The Energy Well of Diradicals, VLll. -1,3,5-Cyclohexatriene-l,4-diyl and 2,4-Cyclohexadiene-l,.l-diylThe energy profile of the Bergman rearrangement of (2)-3-hexene-1,5-diyne (4) has been established from the NO In vorausgehenden Arbeiten in dieser Serie"] haben wir gezeigt, dalj mit der Sauerstoff-Abfang-Technik die Energiedellen auch kurzlebiger Diradikale bestimmt werden konnen. Mit dieser Methode sollen nun die Dellen der Diradikale 1 und 2 vermessen und die Bildungsenthalpien dieser Diradikale abgeleitet werden. Durch Vergleich der so zuganglichen experimentellen Bildungsenthalpien mit Rechenwerten fur die nichtwechselwirkenden Diradikale 1 b und 2b sol1 der Diradikal-Charakter der Intermediate 1 und 2 abgeschatzt werden.

Purpose: Reliable data on the persistence of tumor expression of cancer-testis (CT) antigens over time and consequent analyses of the effect of CT antigen expression on the clinical course of malignancies are crucial for their evaluation as diagnostic markers and immunotherapeutic targets. Experimental Design: Applying conventional reverse transcription-PCR, real-time PCR, and Western blot, we did the first longitudinal study of CT antigen expression in multiple myeloma analyzing 330 bone marrow samples from 129 patients for the expression of four CT antigens (MAGE-C1/CT7, MAGE-C2/CT10, MAGE-A3, and SSX-2). Results: CT antigens were frequently and surprisingly persistently expressed, indicating that down-regulation of these immunogenic targets does not represent a common tumor escape mechanism in myeloma. We observed strong correlations of CT antigen expression levels with the clinical course of myeloma patients as indicated by the number of bone marrow^residing plasma cells and peripheral paraprotein levels, suggesting a role for CT antigens as independent tumor markers. Investigating the prognostic value of CT antigen expression in myeloma patients after allogeneic stem cell transplantation, we found that expression of genes, such as MAGE-C1, represents an important indicator of early relapse and dramatically reduced survival. Conclusions: Our findings suggest that CTantigens might promote the progression of multiple myeloma and especially MAGE-C1/CT7, which seems to play the role of a ''gatekeeper'' gene for other CT antigens, might characterize a more malignant phenotype. Importantly, our study also strongly supports the usefulness of CTantigens as diagnostic and prognostic markers as well as therapeutic targets in myeloma.Cancer-testis (CT) antigens are a diverse group of genes of which more than 40 families have been identified during the past 15 years (1). CT antigens have been considered promising targets for immunotherapy of human malignancies based on their tumor-restricted expression and on their immunogenicity in cancer patients. Both of these characteristics could render CT antigens important diagnostic and prognostic markers; however, thus far, this aspect of the biology of CT antigens has not intensively been explored.Although an impressive number of studies have shown expression of CT antigens in a large variety of human tumor types on the RNA as well as on the protein level (2), there has not been a single study analyzing the expression of CT antigens in a human cancer over time. This seems surprising because reliable data on the persistence of tumor-related CT antigen expression are a prerequisite for the evaluation of these tumorspecific proteins as diagnostic markers and immunotherapeutic targets, especially considering data suggesting that immunoselection might lead to down-regulation or loss of CT antigen expression in cancer patients (3,4).We have recently shown that CT antigens are commonly expressed and are capable of inducing antibody-mediated and T-cell -mediated immunity in m...

Highly efficient and chemoselective singlet oxygen oxidation of unprotected methionine was performed in water using a continuous mesofluidic reactor. Sustainable process engineering and conditions were combined to maximize process efficiency and atom economy, with virtually no waste generation and safe operating conditions. Three water-soluble metal-free photosensitizers [Rose Bengal, Methylene Blue, and tetrakis­(4-carboxy­phenyl)­porphyrin] were assessed. The best results were obtained with Rose Bengal (0.1 mol %) at room temperature under white light irradiation and a slight excess of oxygen. Process and reaction parameters were monitored in real-time with in-line NMR. Other classical organic substrates (α-terpinene and citronellol) were oxidized under similar conditions with excellent performances.

NY-CO-58/KIF2C has been identified as a tumor antigen by screening antibody responses in patients with colorectal cancer. However, expression had not consequently been examined, and nothing was known about its ability to induce spontaneous T cell responses, which have been suggested to play a role in the development of colorectal cancer. We analyzed 5 colorectal cancer cell lines, and tumor samples and adjacent healthy tissues from 176 patients with epithelial cancers for the expression of NY-CO-58/KIF2C by RT-PCR and Western Blot. T cell responses of 43 colorectal cancer patients and 35 healthy donors were evaluated by ELISpot following stimulation with 30mer peptides or full-length protein. All cell lines and tumor samples from colorectal cancer patients expressed NY-CO-58/KIF2C on the protein and RNA level, and expression levels correlated strongly with Ki-67 expression (r 5 0.69; p 5 0.0003). Investigating NY-CO-58/KIF2C-specific T cell responses, CD81 T cells directed against 1 or more peptides were found in less than 10% of patients, whereas specific CD4 1 T cells were detected in close to 50% of patients. These T cells were of high avidity, recognized the naturally processed antigen and secreted IFN-c and TNF-a. Depletion of CD4 1 CD25 1 T cells before stimulation significantly increased the intensity of the preexisting response. NY-CO-58/KIF2C is significantly overexpressed in colorectal and other epithelial cancers and expression levels correlate with the proliferative activity of the tumor. Importantly, NY-CO-58/KIF2C was able to induce spontaneous CD4 1 T cell responses of the Th1-type, which were tightly controlled by peripheral T regulatory cells.Colorectal cancer is the second leading cause of cancerrelated death in Western countries with $1 million new cases and over 500,000 deaths per year worldwide. 1 In locally advanced colorectal cancer, surgery combined with the selective application of adjuvant chemotherapy represents the treatment of choice providing cure in a significant number of cases. However, about 40% of patients whose primary tumor has surgically been removed will eventually relapse and ultimately die from the disease.2 Therefore, alternative therapeutic strategies, especially in the adjuvant setting, are needed to improve the prognosis of patients with this malignancy.In the case of colorectal carcinoma, there is strong evidence for a role of the T cell-mediated immune system in controlling the development and progression of the disease. Thus, it has convincingly been demonstrated that infiltration

Propargyl Stabilisation EnergyFor the alkynyl-substituted olefines 1-14 activation parameters for the geometrical isomerisation have been determined in the gasphase by the single-pulse shoke-tube technique. By comparison of these barriers with the corresponding one of the isolated double bonds, each corrected by the steric energy contribution of the ground and transition state, a value of 7.8 2 1.3 kcal . mol-1 for the propargyl stabilisation energy (PrSE) has been derived, Die Darstellung von 3, 6 und 8 erfolgte durch eine modifizierte Heck-Kupplung['Ol, bei der das Zinkchlorid der jeweiligen Acetylenverbindung unter Palladium-Katalyse zu dem entsprechenden Endiin umgesetzt wird (Schema 2). Schema 2. Darstellung von 3, 6 und 8 durch Heck-Reaktion""] 9 Br [PPhgIPd \ R-ZnCI + % -1. Substrate Br THF In Schema 4 sind die Olefine zusammengestellt, die in dieser Arbeit anaiysiert wurden. Von diesen waren 1[2], 2f3], lVac V 3,6,8 8L41, ll[sa], 12r6], 13m und 14L8l bekannt. Die Darstellung von 2, 5 und 7 erfolgte durch McMurry-Reaktion['] ausgehend von den entsprechenden [(Trimethyl-sily1)ethinyllketonen (Schema 1). Hierbei wurden im Falle a : R = M e b: R = lsopropyl c: R = tert -Butyl Chem.