bluuebunny/crossref_metadata_2025_split huggingface dataset:
Soft tissue sarcoma as a second malignant neoplasm in the pediatric age group
Authors: Bisogno Gianni , Sotti Guido , Nowicki Yohann , Ferrari Andrea , Garaventa Alberto , Zanetti Ilaria , Favre Claudio , Schiavetti Amalia , Tamaro Paolo , Carli Modesto 
Published: March 2004

AbstractBACKGROUNDSurvivors of childhood malignancies have an increased risk of developing second malignant neoplasms (SMN) due to their prior treatment and/or genetic susceptibility. A small proportion of SMNs are soft tissue sarcomas (STS), whose prognosis is generally thought to be poor, though publications on such patients' treatment and outcome is limited.METHODSThe authors analyzed 25 patients who were registered for the Italian Cooperative Group protocols for pediatric STS from 1979 to 2000. The primary tumor was STS in five patients; Hodgkin disease in five patients; leukemia in four patients; retinoblastoma, neuroblastoma, and Wilms tumor in two patients each; and other tumor types in five patients. SMNs occurred after a median of 8 years (range, 1.9–15.0 years) and included rhabdomyosarcoma (RMS) in 4 patients, malignant peripheral nerve sheath tumor in 4 patients, extraosseous Ewing family tumor (EFT) in 4 patients, leiomyosarcoma in 3 patients, fibrosarcoma in 2 patients, synovial sarcoma in 2 patients, and other tumor types in 6 patients. Treatment generally was administered according to the guidelines for primary STS.RESULTSSeven non‐RMS patients with STS underwent surgery alone, whereas 18 patients received chemotherapy and 8 patients received radiotherapy. Retreatment was feasible with acceptable toxicity. Fifteen patients were alive in complete remission of their SMN at the time of last follow‐up. Responses to chemotherapy and survival were satisfactory for patients with tumors such as RMS and EFT. Complete tumor resection was correlated with a favorable prognosis in patients with other types of STS and in patients with postirradiation sarcoma. Two patients developed a third malignancy.CONCLUSIONSAlthough prior treatment may hinder the management of these patients, pediatric STS second malignancies can be cured using the same strategies used for de novo pediatric sarcomas. Long‐term follow‐up is mandatory given the risks of further malignancies and more severe, treatment‐related side effects. Cancer 2004. © 2004 American Cancer Society.
p53 apoptotic pathway molecules are frequently and simultaneously altered in nonsmall cell lung carcinoma
Authors: Mori Shoichi , Ito Genshi , Usami Noriyasu , Yoshioka Hiromu , Ueda Yuichi , Kodama Yoshinori , Takahashi Masahide , Fong Kwun M. , Shimokata Kaoru , Sekido Yoshitaka 
Published: March 2004

AbstractBACKGROUNDLung carcinomas show frequent inactivation of the p53 tumor suppressor, which regulates an apoptotic pathway. The objective of the current study was to assess how the p53 apoptotic pathway is altered in nonsmall cell lung carcinoma (NSCLC), especially in tumors without p53 alterations.METHODSp53, its upstream regulators (p14ARF and HDM2), and downstream effectors of the apoptotic pathway (BAX and BCL2) were studied in 118 NSCLC specimens. p53 was analyzed by single‐stranded conformation polymorphism analysis covering exons 2–11 and by immunohistochemistry (IHC). p14ARF was analyzed by methylation‐specific polymerase chain reaction and IHC. HDM2 was analyzed using Southern blot analysis and IHC. BAX and BCL2 were analyzed by IHC. Two other upstream regulators that regulate the stability of HDM2, PTEN and HAUSP, also were studied.RESULTSOf 118 NSCLC specimens that were analyzed, p53 alterations were detected in 74 tumors (63%), p14ARF inactivation was detected in 53 tumors (45%), and overexpression of HDM2 was found in 31 tumors (26%), including 6 tumors with gene amplification. Although p53 inactivation and HDM2 overexpression were detected simultaneously, HDM2 gene amplification was observed only in tumor specimens without p53 mutations. IHC revealed PTEN down‐regulation in 22 of 88 tumors (25%). HAUSP Northern blot analysis demonstrated several‐fold differences in gene expression that did not correlate with p53 alterations. Of 118 NSCLC specimens, expression of BAX and BCL2 expression were detected in 46 tumors (39%) and 17 tumors (14%), respectively. Finally, ASPP1 and ASPP2, molecules involved in mediating the transcription function of p53, were not found to be aberrantly expressed when tested by Northern blot analysis.CONCLUSIONSOverall, two or more p53 pathway components were found to be frequently altered in patients with NSCLC. Greater than 90% of the alterations were due to abnormalities of p53, p14ARF, or HDM2. Therefore, the inactivation of one or more components of the p53 pathway appears to be a prerequisite for the development of most NSCLCs. Cancer 2004. © 2004 American Cancer Society.
Mature results of a phase III randomized trial of bacillus Calmette–Guerin (BCG) versus observation and BCG plus dacarbazine versus BCG in the adjuvant therapy of American Joint Committee on Cancer Stage I–III melanoma (E1673)
Authors: Agarwala Sanjiv S. , Neuberg Donna , Park Yuhyun , Kirkwood John M. 
Published: March 2004

AbstractBACKGROUNDThe local and systemic effects of bacillus Calmette–Guerin (BCG) have been known for decades. To investigate the adjuvant effect of BCG on resected American Joint Committee on Cancer (AJCC) Stage I–III melanoma, the Eastern Cooperative Oncology Group conducted a large trial to study the use of BCG alone or a combination of BCG and dacarbazine between 1974 and 1978.METHODSA total of 734 patients were randomized to 4 clinical groups consolidated into 2 cohorts. Cohort I compared BCG with observation and Cohort II compared BCG with a combination of BCG and dacarbazine. The primary end points were survival time and time to disease progression.RESULTSWithin Cohort I, no statistically significant difference in disease‐free survival (DFS) (P= 0.84) or overall survival (OS) (5‐year survival 67% vs. 62%;P= 0.40) was observed between BCG treatment and observation. Within Cohort II, the addition of dacarbazine to BCG did not improve DFS (P= 0.74) or OS (P= 0.81) compared with BCG alone. Toxicity was mild to moderate in both cohorts. Although toxicity with this agent is mild, the use of BCG is associated with the development of punctate abscesses in greater than two‐thirds of patients treated.CONCLUSIONSIn what to our knowledge is the largest ever trial to test the role of BCG as adjuvant therapy for melanoma, no benefit for BCG was observed for patients with AJCC Stage I–III disease. The mature results of the current trial projected to 30 years confirmed the negative results of previous smaller studies utilizing this agent. Cancer 2004. © 2004 American Cancer Society.
Stereotactic radiosurgery for multiple brain metastases from breast carcinoma
Authors: Muacevic Alexander , Kreth Friedrich W. , Tonn Jörg‐Christian , Wowra Berndt 
Published: March 2004

AbstractBACKGROUNDThe current study analyzed the feasibility and outcome of stereotactic radiosurgery (SRS) for treatment of brain metastases from breast carcinoma.METHODSDuring an 8‐year period, 151 patients with a combined total of 620 brain metastases from breast carcinoma underwent 197 outpatient SRS procedures. Sixty‐three percent of all patients had multiple brain metastases. The median tumor volume was 2.2 cm3 (range, 0.1–20.9 cm3). The mean prescribed tumor dose was 19 ± 4 grays. Local/distant tumor recurrences were treated with additional radiosurgical therapy for patients with stable systemic disease. All patients were categorized according to the Radiation Therapy Oncology Group classification. Survival time and freedom from local tumor recurrence were analyzed using the Kaplan–Meier method. Prognostic factors were identified using the Cox proportional hazards model.RESULTSThe overall median survival duration was 10 months after SRS. Ninety‐four percent of patients did not experience local brain tumor recurrence after radiosurgery. In addition, 70.2% of patients did not have disease recurrence in the brain. Most patients died of systemically progressing malignancy. A Karnofsky performance score > 70 and recursive partitioning analysis Class I were related to prolonged survival in the univariate and multivariate analyses. Age, whole‐brain radiotherapy, surgery, number of metastases, chemotherapy, and latency period from diagnosis of the primary tumor to the development of brain metastases did not reach prognostic relevance in the multivariate model. Patients with RPA I, II, and III survived 34.9, 9.1, and 7.9 months, respectively. There was no treatment related permanent morbidity and mortality. The transient morbidity rate was 17%. Sixteen patients exhibited symptomatic transient complications related to treatment.CONCLUSIONSThe results of the current study indicate that SRS is a feasible treatment concept for selected patients with multiple brain metastases from breast carcinoma. Cancer 2004. © 2004 American Cancer Society.
Sentinel lymph nodes in malignant melanoma
Authors: Abrahamsen Helene Nortvig , Hamilton‐Dutoit Stephen J. , Larsen Jørn , Steiniche Torben 
Published: March 2004

AbstractBACKGROUNDThe optimal technique for sentinel lymph node (SN) assessment in patients with melanoma is controversial. Molecular analysis (reverse transcriptase–polymerase chain reaction) detects significantly greater numbers of SNs with suspected micrometastases (up to 71%) than does routine histopathology (approximately 20%). The authors sought to identify possible reasons for this discrepancy and to determine whether using an extended histopathologic protocol could improve diagnostic precision.METHODSTwo hundred thirty‐one SNs from 100 consecutive patients with cutaneous melanomas that measured 1–4 mm in thickness were bisected, and half of the lymph node was examined according to an extensive histopathologic protocol involving serial sectioning and immunohistochemical analysis of 3 melanocyte‐associated markers (S‐100, HMB‐45, and Melan‐A).RESULTSLymph node melanocytic lesions were frequent, with micrometastases and benign nevus inclusions (BNI) found in SNs in 28% and 28% of patients, respectively (4 SNs contained both). Melan‐A was the most sensitive immunohistochemical marker and was positive in all BNI‐positive SNs and 97% of micrometastasis‐positive SNs. Although HMB‐45 showed differential labeling in micrometastases compared with BNI (82% vs. 16%), immunohistochemistry could not distinguish between those lesions. Micrometastases were already identified on the first central level in 49% of positive SNs, whereas only 23% of SNs with BNI were diagnosed on the first level.CONCLUSIONSExtensive serial sectioning with immunohistochemical analysis substantially increased the histopathologic detection of micrometastases and BNI in melanoma SNs to a level approaching the level reported for molecular techniques. The large number of BNIs represents an important potential source of imprecision (false positivity) in SN assays based on nonmorphologic methods. Cancer 2004. © 2004 American Cancer Society.
Nuclear factor‐KappaB modulation as a therapeutic approach in hematologic malignancies
Authors: Panwalkar Amit , Verstovsek Srdan , Giles Francis 
Published: March 2004

AbstractNuclear factor‐kappaB (NF‐κB) is a collective term that refers to a small class of dimeric transcription factors for a number of genes, including growth factors, angiogenesis modulators, cell‐adhesion molecules, and antiapoptotic factors. Although most NF‐κB proteins promote transcription, some act as inactivating or repressive complexes. The most common p50‐RelA (p65) dimer known “specifically” as NF‐κB, is relatively abundant, controls the expression of numerous genes, and exists as an inactive cytoplasmic complex bound to inhibitory proteins of the NF‐κB inhibitor (IκB) family. The inactive NF‐κB‐IκB complex is activated by a variety of stimuli, including proinflammatory cytokines, mitogens, growth factors, and stress‐inducing agents. The release of NF‐κB facilitates its translocation to the nucleus, where it promotes cell survival by initiating the transcription of genes encoding stress‐response enzymes, cell‐adhesion molecules, proinflammatory cytokines, and antiapoptotic proteins. Constitutive activation of NF‐κB in the nucleus is observed in some hematologic disorders. With the recent approval of bortezomib for patients with advanced multiple myeloma, NF‐κB modulation is likely to be a therapeutic endeavor of increasing interest in coming years. Cancer 2004. © 2004 American Cancer Society.
A Phase II trial of vinorelbine tartrate in patients with disseminated malignant melanoma and one prior systemic therapy
Authors: Whitehead Robert P. , Moon James , McCachren S. Spence , Hersh Evan M. , Samlowski Wolfram E. , Beck J. Thaddeus , Tchekmedyian Nerses S. , Sondak Vernon K. 
Published: March 2004

AbstractBACKGROUNDSingle‐agent chemotherapy with dacarbazine continues to be the standard of care for the treatment of metastatic melanoma. However, there is a large population of patients who have failed first‐line therapy and might benefit from additional treatment. In the current study, the authors evaluated the antitumor effects and toxicity of vinorelbine therapy in patients who had failed one prior systemic therapy.METHODSPatients were required to have a histologic diagnosis of melanoma and be of Stage IV with measurable disease, a Southwest Oncology Group (SWOG) performance status (PS) of 0–2, no evidence of brain metastases, and adequate bone marrow and liver function. Treatment was comprised of vinorelbine given at a dose of 30 mg/m2/week by intravenous bolus.RESULTSTwenty‐four patients were registered to the study, 3 of whom were determined to be ineligible. The 21 eligible patients had a median age of 58 years with a SWOG PS of 0 in 7 patients, 1 in 13 patients, and 2 in 1 patient. There were no complete or partial responses observed, for a response rate of 0 of the 21 patients studied (95% confidence interval [95% CI], 0–16%); the study closed after the first stage of accrual. The estimated median progression‐free survival was 2 months (95% CI, 1.5–3.3 months) and the estimated median overall survival was 6 months (95% CI, 3.7–8.3 months). There was one death due to febrile neutropenia reported, with six patients experiencing one or more Grade 4 toxicities, including neutropenia/granulocytopenia, leukopenia, dyspnea, and fatigue.CONCLUSIONSDespite impressive preclinical activity against melanoma, vinorelbine does not appear to have enough clinical activity to be of interest in previously treated patients with disseminated melanoma. The progression‐free and overall survival results noted in previously treated patients in the current study were similar to results reported in prior SWOG Phase II trials in untreated patients. The group of previously treated patients may be used to evaluate new agents for the treatment of disseminated melanoma. Cancer 2004. © 2004 American Cancer Society.
High‐dose calcitriol, zoledronate, and dexamethasone for the treatment of progressive prostate carcinoma
Authors: Morris Michael J. , Smaletz Oren , Solit David , Kelly W. Kevin , Slovin Susan , Flombaum Carlos , Curley Tracy , Delacruz Anthony , Schwartz Lawrence , Fleisher Martin , Zhu Andrew , Diani Meghan , Fallon Mary , Scher Howard I. 
Published: March 2004

AbstractBACKGROUNDPreclinical and clinical data have suggested that high‐dose calcitriol (1,25‐dihydroxycholecalciferol) has activity against prostate carcinoma. Pulse‐dosed calcitriol and dexamethasone may maximize tolerability and efficacy. The authors examined the toxicity of pulse‐dosed calcitriol with zoledronate and with the addition of dexamethasone at the time of disease progression.METHODSPatients with progressive prostate carcinoma were eligible for the current study. In cohorts of 3–6 patients, calcitriol was administered for 3 consecutive days per week, starting at a dose of 4 μg per day. Doses were escalated to 30 μg per day. Intravenous zoledronate (4 mg) was administered monthly. Dexamethasone could be added to the regimen at disease progression. Toxicities, markers of bone turnover, plasma calcitriol levels, and clinical outcomes were recorded.RESULTSThirty‐one patients were treated in cohorts that were defined by the calcitriol dose administered (4, 6, 8, 10, 14, 20, 24, or 30 μg). Seven patients received dexamethasone. Three patients had their doses reduced due to calcium‐related laboratory findings. Patients tolerated therapy well, even in the 30 μg cohort; therefore, a maximum tolerated dose was not defined. Peak plasma levels observed in the 24 μg and 30 μg cohorts ranged from 391 to 968 pg/mL. Minimal antitumor effects were observed.CONCLUSIONSCalcitriol was well tolerated at doses up to and including 30 μg 3 times per week in combination with intravenous zoledronate 4 mg monthly, with or without dexamethasone, in patients with progressive prostate carcinoma. Peak plasma levels in the 24 μg and 30 μg cohorts were greater than the levels associated with antitumor effects preclinically. Due to the cumbersome dosing schedule and the lack of significant activity observed, Phase II trials of this regimen are not planned. Cancer 2004. © 2004 American Cancer Society.
Characterization of FAMPAC, a newly identified human pancreatic carcinoma cell line with a hereditary background
Authors: Eisold Sven , Ryschich Eduard , Linnebacher Michael , Giese Thomas , Nauheimer Dirk , Wild Anja , Bartsch Detlef K. , Büchler Markus W. , Schmidt Jan 
Published: March 2004

AbstractBACKGROUNDA novel pancreatic carcinoma cell line, FAMPAC, was identified from investigation of poorly differentiated pancreatic adenocarcinoma cells found in a patient with a familial predisposition to pancreatic carcinoma. A gene responsible for familial pancreatic carcinoma has not been identified to date.METHODSThe FAMPAC cell line was characterized by its morphology, growth rate, tumorigenicity, and chromosomal analysis. Three known tumor suppressor genes, p16/CDKN2, BRCA2, and p53, all of which are important in the development of pancreatic carcinoma and frequently are involved in a variety of cancer syndromes, were analyzed.RESULTSFAMPAC cells grew as an adhering monolayer in culture medium supplemented with 10% fetal bovine serum and formed tumors rapidly in nude mice. The doubling time ranged from 24 to 48 hours. Karyotype analysis demonstrated the complexity of chromosomal deletions and rearrangements. The cells were negative for ductal differentiation markers such as cytokeratin 7 and MUC1, indicating poor differentiation. Analysis of FAMPAC cells revealed overexpression of the mutated p53 gene (exon 5, codon 175: CGC → CAC), the presence of a homozygous deletion in the p16 gene, and the presence of wild‐type BRCA2 in the tested hot spots.CONCLUSIONSTo the authors' knowledge, FAMPAC is the first established human pancreatic carcinoma cell line associated with a familial background. FAMPAC is a tumorigenic cell line with a complex molecular pattern of mutations. These findings may be useful in understanding the mechanisms responsible for the development of sporadic or hereditary forms of pancreatic carcinoma. Cancer 2004. © 2004 American Cancer Society.
Primary mucosal melanoma of the head and neck
Authors: Prasad Manju L. , Patel Snehal G. , Huvos Andrew G. , Shah Jatin P. , Busam Klaus J. 
Published: March 2004

AbstractBACKGROUNDThe current study was conducted to identify histologic predictors of survival in patients with localized, lymph node‐negative (Stage I, N0M0) primary mucosal melanomas of the head and neck (HNMM).METHODSThe histology of 39 sinonasal, 20 oral, 1 pharyngeal, and 1 laryngeal Stage I HNMM was reviewed by 2 pathologists without knowledge of patient outcome. The invasion was evaluated as Level I: melanoma in situ (without invasion or with microinvasion only); Level II: invasion into the lamina propria only; and Level III: invasion into deep tissue (e.g., skeletal muscle, bone, or cartilage). The tumor architecture was defined as pseudopapillary when tumor cells clustered around blood vessels resembling papillae and sarcomatoid when they resembled high‐grade pleomorphic sarcoma. Survival analysis was performed with Kaplan–Meier survival curves using disease‐specific survival (DSS) as the endpoint.RESULTSThe 5‐year DSS rate was 43% (median, 41.5 months). The median survival was found to decrease significantly with increasing level of invasion: Level I (n = 4): 138 months; Level II (n = 29): 69 months; and Level III (n = 28): 17 months (P = 0.003). The presence of pseudopapillary and sarcomatoid architecture (n = 20) and undifferentiated cells (n = 16) were found to be associated with a significantly poor DSS (P < 0.05). However, on multivariate analysis, only the level of invasion remained an independent predictor of survival (P = 0.03). Tumor thickness, vascular invasion, and necrosis were found to have no significant influence on survival.CONCLUSIONSMicrostaging according to invasion into three tissue compartments was found to be a significant and independent predictor of poor survival in patients with localized, lymph node‐negative, Stage I HNMM. The presence of sarcomatoid and pseudopapillary architecture and undifferentiated cells also appear to be associated with significantly poor DSS. Cancer 2004. © 2004 American Cancer Society.
The aftermath of therapist–client sex: exploited women struggle with the consequences
Authors: Ben‐Ari Adital , Somer Eli 
Published: March 2004

AbstractThis study explores the ongoing experience of women who were sexually involved with their psychotherapists (therapist–client sex, TCS). Fourteen women who had been engaged in TCS were interviewed to examine the constructed meanings associated with their experiences. Respondents described themselves as having been problem‐saturated, lonely, and victimized by pre‐TCS sexual abuse. Many respondents resolved their TCS betrayal in subsequent therapy. For most interviewees, a significant step towards confronting their painful TCS experience was their initiated agreement to partake in this study. Our data suggest that participants went through a significant personal transformation process that encompassed four main themes: self‐perception; interpersonal relationships; the dilemma of filing a lawsuit; and their motivation to participate in this study. Copyright © 2004 John Wiley & Sons, Ltd.
Intrusive thoughts in non‐clinical subjects: the role of frequency and unpleasantness on appraisal ratings and control strategies
Authors: Belloch Amparo , Morillo Carmen , Lucero Mariela , Cabedo Elena , Carrió Carmen 
Published: March 2004

AbstractThis study explores the frequency of the appearance of intrusive thoughts in normal people, as well their association with cognitive appraisals and control strategies. A total of 336 subjects completed the Spanish adaptation of the Obsessional Intrusions Inventory‐Revised (ROII), designed by Purdon and Clark (1993, 1994a, 1994b). Most of the subjects (99.4%) reported experiencing intrusive thoughts occasionally, but only 13% reported having them with some frequency. The intrusions were included in two factors: aggression, sexually and socially inappropriate behaviours, and doubts, checking, and cleanliness. The frequency of appearance of the most upsetting intrusive thought was associated with: the likelihood/probability bias, the need to control the thoughts, and neutralizing strategies. Nevertheless, the unpleasantness was associated with the morality bias and a broad range of control strategies. These results are discussed in relation to the different roles that the appraisal and the thought control responses play, both regarding the persistence as well as the unpleasantness associated with the most upsetting intrusions. Copyright © 2004 John Wiley & Sons, Ltd.