Immunotherapy of lung cancer: An update

In Germany lung cancer is the leading cause of cancer-associated death in men. Surgery, chemotherapy and radiation may enhance survival of patients suffering from lung cancer but the enhancement is typically transient and mostly absent with advanced disease; eventually more than 90% of lung cancer patients will die of disease. New approaches to the treatment of lung cancer are urgently needed. Immunotherapy may represent one new approach with low toxicity and high specificity but implementation has been a challenge because of the poor antigenic characterization of these tumors and their ability to escape immune responses. Several different immunotherapeutic treatment strategies have been developed. This review examines the current state of development and recent advances with respect to non-specific immune stimulation, cellular immunotherapy ( specific and non-specific), therapeutic cancer vaccines and gene therapy for lung cancer. The focus is primarily placed on immunotherapeutic cancer treatments that are already in clinical trial or well progressed in preclinical studies. Although there seems to be a promising future for immunotherapy in lung cancer, presently there is not standard immunotherapy available for clinical routine

East Bay Coalition for the Homeless: Branding Study and Marketing Strategy

There are a number of potential positioning strategies. The two which make the most sense for the EBCH are to “position the EBCH away from others in the category” and to “position the EBCH as unique.” These strategies have the advantage of setting the EBCH apart from the other organizations that address homelessness. Occupying its own “position” in the minds of potential and current donors is not only an effective communications/marketing strategy but also a less costly one because it avoids head-to-head competition and comparisons

The art of the wilderness : a field guide to integrating art + outdoor education

This thesis serves as both a comprehensive review of the fields of art and outdoor education, and as a practical handbook. Through an exploration of the definitions of art and wilderness to the pedagogy of art, outdoor, and experimental education, this thesis endeavors to make evident meaningful ways of learning. Interdisciplinary learning and multiple intelligence theory support a holistic and interconnected approach to education. Place-based and project-based learning emphasize a multidimensional line of inquiry rooted within a meaningful and personal context. The goal of integrating art + outdoor education is to design learning adventures that cultivate: creativity, leadership, problem-solving, collaboration, challenge, and inspiration. Through a comparison of the pedagogy of art and outdoor education, points of intersection, overlap, and difference emerge. Exemplars are provided from singular to broad, showing how the combined power of art + outdoor education has impacted local communities and national institutions, and created lasting social and political effects. Finally, an appendix of lesson plans, workshops, program outlines, and outdoor artist resources is offered as a field guide to applying art + outdoor education in a variety of contexts. Throughout the thesis, hand-drawn illustrations interpret the academic context while digital photographs provide documentation of experiences. The thesis is encased within a map of the John Muir Trail, in honor of the naturalist, environmental philosopher, and early advocate for the preservation of the wilderness within the United States

Detecting T-cell Reactivity to Whole Cell Vaccines

BCR-ABL$^+$ K562 cells hold clinical promise as a component of cancer vaccines, either as bystander cells genetically modified to express immunostimulatory molecules, or as a source of leukemia antigens. To develop a method for detecting T-cell reactivity against K562 cell-derived antigens in patients, we exploited the dendritic cell (DC)-mediated cross-presentation of proteins generated from apoptotic cells. We used UVB irradiation to consistently induce apoptosis of K562 cells, which were then fed to autologous DCs. These DCs were used to both stimulate and detect antigen-specific CD8+ T-cell reactivity. As proof-of-concept, we used cross-presented apoptotic influenza matrix protein-expressing K562 cells to elicit reactivity from matrix protein-reactive T cells. Likewise, we used this assay to detect increased anti-CML antigen T-cell reactivity in CML patients that attained long-lasting clinical remissions following immunotherapy (donor lymphocyte infusion), as well as in 2 of 3 CML patients vaccinated with lethally irradiated K562 cells that were modified to secrete high levels of granulocyte macrophage colony-stimulating factor (GM-CSF). This methodology can be readily adapted to examine the effects of other whole tumor cell-based vaccines, a scenario in which the precise tumor antigens that stimulate immune responses are unknown

From Trusteeship to Containment: American Involvement in Vietnam 1945-1950

The American involvement in Vietnam has motivated extensive scholarship and reflection from diverse segments of American society. The Vietnamese war for independence and the dynamics and nature of American intervention have been approached from the perspectives of many different disciplines and from all points on the political continuum. The majority of these works address, either directly or implicitly, the fundamental issue of how American involvement can be explained and understood. The historiography of American involvement in Vietnam covers a wide range of interpretations of the impetus behind the initial commitment, the reasons for progressive escalation, and the rationales for why the United States didn\u27t win. Though categorizing these analyses runs the risk of oversimplification, in the interest of clarity they are classifiable in terms of the central imperatives behind intervention which they address. The salient issues these scholars bring to light can be further subdivided in that some are concerned with the motivations of intervention and others with the decision making process. The interpretations to be discussed herein base the fact or character of United States involvement on the imperatives of the balance of power, the capitalist system, American ideology, the bureaucratic establishment, domestic electoral politics, and the concept of credibility. The balance of power approach bases American decision making toward Vietnam in pragmatism and traditional power politics. The proponents of this approach interpret American actions as the result of realistic consideration of the international situation and of the necessities of national security. This interpretation takes two main directions: one finds the motivation behind involvement in the need to maintain the balance of world power with the Soviet Union, and the other sees the maintenance of Western power on Asia as the determining factor

Somatic gene therapy for cancer. The utility of transferrinfection in generating ‘tumor vaccines’

The last few years have seen the development of a branch of somatic gene therapy which aims at strengthening the immune surveillance of the body, leading to eradication of disseminated cancer tumor cells and occult micrometastases after surgical removal of the primary tumor. Such a tumor vaccination protocol calls for cultivation of the primary tumor tissue and the insertion of one of three types of genes into the isolated cultured tumor cells followed by irradiation of the transfected or transduced cells to render them incapable of further proliferation. The cells so treated constitute the ‘tumor vaccine’. A review of the literature suggests that for mouse models, in the initial period after inoculation, rejection of the tumor cells is usually effected by non-T-cell immunity, whereas the long-term systemic immune response is based on cytotoxic T-cells. High expression of the gene inserted into the tumor cells may be critical for the success of the vaccination procedure. Examples are given which indicate that transferrinfection, a procedure to introduce genes by adenovirus-augmented receptor-mediated endocytosis, meets some important prerequisites for successful application of this type of gene therapy

Toxicity of ethanol and acetaldehyde in hepatocytes treated with ursodeoxycholic or tauroursodeoxycholic acid

AbstractIn hepatocytes ethanol (EtOH) is metabolized to acetaldehyde and to acetate. Ursodeoxycholic acid (UDCA) and tauroursodeoxycholic acid (TUDCA) are said to protect the liver against alcohol. We investigated the influence of ethanol and acetaldehyde on alcohol dehydrogenase (ADH)-containing human hepatoma cells (SK-Hep-1) and the protective effects of UDCA and TUDCA (0.01 and 0.1 mM). Cells were incubated with 100 and 200 mM ethanol, concentrations in a heavy drinker, or acetaldehyde. Treatment with acetaldehyde or ethanol resulted in a decrease of metabolic activity and viability of hepatocytes and an increase of cell membrane permeability. During simultaneous incubation with bile acids, the metabolic activity was better preserved by UDCA than by TUDCA. Due to its more polar character, acetaldehyde mostly damaged the superficial, more polar domain of the membrane. TUDCA reduced this effect, UDCA was less effective. Damage caused by ethanol was smaller and predominantly at the more apolar site of the cell membrane. In contrast, preincubation with TUDCA or UDCA strongly decreased metabolic activity and cell viability and led to an appreciable increase of membrane permeability. TUDCA and UDCA only in rather high concentrations reduce ethanol and acetaldehyde-induced toxicity in a different way, when incubated simultaneously with hepatocytes. In contrast, preincubation with bile acids intensified cell damage. Therefore, the protective effect of UDCA or TUDCA in alcohol- or acetaldehyde-treated SK-Hep-1 cells remains dubious