, Mansoura, Egypt; 10Department of Biochemistry, Faculty of Medicine, Northern Border University, Arar, Saudi Arabia; 11Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt; 12Emergency Nursing Department, Faculty of Nursing, Northern Border University, Arar, Saudi Arabia; 13Medical Surgical Nursing Department, Faculty of Nursing, Ain Shams University, Cairo, Egypt; 14Department of Pharmaceutics, Faculty of Pharmacy, Northern Border University, Rafha, Saudi Arabia; 15Medical and Surgical Nursing Department, Faculty of Nursing, Northern Border University, Arar, Saudi Arabia; 16Faculty of Medicine, Northern Border University, Arar, Saudi ArabiaCorrespondence: Manal S Fawzy; Awdah M Al-Hazimi, Tel +966 583241944 ; +966 505375690, Fax +966 146640705, Email manal2_khashana@ymail.com; phsaaa7@hotmail.comAbstract: Estimation of the prevalence of chronic conditions is pivotal to effective healthcare planning and management. Therefore, our objective was to systemically review previous literature about the prevalence of chronic diseases among residents of Northern Borders Province (NBP) in Saudi Arabia. The electronic search has been done using scientific databases (PubMed, Ebsco, SciFinder, and Web of Science) and search engines up to September 2021. The following main key terms: chronic disease OR chronic conditions AND prevalence AND Northern Borders Province OR Northern Borders AND Saudi Arabia were applied. Other related terms with a more specific search were done with names of the main cities in the province and the most common diseases in Saudi Arabia. Duplicates were removed electronically by Endnote and manually. Extracted data were tabulated in the literature matrix. The risk of bias and quality of included studies were assessed using the “Strengthening the Reporting of Observational Studies in Epidemiology” (STROBE) checklist. Out of 63 observational studies that were assessed for eligibility, 21 observational studies were included to synthesize the evidence. These studies were conducted on Arar (n=16), Turaif (n=2), and Rafha (n=1), while the remaining were national studies in which NBP was one of the included regions (n=2). The most frequently studied diseases were diabetes (4 records), psychological diseases (4 records), and obesity (3 records). The most prevalent disease was gastroesophageal reflux disease (GERD), with an estimated prevalence of 61% among adults in Arar city. In conclusion, although some research is conducted about chronic diseases somewhere in NBP, further studies are needed to study chronic diseases using a representative sample of the whole NBP population.Keywords: chronic diseases, medical healthcare, northern borders province, systematic review

Published
2023

5. Race Against the Clock: On the Transmission Dynamics of COVID-19 in Africa [Letter]

Author

Zehra SS and Fatima W

Subjects
covid-19, africa, pakistan, reproduction number, asymptomatic, vaccine, measles, Infectious and parasitic diseases, RC109-216
Abstract

Syeda Sakina Zehra, Wara Fatima Karachi Medical and Dental College, Karachi, PakistanCorrespondence: Syeda Sakina Zehra, Tel +92 3322609216, Email szehra362@gmail.com

Published
2022

6. Identification and Characterization of Xanthan Gum Produced from Date Juice by a Local Isolate of Bacteria Xanthomonas campestris

Author

Fatima W. Al-Roomi and Shayma T. G. Al-Sahlany

Subjects
Date juice, Xanthomonas campestris, Xanthan gum, Agriculture (General), S1-972
Abstract

Xanthan gum is a microbial polysaccharide produced by the bacteria Xanthomonas spp. Seven local isolates of Xanthomonas campestris were used after microscopic and biochemical tests identified them. The isolates were subjected to a screening for xanthan production in medium broth consisting of 20 g.L-1 sucrose, 0.1 g.L-1 urea, and 1 g.L-1 K2HPO4. Isolate X1 showed the highest yield, which reached 6.26 g.l-1. The isolate was confirmed by a 16S rRNA test, and it was recorded in the gene bank with the code MZ262533. Xanthan gum was produced from date juice at a concentration of 3.5 ml (1.5 g glucose.100 ml-1 from the production medium, with the highest yield being 18.9 g.l-1. The resulting xanthan gum was identified by using FTIR, TLC and HPLC techniques, and it was the same chemical as xanthan gum. In the manufacture of xanthan gum and its usage in food, alternative media made from agricultural waste can be employed.

Published
2022
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9. Calculation of Thermal Conductivity, Mechanical Properties Values at Adding Copper to a Base of Zirconia by Powder Method.

Author

Ridha, Fatima W.

Subjects
THERMAL conductivity, THERMAL resistance, THERMAL diffusivity, VALUATION of real property, ZIRCONIUM oxide, HEAT capacity, VICKERS hardness
Abstract

Powder metallurgy has a wide range of industrial applications in the manufacture of tools, brushes, filters, and others. As a base of zirconia metal was used and supported by silicon at a constant rate of 3% Si with different reinforcement percentages of copper, which are (3,6,9,12,15)%. The pressing process was carried out at a pressure of 5 tons with a hydraulic press. A pressing mold with a diameter of 10 mm was used. The samples resulting from the press were sintered at 1000 °C for one hour, and the thermal, mechanical, and structural properties were calculated after sintering, which included thermal conductivity, thermal diffusion, heat flow, heat capacity, thermal resistance, Vickers hardness, compressive strength, wear, and scanning electron microscopy. Under ideal conditions of thermal sintering at 1000 °C, and a mixing ratio of 15%Cu, encouraging results were obtained, with a thermal conductivity of 66.34 W/m.K, a thermal diffusivity of 2.2416 mm2/sec, a heat flux of 420.424 W½/m2.K, and a heat capacity of 440.2512 J/kg.K, with a thermal resistance of 0.00103 m2.K/W. While the Vickers hardness was 602Kg/mm2, the compressive strength was 71 MPa, and the wear and tear was 3 £ 10-8 g/cm. As for the synthetic results, which included the scanning electron microscope, it showed that the best homogeneity and reticular consistency was at the addition rate of 15%, and it was also noted that the spread of zirconia on the surface of copper was significant. [ABSTRACT FROM AUTHOR]

Published
2024
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10. Association of common BRCA1 variants with predisposition to breast tumors in Pakistan

Author

Siddique, Ayesha, Fatima, W., Shahid, Naeem, Siddique, Ayesha, Fatima, W., and Shahid, Naeem

Abstract

BRCA1 variants are extensively associated with increased risk of breast cancer. Early detection and screening of variants is still rare in developing countries. Here, we investigated six BRCA1 variants in 300 subjects from Pakistani population using tetra amplification-refractory mutation system (T-ARMS) PCR. Our results indicate significant association of BRCA1 variants rs8176237 (AA; OR 8.2, 95% CI 3.02–22.64, p < 0.0001), rs1060915 (CC; OR 4.29, 95% CI 1.94–9.48, p = 0.0003), and rs799912 (TT; OR 3.16, 95% CI 1.44–6.94, p = 0.004) with up to 8-fold increased odds of breast cancer under recessive model. Furthermore, BRCA1 haplotypes AGCACG and AGCCCT were associated with up to 18% breast cancer cases (p < 0.05). Additionally, we found association of these variants with up to 11-fold increased odds of benign breast tumors. Linkage disequilibrium (LD) block-wise analysis revealed haplotypes GCAC and ATAC were associated with significantly increased risk. To our knowledge, this is the first study that identifies the association of these BRCA1 variants with breast tumors in Pakistani population. In conclusion, BRCA1 variants investigated in the present study are associated with high odds of benign- and malignant breast tumors. Studies with bigger sample size may help early detection and screening to reduce the odds of breast cancer.

Published
2023

11. The global burden of cancer attributable to risk factors, 2010–19: a systematic analysis for the Global Burden of Disease Study 2019

Author

Tran, K, Lang, J, Compton, K, Xu, R, Acheson, A, Henrikson, H, Kocarnik, J, Penberthy, L, Aali, A, Abbas, Q, Abbasi, B, Abbasi-Kangevari, M, Abbasi-Kangevari, Z, Abbastabar, H, Abdelmasseh, M, Abd-Elsalam, S, Abdelwahab, A, Abdoli, G, Abdulkadir, H, Abedi, A, Abegaz, K, Abidi, H, Aboagye, R, Abolhassani, H, Absalan, A, Abtew, Y, Abubaker Ali, H, Abu-Gharbieh, E, Achappa, B, Acuna, J, Addison, D, Addo, I, Adegboye, O, Adesina, M, Adnan, M, Adnani, Q, Advani, S, Afrin, S, Afzal, M, Aggarwal, M, Ahinkorah, B, Ahmad, A, Ahmad, R, Ahmad, S, Ahmadi, S, Ahmed, H, Ahmed, L, Ahmed, M, Ahmed Rashid, T, Aiman, W, Ajami, M, Akalu, G, Akbarzadeh-Khiavi, M, Aklilu, A, Akonde, M, Akunna, C, Al Hamad, H, Alahdab, F, Alanezi, F, Alanzi, T, Alessy, S, Algammal, A, Al-Hanawi, M, Alhassan, R, Ali, B, Ali, L, Ali, S, Alimohamadi, Y, Alipour, V, Aljunid, S, Alkhayyat, M, Al-Maweri, S, Almustanyir, S, Alonso, N, Alqalyoobi, S, Al-Raddadi, R, Al-Rifai, R, Al-Sabah, S, Al-Tammemi, A, Altawalah, H, Alvis-Guzman, N, Amare, F, Ameyaw, E, Aminian Dehkordi, J, Amirzade-Iranaq, M, Amu, H, Amusa, G, Ancuceanu, R, Anderson, J, Animut, Y, Anoushiravani, A, Anoushirvani, A, Ansari-Moghaddam, A, Ansha, M, Antony, B, Antwi, M, Anwar, S, Anwer, R, Anyasodor, A, Arabloo, J, Arab-Zozani, M, Aremu, O, Argaw, A, Ariffin, H, Aripov, T, Arshad, M, Artaman, A, Arulappan, J, Aruleba, R, Aryannejad, A, Asaad, M, Asemahagn, M, Asemi, Z, Asghari-Jafarabadi, M, Ashraf, T, Assadi, R, Athar, M, Athari, S, Atout, M, Attia, S, Aujayeb, A, Ausloos, M, Avila-Burgos, L, Awedew, A, Awoke, M, Awoke, T, Ayala Quintanilla, B, Ayana, T, Ayen, S, Azadi, D, Azadnajafabad, S, Azami-Aghdash, S, Azanaw, M, Azangou-Khyavy, M, Azari Jafari, A, Azizi, H, Azzam, A, Babajani, A, Badar, M, Badiye, A, Baghcheghi, N, Bagheri, N, Bagherieh, S, Bahadory, S, Baig, A, Baker, J, Bakhtiari, A, Bakshi, R, Banach, M, Banerjee, I, Bardhan, M, Barone-Adesi, F, Barra, F, Barrow, A, Bashir, N, Bashiri, A, Basu, S, Batiha, A, Begum, A, Bekele, A, Belay, A, Belete, M, Belgaumi, U, Bell, A, Belo, L, Benzian, H, Berhie, A, Bermudez, A, Bernabe, E, Bhagavathula, A, Bhala, N, Bhandari, B, Bhardwaj, N, Bhardwaj, P, Bhattacharyya, K, Bhojaraja, V, Bhuyan, S, Bibi, S, Bilchut, A, Bintoro, B, Biondi, A, Birega, M, Birhan, H, Bjorge, T, Blyuss, O, Bodicha, B, Bolla, S, Boloor, A, Bosetti, C, Braithwaite, D, Brauer, M, Brenner, H, Briko, A, Briko, N, Buchanan, C, Bulamu, N, Bustamante-Teixeira, M, Butt, M, Butt, N, Butt, Z, Caetano dos Santos, F, Camera, L, Cao, C, Cao, Y, Carreras, G, Carvalho, M, Cembranel, F, Cerin, E, Chakraborty, P, Charalampous, P, Chattu, V, Chimed-Ochir, O, Chirinos-Caceres, J, Cho, D, Cho, W, Christopher, D, Chu, D, Chukwu, I, Cohen, A, Conde, J, Cortes, S, Costa, V, Cruz-Martins, N, Culbreth, G, Dadras, O, Dagnaw, F, Dahlawi, S, Dai, X, Dandona, L, Dandona, R, Daneshpajouhnejad, P, Danielewicz, A, Dao, A, Darvishi Cheshmeh Soltani, R, Darwesh, A, Das, S, Davitoiu, D, Davtalab Esmaeili, E, De la Hoz, F, Debela, S, Dehghan, A, Demisse, B, Demisse, F, Denova-Gutierrez, E, Derakhshani, A, Derbew Molla, M, Dereje, D, Deribe, K, Desai, R, Desalegn, M, Dessalegn, F, Dessalegni, S, Dessie, G, Desta, A, Dewan, S, Dharmaratne, S, Dhimal, M, Dianatinasab, M, Diao, N, Diaz, D, Digesa, L, Dixit, S, Doaei, S, Doan, L, Doku, P, Dongarwar, D, dos Santos, W, Driscoll, T, Dsouza, H, Durojaiye, O, Edalati, S, Eghbalian, F, Ehsani-Chimeh, E, Eini, E, Ekholuenetale, M, Ekundayo, T, Ekwueme, D, El Tantawi, M, Elbahnasawy, M, Elbarazi, I, Elghazaly, H, Elhadi, M, El-Huneidi, W, Emamian, M, Engelbert Bain, L, Enyew, D, Erkhembayar, R, Eshetu, T, Eshrati, B, Eskandarieh, S, Espinosa-Montero, J, Etaee, F, Etemadimanesh, A, Eyayu, T, Ezeonwumelu, I, Ezzikouri, S, Fagbamigbe, A, Fahimi, S, Fakhradiyev, I, Faraon, E, Fares, J, Farmany, A, Farooque, U, Farrokhpour, H, Fasanmi, A, Fatehizadeh, A, Fatima, W, Fattahi, H, Fekadu, G, Feleke, B, Ferrari, A, Ferrero, S, Ferro Desideri, L, Filip, I, Fischer, F, Foroumadi, R, Foroutan, M, Fukumoto, T, Gaal, P, Gad, M, Gadanya, M, Gaipov, A, Galehdar, N, Gallus, S, Garg, T, Gaspar Fonseca, M, Gebremariam, Y, Gebremeskel, T, Gebremichael, M, Geda, Y, Gela, Y, Gemeda, B, Getachew, M, Ghaffari, K, Ghafourifard, M, Ghamari, S, Ghasemi Nour, M, Ghassemi, F, Ghimire, A, Ghith, N, Gholamalizadeh, M, Gholizadeh Navashenaq, J, Ghozy, S, Gilani, S, Gill, P, Ginindza, T, Gizaw, A, Glasbey, J, Godos, J, Goel, A, Golechha, M, Goleij, P, Golinelli, D, Golitaleb, M, Gorini, G, Goulart, B, Grosso, G, Guadie, H, Gubari, M, Gudayu, T, Guerra, M, Gunawardane, D, Gupta, B, Gupta, S, Gupta, V, Gurara, M, Guta, A, Habibzadeh, P, Haddadi Avval, A, Hafezi-Nejad, N, Hajj Ali, A, Haj-Mirzaian, A, Halboub, E, Halimi, A, Halwani, R, Hamadeh, R, Hameed, S, Hamidi, S, Hanif, A, Hariri, S, Harlianto, N, Haro, J, Hartono, R, Hasaballah, A, Hasan, S, Hasani, H, Hashemi, S, Hassan, A, Hassanipour, S, Hayat, K, Heidari, G, Heidari, M, Heidarymeybodi, Z, Herrera-Serna, B, Herteliu, C, Hezam, K, Hiraike, Y, Hlongwa, M, Holla, R, Holm, M, Horita, N, Hoseini, M, Hossain, M, Hosseini, M, Hosseinzadeh, A, Hosseinzadeh, M, Hostiuc, M, Hostiuc, S, Househ, M, Huang, J, Hugo, F, Humayun, A, Hussain, S, Hussein, N, Hwang, B, Ibitoye, S, Iftikhar, P, Ikuta, K, Ilesanmi, O, Ilic, I, Ilic, M, Immurana, M, Innos, K, Iranpour, P, Irham, L, Islam, M, Islam, R, Islami, F, Ismail, N, Isola, G, Iwagami, M, J, L, Jaiswal, A, Jakovljevic, M, Jalili, M, Jalilian, S, Jamshidi, E, Jang, S, Jani, C, Javaheri, T, Jayarajah, U, Jayaram, S, Jazayeri, S, Jebai, R, Jemal, B, Jeong, W, Jha, R, Jindal, H, John-Akinola, Y, Jonas, J, Joo, T, Joseph, N, Joukar, F, Jozwiak, J, Jurisson, M, Kabir, A, Kacimi, S, Kadashetti, V, Kahe, F, Kakodkar, P, Kalankesh, L, Kalhor, R, Kamal, V, Kamangar, F, Kamath, A, Kanchan, T, Kandaswamy, E, Kandel, H, Kang, H, Kanno, G, Kapoor, N, Kar, S, Karanth, S, Karaye, I, Karch, A, Karimi, A, Kassa, B, Katoto, P, Kauppila, J, Kaur, H, Kebede, A, Keikavoosi-Arani, L, Kejela, G, Kemp Bohan, P, Keramati, M, Keykhaei, M, Khajuria, H, Khan, A, Khan, E, Khan, G, Khan, M, Khanali, J, Khatab, K, Khatatbeh, M, Khatib, M, Khayamzadeh, M, Khayat Kashani, H, Khazeei Tabari, M, Khezeli, M, Khodadost, M, Kim, M, Kim, Y, Kisa, A, Kisa, S, Klugar, M, Klugarova, J, Kolahi, A, Kolkhir, P, Kompani, F, Koul, P, Koulmane Laxminarayana, S, Koyanagi, A, Krishan, K, Krishnamoorthy, Y, Kucuk Bicer, B, Kugbey, N, Kulimbet, M, Kumar, A, Kumar, G, Kumar, N, Kurmi, O, Kuttikkattu, A, La Vecchia, C, Lahiri, A, Lal, D, Lam, J, Lan, Q, Landires, I, Larijani, B, Lasrado, S, Lau, J, Lauriola, P, Ledda, C, Lee, S, Lee, W, Lee, Y, Legesse, S, Leigh, J, Leong, E, Li, M, Lim, S, Liu, G, Liu, J, Lo, C, Lohiya, A, Lopukhov, P, Lorenzovici, L, Lotfi, M, Loureiro, J, Lunevicius, R, Madadizadeh, F, Mafi, A, Magdeldin, S, Mahjoub, S, Mahmoodpoor, A, Mahmoudi, M, Mahmoudimanesh, M, Mahumud, R, Majeed, A, Majidpoor, J, Makki, A, Makris, K, Malakan Rad, E, Malekpour, M, Malekzadeh, R, Malik, A, Mallhi, T, Mallya, S, Mamun, M, Manda, A, Mansour-Ghanaei, F, Mansouri, B, Mansournia, M, Mantovani, L, Martini, S, Martorell, M, Masoudi, S, Masoumi, S, Matei, C, Mathews, E, Mathur, M, Mathur, V, Mckee, M, Meena, J, Mehmood, K, Mehrabi Nasab, E, Mehrotra, R, Melese, A, Mendoza, W, Menezes, R, Mengesha, S, Mensah, L, Mentis, A, Mera-Mamian, A, Meretoja, T, Merid, M, Mersha, A, Meselu, B, Meshkat, M, Mestrovic, T, Miao Jonasson, J, Miazgowski, T, Michalek, I, Mijena, G, Miller, T, Mir, S, Mirinezhad, S, Mirmoeeni, S, Mirza-Aghazadeh-Attari, M, Mirzaei, H, Misganaw, A, Misra, S, Mohammad, K, Mohammadi, E, Mohammadi, M, Mohammadian-Hafshejani, A, Mohammadpourhodki, R, Mohammed, A, Mohammed, S, Mohan, S, Mohseni, M, Moka, N, Mokdad, A, Molassiotis, A, Molokhia, M, Momenzadeh, K, Momtazmanesh, S, Monasta, L, Mons, U, Montasir, A, Montazeri, F, Montero, A, Moosavi, M, Moradi, A, Moradi, Y, Moradi Sarabi, M, Moraga, P, Morawska, L, Morrison, S, Morze, J, Mosapour, A, Mostafavi, E, Mousavi, S, Mousavi Isfahani, H, Mousavi Khaneghah, A, Mpundu-Kaambwa, C, Mubarik, S, Mulita, F, Munblit, D, Munro, S, Murillo-Zamora, E, Musa, J, Nabhan, A, Nagarajan, A, Nagaraju, S, Nagel, G, Naghipour, M, Naimzada, M, Nair, T, Naqvi, A, Narasimha Swamy, S, Narayana, A, Nassereldine, H, Natto, Z, Nayak, B, Ndejjo, R, Nduaguba, S, Negash, W, Nejadghaderi, S, Nejati, K, Neupane Kandel, S, Nguyen, H, Niazi, R, Noor, N, Noori, M, Noroozi, N, Nouraei, H, Nowroozi, A, Nunez-Samudio, V, Nzoputam, C, Nzoputam, O, Oancea, B, Odukoya, O, Oghenetega, O, Ogunsakin, R, Oguntade, A, Oh, I, Okati-Aliabad, H, Okekunle, A, Olagunju, A, Olagunju, T, Olakunde, B, Olufadewa, I, Omer, E, Omonisi, A, Ong, S, Onwujekwe, O, Orru, H, Otstavnov, S, Oulhaj, A, Oumer, B, Owopetu, O, Oyinloye, B, P A, M, Padron-Monedero, A, Padubidri, J, Pakbin, B, Pakshir, K, Pakzad, R, Palicz, T, Pana, A, Pandey, A, Pant, S, Pardhan, S, Park, E, Park, S, Patel, J, Pati, S, Paudel, R, Paudel, U, Paun, M, Pazoki Toroudi, H, Peng, M, Pereira, J, Pereira, R, Perna, S, Perumalsamy, N, Pestell, R, Pezzani, R, Piccinelli, C, Pillay, J, Piracha, Z, Pischon, T, Postma, M, Pourabhari Langroudi, A, Pourshams, A, Pourtaheri, N, Prashant, A, Qadir, M, Quazi Syed, Z, Rabiee, M, Rabiee, N, Radfar, A, Radhakrishnan, R, Radhakrishnan, V, Raeisi, M, Rafiee, A, Rafiei, A, Raheem, N, Rahim, F, Rahman, M, Rahmani, A, Rahmani, S, Rahmanian, V, Rajai, N, Rajesh, A, Ram, P, Ramezanzadeh, K, Rana, J, Ranabhat, K, Ranasinghe, P, Rao, C, Rao, S, Rashedi, S, Rashidi, A, Rashidi, M, Ratan, Z, Rawaf, D, Rawaf, S, Rawal, L, Rawassizadeh, R, Razeghinia, M, Rehman, A, Rehman, I, Reitsma, M, Renzaho, A, Rezaei, M, Rezaei, N, Rezaei, S, Rezaeian, M, Rezapour, A, Riad, A, Rikhtegar, R, Rios-Blancas, M, Roberts, T, Rohloff, P, Romero-Rodriguez, E, Roshandel, G, Rwegerera, G, S, M, Saber-Ayad, M, Saberzadeh-Ardestani, B, Sabour, S, Saddik, B, Sadeghi, E, Saeb, M, Saeed, U, Safaei, M, Safary, A, Sahebazzamani, M, Sahebkar, A, Sahoo, H, Sajid, M, Salari, H, Salehi, S, Salem, M, Salimzadeh, H, Samodra, Y, Samy, A, Sanabria, J, Sankararaman, S, Sanmarchi, F, Santric-Milicevic, M, Saqib, M, Sarveazad, A, Sarvi, F, Sathian, B, Satpathy, M, Sayegh, N, Schneider, I, Schwarzinger, M, Sekerija, M, Senthilkumaran, S, Sepanlou, S, Seylani, A, Seyoum, K, Sha, F, Shafaat, O, Shah, P, Shahabi, S, Shahid, I, Shahrbaf, M, Shahsavari, H, Shaikh, M, Shaka, M, Shaker, E, Shannawaz, M, Sharew, M, Sharifi, A, Sharifi-Rad, J, Sharma, P, Shashamo, B, Sheikh, A, Sheikh, M, Sheikhbahaei, S, Sheikhi, R, Sheikhy, A, Shepherd, P, Shetty, A, Shetty, J, Shetty, R, Shibuya, K, Shirkoohi, R, Shirzad-Aski, H, Shivakumar, K, Shivalli, S, Shivarov, V, Shobeiri, P, Shokri Varniab, Z, Shorofi, S, Shrestha, S, Sibhat, M, Siddappa Malleshappa, S, Sidemo, N, Silva, D, Silva, L, Silva Julian, G, Silvestris, N, Simegn, W, Singh, A, Singh, G, Singh, H, Singh, J, Singh, P, Singh, S, Sinha, D, Sinke, A, Siraj, M, Sitas, F, Siwal, S, Skryabin, V, 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Alvis-Guzman, N, Amare, F, Ameyaw, E, Aminian Dehkordi, J, Amirzade-Iranaq, M, Amu, H, Amusa, G, Ancuceanu, R, Anderson, J, Animut, Y, Anoushiravani, A, Anoushirvani, A, Ansari-Moghaddam, A, Ansha, M, Antony, B, Antwi, M, Anwar, S, Anwer, R, Anyasodor, A, Arabloo, J, Arab-Zozani, M, Aremu, O, Argaw, A, Ariffin, H, Aripov, T, Arshad, M, Artaman, A, Arulappan, J, Aruleba, R, Aryannejad, A, Asaad, M, Asemahagn, M, Asemi, Z, Asghari-Jafarabadi, M, Ashraf, T, Assadi, R, Athar, M, Athari, S, Atout, M, Attia, S, Aujayeb, A, Ausloos, M, Avila-Burgos, L, Awedew, A, Awoke, M, Awoke, T, Ayala Quintanilla, B, Ayana, T, Ayen, S, Azadi, D, Azadnajafabad, S, Azami-Aghdash, S, Azanaw, M, Azangou-Khyavy, M, Azari Jafari, A, Azizi, H, Azzam, A, Babajani, A, Badar, M, Badiye, A, Baghcheghi, N, Bagheri, N, Bagherieh, S, Bahadory, S, Baig, A, Baker, J, Bakhtiari, A, Bakshi, R, Banach, M, Banerjee, I, Bardhan, M, Barone-Adesi, F, Barra, F, Barrow, A, Bashir, N, Bashiri, A, Basu, S, Batiha, A, Begum, A, 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B., Lang J. J., Compton K., Xu R., Acheson A. R., Henrikson H. J., Kocarnik J. M., Penberthy L., Aali A., Abbas Q., Abbasi B., Abbasi-Kangevari M., Abbasi-Kangevari Z., Abbastabar H., Abdelmasseh M., Abd-Elsalam S., Abdelwahab A. A., Abdoli G., Abdulkadir H. A., Abedi A., Abegaz K. H., Abidi H., Aboagye R. G., Abolhassani H., Absalan A., Abtew Y. D., Abubaker Ali H., Abu-Gharbieh E., Achappa B., Acuna J. M., Addison D., Addo I. Y., Adegboye O. A., Adesina M. A., Adnan M., Adnani Q. E. S., Advani S. M., Afrin S., Afzal M. S., Aggarwal M., Ahinkorah B. O., Ahmad A. R., Ahmad R., Ahmad S., Ahmadi S., Ahmed H., Ahmed L. A., Ahmed M. B., Ahmed Rashid T., Aiman W., Ajami M., Akalu G. T., Akbarzadeh-Khiavi M., Aklilu A., Akonde M., Akunna C. J., Al Hamad H., Alahdab F., Alanezi F. M., Alanzi T. M., Alessy S. A., Algammal A. M., Al-Hanawi M. K., Alhassan R. K., Ali B. A., Ali L., Ali S. S., Alimohamadi Y., Alipour V., Aljunid S. M., Alkhayyat M., Al-Maweri S. A. A., Almustanyir S., Alonso N., Alqalyoobi S., Al-Raddadi R. M., Al-Rifai R. H. H., Al-Sabah S. K., Al-Tammemi A. B., Altawalah H., Alvis-Guzman N., Amare F., Ameyaw E. K., Aminian Dehkordi J. J., Amirzade-Iranaq M. H., Amu H., Amusa G. A., Ancuceanu R., Anderson J. A., Animut Y. A., Anoushiravani A., Anoushirvani A. A., Ansari-Moghaddam A., Ansha M. G., Antony B., Antwi M. H., Anwar S. L., Anwer R., Anyasodor A. E., Arabloo J., Arab-Zozani M., Aremu O., Argaw A. M., Ariffin H., Aripov T., Arshad M., Artaman A., Arulappan J., Aruleba R. T., Aryannejad A., Asaad M., Asemahagn M. A., Asemi Z., Asghari-Jafarabadi M., Ashraf T., Assadi R., Athar M., Athari S. S., Atout M. M. W., Attia S., Aujayeb A., Ausloos M., Avila-Burgos L., Awedew A. F., Awoke M. A., Awoke T., Ayala Quintanilla B. P., Ayana T. M., Ayen S. S., Azadi D., Azadnajafabad S., Azami-Aghdash S., Azanaw M. M., Azangou-Khyavy M., Azari Jafari A., Azizi H., Azzam A. Y. Y., Babajani A., Badar M., Badiye A. D., Baghcheghi N., Bagheri N., Bagherieh S., Bahadory S., Baig A. A., Baker J. L., Bakhtiari A., Bakshi R. K., Banach M., Banerjee I., Bardhan M., Barone-Adesi F., Barra F., Barrow A., Bashir N. Z., Bashiri A., Basu S., Batiha A. -M. M., Begum A., Bekele A. B., Belay A. S., Belete M. A., Belgaumi U. I., Bell A. W., Belo L., Benzian H., Berhie A. Y., Bermudez A. N. C., Bernabe E., Bhagavathula A. S., Bhala N., Bhandari B. B., Bhardwaj N., Bhardwaj P., Bhattacharyya K., Bhojaraja V. S., Bhuyan S. S., Bibi S., Bilchut A. H., Bintoro B. S., Biondi A., Birega M. G. B., Birhan H. E., Bjorge T., Blyuss O., Bodicha B. B. A., Bolla S. R., Boloor A., Bosetti C., Braithwaite D., Brauer M., Brenner H., Briko A. N., Briko N. I., Buchanan C. M., Bulamu N. B., Bustamante-Teixeira M. T., Butt M. H., Butt N. S., Butt Z. A., Caetano dos Santos F. L., Camera L. A., Cao C., Cao Y., Carreras G., Carvalho M., Cembranel F., Cerin E., Chakraborty P. A., Charalampous P., Chattu V. K., Chimed-Ochir O., Chirinos-Caceres J. L., Cho D. Y., Cho W. C. S., Christopher D. J., Chu D. -T., Chukwu I. S., Cohen A. J., Conde J., Cortes S., Costa V. M., Cruz-Martins N., Culbreth G. T., Dadras O., Dagnaw F. T., Dahlawi S. M. A., Dai X., Dandona L., Dandona R., Daneshpajouhnejad P., Danielewicz A., Dao A. T. M., Darvishi Cheshmeh Soltani R., Darwesh A. M., Das S., Davitoiu D. V., Davtalab Esmaeili E., De la Hoz F. P., Debela S. A., Dehghan A., Demisse B., Demisse F. W., Denova-Gutierrez E., Derakhshani A., Derbew Molla M., Dereje D., Deribe K. S., Desai R., Desalegn M. D., Dessalegn F. N., Dessalegni S. A. A., Dessie G., Desta A. A., Dewan S. M. R., Dharmaratne S. D., Dhimal M., Dianatinasab M., Diao N., Diaz D., Digesa L. E., Dixit S. G., Doaei S., Doan L. P., Doku P. N., Dongarwar D., dos Santos W. M., Driscoll T. R., Dsouza H. L., Durojaiye O. C., Edalati S., Eghbalian F., Ehsani-Chimeh E., Eini E., Ekholuenetale M., Ekundayo T. C., Ekwueme D. U., El Tantawi M., Elbahnasawy M. A., Elbarazi I., Elghazaly H., Elhadi M., El-Huneidi W., Emamian M. H., Engelbert Bain L., Enyew D. B., Erkhembayar R., Eshetu T., Eshrati B., Eskandarieh S., Espinosa-Montero J., Etaee F., Etemadimanesh A., Eyayu T., Ezeonwumelu I. J., Ezzikouri S., Fagbamigbe A. F., Fahimi S., Fakhradiyev I. R., Faraon E. J. A., Fares J., Farmany A., Farooque U., Farrokhpour H., Fasanmi A. O., Fatehizadeh A., Fatima W., Fattahi H., Fekadu G., Feleke B. E., Ferrari A. A., Ferrero S., Ferro Desideri L., Filip I., Fischer F., Foroumadi R., Foroutan M., Fukumoto T., Gaal P. A., Gad M. M., Gadanya M. A., Gaipov A., Galehdar N., Gallus S., Garg T., Gaspar Fonseca M., Gebremariam Y. H., Gebremeskel T. G., Gebremichael M. A., Geda Y. F., Gela Y. Y., Gemeda B. N. B., Getachew M., Getachew M. E., Ghaffari K., Ghafourifard M., Ghamari S. -H., Ghasemi Nour M., Ghassemi F., Ghimire A., Ghith N., Gholamalizadeh M., Gholizadeh Navashenaq J., Ghozy S., Gilani S. A., Gill P. S., Ginindza T. G., Gizaw A. T. T., Glasbey J. C., Godos J., Goel A., Golechha M., Goleij P., Golinelli D., Golitaleb M., Gorini G., Goulart B. N. G., Grosso G., Guadie H. A., Gubari M. I. M., Gudayu T. W., Guerra M. R., Gunawardane D. A., Gupta B., Gupta S., Gupta V. B., Gupta V. K., Gurara M. K., Guta A., Habibzadeh P., Haddadi Avval A., Hafezi-Nejad N., Hajj Ali A., Haj-Mirzaian A., Halboub E. S., Halimi A., Halwani R., Hamadeh R. R., Hameed S., Hamidi S., Hanif A., Hariri S., Harlianto N. I., Haro J. M., Hartono R. K., Hasaballah A. I., Hasan S. M. M., Hasani H., Hashemi S. M., Hassan A. M., Hassanipour S., Hayat K., Heidari G., Heidari M., Heidarymeybodi Z., Herrera-Serna B. Y., Herteliu C., Hezam K., Hiraike Y., Hlongwa M. M., Holla R., Holm M., Horita N., Hoseini M., Hossain M. M., Hossain M. B. H., Hosseini M. -S., Hosseinzadeh A., Hosseinzadeh M., Hostiuc M., Hostiuc S., Househ M., Huang J., Hugo F. N., Humayun A., Hussain S., Hussein N. R., Hwang B. -F., Ibitoye S. E., Iftikhar P. M., Ikuta K. S., Ilesanmi O. S., Ilic I. M., Ilic M. D., Immurana M., Innos K., Iranpour P., Irham L. M., Islam M. S., Islam R. M., Islami F., Ismail N. E., Isola G., Iwagami M., J L. M., Jaiswal A., Jakovljevic M., Jalili M., Jalilian S., Jamshidi E., Jang S. -I., Jani C. T., Javaheri T., Jayarajah U. U., Jayaram S., Jazayeri S. B., Jebai R., Jemal B., Jeong W., Jha R. P., Jindal H. A., John-Akinola Y. O., Jonas J. B., Joo T., Joseph N., Joukar F., Jozwiak J. J., Jurisson M., Kabir A., Kacimi S. E. O., Kadashetti V., Kahe F., Kakodkar P. V., Kalankesh L. R., Kalhor R., Kamal V. K., Kamangar F., Kamath A., Kanchan T., Kandaswamy E., Kandel H., Kang H., Kanno G. G., Kapoor N., Kar S. S., Karanth S. D., Karaye I. M., Karch A., Karimi A., Kassa B. G., Katoto P. D., Kauppila J. H., Kaur H., Kebede A. G., Keikavoosi-Arani L., Kejela G. G., Kemp Bohan P. M., Keramati M., Keykhaei M., Khajuria H., Khan A., Khan A. A. K., Khan E. A., Khan G., Khan M. N., Khan M. A., Khanali J., Khatab K., Khatatbeh M. M., Khatib M. N., Khayamzadeh M., Khayat Kashani H. R., Khazeei Tabari M. A., Khezeli M., Khodadost M., Kim M. S., Kim Y. J., Kisa A., Kisa S., Klugar M., Klugarova J., Kolahi A. -A., Kolkhir P., Kompani F., Koul P. A., Koulmane Laxminarayana S. L., Koyanagi A., Krishan K., Krishnamoorthy Y., Kucuk Bicer B., Kugbey N., Kulimbet M., Kumar A., Kumar G. A., Kumar N., Kurmi O. P., Kuttikkattu A., La Vecchia C., Lahiri A., Lal D. K., Lam J., Lan Q., Landires I., Larijani B., Lasrado S., Lau J., Lauriola P., Ledda C., Lee S. -W., Lee S. W. H., Lee W. -C., Lee Y. Y., Lee Y. H., Legesse S. M., Leigh J., Leong E., Li M. -C., Lim S. S., Liu G., Liu J., Lo C. -H., Lohiya A., Lopukhov P. D., Lorenzovici L., Lotfi M., Loureiro J. A., Lunevicius R., Madadizadeh F., Mafi A. R., Magdeldin S., Mahjoub S., Mahmoodpoor A., Mahmoudi M., Mahmoudimanesh M., Mahumud R. A., Majeed A., Majidpoor J., Makki A., Makris K. C., Malakan Rad E., Malekpour M. -R., Malekzadeh R., Malik A. A., Mallhi T. H., Mallya S. D., Mamun M. A., Manda A. L., Mansour-Ghanaei F., Mansouri B., Mansournia M. A., Mantovani L. G., Martini S., Martorell M., Masoudi S., Masoumi S. Z., Matei C. N., Mathews E., Mathur M. R., Mathur V., McKee M., Meena J. K., Mehmood K., Mehrabi Nasab E., Mehrotra R., Melese A., Mendoza W., Menezes R. G., Mengesha S. D., Mensah L. G., Mentis A. -F. A., Mera-Mamian A. Y. M., Meretoja T. J., Merid M. W., Mersha A. G., Meselu B. T., Meshkat M., Mestrovic T., Miao Jonasson J., Miazgowski T., Michalek I. M., Mijena G. F. W., Miller T. R., Mir S. A., Mirinezhad S. K., Mirmoeeni S., Mirza-Aghazadeh-Attari M., Mirzaei H., Mirzaei H. R., Misganaw A. S., Misra S., Mohammad K. A., Mohammadi E., Mohammadi M., Mohammadian-Hafshejani A., Mohammadpourhodki R., Mohammed A., Mohammed S., Mohan S., Mohseni M., Moka N., Mokdad A. H., Molassiotis A., Molokhia M., Momenzadeh K., Momtazmanesh S., Monasta L., Mons U., Montasir A. A., Montazeri F., Montero A., Moosavi M. A., Moradi A., Moradi Y., Moradi Sarabi M., Moraga P., Morawska L., Morrison S. D., Morze J., Mosapour A., Mostafavi E., Mousavi S. M., Mousavi Isfahani H., Mousavi Khaneghah A., Mpundu-Kaambwa C., Mubarik S., Mulita F., Munblit D., Munro S. B., Murillo-Zamora E., Musa J., Nabhan A. F., Nagarajan A. J., Nagaraju S. P., Nagel G., Naghipour M., Naimzada M. D., Nair T. S., Naqvi A. A., Narasimha Swamy S., Narayana A. I., Nassereldine H., Natto Z. S., Nayak B. P., Ndejjo R., Nduaguba S. O., Negash W. W., Nejadghaderi S. A., Nejati K., Neupane Kandel S., Nguyen H. V. N., Niazi R. K., Noor N. M., Noori M., Noroozi N., Nouraei H., Nowroozi A., Nunez-Samudio V., Nzoputam C. I., Nzoputam O. J., Oancea B., Odukoya O. O., Oghenetega O. B., Ogunsakin R. E., Oguntade A. S., Oh I. -H., Okati-Aliabad H., Okekunle A. P., Olagunju A. T., Olagunju T. O., Olakunde B. O., Olufadewa I. I., Omer E., Omonisi A. E. E., Ong S., Onwujekwe O. E., Orru H., Otstavnov S. S., Oulhaj A., Oumer B., Owopetu O. F., Oyinloye B. E., P A M., Padron-Monedero A., Padubidri J. R., Pakbin B., Pakshir K., Pakzad R., Palicz T., Pana A., Pandey A., Pant S., Pardhan S., Park E. -C., Park E. -K., Park S., Patel J., Pati S., Paudel R., Paudel U., Paun M., Pazoki Toroudi H., Peng M., Pereira J., Pereira R. B., Perna S., Perumalsamy N., Pestell R. G., Pezzani R., Piccinelli C., Pillay J. D., Piracha Z. Z., Pischon T., Postma M. J., Pourabhari Langroudi A., Pourshams A., Pourtaheri N., Prashant A., Qadir M. M. F., Quazi Syed Z., Rabiee M., Rabiee N., Radfar A., Radhakrishnan R. A., Radhakrishnan V., Raeisi M., Rafiee A., Rafiei A., Raheem N., Rahim F., Rahman M. O., Rahman M., Rahman M. A., Rahmani A. M., Rahmani S., Rahmanian V., Rajai N., Rajesh A., Ram P., Ramezanzadeh K., Rana J., Ranabhat K., Ranasinghe P., Rao C. R., Rao S. J., Rashedi S., Rashidi A., Rashidi M., Rashidi M. -M., Ratan Z. A., Rawaf D. L., Rawaf S., Rawal L., Rawassizadeh R., Razeghinia M. S., Rehman A. U., Rehman I. U., Reitsma M. B., Renzaho A. M. N., Rezaei M., Rezaei N., Rezaei S., Rezaeian M., Rezapour A., Riad A., Rikhtegar R., Rios-Blancas M., Roberts T. J., Rohloff P., Romero-Rodriguez E., Roshandel G., Rwegerera G. M., S M., Saber-Ayad M. M., Saberzadeh-Ardestani B., Sabour S., Saddik B., Sadeghi E., Saeb M. R., Saeed U., Safaei M., Safary A., Sahebazzamani M., Sahebkar A., Sahoo H., Sajid M. R., Salari H., Salehi S., Salem M. R., Salimzadeh H., Samodra Y. L., Samy A. M., Sanabria J., Sankararaman S., Sanmarchi F., Santric-Milicevic M. M., Saqib M. A. N., Sarveazad A., Sarvi F., Sathian B., Satpathy M., Sayegh N., Schneider I. J. C., Schwarzinger M., Sekerija M., Senthilkumaran S., Sepanlou S. G., Seylani A., Seyoum K., Sha F., Shafaat O., Shah P. A., Shahabi S., Shahid I., Shahrbaf M. A., Shahsavari H. R., Shaikh M. A., Shaka M. F., Shaker E., Shannawaz M., Sharew M. M. S., Sharifi A., Sharifi-Rad J., Sharma P., Shashamo B. B., Sheikh A., Sheikh M., Sheikhbahaei S., Sheikhi R. A., Sheikhy A., Shepherd P. R., Shetty A., Shetty J. K., Shetty R. S., Shibuya K., Shirkoohi R., Shirzad-Aski H., Shivakumar K. M., Shivalli S., Shivarov V., Shobeiri P., Shokri Varniab Z., Shorofi S. A., Shrestha S., Sibhat M. M., Siddappa Malleshappa S. K., Sidemo N. B., Silva D. A. S., Silva L. M. L. R., Silva Julian G., Silvestris N., Simegn W., Singh A. D., Singh A., Singh G., Singh H., Singh J. A., Singh J. K., Singh P., Singh S., Sinha D. N., Sinke A. H., Siraj M. S., Sitas F., Siwal S. S., Skryabin V. Y., Skryabina A. A., Socea B., Soeberg M. J., Sofi-Mahmudi A., Solomon Y., Soltani-Zangbar M. S., Song S., Song Y., Sorensen R. J. D., Soshnikov S., Sotoudeh H., Sowe A., Sufiyan M. B., Suk R., Suleman M., Suliankatchi Abdulkader R., Sultana S., Sur D., Szocska M., Tabaeian S. P., Tabares-Seisdedos R., Tabatabaei S. M., Tabuchi T., Tadbiri H., Taheri E., Taheri M., Taheri Soodejani M., Takahashi K., Talaat I. M., Tampa M., Tan K. -K., Tat N. Y., Tat V. Y., Tavakoli A., Tehrani-Banihashemi A., Tekalegn Y., Tesfay F. H., Thapar R., Thavamani A., Thoguluva Chandrasekar V., Thomas N., Thomas N. K., Ticoalu J. H. V., Tiyuri A., Tollosa D. N., Topor-Madry R., Touvier M., Tovani-Palone M. R., Traini E., Tran M. T. N., Tripathy J. P., Ukke G. G., Ullah I., Ullah S., Unnikrishnan B., Vacante M., Vaezi M., Valadan Tahbaz S., Valdez P. R., Vardavas C., Varthya S. B., Vaziri S., Velazquez D. Z., Veroux M., Villeneuve P. J., Violante F. S., Vladimirov S. K., Vlassov V., Vo B., Vu L. G., Wadood A. W., Waheed Y., Walde M. T., Wamai R. G., Wang C., Wang F., Wang N., Wang Y., Ward P., Waris A., Westerman R., Wickramasinghe N. D., Woldemariam M., Woldu B., Xiao H., Xu S., Xu X., Yadav L., Yahyazadeh Jabbari S. H., Yang L., Yazdanpanah F., Yeshaw Y., Yismaw Y., Yonemoto N., Younis M. Z., Yousefi Z., Yousefian F., Yu C., Yu Y., Yunusa I., Zahir M., Zaki N., Zaman B. A., Zangiabadian M., Zare F., Zare I., Zareshahrabadi Z., Zarrintan A., Zastrozhin M. S., Zeineddine M. A., Zhang D., Zhang J., Zhang Y., Zhang Z. -J., Zhou L., Zodpey S., Zoladl M., Vos T., Hay S. I., Force L. M., and Murray C. J. L.

Abstract

Background: Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods: The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings: Globally, in 2019, the risk factors included in this analysis accounted for 4·45 million (95% uncertainty interval 4·01-4·94) deaths and 105 million (95·0-116) DALYs for both sexes combined, representing 44·4% (41·3-48·4) of all cancer deaths and 42·0% (39·1-45·6) of all DALYs. There were 2·88 million (2·60-3·18) risk-attributable cancer deaths in males (50·6% [47·8-54·1] of all male cancer deaths) and 1·58 million (1·36-1·84) risk-attributable cancer deaths in females (36·3% [32·5-41·3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20·4% (12·6-28·4) and DALYs by 16·8% (8·8-25·0), with the greatest percentage increase in metabolic risks (34·7% [2

Published
2022

13. Data from Attractin Is Elevated in the Cerebrospinal Fluid of Patients with Malignant Astrocytoma and Mediates Glioma Cell Migration

Author

Erwin G. Van Meir, Daniel J. Brat, Jonathan S. Duke-Cohan, and Fatima W. Khwaja

Abstract

Purpose: There are a limited number of noninvasive methods available for the monitoring of neoplastic disease in the central nervous system. The goal of our study was to find reliable markers that could be used for disease monitoring as well as to identify new targets for the therapeutic intervention for malignant astrocytoma (WHO grades 3 and 4).Experimental Design: We employed proteomic techniques to identify secreted proteins in the cerebrospinal fluid that were specific to patients with malignant astrocytoma.Results: Among 60 cerebrospinal fluid samples of patients with various central nervous system diseases, attractin was consistently found to be elevated in the samples of patients with malignant astrocytoma. To independently validate these results, we examined attractin expression in a new set of 108 normal and tumoral brain tissue specimens and found elevated expression in 97% of malignant astrocytomas, with the highest levels in grade 4 tumors. Using immunohistochemistry, we further showed that attractin is produced and secreted by the tumor cells. Finally, we showed that cerebrospinal fluid from brain tumor patients induces glioma cell migration and that attractin is largely responsible for this promigratory activity.Conclusions: Our results find attractin to be a reliable secreted marker for high-grade gliomas. Additionally, our migration studies suggest that it may be an important mediator of tumor invasiveness, and thus, a potential target in future therapies.

Published
2023

23. ICES Scientific Reports Volume 2 | Issue 85 JOINT EIFAAC/ICES/GFCM WORKING GROUP ON EELS (WGEEL)

Author

Elsa, A, Jânis, B, Laurent, B, Claude, B, Priit, B, Clarisse, B, Uwe, B, Cédric, B, Andreas, B, Mads, C, Ciccotti, E, Willem, D, Estibaliz, D, Isabel, D, Hilaire, D, Caroline, D, Derek, E, Marko, F, Jason, G, Matthew, G, Tessa van der Hammen, Reinhold, H, Leone, C, Linas, L, Lasse, M, Tomasz, N, Ciara, O, Sukran Yalçin Özdilek, Michael Ingemann Pedersen, Jan-Dag, P, Russell, P, Robert, R, Argyris, S, Kerry, S, Josefin, S, Rimantè, S, Arvydas, S, Ayesha, T, Eva, T, Rüdolfs, T, Sami, V, Alan, W, Fatima, W, Håkan, W, and Klaus, W

Subjects
Settore BIO/07
Published
2020

29. Safety of combination antiretroviral prophylaxis in high-risk HIV-exposed newborns: a retrospective review of the Canadian experience

Author

Kakkar, Fatima W., Samson, Lindy, Vaudry, Wendy, Brophy, Jason, Le Meur, Jean-Baptiste, Lapointe, Normand, Read, Stanley E., and Bitnun, Ari

Subjects
Prophylaxis -- Research -- Health aspects, Highly active antiretroviral therapy -- Safety and security measures -- Health aspects, HIV infections -- Drug therapy -- Risk factors, Newborn infants -- Drug therapy -- Safety and security measures, Health
Abstract

Introduction: The optimal management of infants born to HIV-positive mothers who are untreated or have detectable viral load prior to delivery remains controversial. Despite the increasing use of combination antiretroviral therapy (cART) for post-exposure prophylaxis (PEP) of neonates at high risk of HIV infection, there is little safety and pharmacokinetic data to support this approach. The objective of this study was to evaluate the safety and tolerability of cART for PEP in HIV-exposed neonates. Methods: Retrospective study on 148 cART and 145 Zidovudine (ZDV) monotherapy-exposed infants identified from four Canadian centres where cART for PEP has routinely been prescribed in high-risk situations. Physician-reported adverse events and clinical outcomes were extracted by chart review. Haematological and growth parameters at birth, one and six months of age were compared between cART and ZDV-exposed infants using multivariate mixed effects modelling. Results: Non-specific signs and symptoms were reported in 10.2% of cART recipients versus none of the ZDV recipients. Treatment was discontinued prematurely in 9.5% of cART recipients versus 2.1% of ZDV recipients (p = 0.01). In the multivariate model, cART recipients had lower mean haemoglobin (decrease of 2.07 g/L) over the 6-month period compared with ZDV recipients (p = 0.04), but no effect was seen on absolute neutrophil count. cART recipients had lower weight and smaller head circumference at birth and one month of age compared with ZDV-exposed infants; these differences were no longer significant at six months of age. Conclusions: cART administered at treatment doses for PEP in neonates was generally well tolerated, though a higher incidence of non-specific signs and symptoms and early treatment discontinuation occurred among cART recipients. Keywords: Prevention of mother-to-child transmission; HIV; neonatal prophylaxis; safety; combination antiretroviral therapy., Introduction While the overall risk of perinatal HIV transmission in the developed world has decreased to less than 1%, transmission still occurs, most often due to failure to diagnose HIV [...]

Published
2016
Full Text
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30. Performance Evaluation and Comparison of Software Defined Networks Controllers

Author

Mahmood Z. Abdullah, Nasir A. Al-awad, and Fatima W. Hussein

Abstract

Software Defined Networking (SDN) is a new network architecture, the controller which is one of its components represents the intelligent part of it. Today, there exists many SDN controllers including: Beacon, Floodlight, Iris, Libfluid, Maestro, NOX, ONOS, and others. The question is which controller can perform better in which situations. Several works were done to compare these controllers with respect to efficiency, controllers’ features, and architecture. Because of the controller importance in the SDN architecture, it should be given a proper attention to any proposal or design. In this paper, a Performance evaluation test of five controllers (libfluid, ONOS, OpenDaylight, POX and Ryu) is done in terms of End to End throughput and End to End delay by using Iperf and Ping commands. The test is done using linear topology that is built in Mininet emulator, with different number of switches. This paper introduces a new contribution in measuring the ability of the five controllers to give a throughput and delay responses while increasing the load on the linear topology and at what point of network load (number of switches) the controllers stop responding. Even though the results show that libfluid gives the best throughput performance and POX gives the best delay performance, the selection of the best performing controller should be based on several criteria, per the user requirements.

Published
2018
Full Text
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36. Safety of combination antiretroviral prophylaxis in high-risk HIV-exposed newborns: a retrospective review of the Canadian experience

Author

Wendy Vaudry, Lindy Samson, Ari Bitnun, Normand Lapointe, Jason Brophy, Fatima W Kakkar, Jean-Baptiste Le Meur, and Stanley E. Read

Subjects
0301 basic medicine, Cart, Adult, Male, safety, Pediatrics, medicine.medical_specialty, Canada, Anti-HIV Agents, 030106 microbiology, Short Report, HIV Infections, 03 medical and health sciences, Zidovudine, neonatal prophylaxis, 0302 clinical medicine, Acquired immunodeficiency syndrome (AIDS), immune system diseases, Pregnancy, medicine, Humans, 030212 general & internal medicine, Adverse effect, Retrospective Studies, Prevention of mother-to-child transmission, business.industry, Public Health, Environmental and Occupational Health, Infant, Newborn, virus diseases, HIV, Retrospective cohort study, medicine.disease, Infectious Disease Transmission, Vertical, Discontinuation, Infectious Diseases, Tolerability, combination antiretroviral therapy, Drug Therapy, Combination, Female, business, Viral load, medicine.drug
Abstract

Introduction : The optimal management of infants born to HIV-positive mothers who are untreated or have detectable viral load prior to delivery remains controversial. Despite the increasing use of combination antiretroviral therapy (cART) for post-exposure prophylaxis (PEP) of neonates at high risk of HIV infection, there is little safety and pharmacokinetic data to support this approach. The objective of this study was to evaluate the safety and tolerability of cART for PEP in HIV-exposed neonates. Methods : Retrospective study on 148 cART and 145 Zidovudine (ZDV) monotherapy-exposed infants identified from four Canadian centres where cART for PEP has routinely been prescribed in high-risk situations. Physician-reported adverse events and clinical outcomes were extracted by chart review. Haematological and growth parameters at birth, one and six months of age were compared between cART and ZDV-exposed infants using multivariate mixed effects modelling. Results : Non-specific signs and symptoms were reported in 10.2% of cART recipients versus none of the ZDV recipients. Treatment was discontinued prematurely in 9.5% of cART recipients versus 2.1% of ZDV recipients ( p= 0.01). In the multivariate model, cART recipients had lower mean haemoglobin (decrease of 2.07 g/L) over the 6-month period compared with ZDV recipients ( p= 0.04), but no effect was seen on absolute neutrophil count. cART recipients had lower weight and smaller head circumference at birth and one month of age compared with ZDV-exposed infants; these differences were no longer significant at six months of age. Conclusions : cART administered at treatment doses for PEP in neonates was generally well tolerated, though a higher incidence of non-specific signs and symptoms and early treatment discontinuation occurred among cART recipients. Keywords: Prevention of mother-to-child transmission; HIV; neonatal prophylaxis; safety; combination antiretroviral therapy. To access the supplementary material to this article please see Supplementary Files in the column to the right (under Article Tools). (Published: 12 February 2016) Citation: Kakkar FW. Journal of the International AIDS Society 2016, 19 :20520 http://www.jiasociety.org/index.php/jias/article/view/20520 | http://dx.doi.org/10.7448/IAS.19.1.20520

Published
2015

37. Implementation of Entropy-based Distributed Denial of Service Attack Detection Method in Multiple POX Controllers.

Author

Abdullah, Mahmood Z., Al-awad, Nasir A., and Hussein, Fatima W.

Subjects
COMPUTER network security, DENIAL of service attacks, COMPUTER algorithms, COMPUTER software, ELECTRONIC controllers
Abstract

Software Defined Networks (SDN) differs from traditional networks, it splits the control from the data plane. The controller is an essential and important part in SDN architecture; and it is exposed to many potential security challenges, one of such critical challenges is the impact of Distributed Denial of Service (DDoS) attack. The objective of this study is to implement an Entropy-based detection algorithm for DDoS attacks in SDN networks using POX controller to improve the network security, and to test the performance of this algorithm using POX controller in different topologies and different number of controllers. In this paper the Entropybased detection algorithm was carried out in different tests that include connecting POX controller to single topology with 64 hosts and then different number of POX controller had been connected to linear topology with 64 hosts. Through this study, it was found that the Entropy detection method works better in lightly loaded network and the results indicate that increasing the number of controllers can improve the security of the network. This paper introduces a new contribution in implementing a statistical DDoS detection method in multiple POX controllers and in different topologies to improve the security of the SDN network. [ABSTRACT FROM AUTHOR]

Published
2019
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38. Hypoxia and the hypoxia-inducible-factor pathway in glioma growth and angiogenesis

Author

Erwin G. Van Meir, Daniel J. Brat, Balveen Kaur, Fatima W. Khwaja, Shannon L. Matheny, and Eric Allan Severson

Subjects
Cancer Research, medicine.medical_specialty, Hypoxia-Inducible Factor 1, Tumor microenvironment, Angiogenesis, Biology, Vascular endothelial growth factor, Angiopoietin, chemistry.chemical_compound, Endocrinology, Oncology, Hypoxia-inducible factors, chemistry, Internal medicine, medicine, Hypoxia-Inducible Factor Pathway, Cancer research, Neurology (clinical), Transforming growth factor
Abstract

Glioblastomas, like other solid tumors, have extensive areas of hypoxia and necrosis. The importance of hypoxia in driving tumor growth is receiving increased attention. Hypoxia-inducible factor 1 (HIF-1) is one of the master regulators that orchestrate the cellular responses to hypoxia. It is a heterodimeric transcription factor composed of alpha and beta subunits. The alpha subunit is stable in hypoxic conditions but is rapidly degraded in normoxia. The function of HIF-1 is also modulated by several molecular mechanisms that regulate its synthesis, degradation, and transcriptional activity. Upon stabilization or activation, HIF-1 translocates to the nucleus and induces transcription of its downstream target genes. Most important to gliomagenesis, HIF-1 is a potent activator of angiogenesis and invasion through its upregulation of target genes critical for these functions. Activation of the HIF-1 pathway is a common feature of gliomas and may explain the intense vascular hyperplasia often seen in glioblastoma multiforme. Activation of HIF results in the activation of vascular endothelial growth factors, vascular endothelial growth factor receptors, matrix metalloproteinases, plasminogen activator inhibitor, transforming growth factors alpha and beta, angiopoietin and Tie receptors, endothelin-1, inducible nitric oxide synthase, adrenomedullin, and erythropoietin, which all affect glioma angiogenesis. In conclusion, HIF is a critical regulatory factor in the tumor microenvironment because of its central role in promoting proangiogenic and invasive properties. While HIF activation strongly promotes angiogenesis, the emerging vasculature is often abnormal, leading to a vicious cycle that causes further hypoxia and HIF upregulation.

Published
2005

39. Cervical surveillance in HIV-positive women: a genitourinary medicine clinic experience

Author

Jyoti Dhar, Fatima W Ibrahim, Sati Ariyanayagam, Gabriel Schembri, and Huda Taha

Subjects
Adult, medicine.medical_specialty, Adolescent, Referral, Dyskaryosis, Uterine Cervical Neoplasms, HIV Infections, Cervical intraepithelial neoplasia, Young Adult, Prevalence, Humans, Mass Screening, Medicine, Cervix, Mass screening, Retrospective Studies, Colposcopy, Gynecology, Cervical screening, medicine.diagnostic_test, business.industry, Obstetrics and Gynecology, Retrospective cohort study, General Medicine, Middle Aged, Uterine Cervical Dysplasia, medicine.disease, United Kingdom, medicine.anatomical_structure, Reproductive Medicine, Family medicine, Female, business
Abstract

Background The prevalence of cervical intraepithelial neoplasia (CIN) is increased in HIV infection. The UK National Health Service Cervical Screening Programme (NHSCSP) guidelines therefore provide specific recommendations for HIV-positive women. An audit of cervical surveillance in HIV-positive women who attend the genitourinary medicine (GUM) department at the Leicester Royal Infirmary, Leicester, UK was conducted. The objectives were to assess adherence to UK and local screening guidelines, prevalence of cervical pathology and appropriate referral for colposcopy. Methods A retrospective case note review of 130 HIV-infected women attending the GUM department between January 2000 and December 2005 was undertaken. Results Results showed that 76.2% of patients had cervical cytology within a year of HIV diagnosis and 42.4% of patients had abnormal cytology. All patients with dyskaryosis were referred for colposcopy according to local and national guidelines. Cytology results were consistent with histological findings and the prevalence of CIN was 15.2%. CD4 counts at presentation were significantly lower in those with dyskaryosis compared with those without dyskaryosis ( p = 0.038). Twenty-two patients were lost to follow-up after initial cytology. Discussion and conclusions A designated health advisor in the GUM department co-ordinates cervical surveillance in HIV-positive women. This, together with an increasingly integrated service with family planning services, may contribute to relatively successful surveillance. Overall, patients are carefully monitored to ensure that surveillance is adequate. Extra vigilance is, however, required and further cost-effective measures in future may include more active involvement of general practitioners.

Published
2009

40. Prognostic markers of astrocytoma: how to predict the unpredictable?

Author

Fatima W Khwaja

Subjects
Oncology, medicine.medical_specialty, Pathology, Stereotactic biopsy, medicine.diagnostic_test, Performance status, business.industry, Biochemistry (medical), Tumor resection, Biomedical Engineering, Astrocytoma, Patient characteristics, General Medicine, medicine.disease, World health, Glioma, Internal medicine, medicine, Molecular Medicine, Who classification, business
Abstract

Astrocytomas are the most frequent tumors originating in the human nervous system. They carry a dismal prognosis as high-grade astroctyoma patients (World Health Organization [WHO] grade III and IV) rarely live beyond 5 years. At present, these tumors are mainly diagnosed through the difficult task of histologic examination of tissue obtained through stereotactic biopsy or tumor resection. In addition to determining the malignancy grade through histologic studies, the only other prognostic factors used in clinical setting are patient age and performance status. To overcome current limitations, research is underway to develop molecular approaches for glioma classification. These include identification, characterization and expansion of clinical (patient characteristics and imaging variables), histologic (WHO classification criteria) and molecular (genetic and proteomic) factors with prognostic potential. In this review the established classification characteristics, along with recent advances that may lead to the addition of new parameters and thus improve patient management and survival, are discussed.

Published
2013

41. Proteomic Discovery of Biomarkers in the Cerebrospinal Fluid of Brain Tumor Patients

Author

Fatima W. Khwaja and Erwin G. Van Meir

Subjects
Antibody microarray, Proteomic Profiling, business.industry, Central nervous system, Brain tumor, medicine.disease, Bioinformatics, Pathogenesis, Cns neoplasms, Cerebrospinal fluid, medicine.anatomical_structure, medicine, business, CSF albumin
Abstract

Central nervous system (CNS) diseases often induce changes in the protein composition of the cerebrospinal fluid (CSF) as this liquid bathes the brain and collects its secreted products. The detection and monitoring of such pathology-related changes can be exploited for their relation to tumor growth in the brain. The potential of using differential proteomic profiling in CNS malignancies to identify diagnostic, prognostic, and therapeutic response markers as well as therapeutic targets is currently being actively investigated. Furthermore, elucidation of the CSF oncoproteome may yield important biological insights into the pathogenesis of CNS neoplasms. New proteomic technology forecasts rapid screening, low sample consumption, and accurate protein identification in the CSF. These technological improvements will permit the gathering of reliable data on CSF protein composition in a clinically relevant microchip format in the foreseeable future. Here we review the current status of proteomic technology and its application to CNS cancers, with a focus on translational studies.

Published
2009

42. Proteomic identification of biomarkers in the cerebrospinal fluid (CSF) of astrocytoma patients

Author

Erwin G. Van Meir, G. Yancey Gillespie, Fatima W. Khwaja, Jan Pohl, Matthew S. Reed, Abhijit Guha, Santosh Kesari, Jeffrey J. Olson, Brian Schmotzer, and Morris D. Groves

Subjects
Pathology, medicine.medical_specialty, Two-dimensional gel electrophoresis, Proteome, Brain tumor, Astrocytoma, Affinity Labels, General Chemistry, Glioma, Biology, Proteomics, medicine.disease, Bioinformatics, Biochemistry, Sensitivity and Specificity, Article, Neoplasm Proteins, Cerebrospinal fluid, medicine, Biomarkers, Tumor, Humans, Biomarker discovery
Abstract

The monitoring of changes in the protein composition of the cerebrospinal fluid (CSF) can be used as a sensitive indicator of central nervous system (CNS) pathology, yet its systematic application to analysis of CNS neoplasia has been limited. There is a pressing need for both a better understanding of gliomagenesis and the development of reliable biomarkers of the disease. In this report, we used two proteomic techniques, two-dimensional gel electrophoresis (2-DE), and cleavable Isotope-Coded Affinity Tag (cICAT) to compare CSF proteomes to identify tumor- and grade-specific biomarkers in patients bearing brain tumors of differing histologies and grades. Retrospective analyses were performed on 60 samples derived from astrocytomas WHO grade II, III, and IV, schwannomas, metastastic brain tumors, inflammatory samples, and non-neoplastic controls. We identified 103 potential tumor-specific markers of which 20 were high-grade astrocytoma-specific. These investigations allowed us to identify a spectrum of signature proteins that could be used to distinguish CSF derived from control patients versus those with low- (AII) or high-grade (AIV) astrocytoma. These proteins may represent new diagnostic, prognostic, and disease follow-up markers when used alone or in combination. These candidate biomarkers may also have functional properties that play a critical role in the development and malignant progression of human astrocytomas, thus possibly representing novel therapeutic targets for this highly lethal disease.

Published
2007

43. Attractin is elevated in the cerebrospinal fluid of patients with malignant astrocytoma and mediates glioma cell migration

Author

Erwin G. Van Meir, Fatima W. Khwaja, Jonathan S. Duke-Cohan, and Daniel J. Brat

Subjects
Cancer Research, Pathology, medicine.medical_specialty, Central nervous system, Blotting, Western, Brain tumor, Biology, Astrocytoma, Central nervous system disease, Cerebrospinal fluid, Cell Movement, Glioma, medicine, Humans, Electrophoresis, Gel, Two-Dimensional, Neoplasm Invasiveness, Brain Neoplasms, Membrane Proteins, Cell migration, medicine.disease, Immunohistochemistry, Blot, medicine.anatomical_structure, Oncology
Abstract

Purpose: There are a limited number of noninvasive methods available for the monitoring of neoplastic disease in the central nervous system. The goal of our study was to find reliable markers that could be used for disease monitoring as well as to identify new targets for the therapeutic intervention for malignant astrocytoma (WHO grades 3 and 4).Experimental Design: We employed proteomic techniques to identify secreted proteins in the cerebrospinal fluid that were specific to patients with malignant astrocytoma.Results: Among 60 cerebrospinal fluid samples of patients with various central nervous system diseases, attractin was consistently found to be elevated in the samples of patients with malignant astrocytoma. To independently validate these results, we examined attractin expression in a new set of 108 normal and tumoral brain tissue specimens and found elevated expression in 97% of malignant astrocytomas, with the highest levels in grade 4 tumors. Using immunohistochemistry, we further showed that attractin is produced and secreted by the tumor cells. Finally, we showed that cerebrospinal fluid from brain tumor patients induces glioma cell migration and that attractin is largely responsible for this promigratory activity.Conclusions: Our results find attractin to be a reliable secreted marker for high-grade gliomas. Additionally, our migration studies suggest that it may be an important mediator of tumor invasiveness, and thus, a potential target in future therapies.

Published
2006

44. Proteomic analysis of cerebrospinal fluid discriminates malignant and nonmalignant disease of the central nervous system and identifies specific protein markers

Author

James C. Ritchie, Erwin G. Van Meir, Savaas E. Mendrinos, Daniel J. Brat, Melinda M. Lewis, Jeffrey J. Olson, Fatima W. Khwaja, Jan Pohl, and John D. L. Nolen

Subjects
Adult, Male, Proteomics, Central nervous system, Brain tumor, Disease, Biology, Biochemistry, Central nervous system disease, Cerebrospinal fluid, Central Nervous System Diseases, Tandem Mass Spectrometry, medicine, Humans, Molecular Biology, Aged, Inflammation, Brain Neoplasms, Cerebrospinal Fluid Proteins, Middle Aged, medicine.disease, Molecular biology, medicine.anatomical_structure, Cystatin C, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Proteome, Immunology, biology.protein, Female, Biomarkers
Abstract

CNS diseases are often accompanied by changes in the protein composition of cerebrospinal fluid (CSF). SELDI-TOF-MS provides an approach for identifying specific protein markers of disease in biological fluids. We compared the CSF proteomes from patients with neoplastic and reactive/inflammatory CNS diseases to identify potential biomarkers. SELDI-TOF-MS was performed on CSF derived from lumbar puncture of 32 patients, including 10 with CNS malignancies, 12 with inflammatory or reactive conditions, and 10 with unknown CNS disease. Using the SAX-2 (strong anionic exchange) chip, we uncovered three conserved protein peak ranges within each disease category. For neoplastic diseases, we identified conserved peaks at 7.5-8.0 kDa (9/10 samples), 15.1-15.9 kDa (8/10 samples), and 30.0-32.0 kDa (5/10 samples). In reactive/inflammatory diseases, conserved peaks were found at 6.7-7.1 kDa (10/12 samples), 11.5-11.9 kDa (12/12 samples), and 13.3-13.7 kDa (9/12 samples). A protein from the 30.0 to 32.0 kDa peak range found in neoplastic CSF was identified by MALDI analysis as carbonic anhydrase, a protein overexpressed in many malignancies including high-grade gliomas. Similarly, cystatin C was identified in the 13.3-13.7 kDa peak range in non-neoplastic CSF and was most prominent in inflammatory conditions. Our approach provides a rational basis for identifying biomarkers that could be used for detection, diagnosis, and monitoring of CNS diseases.

Published
2006

45. Proteomic identification of the wt-p53-regulated tumor cell secretome

Author

Fatima W. Khwaja, Jan Pohl, Pavel Svoboda, Matthew S. Reed, Beata Pyrzynska, and E. G. Van Meir

Subjects
Cancer Research, Tumor suppressor gene, Proteome, Cell, Biology, medicine.disease_cause, Proteomics, Cell Line, Tumor, Genetics, medicine, Humans, Secretion, Electrophoresis, Gel, Two-Dimensional, Molecular Biology, Tumor microenvironment, Cell biology, Neoplasm Proteins, Gene Expression Regulation, Neoplastic, Protein Transport, medicine.anatomical_structure, Secretory protein, Cell Transformation, Neoplastic, Isotope Labeling, Immunology, Tumor Suppressor Protein p53, Carcinogenesis, Glioblastoma, Protein Processing, Post-Translational, Intracellular
Abstract

Tumor-stroma interactions play a major role in tumor development, maintenance and progression. Yet little is known on how the genetic alterations that underlie cell transformation elicit cell extrinsic changes modulating heterotypic cell interactions. We hypothesized that these events involve a modification in the complement of secreted proteins by the cell, acting as mediators of intercellular communication. To test this hypothesis, we examined the role of wt-p53, a major tumor suppressor, on the tumor microenvironment through its regulation of secreted factors. Using a combination of 2-DE and cICAT proteomic techniques, we found a total of 111 secreted proteins, 39 of which showed enhanced and 21 inhibited secretion in response to wt-p53 expression. The majority of these were not direct targets of p53 transcription factor activity, suggesting a novel role for wt-p53 in the control of intracellular protein trafficking and/or secreted protein stability. Evidence for p53-controlled post-translational modifications on nine secreted proteins was also found. These findings will enhance our understanding of wt-p53 modulated interactions of the tumor with its environment.

Published
2006

46. Regulation of Bim by TCR signals in CD4/CD8 double-positive thymocytes

Author

Anna Bunin, Fatima W. Khwaja, and Gilbert J. Kersh

Subjects
CD3 Complex, CD8 Antigens, Immunology, Double negative, Dose-Response Relationship, Immunologic, Receptors, Antigen, T-Cell, bcl-X Protein, chemical and pharmacologic phenomena, Apoptosis, Thymus Gland, Mitochondrion, Microtubules, Dexamethasone, Negative selection, Mice, T-Lymphocyte Subsets, Proto-Oncogene Proteins, Immunology and Allergy, Animals, Phosphorylation, Mice, Knockout, Bcl-2-Like Protein 11, Chemistry, T-cell receptor, Models, Immunological, Antibodies, Monoclonal, Membrane Proteins, hemic and immune systems, Subcellular localization, Mice, Inbred C57BL, Cross-Linking Reagents, Proto-Oncogene Proteins c-bcl-2, CD4 Antigens, Injections, Intravenous, Cancer research, biological phenomena, cell phenomena, and immunity, Apoptosis Regulatory Proteins, Carrier Proteins, CD8, Protein Binding, Signal Transduction
Abstract

Bim, a BH3-only Bcl-2 family member, is required for apoptosis of thymocytes in response to negative selection signals. Regulation of the apoptotic activity of Bim during negative selection is not understood. In this study we demonstrate that in murine thymocytes undergoing apoptosis in response to anti-CD3ε injection, levels of Bim protein expression do not change. In immature thymocytes, Bim is associated with mitochondria before stimulation and is not regulated by a change in subcellular localization during apoptosis. We also show that BimEL is rapidly phosphorylated in thymocytes in response to CD3ε cross-linking both in vivo and in vitro, and that phosphorylation is sustained for at least 24 h. Analysis of MHC-deficient mice shows that phosphorylation of Bim occurs in CD4/CD8 double-positive thymocytes and does not depend on activation of mature T cells. We also find that TCR cross-linking on thymocytes induces an increase in the proportion of Bcl-xL bound to Bim at late time points. Our results favor a model in which strong TCR signals regulate the apoptotic activity of Bim by phosphorylation and subsequent changes in binding to Bcl-xL in immature thymocytes.

Published
2005

47. Hypoxia and the hypoxia-inducible-factor pathway in glioma growth and angiogenesis1

Author

Kaur, Balveen, Khwaja, Fatima W., Severson, Eric A., Matheny, Shannon L., Brat, Daniel J., and Van Meir, Erwin G.

Subjects
DNA-Binding Proteins, Neovascularization, Pathologic, Brain Neoplasms, Humans, Nuclear Proteins, Symposium on Angiogenesis, Part 1, Glioma, Hypoxia-Inducible Factor 1, Hypoxia, Hypoxia-Inducible Factor 1, alpha Subunit, Signal Transduction, Transcription Factors
Abstract

Glioblastomas, like other solid tumors, have extensive areas of hypoxia and necrosis. The importance of hypoxia in driving tumor growth is receiving increased attention. Hypoxia-inducible factor 1 (HIF-1) is one of the master regulators that orchestrate the cellular responses to hypoxia. It is a heterodimeric transcription factor composed of alpha and beta subunits. The alpha subunit is stable in hypoxic conditions but is rapidly degraded in normoxia. The function of HIF-1 is also modulated by several molecular mechanisms that regulate its synthesis, degradation, and transcriptional activity. Upon stabilization or activation, HIF-1 translocates to the nucleus and induces transcription of its downstream target genes. Most important to gliomagenesis, HIF-1 is a potent activator of angiogenesis and invasion through its upregulation of target genes critical for these functions. Activation of the HIF-1 pathway is a common feature of gliomas and may explain the intense vascular hyperplasia often seen in glioblastoma multiforme. Activation of HIF results in the activation of vascular endothelial growth factors, vascular endothelial growth factor receptors, matrix metalloproteinases, plasminogen activator inhibitor, transforming growth factors alpha and beta, angiopoietin and Tie receptors, endothelin-1, inducible nitric oxide synthase, adrenomedullin, and erythropoietin, which all affect glioma angiogenesis. In conclusion, HIF is a critical regulatory factor in the tumor microenvironment because of its central role in promoting proangiogenic and invasive properties. While HIF activation strongly promotes angiogenesis, the emerging vasculature is often abnormal, leading to a vicious cycle that causes further hypoxia and HIF upregulation.

Published
2005

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