bluuebunny/crossref_metadata_2025 huggingface dataset:
Maturation of DC is associated with changes in motile characteristics and adherence
Authors: Burns Siobhan , Hardy Samantha J. , Buddle Joanna , Yong Kwee L. , Jones Gareth E. , Thrasher Adrian J.
Published: December 2003

Migration of dendritic cells (DC) from sentinel sites to lymphoid tissue entails the initiation and coordination of a complex series of cytoskeletal rearrangements resulting in polarised protrusion, formation of new adhesion points, and detachment. Although many diverse receptor‐ligand interactions stimulating DC maturation and migration have been identified, the changes that occur in the structure of the actin cytoskeleton during these processes have received little attention. When derived in vitro, immature DC floated in clumps, and upon addition of maturation stimuli such as lipopolysaccharide (LPS), they rapidly adhered, developed polarity, and assembled actin‐rich structures known as podosomes at the leading edge of the cell. Podosome assembly was associated with the specific recruitment of β2 integrins, which in the absence of the Wiskott Aldrich Syndrome protein (WASp), did not occur. As maturation progressed, normal DC once again became rounded and devoid of podosomes. This change in morphology was closely associated with a quantitatively reduced ability to adhere to fibronectin or ICAM‐1‐coated surfaces. In immature DC, failure to form podosomes or selective inhibition of the CD18 component of podosomes resulted in a similarly reduced ability to adhere to ICAM‐1, indicating that podosomes, through CD18, are necessary for tight adhesion to this ligand. We, therefore, propose that podosomes provide an essential link between directional cell protrusion and achievement of DC translocation by establishing new dynamic anchor points at the front of the cell. The temporal regulation of podosome assembly during DC maturation also suggests that they may be most critical for early movement, perhaps during transmigration of lymphatic endothelium. Cell Motil. Cytoskeleton 57:118–132, 2004. © 2004 Wiley‐Liss, Inc.
Is breast cancer survival improving?
Authors: Giordano Sharon H. , Buzdar Aman U. , Smith Terry L. , Kau Shu‐Wan , Yang Ying , Hortobagyi Gabriel N.
Published: December 2003

BACKGROUND

Despite advances in therapies for breast cancer, improvement in survival for patients with recurrent or metastatic breast cancer has been difficult to establish. The objective of the current study was to determine whether the survival of women with recurrent breast cancer has improved from 1974 to 2000.

METHODS

The authors analyzed the survival experience of 834 women who developed recurrent breast cancer between November 1974 and December 2000. All patients had been treated previously with adjuvant anthracycline‐based protocols. Patients were divided into five consecutive groups based on year of breast cancer recurrence, and survival was compared across the five groups. Because some prognostic variables were divided unevenly divided among the cohorts, a multivariate model was created to determine the association of year of recurrence and survival after accounting for other prognostic factors.

RESULTS

In the unadjusted analysis, there was a statistically significant improvement in survival across the five groups, and the more recent cohorts had longer survival (P< 0.001). Other variables that predicted longer survival after breast cancer recurrence included smaller initial tumor size, lower stage of disease, fewer lymph nodes involved, longer disease‐free interval, estrogen receptor–positive tumors, and nonvisceral dominant site of disease recurrence. In the multivariate analysis, which adjusted for these prognostic factors, year of recurrence was associated with a trend toward improved survival, with a 1% reduction in risk for each increasing year.

CONCLUSIONS

For these cohorts of patients, the authors present data suggesting that the prognosis for patients with recurrent breast cancer improved between 1974 and 2000. Cancer 2004;100:44–52. © 2003 American Cancer Society.
Rare ductal adenocarcinoma of the pancreas in patients younger than age 40 years
Authors: Lüttges Jutta , Stigge Claudia , Pacena Maike , Klöppel Günter
Published: December 2003

BACKGROUND

Pancreatic ductal adenocarcinomas (PDACs) are extremely rare before age 40 years. The objective of the current study was to determine whether the features of PDACs in patients age < 40 years differ from those in older patients. The authors reviewed the literature and their own files.

METHODS

The cases reported in the literature were evaluated to determine their precise diagnoses and characteristic features. In a series of 439 PDACs from the authors' files, tumors in patients age < 40 years were identified, and their clinicopathologic features and certain genetic features were compared with those in a selected group of patients age > 40 years.

RESULTS

Of 71 pancreatic carcinomas reported in patients age < 40 years, only 20 fully qualified as PDACs. The remaining tumors represented malignancies other than PDACs, such as pancreatoblastoma, solid‐pseudopapillary neoplasms, acinar cell carcinomas, and endocrine tumors. PDACs in patients age < 20 years were the absolute exception and commonly were associated with risk factors such as Peutz–Jeghers syndrome, hereditary pancreatic cancer syndrome, and preceding radiotherapy. In the authors' series of patients, there were 6 PDACs and 4 PDAC variants in patients age < 40 years (0.2%), all in male patients. These tumors compared well with the PDACs in patients age > 40 years in their pathologic and molecular findings. Three patients were age ≤ 20 years, and 2 of those patients had a mucinous component with MUC2 positivity.

CONCLUSIONS

The incidence of PDACs in patients age < 40 years was approximately 0.3%, and the incidence in patients age < 20 years was 0.1%. Their clinicopathologic findings were comparable to those in patients age > 40 years, but they seemed to include more variants, particularly mucinous carcinomas. In addition, PDACs in younger patients frequently appeared to be associated with genetic factors. Cancer 2004;100:173–82. © 2003 American Cancer Society
Increased risk of myelotoxicity in elderly patients with non‐Hodgkin lymphoma
Authors: Balducci Lodovico , Repetto Lazzaro
Published: December 2003

Neutropenia is the major dose‐limiting toxicity of myelosuppressive chemotherapy in patients with cancer. Because of the high incidence of neutropenic complications and death in the early cycles of chemotherapy and the potential for improved outcomes, prophylaxis with colony‐stimulating factor beginning in the first cycle should be routinely considered in elderly patients with non‐Hodgkin lymphoma who are treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP‐like chemotherapy regimens.
The significance of myelosuppression during therapy with imatinib mesylate in patients with chronic myelogenous leukemia in chronic phase
Authors: Sneed Thomas B. , Kantarjian Hagop M. , Talpaz Moshe , O'Brien Susan , Rios Mary Beth , Bekele B. Nebiyou , Zhou Xian , Resta Debra , Wierda William , Faderl Stefan , Giles Francis , Cortes Jorge E.
Published: December 2003

BACKGROUND

Imatinib mesylate induces high rates of hematologic and cytogenetic response in patients with chronic myelogenous leukemia (CML). During therapy with imatinib, up to 45% of patients with CML reportedly experience myelosuppression ≥ Grade 3, requiring interruption of therapy and/or dose reductions. The significance of myelosuppression for response to imatinib is unknown.

METHODS

The authors analyzed 143 patients with late chronic‐phase CML who were treated with imatinib after failing interferon. Univariate and multivariate analyses were performed to determine patient characteristics that were correlated with myelosuppression response and the association between myelosuppression and cytogenetic response.

RESULTS

Neutropenia ≥ Grade 3 (according to National Cancer Institute Common Toxicity Criteria) occurred in 64 patients (45%), and thrombocytopenia ≥ Grade 3 occurred in 31 patients (22%). Any myelosuppression ≥ Grade 3 was associated with a lower rate of major (P = 0.04) or complete (P = 0.01) cytogenetic responses. This was more pronounced with myelosuppression that lasted > 2 weeks. The major cytogenetic response rate was 58% with Grade ≥ 3 myelosuppression compared with a rate of 75% without Grade ≥3 myelosuppression (P = 0.03); the complete cytogenetic response rates were 36% and 63%, respectively (P = 0.001). In a multivariate analysis, pretreatment platelet count, imatinib dose reductions, and duration of myelosuppression were associated significantly with response.

CONCLUSIONS

Myelosuppression is an independent adverse factor for achieving cytogenetic response with imatinib in patients with CML. Intervention with hematopoietic growth factors in patients with CML who are treated with imatinib should be investigated. Cancer 2004;100:116–21. © 2003 American Cancer Society.
A Phase II trial of suramin monthly × 3 for hormone‐refractory prostate carcinoma
Authors: Vogelzang Nicholas J. , Karrison Theodore , Stadler Walter M. , Garcia Juan , Cohn Helene , Kugler John , Troeger Thomas , Giannone Leonard , Arrieta Rose , Ratain Mark J. , Vokes Everett E.
Published: December 2003

BACKGROUND

The goal of the current study was to determine the prostate‐specific antigen (PSA) and objective response rates and the pharmacokinetics associated with a monthly × 3 one‐hour infusion of suramin in 58 patients with hormone‐refractory prostate carcinoma.

METHODS

A PSA response was defined as a > 50% reduction in the PSA level from baseline for at least 3 consecutive evaluations over a minimum of 6 weeks. The suramin dose was 2400 mg/m2 taken intravenously on Day 1, 1620 mg/m2 on Day 29, and 1292 mg/m2 on Day 57. All patients received 0.5 mg dexamethasone twice daily.

RESULTS

Among 56 evaluable patients (median entry PSA level, 229.5 ng/mL), there were 21 PSA responders (37.5%). Among 27 patients with measurable disease, there were 5 responders (4 partial and 1 complete). The median overall survival time was 15.3 months. Grade III fatigue (14.1%) was the predominant toxicity observed. Suramin plasma levels remained high even 3 months after treatment was discontinued. Among the 12 evaluable patients who previously had received chemotherapy, the PSA response rate was 42%; one response was observed among 4 patients with measurable disease, and the median survival was 12 months.

CONCLUSIONS

Monthly bolus suramin was well tolerated, reduced PSA levels, and induced objective responses, even in patients who previously had received chemotherapy. Cancer 2004;100:65–71. © 2003 American Cancer Society.
Prolonged survival after complete resection of metastases from intraocular melanoma
Authors: Hsueh Eddy C. , Essner Richard , Foshag Leland J. , Ye Xing , Wang He‐Jing , Morton Donald L.
Published: December 2003

BACKGROUND

The median survival time is only 2–6 months after a diagnosis of metastases from intraocular melanoma. Because complete resection of metastatic melanoma from a cutaneous primary tumor can prolong survival, the authors hypothesized that resection also might benefit patients with metastases from an intraocular site.

METHODS

From 1971 to 1999, 112 patients with metastatic melanoma from an intraocular site were enrolled in various treatment protocols after informed consent was obtained. Prospectively recorded clinical variables and follow‐up information were retrieved from the patient database. Survival curves were estimated using the Kaplan–Meier method. Univariate analysis was performed with the log‐rank test. Multivariate analysis was performed using the Cox proportional hazards regression model. Propensity score analysis was used to reduce the imbalance between subgroups and to assess treatment effect.

RESULTS

Seventy‐eight patients (70%) presented with liver involvement. Twenty‐four patients (21%) underwent resection of metastatic lesions. At a median follow‐up time of 11 months (range, 1–97 months; > 36 months for survivors), the median survival period was 11 months and the 5‐year survival rate was 7%. Univariate analysis showed that surgical resection, site of metastases, number of metastatic lesions, and disease‐free interval were correlated significantly with survival (P < 0.001, P < 0.001, P < 0.001, and P = 0.031, respectively). Multivariate analysis showed that surgical resection was significant (P = 0.008) but that the site of metastases was not (P = 0.146). The median survival and the 5‐year survival rate were 38 months and 39%, respectively, for surgical patients, versus 9 months and 0%, respectively, for nonsurgical patients. After adjusting for covariate imbalance by propensity score analysis, surgery remained significant (P = 0.021) on multivariate analysis.

CONCLUSIONS

Complete resection may prolong survival in certain patients with distant metastases from intraocular primary melanoma. However, the overall unfavorable prognosis indicates an urgent need for more effective nonsurgical interventions. Cancer 2004;100:122–9. © 2003 American Cancer Society.
Association of nonmelanoma skin cancer with second malignancy
Authors: Rosenberg Carol A. , Greenland Philip , Khandekar Janardan , Loar Aimee , Ascensao Joao , Lopez Ana Maria
Published: December 2003

BACKGROUND

Heightened risks of second cancers have been reported in patients with nonmelanoma cancer of the skin (NMSC), but this association has not been studied in a large, ethnically diverse, multigeographic population.

METHODS

This cross‐sectional study assessed the association of NMSC with another malignancy in the Women's Health Initiative Observational Study, a study that was conducted in 40 communities throughout the U.S. and involved 93,676 postmenopausal women ages 50–79 years. Cancer history, demographics, and previous and current risk exposures were determined by questionnaire at a baseline examination. Logistic regression was used to assess the association (odds ratio) of a history of NMSC with a history of other (non‐NMSC) cancers controlling for age and potential confounding factors. Complete cancer data were available in 92,658 women.

RESULTS

In age‐adjusted analyses, women with a history of NMSC (n = 7554 women) were 2.30 times as likely to report a history of another cancer, other than NMSC, compared with women who had no history of NMSC (95% confidence interval [95% CI], 2.18–2.44). In a subgroup analysis, black women with NMSC had 7.46 times the odds (95% CI, 3.08–18.0) of reporting a second malignancy compared with black women without NMSC.

CONCLUSIONS

This study provides additional evidence of an association between NMSC and another malignancy in a large, multiethnic population. Cancer 2004;100:130–8. © 2003 American Cancer Society.
The significance of isolation of saprophytic molds from the lower respiratory tract in patients with cancer
Authors: Lionakis Michail S. , Kontoyiannis Dimitrios P.
Published: December 2003

BACKGROUND

Invasive infections caused by molds other thanAspergillus,Fusarium, andZygomyceteshave been reported sporadically in patients with leukemia and allogeneic bone marrow transplantation (BMT). However, the significance of lower respiratory tract cultures that are positive for these saprophytic molds in an unselected population of patients with cancer remains unclear.

METHODS

The authors evaluated the significance of respiratory specimens positive for saprophytic molds in patients with cancer using the criteria set by the European Organization for Research and Treatment of Cancer (EORTC)/Mycoses Study Group (MSG). They included the diagnostic category of indeterminate pulmonary invasive mold infection (IMI) for cases that met the criteria for probable IMI but had other pathogens concomitantly isolated from the respiratory tract.

RESULTS

Eighty‐five cases with at least 1 positive culture were identified in 79 patients. Two cases were proven IMI, 29 were indeterminate IMI, 5 were possible IMI, and 49 were no IMI. All 38 cases from patients with solid tumors represented colonization compared with only 11 of the 47 cases (23%) from high‐risk patients (P< 0.0001). The positive predictive value (PPV) of cultures was 0% in patients with solid tumors and ranged from 4.3% to 76.6%, depending on the analytic model used, in high‐risk patients with leukemia and recipients of BMT. Cultures positive forScedosporiumspp. had a higher PPV (9.1–100%) than did cultures positive for non‐Scedosporiumspp. (2.8– 69.4%).

CONCLUSIONS

Adjustments of the EORTC/MSG criteria may be required for the diagnosis of invasive infections caused by saprophytic molds, especially non‐Scedosporiumspp., in patients with cancer. Cancer 2004;100:165–72. © 2003 American Cancer Society.
Correlation of tumor volume and surface area with lymph node status in patients with multifocal/multicentric breast carcinoma
Authors: Andea Aleodor A. , Bouwman David , Wallis Tracie , Visscher Daniel W.
Published: December 2003

BACKGROUND

Multicentric breast carcinomas have a higher frequency of axillary lymph node metastasis than unifocal tumors of similar stage. It remains unclear whether this merely reflects larger tumor volumes or a different biologic behavior. The authors have shown previously that when aggregate tumor diameter are used for staging, unifocal and multifocal tumors have a similar frequency of axillary lymph node metastasis. However, summing diameter overestimates actual tumor volume because volume is proportional to the third power of the diameter. Therefore, the aim of the current study was to reanalyze the relation between size and axillary lymph node status by correcting for tumor volumes and surface areas.

METHODS

Volumes and surface areas of 122 breast tumor specimens with multiple macroscopic nodules (two foci: n = 95; three foci: n = 22; three foci: n = 5) were calculated by approximating the shape of each tumor nodule to an ellipsoid (for volume) or to a prolate spheroid (for area). For comparison, the authors used an internal control series, comprised of 469 macroscopic unifocal tumors. For all patients, multiple assessments of largest tumor size and combined size of all foci were correlated with the status of axillary lymph nodes. The associations between lymph node status, tumor volume or area, and multifocality were modeled using univariate and multivariate logistic regression.

RESULTS

When either the largest or the aggregate tumor volume was used as a size estimate, tumor specimens with multiple nodules had a higher frequency of lymph node involvement compared with unifocal tumors of a similar volume or area. The odds ratio (OR) for having positive lymph nodes was 2.34 for aggregate volume measurement (P < 0.001). Surface area estimates yielded similar results (OR = 2.2, P < 0.001).

CONCLUSIONS

Breast tumors with multiple macroscopic nodules had a different biology, with a propensity to dissemination at smaller tumor volumes (i.e., there was another factor besides volume alone that accounted for the differences in behavior). Cancer 2004;100:20–7. © 2003 American Cancer Society.
Uncertain benefit from surgery in patients with lung metastases from breast carcinoma
Authors: Planchard David , Soria Jean‐Charles , Michiels Stefan , Grunenwald Dominique , Validire Pierre , Caliandro Raffaele , Girard Philippe , Le Chevalier Thierry
Published: December 2003

BACKGROUND

Isolated lung metastases have been reported to occur in 10–20% of all women with breast carcinoma. The authors described a series of patients who underwent surgery for lung metastases from breast carcinoma.

METHODS

They reviewed the files of 125 consecutive patients who underwent surgery with a curative intent for lung metastases from breast carcinoma between 1972 an 1998 at a single institution. Survival curves were plotted by the Kaplan–Meier method. Prognostic factors were identified using the log‐rank test and a Cox proportional hazards model for univariate and multivariate analyses, respectively.

RESULTS

The median age at surgery was 53 years. There was a median of 1 resected metastasis (range, 1–16 resected metastases). The median size of the largest metastasis was 19 mm (range, 5–70 mm). The median disease‐free interval (DFI) was 3 years. The median follow‐up time after surgery was 8.5 years (range, 25 days to 22 years). The 3‐year, 5‐year, and 10‐year probabilities of survival were 58% (95% confidence interval [95% CI], 49–67%), 45% (95% CI, 36–55%), and 30% (95% CI, 21–41%), respectively. The median survival time after surgery was 4.2 years. Complete resection was achieved in 96 patients. The quality of the resection (complete vs. incomplete) was not a statistically significant prognostic factor by univariate analysis and there was no significant difference between these two groups in terms of adjuvant postoperative therapy. The characteristics of the primary tumor and the number of metastases (one vs. two or more) had no detectable influence on survival. The size of the largest metastasis (> 20 mm or ≤ 20 mm) and the DFI (≤ 3 years vs. > 3 years) were highly significant prognostic factors (P = 0.006 and P = 0.003, respectively). This was confirmed by multivariate analysis. Patients with a DFI ≤ 3 years and/or the largest metastasis > 20 mm reportedly had a poor outcome (median survival, 2.6 years vs. 8.5 years for patients with none of these poor prognostic factors).

CONCLUSIONS

Resection of lung metastases from breast carcinoma was associated with a significant 5‐year survival rate of 45%. Whether these encouraging findings resulted from the surgical procedure itself or the preoperative selection of patients remained uncertain. When surgery is considered in this setting, the size of the largest metastasis and the DFI should be taken into account. Cancer 2004;100:28–35.© 2003 American Cancer Society.
Splenic and nodal marginal zone lymphomas are indolent disorders at high hepatitis C virus seroprevalence with distinct presenting features but similar morphologic and phenotypic profiles
Authors: Arcaini Luca , Paulli Marco , Boveri Emanuela , Vallisa Daniele , Bernuzzi Patrizia , Orlandi Ester , Incardona Paolo , Brusamolino Ercole , Passamonti Francesco , Burcheri Sara , Schena Claudio , Pascutto Cristiana , Cavanna Luigi , Magrini Umberto , Lazzarino Mario
Published: December 2003

BACKGROUND

Splenic and nodal marginal zone lymphomas (MZL) are subtypes of marginal zone‐derived neoplasms. Due to their rarity, little is known concerning their relation, pattern of dissemination, and treatment outcome.

METHODS

The authors analyzed the clinicopathologic features and outcome of 43 patients (34 patients with splenic MZL and 9 patients with nodal MZL). All lesional tissues obtained at diagnosis were reviewed histologically.

RESULTS

Among the patients with splenic MZL, 30 patients had Stage IV disease (based on the Ann Arbor staging system). Twenty‐six patients presented with splenomegaly with or without limited involvement of abdominal lymph nodes, whereas 7 patients showed disease extension to superficial lymph nodes. Hepatitis C virus (HCV) serology was positive in 35% of patients. Seventeen patients underwent splenectomy, 8 patients received chemotherapy, and 7 patients were followed without initial treatment. Interferon produced a lymphoma response in three of four HCV positive patients. Of 27 treated patients, 13 patients achieved a complete response, and 12 patients achieved a partial response. The median event‐free survival (EFS) was 3.3 years (5.1 years for patients with disease confined to the abdomen and 2.1 years for patients with disease extension to superficial lymph nodes). Among nine patients with nodal MZL, four patients had Stage IV disease. HCV serology was positive in two patients. Five patients responded to chemotherapy. The median EFS was 2.8 years. The median overall survival was not reached for patients with both types of MZL.

CONCLUSIONS

The results of the current study demonstrated that splenic and nodal MZL are indolent lymphomas with different presenting features but common morphologic and biologic characteristics, including high HCV seroprevalence. Studies will be required to identify specific biologic markers and to define the best treatment. Cancer 2004;100:107–15. © 2003 American Cancer Society.
The process for continuous improvement of the TNM classification
Authors: Gospodarowicz Mary K. , Miller Daniel , Groome Patti A. , Greene Frederick L. , Logan Pamela A. , Sobin Leslie H.
Published: December 2003

The TNM classification is a worldwide benchmark for reporting the extent of malignant disease and is a major prognostic factor in predicting the outcome of patients with cancer. The objectives for cancer staging were defined by the International Union Against Cancer (UICC) TNM Committee almost 50 years ago and are still broadly applicable today. To keep pace with the modern demands of evidence‐based practice, the UICC introduced a structured process for introducing changes to the TNM classification. The elements of the TNM process were determined to include the development of unambiguous criteria for the information and documentation required to consider changes in the classification, establishment of a well‐defined process for the annual review of relevant literature, formation of site‐specific expert panels, and the participation of experts from all over the world in the TNM review process. Communication between the oncology community and those involved in the TNM classification was established as being essential to the success of the process. The process, which was introduced in 2002, will be tested over the next 3–4 years and evaluated. In addition to the formal process, individual initiative, involvement by the national staging committees, and group consensus are required. Furthermore, increased involvement by the experts should improve the understanding and dissemination of the TNM classification. Cancer 2004;100:1–5. Published 2003 by the American Cancer Society.
Hereditary nonpolyposis colorectal carcinoma (HNPCC) and HNPCC‐like families: Problems in diagnosis, surveillance, and management
Authors: Lynch Henry T. , Riley Bronson D. , Weismann Scott , Coronel Stephanie M. , Kinarsky Yulia , Lynch Jane F. , Shaw Trudy G. , Rubinstein Wendy S.
Published: December 2003

BACKGROUND

To the authors' knowledge, hereditary nonpolyposis colorectal carcinoma (HNPCC) is the most commonly occurring hereditary disorder that predisposes to colorectal carcinoma (CRC), accounting for approximately 2–7% of all CRC cases diagnosed in the U.S each year. Its diagnosis is wholly dependent on a meticulously obtained family history of cancer of all anatomic sites, with particular attention to the pattern of cancer distribution within the family.

METHODS

The objective of the current study was to illustrate various vexing problems that can deter the diagnosis of HNPCC and, ultimately, its management. This was an observational cohort study. Sixteen HNPCC and HNPCC‐like families were selected from a large resource of highly extended HNPCC families. High‐risk patients were selected from these HNPCC families. An ascertainment bias was imposed by the lack of a population‐based data set. Personal interviews and questionnaires were used for data collection.

RESULTS

There was an array of difficulties highlighted by limitations in compliance, lack of a clinical or molecular basis for an HNPCC diagnosis, ambiguous DNA findings, problems in genetic counseling, failure to meet Amsterdam or Bethesda criteria, small families, lack of medical and pathologic documentation, poor cooperation of family members and/or their physicians, cultural barriers, economic stress, frequent patient fear and anxiety, perception of insurance discrimination, and limited patient and/or physician knowledge regarding hereditary cancer.

CONCLUSIONS

The diagnosis and management of HNPCC is predicated on physician knowledge of its phenotypic and genotypic heterogeneity, in concert with the multifaceted problems that impact on patient compliance. Cancer 2004;100:53–64. © 2003 American Cancer Society.
Long‐term risk of malignant neoplasm associated with gestational glucose intolerance
Authors: Dawson Shelagh I.
Published: December 2003

BACKGROUND

Previous studies have demonstrated an association between diabetes mellitus and cancer risk. However to the author's knowledge, no data regarding the risk of cancer associated with subclinical impaired glucose tolerance have been published to date. An association between various types of cancer and any continuum of risk across the spectrum of glucose tolerance may be important in determining the nature of the association between diabetes mellitus and the risk of malignancy.

METHODS

The current study was conducted to examine the long‐term risk of malignant neoplasms associated with maternal glucose intolerance. A 20‐year follow‐up study of a cohort of women who had previously taken part in a study in 1980 that investigated maternal glucose metabolism and fetal outcome was performed. Gestational glucose metabolism, smoking behavior, and weight and height measured at the time of index pregnancy, as well as weight, height, and smoking behavior assessed by questionnaire in 1999, were examined. The main endpoint of the study was hospital admission with a diagnosis of malignant neoplasm as ascertained by linkage data.

RESULTS

Thirty‐four of the 753 women living in Grampian (4.5%) were admitted to the hospital with a diagnosis of malignant neoplasm; of these, 18 cases were malignant neoplasms of the breast. After adjustment for known risk factors, both malignant neoplasm and malignant neoplasm of the breast were found to be significantly associated with gestational glucose intolerance.

CONCLUSIONS

Subclinical glucose intolerance during pregnancy was found to be associated with a dose‐related increase in the risk of malignant neoplasm, particularly malignant neoplasm of the breast. Cancer 2004;100:149–55. © 2003 American Cancer Society.
Stability of poly(Acrylic Acid)‐grafted phospholipid liposomes in gastrointestinal conditions
Authors: Lee Hyun Sup , Kim Kwangmeyung , Jeong Bong Hyun , Moon Hyun Tae , Byun Youngro
Published: December 2003

Major limitations in the use of liposomes for oral formulation relate to their physical and chemical instability in the GI tract. In this study, the conjugate (PAA‐DSPE) of poly(acrylic acid) and distearoylphosphatidylethanolamine (DSPE) was synthesized, and liposomes were prepared with the mixture of PAA‐DSPE and DSPE to improve the stability of liposomes in the GI tract. The prepared PAA‐DSPE was characterized by FT‐IR and 13C‐NMR to confirm the coupling between PAA and DSPE. In the elemental analysis, the coupling ratio of PAA and DSPE in PAA‐DSPE was calculated as 1:1.73. The average size of a PAA‐DSPE/DSPE liposome, measured by dynamic light scattering, was in the range of 300–500 nm, and the minimum average size was 320 nm at 6 mol% of PAA‐DSPE. The stability of the prepared liposomes was evaluated in different pH (2, 5, 7.4) solutions, and in different concentrations of bile acid (0, 0.1, 1, 10%) and pancreatin solutions (0, 0.03, 0.3, 3%). The stability of liposomes in different conditions was determined by measuring the fluorescence intensity of 5(6)‐CF leaked from liposomes. The amount of the 5(6)‐CF leakage from the PAA‐DSPE/DSPE liposomes of 6 mol% PAA‐DSPE was the lowest in all the cases of acidic, bile, and pancreatin solutions. In conclusion, the optimum amount of PAA‐DSPE in liposome was 6 mol%, and PAA‐DSPE/DSPE liposomes could improve the stability in the GI tract. Drug Dev. Res. 61:13–18, 2004. © 2004 Wiley‐Liss, Inc.
The preparation of genistein and LC‐MS/MS on‐line analysis
Authors: Tian Zhongmin , Wan Mingxi , Wang Zenglu , Wang Bo
Published: December 2003

Genistein, a promising agent for cancer chemoprevention or treatment, can be obtained from soybean seeds, via a complex isolation procedure. The objective of this study was to investigate whether natural and high purity genistein could be acquired from Sophora japonica L. via a simple approach. High‐performance liquid chromatography electrospray ionization combined with tandem mass spectrometry (LC‐ESI‐MS/MS) was used to monitor the whole process of genistein preparation. The results showed there were at least 13 types of flavonoid in the crude extracts from sophora fruits with sophoricoside being the predominant component. The products obtained from our preparation were unambiguously identified as genistein based on molecular ion [M+H]+, UV spectra, retention time, IR spectra, 1HNMR, 14CNMR spectra, and tandem mass spectrometric analysis. It demonstrated that 99.6% (w/w) genistein could be obtained via our preparation protocol. Drug Dev. Res. 61: 6–12, 2004. © 2004 Wiley‐Liss, Inc.
Involvement of cytotoxicity and variation of the mitochondrial membrane potential induced by hybrid agent
Authors: Hu Wan‐Ping , Wang Jeh‐Jeng , Huang Shu‐Mei , Hein‐Su‐Yu
Published: December 2003

The pyrrolo[2,1‐c][1,4]benzodiazepine (PBD) derivative DC‐81 is a potent antitumor antibiotic produced by Streptomyces species. The marked cytotoxic potential of this drug may be the result of its interaction with DNA. Because DC‐81 only recognizes three DNA base pairs this has precluded its clinical utility. Combination of DC‐81 with an indole carboxylate moiety was a hybrid designed to have much higher sequence selectivity in DNA Interactivity. In this paper, the association between cytotoxicity and the changes of mitochondria membrane potential ΔΨmt after exposing human melanoma cell line A375 to the hybrid agent was examined using MTS cell proliferation assay and flow cytometry using the fluorochrome rhodamine 123. Our results indicated that the hybrid induced cytotoxity and a significant reduction in ΔΨmt of A375 cells. We suggest that the hybrid agent is a potent inducer of cell apoptosis in A375 cells. Drug Dev. Res. 61: 1–5, 2004. © 2004 Wiley‐Liss, Inc.
An experimental study on seismic responses of multifunctional vibration‐absorption reinforced concrete megaframe structures
Authors: Lan Zongjian , Tian Yuji , Fang Liang , Liang Shuting , Wang Xinde
Published: December 2003

Two models are tested on a shake‐table. One of the models is a normal reinforced concrete megaframe structure and the other is a multifunctional vibration‐absorption reinforced concrete megaframe structure in which the laminated rubber bearings are placed between the major frame and the minor frames. Two earthquake motions (the El Centro wave and the Taft wave) are used during the test. This paper presents the dynamic characteristic, the seismic responses and the failure mechanism of these two models under varying peak acceleration levels for each of the earthquake motions. The test results demonstrate that the aseismic behavior of a multifunctional vibration‐absorption reinforced concrete megaframe structure is much better than that of a normal reinforced concrete megaframe structure. Copyright © 2003 John Wiley & Sons, Ltd.
Dynamic performance of twin curved cable‐stayed bridges
Authors: Gentile C. , Cabrera F. Martinez y
Published: December 2003

The dynamic behaviour of two curved cable‐stayed bridges, recently constructed in northern Italy, has been investigated by full‐scale testing and theoretical models. Two different excitation techniques were employed in the dynamic tests: traffic‐induced ambient vibrations and free vibrations. Since the modal behaviour identified from the two types of test are very well correlated and a greater number of normal modes was detected during ambient vibration tests, the validity of the ambient vibration survey is assessed in view of future monitoring.

For both bridges, 11 vibration modes were identified in the frequency range of 0ndash;10Hz, being a one‐to‐one correspondence between the observed modes of the two bridges. Successively, the information obtained from the field tests was used to validate and improve 3D finite elements so that the dynamic performance of the two systems were assessed and compared based on both the experimental results and the updated theoretical models. Copyright © 2003 John Wiley & Sons, Ltd.
Energy‐based hysteresis and damage models for deteriorating systems
Authors: Sucuoǧlu Haluk , Erberik Altuǧ
Published: December 2003

The low‐cycle fatigue model presented in the companion paper is employed for developing hysteresis and damage models for deteriorating systems. The hysteresis model performs strength reduction at a current displacement cycle by evaluating the loss in the energy dissipation capacity along the completed displacement path. Hence it is completely memory dependent. Pinching is accounted for implicitly by a reduced energy dissipation capacity in a displacement cycle. The model predicts the experimental results obtained from variable‐amplitude tests reasonably well. Response analysis under earthquake excitations reveals that both the maximum displacements and the number of large‐amplitude displacement response cycles increase significantly with the reduction in energy dissipation capacity, resulting in higher damage. Damage is defined as the deterioration in the effective stiffness of a displacement cycle, which is in turn related to the reduction in the energy dissipation capacity. A simple damage function is developed accordingly, consisting of displacement and fatigue components. It is observed that the fatigue component of damage is more significant than the displacement component for deteriorating systems under ground motions with significant effective durations. Copyright © 2003 John Wiley & Sons, Ltd.
A viscous boundary for transient analyses of saturated porous media
Authors: Zerfa Zohra , Loret Benjamin
Published: December 2003

An absorbing boundary for saturated porous media is developed that can be used for transient analyses in the time domain. The elastic constitutive equations for the saturated porous media follow Bowen's formulation. The method consists of applying viscous tractions along the artificial boundary. The absorbing boundary behaviour is assumed linear and isotropic. Hadamard's conditions provide the speeds of the dilatational and shear waves that propagate in saturated porous media. Since these expressions are frequency independent, the intensities of the viscous tractions are evaluated in the time domain, and the two dilatational waves are accounted for. The viscous tractions are defined from the drained characteristics, assuming an infinite permeability, at variance with the traditional ‘undrained’ method based on undrained characteristics and a null permeability. Solid media and materials with low permeability are also retrieved as subcases.

The results show that, at no additional cost, this ‘drained’ method is more accurate for all permeabilities than the ‘undrained’ method, which disregards the existence of the second dilatational wave. Copyright © 2003 John Wiley & Sons, Ltd.
Non‐iterative time integration scheme for non‐linear dynamic FEM analysis
Authors: Honda Riki , Sakai Hisakazu , Sawada Sumio
Published: December 2003

This paper proposes a non‐iterative time integration (NITI) scheme for non‐linear dynamic FEM analysis. The NITI scheme is constructed by combining explicit and implicit schemes, taking advantage of their merits, and enables stable computation without an iteration process for convergence even when used for non‐linear dynamic problems. Formulation of the NITI scheme is presented and its stability is studied. Although the NITI scheme is not unconditionally stable when applied to non‐linear problems, it is stable in most cases unless stiffness hardening occurs or the problem has a large velocity‐dependent term.

The NITI scheme is applied to dynamic analysis of the non‐linear soil–structure system and computation results are compared with those by the central difference method (CDM). Comparison shows that the stability of the NITI scheme is superior to that of the CDM. Accuracy of the NITI scheme is verified because its results are identical with those by the CDM in which the time step is set as 1/10 of that for the NITI scheme. The application of the NITI scheme to the mesh‐partitioned FEM is also proposed. It is applied to dynamic analysis of the linear soil–structure system. It yields the same results as a conventional single‐domain FEM analysis using the Newmark β method. This result verifies the usability of mesh‐partitioned FEM analysis using the NITI scheme. Copyright © 2003 John Wiley& Sons, Ltd.
Identification of base‐excited structures using output‐only parameter estimation
Authors: Pridham Brad A. , Wilson John C.
Published: December 2003

This paper presents a new identification technique for the extraction of modal parameters of structural systems subjected to base excitation. The technique uses output‐only measurements of the structural response. A combined subspace‐maximum likelihood algorithm is developed and applied to a three‐degree‐of‐freedom simulation model. Five ensembles of synthetically generated input signals, representing varying input characteristics, are employed in Monte Carlo simulations to illustrate the applicability of the method. The technique is able to circumvent some of the difficulties arising from short data sets by employing the Expectation Maximization (EM) algorithm to refine the subspace state estimates. This approach is motivated by successful application by previous authors on speech signals. Results indicate that, for certain system characteristics, more accurate pole estimates can be identified using the combined subspace‐EM formulation. In general, the damping ratios of the system are difficult to identify accurately due to limitations on data set length. The applicability of the technique to structural vibration signals is illustrated through the identification of seismic response data from the Vincent Thomas Bridge. Copyright © 2003 John Wiley & Sons, Ltd.
Distributions implied by American currency futures options: A ghost's smile?
Authors: Cincibuch Martin
Published: December 2003

A new and easily applicable method for estimating risk‐neutral distributions (RND) implied by American futures options is
proposed. It amounts to inverting the Barone‐Adesi and Whaley method (BAW method) to get the BAW implied volatility smile. Extensive
empirical tests show that the BAW smile is equivalent to the volatility smile implied by corresponding European options. Therefore, the procedure
leads to a legitimate RND estimation method. Further, the investigation of the currency options traded on the Chicago Mercantile Exchange and OTC
markets in parallel provides us with insights on the structure and interaction of the two markets. Unequally distributed liquidity in the OTC market
seems to lead to price distortions and an ensuing interesting “ghost‐like” shape of the RND density implied by CME options.
Finally, using the empirical results, we propose a parsimonious generalization of the existing methods for estimating volatility smiles from OTC
options. A single free parameter significantly improves the fit. © 2004 Wiley Periodicals, Inc. Jrl Fut Mark 24:147–178, 2004
A theoretical framework to evaluate different margin‐setting methodologies
Authors: Lam Kin , Sin Chor‐Yiu , Leung Rico
Published: December 2003

The margin system is the first line of defense against the default risk of a clearinghouse. From the perspectives of a clearinghouse, the utmost
concern is to have a prudential system to control the default exposure. Once the level of prudentiality is set, the next concern will
be the opportunity cost of the investors, because high opportunity cost discourages people from hedging futures, and thus defeats the
function of a futures market. In this article, we first develop different measures of prudentiality and opportunity cost. We then formulate a
statistical framework to evaluate different margin‐setting methodologies, all of which strike a balance between prudentiality and opportunity
cost. Three margin‐setting methodologies, namely, (1) using simple moving averages; (2) using exponentially weighted
moving averages; (3) using a GARCH approach, are applied to the Hang Seng Index futures. Keeping the same prudentiality
level, it is shown that the one using a GARCH approach by and large gives the lowest average overcharge. © 2004 Wiley Periodicals,
Inc. Jrl Fut Mark 24:117–145, 2004
The impacts of errors in individual genotyping and DNA pooling on association studies
Authors: Zou Guohua , Zhao Hongyu
Published: December 2003

Case‐control association studies using unrelated individuals may offer an effective approach for identifying genetic variants that have small to moderate disease risks. In general, two different strategies may be employed to establish associations between genotypes and phenotypes: (1) collecting individual genotypes or (2) quantifying allele frequencies in DNA pools. These two technologies have their respective advantages. Individual genotyping gathers more information, whereas DNA pooling may be more cost effective. Recent technological advances in DNA pooling have generated great interest in using DNA pooling in association studies. In this article, we investigate the impacts of errors in genotyping or measuring allele frequencies on the identification of genetic associations with these two strategies. We find that, with current technologies, compared to individual genotyping, a larger sample is generally required to achieve the same power using DNA pooling. We further consider the use of DNA pooling as a screening tool to identify candidate regions for follow‐up studies. We find that the majority of the positive regions identified from DNA pooling results may represent false positives if measurement errors are not appropriately considered in the design of the study. Genet Epidemiol 26:1–10, 2004. © 2003 Wiley‐Liss, Inc.
Analysis of SNPs in pooled DNA: A decision theoretic model
Authors: König Inke R. , Ziegler Andreas
Published: December 2003

Systematic analysis of the genetic background of complex diseases using single nucleotide polymorphisms (SNPs) affords a tremendous amount of genotypings. To reduce the amount of genotypings necessary and hence the overall cost of a case‐control study with SNPs, the genotyping is often performed in two stages: In the first, the DNA of all cases and all controls are mixed into two pools and genotyped for each SNP. The frequency of both alleles is determined in both pooled DNA samples. If different frequencies are observed in the pools of cases and controls, genotyping is performed individually in the second stage and analyzed conventionally. However, so far no well‐founded algorithm is available to guide the decision on whether to genotype a SNP individually. In this report, an approach is introduced for the decision on individual genotyping based on the results from pooled DNA. The analysis is modeled as a decision process with the specific goal to decide on whether to genotype a specific SNP individually. For a given situation, the resulting decision criteria are aimed to be optimal for those conducting the study. Different loss functions and decision rules are presented. Using Monte‐Carlo simulations, we show that for a given situation, the genotyping rates and hence the costs can be reduced remarkably while maintaining acceptable overall error rates. Genet Epidemiol 26:31–43, 2004. © 2003 Wiley‐Liss, Inc.