bluuebunny/crossref_metadata_2025 huggingface dataset:
Ignorance Management: The Lessons of Small Enterprises for Knowledge Management
Authors: Lambe Patrick
Published: September 2003

Knowledge management as traditionally espoused has two main strands: dealing with the aggregation of knowledge, and the transfer of knowledge. However, this official discourse and its key concepts grew out of the experience of large, mature, highly structured and dispersed enterprises. A look at the environment in which small enterprises work suggests a different set of key concepts, considering the notions of experience and structural capital as key knowledge manipulation tools. These tools are particularly relevant to environments of high uncertainty, volatility and risk — and so also have a significant contribution to make to the direction of knowledge management for larger enterprises, where adaptiveness and ignorance management tools are becoming increasingly important.
Exploring Knowledge Management Perceptions of Human Resource and Business Managers in Singapore
Authors: Law David Yuh Foong , Lee-Partridge Joo Eng , Chia Ho Beng , Wong Ming Fen
Published: September 2003

The field of knowledge management (KM) research is wide and interdisciplinary in nature. From an implementation perspective, it is often associated with information technologies (IT) and information systems (IS) professionals. In our study, we chose to focus on understanding the perceptions of non-IS professionals in order to gain a first-hand understanding of KM issues from their perspectives. This paper reports the preliminary findings of an ongoing research which aims at exploring some of the issues and concerns commonly associated with the notion of KM among non-IS practitioners. Our research subjects were targeted at very senior executives, managers and consultants engaged in human resource (HR) and other management functions. The main objective was to elicit a variety of KM perceptions and concerns common to these non-IS professionals based in Singapore. Through a series of focus group sessions, a range of issues is surfaced and categorised broadly into themes such as organisational culture, KM vision and leadership, roles of human resource management, knowledge sharing, talent shortage, accessing and documenting knowledge, knowledge regeneration and learning. The findings also raise new challenges for HR management in the context of KM research and practice.
KKM theorem with applications to lower and upper bounds equilibrium problem in G‐convex spaces
Authors: Fakhar M. , Zafarani J.
Published: September 2003

We give some new versions of KKM theorem
for generalized convex spaces. As an application, we answer a
question posed by Isac et al. (1999) for the lower and upper
bounds equilibrium problem.
Chaos and shadowing around a homoclinic tube
Authors: Li Yanguang (Charles)
Published: September 2003

Let F be a C3 diffeomorphism on a Banach space B. F has a homoclinic tube asymptotic to an invariant manifold. Around the
homoclinic tube, Bernoulli shift dynamics of submanifolds is
established through a shadowing lemma. This work removes an
uncheckable condition of Silnikov (1968). Also, the result of Silnikov does not imply
Bernoulli shift dynamics of a single map, but rather only provides a
labeling of all invariant tubes around the homoclinic tube. The
work of Silnikov was done in ℝn and the current work is done in a Banach space.
Rothe method for a mixed problem with an integral condition for the two‐dimensional diffusion equation
Authors: Merazga Nabil , Bouziani Abdelfatah
Published: September 2003

This paper deals with an initial boundary value problem with an
integral condition for the two‐dimensional diffusion equation.
Thanks to an appropriate transformation, the study of the given
problem is reduced to that of a one‐dimensional problem.
Existence, uniqueness, and continuous dependence upon data of a
weak solution of this latter are proved by means of the Rothe
method. Besides, convergence and an error estimate for a
semidiscrete approximation are obtained.
Gene expression profiling in CD34 cells to identify differences between aplastic anemia patients and healthy volunteers
Authors: Zeng Weihua , Chen Guibin , Kajigaya Sachiko , Nunez Olga , Charrow Alexandra , Billings Eric M. , Young Neal S.
Published: September 2003

An immune pathophysiology for acquired aplastic anemia (AA) has been inferred from the responsiveness of the patients to immunosuppressive therapies and experimental laboratory data. To address the transcriptome of hematopoietic cells in AA, we undertook GeneChip analysis of the extremely limited numbers of progenitor and stem cells in the marrow of patients with this disease. We pooled total RNA from highly enriched bone marrow CD34 cells of 36 patients with newly diagnosed AA and 12 healthy volunteers for analysis on oligonucleotide chips. A large number of genes implicated in apoptosis and cell death showed markedly increased expression in AA CD34 cells, and negative proliferation control genes also had increased activity. Conversely, cell cycle progress–enhancing genes showed low expression in AA. Cytokine/chemokine signal transducer genes, stress response genes, and defense/immune response genes were up-regulated, as anticipated from other evidence of the heightened immune activity in AA patients' marrow. In summary, detailed genetic analysis of small numbers of hematopoietic progenitor cells is feasible even in marrow failure states where such cells are present in very small numbers. The gene expression profile of primary human CD34 hematopoietic stem cells from AA was consistent with a stressed, dying, and immunologically activated target cell population. Many of the genes showing differential expression in AA deserve further detailed analysis, including comparison with other marrow failure states and autoimmune disease.
Efficient and Clean Aldol Condensation Catalyzed by Sodium Carbonate in Water
Authors: Zhang Ze , Dong Ya-Wei , Wang Guan-Wu
Published: September 2003

Efficient and environmentally friendly synthesis of chalcone and azachalcone was performed by aldol condensation of aldehydes with ketones in pure water catalyzed by sodium carbonate. In this convenient methodology, side reactions were avoided and thus high yields were achieved.
Spontaneous rupture of the spleen in AL amyloidosis
Authors: Oran B. , Wright D.G. , Seldin D.C. , McAneny D. , Skinner M. , Sanchorawala V.
Published: September 2003

The frequency of splenic involvement in AL amyloidosis is not precisely known. However, splenomegaly has been reported in 4–13% of patients. We report four cases of spontaneous splenic rupture in patients with AL amyloidosis. Splenic rupture was the initial manifestation of the disease in one of these patients. The other three experienced splenic rupture during or after high‐dose intravenous melphalan with autologous peripheral blood stem cell transplantation (HDM/SCT): one during stem cell mobilization with G‐CSF prior to HDM/SCT and two after hematopoietic recovery following treatment. Two of the four patients had Factor X deficiency, the most common coagulation abnormality associated with AL amyloidosis. All four patients underwent splenectomy without significant postoperative complications. Splenic rupture in AL amyloidosis as a complication of aggressive treatment with HDM/SCT has not been reported previously. Am. J. Hematol. 74:131–135, 2003. © 2003 Wiley‐Liss Inc.
Type I Glanzmann thrombasthenia: Most common subtypes in North Indians
Authors: Kannan M. , Ahmed Rafeeq P.H. , Jain Paresh , Kumar Rajive , Choudhry V.P. , Saxena Renu
Published: September 2003

The expression of GPIIb/IIIa on the platelet surface was assessed in 10 patients with Glanzmann thrombasthenia and their families by flow cytometry to determine the common subtype in North Indians. Glanzmann thrombasthenia was diagnosed in patients with bleeding manifestations accompanied by absent/reduced platelet aggregation, secondary to ADP, ADR, arachidonic acid, and collagen. Flow cytometry revealed variable GPIIb/IIIa expression by CD61 and CD41 in patients with Glanzmann thrombasthenia on the basis of CD61 levels, six patients were subtyped as type I because they had absent GPIIb/IIIa, three patients were subtyped as type II because their GPIIb/IIIa levels varied from 7.72% to 20.40%, and one patient was diagnosed as type III, because his clot retraction was 60% and GPIIb/IIIa was 46.0% of normal. Four fathers, three mothers, and five siblings were found to have GPIIb/IIIa levels less than 35% of normal. It is possible that low GPIIb/IIIa levels in family members may reflect their carrier status. It is postulated that flow cytometric estimation of GPIIb/IIIa in parents/siblings may detect carrier status in Glanzmann thrombasthenia. Am. J. Hematol. 74:139–141, 2003. © 2003 Wiley‐Liss Inc.
c‐Met expression in tall cell variant papillary carcinoma of the thyroid
Authors: Nardone Heather C. , Ziober Amy F. , LiVolsi Virginia A. , Mandel Susan J. , Baloch Zubair W. , Weber Randal S. , Mick Rosemarie , Ziober Barry L.
Published: September 2003

BACKGROUND

Tall cell variant papillary carcinoma of the thyroid demonstrates unusually aggressive clinical behavior compared with the usual form of papillary thyroid carcinoma. The proto‐oncogene c‐met encodes a tyrosine kinase receptor known to influence cell invasion. This current study examined c‐Met expression in tall cell variant tumors compared with other types of papillary thyroid carcinoma and benign thyroid disease.

METHODS

c‐Met expression in 60 archived thyroid specimens was evaluated by immunohistochemical staining.

RESULTS

Tall cell variant specimens expressed significantly greater levels of c‐Met than other forms of papillary thyroid carcinoma and benign thyroid disease (P < 0.0001). c‐Met expression was significantly different for the following pairs of histologies: tall cell variant versus usual papillary carcinoma of the thyroid (P < 0.0001), tall cell variant versus follicular variant papillary thyroid carcinoma (P < 0.0001), tall cell variant versus benign thyroid (P < 0.0001), and usual papillary carcinoma of the thyroid versus benign thyroid (P = 0.005). In addition, for all types of papillary carcinomas evaluated, c‐Met expression was significantly higher in specimens with extracapsular spread (P = 0.01) and skeletal muscle invasion (P = 0.02), and approached significance for specimens with lymphatic invasion (P = 0.06). After adjusting for extracapsular spread, c‐Met expression was still found to be associated significantly with tall cell histology (P < 0.0001).

CONCLUSIONS

c‐Met expression is a significant marker for tall cell variant papillary carcinoma of the thyroid and its invasive behavior. This finding may explain the unusually aggressive behavior of this tumor and suggests a role for c‐Met in the early identification of patients with tall cell variant thyroid disease. Cancer 2003;98:1386–93. © 2003 American Cancer Society.

DOI 10.1002/cncr.11638
Genetic polymorphisms of estrogen receptor alpha, CYP19, catechol‐O‐methyltransferase are associated with familial prostate carcinoma risk in a Japanese population
Authors: Suzuki Kazuhiro , Nakazato Haruki , Matsui Hiroshi , Koike Hidekazu , Okugi Hironobu , Kashiwagi Bunzo , Nishii Masahiro , Ohtake Nobuaki , Nakata Seiji , Ito Kazuto , Yamanaka Hidetoshi
Published: September 2003

BACKGROUND

Estrogen is one of the crucial hormones participating in the proliferation and carcinogenesis of the prostate glands. Genetic polymorphisms in the estrogen metabolism pathway might be involved in the risk of prostate carcinoma development. The authors evaluated the association between genetic polymorphisms in estrogen‐related enzymes and receptors and the risk of developing familial prostate carcinoma.

METHODS

In the current study, 101 cases with prostate carcinoma whose first‐degree relatives had prostate carcinoma and 114 healthy age and residence‐matched male controls were enrolled. The genotypes of estrogen receptor (ER) alpha, aromatase (CYP19), and catechol‐O‐methyltransferase (COMT) genes were analyzed.

RESULTS

For single polymorphisms, a significant association of the T/T genotype of the PvuII site in the ER alpha gene (odds ratio [OR], 3.44; 95% confidence interval [CI], 1.97–5.99; P = 0.0028), and the C/T and T/T genotypes of the CYP19 gene (OR, 1.77; 95% CI, 1.02–3.09; P = 0.037) with prostate carcinoma risk, was observed. The G/A genotype of the COMT gene showed a weak tendency toward increased risk (OR, 1.48; 95% CI, 0.85–2.57; P = 0.18). Stratification of cases according to clinical stage and pathologic grade showed that the C/T and T/T genotypes of the CYP19 gene were associated significantly with high‐grade carcinoma (OR, 2.59; 95% CI, 1.47–4.46; P = 0.048). The number of high‐risk genotypes (the T/T in ER alpha, the C/T and T/T in CYP19, and the G/A in COMT) significantly increased the risk of developing prostate carcinoma (2 genotypes: OR, 3.00; 95% CI, 1.72–5.23; P = 0.008; 3 genotypes: OR, 6.30; 95% CI, 3.61–10.99; P = 0.002).

CONCLUSIONS

Genetic polymorphisms of genes in the estrogen metabolism pathway were associated significantly with familial prostate carcinoma risk. Single nucleotide polymorphisms of low‐penetrance genes are targets for understanding the genetic susceptibility of familial prostate carcinoma. Cancer 2003;98:1411–6. © 2003 American Cancer Society.

DOI 10.1002/cncr.11639
Use of tamoxifen in the treatment of malignant melanoma
Authors: Lens Marko B. , Reiman Tony , Husain Amna F.
Published: September 2003

BACKGROUND

Tamoxifen has been used in the treatment of patients with metastatic malignant melanoma either as a single agent or, more commonly, in combination with other chemotherapeutic agents. The aim of the current study was to summarize the available clinical evidence on the role of the tamoxifen in different combination chemotherapy regimens because clinical studies including tamoxifen have produced inconclusive results.

METHODS

The authors designed a systematic review and metaanalysis of published randomized controlled trials to assess the benefit of tamoxifen added to various single‐agent or multiagent chemotherapy or biochemotherapy regimens.

RESULTS

Six randomized trials met the inclusion criteria and were analyzed. These 6 trials involved a combined total of 912 patients. Of this number, 455 patients were randomized to receive tamoxifen added to chemotherapy or biochemotherapy regimens and 457 were randomized to receive chemotherapy or biochemotherapy without tamoxifen. The overall response rate was not improved significantly by the addition of tamoxifen to the chemotherapy regimen (odds ratio [OR], 1.16; 95% confidence interval [CI], 0.75–1.82; test for overall effect: P = 0.14). The results were not statistically significant for complete response (OR, 0.64; 95% CI, 0.33–1.25; test for overall effect: P = 0.19).

CONCLUSIONS

The current metaanalysis demonstrated that tamoxifen does not improve the overall response rate, complete response rate, or survival rate when administered along with combined chemotherapy regimens. Currently, the strength of evidence does not support the use of tamoxifen in combination with other systemic chemotherapy for the treatment of metastatic melanoma. Cancer 2003;98:1355–61. © 2003 American Cancer Society.

DOI 10.1002/cncr.11644
Isolated limb perfusion with tumor necrosis factor‐α and melphalan for patients with unresectable soft tissue sarcoma of the extremities
Authors: Noorda Eva M. , Vrouenraets Bart C. , Nieweg Omgo E. , van Coevorden Frits , van Slooten Gooike W. , Kroon Bin B. R.
Published: September 2003

BACKGROUND

Since 1992, isolated limb perfusion (ILP) with tumor necrosis factor‐α (TNFα) and melphalan has been used for the treatment of patients with unresectable soft tissue sarcomas of the extremities. The authors retrospectively studied the results of limb salvage surgery using TNFα‐ILP at their institution.

METHODS

From 1992 to 2001, 49 patients (mean age, 51 years; range, 14–85 years) underwent ILP for unresectable soft tissue sarcomas of the extremities. All patients received melphalan and TNFα (four patients also received interferon‐γ). The median follow‐up was 26 months (range, from 2 days to 103 months).

RESULTS

In 1 patient (2%) who died 2 days after undergoing ILP, response and acute limb toxicity could not be assessed. One patient (2%) attained a clinical complete response (2%), 23 patients (47%) attained a clinical partial response, 17 patients (35%) demonstrated no change, and 7 patients (14%) had tumor progression. Thirty‐one patients (63%) underwent tumor resection. Histologic material also was available from eight amputations and three punctures/biopsies. Pathologic response was complete in 4 patients (8%), partial in 14 patients (29%), and no change was observed in 24 patients (49%). Final response, based on both clinical and pathologic assessment in which pathology was decisive, was complete in 4 patients (8%) and partial in 27 patients (55%), resulting in a final overall response rate of 63%. Local control with preservation of the limb was attained in 28 patients (57%). Four of 32 patients (13%) who had been rendered tumor free by ILP with or without undergoing resection and radiation therapy, developed a local recurrence. The 5‐year disease specific survival rate was 48% for the 49 patients. Acute limb toxicity after ILP was a mild Grade 1–2 reaction in 35 patients (71%) patients, a Grade 3 reaction in 12 patients (25%), and a Grade 4 reaction in 1 patient (2%). Three major ILP‐related complications were encountered, including arterial thrombosis in two patients and a fulminant Clostridial infection leading to death in one patient. There were no severe cardiovascular reactions after ILP.

CONCLUSIONS

In patients with unresectable soft tissue sarcomas of the limbs who underwent ILP with TNFα and melphalan followed by resection of the tumor remnant when possible, a 63% overall tumor response rate and a 57% local control rate with limb preservation was achieved. Cancer 2003;98:1483–90. © 2003 American Cancer Society.

DOI 10.1002/cncr.11648
Preclinical evaluation of therapeutic effects of targeted cytotoxic analogs of somatostatin and bombesin on human gastric carcinomas
Authors: Szepeshazi Karoly , Schally Andrew V. , Nagy Attila , Wagner Brady W. , Bajo Ana Maria , Halmos Gabor
Published: September 2003

BACKGROUND

New modalities are necessary for the treatment of patients with unresectable gastric carcinoma. The authors investigated whether receptors for somatostatin and bombesin were present in human gastric carcinoma lines and tested the antitumor effects of cytotoxic somatostatin analog AN‐238 and cytotoxic bombesin conjugate AN‐215.

METHODS

Nude mice bearing AGS, Hs 746T, and NCI‐N87 human gastric carcinomas were treated with AN‐238, AN‐215, or their cytotoxic moiety 2‐pyrrolinodoxorubicin (AN‐201). Tumor growth reduction and tumor doubling times were calculated, and histologic characteristics of cell proliferation and apoptosis were examined. The expression of mRNA for somatostatin and bombesin receptors in tumors was investigated by reverse transcriptase–polymerase chain reaction. Subtypes 2 and 5 of somatostatin receptor proteins (sst2 and sst5, respectively) were analyzed using immunohistochemistry and immunoblotting. Binding assays were performed with radiolabeled somatostatin and bombesin analogs.

RESULTS

Cytotoxic bombesin analog AN‐215 powerfully inhibited the growth of AGS carcinomas that expressed high‐affinity subtype 1 bombesin receptors. All three carcinomas expressed high‐affinity sst2 and sst5 receptors. Cytotoxic somatostatin analog AN‐238 exerted a strong inhibitory effect on NCI‐N87 and Hs 746T carcinomas, which exhibited high concentrations of somatostatin receptors, but had a weaker effect on AGS tumors, which expressed the lowest receptor levels. AN‐201 had only nonsignificant effects.

CONCLUSIONS

Experimental human gastric carcinomas that expressed high‐affinity subtype 1 bombesin receptors were inhibited by cytotoxic bombesin analog AN‐215, and tumors with high concentrations of sst2 or sst5 somatostatin receptors were suppressed by cytotoxic somatostatin analog AN‐238. These findings suggest that this class of targeted compounds should be considered for the therapy of patients with advanced gastric carcinoma. Cancer 2003;98:1401–10. © 2003 American Cancer Society.

DOI 10.1002/cncr.11649
The effect of cyclooxygenase‐2 expression on tumor vascularity in advanced stage ovarian serous carcinoma
Authors: Ali‐Fehmi Rouba , Che Mingxin , Khalifeh Ibrahim , Malone John M. , Morris Robert , Lawrence W. Dwayne , Munkarah Adnan R.
Published: September 2003

BACKGROUND

Cyclooxygenase‐2 (COX‐2) seems to be involved at various steps in the processes of malignant transformation and tumor progression. Investigations have shown that COX‐2 overexpression is associated with increased proliferation, reduced apoptosis, and angiogenesis.

METHODS

Specimens from 125 patients with high‐grade, advanced‐stage (Stage III–IV) serous ovarian carcinoma were evaluated by immunohistochemistry for COX‐2, p53, bcl‐2, epidermal growth factor receptor (EGFR), and Her‐2/neu expression and for CD34‐stained microvessel density (MVD). Statistical analysis was performed to investigate the correlations between COX‐2 expression and 1) clinicopathologic characteristics, 2) tumor MVD, and 3) expression of other molecular markers. The effect of COX‐2 expression on survival was determined using survival analysis.

RESULTS

Increased COX‐2 expression was significantly correlated with tumor MVD (Spearman rank correlation test: r = 0.41; P < 0.001). There was no association observed between COX‐2 expression and expression levels of EGFR, Her‐2/neu, bcl‐2, or p53. Patients who had tumors that showed high COX‐2 expression had a worse prognosis compared with patients who had tumors with low expression (death hazard ratio, 2.0; 95% confidence interval, 1.2–3.5; P < 0.001). A multivariate analysis revealed that COX‐2 expression was the strongest predictor of survival among the different prognostic factors analyzed.

CONCLUSIONS

The current study demonstrated that COX‐2 expression was correlated significantly with survival in patients with high‐grade, high‐stage serous ovarian carcinoma. Expression of COX‐2 also was correlated with tumor angiogenesis but not with EGFR, Her‐2/neu, or p53 expression. In addition to their prognostic significance, a better understanding of the biology of these molecular changes may help identify new targets for therapy in patients with ovarian carcinoma. Cancer 2003;98:1423–9. © 2003 American Cancer Society.

DOI 10.1002/cncr.11650
Prognostic value of serum MUC5AC mucin in patients with cholangiocarcinoma
Authors: Boonla Chanchai , Wongkham Sopit , Sheehan John Kieran , Wongkham Chaisiri , Bhudhisawasdi Vajarabhongsa , Tepsiri Nisana , Pairojkul Chawalit
Published: September 2003

BACKGROUND

The authors recently showed that MUC5AC mucin, which is expressed aberrantly in tumor tissue, is present in significant concentrations in serum from patients with cholangiocarcinoma. Subsequently, determination of serum MUC5AC had high sensitivity and specificity for cholangiocarcinoma. In this study, the possible association between serum MUC5AC mucin and the clinical findings of the patients and their prognostic value were explored.

METHODS

The expression of MUC5AC mucin in serum samples from 179 patients with histologically confirmed cholangiocarcinoma were determined using immunoblotting.

RESULTS

Detection of serum MUC5AC was associated with patients with blood group Type A, larger‐sized tumors (> 5 cm), and advanced‐stage disease. Patients who had positive serum MUC5AC status had a significantly poorer prognosis (median survival, 127 days; 95% confidence interval [95% CI], 107–180 days) compared with patients who had negative serum MUC5AC status (median survival, 329 days; 95% CI, 199–458 days; P < 0.001). Multivariate analysis with adjustment for all covariates showed that patients who had positive serum MUC5AC status had a 2.5‐fold higher risk of death compared with patients who had negative serum MUC5AC status (P < 0.001).

CONCLUSIONS

Serum MUC5AC was associated with tumor burden. The determination of serum MUC5AC may be predictive of poor patient outcome and may be useful in selecting possible treatment options for patients with cholangiocarcinoma. Cancer 2003;98:1438–43. © 2003 American Cancer Society.

DOI 10.1002/cncr.11652
Expression of hepatoma‐derived growth factor in hepatocellular carcinoma
Authors: Hu Tsung‐Hui , Huang Chao‐Cheng , Liu Li‐Feng , Lin Pey‐Ru , Liu Shang‐Yun , Chang Hsueh‐Wen , Changchien Chi‐Sin , Lee Chuan‐Mo , Chuang Jiin‐Haur , Tai Ming Hong
Published: September 2003

BACKGROUND

Hepatoma‐derived growth factor (HDGF) is a novel growth factor derived from a hepatoma cell line. The current study was designed to elucidate the role of HDGF expression during the pathogenesis of hepatocellular carcinoma (HCC).

METHODS

HDGF expression in hepatoma cell lines was analyzed using the reverse transcriptase–polymerase chain reaction (RT‐PCR), Western blot analysis, and immunofluorescence analysis. Immunohistochemical studies were performed to examine the intensity and spatial distribution of HDGF immunostaining in 105 HCC specimens. To evaluate its prognostic value, the labeling index of HDGF immunostaining was analyzed for potential correlations with the clinicopathologic characteristics of HCC.

RESULTS

RT‐PCR and Western blot analysis detected increased HDGF expression in malignant hepatoma cell lines. In resected HCC specimens, HDGF immunostaining was detected in the nuclei and cytoplasm of hepatocytes and hepatoma cells. HDGF levels in hepatoma tissue samples were significantly higher than in adjacent nontumor tissue samples (P < 0.05). Elevated nuclear HDGF levels were found to be correlated with loss of differentiation features (P < 0.05), absence of tumor capsules (P < 0.01), high α‐fetoprotein levels (P < 0.05), and overexpression of proliferating cell nuclear antigen (P < 0.001). Kaplan–Meier analysis indicated that patients with higher nuclear HDGF levels had a shorter duration of survival and a higher incidence of recurrence (P < 0.001). Multivariate analysis indicated that for patients with HCC, the nuclear HDGF level is an independent prognostic factor for overall and disease‐free survival.

CONCLUSIONS

Increased HDGF expression is correlated with the proliferating states of HCC and represents a novel prognostic factor for patients with HCC who have undergone surgery. Cancer 2003;98:1444–56. © 2003 American Cancer Society.

DOI 10.1002/cncr.11653
Analysis of the impact of imatinib mesylate therapy on the prognosis of patients with Philadelphia chromosome–positive chronic myelogenous leukemia treated with interferon‐α regimens for early chronic phase
Authors: Kantarjian Hagop , O'Brien Susan , Cortes Jorges , Shan Jianqin , Giles Francis , Garcia‐Manero Guillermo , Verstovsek Srdan , Faderl Stefan , Rios Mary Beth , Talpaz Moshe
Published: September 2003

BACKGROUND

The effect on prognosis of adding imatinib mesylate to the treatment of patients with Philadelphia chromosome (Ph)‐positive chronic myelogenous leukemia (CML) has not been explored fully. The objective of the current study was to evaluate the benefit of adding imatinib to the treatment sequence of patients with early chronic phase Ph‐positive CML who received interferon α (IFN)‐based regimens as frontline therapy.

METHODS

A total of 201 patients with early chronic phase Ph‐positive CML who were treated on our 3 recent frontline IFN–based programs and were impacted early by the availability of sequential therapy with imatinib were analyzed. Their outcome was compared with that of a historical control group of 293 patients treated from 1982 until 1990 who were treated with IFN programs for early chronic phase CML and who did not have the opportunity of early access to imatinib (because it was not available during that period). Multivariate analysis was used to evaluate the independent effect of imatinib therapy on survival.

RESULTS

Of 201 patients who were treated, 159 patients (79%) had their regimen changed sequentially to imatinib after a median duration of 14 months of IFN therapy. Of 139 patients who continued evaluation at our institution, 101 patients (73%; 64% of the total group) achieved a complete cytogenetic response, and 20 of 80 patients analyzed (25%; 10% of the total group) had no disease according to molecular studies (quantitative polymerase chain reaction studies). The estimated 5‐year survival rate for the total study group of 201 patients was 86%. Survival of this group was significantly superior to the historic control group of IFN‐treated patients who did not have the benefit of imatinib (P= 0.03). The trend also was observed within defined CML risk groups. Imatinib therapy was confirmed as an independent, significant, favorable prognostic factor for survival by multivariate analysis, after accounting for the independent prognostic effect of pretreatment prognostic factors (P= 0.005).

CONCLUSIONS

The current analysis is the first to indicate the independent, favorable effect of imatinib on the survival of patients with Ph‐positive CML. Cancer 2003;98:1430–7. © 2003 American Cancer Society.

DOI 10.1002/cncr.11665
Effects of smoking and radiotherapy on lung carcinoma in breast carcinoma survivors
Authors: Ford Melissa B. , Sigurdson Alice J. , Petrulis Elaine S. , Ng Chaan S. , Kemp Bonnie , Cooksley Catherine , McNeese Marsha , Selwyn Beatrice J. , Spitz Margaret R. , Bondy Melissa L.
Published: September 2003

BACKGROUND

The combined effects of thoracic radiotherapy (XRT) and cigarette smoking are not known with certainty, but they have important implications for lung carcinogenesis after cancer therapy in some patients. The authors analyzed smoking, radiation, and both exposures on lung carcinoma development in women who were treated previously for breast carcinoma.

METHODS

Case patients (n = 280) were female residents of the United States, ages 30–89 years, with breast carcinoma prior to primary lung carcinoma diagnosed between 1960 and 1997. Control patients (n = 300) were selected randomly from 37,000 patients with breast carcinoma who were treated at The University of Texas M. D. Anderson Cancer Center and frequency matched with women in the case group based on age at diagnosis (5‐year strata), ethnicity, year of breast carcinoma diagnosis (5‐year strata), and survival from breast carcinoma diagnosis to lung carcinoma diagnosis. Using stratified analysis and unconditional logistic regression, the authors evaluated the main and combined effects of smoking and XRT on lung carcinoma risk.

RESULTS

At the time of breast carcinoma diagnosis, 84% of case patients had ever smoked cigarettes, compared with 37% of control patients, whereas 45% of case patients and control patients received XRT for breast carcinoma. Smoking increased the odds of lung carcinoma in women without XRT (odds ratio [OR], 6.0; 95% confidence interval [95% CI], 3.6–10.1), but XRT did not increase lung carcinoma risk in nonsmoking women (OR, 0.5; 95% CI, 0.3–1.1). Overall, the OR for both XRT and smoking, compared with no XRT or smoking, was 9.0 (95% CI, 5.1–15.9). Logistic regression modeling yielded an adjusted OR of 5.6 for the smoking main effect (95% CI, 2.9–10.5), 0.6 for the XRT main effect (95% CI, 0.3–1.4), and 8.6 (P = 0.08) for the combined effect.

CONCLUSIONS

Smoking was a significant independent risk factor for lung carcinoma after breast carcinoma, but XRT alone was not. Smoking and XRT combined enhanced the effect of either alone, with marked increased risks of lung carcinoma after XRT for breast carcinoma. Cancer 2003;98:1457–64. © 2003 American Cancer Society.

DOI 10.1002/cncr.11669
The burdens of cancer therapy
Authors: Elting Linda S. , Cooksley Catherine , Chambers Mark , Cantor Scott B. , Manzullo Ellen , Rubenstein Edward B.
Published: September 2003

BACKGROUND

Mucositis is a common but poorly studied problem among patients with solid tumors. The authors examined the clinical and economic outcomes of oral and gastrointestinal (GI) mucositis among patients receiving myelosuppressive chemotherapy.

METHODS

A retrospective, random sample of 599 patients who developed chemotherapy‐induced myelosuppression was followed for development of oral or GI mucositis and for development of subsequent episodes of bleeding or infection. Multilevel regression models of the risk of bleeding and infection were fit with chemotherapy cycles nested within patients.

RESULTS

Mucositis developed during 37% of 1236 cycles of chemotherapy. Episodes of bleeding were significantly more common during cycles with GI mucositis than during cycles without GI mucositis (13% vs. 8%; P = 0.04). Episodes of infection were significantly more common during cycles with mucositis (especially GI mucositis) than during cycles without mucositis (73% vs. 36%; P < 0.0001). The mean durations of hospitalization were 4 days, 6 days, and 12 days during cycles with no mucositis, oral mucositis, and GI mucositis, respectively. After accounting for the depth and duration of myelosuppression and for other predictive factors, GI mucositis was associated with both bleeding (odds ratio [OR], 2.0; P = 0.01) and infection (OR, 2.24; P < 0.0001), whereas oral mucositis was associated with infection only (OR, 2.4; P < 0.0001).

CONCLUSIONS

Mucositis was clinically and economically significant among patients with solid tumors who were receiving myelosuppressive chemotherapy. New preventive and therapeutic agents are needed. Cancer 2003;98:1531–9. © 2003 American Cancer Society.

DOI 10.1002/cncr.11671
Breast carcinoma and antihypertensive therapy
Authors: Giordano Sharon H.
Published: September 2003

Li et al. reported that the use of certain types of antihypertensive medication is associated with a modest increase in the risk of developing breast carcinoma. However, these findings should be interpreted with caution, as the number of comparisons made in the study was large, the magnitude of the observed effects was small, and the potential for biases was present. A number of studies have found no link between increased cancer risk and antihypertensive use. The findings of Li et al. should stimulate interest in the way in which specific classes of medication may influence breast carcinoma risk, but the bulk of the existing evidence suggests the absence of a significant link between antihypertensive use and breast carcinoma risk.

See referenced original article on pages 1504–13, this issue.
Increased incidence of symptomatic venous thrombosis in patients with cervical carcinoma treated with concurrent chemotherapy, radiation, and erythropoietin
Authors: Wun Ted , Law Lisa , Harvey Danielle , Sieracki Barbara , Scudder Sidney A. , Ryu Janice K.
Published: September 2003

BACKGROUND

Because studies have suggested that anemia has an adverse effect on outcome for patients with cervical carcinoma who are treated with radiation, recombinant human erythropoietin (rHuEpo) has been used increasingly to maintain hemoglobin levels in these patients. Erythropoietin may increase the risk of thrombosis. The authors performed a retrospective analysis to determine whether there was an increased rate of symptomatic venous thrombosis associated with the use of rHuEpo in patients with carcinoma of the uterine cervix and vagina.

METHODS

A retrospective, case–control study was performed on consecutive patients with localized carcinoma of the uterine cervix or vagina who were treated with chemotherapy and radiation (chemoradiotherapy). The primary outcome was symptomatic venous thrombosis.

RESULTS

One hundred forty‐seven patients were reviewed. When they were divided into women who received rHuEpo (n = 75 patients) and women who did not receive rHuEpo (n = 72 patients), there were no significant differences in age, height, weight, disease stage, or body mass index. Fewer patients in the rHuEpo group required transfusions. In the rHuEpo group, 17 of 75 patients had either an upper extremity thrombosis (n = 12 patients) or a lower extremity thrombosis (n = 7 patients): 2 patients had both, and 2 patients had more than 1 event. Two of 72 patients who did not receive rHuEpo had symptomatic thrombosis. Patients who received rHuEpo had an odds ratio (OR) of developing thrombosis of 10.3 (95% confidence interval [95% CI], 2.3–46.2). Multiple logistic regression revealed that only the use of rHuEpo was associated with an increased risk of thrombosis (OR, 15.3; 95% CI, 3.1–76.7).

CONCLUSIONS

Patients with cervical carcinoma who received chemoradiotherapy and rHuEpo had an increased risk of symptomatic venous thrombosis. Cancer 2003;98:1514–20. © 2003 American Cancer Society.

DOI 10.1002/cncr.11700
What difference does the choice of SES make in health inequality measurement?
Authors: Wagstaff Adam , Watanabe Naoko
Published: September 2003

This note explores the implications for measuring socioeconomic inequality in health of choosing one measure of SES rather than another. Three points emerge. First, whilst similar rankings in the two the SES measures will result in similar inequalities, this is a sufficient condition not a necessary one. What matters is whether rank differences are correlated with health – if they are not, the measured degree of inequality will be the same. Second, the statistical importance of choosing one SES measure rather than another can be assessed simply by estimating an artificial regression. Third, in the 19 countries examined here, it seems for the most part to make little difference to the measured degree of socioeconomic inequalities in malnutrition among under‐five children whether one measures SES by consumption or by an asset‐based wealth index. Copyright © 2003 John Wiley & Sons, Ltd.
Measuring income related inequality in health: standardisation and the partial concentration index
Authors: Gravelle Hugh
Published: September 2003

The partial concentration index (PCI) is commonly used as a measure of income related inequality in health after removing the effects of standardising variables such as age and gender which affect health, are correlated with income, but not amenable to policy. Both direct and indirect standardisation have been used to remove the effects of standardising variables. The paper shows that with individual level data direct standardisation is possible using the coefficients from a linear regression of health on income and the standardising variables and yields a consistent estimate of the PCI. Indirect standardisation estimates the effects of the standardising variables on health from a health regression which excludes income. The coefficients on the standardising variables include some of the effects of income on health if income is correlated with the standardising variables. Using these coefficients to remove the effects of the standardising variables also removes some of the effect of income on health and leads to an inconsistent estimate of the PCI. Indirect standardisation underestimates the PCI irrespective of the signs of the correlations of standardising variables and income with each other and with health. An adaptation of the PCI when the marginal effect of income on health depends on the standardising variables is also proposed. Copyright © 2003 John Wiley & Sons, Ltd.
Homology in comparative, molecular, and evolutionary developmental biology: The radiation of a concept
Authors: Brigandt Ingo
Published: September 2003

The present paper analyzes the use and understanding of the homology concept across different biological disciplines. It is argued that in its history, the homology concept underwent a sort of adaptive radiation. Once it migrated from comparative anatomy into new biological fields, the homology concept changed in accordance with the theoretical aims and interests of these disciplines. The paper gives a case study of the theoretical role that homology plays in comparative and evolutionary biology, in molecular biology, and in evolutionary developmental biology. It is shown that the concept or variant of homology preferred by a particular biological field is used to bring about items of biological knowledge that are characteristic for this field. A particular branch of biology uses its homology concept to pursue its specific theoretical goals. J. Exp. Zool. (Mol. Dev. Evol.) 299B:9–17, 2003. © 2003 Wiley‐Liss, Inc.
The effect of brain tumor angiogenesis on the in vivo relationship between the gradient‐echo relaxation rate change (ΔR2*) and contrast agent (MION) dose
Authors: Pathak Arvind P. , Rand Scott D. , Schmainda Kathleen M.
Published: September 2003

Purpose

To determine in vivo if the susceptibility calibration factor for gradient‐echo imaging (kG), which characterizes the relationship between the tissue T2* relaxation rate change (ΔR2*) and tissue contrast agent concentration, is independent of tissue type and condition; in addition, to assess the consequences of such an assumption on the use of relative cerebral blood volume (rCBV) measurements as a direct index of tumor angiogenesis.

Materials and Methods

The ΔR2* was measured as a function of monocrystalline iron oxide nanoparticles (MION) contrast agent dose in a rat brain tumor (9L gliosarcoma) model, the blood volume fraction independently measured, and kG calculated and compared for the normal gray matter, normal white matter, tumor, and contralateral brain.

Results

The kG was found to be the same for gray and white matter (P = 0.53), but statistically different for tumor compared to contralateral brain (P = 0.005) with k < k

Conclusion

The gradient‐echo calibration factor, kG, is the same for brain gray and white matter, but not the same for brain and tumor tissue. This difference may be attributed to the grossly different vascular morphology of tumors, dueto tumor angiogenesis, compared to normal brain and/or possibly differing blood rheological factors such as hematocrit. Consequently, the sensitivity to blood volume differ‐ences between tumor and normal brain tissue may be lessened when using gradient‐echo susceptibility contrast agent methods. J. Magn. Reson. Imaging 2003;18:397–403. © 2003 Wiley‐Liss, Inc.
Pediatric perfusion imaging using pulsed arterial spin labeling
Authors: Wang Jiongjiong , Licht Daniel J. , Jahng Geon‐Ho , Liu Chia‐Shang , Rubin Joan T. , Haselgrove John , Zimmerman Robert A. , Detre John A.
Published: September 2003

Purpose

To test the feasibility of pediatric perfusion imaging using a pulsed arterial spin labeling (ASL) technique at 1.5 T.

Materials and Methods

ASL perfusion imaging was carried out on seven neurologically normal children and five healthy adults. The signal‐to‐noise ratio (SNR) of the perfusion images along with T1, M0, arterial transit time, and the temporal fluctuation of the ASL image series were measured and compared between the two age groups. In addition, ASL perfusion magnetic resonance (MR) was performed on three children with neurologic disorder.

Results

In the cohort of neurologically normal children, a 70% increase in the SNR of the ASL perfusion images and a 30% increase in the absolute cerebral blood flow compared to the adult data were observed. The measures of ASL SNR, T1, and M0 were found to decrease linearly with age. Transit time and temporal fluctuation of the ASL perfusion image series were not significantly different between the two age groups. The feasibility of ASL in the diagnosis of pediatric neurologic disease was also illustrated.

Conclusion

ASL is a promising tool for pediatric perfusion imaging given the unique and reciprocal benefits in terms of safety and image quality. J. Magn. Reson. Imaging 2003;18:404–413. © 2003 Wiley‐Liss, Inc.
Use of fast spin echo for phase shift magnetic resonance thermometry
Authors: Vogel Mika W. , Pattynama Peter M.T. , Lethimonnier Franck L. , Le Roux Patrick
Published: September 2003

Purpose

To propose a modified fast spin echo (FSE) magnetic resonance imaging sequence for MR thermometry, employing the proton resonance frequency (PRF) shift by means of MR phase maps. Despite their obvious advantages of speed and high signal‐to‐noise ratio (SNR), FSE sequences have not until now been used for this purpose due to the restraints imposed by the Carr‐Purcell‐Meiboom‐Gill (CPMG) conditions.

Materials and Methods

The new FSE combines a new phase modulation scheme that maintains magnetization that ordinarily is destroyed under CPMG conditions, while employing conventional FSE gradient waveforms. The echoes are read in a single shot using 128 readouts in 650 msec, with a phase sensitive preparation using an optional time shift τ before the start of the refocusing gradient waveforms. This feature allows the quantification of temperature dependent phase shifts. We tested the sequence by imaging a heated agar gel phantom while cooling, using different values for τ.

Results

There was good correlation between FSE and fiberoptic‐based temperature measurements in the phantom(r2 ≥ 0.95). Temperature sensitivity could be adjusted by varying the τ value.

Conclusion

With the proposed non‐CPMG FSE sequence it is feasible to quantify temperature changes by means of the PRF shift. J. Magn. Reson. Imaging 2003;18:507–512. © 2003 Wiley‐Liss, Inc.
Radiation therapy alone in early stage non‐small cell lung cancer
Authors: Zimmermann Frank B. , Bamberg Michael , Molls Michael , Jeremic Branislav
Published: September 2003

Among the patients with early stage (I/II) non‐small cell lung cancer (NSCLC), there are those who, due to medical comorbidities, advanced age, or refusal, never undergo surgery. For them, exclusive radiation therapy (RT) has been the treatment of choice, achieving median survival times of 30 months and 5‐year survival of up to 42%. Doses of ≥65 Gy with standard fractionation (or its radiobiological equivalent when altered fractionation is used) are necessary for long‐lasting local control of the disease, with smaller tumors having a more favorable prognosis. The issue of elective nodal irradiation (ENI) remains controversial, since failure patterns identified local failure as the predominant pattern. None of the potential pretreatment patient‐ and tumor‐related prognostic factors has been shown to clearly influence survival. Toxicity is generally mild to moderate, although high doses (e.g., 80 Gy) may carry a risk for an excessive rate of side effects. Conformal treatment and consideration of comorbidities such as altered lung function may be essential, since simultaneous supportive treatment of acute sequelae (mainly acute esophagitis) is necessary. RT is an effective treatment modality in technically operable, but medically inoperable patients with early stage NSCLC and offers a long‐lasting cure. Semin. Surg. Oncol. 21:91–97, 2003. © 2003 Wiley‐Liss, Inc.
Treatment of recurrent disease in lung cancer
Authors: Zimmermann Frank B. , Molls Michael , Jeremic Branislav
Published: September 2003

Recurrence is a common event after treatment of lung cancer. Retreatment options depend on previous therapies, location of recurrence, and physical condition of the patient. Locoregional relapse can be treated the same way as initial lung cancer, including surgery, radiotherapy (RT), and chemotherapy (CHT), or combined treatment. Approximately 1% to 2% of all recurrent lung cancer is treated with curative reoperation, with somewhat dismal results. RT has been used for either postsurgical or post‐RT locoregional recurrences. In the former case, external beam RT was particularly effective in isolated bronchial stump recurrences, with median survival time of approximately 28.5 months and a 5‐year survival of approximately 31.5%. In the latter case, reirradiation, generally with endobronchial brachytherapy, was successful in palliation of intrathoracic symptoms (in at least two‐thirds of cases), carrying a low incidence of radiation pneumonitis (up to 5%) although cumulative doses went up to 120–150 Gy. Besides external beam RT, endobronchial RT was used to treat symptomatic intraluminal recurrences, with the vast majority of studies using high‐dose rate brachytherapy. Finally, CHT has been used in relapsed/refractory advanced or metastatic non‐small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) with the major emphasis on the third‐generation drugs that show good response after previously used platinum‐based CHT. Semin. Surg. Oncol. 21:122–127, 2003. © 2003 Wiley‐Liss, Inc.