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Schweinfurt, Germany

Kehl S.,University of Mannheim | Weigel M.,Leopoldina Hospital | Muller D.,University of Mannheim | Gentili M.,University of Mannheim | And 3 more authors.
Archives of Gynecology and Obstetrics | Year: 2011

Purpose: Serodiscordant couples with a human immunodeficiency virus type 1 (HIV-1)-infected man request assisted reproductive technology (ART) in order to achieve safe conception. Most of these men are on highly active antiretroviral therapy (HAART). HIV-1 infection and the antiretroviral drugs are blamed for semen alterations. The aim of our study was to investigate the semen parameters in HIV-1-infected patients with and without HAART and to compare their sperm characteristics with those of healthy men. Materials and methods: A prospective study of 226 men attended the university fertility center of Mannheim between May 1996 and July 2003. The patients were divided into three groups: HIV-infected men taking antiretroviral therapy, HIV-infected patients who did not take antiretroviral therapy until now and a control group with 93 men consulting our fertility center together with their wives because of tubal sterility. Semen samples were examined with regard to ejaculate volume, sperm concentration, motility, and morphology. Results: The study showed significant differences between the ejaculate of HIV-infected and non-infected men. The HIV-infected men as a whole group and the subgroup of men with HAART had a lower ejaculate volume, less slow progressive and more abnormally shaped spermatozoa compared with the control group. The HIV-infected men without an antiretroviral therapy had a significant lower ejaculate volume compared with the control group; the other parameters were not altered significantly. Differences between the subgroups with and without HAART were not significant. Conclusion: The spermiogram in HIV-1-infected men in comparison to a control group of healthy men is negatively altered. Especially in men with HAART, ejaculate volume as well as sperm morphology and motility changed significantly. © 2011 Springer-Verlag.


Thieringer F.R.,Johannes Gutenberg University Mainz | Maass T.,Johannes Gutenberg University Mainz | Anthon B.,Johannes Gutenberg University Mainz | Meyer E.,Johannes Gutenberg University Mainz | And 5 more authors.
Molecular Carcinogenesis | Year: 2012

Matrix metalloproteinase-9 (MMP-9) plays a central role in tumor invasion and development of metastases. Expression of MMP-9 had been shown in human hepatocellular carcinomas (HCCs). However, it remained unclear whether MMP-9 could influence development of HCC. In order to address this issue, we generated transgenic mice overexpressing MMP-9 in the liver. In order to avoid embryonic lethality a Cre-lox system was utilized for conditional overexpression of MMP-9 under control of an albumin enhancer and promoter. Induction of MMP-9 overexpression in transgenic mice was achieved by i.v. injection of an adenovirus coding for the Cre recombinase. Initiation of liver carcinogenesis was achieved by injection of diethylnitrosamine (DEN) followed by Phenobarbital administration in drinking water. Transgene expression was induced at the age of 6wk. Four and six months later mice were sacrificed and examined macroscopically and microscopically in a blinded manner. Alb/Cre/MMP-9-transgenic mice showed liver specific overexpression of MMP-9-mRNA and protein after induction. At the age of 6 months livers of transgenic mice showed 15.7±11.6 tumors (mean±SD) in contrast to wildtype mice with only 7.9±11.0 tumors (P<0.03). By histopathology examination of the livers HCCs were identified in 42% of the transgenic mouse livers but only 8% in wildtype animals. In summary, we established a novel MMP-9 transgenic mouse model, and report on a significantly increased susceptibility of MMP-9 transgenic mice to chemically induced carcinogenesis. This is the first in vivo proof that MMP-9 overexpression promotes liver tumor development. © 2011 Wiley Periodicals, Inc.


Klement R.J.,Leopoldina Hospital
Trends in molecular medicine | Year: 2014

As ongoing research continues to reveal the links between metabolism, cancer, and aging it is good to see non-toxic interventions such as caloric restriction (CR) coming into focus. Recently, Meynet and Ricci provided a timely review summarizing the current state of research on the possible role of CR in cancer treatment. In discussing ways to implement clinically the beneficial effects of CR without a need for overall reduced food intake these authors focused on CR-mimicking drugs that have several limitations. I propose carbohydrate restriction as probably the best way to mimic CR in humans without the need to restrict energy intake. Copyright © 2014 Elsevier Ltd. All rights reserved.


Klement R.J.,Leopoldina Hospital
Cancer Biology and Medicine | Year: 2014

Head and neck cancers (HNCs) are aggressive tumors that typically demonstrate a high glycolytic rate, which results in resistance to cytotoxic therapy and poor prognosis. Due to their location these tumors specifically impair food intake and quality of life, so that prevention of weight loss through nutrition support becomes an important treatment goal. Dietary restriction of carbohydrates (CHOs) and their replacement with fat, mostly in form of a ketogenic diet (KD), have been suggested to accommodate for both the altered tumor cell metabolism and cancer-associated weight loss. In this review, I present three specific rationales for CHO restriction and nutritional ketosis as supportive treatment options for the HNC patient. These are (1) targeting the origin and specific aspects of tumor glycolysis; (2) protecting normal tissue from but sensitizing tumor tissue to radiation- and chemotherapy induced cell kill; (3) supporting body and muscle mass maintenance. While most of these benefits of CHO restriction apply to cancer in general, specific aspects of implementation are discussed in relation to HNC patients. While CHO restriction seems feasible in HNC patients the available evidence indicates that its role may extend beyond fighting malnutrition to fighting HNC itself. Copyright © 2014 by Cancer Biology & Medicine.


Thomaidis T.,Johannes Gutenberg University Mainz | Weinmann A.,Johannes Gutenberg University Mainz | Sprinzl M.,Johannes Gutenberg University Mainz | Kanzler S.,Leopoldina Hospital | And 6 more authors.
International Journal of Clinical Oncology | Year: 2014

Background: The impact of erythropoiesis-stimulating agents in chemotherapy-induced anemia has been a constant topic of debate over recent years. We prospectively assessed the efficacy of epoetin beta (Epo-b) in improving hemoglobin (Hb) levels and outcome in patients within an open label, randomized clinical phase II trial with advanced or metastatic gastric/esophagogastric cancer. Methods: Previously untreated patients were randomized to receive 3-weekly cycles of capecitabine (1000 mg/m2 bid) for 14 days plus on day 1 either irinotecan 250 mg/m2 or cisplatin 80 mg/m2. Epo-b (30000 IU once weekly) was initiated in patients with Hb <11 g/dl and continued until Hb ≥12 g/dl was reached. If after 4 weeks the Hb increase was <0.5 g/dl, Epo-b was increased to 30000 IU, twice weekly. Results: Of 118 patients enrolled, 32 received Epo-b treatment; of these, 65 % achieved an increase in Hb levels of at least 2 g/dl, with 74 % achieving the target Hb of ≥12 g/dl. Within the study population, patients receiving Epo-b showed better overall survival (median 14.5 vs. 8.0 months, P = 0.056) as well as a significantly improved disease control rate (78 vs. 55 %, P = 0.025). Patients in the irinotecan group profited significantly (P < 0.05) in terms of progression-free survival and overall survival under Epo-b treatment (median 6.5 vs 4.1 months and median 15.4 vs 8.4 months, respectively). Conclusions: Epo-b was effective in raising Hb levels in patients with advanced esophagogastric cancer. Patients receiving Epo-b had a significantly increased response to chemotherapy and a clear trend to improved survival. © 2013 Japan Society of Clinical Oncology.

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