Humor. A therapeutic approach in oncology nursing

Humor theory has evolved from various disciplines. Numerous professionals have published literature and research studies that examine the historical perspective of humor and the current practice of humor in health care. Historically, researchers have found humor to be an unconscious activity developed from childhood to adulthood. They describe humor as spontaneous and incongruent, involving a changing state of mind. Currently, health care professionals and patients are utilizing humor as a coping mechanism, as a communication skill, and as a tool to promote the psychological and physiological healing process. This article describes how humor theory has evolved, the use of humor in health care, and humor as an adjunct therapy in oncology. Oncology nurses can utilize humor as a part of the nursing process in the care provided to patients and families.     

Biomaterial-enabled therapeutic modulation of cGAS-STING signaling for enhancing antitumor immunity

1. Download : Download high-res image (238KB)
2. Download : Download full-size image

     

Endothelial targeting of high-affinity multivalent polymer nanocarriers directed to intercellular adhesion molecule 1

Targeting of diagnostic and therapeutic agents to endothelial cells (ECs) provides an avenue to improve treatment of many maladies. For example, intercellular adhesion molecule 1 (ICAM-1), a constitutive endothelial cell adhesion molecule up-regulated in many diseases, is a good determinant for endothelial targeting of therapeutic enzymes and polymer nanocarriers (PNCs) conjugated with anti-ICAM (anti-ICAM/PNCs). However, intrinsic and extrinsic factors that control targeting of anti-ICAM/PNCs to ECs (e.g., anti-ICAM affinity and PNC valency and flow) have not been defined. In this study we tested in vitro and in vivo parameters of targeting to ECs of anti-ICAM/PNCs consisting of either prototype polystyrene or biodegradable poly(lactic-coglycolic) acid polymers (approximately 200 nm diameter spheres carrying approximately 200 anti-ICAM molecules). Anti-ICAM/PNCs, but not control IgG/PNCs 1) rapidly (t1/2 approximately 5 min) and specifically bound to tumor necrosis factor-activated ECs in a dose-dependent manner (Bmax approximately 350 PNC/cell) at both static and physiological shear stress conditions and 2) bound to ECs and accumulated in the pulmonary vasculature after i.v. injection in mice. Anti-ICAM/PNCs displayed markedly higher EC affinity versus naked anti-ICAM (Kd approximately 80 pM versus approximately 8 nM) in cell culture and, probably because of this factor, higher value (185.3 +/- 24.2 versus 50.5 +/- 1.5% injected dose/g) and selectivity (lung/blood ratio 81.0 +/- 10.9 versus 2.1 +/- 0.02, in part due to faster blood clearance) of pulmonary targeting. These results 1) show that reformatting monomolecular anti-ICAM into high-affinity multivalent PNCs boosts their vascular immuno-targeting, which withstands physiological hydrodynamics and 2) support potential anti-ICAM/PNCs utility for medical applications.     

A therapeutic cancer vaccine targeting carcinoembryonic antigen in intestinal carcinomas

A genetic vaccine platform based on DNA electroporation (DNA-EP) and adenovirus (Ad) was used to generate immune response against human carcinoembryonic antigen (CEA) and antitumor effects in murine models with spontaneous tumors arising in an orthotopic location. CEA transgenic (CEA.Tg) mice treated with the carcinogen 1,2-dimethylhydrazine developed CEA-overexpressing tumors that resembled human sporadic colorectal cancer. APC1638N/CEA hybrid mice, generated by crossing mice carrying the adenomatous polyposis coli (Apc1638N) gene mutation with CEA.Tg mice, are representative of human familial polyposis and develop polyps that overexpress the antigen. In both models, the DNA-EP/Ad vaccine succeeded in breaking immune tolerance and achieved significant antitumor effects in therapeutic settings. Our data suggest that genetic vaccines targeting CEA may be feasible strategies against gut tumors that overexpress the antigen. In addition, these models are powerful systems for evaluating antigen-specific tumor immunity and assessing therapeutic vaccine strategies for human colorectal cancer.     

Clinical problem solving and therapeutic noncompliance: A heuristic for enhancing the clinician's generation of alternatives

A social-cognitive model of rule-governed interpersonal request processes is adapted from sociolinguistic research and applied to the context of therapeutic noncompliance. It is predicted that the categories of the model will function as a superior heuristic aid to clinicians' generation of alternative reasons for noncompliance. A study using 38 professional nurses as subjects provided strong support for the hypothesis.     

Memory: therapeutic approach. Clinical evaluation

Memory assessment in pharmaceutical trials has to date been mainly performed in Alzheimer's disease. North American and European Medical Evaluating Agencies recommend guidelines. Tests need to be simple and short, and sensitive enough to assess changes over a wide range of severity to avoid floor or ceiling effect. They require inter-rater reliability and face validity. They should be at least appropriate for different languages and culture, correlate well with universally accepted estimates of a function and have several parallel forms available to avoid a training effect. Memory is assessed with sub-tests of composite scales assessing a number of cognitive functions including episodic memory. The ADAS-Cog has become the standard instrument since it was used for the approval of tacrine and other cholinesterase inhibitors. Some studies have assessed more specifically different sub-systems of memory. However, autobiographical, remote or prospective memory, as well as metamemory, has not been explored in pharmaceutical trials.     

Community-acquired pneumonia. Diagnostic and therapeutic approach

Optimal empiric therapy of CAP is with appropriate monotherapy (e.g., doxycycline, levofloxacin). Combination therapy is problematic because of potential side effects and high cost. Empiric coverage should have a high degree of activity against both typical and atypical pathogens. The antibiotic selected should have an excellent side-effect profile and be relatively inexpensive. Clinicians should be selective in their choice of antibiotic for CAP and choose an antimicrobial that has little or no resistance potential, is relatively inexpensive, and permits i.v.-to-PO switch monotherapy.     

Extracorporeal photochemotherapy: a new therapeutic approach for allograft rejection.

Photopheresis (ECP) is a new immunomodulatory therapy in which recipient lymphocytes are treated extracorporeally with 8-methoxypsoralen (8-MOP) and ultraviolet light. The treatment seems to induce an inhibition of both umoral and cellular rejections after transplantation. More than 160 transplanted patients have been treated with ECP (107 heart, 30 kidney, 24 lung and I liver) in different studies. Indication for ECP included acute rejection, recurrent/refractory rejection, prophilaxis of rejection, need of reducing standard immunosuppression. Patient survival is satisfactory. Only one study where ECP was used as the last therapeutic resource in very compromised patients shows a high rate of mortality. On the contrary, when ECP was used earlier after the failure of a first immunosuppressive line the outcome was better with a very low mortality. An hystological resolution of acute rejection is reported in 89% of cardiac transplant patients. The rate of response is similar even in the other transplanted patients treated with ECP. A better control of alloreactivity has been also reported in both cardiac and renal transplant patients with recurrent rejection. In renal allograft the treatment induces a reduction of both lymphocytes and monocytes infiltrate and downregulates the expression of HLA-DR and integrins ICAM-1 and VCAM-1 on tubular cells. Markers of fibrogenesis such as TGFbeta1 and ASMA are only moderately reduced with a more focal pattern of distribution in the post-ECP specimens. The optimal schedule and the length of treatment are still unclear and probably a patient-tailored treatment is needed at least in responder patients. ECP is effective for patients resistant to conventional treatments, particularly when it is started early. This beneficial effect is obtained without the complications typically encountered with immunosuppressive regimens used to control rejection.     

Diagnostic and therapeutic approach to pancreatic cancer.

Adenocarcinoma of the pancreas ranks fourth as a cause of cancer death in adults in the United States and is the second most common cause of cancer deaths of all GI-related carcinomas. It usually presents late in its course. The clinical features are discussed, with emphasis on those that allow early detection of the disease, as well as a review of diagnostic methods and pre- and perioperative staging, which will allow the appropriate application of surgical and palliative therapeutic modalities. Despite the significant progress that has been made, further research studies are needed to advance our therapeutic approach to this aggressive cancer.     

Anorexia nervosa: a combined therapeutic approach.

Ten female patients with a diagnosis of anorexia nervosa were treated with a combination of behavior modification and psychotherapy and, when appropriate, psychotropic medication. All patients had favorable weight gain and improvement in adjustment during hospitalization. Later crises for each patient thus far have not significantly affected their weight. Three case histories illustrate the method used. The interrelationship between weight gain and the process in psychotherapy is illustrated and the psychopathologic features typical of this patient population are discussed. We conclude that the combined therapeutic method described is an effective and appropriate approach to the treatment of patients with anorexia nervosa.     

Gold nanoparticles conjugated with anti-CD133 monoclonal antibody and 5-fluorouracil chemotherapeutic agent as nanocarriers for cancer cell targeting

The enhanced permeability and retention effect allows for passive targeting of solid tumours by nanoparticles carrying anticancer drugs. However, active targeting by incorporation of various ligands onto nanoparticles can provide for a more selective and enhanced chemotherapeutic effect and complement the deficiencies of the passive targeting approach. Here we report on the design of the carboxyl-terminated PEGylated gold nanoparticles (AuNPs), their functionalization with anti-CD133 monoclonal antibody (mAb) via a crosslinking reaction, and subsequent 5-fluorouracil (5-FU) drug loading. The synthesized products in the form of stable colloids were characterised using a range of physicochemical techniques, including X-ray diffraction (XRD), UV-Vis spectroscopy, transmission electron microscopy (TEM), and dynamic light scattering (DLS). Conjugation of anti-CD133 mAb onto PEGylated AuNPs was confirmed with the use of UV-Vis, BCA protein assay and fluorescence microscopy. HCT116 colorectal cancer cells abundantly expressed CD133: 92.4 ± 1.3%, as measured by flow cytometry. Whereas PEGylated AuNPs not conjugated with anti-CD133 mAb accumulated mainly at the cellular membrane, nanoparticles conjugated with anti-CD133 mAb were contained within the nuclear region of the cells. Anti-CD133 mAb conjugation facilitated the specific intracellular uptake due to specific antigen–antibody binding interaction. In vitro cytotoxicity studies on HCT116 cells showed that PEGylated AuNPs and PEGylated AuNPs-CD133 did not elicit any toxicity at any of the tested concentrations. Meanwhile, 5-FU-PEGylated AuNPs-CD133 significantly reduced the cell viability relative to the treatment with 5-FU-PEGylated AuNPs without anti-CD133 mAb conjugates (p < 0.0001). This study shows that the conjugation of nanocarriers with the anti-CD133 antibody improves the specific targeting of 5-FU against colorectal cancer cells. These results demonstrate that simultaneous functionalisation of PEGylated AuNPs with antibodies and chemotherapeutic drugs is a viable strategy to combat cancer through targeted drug delivery.

5-FU-PEGylated AuNPs-CD133 is designed to improve specific targeting of 5-FU against colorectal cancer cells which abundantly express CD133.     

One-pot synthesis of biodegradable polydopamine-doped mesoporous silica nanocomposites (PMSNs) as pH-sensitive targeting drug nanocarriers for synergistic chemo-photothermal therapy

Nanomaterials have been widely used as drug carriers in the biomedical field. However, most of them have limited application because of their poor biocompatibility, targeting, and degradability. Therefore, exploring and developing novel drug nanocarriers to overcome these problems has widely attracted attention. In this study, polydopamine-doped mesoporous silica nanocomposites (PMSNs) were controllably synthesized by a one-pot oil-water biphase stratification approach. PMSNs showed good biodegradability in degradation experiments and also proved to have superior biocompatibility toward hepatocellular carcinoma cells (HepG2) compared with mesoporous silica nanoparticles (MSNs). And PMSNs loaded doxorubicin (DOX) (PMSNs@DOX) exhibited a pH-responsive release effect. Meanwhile, compared with PMSNs@DOX, folic acid-modified PMSNs@DOX (PMSNs@DOX@FA) displayed a targeted uptake and higher inhibition of HepG2 cells. Additionally, PMSNs@DOX@FA had excellent ability to kill tumor cells under synergistic chemo-photothermal therapy. Moreover, this synthetic strategy is promising for the fabrication of unique nanocomposites with various functional cores with PMSNs shells for diverse applications.

Polydopamine-doped mesoporous silica nanocomposites (PMSNs) were controllably synthesized by a one-pot approach. They were demonstrated to be good biodegradability, pH-responsive drug release and targeting synergistic chemo-photothermal therapy.     

Active targeting drug-gold nanorod hybrid nanoparticles for amplifying photoacoustic signal and enhancing anticancer efficacy

The development of theranostic nanomaterials with limited side effects and increased therapeutic efficacy is a promising approach for cancer imaging and therapy. In the present study, the development of a multifunctional metal–organic hybrid nanoparticle (NP) with enhanced photoacoustic (PA) imaging performance able to be actively uptaken by cancer cells for synergistic chemo-photothermal cancer therapy was reported. The theranostic NP was composed through the coordination effect between an ultrasmall gold nanorod (AuNR), a thick coating layer of the organic near-infrared dye IR780, and the anticancer drug doxorubicin (DOX), named AuNR@IR780/DOX-RGD-PEG. In addition, the theranostic NP surface was conjugated with targeting ligand RGD and a protective PEG shell, where the PEG played a role in concealing or exposing the RGD for specific targeting of the NPs to the cancer cells. The theranostic NP demonstrated a greatly enhanced PA imaging signal compared to AuNR or IR780, due to the fact that the electromagnetic field of the AuNR increased the light absorption efficiency of the IR780 coating based on the theoretical simulation results. Furthermore, the “Trojan-horse” active targeting strategy not only increased the uptake of NPs by tumor cells, but also decreased the non-specific uptake by healthy cells, thus limiting the side effects. This study developed a smart theranostic NP for enhanced cancer PA imaging and specific cancer therapy.

We developed a multifunctional metal–organic hybrid nanoparticle with enhanced photoacoustic imaging performance and specific chemo-photothermal cancer therapy.     

Human endotoxemia: a model for mechanistic insight and therapeutic targeting

The diversity of phenotypic manifestations, comorbidities, and therapeutic algorithms in patients with severe inflammation have confounded efforts to translate mechanistic insights from the bench top to the bedside. This dilemma has negatively impacted upon many therapeutic interventions that exhibited seemingly well-reasoned preclinical portfolios. Prudence urges the assessment of potent immunoregulatory therapies, wherever possible, in models that replicate the clinical phenotype absent overt manifestations of genetically or environmentally modified processes. The healthy human model of endotoxin administration (systemic or endobronchial) provides such an opportunity and has been used to great advantage for gaining insight into mechanisms of disease and for determination of therapeutic signal strength. When thoughtfully interpreted, the model may provide proof of principle as well as lessen the unpredictability of clinical responses. Although the broad characteristics of this model are well described in the literature, it is recognized that this model does not fully replicate the magnitude of initial inflammatory stress nor the latent spectrum of inflammation/sepsis-inducible organ system pathologies. Nevertheless, the similarities between the early, transient clinical phenotype, inducible physiochemical change, and biochemical pathway activation of this model to the early hyperdynamic phase of resuscitated injury and infection are striking. Rational testing of a therapeutic mechanism requires a quantifiable and reproducibly altered marker of the hypothetical mechanism. Given the modest nature of endotoxin induced insult, interventions that demonstrate target specific efficacy in conjunction with attenuated phenotype responses are more likely to exhibit efficacy within lower risk patient populations. By contrast, the model cannot predict clinical efficacy among higher risk patients nor in those who have endured extended periods of inflammatory stress.     

Pharmacokinetic and pharmacodynamic approach for comparing two therapeutic regimens using amikacin.

The efficiencies of two dosage schedules of amikacin (2 x 10 mg/kg of body weight per 24 h and 1 x 20 mg/kg/24 h intramuscularly for 5 days) against Pseudomonas aeruginosa sepsis in rabbits were compared. Blood samples were drawn at various times after the first application, and amikacin concentrations in serum were assayed microbiologically. The dynamics of the bactericidal effect of amikacin was simulated in vitro with the same strain of P. aeruginosa. No regrowth was found with the 20-mg/kg dose when the bacterial inoculum was in contact with experimental and theoretically predicted serum amikacin concentrations. The killing effect was present even when the drug levels decreased considerably below the MIC. The interrelationship between simulated amikacin concentrations in serum and the corresponding average killing rates was described appropriately by the standard Emax model. The higher amikacin dose performed its bacterial effect faster and the drug persisted longer in the blood. The two amikacin regimens were therapeutically equivalent, but the once-daily schedule had some advantages over the twice-daily drug administration which became evident when both the pharmacokinetic and the pharmacodynamic parameters of the drug were considered.