Optimal Multi-Drug Chemotherapy Control Scheme for Cancer Treatment. Design and development of a multi-drug feedback control scheme for optimal chemotherapy treatment for cancer. Evolutionary multi-objective optimisation algorithms were used to achieve the optimal parameters of the controller for effective treatment of cancer with minimum side effects.
SupervisorHossain, M. Alamgir
Majumder, Md A.A.
Tumour growth, control
The University of Bradford theses are licenced under a Creative Commons Licence.
InstitutionUniversity of Bradford
DepartmentSchool of Computing, Informatics and Media
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AbstractCancer is a generic term for a large group of diseases where cells of the body lose their normal mechanisms for growth so that they grow in an uncontrolled way. One of the most common treatments of cancer is chemotherapy that aims to kill abnormal proliferating cells; however normal cells and other organs of the patients are also adversely affected. In practice, it¿s often difficult to maintain optimum chemotherapy doses that can maximise the abnormal cell killing as well as reducing side effects. The most chemotherapy drugs used in cancer treatment are toxic agents and usually have narrow therapeutic indices, dose levels in which these drugs significantly kill the cancerous cells are close to the levels which sometime cause harmful toxic side effects. To make the chemotherapeutic treatment effective, optimum drug scheduling is required to balance between the beneficial and toxic side effects of the cancer drugs. Conventional clinical methods very often fail to find drug doses that balance between these two due to their inherent conflicting nature. In this investigation, mathematical models for cancer chemotherapy are used to predict the number of tumour cells and control the tumour growth during treatment. A feedback control method is used so as to maintain certain level of drug concentrations at the tumour sites. Multi-objective Genetic Algorithm (MOGA) is then employed to find suitable solutions where drug resistances and drug concentrations are incorporated with cancer cell killing and toxic effects as design objectives. Several constraints and specific goal values were set for different design objectives in the optimisation process and a wide range of acceptable solutions were obtained trading off among different conflicting objectives. Abstract v In order to develop a multi-objective optimal control model, this study used proportional, integral and derivative (PID) and I-PD (modified PID with Integrator used as series) controllers based on Martin¿s growth model for optimum drug concentration to treat cancer. To the best of our knowledge, this is the first PID/I-PD based optimal chemotherapy control model used to investigate the cancer treatment. It has been observed that some solutions can reduce the cancer cells up to nearly 100% with much lower side effects and drug resistance during the whole period of treatment. The proposed strategy has been extended for more drugs and more design constraints and objectives.
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The effect of oxidative stress in lymphocytes from patients with inflammatory bowel disease and various cancer states compared with healthy control individuals.Anderson, Diana; Najafzadeh, Mojgan (University of BradfordSchool of Life Sciences, Biomedical Sciences, 2012-01-11)In the present investigation peripheral blood lymphocytes from patients with inflammatory bowel disease (IBD) and different cancer states were treated with various agents and compared with lymphocytes from healthy control individuals (HCI) treated in the same way and measured in the Comet assay. For inflammatory bowel disease, patient¿s responses in IBD patients treated with H2O2 were higher than in HCI and crohn¿s patients (CD) were found to have higher responses than Ulcerative colitis (UC) patients. The responses for all IBD and HCI were all reduced in the presence of chaga mushroom extract which behaved in an antioxidant manner. A second group of IBD patients were treated with the heterocyclic amine (food mutagen), IQ and H2O2 and responses were reduced in the presence of the flavonoids, quercetin and epicatechin and compared with HCI similarity treated. In all cells responses were reduced with flavonoids and again CD had higher responses than the UC patients and IBD patients higher than HCI. The responses with CD and UC were that confirmed in two independent studies with IBD, one with chaga mushroom extract and the other with flavonoids. Peripheral lymphocytes from malignant melanoma and suspected melanoma patients and colon cancer and polyposis patients were compared to the lymphocytes from HCI and treated with UVA. There were differential sensitivities when measured in the micronucleus and Comet assays. The cancer patients had higher responses than those in the precancerous states and they in turn were higher than responses in HCI. In all the studies, untreated baseline DNA damage values were also higher in IBD and cancer patients and pre-cancerous patients than HCIs. This would suggest that baseline frequencies of different diseases compared to controls could be an important biomarker in the diagnosis of pre-cancers and early stage cancers. Also peripheral lymphocytes are a useful surrogate for cancers and pre-cancerous disease states since, blood is present in all organs and tissues and DNA is basically the same in all cells.
A randomised controlled trial of two programmes of shoulder exercise following axillary node dissection for invasive breast cancer.Todd, J.; Scally, Andy J.; Dodwell, D.; Horgan, K.; Topping, Annie (2008)Objective To compare the incidence of treatment-related complications, including lymphoedema, after two programmes of shoulder mobilisation in women with invasive breast cancer when surgical treatment included axillary lymph node dissection. Design Randomised controlled trial. Setting Two secondary care National Health Service trusts. Participants One hundred and sixteen women (mean age 57 years, standard deviation 13.1 years) recruited from November 2003 to March 2006 (58 intervention group, 58 control group). Seven patients (6%) did not complete the study. Intervention Arm exercises and shoulder movement restricted to below shoulder level for the first 7 days after surgery. Controls commenced an exercise programme that incorporated exercises above shoulder level within 48 hours. Outcome measures All outcomes were recorded at baseline (pre-operatively) and at 1 year. The primary outcome was incidence of lymphoedema, defined by a limb volume difference of 200 ml or more compared with the contralateral arm. This outcome was measured using volume displacement. Secondary outcome measures included volume differences between the two limbs measured by actual volume displacement difference, wound drainage volumes, range of shoulder movement (manual goniometer), grip strength (hand-held dynamometer) and health-related quality of life (Shoulder Disability Questionnaire, Functional Assessment of Cancer Therapy ¿ Breast). Results All statistical tests were two-sided. Data were analysed using intention-to-treat principles. The incidence of lymphoedema (200 ml or more) increased significantly in women who had undertaken a programme of early full shoulder mobilisation. Twenty-two women (19%) developed lymphoedema (200 ml or more) in their first postoperative year. There were significantly more women with lymphoedema in the early full shoulder mobilisation group (n = 16) compared with the delayed full shoulder mobilisation group (n = 6). The relative risk of developing lymphoedema after early mobilisation was 2.7 (95% confidence interval 1.1 to 6.3; P = 0.031). Limb volume differences were significantly higher in the early mobilisation group. This was apparent in differences in limb volume displacement (P = 0.004) and percentage difference between the two limbs (P = 0.007). There were no statistically significant differences in shoulder movement, grip strength or self-evaluated outcomes between the two groups at 1 year. Conclusion A programme of exercise that delays full shoulder mobilisation for 1 week is recommended after axillary node dissection for invasive breast cancer.
A randomised controlled trial of eicosapentaenoic acid and/or aspirin for colorectal adenoma (or polyp) prevention during colonoscopic surveillance in the NHS Bowel Cancer Screening Programme: The seAFOod (Systematic Evaluation of Aspirin and Fish Oil) Polyp Prevention TrialHull, M.A.; Sandell, A.C.; Montgomery, A.A.; Logan, R.F.A.; Clifford, G.M.; Rees, C.J.; Loadman, Paul M.; Whitham, D. (2013-07-29)The naturally-occurring omega (ω)-3 polyunsaturated fatty acid (PUFA) eicosapentaenoic acid (EPA) reduces colorectal adenoma (polyp) number and size in patients with familial adenomatous polyposis. The safety profile and potential cardiovascular benefits associated with ω-3 PUFAs make EPA a strong candidate for colorectal cancer (CRC) chemoprevention, alone or in combination with aspirin, which itself has recognized anti-CRC activity. Colorectal adenoma number and size are recognized as biomarkers of future CRC risk and are established as surrogate end-points in CRC chemoprevention trials. The seAFOod Polyp Prevention Trial is a randomized, double-blind, placebo-controlled, 2 × 2 factorial ‘efficacy’ study, which will determine whether EPA prevents colorectal adenomas, either alone or in combination with aspirin. Participants are 55–73 year-old patients, who have been identified as ‘high risk’ (detection of ≥5 small adenomas or ≥3 adenomas with at least one being ≥10 mm in diameter) at screening colonoscopy in the English Bowel Cancer Screening Programme (BCSP). Exclusion criteria include the need for more than one repeat endoscopy within the three-month BCSP screening period, malignant change in an adenoma, regular use of aspirin or non-aspirin non-steroidal anti-inflammatory drugs, regular use of fish oil supplements and concomitant warfarin or anti-platelet agent therapy. Patients are randomized to either EPA-free fatty acid 1 g twice daily or identical placebo AND aspirin 300 mg once daily or identical placebo, for approximately 12 months. The primary end-point is the number of participants with one or more adenomas detected at routine one-year BCSP surveillance colonoscopy. Secondary end-points include the number of adenomas (total and ‘advanced’) per patient, the location (left versus right colon) of colorectal adenomas and the number of participants re-classified as ‘intermediate risk’ for future surveillance. Exploratory end-points include levels of bioactive lipid mediators such as ω-3 PUFAs, resolvin E1 and PGE-M in plasma, urine, erythrocytes and rectal mucosa in order to gain insights into the mechanism(s) of action of EPA and aspirin, alone and in combination, as well as to discover predictive biomarkers of chemopreventive efficacy. The recruitment target is 904 patients.