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We examined the cytotoxic effects of chaetocin on clear cell renal cell carcinoma (ccRCC) cells and the possibility to combine the effects of chaetocin with the effects of cytokine-induced killer cells (CIK) assayed by MTT assay and FACS analysis. Chaetocin is a thiodioxopiperazine produced by fungi belonging to the chaetomiaceae family. In 2007, it was first reported that chaetocin shows potent and selectiveanti-cancer activity by inducing reactive oxygen species. CIK cells are generated from CD3+/CD56- T lymphocytes with double negative phenotype that are isolated from human blood. The addition of distinct interleukins and antibodies results in the generation of CIK cells that are able to specifically target and destroy renal carcinoma cells. The results of this research state that the anti-ccRCC activity of chaetocin is weak and does not show a high grade of selectivity on clear cell renal cell carcinoma cells. Although the CIK cells show a high grade of selective anti-ccRCC activity, this effect could not be improved by the addition of chaetocin. So chaetocin seems to be no suitable agent for specific targeting ccRCC cells or for the combination therapy with CIK cells in renal cancer.

[english] We analysed the typical features of primary small cell carcinoma of the esophagus (SCCE) with emphasis on occurrence, behaviour, outcome and treatment options. This metaanalysis was aimed at collecting and analyzing information from international studies about handling this disease. This seems necessary due to the rarity of this disease. Studies were acquired from electronic databases and reference lists. We finally analysed 313 patient cases from the literature with oesophageal SCC. A data extraction was accomplished referring to 13 evaluable features that are described in the “methods”, whereof 7 were analyzed with univariate and multivariate tests. Three hundred thirteen cases were analyzed, 109 patients (35%) had limited stage (LS), whereas 167 (54%) had extensive stage (ES). There is no information about the remaining 35 patients concerning the stage. Univariate and multivariate analysis showed only age (50 years, HR 1.024; 95% CI 1.000–1.041, 50 years) and therapy are independent significant predictors of prognosis.[german] Gegenstand unserer Untersuchungen war die Erhebung typischer Eigenschaften des kleinzelligen Ösophaguskarzinoms mit Berücksichtigung des Auftretens, des Verlaufs, der Auswirkung und der Behandlungsoptionen. Ziel unserer Metaanalyse bestand darin, Informationen aus internationalen Studien, die sich mit dieser Krankheit befassten, zu sammeln und auszuwerten. Dies scheint notwendig aufgrund der Seltenheit der Krankheit. Die verwendeten Studien wurden von elektronischen Datenbanken und Referenzlisten ermittelt. Insgesamt wurden 313 Patientenfälle mit einem kleinzelligen Ösophaguskarzinom aus der Literatur ausgewertet. Die erhobenen Daten beziehen sich auf 13 auswertbare Kriterien, die in den „Methoden“ beschrieben sind, wovon sieben Kriterien mit univariaten und multivariaten Tests untersucht worden sind. Von 313 analysierten Patientenfällen waren 109 (35%) Patienten im limitierten Stadium der Erkrankung und 167 (54%) im ausgedehnten Stadium. Über die übrigen 35 Patienten sind keine Informationen bezüglich des Stadiums bekannt. Univariate und multivariate Analysen zeigten nur das Alter (50 Jahre, HR 1.024; 95% CI 1.000–1.041, 50 Jahre) und die Therapie als Kriterien eigenständige, signifikante Anzeichen für eine Prognose sind.

Background: Until now, cytokine-induced killer (CIK) cells were assumed to be part of the type I natural killer T (NKT) cell population, but it was not yet investigated if this is correct. Methods: For analysis, CIK cells were generated by various culture conditions. Human type I NKT cells express a T cell receptor (TCR) composed of an invariant Vα24-JαQ chain combined with one of several Vβ chains. The Vα24 is a reliable marker for the presence of these TCRs. Results: While comparing cultures stimulated with different substances, we observed the lack of any Vα24 on the surface of CIK culture cells. Conclusion: We conclude that CIK cells do not belong to the type I NKT cells.

Background: High-dose chemotherapy (HDT) with autologous stem cell transplantation (ASCT) plays an important role in the treatment of aggressive non-Hodgkin’s lymphoma (NHL). We report on a retrospective analysis of all patients with diffuse large B-cell lymphoma who were consecutively treated with HDT followed by ASCT at the University Hospital of Bonn, Germany, between 1996 and 2004. Methods: A total of 25 patients were transplanted for biopsy-proven diffuse large B-cell lymphoma (DLBCL). Eight patients received up-front HDT as first-line therapy, four patients received HDT due to incomplete response to conventional induction chemotherapy, and six patients were treated for primary refractory disease. Seven patients had recurrent lymphoma. Results: A complete remission (CR) was achieved in 14 of 25 patients (56%). Estimated 3-year survival for patients treated with upfront HDT, chemosensitive patients with incomplete response to first line therapy, and patients with chemosensitive relapsed disease was 87.5%, 50.0% and 60.0%, respectively. In contrast, no patient with primary refractory disease or relapsed disease lacking chemosensitivity lived longer than 8 months. Chemosensitivity was the only significant prognostic factor for overall survival (OS) in multivariate analysis. Conclusions: Our results confirm that HDT and ASCT is a highly effective therapy in patients with DLBCL leading to long-term survival in a substantial proportion of patients. Patients treated upfront for high-risk disease, incomplete response to conventional first-line therapy, or for chemosensitive relapse have a good prognosis. In contrast, patients with primary chemorefractory disease and patients with relapsed disease lacking chemosensitivity do not benefit from HDT with ASCT.

Objective: Therapeutic vaccination with dendritic cells (DC) showed promising results in first clinical trials in cases of metastatic renal cell carcinoma (RCC). Human telomerase reverse transcriptase (hTERT) could be a potential target because it is detectable in more than 85% of human tumors including RCC. Design: 10 patients with progressive metastatic RCC were enrolled in a clinical phase I/II trial using DC pulsed with hTERT-peptide. Beside toxicity and feasibility aspects, a complex immune monitoring including in vitro data were evaluated. In addition to detection of tumor-specific effector cells we investigated their functionality like IFN-γ secretion and cytotoxic activity against tumor cells. Results: The vaccine was well tolerated. Two patients showed a mixed response (MR) and one patient a stable disease (SD). Interestingly, responders showed cytotoxic activity already before start of therapy and there was a significant increase in cytotoxic activity of effector cells from all responders (SD and MR patients) after the first vaccination. In contrast non-responders showed no cytotoxic activity before and during treatment. Therefore, cytotoxic activity might be used as a predictive marker in the future. Tetramer staining detected higher amounts of tumor-specific cytotoxic cells in responding patients compared to non-responders. Also, responders possessed increasing amounts of IFN-γ producing immunological effector cells. Conclusion: Telomerase-pulsed DC could enhance a tumor-specific immune response against RCC.

We report of a 34-year old man with second intracranial relapse of a suprasellar germinoma. Despite of extensive pretreatment with radiation and conventional chemotherapy relapse occurred and was treated with sequential high-dose chemotherapy followed by transfusion of autologous peripheral stem cells. The high-dose chemotherapy course was complicated by refractory derailment of pineal gland insufficiency. The patient achieved a complete remission after high dose chemotherapy which lasted for 13 months. Subsequently, he developed a third relapse and died.

Introduction: The trend toward personalized medicine leads to very small study cohorts for clinical trials, which makes it difficult to recruit patients in a single study center. On the other hand, the administrative effort required to initiate a clinical trial is very high. As a result, Germany runs the risk of falling behind other countries as a trial location. For this reason, the Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD) has been working on the challenge of a new satellite model in which the main trial center is the only one to conclude a trial center contract with the sponsor and also handles all formalities with it. The remaining sites constitute the satellites. In contrast to former satellite models, the entire study-related interventions are carried out at each site in the present model. Methods: In order to evaluate the approvability of the model, contact was made with both higher federal authorities and the responsible inspectorate, and none of them declared themselves responsible for a possible basic approval. The four ethics committees contacted agreed to the model subject to certain framework conditions. In addition, the model was validated by the preparation of several legal opinions on various issues (medical, labor, antitrust law). Conclusion: Study participation close to home is a decisive advantage for multimorbid patients. As up to four locations form a trial site in the model, a large catchment area can be covered with reduced administrative costs. The satellite model developed is intended to give patients broader access to medical innovations in cancer therapy. [ABSTRACT FROM AUTHOR]

A firm link between endoplasmic reticulum (ER) stress and tumors has been wildly reported. Endoplasmic reticulum oxidoreductase 1 alpha (ERO1α), an ER-resident thiol oxidoreductase, is confirmed to be highly upregulated in various cancer types and associated with a significantly worse prognosis. Of importance, under ER stress, the functional interplay of ERO1α/PDI axis plays a pivotal role to orchestrate proper protein folding and other key processes. Multiple lines of evidence propose ERO1α as an attractive potential target for cancer treatment. However, the unavailability of specific inhibitor for ERO1α, its molecular inter-relatedness with closely related paralog ERO1β and the tightly regulated processes with other members of flavoenzyme family of enzymes, raises several concerns about its clinical translation. Herein, we have provided a detailed description of ERO1α in human cancers and its vulnerability towards the aforementioned concerns. Besides, we have discussed a few key considerations that may improve our understanding about ERO1α in tumors. [ABSTRACT FROM AUTHOR]

A research proved that overall survival improved with Temsirolimus than with Interferon Alfa in patients suffering from advanced renal-cell carcinoma.