bluuebunny/crossref_metadata_2025 huggingface dataset:
Antiandrogen Withdrawal Alone or in Combination With Ketoconazole in Androgen-Independent Prostate Cancer Patients: A Phase III Trial (CALGB 9583)
Authors: Small Eric J. , Halabi Susan , Dawson Nancy A. , Stadler Walter M. , Rini Brian I. , Picus Joel , Gable Preston , Torti Frank M. , Kaplan Ellen , Vogelzang Nicholas J.
Published: March 2004

Purpose

Antiandrogen withdrawal (AAWD) results in a prostate-specific antigen (PSA) response (decline in PSA level of ≥ 50%) in 15% to 30% of androgen-independent prostate cancer (AiPCa) patients. Thereafter, adrenal androgen ablation with agents such as ketoconazole (K) is commonly utilized. The therapeutic effect of AAWD alone was compared with simultaneous AAWD and K therapy.

Patients and Methods

AiPCa patients were randomized to undergo AAWD alone (n = 132), or together with K (400 mg orally [po] tid) and hydrocortisone (30 mg po each morning, 10 mg po each evening; n = 128). Patients who developed progressive disease after AAWD alone were eligible for deferred treatment with K.

Results

Eleven percent of patients undergoing AAWD alone had a PSA response, compared to 27% of patients who underwent AAWD and simultaneous K (P = .0002). Objective responses were observed in 2% of patients treated with AAWD alone compared to 20% in patients treated with AAWD/K (P = .02). There was no difference in survival. PSA and objective responses were observed in 32% and 7%, respectively, of patients receiving deferred K, and were more common in patients with prior AAWD response. Treatment with K was well tolerated, and resulted in a decline in adrenal androgen levels, which rose at the time of disease progression.

Conclusion

K has modest activity in AiPCa patients, while AAWD alone has minimal activity. Adrenal androgen levels fall with treatment with K and then climb at the time of progression, suggesting that progressive disease while on K may be due to tachyphylaxis to the adrenolytic properties of K.
Evaluation of Diagnostic Assessment Units in Oncology: A Systematic Review
Authors: Gagliardi Anna , Grunfeld Eva , Evans William K.
Published: March 2004

Purpose

This systematic review was undertaken to identify clinical and economic evaluations of diagnostic assessment units for cancer; summarize measures used to evaluate such programs; and discuss the strengths and weaknesses of these evaluations.

Methods

The review was conducted to identify randomized controlled trials, case control studies, and prospective or retrospective cohort studies examining the outcomes of diagnostic centers for patients with a presumptive diagnosis of breast, colorectal, lung, head and neck, or prostate cancer. Data on methodology and study results were tabulated.

Results

Twenty articles were eligible for review. Eleven studies examined outcomes associated with breast cancer assessment units: six with head and neck assessment units and three with colorectal assessment units. No studies were found that examined one-stop diagnostic assessment centers for lung cancer or prostate cancer. Seventeen studies were case series, one was a case-control study, and two were randomized controlled trials. No thorough economic analyses have been undertaken. There were no studies that based their assessment on measures suggested by a conceptual framework or validated model of diagnostic care. Few studies explicitly based their investigations on established quality indicators or clinical practice guideline recommendations. Diagnostic assessment centers appear to decrease the time to arrive at a diagnosis, which in turn appears to decrease patient anxiety and increase patient satisfaction.

Conclusion

A comprehensive understanding of the benefit of diagnostic assessment centers can only be determined if such services are developed for a variety of disease sites and more rigorous evaluations are carried out to assess their benefit.
Psychological Outcomes in Long-Term Survivors of Childhood Brain Cancer: A Report From the Childhood Cancer Survivor Study
Authors: Zebrack Brad J. , Gurney James G. , Oeffinger Kevin , Whitton John , Packer Roger J. , Mertens Ann , Turk Norman , Castleberry Robert , Dreyer ZoAnn , Robison Leslie L. , Zeltzer Lonnie K.
Published: March 2004

Purpose

To evaluate and compare psychological outcomes in long-term survivors of pediatric brain cancer and siblings of childhood cancer survivors, and to identify significant correlates of psychological distress.

Methods

One thousand one hundred one adult survivors of childhood brain cancer and 2,817 siblings completed a long-term follow-up questionnaire allowing assessment of symptoms associated with depression, somatization, and anxiety, as well as demographic, health, and medical information.

Results

A large majority of siblings and survivors report few, if any, symptoms of psychological distress. The prevalence of distress approximating clinically significant levels for both survivors (11%) and siblings (5%) reflects rates found in the general population. Yet when accounting for significant sociodemographic, socioeconomic, and health-status variables, survivors of childhood brain cancer, in the aggregate, appear to report significantly higher global distress and depression scores than do siblings. As in the general population, higher levels of distress among survivors and siblings were associated with female sex, low household income, lower educational attainment, being unmarried, not being employed in the past 12 months, and poor physical health status. No diagnostic or treatment-related variables were directly and significantly associated with increases in distress symptoms for survivors of childhood brain cancer.

Conclusion

Cancer treatment does not appear to contribute directly to increased psychological distress. Instead, distress appears to be associated with diminished social functioning that may be related to cancer type or treatment. Implementation and evaluation of supportive interventions that enhance survivors' social and vocational skills should be considered.
Safety of Treatment of Metastatic Breast Cancer With Trastuzumab Beyond Disease Progression
Authors: Tripathy Debu , Slamon Dennis J. , Cobleigh Melody , Arnold Andrew , Saleh Mansoor , Mortimer Joanne E. , Murphy Maureen , Stewart Stanford J.
Published: March 2004

Purpose

In a pivotal phase III trial, the addition of trastuzumab to chemotherapy significantly improved response rate, time to disease progression, and overall survival in women with HER2 overexpressing metastatic breast cancer. We conducted an extension study to this trial to obtain additional safety information and to provide trastuzumab following disease progression.

Patients and Methods

A total of 247 patients with documented disease progression received weekly intravenous trastuzumab in the extension study. Concurrent therapies were administered at the discretion of the treating physician. Patient groups were based on initial study treatment: chemotherapy alone (group 1, n = 154) or chemotherapy plus trastuzumab (group 2, n = 93).

Results

Sixty-eight percent of group 1 and 76% of group 2 received chemotherapy plus trastuzumab in the extension trial; the remainder received trastuzumab alone or combined with palliative radiotherapy or hormonal therapy. Seventy-six percent of group 1 and 55% of group 2 experienced at least one adverse event, similar to effects observed in the pivotal trial. Symptomatic or asymptomatic cardiac dysfunction occurred in 9% of group 1 and 2% of group 2 patients. Overall objective response rates were 14% in group 1 and 11% in group 2; median durations of response exceeded 6 months in both groups.

Conclusion

Our results suggest that prolonged use of trastuzumab therapy is safe and well tolerated. Longer durations of therapy did not appear to increase the risk of cardiac dysfunction. Patients progressing on trastuzumab-containing therapy demonstrate some response to a second trastuzumab-containing regimen. The independent contribution of trastuzumab in this setting merits further study.
Repetitive Cycles of High-Dose Cytarabine Benefit Patients With Acute Myeloid Leukemia and inv(16)(p13q22) or t(16;16)(p13;q22): Results from CALGB 8461
Authors: Byrd John C. , Ruppert Amy S. , Mrózek Krzysztof , Carroll Andrew J. , Edwards Colin G. , Arthur Diane C. , Pettenati Mark J. , Stamberg Judith , Koduru Prasad R.K. , Moore Joseph O. , Mayer Robert J. , Davey Frederick R. , Larson Richard A. , Bloomfield Clara D.
Published: March 2004

Purpose

To study the impact of repetitive (three to four courses) versus a single course of high-dose cytarabine (HDAC) consolidation therapy on outcome of patients with acute myeloid leukemia (AML) and inv(16)(p13q22) or t(16;16)(p13;q22).

Patients and Methods

We examined the cumulative incidence of relapse (CIR), relapse-free survival (RFS), and overall survival (OS) for 48 adults younger than 60 years with inv(16)/t(16;16) who had attained a complete remission on one of four consecutive clinical trials and were assigned to receive HDAC consolidation therapy. Twenty-eight patients were assigned to either three or four courses of HDAC, and 20 patients were assigned to one course of HDAC followed by alternative intensive consolidation therapy.

Results

Pretreatment features were similar for the two groups. The CIR was significantly decreased in patients assigned to receive three to four cycles of HDAC compared with patients assigned to one course (P = .03; 5-year CIR, 43% v 70%, respectively). The difference in RFS also approached statistical significance (P = .06). In a multivariable analysis that adjusted for potential confounding covariates, only treatment assignment (three to four cycles of HDAC) predicted for superior RFS (P = .02). The OS of both groups was similar (P = .93; 5-year OS, 75% for the three to four cycles of HDAC group v 70% for the one cycle of HDAC group), reflecting a high success rate with stem-cell transplantation salvage treatment administered among patients in both treatment groups.

Conclusion

We conclude that, in AML patients with inv(16)/t(16;16), repetitive HDAC therapy decreases the likelihood of relapse compared with consolidation regimens including less HDAC.
Mitoxantrone, Etoposide, and Cytarabine With or Without Valspodar in Patients With Relapsed or Refractory Acute Myeloid Leukemia and High-Risk Myelodysplastic Syndrome: A Phase III Trial (E2995)
Authors: Greenberg Peter L. , Lee Sandra J. , Advani Ranjana , Tallman Martin S. , Sikic Branimir I. , Letendre Louis , Dugan Kathleen , Lum Bert , Chin David L. , Dewald Gordon , Paietta Elisabeth , Bennett John M. , Rowe Jacob M.
Published: March 2004

Purpose

To determine whether adding the multidrug resistance gene-1 (MDR-1) modulator valspodar (PSC 833; Novartis Pharmaceuticals, Hanover, NJ) to chemotherapy provided clinical benefit to patients with poor-risk acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS).

Patients and Methods

A phase III randomized study was performed using valspodar plus mitoxantrone, etoposide, and cytarabine (PSC-MEC; n = 66) versus MEC (n = 63) to treat patients with relapsed or refractory AML and high-risk MDS.

Results

For the PSC-MEC versus MEC arms, complete response (CR) was achieved in 17% versus 25% of patients, respectively (P = not significant). For patients who had not received prior intensive chemotherapy (ie, with secondary AML or high-risk MDS), the CR rate was increased—35% versus 15% for the remaining patients (P = .018); CR rates did not differ between treatment arms. The median disease-free survival in those achieving CR was similar in the two arms (10 versus 9.3 months) as was the patients’ overall survival (4.6 versus 5.4 months). The CR rates in MDR+ (69% of patients) versus MDR− patients were similar for those receiving either chemotherapy regimen (16% versus 24%). The CR rate for unfavorable cytogenetic patients (45% of patients) was 13% compared to the remainder, 28% (P = .09). Population pharmacokinetic analysis demonstrated that the clearances of mitoxantrone and etoposide were decreased by 59% and 50%, respectively, supporting the empiric dose reductions in the PSC-MEC arm designed in anticipation of drug interactions between valspodar and the chemotherapeutic agents.

Conclusion

CR rates and overall survival were not improved by using PSC-MEC compared to MEC chemotherapy alone in patients with poor-risk AML or high-risk MDS.
Rapid Mobilization of CD34+ Cells Following Administration of the CXCR4 Antagonist AMD3100 to Patients With Multiple Myeloma and Non-Hodgkin's Lymphoma
Authors: Devine Steven M. , Flomenberg Neal , Vesole David H. , Liesveld Jane , Weisdorf Daniel , Badel Karin , Calandra Gary , DiPersio John F.
Published: March 2004

Purpose

Interactions between the chemokine receptor CXCR4 and its ligand stromal derived factor-1 regulate hematopoietic stem-cell trafficking. AMD3100 is a CXCR4 antagonist that induces rapid mobilization of CD34+ cells in healthy volunteers. We performed a phase I study assessing the safety and clinical effects of AMD3100 in patients with multiple myeloma (MM) and non-Hodgkin's lymphoma (NHL).

Patients and Methods

Thirteen patients (MM, n = 7; NHL, n = 6) received AMD3100 at a dose of either 160 μg/kg (n = 6) or 240 μg/kg (n = 7). WBC and peripheral blood (PB) CD34+ cell counts were analyzed at 4 and 6 hours following injection.

Results

AMD3100 caused a rapid and statistically significant increase in the total WBC and PB CD34+ counts at both 4 and 6 hours following a single injection. The absolute CD34+ cell count increased from a baseline of 2.6 ± 0.7/μL (mean ± SE) to 15.6 ± 3.9/μL and 16.2 ± 4.3/μL at 4 hours (P = .002) and 6 hours after injection (P = .003), respectively. The absolute CD34+ cell counts observed at 4 and 6 hours following AMD3100 were higher in the 240 μg/kg group (19.3 ± 6.9/μL and 20.4 ± 7.6/μL, respectively) compared with the 160 μg/kg group (11.3 ± 2.7/μL and 11.3 ± 2.5/μL, respectively). The drug was well tolerated and only grade 1 toxicities were encountered.

Conclusion

AMD3100 appears to be a safe and effective agent for the rapid mobilization of CD34+ cells in patients who have received prior chemotherapy. Further studies in combination with granulocyte colony-stimuating factor in patients with lymphoid malignancies are warranted.
2-18fluoro-deoxy-D-glucose Positron Emission Tomography Is a Reliable Predictor for Viable Tumor in Postchemotherapy Seminoma: An Update of the Prospective Multicentric SEMPET Trial
Authors: De Santis Maria , Becherer Alexander , Bokemeyer Carsten , Stoiber Franz , Oechsle Karin , Sellner Franz , Lang Alois , Kletter Kurt , Dohmen Bernhard M. , Dittrich Christian , Pont Jörg
Published: March 2004

Purpose

To define the clinical value of 2-18fluoro-deoxy-D-glucose positron emission tomography (FDG PET) as a predictor for viable residual tumor in postchemotherapy seminoma residuals in a prospective multicentric trial.

Patients and Methods

FDG PET studies in patients with metastatic pure seminoma who had radiographically defined postchemotherapy residual masses were correlated with either the histology of the resected lesion or the clinical outcome documented by computer tomography (CT), tumor markers, and/or physical examination during follow-up. The size of the residual lesions on CT, either > 3 cm or ≤ 3 cm, was correlated with the presence or absence of viable residual tumor.

Results

Fifty-six FDG PET scans of 51 patients were assessable. All 19 cases with residual lesions > 3 cm and 35 (95%) of 37 with residual lesions ≤ 3 cm were correctly predicted by FDG PET. The specificity, sensitivity, positive predictive value, and negative predictive value of FDG PET were 100% (95% CI, 92% to 100%), 80% (95% CI, 44% to 95%), 100%, and 96%, respectively, versus 74% (95% CI, 58% to 85%), 70% (95% CI, 34% to 90%), 37%, and 92%, respectively, for CT discrimination of the residual tumor by size (> 3 cm/≤ 3 cm).

Conclusion

This investigation confirms that FDG PET is the best predictor of viable residual tumor in postchemotherapy seminoma residuals and should be used as a standard tool for clinical decision making in this patient group.
Mucinous Epithelial Ovarian Cancer: A Separate Entity Requiring Specific Treatment
Authors: Hess Viviane , A'Hern Roger , Nasiri Nazar , King D. Michael , Blake Peter R. , Barton Desmond P.J. , Shepherd John H. , Ind T. , Bridges J. , Harrington K. , Kaye Stanley B. , Gore Martin E.
Published: March 2004

Purpose

Invasive mucinous carcinoma of the ovary (mucinous epithelial ovarian cancer [mEOC]) is a histologic subgroup of epithelial ovarian cancer (EOC). Chemotherapy for mEOC is chosen according to guidelines established for EOC. The purpose of this study is to determine whether this is appropriate.

Patients and Methods

Women with advanced mEOC (International Federation of Gynecology and Obstetrics stage III or IV) who underwent first-line platinum-based chemotherapy were compared with women with other histologic subtypes of EOC in a case-controlled study.

Results

Eighty-one patients (27 cases, 54 controls) treated with platinum-based regimens were analyzed. The response rates for cases and controls were 26.3% (95% CI, 9.2% to 51.2%) and 64.9% (95% CI, 47.5% to 79.8%), respectively (P = .01). The odds ratio for complete or partial response to chemotherapy for mEOC was 0.19 (95% CI, 0.06 to 0.66; P = .009) compared with other histologic subtypes of EOC. Median progression-free survival was 5.7 months (95% CI, 1.9 to 9.6 months) versus 14.1 months (95% CI, 12.0 to 16.2 months; P < .001) and overall survival was 12.0 months (95% CI, 8.0 to 15.6 months) versus 36.7 months (95% CI, 25.2 to 48.2 months; P < .001) for cases and controls, respectively. The hazard ratio for progression and death was 2.94 (95% CI, 1.71 to 5.07; P < .001) and 3.08 (95% CI, 1.69 to 5.6; P < .001), respectively, for mEOC patients as compared with controls.

Conclusion

Patients with advanced mEOC have a poorer response to platinum-based first-line chemotherapy compared with patients with other histologic subtypes of EOC, and their survival is worse. Specific alternative therapeutic approaches should be sought for this group of patients, perhaps involving fluorouracil-based chemotherapy.
Bronchioloalveolar Pathologic Subtype and Smoking History Predict Sensitivity to Gefitinib in Advanced Non–Small-Cell Lung Cancer
Authors: Miller Vincent A. , Kris Mark G. , Shah Neelam , Patel Jyoti , Azzoli Christopher , Gomez Jorge , Krug Lee M. , Pao William , Rizvi Naiyer , Pizzo Barbara , Tyson Leslie , Venkatraman Ennapadam , Ben-Porat Leah , Memoli Natalie , Zakowski Maureen , Rusch Valerie , Heelan Robert T.
Published: March 2004

Purpose

Gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, induces radiographic regressions and symptomatic improvement in patients with non–small-cell lung cancer (NSCLC). Phase II trials suggested female sex and adenocarcinoma were associated with response. We undertook this analysis to identify additional clinical and pathologic features associated with sensitivity to gefitinib.

Patients and Methods

We reviewed medical records, pathologic material, and imaging studies of all 139 NSCLC patients treated on one of three consecutive studies of gefitinib monotherapy performed at our institution. We identified patients experiencing a major objective response and compared their clinical and pathologic features with the others. Univariate and multivariable analyses were performed on potential predictive features associated with sensitivity to gefitinib.

Results

Of 139 patients, 21 (15%; 95% CI, 9% to 21%), experienced a partial radiographic response. Variables identified as significant in univariate analysis included adenocarcinoma versus other NSCLC (19% v 0%; P = .004), adenocarcinoma with bronchioloalveolar features versus other adenocarcinomas (38% v 14%; P < .001), never smoker status versus former/current (36% v 8%; P < .001), and Karnofsky performance status ≥ 80% versus ≤ 70% (22% v 8%; P = .03). Multivariable analysis revealed the presence of adenocarcinoma with any bronchioloalveolar features (P = .004) and being a never smoker (P = .006) were independent predictors of response.

Conclusion

Our data suggest that individuals in whom gefitinib is efficacious are more likely to have adenocarcinomas of the bronchioloalveolar subtype and to be never smokers. These observations may provide clues to mechanisms determining sensitivity to this agent and suggest that NSCLC has a different biology in patients who never smoked and those with bronchioloalveolar carcinoma.
Tolerance and Cancer: Mechanisms of Tumor Evasion and Strategies for Breaking Tolerance
Authors: Mapara Markus Y. , Sykes Megan
Published: March 2004

The development of malignant disease might be seen as a failure of immune surveillance. However, not all tumors are naturally immunogenic, and even among those that are immunogenic, the uncontrolled rapid growth of a tumor may sometimes out-run a robust immune response. Nevertheless, recent evidence suggests that mechanisms of tolerance that normally exist to prevent autoimmune disease may also preclude the development of an adequate antitumor response and that tumors themselves have the ability to thwart the development of effective immune responses against their antigens. A major challenge has been to develop approaches to breaking this tolerance in tumor-bearing hosts, and recent advances in our understanding of antigen presentation and tolerance have led to some promising strategies. An alternative approach is to use T cells from nontumor-bearing, allogeneic hosts in the form of lymphocyte infusions, with or without hematopoietic cell transplantation. Immunotherapy may occur in this setting via the response of nontolerant, tumor antigen-specific T cells from nontumor-bearing hosts or via the powerful destructive effect of an alloresponse directed against antigens shared by malignant cells in the recipient. Approaches to exploiting this beneficial effect without the deleterious consequence of graft-versus-host disease in allogeneic hematopoietic cell recipients are discussed.
Docetaxel Combined With Trastuzumab Is an Active Regimen in HER-2 3+ Overexpressing and Fluorescent In Situ Hybridization–Positive Metastatic Breast Cancer: A Multi-Institutional Phase II Trial
Authors: Tedesco K.L. , Thor A.D. , Johnson D.H. , Shyr Y. , Blum K.A. , Goldstein L.J. , Gradishar W.J. , Nicholson B.P. , Merkel D.E. , Murrey D. , Edgerton S. , Sledge G.W.
Published: March 2004

Purpose

To determine the efficacy and safety of weekly docetaxel and trastuzumab as first- or second-line therapy in women with HER-2–overexpressing metastatic breast cancer and to correlate the efficacy of trastuzumab with HER-2 status as determined by immunohistochemistry assay and fluorescent in situ hybridization (FISH).

Patients and Methods

Twenty-six women with HER-2–positive (HercepTest [Dako Corp, Carpenteria, CA]2 to 3+) metastatic breast cancer were enrolled onto this study of trastuzumab (4 mg/kg load; 2 mg/kg/wk administered intravenously) and docetaxel (35 mg/m2/wk for 6 weeks).

Results

Using an intent-to-treat analysis, the overall response rate was 50% (13 of 26 patients). Eight patients (31%) had a period of stable disease posttherapy. Among HER-2 3+ patients, the overall response rate was 63% (12 of 19 patients) compared with a 14% response rate (one of seven patients) for HER-2 2+ patients (P = .07). Patients with FISH-positive tumors experienced an overall response rate of 64%. Median time to progression was 12.4 months for the entire cohort (HER-2 3+ tumors, 12.3 months; HER-2 2+ lesions, 9.5 months) and median survival was 22.1 months. All HER-2 3+ patients were FISH-positive; the only HER-2 2+ patient responding to treatment was also FISH-positive. Grade 4 toxicities occurred in four patients; most toxicities were mild.

Conclusion

Trastuzumab plus docetaxel is an active and well-tolerated regimen in women with HER-2 3+ overexpressing or FISH-positive metastatic breast cancer.
Phase I Study of G3139, a bcl-2 Antisense Oligonucleotide, Combined With Carboplatin and Etoposide in Patients With Small-Cell Lung Cancer
Authors: Rudin Charles M. , Kozloff Mark , Hoffman Philip C. , Edelman Martin J. , Karnauskas Robyn , Tomek Ronald , Szeto Livia , Vokes Everett E.
Published: March 2004

Purpose

Bcl-2 is expressed in the majority of cases of small cell lung cancer (SCLC) and may contribute to chemotherapeutic resistance. Bcl-2 suppression by G3139 (oblimersen sodium), a phosphorothioate oligonucleotide complementary to the bcl-2 mRNA, has the potential to enhance the antitumor efficacy of standard cytotoxic chemotherapy. A dose-finding study was performed evaluating the combination of G3139, carboplatin, and etoposide in patients with previously untreated extensive stage SCLC.

Patients and Methods

Sixteen patients were treated in three consecutive cohorts. Cohort 1 (n = 5) received G3139 5 mg/kg/d on days 1 to 8 of a 21 day cycle, with carboplatin area under the curve (AUC) = 6 on day 6, and etoposide 80 mg/m2/d on days 6 to 8. In cohort 2 (n = 4), carboplatin dose was reduced to AUC = 5. In cohort 3 (n = 7), G3139 dose was escalated to 7 mg/kg/d. G3139 plasma concentrations and Bcl-2 protein levels in peripheral blood mononuclear cells were evaluated.

Results

Two of three assessable patients in cohort 1 experienced cycle 1 dose-limiting toxicity (grade 4 neutropenia). No cycle 1 dose-limited toxicity was observed in cohorts 2 or 3. Of 14 patients assessable for response, partial response was documented in 12 patients (86%), and stable disease in two. Median time to progression was 5.9 months. Carboplatin and etoposide administration did not appear to alter G3139 pharmacokinetics. No evidence of Bcl-2 suppression in peripheral blood mononuclear cells was observed.

Conclusion

The combination of G3139, carboplatin, and etoposide is well tolerated and results in an encouraging response rate and time to progression in patients with extensive stage SCLC.
Multi-Mode Molecular Switching Properties and Functions of Azo-Conjugated Metal Complexes
Authors: Nishihara Hiroshi
Published: March 2004

Recent studies on the azo-group-combined photochromic metal complexes are reviewed. These studies show unique trans–cis isomerization behaviors that have not been observed in regular organic azobenzenes. In the case of azobenzene-bound bis(terpyridine) complexes of transition metals, photoisomerization behavior depends strongly on the central metals, counterions, and solvents. Rh and Co complexes undergo photoisomerization smoothly, but the isomerization of Ru and Fe complexes is substantially retarded due to the energy transfer from the π–π* excited state to the MLCT transition. The photoluminescence property of an azobenzene-attached Pt complex is switched by photoisomerization of the azo moiety. Tris(azobenzene-bound bipyridine)cobalt undergoes reversible trans–cis isomerization using a combination of the CoIII/CoII redox change and a single UV light source exciting the π–π* transition. The trans–cis conversion yield is higher for the meta isomer (with respect to the position of the azo group against the pyridyl group) than for the para isomer. The trans–cis photoisomerization behavior of a 6,6′-dimethyl-substituted azobenzene-bipyridine ligand is synchronized with coordination of the bipyridine moiety to copper, and the trans/cis isomerization can be controlled reversibly through CuII/CuI redox and a single UV light irradiation. Photoreaction of azoferrocene occurs not only by UV-light irradiation but also by green light irradiation that excites the MLCT transition. 3-Ferrocenylazobenzene undergoes reversible trans–cis isomerization using a single green light source and the FeIII/FeII redox change. Azo-conjugated metalladithiolenes of NiII, PdII, and PtII with diphenylphosphinoethane as a co-ligand show facile photoisomerization. The energy of the reversible trans-to-cis photoisomerization is considerably lower than that of azobenzene. The thermal stability of the cis form is, however, much higher than that of the organic azobenzene derivatives showing similar low-energy trans-to-cis photoisomerization. A novel proton response of the azo group occurs, and the combination of photoisomerization and protonation leads to a novel proton-catalyzed cis-to-trans isomerization. These results indicate that several kinds of multi-photo-functionalities can be realized for the azo-conjugated transition metal complexes by tuning the interaction between the azo moiety and the metal complex unit.
Synthesis of Aromatic Species Containing a Heavier Group 14 Element by Taking Advantage of Kinetic Stabilization
Authors: Tokitoh Norihiro
Published: March 2004

In this Account, the syntheses, structures, and properties of novel aromatic species containing a heavier group 14 element were delineated with systematic comparison, focusing on their aromaticity. Several kinds of silaaromatic compounds, such as silabenzene, 1- and 2-silanaphthalenes, and 9-silaanthracene, which are a very interesting class of novel π-bonding systems containing a silicon atom, were successfully synthesized and isolated as stable compounds by taking advantage of the kinetic stabilization afforded by introduction of an efficient steric protection group, 2,4,6-tris[bis(trimethylsilyl)methyl]phenyl (Tbt). A similar synthetic approach can be applied to the cases of the first stable germaaromatics, such as germabenzene and 2-germanaphthalene. The molecular structures of the newly obtained metallaaromatic species were systematically investigated based on X-ray crystallographic analysis and spectroscopic studies together with theoretical calculations. During this study, a variety of new reactivities for these metallaaromatic species were revealed and some new insights and deeper knowledge were obtained about the aromaticity of metallaaromatic compounds of heavier group 14 elements.
Bioorganic Studies on Marine Natural Products with Bioactivity, Such as Antitumor Activity and Feeding Attractance
Authors: Suenaga Kiyotake
Published: March 2004

This account describes bioorganic studies on marine natural products with bioactivity, such as antitumor activity and feeding attractance. Chemical studies on the following bioactive compounds of marine origin have been carried out: 1) feeding attractants for the starfish Acanthaster planci, 2) potent toxins from shellfish of the genus Pinna that cause food poisoning, and 3) a variety of cytotoxic and antitumor compounds from marine invertebrates including sea hares, Dolabella auricularia and Aplysia kurodai. Their isolation, structure elucidation, synthesis, and some aspects of their biological activities are summarized.
Armed Cyclen Receptors: From Three Dimensional Cation Recognition to Supramolecular Architecture
Authors: Tsukube Hiroshi , Shinoda Satoshi
Published: March 2004

The concept and examples of armed cyclens are described and some of their recent applications in molecular recognition and supramolecular chemistry are explained. Armed cyclens are characterized by a parent tetraamine ring and functionalized sidearms. They can act as three-dimensional ligands for octadentate metal complexation. They exhibit comparable logK values for Na+ complexation to bicyclic cryptands, though they have flexible, open-chained structures. Since the resulting octacoordinate metal complexes have quadruple helicated structures, they can work as unique building blocks having C4 symmetry for chiral supramolecular architecture. Cholesterol-armed cyclen typically formed a self-aggregate with the integrated chirality in aqueous solution, in which asymmetrically helicated cyclen complexes were arrayed on a supramolecular scale. The self-aggregate had asymmetrically ordered domains, in which achiral organic anions and racemic metal complexes were nicely accommodated in stereo-controlled fashions. Since the armed cyclens have broad structural variations, they are applicable as specific receptors for cation recognition at the molecular level and also as building blocks for supramolecular architecture.
Synthesis, Crystal Structures, and Electrical Properties of Anion Radical Salts of Novel Electron Acceptors, 2,6-Dicyanomethylene-4-oxo-2,6-dihydrocyclopentadithiophene (CPDT-TCNQ) and Its Diselenophene Analogue (CPDS-TCNQ), Having Three Electron-Withdrawing Groups
Authors: Tarutani Shinji , Takahashi Kazuko
Published: March 2004

Novel heterophene analogues of tetracyanodiphenoquinodimethane (TCNDQ) having three electron-withdrawing groups in one molecule, 2,6-dicyanomethylene-4-oxo-2,6-dihydrocyclopentadithiophene (CPDT-TCNQ: 1) and 2,6-dicyanomethylene-4-oxo-2,6-dihydrocyclopentadiselenophene (CPDS-TCNQ: 2), have been synthesized. CPDT-TCNQ and CPDS-TCNQ have a good coplanar conformation and have a fairly high electron-accepting ability due to the existence of the central carbonyl group in addition to the two terminal dicyanomethylene groups. The anion radical salts, Me4X(CPDT-TCNQ)2 (X = N, P, and As), Et4N(CPDT-TCNQ)2, and Me4X(CPDS-TCNQ)2 (X = P and As), showed a metallic conducting behavior (σrt = 260 to 42 S cm−1) down to 130–255 K. In the crystal structures of Me4X(CPDT-TCNQ)2 (X = N, P, and As), which are isostructural with each other, the acceptor molecules form rigid and tight two-dimensional networks consisting of strong S···N and O···H inter-column contacts in the side-by-side direction. However, these salts have an extremely one-dimensional electronic structure along the stacking direction. This fact indicates that the chalcogen atoms in the acceptor molecules do not increase the dimensionality of the electronic structures of the anion radical salts; that property is significantly different from the role of chalcogen atoms of TTF or BEDT-TTF type donor molecules. The existence of the central carbonyl group in CPDT-TCNQ and in CPDS-TCNQ plays a very important role to give metallic anion radical salts due to the rigid conformation. The phase transition at 130 K on Me4N(CPDT-TCNQ)2 is regarded as 2kF CDW instability. The origins of the phase transitions at 165 K for Me4P(CPDT-TCNQ)2 and 185 K for Me4As(CPDT-TCNQ)2 are regarded as 4kF CDW. Thus the phase transition mechanisms of these salts are significantly different from each other, although the crystal structures are isostructural.
Pressure-Induced Phase Transitions in trans-Stilbene Crystals
Authors: Takeshita Hideyoshi , Suzuki Yoshio , Hirai Yuko , Nibu Yoshinori , Shimada Hiroko , Shimada Ryoichi
Published: March 2004

Pressure effects on the phase transitions in [1H12] and [2H12]trans-stilbene crystals were studied. Pressure–frequency plots and pressure–half band width plots for the Raman bands due to the inter- and intramolecular vibrations of [1H12] and [2H12]trans-stilbene crystals showed inflectional variations of the slopes of the plots at about 2 and 4 GPa. The fact that no clear discontinuous changes of the slopes of the plots were observed indicates that the second-order phase transitions take place at about 2 and 4 GPa. The low-frequency Raman bands of [1H12] and [2H12]trans-stilbene crystals were reinvestigated and assignments to the intermolecular rotational vibrations about the x, y, and z axes were made on the basis of the isotopic effect on the vibrational frequency.
Electrochemical and Thermodynamic Studies of Inclusion Complex Formation between Tetradecyltrimethylammonium Bromide (TTAB) and β-Cyclodextrin (β-CD)
Authors: Rafati Amir Abbas , Bagheri Ahmad
Published: March 2004

The behavior of the inclusion complex consisting of tetradecyltrimethylammonium bromide (TTAB) and β-cyclodextrin (β-CD) was studied using ion selective electrodes sensitive to surfactant ions. Two different methods were used in the construction of the ion selective electrode: (i) Membrane ion selective electrode (MISE) and (ii) Coating wire ion selective electrode (CWISE). The data obtained from two methods showed a consistency between two methods under all conditions. The CWISE method showed a faster response relative to the MISE ones. The experiments were carried out at different temperatures and in different concentrations of cyclodextrin. The data obtained indicate that the inclusion complexes S(CD) and S(CD)2 had formed between TTAB and β-cyclodextrin in an aqueous environment. In addition to the 1:1 complex, TTAB formed 1:2 complexes with β-cyclodextrin. Further investigation showed that K1 for S(CD) was greater than K2 for S(CD)2. Finally, thermodynamic parameters of the complexation, i.e., ΔH°, ΔG°, and ΔS° were also calculated.
A Concealed Property of the Topological Index Z
Authors: Gutman Ivan , Furtula Boris , Vidovic Dušica , Hosoya Haruo
Published: March 2004

Examination of the structure-dependence of the total π-electron energy leads to the equation F(G, x) = ln Z(G), where F(G, x) is the Coulson function (of the molecular graph G) and Z(G) is the corresponding topological index Z. The (positive and unique) solution of this equation is called the Z-point of G and is denoted by xH. By the analysis of the Z-points of trees and chemical trees the following generally valid regularities were established: (a) Not all trees have a Z-point, but all chemical trees have a Z-point. (b) The Z-points of all chemical trees (irrespective of their size and other structural features) are nearly equal; for all chemical trees, xH ≈ 1.2.
Effects of an Eruption on Miyake Island on the Behavior of Air Pollutants and Chemical Components of Rainwater in Kyoto
Authors: Yamada Etsu , Nishimura Yoshiaki , Furuya You , Huang Song-Nan , Fuse Yasuro
Published: March 2004

Continuous measurements of air pollutants (NOx, SO2, O3) by passive samplers and chemical components of rainwater in Kyoto were made from 1996 to 2002. An eruption on Miyake Island and urban climate changes were found to greatly affect the seasonal changes of air pollutants and chemical components of rainwater in 2000 and 2001. Several peaks of NO2 concentrations at mountains around the Kyoto basin occurred in the spring and summer of 2000 and 2001. The higher NO2 concentration in the summer of 2000 and 2001 may be attributed to the formation of a temperature-inversion layer. Atmospheric SO2 concentrations became abruptly higher in September 2000, and the concentration range of atmospheric SO2 in mountains around the Kyoto basin was 1.0–7.9 ppb from September 2000 to July 2001, which was about two-times higher than that until 1999. These results suggest that a large quantity of SO2 discharge by the eruption on Miyake Island may have affected the increase of atmospheric SO2 concentrations in Kyoto. The O3 concentrations in the summer of 2000 and 2001 were higher than that until 1999. The cause may be O3 production by a photochemical reaction with an increase of anthropogenic NOx in the warm months after 2000. The concentration of gaseous H2O2 was very low when the SO2 content was high in September, 2000, and in June and July, 2001, which may have been due to a large quantity of SO2 discharge that occurred as a result of the eruption on Miyake Island. These results indicate that gaseous H2O2 may largely determine the formation of aerosol sulfate in the warm months. Thus, the increase of anthropogenic or natural SO2 emission may significantly affect the increase of SO42− concentration in rainwater.
Syntheses and Crystal Structures of New Quaternary Ag-Containing Group 5 Chalcogenides: KAg2MVSe4 and K3Ag3MV2S8 (MV = Nb, Ta)
Authors: Chen Wen-Tong , Ma Hong-Wei , Guo Guo-Cong , Deng Lei , Zhou Guo-Wei , Dong Zhen-Chao , Huang Jin-Shun
Published: March 2004

Four new quaternary Ag-containing group 5 chalcogenides, KAg2NbSe4 (1), KAg2TaSe4 (2), K3Ag3Nb2S8 (3), and K3Ag3Ta2S8 (4), have been prepared through the use of molten alkali metal polychalcogenides as reactive fluxes and structurally characterized by single-crystal X-ray diffraction techniques. The layer-type structures of 1 and 2 can be regarded as constructed from the basic building block of the incomplete cubane [Ag3MVSe3], which are corner-shared to form an infinite chain along the a direction. These incomplete cubane chains are interconnected and further bridged by Se atoms along the c direction, leading to a two-dimensional structure. The crystal structure of 3 and 4 consists of one-dimensional triple-metal [Ag3MV2S8]3− anionic chains seperated by K+ cations. The alternate packing of MVS4 and AgS4 tetrahedra via edge-sharing along the b direction leads to mixed-metal sub-chains, every two of which are further linked by AgS4 tetrahedra along the a direction through edge-sharing to the MVS4 tetrahedra, thus yielding the so-called triple-metal chains.
Propiononitrile as an Extraction Solvent for the Ion-Pair Complexes of Water-Soluble Tetracationic Porphyrinatocopper(II) with Perchlorate: The Effect of Sodium Chloride
Authors: Fujii Kenta , Nishimoto Jun , Yamada Shiro , Fukamachi Mizue , Tabata Masaaki
Published: March 2004

The ion-pair extraction of 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphyrinatocopper(II) ([CuII(tmpyp)]4+, CuP4+) with perchlorate ion has been studied for a water–propiononitrile (PN) system in the presence of sodium chloride. The [CuII(tmpyp)]4+ was extracted as [CuP·4ClO4] and dissociated to [CuP·2ClO4]2+ and [CuP·ClO4]3+ in the PN phase. The high concentration of NaCl in the aqueous phase suppressed the extraction of [CuP·nClO4](4−n)+ (n = 1, 2) due to the increased partition of ClO4− into the PN phase. The extraction constants of [CuII(tmpyp)]4+ with ClO4− into the PN phase at different concentrations of NaCl were found to be KexKdis1Kdis2Kdis3 (mol−1 dm3) = [CuP·ClO43+]o[ClO4−]o3[CuP4+]a−1[ClO4−]a−4 = 9.1 ± 1.9, (3.0 ± 0.2) × 10−1, and (2.5 ± 2.2) × 10−1 for 0, 0.5, and 1.0 mol dm−3 NaCl, respectively, and KexKdis1Kdis2 (mol−2 dm6) = [CuP·2ClO42+]o[ClO4−]o2[CuP4+]a−1[ClO4−]a−4 = 31 ± 18 for 1.0 mol dm−3 NaCl. The extraction constants of NaClO4 were found to be Kex(NaClO4) (mol−1 dm3) = [NaClO4]o[Na+]a−1[ClO4−]a−1 = (8.8 ± 1.6) × 10−2 and (5.1 ± 0.7) × 10−2 for 0.5 and 1.0 mol dm−3 NaCl, respectively. The dissociation constants of NaClO4 in the PN phase were determined: Kdis(NaClO4) (mol dm−3) = [Na+]o[ClO4−]o[NaClO4]o−1 = (1.5 ± 0.3) × 10−2 and (2.8 ± 0.4) × 10−2 for 0.5 and 1.0 mol dm−3 NaCl, respectively, and Kex(NaClO4)Kdis(NaClO4) = [Na+]o[ClO4−]o[Na+]a−1[ClO4−]a−1 = (2.37 ± 0.05) × 10−3 for 0 mol dm−3 NaCl. The detailed extraction mechanism of [CuII(tmpyp)]4+ is discussed by taking into account the chemical species of [CuP·nClO4](4−n)+ in the PN phase and the extraction of NaClO4 and comparing these with the results obtained for acetonitrile.
Preparation and Characterization of an α-Keggin-Type [SW12O40]2− Complex
Authors: Himeno Sadayuki , Takamoto Masayo , Hoshiba Mitsuru , Higuchi Ayumi , Hashimoto Masato
Published: March 2004

A divanadium-substituted derivative of 12-tungstosulfate(VI), [S(V2W10)O40]4− was prepared as the tetrabutylammonium (n-Bu4N+) salt by heating a 50 mM (M = mol dm−3) W(VI)–20 mM V(V)–0.5 M H2SO4–50% (v/v) CH3CN system at 70 °C for 24 h. The [S(V2W10)O40]4− anion was transformed spontaneously into a monovanadium-substituted derivative, [S(VW11)O40]3− in a 70% (v/v) CH3CN–1.0 M HCl system at 70 °C. On the other hand, [SW12O40]2− was precipitated as the n-Bu4N+ salt upon heating a 95% (v/v) CH3CN–0.5 M HCl system containing [S(V2W10)O40]4−. The single-crystal X-ray structural analysis revealed that the structure consisted of an α-Keggin-type [SW12O40]2− anion. The [SW12O40]2− anion was characterized by IR and UV–vis spectroscopy, and voltammetry.
A High-Throughput Screening Assay of Endocrine-Disrupting Chemicals Using a Receptor-Modified Au-Electrode
Authors: Murata Masaharu , Yano Kentaro , Fukuma Kaori , Maeda Mizuo , Katayama Yoshiki
Published: March 2004

There is a great deal of concern that wildlife and human health have been adversely affected by anthropogenic chemicals that can disrupt normal endocrine homeostasis. In order to identify the binding ability of chemicals to human estrogen receptors (hER), we have constructed a biosensor which carries the hER ligand-binding domain on the surface. The receptor was expressed as an in-frame fusion with ten consecutive histidine residues using a bacterial system, and then the recombinant protein was immobilized on an Au-electrode via Ni(II)-mediated chemisorption using the histidine tag and thiol-modified nitrilotriacetic acid. This receptor-modified electrode was used to define the binding capacity of several xenoestrogens and anti-estrogen to the hER. The biosensor showed a linear response to the chemicals in a concentration-dependent manner. The order of the detection limits was: 17β-estradiol (10−10 M) > diethylstilbestrol (DES; 10−8 M), ICI 182780 (10−8 M), dibutyl phthalate (10−8 M), bisphenol A (10−8 M) > p-nonylphenol (10−6 M), testosterone (10−6 M). Compared to the traditional binding assay, our method has the advantage of being more feasible, due to the high-throughput screening assay for evaluating the binding ability of chemicals to the receptors.
Blue Phosphorescence of the Novel Dinuclear Gold(I) Complex Bridged by 1,3-Benzenedithiolate in Solution
Authors: Watase Seiji , Kitamura Takayuki , Hasegawa Yasuchika , Kanehisa Nobuko , Nakamoto Masami , Kai Yasushi , Yanagida Shozo
Published: March 2004

A novel dinuclear benzenedithiolatogold(I) complex was synthesized and characterized spectroscopically. This complex showed intense blue emission [quantum yield at 1.0 × 10−4 mol dm−3: Φ = 0.026(2)] at room temperature in fluid solvents. This emission originates from a metal-perturbed ligand-centered transition. The relatively long life time of the excited state (τ50 = ca. 2 μsec) and the large stokes shift suggest that the emission is phosphorescence. The X-ray single crystal structural determination showed that the complex has a distorted 12-membered macrocyclic structure bridged by two benzenedithiolate ligands, with no gold–gold interactions.
Cytotoxic Antifeedant from Dionaea muscipula Ellis: A Defensive Mechanism of Carnivorous Plants against Predators
Authors: Tokunaga Takashi , Dohmura Atsushi , Takada Noboru , Ueda Minoru
Published: March 2004

We revealed that Dionaea muscipula Ellis accumulates a great amount of cytotoxic naphthoquinone derivatives, of which the main component is plumbagin (1). It was also revealed that 1 showed strong antifeedant activity against Spodoptera litura. These results strongly suggest that 1 in D. muscipula operates as an antifeedant which prevents them from being consumed by predators. The accumulation of a great amount of 1 would be an important strategy of carnivorous plants for their survival. Also, we discuss the structure–activity relationship of the cytotoxicity of naphthoquinones using isolated naphthoquinones and their derivatives.
How Does Lipase Flexibility Affect Its Enantioselectivity in Organic Solvents? A Possible Role of CH···π Association in Stabilization of Enzyme–Substrate Complex
Authors: Watanabe Keiichi , Uno Tetsuya , Koshiba Takashi , Okamoto Takashi , Ebara Yasuhito , Ueji Shin-ichi
Published: March 2004

For lipase-catalyzed reactions of 2-(4-substitued phenoxy)propionic acids with alcohols in organic solvents containing a small amount of water, the increase of the lipase flexibility brought about by addition of water is found to be favorable for the induced-fit motion of the lipase for the correctly binding enantiomer of the substrate used, thus resulting in the improvement of the lipase enantioselectivity. In particular, for the reaction of the substrate with rich π electron density on its aromatic ring, the enantioselectivity was much more sensitive to the change of the lipase flexibility. Thus, in the induced fit motion, the CH···π association between amino acids side chains around the lipase’s active site and the aromatic ring of the correctly binding enantiomer is assumed to accelerate the accommodation of the substrate into the lipase’s active site and the stabilization of the complex between the enzyme and the substrate. This assumption is also supported by a discussion based on the value of the Michaelis constant obtained. Furthermore, on the basis of a model concerning the acyl-enzyme structure for the incorrectly binding enantiomer, the long alkyl chain alcohols as a nucleophile are found to improve the lipase enantioselectivity markedly.