Insights into the different mechanistic stages of light-induced hydrogen evolution of a 5,5'-bisphenanthroline linked RuPt complex.

Herein, the synthesis in conjunction with the structural, electrochemical, and photophysical characterization of a 5,5'-bisphenanthroline (phenphen) linked heterodinuclear RuPt complex (Ru(phenphen)Pt) and its light-driven hydrogen formation activity are reported. A single crystal X-ray diffraction (SC-XRD) analysis identified a perpendicular orientation of the two directly linked 1,10-phenanthroline moieties. The disruption of π-conjugation blocks intramolecular electron transfer as evidenced by a comparative time-resolved optical spectroscopy study of Ru(phenphen)Pt and the reference complexes Ru(phenphen) and Ru(phenphen)Ru. However, reductive quenching is observed in the presence of an external electron donor such as triethylamine. Irradiating Ru(phenphen)Pt with visible light (470 nm) leads to H2 formation. We discuss a potential mechanism that mainly proceeds via Pt colloids and provide indications that initial hydrogen generation may also proceed via a molecular pathway. As previous reports on related heterodinuclear RuPt-based photocatalysts revealed purely molecular hydrogen evolution, the present work thus highlights the role of the bridging ligand in stabilizing the catalytic center and consequently determining the mechanism of light-induced hydrogen evolution in these systems.

Carbene based photochemical molecular assemblies for solar driven hydrogen generation.

Novel photocatalysts based on ruthenium complexes with NHC (N-heterocyclic carbene)-type bridging ligands have been prepared and structurally and photophysically characterised. The identity of the NHC-unit of the bridging ligand was established unambiguously by means of X-ray structural analysis of a heterodinuclear ruthenium-silver complex. The photophysical data indicate ultrafast intersystem crossing into an emissive and a non-emissive triplet excited state after excitation of the ruthenium centre. Exceptionally high luminescence quantum yields of up to 39% and long lifetimes of up to 2 µs are some of the triplet excited state characteristics. Preliminary studies into the visible light driven photocatalytic hydrogen formation show no induction phase and constant turnover frequencies that are independent on the concentration of the photocatalyst. In conclusion this supports the notion of a stable assembly under photocatalytic conditions.

Modified bibenzimidazole ligands as spectator ligands in photoactive molecular functional Ru-polypyridine units? Implications from spectroscopy.

The photophysical properties of Ruthenium-bipyridine complexes bearing a bibenzimidazole ligand were investigated. The nitrogens on the bibenzimidazole-ligand were protected, by adding either a phenylene group or a 1,2-ethandiyl group, to remove the photophysical dependence of the complex on the protonation state of the bibenzimidazole ligand. This protection results in the bibenzimidazole ligand contributing to the MLCT transition, which is experimentally evidenced by (resonance) Raman scattering in concert with DFT calculations for a detailed mode assignment in the (resonance) Raman spectra.

[Clinical outcome of a cohort of 63 patients with hepatocellular carcinoma treated with octreotide].

Unresectable hepatocellular carcinoma (HCC) are associated with a poor prognosis. Recently, one controlled study reported a strikingly prolonged survival of patients with HCC who were treated with octreotide. Until other randomised controlled trials become available, this multicentric retrospective study therefore assesses the outcome of HCC-patients who received octreotide treatment. 63 patients (53 males, 10 females) who had been treated with octreotide at 13 participating German centres were included in the analysis. In 54 cases liver cirrhosis was present (25 Child-Pugh A, 20 Child-Pugh B, 7 Child-Pugh C, 2 unknown). The liver disease was associated with alcohol abuse in 19 patients, alcohol and viral hepatitis in four patients, while 12 patients had only markers of past or present hepatitis B infection, 11 patients suffered of chronic hepatitis C infection, and four patients were seropositive for both hepatitis B and hepatitis C markers. The Okuda stage was stage I in 23, stage II in 33, and stage III in 7 patients. The patients initially received octreotide as a long-acting release formula (20-30 mg/month) in 43 cases or through subcutaneous injection (dose 3 x 50-3 x 300 ug/day) in the remaining cases. 11 of the patients receiving subcutaneous treatment were later converted to the long-acting release form of the drug. At three months, a partial remission was achieved in two patients, while 22 tumours showed no change and 26 tumours progressed. At six months, 11 tumours showed no change, while 15 tumours progressed. The patients' median survival was 9 months (Okuda stage I 16 months, stage II 9 months, stage III 4 months). In conclusion, octreotide treatment did not result in markedly prolonged survival in this retrospective series of 63 patients.

Paratesticular rhabdomyosarcoma: report from the Italian and German Cooperative Group.

PURPOSE: We report the experience of the German-Italian Cooperative Group with 216 pediatric patients with paratesticular rhabdomyosarcoma treated over 20 years. PATIENTS AND METHODS: At diagnosis, 198 patients had localized disease and 18 had distant metastases. Among the nonmetastatic patients, complete tumor resection was performed in 83% of cases. Evaluation of the retroperitoneal lymph nodes changed over the years from routine surgical staging to radiologic assessment. All patients received chemotherapy, which was reduced in intensity and duration for patients with low-risk features in subsequent protocols. Radiotherapy was administered to 10% of patients. RESULTS: Among 72 patients with a negative retroperitoneal computed tomography (CT) scan, surgical assessment detected nodal involvement in only one case. Among 23 patients with enlarged nodes on CT scans, surgery confirmed nodal spread in 65% of patients. No differences in the rate of nodal involvement were observed over the years. With a median follow-up of 110 months, 5-year survival was 85.5% for the series as a whole, 94.6% for patients with localized disease, and 22.2% for metastatic cases. Retroperitoneal nodal recurrence was the major cause of treatment failure. Univariate analysis revealed the prognostic value of tumor invasiveness, size, and resectability, as well as of nodal involvement and age, in patients with localized tumor. CONCLUSION: The outcome for patients with localized paratesticular rhabdomyosarcoma is excellent, despite the reduction in chemotherapy over the years: an alkylating agent-free and anthracycline-free regimen is adequate treatment for low-risk patients. Surgical assessment of the retroperitoneum must be reserved for patients with enlarged nodes on CT scans. Children over 10 years old carry a higher risk of nodal involvement and relapse.

Clinical characteristics and outcome of a cohort of 101 patients with hepatocellular carcinoma.

AIM: To conduct a cohort study of 101 patients with hepatocellular carcinoma (HCC) presenting to a tertiary care medical referral center in Germany between 1997 and 1999. METHODS AND RESULTS: Data were retrospectively analyzed by chart review. In 95 cases (72 males and 23 females) sufficient data were available for analysis. Twenty five (29%) of 85 patients were HBsAg or anti HBc positive, 21/85 (25%) were anti HCV positive, and 6/85 (7%) were positive for both HBV and HCV-markers. Age was significantly lower in HBV positive patients than in the other two groups. Thirty one (34%) of 90 patients had histories of alcohol abuse. In 79/94 (84%) patients, cirrhosis was diagnosed. Of these cirrhotic patients, 29/79 (37%) belonged to Child Pugh's group (CHILD) A, 32/79 (40%) to CHILD B, and 18/79 (23%) to CHILD C. AFP was elevated in 61/91 (67%) patients. A single tumor nodule was found in 38/94 (40%), more than one nodule in 31/94 (34%), and 25/94 (26%) had a diffusely infiltrating tumor, i.e. the tumor margins could not be seen on imaging procedures. Portal vein thrombosis was present in 19/94 (20%). Imaging data consistent with lymph node metastases were found in 10/92 (11%), while distant metastases were found in 8/93 (9%). According to Okuda 28/94 (30%) were grouped to stage I, 53/94 (56%) were grouped to stage II, and 13/94 (14%) were grouped to stage II. Survival data were available for 83 patients. The Kaplan-Meier estimate for median survival was 8 4 months. Factors influencing survival were the Okuda score, the presence of portal vein thrombosis, and the presence of ascites. The presence of non complicated liver cirrhosis by itself, distant metastases, or infection with hepatitis viruses did not influence survival. AFP positivity by itself did not influence survival, though patients with an AFP value greater than 100 microg/L did experience shortened survival. Treatment besides tamoxifen or supportive care was associated with prolonged survival. The influence of therapy on survival was most pronounced in Okuda stage II patients. There was longer survival in those Okuda stage II patients who were treated with percutaneous ethanol injection. CONCLUSION: Even in a low incidence area such as Germany, the majority of HCC is caused by viral hepatitis and therefore potentially preventable. Reflecting the high proportion of advanced stage tumors in our patients, the median survival was poor. Patients who received active therapy had a longer survival.

[Chemotherapy in fibromatoses of childhood and adolescence: results from the Cooperative soft tissue sarcoma study (CWS) and the Italian Cooperative study group (ICG-AIEOP)]. / Chemotherapie bei Fibromatosen im Kindes- und Jugendalter: Erfahrungen der Cooperativen Weichteilsarkom Studie (CWS) und Italienischen Cooperativen Studiengruppe (ICG--AIEOP).

BACKGROUND: Fibromatoses are a group of semimalignant tumors which grow infiltratively without metastases. If radical surgery is not at all possible or only by mutilation the question of neoadjuvant concepts arises. PATIENTS: We report on therapy and outcome of 36 patients registered to the German CWS study group and the Italian ICG study group for soft tissue sarcoma who were between 0 and 23 years of age. 15 had a histology of infantile (myo-) fibromatosis (9 unifocal, 6 multifocal). 15 patients had desmoid-like, aggressive fibromatosis. METHODS: We performed a retrospective analysis of the patients registered to the CWS and ICG study group. For literature review a medline search was performed. RESULTS: 23 patients received chemotherapy with anthracyclines (VAIA) or without (VAC) or monotherapy with alkylating agents. In 19 cases response to chemotherapy was measurable. In 9 patients tumors responded to chemotherapy. In some cases response was evident only after 20 weeks of treatment. In the group of non responders treatment was stopped early (after 4 weeks) in some cases. Relapses occurred mainly in the group of desmoid-like, aggressive fibromatosis (7 out of 15). In the group of infantile (myo-) fibromatosis only one patient suffered a relapse (1 out of 9). The literature review showed that mainly ADR/DTIC, VAC and MTX/VBL was used for inoperable fibromatoses. Concerning the response rates there where no major differences. Concerning toxicity the regimen with methotrexate and vinblastine seems superior to the others. CONCLUSIONS: As a chemotherapy regimen of first choice vinblastine with low dose methotrexate can be recommended. The therapy should not be stopped before the 20th week of treatment. The histological subgroup can provide good information on the relapse rate and aggressivity to be expected.

[Radiation therapy in juvenile aggressive fibromatosis]. / Strahlentherapie bei juvenilen aggressiven Fibromatosen.

BACKGROUND: In about one third of patients suffering from a desmoid tumor primary complete resection is not feasible. Furthermore in locally relapsing tumors reoperation alone does not result in cure in many cases. Radiotherapy can be applied in both groups of patients with curative intention. But the indication of radiotherapy is challenging particularly in children and adolescents due to the impending late radiation sequelae such as growth delay, fibrosis and radiation induced secondary malignancy. PATIENTS AND METHOD: The follow up and outcome of five irradiated children/adolescents with desmoid tumors, registered in the German-Cooperative-Soft-Tissue-Sarcoma Study (CWS) was looked at, and the corresponding literature was reviewed. RESULTS: Radiotherapy of gross residual or relapsing tumors resulted in long lasting event free survival in two cases (3/8 years), but in one patient local progression occurred despite irradiation. Postoperative radiotherapy in patients with microscopic residual disease resulted in both, long lasting event free survival (14 years, 1 patient) and in early local relapse (1.5 years, 1 patient). The role of radiotherapy could not be evaluated clearly by the CWS-experience due to the fact that the irradiated patients were treated individually also by chemotherapy and/or tamoxifen. But despite sparse and retrospective data there is evidence in the literature, that radiotherapy is able to control 65-90% of the unresectable desmoid tumors and that the local relapse rate can be reduced by radiotherapy by 10-20% in patients with microscopic residual disease following resection. CONCLUSIONS: Radiotherapy as primary treatment should be given if complete tumor resection is not feasible without mutilation. Radiotherapy can be applied postoperatively if the risk of local relapse seems to be highly life- or function threatening.

Molecular cytogenetic analysis of RB-1 deletions in chronic B-cell leukemias.

Deletions or translocations of 13q, most commonly involving band 13q14, belong to the most frequent structural chromosome abnormalities in B-cell chronic lymphocytic leukemia (B-CLL). In a combined metaphase and interphase cytogenetic study using conventional G-banding analysis and fluorescence in situ hybridization (ISH) we previously analysed the retinoblastoma susceptibility gene (RB-1) and its chromosomal locus 13q14 in 35 patients with chronic B-cell leukemias. We report here on the interphase cytogenetic analysis of 109 cases with chronic B-cell leukemias [B-CLL = 90; B-prolymphocytic leukemia (B-PLL) = 6, hairy cell leukemia (HCL) = 13]; a subset of 49 patients (B-CLL = 45; B-PLL = 4) was studied by conventional G-banding analysis. By G-banding, 5/45 (11%) patients with B-CLL had deletions or translocations affecting band 13q14; in contrast, ISH to interphase cells showed RB-1 deletion in 19/90 (21%) patients with B-CLL. No 13q14 abnormalities or RB-1 deletion were detected in patients with B-PLL and HCL. Our data confirm the high frequency of RB-1 deletions in B-CLL and further emphasize the possible pathogenetic role of this genomic region.