bluuebunny/crossref_metadata_2025 huggingface dataset:
An Efficient Approach for Aromatic Epoxidation Using Hydrogen Peroxide and Mn(III) Porphyrins.
Authors: Rebelo Susana L. H. , Simoes Mario M. Q. , Neves M. Graca P. M. S. , Silva Artur M. S. , Cavaleiro Jose A. S.
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Polymer‐Supported Thioanisole: A Versatile Platform for Organic Synthesis Reagents.
Authors: Choi Matthew Kwok Wai , Toy Patrick H.
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Preparation of β‐ and γ‐Lactams from Carbamoyl Radicals Derived from Oxime Oxalate Amides.
Authors: Scanlan Eoin M. , Slawin Alexandra M. Z. , Walton John C.
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Palladium‐Catalyzed Oxidative Alkoxylation of α‐Alkenyl β‐Diketones to Form Functionalized Furans.
Authors: Han Xiaoqing , Widenhoefer Ross A.
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Synthesis, Crystal Structures, and Electrical Properties of Anion Radical Salts of Novel Electron Acceptors, 2,6‐Dicyanomethylene‐4‐oxo‐2,6‐dihydrocyclopentadithiophene (CPDT‐TCNQ) and Its Diselenophene Analogue (CPDS‐TCNQ), Having Three Electron‐Withdrawing Groups.
Authors: Tarutani Shinji , Takahashi Kazuko
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
DNA Binding Ligands Targeting Drug‐Resistant Gram‐Positive Bacteria. Part 2. C‐Terminal Benzimidazoles and Derivatives
Authors: Buerli Roland W. , Jones Peter , McMinn Dustin , Le Quan , Duan Jian‐Xin , Kaizerman Jacob A. , Difuntorum Stacey , Moser Heinz E.
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Enecarbamates as Selective Substrates in Oxidations: Chiral‐Auxiliary‐Controlled Mode Selectivity and Diastereoselectivity in the [2 + 2] Cycloaddition and Ene Reaction of Singlet Oxygen and in the Epoxidation by DMD and mCPBA.
Authors: Adam Waldemar , Bosio Sara G. , Turro Nicholas J. , Wolff Barbara T.
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Synthesis and Bioactivity of Isoxazolylthiazoles, Isoxazolylthiazolylchromen‐2‐ones, Isoxazolylthiazinanes and Isoxazolylthiazolidinones.
Authors: Rajanarendar E. , Karunakar D. , Srinivas M.
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Liposome/Water Lipophilicity: Methods, Information Content, and Pharmaceutical Applications
Authors: Plemper van Balen Georgette , Martinet Catherine a Marca , Caron Giulia , Bouchard Geraldine , Reist Marianne , Carrupt Pierre‐Alain , Fruttero Roberta , Gasco Alberto , Testa Bernard
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Subphthalocyanines: Non‐Planar Aromatic Compounds as Electroactive and Photoactive Components in Fullerene Covalent and Non‐Covalent Assemblies
Authors: Claessens Christian , Torres Tomas
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Highly Enantioselective or Not? — Chiral Monodentate Monophosphorus Ligands in the Asymmetric Hydrogenation
Authors: Komarov Igor V. , Boerner Armin
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Quality of BSH and BPA : Challenge to Synthetic Chemist
Authors: Kriz O. , Plzak Z. , Gruner B.
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Electrolysis of Nitro Compound Salts: Application in Ketone Synthesis
Authors: Ogibin Yu. N. , Ilovaiskii A. I. , Merkulova V. M. , Nikishin G. I.
Published: June 2004

For Abstract see ChemInform Abstract in Full Text.
Inhibitors arrest myofibrillogenesis in skeletal muscle cells at early stages of assembly
Authors: Golson Maria L. , Sanger Jean M. , Sanger Joseph W.
Published: June 2004

A three‐step model for myofibrillogenesis has been proposed for the formation of myofibrils [Rhee et al., 1994: Cell Motil. Cytoskeleton 28:1–24; Sanger et al., 2002: Adv. Exp. Med. 481:89–105]: premyofibril to nascent myofibril to mature myofibril. We have found two chemically related inhibitors that will arrest development at both the first and second step. Cultured quail embryonic skeletal myoblasts were treated with ethyl methane sulfonate (EMS) or 2‐aminoethyl‐methanesulfonate (MTSEA+). When the myoblasts fused in the presence of either of these compounds, myosheets rather than myotubes formed. Treated cells were fixed and immunostained against multiple proteins commonly found in muscle cells. Protein expression and localization throughout the myosheet were similar to that of developing myotube tips. Cells treated with high concentrations of EMS (10 mM) stained for non‐muscle myosin II, sarcomeric alpha‐actinin, and tropomyosin. No zeugmatin (Z‐band region of titin) or muscle myosin II antibody staining was detected in fibers in this treatment group. These fibers are comparable to premyofibrils in control myotubes. At lower concentrations of EMS (7.5 to 5 mM), fibers that formed stained for muscle myosin II and titin as well as for non‐muscle myosin IIB, sarcomeric alpha‐actinin, and tropomyosin. Muscle myosin II was in an unbanded pattern. These fibers are comparable to nascent myofibrils observed during normal myofibrillogenesis. Similar effects to those obtained by treating cells with EMS were obtained when we treated cultured cells with MTSEA+ (5 mM) and stained them with sarcomeric alpha‐actinin. MTSEA+ is chemically related to EMS, and is a well‐known inhibitor of ryanodine receptors in skeletal muscle cells. Some abnormalities such as nemaline‐like rods and other protein aggregates also appear within the myosheet during EMS and MTSEA+ treatment. Removal of these two inhibitors of myofibrillogenesis allows the premyofibrils and nascent myofibrils to form mature myofibrils. Cell Motil. Cytoskeleton 59:1–16, 2004. © 2004 Wiley‐Liss, Inc.
Lobular neoplasia on core‐needle biopsy—Clinical significance
Authors: Arpino Grazia , Allred D. Craig , Mohsin Syed Khalid , Weiss Heidi L. , Conrow David , Elledge Richard M.
Published: June 2004

BACKGROUND

Approximately 25% of all cases of atypical ductal hyperplasia (ADH) diagnosed on core biopsy of the breast are associated with ductal carcinoma in situ (DCIS) or invasive malignancy at the same site. As a result, surgical excision has become the standard of care for patients with ADH. In contrast, because data on the relation between breast malignancy and lobular neoplasia (LN) detected on core biopsy are limited, clinical management of patients with LN remains controversial. The goal of the current study was to determine the incidence of breast carcinoma at sites of core biopsy exhibiting LN compared with sites of core biopsy exhibiting ADH.

METHODS

The results of 2053 core biopsies were reviewed to identify cases of LN and cases of ADH. Follow‐up findings on excisional biopsy were categorized as malignancy (DCIS or invasive malignancy) or no malignancy and were compared between the LN group and the ADH group. Mammograms and medical records were reviewed for patients with atypical findings on core biopsy.

RESULTS

One hundred six (5.2%) of 2053 biopsy samples exhibited atypia on core biopsy. Among these 106 samples, ADH was found in 49 (46%), LN was found in 45 (42%), and both ADH and LN were found in 12 (12%). Malignant disease was detected on follow‐up excisional biopsy in 22% of patients with ADH (9 of 41), 14% of patients with LN (3 of 21), and 33% of patients with both ADH and LN (4 of 12) on core biopsy. In the LN group, two cases of malignant disease were associated with lobular carcinoma in situ, and the third case was associated with atypical lobular hyperplasia. Mammographic and clinical features were unable to distinguish patients with malignant findings on excisional biopsy from patients without malignant findings.

CONCLUSIONS

Malignant disease was found in a substantial percentage of excisional biopsy samples (14%) following the detection of LN on core biopsy. Thus, like patients with ADH, patients with LN on core biopsy could be considered candidates for surgical excision, which would allow full assessment of breast carcinoma risk and thereby facilitate the planning of prevention strategies. Cancer 2004. © 2004 American Cancer Society.
Lack of association between amplification of her‐2 and response to preoperative taxanes in patients with breast carcinoma
Authors: Gonzalez‐Angulo Ana M. , Krishnamurthy Savitri , Yamamura Yuko , Broglio Kristine R. , Pusztai Lajos , Buzdar Aman U. , Hortobagyi Gabriel N. , Esteva Francisco J.
Published: June 2004

BACKGROUND

The objective of the current study was to determine whether her‐2 amplification was associated with a pathologic response to preoperative chemotherapy with taxanes in patients with early‐stage breast carcinoma.

METHODS

The authors evaluated 71 patients treated for AJCC Stage II and III breast carcinoma with preoperative taxanes whose tissue specimens were still available. Fifty‐seven patients (80%) had received paclitaxel and 14 (20%) had received docetaxel (4 cycles of either drug). Amplification of the her‐2 gene was determined using fluorescence in situ hybridization.

RESULTS

The median patient age was 49 years (range, 21–70 years). Forty‐eight patients (68%) had Stage II breast carcinoma and 23 (32%) had Stage III disease. her‐2 gene amplification was detected in 19 tumor specimens (28%). Hormone receptors (estrogen and/or progesterone) were detected in 11 her‐2–positive tumor specimens (58%) and in 31 her‐2–negative tumor specimens (85%). Eight pathologic complete responses (pCR; breast and axillary lymph nodes) occurred, 3 (16%) in patients with her‐2–positive tumor specimens and five (10%) in patients with her‐2–negative tumor specimens (P = 0.68). Twelve patients achieved pCR in the breast, 5 (26%) in patients with her‐2–positive tumors and 7 (15%) in patients with her‐2–negative tumors (P = 0.3). At a median follow‐up of 61 months, none of the patients with a pCR developed recurrent disease, regardless of their her‐2 status. The progression‐free and overall survival rates were similar in both HER‐2–positive and her‐2–negative groups (P = 0.45 and P = 0.14, respectively).

CONCLUSIONS

her‐2 gene amplification was not found to be predictive of a pathologic response to preoperative taxanes in patients with early‐stage breast carcinoma. Cancer 2004. © 2004 American Cancer Society.
Malignancy‐related causes of death in human immunodeficiency virus–infected patients in the era of highly active antiretroviral therapy
Authors: Bonnet Fabrice , Lewden Charlotte , May Thierry , Heripret Laurence , Jougla Eric , Bevilacqua Sibylle , Costagliola Dominique , Salmon Dominique , Chêne Geneviève , Morlat Philippe
Published: June 2004

BACKGROUND

Before the introduction of highly active antiretroviral therapy (HAART), malignancies accounted for less than 10% of all deaths among human immunodeficiency virus (HIV)‐infected patients. This figure may have increased, and the observed types of malignant disease may have been modified, as a result of decreased occurrence of opportunistic infections, the chronicity of HIV infection, the possible oncogenic role of HIV itself, and the aging of the HIV‐infected population.

METHODS

All French hospital wards involved in the management of HIV infection were asked to prospectively document the deaths of HIV‐infected patients in the year 2000. Underlying causes of death were defined using a standardized questionnaire.

RESULTS

Of a total of 964 deaths, 269 (28%) were attributable to malignancies. Acquired immunodeficiency virus (AIDS)‐related malignancies were the underlying cause of 149 deaths (15%); among these malignancies were non‐Hodgkin lymphoma (n = 105 [11%]), noncerebral lymphoma (n = 78 [median CD4 count, 86 × 106 per liter; interquartile range [IQR], 35–231 × 106 per liter), and primary cerebral lymphoma (n = 27 [median CD4 count, 20 × 106 per liter; IQR, 4–109 × 106 per liter). Kaposi sarcoma was associated with 40 deaths (4%), and cervical carcinoma was associated with 5 (0.5%). Non‐AIDS‐related malignancies were the underlying cause of 120 deaths (13%); these non‐AIDS‐related malignancies included 103 solid tumors (50 respiratory tumors, 19 hepatocarcinomas, 9 digestive tumors, and 6 anal tumors; median CD4 count, 218 × 106 per liter; IQR, 108–380 × 106 per liter) and 17 hemopathies (12 Hodgkin lymphomas, 4 myeloid leukemias, and 1 myeloma; median CD4 count, 113 × 106 per liter; IQR, 56–286 × 106 per liter). Compared with patients who died of other causes, patients who died of solid tumors were more likely to be male, to smoke, to be older, and to have higher CD4 counts.

CONCLUSIONS

Malignant disease has been a major cause of death among HIV‐infected patients in industrialized nations since the introduction of HAART. Whereas lethal hemopathies and Kaposi sarcoma are associated with advanced immunosuppression, lethal solid tumors can occur in patients with controlled HIV infection. Cancer 2004. © 2004 American Cancer Society.
Intensity‐modulated radiotherapy and the Internet
Authors: Schomas David A. , Milano Michael T. , Roeske John C. , Mell Loren K. , Mundt Arno J.
Published: June 2004

BACKGROUND

The objective of the current study was to evaluate the content and quality of patient‐oriented information regarding intensity‐modulated radiotherapy (IMRT) on the Internet.

METHODS

IMRT websites were identified by reviewing the first 50 uniform resource locators on 5 search engines using the search terms IMRT and intensity modulated radiation therapy. Each site was evaluated by three observers for informational content, presentation, accuracy, and balance. A score of low, moderate, or high was assigned to each category based on a predefined scoring system. An overall score was assigned to each site, ranging from −35 to 100 points.

RESULTS

Seventy‐seven patient‐oriented IMRT websites were identified (45% private, 21% academic, and 18% commercial). Most sites (58%) had a low level of informational content, with information on fundamental aspects of IMRT planning (target delineation and inverse planning) appearing on < 50% of sites. The most commonly discussed tumors were genitourinary (65%) and head and neck (53%) lesions. Few sites, however, described the potential benefits of IMRT (toxicity and tumor control). Most sites (82%) used patient‐appropriate language. False and/or misleading information was seen on 42% of sites and was equally common on academic, private, and commercial sites. Balance statements were present on 24% of sites (most of which were commercial). The median overall score was 20 points (range, −25 to 70 points). The median overall scores for academic, private, commercial, and other sites were 10, 20, 25, and 20 points, respectively (P = 0.26).

CONCLUSIONS

In general, the content and quality of patient‐oriented information regarding IMRT on the Internet were poor. Patients and their physicians need to be aware of these problems when selecting treatment courses. Cancer 2004. © 2004 American Cancer Society.
Estrogen‐metabolizing gene polymorphisms in the assessment of breast carcinoma risk and fibroadenoma risk in Caucasian women
Authors: Hefler Lukas A. , Tempfer Clemens B. , Grimm Christoph , Lebrecht Antje , Ulbrich Eva , Heinze Georg , Leodolter Sepp , Schneeberger Christian , Mueller Manfred W. , Muendlein Axel , Koelbl Heinz
Published: June 2004

BACKGROUND

Genes encoding enzymes involved in estrogen metabolism are held to be candidate genes for associations with breast disease. In these candidate genes, no critical combination of single‐nucleotide polymorphisms (SNPs) for assessing breast carcinoma risk has been reported to date.

METHODS

In a large case–control study, the authors investigated 10 estrogen‐metabolizing SNPs in 396 patients with breast carcinoma, 154 patients with fibroadenoma, and 1936 healthy control patients without breast carcinoma in their personal history. The following 10 SNPs were analyzed using sequencing‐on‐chip technology via a solid‐phase polymerase chain reaction assay performed on oligonucleotide microarrays: catechol‐O‐methyltransferase Val158Met G→A, 17‐beta‐hydroxysteroid dehydrogenase type 1 vIV A→C, cytochrome P‐450 (CYP) family 17 A2 allele T→C, CYP1A1‐1 MspI restriction fragment length polymorphism (RFLP) T→C, CYP1A1‐2 Ile462Val A→G, CYP19‐1 Trp39Arg T→C, CYP19‐2 Arg264Cys C→T, CYP19‐3 Cys1558Thr C→T, steroid‐5‐alpha reductase type 2 Val89Leu G→C, and vitamin D receptor BsmI RFLP. A total of 21,350 genotypes were evaluated. Associations and two‐way interaction models were calculated using stepwise logistic regression.

RESULTS

In a multiple model, CYP1A1‐1 (P = 0.004) and CYP1A1‐2 (P = 0.03) were found to be associated with significantly decreased and increased risks of breast carcinoma, respectively. When two‐way interactions involving investigated SNPs were ascertained, no significant interactions among polymorphisms were noted. Comparison of patients with fibroadenoma with control patients revealed significantly increased and decreased risks of fibroadenoma when the mutant alleles of CYP17 (P = 0.02) and CYP1A1‐1 (P = 0.04), respectively, were present.

CONCLUSIONS

The authors obtained the first SNP data indicating that CYP17 and CYP1A1‐1 play a role in the pathogenesis of fibroadenoma. Although the authors were not able to develop interaction models involving SNPs, they did provide evidence that CYP1A1 is a low‐penetrance susceptibility gene with respect to breast carcinoma in a large series of Caucasian women. Cancer 2004. © 2004 American Cancer Society.
Phase II study of high‐dose fish oil capsules for patients with cancer‐related cachexia
Authors: Burns C. Patrick , Halabi Susan , Clamon Gerald , Kaplan Ellen , Hohl Raymond J. , Atkins James N. , Schwartz Michael A. , Wagner Brett A. , Paskett Electra
Published: June 2004

BACKGROUND

The authors undertook a multiinstitutional Phase II cooperative group study to examine the potential of oral fish oil fatty acid supplements administered at high doses to slow weight loss and to improve quality of life in patients with malignancy‐related cachexia.

METHODS

Patients with advanced malignancy and weight loss ≥ 2% of body weight in the preceding month took concentrated, high‐dose omega‐3 fatty acid capsules (7.5 g eicosapentaenoic acid plus docosahexaenoic acid for a 70 kg individual) that were supplied by the National Institutes of Health.

RESULTS

Forty‐three patients with moderate or severe malnutrition were enrolled. The median time receiving treatment was 1.2 months. For the 36 patients who took at least 1 capsule and did not have edema, there was a weight change ranging from −6.2 kg to +3.5 kg and an overall median weight loss of 0.8 kg. Twenty‐four patients had weight stabilization (a gain of ≤ 5% or a loss of < 5%), 6 patients gained > 5% of their body weight, and 6 patients lost ≥ 5% of their body weight. There was marked variability in the tolerability of the capsules, and many patients had gastrointestinal side effects. There was a correlation between time receiving treatment and weight gain for the 22 patients who were able to tolerate the capsules for at least 1 month. Quality‐of‐life scores were superior for patients who gained weight.

CONCLUSIONS

A majority of patients did not gain weight, and in that sense, the results of the study were unfavorable. However, a small but definite subset of patients had weight stabilization or weight gain. This suggests that omega‐3 fatty acids have potential utility at the study doses, which were more than twice the doses used in published Phase III studies. Cancer 2004. © 2004 American Cancer Society.
Anal cancer incidence and survival: The Surveillance, Epidemiology, and End Results experience, 1973–2000
Authors: Johnson Lisa G. , Madeleine Margaret M. , Newcomer Laura M. , Schwartz Stephen M. , Daling Janet R.
Published: June 2004

BACKGROUND

Anal cancer is a rare malignancy of the anogenital tract that historically has affected women at a greater rate than men.

METHODS

The authors analyzed changing trends in incidence rates and 5‐year relative survival percentages for patients with anal cancer. The publicly available data used in the current study were obtained from the Surveillance, Epidemiology, and End Results (SEER) Program, a system of population‐based tumor registries in the United States.

RESULTS

The incidence of anal cancer was similar for men and women between 1994 and 2000 (2.04 per 100,000 and 2.06 per 100,000, respectively), the most recent period for which data were available, whereas men had lower rates than did women between 1973 and 1979 (1.06 per 100,000, compared with 1.39 per 100,000), the earliest period for which data were available. In addition, recently, black men had higher incidence rates than did other race‐specific and gender‐specific groups (2.71 per 100,000). From the earliest period for which data were available to the most recent period, relative 5‐year survival improved from 59% to 73% among women, was unchanged among men (∼60%), and decreased from 45% to 27% among black men. Eighteen percent of patients who had distant disease were alive at 5 years, compared with 78% of patients who had localized disease.

CONCLUSIONS

The incidence of anal cancer in the United States increased between 1973 and 2000, particularly among men. There were higher incidence rates and lower survival rates for black men compared with other race‐specific and gender‐specific groups. Later disease stage was inversely associated with the survival rate, indicating that earlier detection may improve the survival of patients with anal cancer. Cancer 2004. © 2004 American Cancer Society.
Prognostic impact of hemoglobin levels on treatment outcome in patients with nasopharyngeal carcinoma treated with sequential chemoradiotherapy or radiotherapy alone
Authors: Chua Daniel T. T. , Sham Jonathan S. T. , Choy Damon T. K.
Published: June 2004

BACKGROUND

The goal of the current study was to investigate the impact of hemoglobin (Hb) levels on treatment outcome in a randomized Phase III trial of patients with nasopharyngeal carcinoma (NPC) treated with induction chemotherapy followed by radiotherapy or with radiotherapy alone.

METHODS

Between September 1989 and August 1993, 334 patients with advanced NPC were entered into a randomized trial comparing 3 cycles of induction chemotherapy (cisplatin and epirubicin) followed by radiotherapy with radiotherapy alone. Only evaluable patients who completed radiation were included in the analysis (n = 286). Patients were stratified into normal and low Hb groups according to baseline, preradiation, and midradiation Hb levels. Local recurrence–free, distant metastasis–free, and disease‐specific survival rates were estimated using the Kaplan–Meier method. Multivariate analysis was performed using the Cox model.

RESULTS

In the chemotherapy arm, the mean baseline, preradiation, and midradiation Hb levels were 13.6, 11.0, and 11.8 g/dL, respectively. In the radiotherapy arm, the mean baseline/preradiation and midradiation Hb levels were 13.7 and 12.9 g/dL, respectively. A midradiation Hb level ≤ 11 g/dL was associated with significantly poorer 5‐year local recurrence–free (60% vs. 80%; P = 0.0059) and disease‐specific survival rates (51% vs. 68%; P = 0.001), with no difference in distant metastasis–free rates (69% vs. 67%; P = 0.83). No significant difference in treatment outcome according to baseline or preradiation Hb levels was noted. Multivariate analysis showed that a low midradiation Hb level, but not a low baseline or preradiation Hb level, was an independent predictor of local disease recurrence and malignancy‐related death.

CONCLUSIONS

The current study showed that midradiation Hb level was an important prognostic factor with respect to local control and survival in patients with NPC. The high incidence of anemia after chemotherapy has a negative impact on treatment outcome, and this condition may reduce the benefit of induction chemotherapy. Attempts to correct anemia during radiation and the impact of anemia on treatment outcome requires further study. Cancer 2004. © 2004 American Cancer Society.
Familial risk and clustering of nasopharyngeal carcinoma in Guangdong, China
Authors: Jia Wei‐Hua , Feng Bing‐Jian , Xu Zong‐Li , Zhang Xiao‐Shi , Huang Ping , Huang Li‐Xi , Yu Xing‐Juan , Feng Qi‐Sheng , Yao Ming‐Hong , Shugart Yin Yao , Zeng Yi‐Xin
Published: June 2004

BACKGROUND

Previous studies have suggested that genetic susceptibility may play an important role in the etiology of nasopharyngeal cancer (NPC). However, to date, few large‐scale studies have been conducted on familial risk and clustering of NPC in a high‐risk area of China.

METHODS

In the current study, 2252 patients with NPC who were treated at the Cancer Center of Sun Yat‐Sen University in Guangdong Province, China, were identified as probands. Family histories of NPC and other malignancies were observed in first‐degree relatives (FDRs) and second‐degree relatives, and other information was obtained through interviews. One thousand nine hundred and three Cantonese families were selected for further investigation. To assess familial aggregation, the authors used standardized incidence ratios (SIRs) to measure the risk of NPC for FDRs and compared the observed number of cases with the number predicted by population‐based frequencies in the Cantonese population of Hong Kong.

RESULTS

The current analysis indicated that families with ≥ 3 relatives who had NPC were distributed predominantly among a high‐risk subgroup of the Cantonese population in Guangdong Province and that the frequency of these families was 0.68%. An SIR of 2.09 (95% confidence interval [CI], 1.80–2.40) was observed among 13,833 FDRs in the high‐risk subgroup, and a significantly elevated risk for NPC was observed in FDRs of probands with early age of onset (age < 40 years; SIR, 9.01 [95% CI, 6.10–13.30]). Furthermore, decreased risks of hepatic, lung, esophageal, gastric, and breast carcinoma, as well as malignancy of all sites, were observed among FDRs of probands with NPC when Hong Kong and Shanghai populations were used as reference groups.

CONCLUSIONS

NPC tends to aggregate in Cantonese families in Guangdong Province, and the malignancies in these families appear to be site specific, with no excess of any other malignancy. Cancer 2004. © 2004 American Cancer Society.
Genetic polymorphisms in the human growth hormone‐1 gene (GH1) and the risk of breast carcinoma
Authors: Ren Zefang , Cai Qiuyin , Shu Xiao‐Ou , Cai Hui , Cheng Jia‐Rong , Wen Wan‐Qing , Gao Yu‐Tang , Zheng Wei
Published: June 2004

BACKGROUND

In addition to possessing many physiologic functions, human growth hormone‐1 (GH1) has been shown in recent in vitro and in vivo experiments to induce malignant disease, including breast carcinoma. The authors investigated the association of breast carcinoma with genetic polymorphisms in the GH1 gene in the Shanghai Breast Cancer Study.

METHODS

Included in the current investigation were 1193 women with breast carcinoma (case patients) and 1310 healthy women from the same community (control patients) who completed in‐person interviews and provided blood samples. Genetic polymorphisms in the proximal promoter region (nucleotide [nt] −162 to nt +148 relative to the transcription start site of the GH1 gene) were searched and confirmed by resequencing DNA samples from 43 study participants. A novel polymorphism, a transition from adenine to guanine at nt 69 (A69G), was identified. Samples from all participants were genotyped with TaqMan 5′ nuclease assays for five common single‐nucleotide polymorphisms (SNPs)—four in the proximal region (A‐75G, G‐57T, A‐6G, and A69G) and one in intron 4 (T1169A).

RESULTS

The frequencies of occurrence for the minor alleles in these polymorphic sites were 0.04, 0.60, 0.24, 0.03, and 0.34, respectively, in the control group; these frequencies were comparable to those observed in the case group. After adjusting for potential confounding factors, none of the SNPs investigated in this study showed a statistically significant association with breast carcinoma risk. This null association was found for both younger women (age < 45 years) and older women (age ≥ 45 years). GH1 gene haplotypes were assessed using SNP data and were analyzed in relation to breast carcinoma risk. Again, none of the haplotypes were associated with breast carcinoma risk.

CONCLUSIONS

The results of the current study suggest that genetic polymorphisms in the proximal promoter region and in the fourth intron of the GH1 gene are unrelated to breast carcinoma risk in Chinese women. Cancer 2004. © 2004 American Cancer Society.
Clinical utility of serum amyloid A and macrophage migration inhibitory factor as serum biomarkers for the detection of nonsmall cell lung carcinoma
Authors: Khan Nayela , Cromer Charles J. , Campa Michael , Patz Edward F.
Published: June 2004

BACKGROUND

Early lung carcinoma detection strategies involving imaging studies have yet to demonstrate a reduction in mortality. Identification of serum biomarkers that could complement radiologic studies and facilitate earlier diagnosis of lung carcinoma would be of significant benefit to patients. In the current pilot study, the authors evaluated two overexpressed proteins in lung carcinoma, serum amyloid A (SAA) and macrophage migration inhibitory factor (MIF), as potential diagnostic serum biomarkers for this malignancy.

METHODS

Serum levels of SAA and MIF were measured in 50 patients using enzyme‐linked immunosorbent assays. The sensitivity, specificity, and accuracy of the markers in detecting lung carcinoma were determined.

RESULTS

SAA levels in patients with lung carcinoma were greater than in the control patients (P = 0.07). Serum SAA levels did not exhibit a correlation with tumor size or clinical stage and were higher in patients with squamous cell carcinoma than in patients with other histologic disease types. MIF was unable to differentiate patients with lung carcinoma from patients with other diseases.

CONCLUSIONS

SAA possesses potential utility as a serum biomarker for lung carcinoma, probably in conjunction with other serum markers that improve its diagnostic accuracy. Before a larger study is performed, the discovery of additional biomarkers to enhance the specificity of SAA in the diagnosis of lung carcinoma is recommended. Cancer 2004. © 2004 American Cancer Society.
Novel therapies for myelodysplastic syndromes
Authors: Faderl Stefan , Kantarjian Hagop M.
Published: June 2004

BACKGROUND

The assessment of patients with myelodysplastic syndromes (MDS) and the choice of therapies remain challenging. New therapies are now emerging after the identification of molecular targets that result in improvement of hematologic parameters and may hold promise for the prevention of disease progression.

METHODS

A review of the English literature was performed that included original articles and related reviews from MEDLINE (PubMed) and abstracts based on published meeting material.

RESULTS

MDS is a heterogeneous group of disorders. Although current classification and prognostic schemes have proven valid to define subgroups, they are insufficient to take into consideration the significant biologic diversity of MDS. New molecular targets are identified as the mosaic of pathophysiologic pathways in MDS is being unraveled. Novel and targeted therapeutic agents, such as the inhibition of farnesyl transferases and receptor tyrosine kinases, more potent thalidomide analogs, and arsenic trioxide, have shown encouraging results and may offer durable benefit to patients with MDS.

CONCLUSIONS

Although progress has been made in the understanding of clinical manifestations and some of the molecular pathways underlying ineffective hematopoiesis and leukemic transformation in MDS, intensive clinical and laboratory research continues to 1) identify further relevant pathophysiologic pathways, 2) better define MDS subgroups, and 3) develop new drugs based on a clearer understanding of disease biology. Cancer 2004. © 2004 American Cancer Society.
Long‐term results of the first Italian Association of Pediatric Hematology and Oncology protocol for the treatment of pediatric B‐cell non‐Hodgkin lymphoma (AIEOP LNH92)
Authors: Pillon Marta , Di Tullio Maria Teresa , Garaventa Alberto , Cesaro Simone , Putti Maria Caterina , Favre Claudio , Lippi Alma , Surico Gianmarco , Di Cataldo Andrea , D'Amore Emanuele , Zanesco Luigi , Rosolen Angelo
Published: June 2004

BACKGROUND

Childhood B‐cell lymphomas (B‐NHLs) represent a group of aggressive malignancies that are amenable to high‐intensity chemotherapy regimens. In 1992, the Italian Association of Pediatric Hematology and Oncology (AIEOP) initiated a prospective clinical trial involving the diagnosis and treatment of childhood B‐NHL based on a well established strategy developed by the Berlin–Frankfurt–Munster Group.

METHODS

Between November 1992 and October 1997, 163 children who had B‐NHL were treated prospectively in the first national AIEOP trial. Disease staging was performed according to the St. Jude staging system, and treatment was assigned on the basis of risk group (R1, R2, or R3), which took into account disease stage and resectability and serum lactate dehydrogenase (LDH) levels.

RESULTS

Of the 144 evaluable patients, 11 had Stage I disease, 35 had Stage II disease, 76 had Stage III disease, and 22 had Stage IV disease. Thirteen, 54, and 77 patients were included in risk groups R1, R2, and R3, respectively. The 10‐year overall survival (OS) and event‐free survival (EFS) rates for the overall population were 89.4% and 81.8%, respectively; the EFS rates for patients in risk groups R1, R2, and R3 were 100%, 86.9%, and 75.1%, respectively. Multivariate analysis indicated that age ≥ 10 years, disease histology other than Burkitt or Burkitt‐like lymphoma, and LDH levels ≥ 1000 international units per liter had negative prognostic value. Analysis of the toxicity (according to the World Health Organization grading system) associated with 710 of the 748 chemotherapy cycles administered revealed 855 cases of Grade 3 or 4 toxicity, with 73% being cases of hematologic toxicity. Toxic episodes were most common after the first chemotherapy cycle and were equally common in the R2 and R3 risk groups. To date, the development of a second malignancy has not been observed in any patient in the study cohort.

CONCLUSIONS

Long‐term follow‐up of the current study (AIEOP LNH92) confirms the observation of a favorable outcome for patients with B‐NHL treated with short, intensive chemotherapy regimens and raises the possibility that non‐Burkitt or non‐Burkitt‐like histology and age ≥ 10 years may have negative prognostic value for patients with childhood B‐NHL. Cancer 2004. © 2004 American Cancer Society.
Predictors of place of death for Japanese patients with advanced‐stage malignant disease in home care settings: A nationwide survey
Authors: Fukui Sakiko , Fukui Naoshi , Kawagoe Hiromi
Published: June 2004

BACKGROUND

Although the place of death for patients with advanced malignancy is influenced by multiple factors, few studies have systematically investigated the determinants of place of death. The objective of the current retrospective study was to clarify the predictors of home death throughout the duration of home palliative care for Japanese patients with advanced malignant disease.

METHODS

In the current nationwide survey, the authors investigated predictors involving patient demographics and clinical profiles, the roles and status of family caregivers, and the support provided by the healthcare system in the introductory phase (during the first week of home care), the stable phase (between the introductory and dying phases), and the dying phase (during the final week before death) of home care service in Japan.

RESULTS

Multivariate logistic regression models clarified that 1) patient‐related clinical variables (e.g., functional status and rehospitalization); 2) the support of the healthcare system (e.g., provision of information on the dying process and visitation by home care nurses); and 3) the status and roles of family caregivers (e.g., psychologic distress levels, assistance with patient evacuation, etc.) have an effect on place of death throughout all three phases of home palliative care. Overall, the model used in the current study was able to predict 94% of home deaths accurately.

CONCLUSIONS

A clearer understanding of factors that may influence place of death for patients with advanced‐stage malignant disease would allow healthcare professionals to modify healthcare systems and tailor effective interventions to help patients die in their preferred location. Cancer 2004. © 2004 American Cancer Society.
Reduction in hippocampal cholinergic innervation is unrelated to recognition memory impairment in aged rhesus monkeys
Authors: Calhoun Michael E. , Mao Ying , Roberts Jeffrey A. , Rapp Peter R.
Published: June 2004

Alterations in the basal forebrain cholinergic system have been widely studied in brain aging and Alzheimer's disease, but the magnitude of decline and relationship to cognitive impairment are still a matter of debate. The rhesus monkey (Macaca mulatta) provides a compelling model to study age‐related memory decline, as the pattern of impairment closely parallels that observed in humans. Here, we used antibodies against the vesicular acetylcholine transporter and a new stereological technique to estimate total cholinergic fiber length in hippocampal subregions of behaviorally characterized young and aged rhesus monkeys. The analysis revealed an age‐related decline in the length of cholinergic fibers of 22%, which was similar across the hippocampal subregions studied (dentate gyrus granule cell and molecular layers, CA2/3‐hilus, and CA1), and across the rostral–caudal extent of the hippocampus. This effect, however, was unrelated to performance on the delayed nonmatching‐to‐sample task, a test of recognition memory sensitive to hippocampal system dysfunction and cognitive aging in monkeys. These findings indicate that a decline in cholinergic input fails to account for the influence of normal aging on memory supported by the primate hippocampal region. J. Comp. Neurol. 475:238–246, 2004. © 2004 Wiley‐Liss, Inc.
Postnatal apoptosis, development, and sex difference in the lateral septum of rats
Authors: Tsukahara Shinji , Inami Kouichi , Maekawa Fumihiko , Kakeyama Masaki , Yokoyama Toshifumi , Yuji Midori , Kitagawa Hiroshi , Kannan Yasuyuki , Yamanouchi Korehito
Published: June 2004

To determine whether apoptosis is involved in the formation of the structure and morphological sex difference of the lateral septum (LS), the postnatal developmental changes in the number of apoptotic cells were examined in the LS on postnatal day 1 (PD1 = birth day), 4, 6, 8, 11, 16, and 31 in male and female rats. Apoptotic cells were immunohistochemically detected by antibody against single‐stranded DNA (ssDNA) or active caspase‐3. The volume of the LS was also measured and was found to increase with age. The number of apoptotic cells detected by anti‐ssDNA in the LS increased from PD1 to PD8 but decreased after PD11. Also, the LS was divided into dorsal, intermediate, and ventral parts (LSd, LSi, and LSv), and the volume and number of ssDNA‐immunoreactive cells in each part were measured on PD6, 8, 11, 16, and 31. In both sexes, a large number of ssDNA‐immunoreactive cells was found in the LSd and LSi on PD8 (but not on PD6) and in the LSv on PD6 and PD8. On PD6, the number of active caspase‐3‐immunoreactive cells was significantly greater in the LSv than in the LSd or LSi, in both sexes. Only the LSi of males had a high number of ssDNA‐immunoreacitve cells on PD16; the number was significantly greater than that of females of the same age. However, there was no significant sex difference in the number of active caspase‐3‐immunoreacitve cells in the LSi on PD16. On PD31, the volume of the LSi was significantly greater in females than in males. There was no sex difference in volume or number of apoptotic cells in the LSd or LSv. These findings indicate that loss of cells due to apoptosis, which is partially caused by activation of caspase‐3, occurs in the LS during postnatal development, with regional differences. They also indicate that sex difference in caspase‐3‐independent apoptosis contributes to morphological sexual differentiation of the LSi. J. Comp. Neurol. 475:177–187, 2004. © 2004 Wiley‐Liss, Inc.
Juxtacapsular nucleus of the stria terminalis of the adult rat: Extrinsic inputs, cell types, and neuronal modules: A combined Golgi and electron microscopic study
Authors: Larriva‐Sahd Jorge
Published: June 2004

This study unravels the microscopic organization of the juxtacapsular nucleus of the bed nuclei of the stria terminalis (Ju) by using silver impregnation and electron microscopic techniques. Examination of Golgi‐impregnated specimens demonstrates that the Ju has precise boundaries primarily determined by a conical condensation of fibers of the stria terminalis (StT) around the nucleus. The internal capsule, ansa peduncularis, and medial forebrain bundle together with the StT provide extrinsic afferents to the neuropil of the Ju. Two main neuron types are found in the Ju: interneurons (including basket and neurogliaform cells) and projection neurons (bipolar and small pyramidal cells). The bipolar cell type accounts for about 80% of the sampled neurons. Short‐axon neurons located within the dorsal part of the Ju send descending fibers that appear to terminate on the bipolar neurons, suggesting the existence of vertically oriented functional units within the nucleus. With the electron microscope, Ju neurons are seen in clusters of two or three neurons coupled by gap junctions. The neuropil contains numerous dendrites, axons, myelinated axons, and several types of synaptic interactions, including axospinous, axoshaft, and axosomatic. Within the neuropil, Ju neurons appear to be presynaptically modulated by axoaxonal interactions. The present findings suggest a model wherein bipolar neurons represent the output system of the Ju controlled by the interneurons, which would, in turn, be modulated by collaterals arising from the tributary fiber tracts. Additional neural interaction between Ju neurons utilizes gap junction‐mediated electrotonic coupling. J. Comp. Neurol. 475:220–237, 2004. © 2004 Wiley‐Liss, Inc.
Large deviations for random walks in a mixing random environment and other (non‐Markov) random walks
Authors: Rassoul‐Agha F.
Published: June 2004

We extend a recent work by S. R. S. Varadhan [8] on large deviations for random walks in a product random environment to include more general random walks on the lattice. In particular, some reinforced random walks and several classes of random walks in Gibbs fields are included. © 2004 Wiley Periodicals, Inc.
Transverse Dephasing Optimised NMR Spectroscopy in Solids: Natural‐Abundance 13C Correlation Spectra
Authors: De Paëpe Gaël , Lesage Anne , Steuernagel Stefan , Emsley Lyndon
Published: June 2004

The transverse dephasing optimized (TDOP) approach can be used to obtain heteronuclear decoupling sequences that increase significantly coherence lifetimes in solid‐state NMR spectroscopy, leading to a dramatic improvement in the sensitivity of correlation experiments. Herein we demonstrate experimentally on several model organic compounds that, by applying this procedure, solid‐state 13C‐refocused INADEQUATE experiments are feasible at natural abundance on medium‐sized molecules. Examples are provided for powdered crystalline cholesteryl acetate as well as for a sample of brucine, a less ordered compound. Effects of molecular dynamics on the sensitivity of the experiment are also discussed for a sample of tyrosine ethyl ester.
Complex Morphology of Melt‐Spun Nylon‐6 Fibres Investigated by1H Double‐Quantum‐Filtered NMR Spin‐Diffusion Experiments
Authors: Buda A. , Demco D. E. , Blümich B. , Litvinov V. M. , Penning J. P.
Published: June 2004

The complex morphology of high‐speed melt‐spun nylon‐6 fibres hydrated with D2O was investigated using1H double‐quantum‐filtered spin‐diffusion NMR experiments. The magnetisation exchange from selected crystalline domains along the fibrils and interfibrils was simulated with the help of a three‐dimensional solution of a spin‐diffusion equation approximated by a product of one‐dimensional analytical NMR signals, which correspond to a lamellar morphology. This allows to measure the sizes of crystalline and less‐mobile amorphous domains along the fibrils, as well as the diameter of the fibrils and interfibril distances. A series of nylon‐6 fibres with extreme values of winding speed and draw ratio was investigated. The changes detected in the domain size along the fibrils and interfibrils show the same trend in the data obtained from wide‐angle X‐ray diffraction and small‐angle X‐ray scattering.
Principles of Spin‐Echo Modulation by J‐Couplings in Magic‐Angle‐Spinning Solid‐State NMR
Authors: Duma Luminita , Lai Wai Cheu , Carravetta Marina , Emsley Lyndon , Brown Steven P. , Levitt Malcolm H.
Published: June 2004

In magic‐angle‐spinning solid‐state NMR, the homonuclear J‐couplings between pairs of spin‐1/2 nuclei may be determined by studying the modulation of the spin echo induced by a π‐pulse, as a function of the echo duration. We present the theory of J‐induced spin‐echo modulation in magic‐angle‐spinning solids, and derive a set of modulation regimes which apply under different experimental conditions. In most cases, the dominant spin‐echo modulation frequency is exactly equal to the J‐coupling. Somewhat surprisingly, the chemical shift anisotropies and dipole–dipole couplings tend to stabilise—rather than obscure—the J‐modulation. The theoretical conclusions are supported by numerical simulations and experimental results obtained for three representative samples containing 13C spin pairs.
High‐Performance Selective Excitation Pulses for Solid‐ and Liquid‐State NMR Spectroscopy
Authors: Veshtort Mikhail , Griffin Robert G.
Published: June 2004

Computer‐optimized selective pulses are routinely used in solution‐state NMR spectroscopy. At the same time, their utility and importance for solid‐state applications has yet to be fully realized. We suggest a new computational approach that makes the design of soft selective pulses with desired properties relatively straightforward. By applying this technique to the generic selective excitation problem, we have arrived at a family of high performance selective excitation pulses, dubbed E‐Family, that allows more flexibility and better performance than analogous pulses previously reported in the literature. The new pulses have been successfully tested in both solid‐ and solution‐state NMR experiments. A theoretical treatment of the effects of chemical shift anisotropy (CSA) on the selective excitation in magic‐angle spinning (MAS) experiments in solids is presented. The set of heuristics that comprise our new strategy were incorporated into a general NMR simulation program SPINEVOLUTION.