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Tumor heterogeneity is underestimated as it is not heterogeneity between tumors best purchase for eldepryl medicine upset stomach, but heterogeneity within an individual tumor as well buy cheap eldepryl on line treatment for plantar fasciitis, which has been mapped out K discount eldepryl american express symptoms gallbladder problems. At current incidence rates, the total number of cancer cases is expected to double by 2050 (1. Multiple samples from each patient’s primary and metastatic tumor sites were obtained in a study of renal-cell cancer before and after treatment. About two thirds of the mutations that were found in single biopsies were not uni- formly detectable throughout all the sampled regions of the same patient’s tumor. A “favorable prognosis” gene proﬁle and an “unfavorable prognosis” gene proﬁle were expressed in different regions of the same tumor. Therefore, a single tumor biopsy cannot be considered representative of the landscape of genomic abnormali- ties in a tumor. From the function of the genes that were targeted for different mutations, it would appear that altera- tions in epigenetic mechanisms and signal transduction as the tumor evolves are keys to the tumor’s survival. Genes that are affected by convergent evolution may be suitable targets for functional inhibition or restoration. Systems Biology of Cancer Cancer systems biology addresses the increasing challenge of cancer as a complex, multifactorial disease by using model-based approaches that range from genome- wide regulatory and signaling networks to kinetic models of key pathways. It aims at a holistic view of cancer by use of “omics” technologies and integrates several aspects of cancer including genetics, epigenetics, histology, clinical manifestations and epidemiology. Use of patient-speciﬁc computational and mathematical models of cancer will signiﬁcantly improve the speciﬁcity and efﬁcacy of targeted therapy, and will facilitate the development of personalized management of cancer (Du and Elemento 2014). The authors have pointed out the need for ways to simulate and analyze cancer models efﬁciently as well as of means to personalize complex heterogeneous model in order to devise the most effective therapy for an individual patient. Relationships of Technologies for Personalized Management of Cancer Cancer is a good example of integration of various technologies for personalized management as shown in Fig. The biggest challenge for optimal treatment outcomes in cancer patients is the complex nature of the disease due to cellular heterogeneity and dysfunction of numerous molecular networks as results of genetic as well as environmental distur- bances. Systems biology, with its holistic approach to understanding fundamental principles in biology, and the empowering technologies in genomics, proteomics, single-cell analysis, microﬂuidics, and computational strategies, enables a compre- hensive approach to cancer with attempt to unveil the pathogenic mechanisms of diseases, identify disease biomarkers and provide new strategies for drug target dis- covery. Integration of multidimensional high throughput “omics” measurements from tumor tissues and corresponding blood specimens, together with new systems strategies for diagnostics, enables the identiﬁcation of cancer biomarkers that can enable presymptomatic diagnosis, stratiﬁcation of disease, assessment of disease progression, evaluation of patient response to therapy, and the identiﬁcation of recurrences. Although some aspects of systems medicine are being adopted in Universal Free E-Book Store 202 10 Personalized Therapy of Cancer clinical oncology practice through companion molecular diagnostics for personal- ized therapy, the increasing amount of global quantitative data from both healthy and diseased states is shaping up a transformational paradigm in medicine that is termed ‘predictive’, ‘preventive’, ‘personalized’, and ‘participatory’ (P4) medicine, which requires new scientiﬁc and organizational strategies to translate this approach to the healthcare system (Tian et al. Impact of Molecular Diagnostics on the Management of Cancer Molecular diagnostics inﬂuences cancer management in several ways that lend to personalization (Table 10. These technologies are enabling the classiﬁcation of cancer based on molecular proﬁles as a basis for more effective personalized thera- pies. The new system, which will run assays that detect several variants in parallel, will be used as part of the partners’ clinical trials of targeted cancer therapies. Illumina plans to develop, commercialize, and gain regulatory approval for multi- gene panels for therapy selection, which it previously referred to as Onco Panels. Illumina’s technology will inform physi- cians about the molecular make-up of their patients’ tumors, enabling them to match medicines to the drivers of disease for personalized management. Genetic variations within both the patient and the tumor cause changes in the apoptotic threshold and thus differences in both the toxicity and efﬁcacy of a chemotherapy drug. An antisense approach can be used to target speciﬁc anti- apoptotic splice variants to lower the apoptotic threshold of a tumor cell and there- fore increase the efﬁcacy of chemotherapy drugs. Analysis of Chromosomal Alterations in Cancer Cells Cancer cells have a remarkable ability to disable some genes and overuse others, allowing their unchecked growth into tumors. The most aggressive of these distor- tions occurs when cells delete or multiply chunks of their own chromosomes. Cells can simply snip strings of genes from the chromosome, or make many extra copies of the string and reinsert it into the chromosome. A fast and reliable method can identify alterations to chromosomes that occur when cells become malignant (Myers et al. Genomics tools are used to identify thousands of genes at once and Universal Free E-Book Store 204 10 Personalized Therapy of Cancer show how actively they are being used. The data are analyzed by advanced statistical techniques to accurately detect deletions and additions. Many previ- ously unknown additions and deletions have been found in human breast cancer cells by this method. The technique helps to show how cells modify their own genetic makeup and may allow cancer treatments to be tailored more precisely to a patient’s disease. Cancer Classiﬁcation Using Microarrays Classiﬁcation of a cancer based on gene expression proﬁle is important for person- alizing cancer therapy. A variety of analytic techniques are used to classify cancers on the basis of their gene- expression proﬁles. Pattern-recognition algorithms can be used to identify sub- groups of tumors that have related gene-expression proﬁles. Determination of tumor marker genes from gene expression data requires bioinformatic tools because expression levels of many genes are not measurably affected by carcinogenic changes in the cells. These molecular markers give valuable additional information for tumor diagnosis/prognosis and will be important for the development of person- alized therapy of cancer. An example of the application of microarrays for gene expression is bladder cancer, a common malignant disease characterized by frequent recurrences. The stage of disease at diagnosis and the presence of surrounding carcinoma in situ are important in determining the disease course of an affected individual. Clinically relevant subclasses of bladder carcinoma have been identiﬁed using expression microarray analysis of well-characterized bladder tumors. Gene biomarker panels provide new predictive information on disease progression in tumors compared with conventional staging. Furthermore, gene expression proﬁles characterizing each stage and subtype identify their biological properties, producing new potential targets for therapy. Global gene expression analysis using microarrays has been used to characterize the molecular proﬁle of breast tumors. Universal Free E-Book Store Impact of Molecular Diagnostics on the Management of Cancer 205 These results suggest that gene expression proﬁling of breast biopsies may become a valuable method for adequately characterizing and choosing treatment modality for patients with breast cancer. Gene expression microarray technology is helpful in all phases of the discovery, development and subsequent use of new cancer therapeutics, e. It can be used to identify molecular biomarkers for proof of concept studies, pharmacodynamic endpoints and prog- nostic markers for predicting outcome and patient selection. Catalog of Cancer Genes for Personalized Therapy Personalized medicine for cancer will eventually require a comprehensive catalog of cancer genes to enable physicians to select the best combination therapy for each patient based on the cellular pathways disrupted in their tumor and the speciﬁc nature of the disruptions. Such a catalog will also guide therapeutic development by identifying druggable targets. Although a few cancer genes are mutated in a high proportion of tumors of a given type (>20 %), most are mutated at intermediate frequencies (2–20 %). Using the MutSig tool, which weighs mutational burden as compared to the background mutation rate, mutational clustering, and enrichment of mutations in conserved regions, the researchers searched for candidate cancer genes. By combining the 22 MutSig lists, the researchers developed Cancer5000 set of 254 genes. Down-sampling analysis indicates that larger sample sizes will reveal many more genes mutated at clinically important frequencies.
Mechan- ical ventilators provide warm purchase eldepryl 5mg without a prescription treatment lower back pain, humidiﬁed gas to the airways in accordance with preset ventilator settings purchase 5mg eldepryl amex medications diabetic neuropathy. The ventilator serves as the energy source for inspiration buy discount eldepryl 5mg on line medicine 013, whereas ex- piration is a passive process, driven by the elastic recoil of the lungs and chest wall. This com- plicated interaction leads to a decrease in afterload and may be beneﬁcial to individuals with depressed cardiac function. When utilizing mechanical ventilation, the physician should also be cognizant of other potential physiologic consequences of the ventilator settings. Initial settings chosen by the physician include mode of ventilation, respiratory rate, fraction of inspired oxygen, and tidal volume, if volume-cycled ventilation is used, or maximum pressure, if pressure-cycled ventilation is chosen. The respiratory therapist also has the ability to alter the inspiratory ﬂow rate and waveform for delivery of the cho- sen mode of ventilation. In individuals with obstructive lung disease, it is important to maximize the time for exhalation. This can be done by decreasing the respiratory rate or decreasing the inspiratory time (increase the I:E ratio, prolong expiration), which is accomplished by in- creasing the inspiratory ﬂow rate. Care must also be taken in choosing the inspired tidal volume in volume-cycled ventilatory modes as high inspired tidal volumes can contrib- ute to development of acute lung injury due to overdistention of alveoli. Because these conditions are characterized by expiratory ﬂow limitation, a long expiratory time is re- quired to allow a full exhalation. However, because breath sounds are heard bilaterally, pneumo- thorax is less likely, and tube thoracostomy is not indicated at this time. A ﬂuid bolus may temporarily increase the blood pressure but would not eliminate the underlying cause of the hypotension. Sedation can be accomplished with a combination of benzodiazepines and narcotics or propofol. Initiation of vasopressor support is not indi- cated, unless other measures fail to treat the hypotension and it is suspected that sepsis is the cause of hypotension. It should be stressed that there are two compo- nents to diagnosis: symptoms of daytime sleepiness combined with obstructive breathing while asleep. The central pathogenesis of sleep apnea is pharyngeal narrowing that leads to airway obstruction when somnolent. Insulin resistance has been shown to be related to increasing frequency of apneas and hypopneas. These patients are in a hyperadrenergic state characterized by hypertension, tachycardia, tonic-clonic seizures, dyspnea and ventricular arrhythmias. There is concern with giving beta-blockers in patients with cocaine-induced chest pain or myocar- dial ischemia because of the potential for unopposed alpha activity provoking coronary vasospasm. Calcium channel blockers are often used in patients with cocaine intoxication and potential coronary ischemia to avoid this effect. Hy- dralazine may manage the hypertension but would have no effect on the ventricular arrhythmia and might cause a reﬂex tachycardia. Cardioversion is not indicated for this patient who is in nonsustained ventricular tachycardia. Norepinephrine would be contraindicated as it would exacerbate the hyperadrenergic state. In addition, 67 to 75% of patients with idiopathic pulmonary ﬁbrosis also have a history of ciga- rette use. The clinical presentation and radiogram are consistent with farmer’s lung, a hypersensitivity pneumonitis caused by Actinomyces. In this disorder moldy hay with spores of actinomycetes are inhaled and produce a hypersensitivity pneumonitis. Patients present generally 4 to 8 h after exposure with fever, cough, and shortness of breath with- out wheezing. The exposure history will differentiate this disorder from other types of pneumonia. Pathology shows the presence of granulation tissue plugging airways, alveolar ducts, and alveoli. Azathioprine is an immunosuppressive therapy that is commonly used in interstitial lung disease due to usual interstitial pneumonitis. Hydroxychloroquine is frequently useful for joint symptoms in autoim- mune disorders. In this setting, the alveolar-arterial (A – a) oxygen gradient will be normal but the minute ventilation is low, producing a respiratory acidosis. Diaphragmatic dysfunction and maximal inspiratory or expiratory pressures are commonly impaired with respiratory neuromuscular dysfunction but may be normal in other disorders of central hypoventilation such as stroke. The physical abnormalities caused by the forward and lateral curvature of the spine result in abnormal pulmonary mechanics. This is man- ifested primarily as restrictive lung disease with chronic alveolar hypoventilation. This in turn leads to ventilation-perfusion imbalances that result in hypoxic vasoconstriction and may cause the eventual development of pulmonary hypertension. Other endemic regions in North America are the Mississippi and Ohio River basins, the Great Lake states, and areas along the St. The sub- acute course after an abrupt onset, arthralgias, and alveolar inﬁltrates with a cavity are all suggestive of Blastomyces infection, given the region from which the patient originates. Respiratory failure and dis- seminated infection are more common in immunocompromised patients who may have a mortality of >50%. Legionella pneumonia may present in a similar fashion, but those pa- tients usually have a predisposing condition such as diabetes, advanced age, end-stage renal disease, immunosuppression, or advanced lung disease. Hyponatremia may be seen in Le- gionella pneumonia but is more common in Legionnaire’s disease. Although a bone mar- row aspirate may grow Blastomyces, isolation from more accessible material (i. The Quellung reaction is used to diagnose infection with Streptococcus pneumoniae. However, the time course of this infection is prolonged for pneumococcal pneumonia, and necrotizing infection causing cavitation is rare. The time course of the infection is too rapid for pulmonary tuberculosis, although tuberculosis should be considered in the evaluation of cavitary lesions of the lung. Methotrexate has been associated with an idiosyncratic drug reaction, with particular risk in the elderly and in patients with decreased creatinine clearance. Dis- continuing the medicine and in some cases adding high-dose steroids constitute the initial management. Initiating empirical broad-spectrum antibiotics until a more deﬁnite result could be obtained via a bronchoscopy would be a reasonable approach. In most patients, paralytic agents are used in combination with sedatives to accomplish endotracheal intubation. Succi- nylcholine is a depolarizing neuromuscular blocking agent with a short half-life and is one of the most commonly used paralytic agents.
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Reprogram m ing of the various param eters that govern pacing generic 5mg eldepryl overnight delivery medicine 122, arrhythm ia detection and therapy m ay be necessary from tim e to tim e purchase discount eldepryl line treatment joint pain. Such routine follow up order eldepryl 5 mg online symptoms bone cancer, usually undertaken at established arrhythm ia centres, should occur at 3 to 6 m onthly intervals in the absence of m ajor inter- current events. Som e issues specific to this group of patients can be sum m arised as follow s: 1. O nce this is exceeded for a defined period of tim e, the device m ay deliver therapy irrespective of w hether the arrhythm ia is of ventricular or supra- ventricular origin. Further, if anti- tachycardia pacing is delivered in the ventricle for an atrial arrhythm ia, ventricular arrhythm ias m ay be provoked creating a pro-arrhythm ic situation. Cognisant of the above, it is im perative that atrial arrhythm ias are adequately treated in these patients, particularly the paroxysm al 100 Questions in Cardiology 189 form of atrial fibrillation that is com m only associated w ith rapid rates at its onset. Drugs such as flecainide and am iodarone can increase pacing and defibrillation thresholds. In patients w ith a low m argin of safety for these param eters, use of these drugs m ay result in failure of pacing or defibrillation. Som e rarer interactions include alteration of the T w ave voltage by drugs or hyperkalaem ia resulting in double counting and inappropriate shocks. Sim ilarly, unexplained fever, particularly staphylococcal septicaem ia m ay indicate endocarditis involving the leads and/or tricuspid valve. The cardiologist, technical staff and nurses involved should have a w ide experience and know ledge of pacem akers and general cardiac electrophysiology. Routine follow up m ay occur in a tertiary centre or a local hospital as long as the expert staff and necessary equipm ent such as program m ers and cardiac arrest kit are available. Follow up should start before the device is im planted w ith an educational program m e and support for the patient and im m ediate fam ily m em bers. Previously the patient had to return every m onth or tw o to have a capacitor reform. W ith m ost current devices a 3 to 6 m onth interval is usual but treat each patient according to their individual circum stances. These should include lead im pedance, shock coil im pedance (if possible non-invasively), battery voltage, charge tim e, R and P w ave am plitudes as w ell as pacing thresholds. Som e centres provide a form al patient support group; there are both positive and negative view s on this practice. O bservations of a support group for autom atic im plantable cardioverter defibrillator recipients and their spouses. Life after sudden death: the developm ent of a support group for autom atic im plantable cardioverter defibrillator patients. For this reason, it is im portant to retrieve the stored data from the device using the appropriate program m er even after a single shock. Frequent episodes of ventricular arrhythm ia w ill require antiarrhythm ic drugs for suppression; sotalol is often effective as a first line drug in this situation. Patients experiencing “storm s” of shocks should be adequately sedated, and m onitored in a coronary care setting. Intravenous antiarrhythm ic drugs should be used for rapid arrhythm ia suppression. M yocardial ischaem ia has to be a serious consideration w hen recurrent ventricular fibrillation or polym orphic ventricular tachycardia is responsible for shocks. M ost episodes of repetitive ventricular tachycardia respond to intravenous drugs such as lidocaine, procainam ide or am iodarone allow ing for oral loading w ith an antiarrhythm ic agent in a m ore controlled fashion. Lim itations and late com plications of third-generation autom atic cardioverter-defibrillators. Sara Thorne The m anagem ent of a pregnant w om an w ith dilated cardio- m yopathy should be considered in term s of m aternal risk, and risk to the fetus. M aternal risk This relates to the degree of ventricular dysfunction and the ability to adapt to altered haem odynam ics. They m ay thus contribute to prem ature labour • W arfarin – see Q 93 (page 196) and Q 95 (page 202). Failure of adjusted doses of sub- cutaneous doses of heparin to prevent throm boem bolic phenom ena in pregnant patients w ith m echanical cardiac valve prostheses. Sara Thorne Native or tissue valves In general, regurgitant lesions are w ell tolerated during pregnancy, w hereas left sided stenotic lesions are not (increased circulating volum e and cardiac output lead to a rise in left atrial pressure). Nitrates m ay be useful, but should be used w ith caution in those w ith aortic stenosis. M echanical valves Anticoagulation is the issue here: in particular, the risk of w arfarin em bryopathy vs risk of valve throm bosis. The patient m ust be fully inform ed, and involved in deciding her m ode of anticoagulation (m edicolegal im plications). Failure of adjusted doses of sub- cutaneous doses of heparin to prevent throm boem bolic phenom ena in pregnant patients w ith m echanical cardiac valve prostheses. The key here is to leave the m other off w arfarin for the m inim um tim e possible. An elective section is perform ed at 38 w eeks’ gestation, replacing the w arfarin w ith unfractionated heparin for the m inim um tim e possible • Severe aortic or m itral stenosis. If the m other’s life is at risk, section follow ed by valve replacem ent m ay be necessary. Controversy rem ains over w hether the follow ing patients should undergo elective Caesarean section: 1 Cyanotic congenital heart disease w ith im paired fetal grow th. Section m ay help to avoid further fetal hypoxaem ia, but at the 100 Questions in Cardiology 199 expense of excessive m aternal haem orrhage to w hich cyanotic patients are prone. A balance has to be m ade betw een a spontaneous vaginal delivery w ith the m other in the lateral decubitus position to attenuate haem odynam ic fluctuations, forceps assistance and the sm aller volum e of blood lost during this type of delivery, and the controlled tim ing of an elective section. Probably m ore im portant than the route of delivery is peri-partum planning and team w ork: delivery m ust be planned in advance, and the patient intensively m onitored, kept w ell hydrated and not allow ed to drop her system ic vascular resistance. Consultant obstetric and anaesthetic staff experienced in these conditions should be present, and the cardiologist readily available. Rachael James All anticoagulant options during pregnancy are associated w ith potential risks to the m other and fetus. Any w om an on w arfarin w ho w ishes to becom e pregnant should ideally be seen for pre- pregnancy counselling and should be involved in the anti- coagulation decision as m uch as possible. Potential risks to the fetus need to be balanced against the increased m aternal throm - botic risk during pregnancy. Anticoagulation for m echanical heart valves in pregnancy rem ains an area of som e controversy. The use of w arfarin during pregnancy is associated w ith a low risk of m aternal com plications1 but it readily crosses the placenta and em bryopathy can follow exposure betw een 6–12 w eeks’ gestation, the true incidence of w hich is unknow n. A single study has reported that a m aternal w arfarin dose 5m g is w ithout this em bryopathy risk. Conversion to heparin in the final few w eeks of pregnancy is recom m ended to prevent the delivery of, w hat is in effect, an anticoagulated fetus.
Nanomaterials can be assembled into massively parallel arrays at much higher densities than is achievable with current sensor array platforms and in a format compatible with current microﬂuidic systems purchase eldepryl with visa treatment quad strain. Currently discount eldepryl 5 mg mastercard medicine jobs, quantum dot technology is the most widely employed nanotechnology for diagnostic developments buy cheap eldepryl 5 mg online medications hyperkalemia. Cantilevers for Personalized Medical Diagnostics An innovative method for the rapid and sensitive detection of disease- and treatment- relevant genes is based on cantilevers. Short complementary nucleic acid segments (sensors) are attached to silicon cantilevers which are 450 nm thick and therefore react with extraordinary sensitivity. Binding of targeted gene transcripts to their matching counterparts on cantilevers results in mechanical bending that can be optically mea- sured. Differential gene expression of the gene 1-8U, a potential biomarker for can- cer progression or viral infections, can be observed in a complex background. The measurements provide results within minutes at the picomolar level without target ampliﬁcation, and are sensitive to base mismatches. An array of different gene tran- scripts can even be measured in parallel by aligning appropriately coated cantilevers alongside each other like the teeth of a comb. It could be used as a real-time sensor for continuously monitoring various clinical parame- ters or for detecting rapidly replicating pathogens that require prompt diagnosis. These ﬁndings qualify the technology as a rapid method to validate biomarkers that reveal disease risk, disease progression or therapy response. This will have applications in genomic analysis, proteomics and molecular diagnostics. Cantilever arrays have potential as a tool to evaluate treatment response efﬁcacy for personalized medical diagnostics. Nanobiotechnology for Therapeutics Design and Monitoring Current therapeutic design involves combinatorial chemistry and system biology- based molecular synthesis and bulk pharmacological assays. Therapeutics delivery is usually non-speciﬁc to disease targets and requires excessive dosage. Efﬁcient therapeutic discovery and delivery would require molecular level understanding of Universal Free E-Book Store References 187 the therapeutics-effectors (e. Characterization of nanocarrier-based drug delivery can enable high efﬁciency of in vivo or topical administration of a small dosage of therapeutics. Multidimensional atomic force microscopy for drug discovery: a versatile tool for deﬁning targets, designing therapeutics and monitoring their efﬁcacy. Genomics and epigenomics: new promises of per- sonalized medicine for cancer patients. Cytomics, the human cytome project and systems biology: top-down resolution of the molecular biocomplexity of organisms by single cell analysis. Personalized exposure assessment: promising approaches for human environmental health research. A circadian gene expression atlas in mammals: implications for biology and medicine. Universal Free E-Book Store Chapter 9 Personalized Biological Therapies Introduction Historically blood transfusion and organ transplantation were the ﬁrst personalized therapies as they were matched to the individuals. Some cell therapies that use patient’s own cells are considered to be personalized medicines particularly vac- cines prepared from the individual patient’s tumor cells. More recently recombinant human proteins might provide individualization of therapy. The number of biotechnology-based therapeutics introduced in medical practice is increasing along with their use in a personalized manner (Jain 2012). Recombinant Human Proteins There are a large number of therapeutic proteins approved for clinical use and many more are undergoing preclinical studies and clinical trials in humans. Virtually all therapeutic proteins elicit some level of antibody response, which can lead to potentially serious side effects in some cases. Therefore, immunogenicity of therapeutic proteins is a con- cern for clinicians, manufacturers and regulatory agencies. In order to assess immu- nogenicity of these molecules, appropriate detection, quantitation and characterization of antibody responses are necessary. Immune response to therapeu- tic proteins in conventional animal models has not been, except in rare cases, pre- dictive of the response in humans. In recent years there has been a considerable progress in development of computational methods for prediction of epitopes in protein molecules that have the potential to induce an immune response in a recipi- ent. It is expected that computer driven prediction followed by in vitro and/or in vivo testing of any potentially immunogenic epitopes will help in avoiding, or at least minimizing, immune responses to therapeutic proteins. Another approach to protein therapy is in vivo production of proteins by geneti- cally engineered cells where the delivery of proteins can be matched to the needs of the patient and in vivo production and controlled delivery might reduce adverse effects. Therapeutic Monoclonal Antibodies Compared with small-molecule drugs, antibodies are very speciﬁc and are less likely to cause toxicity based on factors other than the mechanism of action. Orally available small molecules have many targets but they may also hepatotoxic and are involved in drug-drug interactions. From the point of view of a clean safety proﬁle, antibodies are extremely attractive. Antibodies have for many decades been viewed as ideal molecules for cancer therapy. These will be described in more detail in the section on personal- ized cancer therapy in Chap. Many molecular biological and immunological studies have revealed the targeting properties of the host immune system and the biological mechanisms of cancer cells for a more speciﬁc anticancer effect. The accumulating results from many basic, clinical and translational studies may lead to more individualized therapeutic strategies using these agents directed at speciﬁc genetic and immunologic targets. Cell Therapy Cell therapy is the prevention or treatment of human disease by the administration of cells that have been selected, multiplied and pharmacologically treated or altered outside the body (ex vivo). The aim of cell therapy is to replace, repair or enhance the function of damaged tissues or organs. The cells used can originate from the patient or from a donor or from another species. Other sources include cell lines and cells from patients’ tumors to make cancer vaccines. Cells can be encapsulated in selectively permeable membranes that block entry of immune mediators but allow outward diffusion of active molecules produced by the cells. Genetic engineering of Universal Free E-Book Store Cell Therapy 191 cells is part of ex vivo gene therapy. The cells may be introduced by various routes into the body and selectively implanted at the site of action. Autologous Tissue and Cell Transplants The term transplantation, used mostly for organ transplants in the past, is now also used for cells transplanted from one individual to another. Problems associated with transplantation include organ rejection requiring immu- nosuppressive therapy.