bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II trial of gemcitabine in advanced sarcomas
Authors: Okuno Scott , Edmonson John , Mahoney Michelle , Buckner Jan C. , Frytak Stephen , Galanis Evanthia 
Published: October 2002

AbstractBACKGROUNDCare for patients with advanced sarcomas is mainly palliative. Gemcitabine, a nucleoside antimetabolite, is an analog of deoxycytidine that has shown antitumor activity in several tumors. The aim of the current study was to determine the clinical activity of gemcitabine in patients with sarcomas.METHODSThe authors evaluated gemcitabine in patients with histologically confirmed sarcomas; one prior exposure to chemotherapy treatment was allowed. Prior radiation was allowed if given to non‐indicator lesions. Treatment consisted of gemcitabine 1250 mg/m2 intravenously over 30 minutes, every week × three, cycles repeated q28 days.RESULTSTwenty nine of 30 patients were evaluable; one patient refused to initiate study treatment. The mean age was 50 years (range, 22‐81 years); 59% were male, and 35% had an Eastern Cooperative Oncology Group performance status of 0 (vs. 1 or 2). Patients were histologically classified as leiomyosarcoma (seven gastrointestinal, four retroperitoneal, two inferior vena caval, three of the extremity, and two uterine), synovial (two patients), malignant fibrous histiocytoma (two patients), fibrosarcoma (one patient), osteosarcoma (two patients), liposarcoma (one patient), hemangiosarcoma (one patient), or giant cell (one patient). Patients received an average of two cycles (range, one to eight). Eighty three percent of patients discontinued treatment due to progression and 14% due to toxicity/refusal. Hematologic toxicities ≥ Grade 3 were seen in 32% of patients and consisted of leukopenia and thrombocytopenia. Anorexia (Grade 1/2 in 6 patients, Grade 3 in 1 patient), nausea (Grade 1/2 in 7 patients, Grade 3 in 1 patient), and lethargy (Grade 1/2 in 19 patients) were the most frequently observed nonhematologic toxicities. One patient experienced Grade 3 edema and muscle infarction. A different patient experienced unexplained Grade 3 chest pain. One partial response was observed in a uterine leiomyosarcoma patient lasting at least three months. Overall response rate was 3% (95% confidence interval [CI]: 0‐15). Median time ‐to progression was 2.1 months (95% CI: 1.8–3.0).CONCLUSIONSThe current gemcitabine regimen demonstrated acceptable levels of toxicity, but it failed to produce the number of responses needed to justify expansion of the current study. This regimen is not recommended for advanced sarcomas. Cancer 2002;94:3225–9. © 2002 American Cancer Society.DOI 10.1002/cncr.10602
A natural history of melanomas and dysplastic nevi
Authors: Tucker Margaret A. , Fraser Mary C. , Goldstein Alisa M. , Struewing Jeffery P. , King Mary A. , Crawford John T. , Chiazze Ellen A. , Zametkin Deborah P. , Fontaine Laura S. , Clark Wallace H. 
Published: October 2002

AbstractBACKGROUNDFew long‐term clinical and histologic data for melanocytic lesions have been available based on the mutation status of families at an increased risk of melanoma. In the current study, the authors describe the clinical and histologic features of dysplastic nevi and melanoma over time in families at an increased risk of melanoma with differing germline mutations in CDKN2A, CDK4, or not yet identified genes.METHODSThirty‐three families with > 2 living members with invasive melanoma were evaluated clinically and followed prospectively for up to 25 years. All the participants were evaluated by the same study team at the Clinical Center of the National Institutes of Health or in local clinics. After informed consent was obtained, family members (n = 844) were examined and photographed. Blood was obtained for genetic studies; genotyping for CDKN2A and CDK4 was performed. Sequential photographs of melanocytic lesions were taken as part of the clinical evaluations. When melanocytic lesions were removed, the histology was reviewed. Representative photographs and photomicrographs were selected for six classes of lesions and three mutation groups.RESULTSAll the families were found to have members with dysplastic nevi and melanoma; 17 had mutations in CDKN2A, 2 had mutations in CDK4, and 14 had no mutations in either gene identified. The majority of dysplastic nevi either remain stable or regress; few change in a manner that should cause concern for melanoma. With careful surveillance, melanomas can be found early.CONCLUSIONSThe melanomas and dysplastic nevi that were found to occur in the study families did not appear to vary by the type of mutation identified in the families. Cancer 2002;94:3192–209. © 2002 American Cancer Society.DOI 10.1002/cncr.10605
GLI3 is not mutated commonly in sporadic medulloblastomas
Authors: Erez Ayelet , Ilan Tsafra , Amariglio Ninette , Muler Inna , Brok‐Simoni Frida , Rechavi Gideon , Izraeli Shai 
Published: October 2002

AbstractBACKGROUNDMedulloblastoma is a malignant, invasive embryonic tumor of the cerebellum. Sonic hedgehog (SHH) is a secreted glycoprotein that has a major role in the developing cerebellum. Activation of the SHH pathway resulting from mutations in the PATCH gene, which is an inhibitor of the pathway, are associated with hereditary and sporadic medulloblastomas. The GLI3 protein is another negative regulator of SHH signaling. The authors hypothesized that mutations in GLI3 may be associated with meduloblastomas.METHODSThe authors describe a patient with hereditary Greig syndrome, which was caused by mutations in GLI3, and medulloblastoma. Another such patient was described in the literature. They also sequenced the GLI3 gene, including all exon‐intron boundaries, in an additional 12 sporadic medulloblastomas.RESULTSThe authors detected a new nonsense germline mutation in a child with Greig syndrome and medulloblastoma. This mutation generates a stop codon in position 809 of GLI3 that has been predicted to result in massive truncation of the protein. Several new polymorphisms, but no tumor‐associated mutations, were found in sporadic tumors.CONCLUSIONSGli3 is mutated rarely in medulloblastoma. Cancer 2002;95:28–31. © 2002 American Cancer Society.DOI 10.1002/cncr.10642
Changes in presentation and survival of head and neck carcinomas in Northeastern Italy, 1975–1998
Authors: Barzan Luigi , Talamini Renato , Franchin Gianni , Vaccher Emanuela , Politi Doriano , Minatel Emilio , Gobitti Carlo 
Published: October 2002

AbstractBACKGROUNDDuring the last 20 years, survival rates of head and neck carcinoma patients in the United States and Europe have plateaued. To determine the factors that can reduce mortality rates, we examined changes in clinical presentation and survival rates across 24 years of treatment of head and neck carcinoma patients.METHODSA retrospective study of patients with head and neck carcinoma was conducted from January 1, 1975, to December 31, 1998. We identified 2143 eligible patients with squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx. Changes in gender, clinical stage, and therapy were evaluated separately for each site of cancer across five consecutive periods. Probability of dying and overall survival rates were estimated. Odds ratios (ORs) and hazard ratios were calculated.RESULTSAn increase in T1 versus T2 or higher stage carcinoma was more probable for the oral cavity and larynx (OR = 4.1 and 3.0, respectively) in the last versus the earliest period. An increase in radical treatments was more probable for carcinomas of the oral cavity, oropharynx, hypopharynx, and larynx (10.2, 34.8, 12.5, and 2.1‐fold, respectively) in the last versus the earliest period. A decreasing trend of probability of dying from the first head and neck carcinoma during the 1970s versus the 1990s was found. The overall survival rates at 5 years was 32% in 1975–1978 versus 51% in 1989–1993.CONCLUSIONSIn contrast with survival rates in the United States and Europe, our findings show a significant increase in overall survival rates during the last 20 years. This increase is attributable to changes in diagnostic‐therapeutic approaches and to early consultation with a physician for symptoms arising in the head and neck region. Cancer 2002;95:540–52. © 2002 American Cancer Society.DOI 10.1002/cncr.10682
Follicular thyroid carcinoma
Authors: Chow Sin‐Ming , Law Stephen C. K. , Mendenhall William M. , Au Siu‐Kie , Yau Stephen , Yuen Kam‐Tong , Law Chi‐Ching , Lau Wai‐Hon 
Published: October 2002

AbstractBACKGROUNDThe objective of this study was to investigate the patterns of recurrence, various prognostic factors, and the role of radioiodine in the treatment of patients with follicular thyroid carcinoma (FTC).METHODSThe clinical outcomes of 215 patients with FTC who were treated at a single institution were analyzed retrospectively. The mean follow‐up was 10.8 years.RESULTSThe actuarial rates of cause specific survival (CSS), locoregional (LR) control, and freedom from distant metastasis (DM) at 10 years were 81%, 83%, and 72.3%, respectively. The independent prognostic factors for survival were metastasis at presentation (relative risk [RR], 47.7), radioiodine (RAI) treatment (RR, 0.25), extrathyroidal extension (RR, 3.8), and the postoperative absence of macroscopic disease in the neck region (RR, 0.06). In patients who were treated with RAI, both the LR failure rate (RR, 0.24) and the mortality rate (RR, 0.25) were reduced to about 25%. Subgroup analysis revealed that RAI improved the survival of patients with DM at presentation (RR, 0.17) and improved the LR control rate in patients who had no DM at presentation (RR, 0.13). For patients who underwent total thyroidectomy with negative resection margins, RAI significantly reduced the rate of LR recurrence (RR, 0.05). Patients with the minimally invasive type of FTC had a good prognosis. The 10‐year rates for CSS, LR control, and freedom from DM were 97.6%, 100%, and 90.6%, respectively. The prognosis of patients with frankly invasive FTC was much poorer. The 10‐year rates for CSS, LR control, and freedom from DM were 66.7%, 100%, and 45%, respectively.CONCLUSIONSRAI is an effective treatment for patients with FTC. It was associated with improved survival rates and fewer recurrences. Cancer 2002;95:488–98. © 2002 American Cancer Society.DOI 10.1002/cncr.10683
Plasma osteopontin
Authors: Hotte Sebastien J. , Winquist Eric W. , Stitt Larry , Wilson Sylvia M. , Chambers Ann F. 
Published: October 2002

AbstractBACKGROUNDOsteopontin (OPN) is a secreted glycoprotein that is detectable in human body fluids. Its increased expression has been found in many malignancies, and a stimulatory effect on human prostate carcinoma cells in vitro has been demonstrated. Plasma OPN levels have been associated with tumor burden and survival in patients with metastatic breast carcinoma. The authors explored these associations in men with hormone‐refractory prostate carcinoma (HRPC).METHODSPlasma samples from 100 men with HRPC were collected. OPN was measured using an antigen‐capture enzyme‐linked immunosorbent assay technique. Multivariable analyses were performed to identify predictors of OPN and survival.RESULTSAt the time of OPN sampling, the median patient age was 73 years (range, 50–86 years), and 92% of patients had metastases. The median plasma OPN level was 198.5 ng/mL (range, 15.0–2363.0 ng/mL), the median prostate specific antigen level was 67.8 μg/L (range, 0.1–7550.0 μg/L), and the median survival was 13.7 months. OPN plasma levels were higher in patients with versus patients without bone metastases (P = 0.024). Multivariable modeling demonstrated an independent association of the OPN level with alkaline phosphatase, hemoglobin, and creatinine levels. The log‐transformed OPN level (hazard ratio [HR], 2.38; P < 0.0001), performance status (HR, 2.43; P = 0.007), and a history of prior radiotherapy for localized prostate carcinoma (HR, 0.48; P = 0.0229) were independent predictors of survival in a Cox multivariate model.CONCLUSIONSIn this study, in men with established HRPC, the plasma OPN level was associated with the presence of metastases to bone and with other measures of tumor burden, and it was correlated independently and negatively with survival. Cancer 2002;95:506–12. © 2002 American Cancer Society.DOI 10.1002/cncr.10709
Severe periorbital edema secondary to STI571 (Gleevec)
Authors: Esmaeli Bita , Prieto Victor G. , Butler Charles E. , Kim Stella K. , Ahmadi M. Amir , Kantarjian Hagop M. , Talpaz Moshe 
Published: October 2002

AbstractSTI571 (imatinib mesylate; Gleevec) is a selective inhibitor of the bcr‐abl, c‐kit, and platelet‐derived growth factor receptor tyrosine kinases. Mild periorbital edema has been noted as a common side effect in Phase I and II trials of this drug for the treatment of patients with chronic myelogenous leukemia and gastrointestinal stromal tumors. The authors report the case of male patient age 63 years who developed severe periorbital edema after treatment with STI571 for chronic myelogenous leukemia. His edema was severe enough to cause visual obstruction due to lower eyelid festoons that ultimately required surgical debulking. Histopathologic analysis of specimens of the excised upper and lower eyelid tissue revealed dermal dendrocytes that expressed the platelet‐derived growth factor receptor and c‐kit tyrosine kinases, suggesting a possible role for dermal dendrocytes in the development of this toxic effect. Cancer 2002;95:881–7. © 2002 American Cancer Society.DOI 10.1002/cncr.10729
β1‐integrin protects hepatoma cells from chemotherapy induced apoptosis via a mitogen‐activated protein kinase dependent pathway
Authors: Zhang Hao , Ozaki Iwata , Mizuta Toshihiko , Matsuhashi Sachiko , Yoshimura Tohru , Hisatomi Akitaka , Tadano Jutaro , Sakai Takahiro , Yamamoto Kyosuke 
Published: October 2002

AbstractBACKGROUNDβ1‐integrin modulates cellular phenotype by mediating signals from the extracellular matrix (ECM). Although overexpression of integrin molecules in hepatocellular carcinoma (HCC) has been reported, the role of overexpressed β1‐integrin in the disease process of HCC is not fully understood. The authors investigated the effects of β1‐integrin on apoptosis in hepatoma cells.METHODSHuman hepatoma cell lines HepG2, Huh7, and HLE were stably transfected with full‐length β1‐integrin. Cells underwent apoptosis induced by chemotherapeutic reagents, including cis‐platinum (II)‐diammine dichloride, etoposide, and docetaxel. Cell survival and intracellular signaling pathways dependent on β1‐integrin‐mediated apoptosis effects were analyzed by treating cells with PD98059 (ERK inhibitor), SB203580 (p38MAP kinase inhibitor), wortmannin (phosphatidyl inositol‐3‐kinase inhibitor), and herbimycin A (tyrosine kinase inhibitor).RESULTSAll three hepatoma cell lines overexpressing β1‐integrin were protected from apoptosis induced by chemotherapeutic reagents, whereas parental or mock transfected cells were not. Treatment with PD98059 or SB203580 abolished the protective effect on apoptosis in cells overexpressing β1‐integrin. Neither herbimycin nor wortmannin blocked the protective effects of β1‐integrin overexpression.CONCLUSIONSThese data suggest that overexpression of β1‐integrin confers resistance to apoptosis in hepatoma cells via a MAP kinase dependent pathway. β1‐integrin mediated signaling from the ECM in HCC cells may contribute to chemotherapy resistance. Cancer 2002;95:896–906. © 2002 American Cancer Society.DOI 10.1002/cncr.10751
Quantitative ultrastructural analysis of glycine‐ and γ‐aminobutyric acid‐immunoreactive terminals on trigeminal α‐ and γ‐motoneuron somata in the rat
Authors: Bae Yong Chul , Choi Byung Ju , Lee Maan Gee , Lee Hyo Jeong , Park Kuk Pil , Zhang Li Fen , Honma Shiho , Fukami Hideyuki , Yoshida Atsushi , Ottersen Ole Petter , Shigenaga Yoshio 
Published: October 2002

AbstractDetailed knowledge of the inhibitory input to trigeminal motoneurons is needed to understand better the central mechanisms of jaw movements. Here a quantitative analysis of terminals contacting somata of jaw‐closing (JC) and jaw‐opening (JO) α‐motoneurons, and of JC γ‐motoneurons, was performed by use of serial sectioning and postembedding immunogold cytochemistry. For each type of motoneuron, the synaptic boutons were classified into four groups, i.e., immunonegative boutons or boutons immunoreactive to glycine only, to γ‐aminobutyric acid (GABA) only, or to both glycine and GABA. The density of immunolabeled boutons was much higher for the α‐ than for the γ‐motoneurons. In the α‐motoneuron populations, the immunolabeled boutons were subdivided into one large group of boutons containing glycine‐like immunoreactivity only, one group of intermediate size harboring both glycine‐ and GABA‐like immunoreactivity, and a small group of boutons containing GABA‐like immunoreactivity only. The percentage of immunolabeled boutons was higher for JC than JO α‐motoneurons, the most pronounced difference being observed for glycine‐like immunoreactivity. In contrast, on the somatic membrane of γ‐motoneurons, the three types of immunoreactive bouton occurred at similar frequencies. These results indicate that trigeminal motoneurons are strongly and differentially controlled by premotoneurons containing glycine and/or GABA and suggest that these neurons play an important role for the generation of masticatory patterns. J. Comp. Neurol. 442:308–319, 2002. © 2002 Wiley‐Liss, Inc.
Developmental expression of monoamine oxidases A and B in the central and peripheral nervous systems of the mouse
Authors: Vitalis Tania , Fouquet Coralie , Alvarez Chantal , Seif Isabelle , Price David , Gaspar Patricia , Cases Olivier 
Published: October 2002

AbstractMonoamine oxidases A (MAOA) and B (MAOB) are key players in the inactivation pathway of biogenic amines. Their cellular localization has been well established in the mature brain, but nothing is known concerning the localization of both enzymes during development. We have combined in situ hybridization and histochemistry to localize MAOA and MAOB in the developing nervous system of mice. Our observations can be summarized as five key features. (1) MAOA is tightly linked to catecholaminergic traits. MAOA is expressed in all noradrenergic and adrenergic neurons early on, and in several dopaminergic cell groups such as the substantia nigra. MAOA is also expressed in all the neurons that display a transient tyrosine hydroxylase expression in the brainstem and the amygdala and in neurons with transient dopamine‐β‐hydroxylase expression in the cranial sensory ganglia. (2) MAOA and MAOB are coexpressed in the serotoninergic neurons of the raphe from E12 to P7. During postnatal life, MAOA expression declines, whereas MAOB expression remains stable. (3) MAOA is transiently expressed in the cholinergic motor nuclei of the hindbrain, and MAOB is expressed in the forebrain cholinergic neurons. (4) MAOA‐ and MAOB‐expressing neurons are also detected in structures that do not contain aminergic neurons, such as the thalamus, hippocampus, and claustrum. (5) Starting at birth, MAOB expression is found in a variety of nonneuronal cells, the choroid plexus, the ependyma, and astrocytes. These localizations are of importance for understanding the effects of monoaminergic transmission during development. J. Comp. Neurol. 442:331–347, 2002. © 2002 Wiley‐Liss, Inc.
Orcokinin peptides in developing and adult crustacean stomatogastric nervous systems and pericardial organs
Authors: Li Lingjun , Pulver Stefan R. , Kelley Wayne P. , Thirumalai Vatsala , Sweedler Jonathan V. , Marder Eve 
Published: October 2002

AbstractThe orcokinins are a family of neuropeptides recently isolated from several crustacean species. We found orcokinin‐like immunoreactivity in the stomatogastric nervous systems and pericardial organs of three decapod crustacean species, Homarus americanus, Cancer borealis, and Panulirus interruptus. The neuropil of the stomatogastric ganglion was stained in adults of all three species as well as in embryonic and larval H. americanus. In H. americanus, the somata giving rise to this projection were found in the inferior ventricular nerve. Matrix‐assisted laser desorption/ionization mass spectrometry mass profiling and sequencing with postsource decay led to the identification of six different orcokinin family peptides, including those previously described in other decapods and two novel shorter peptides. Application of exogenous [Ala13]orcokinin to the stomatogastric ganglion of H. americanus resulted in changes in the pyloric rhythm. Specifically, the number of lateral pyloric (LP) neuron spikes/burst decreased, and the phase of firing of the pyloric neurons was altered. Together, these data indicate that the orcokinins are likely to function as modulators of the crustacean stomatogastric ganglion. J. Comp. Neurol. 444:227–244, 2002. © 2002 Wiley‐Liss, Inc.
Vesicular glutamate transporter DNPI/VGLUT2 is expressed by both C1 adrenergic and nonaminergic presympathetic vasomotor neurons of the rat medulla
Authors: Stornetta Ruth L. , Sevigny Charles P. , Schreihofer Ann M. , Rosin Diane L. , Guyenet Patrice G. 
Published: October 2002

AbstractThe main source of excitatory drive to the sympathetic preganglionic neurons that control blood pressure is from neurons located in the rostral ventrolateral medulla (RVLM). This monosynaptic input includes adrenergic (C1), peptidergic, and noncatecholaminergic neurons. Some of the cells in this pathway are suspected to be glutamatergic, but conclusive evidence is lacking. In the present study we sought to determine whether these presympathetic neurons express the vesicular glutamate transporter BNPI/VGLUT1 or the closely related gene DNPI, the rat homolog of the mouse vesicular glutamate transporter VGLUT2. Both BNPI/VGLUT1 and DNPI/VGLUT2 mRNAs were detected in the medulla oblongata by in situ hybridization, but only DNPI/VGLUT2 mRNA was present in the RVLM. Moreover, BNPI immunoreactivity was absent from the thoracic spinal cord lateral horn. DNPI/VGLUT2 mRNA was present in many medullary cells retrogradely labeled with Fluoro‐Gold from the spinal cord (T2; four rats). Within the RVLM, 79% of the bulbospinal C1 cells contained DNPI/VGLUT2 mRNA. Bulbospinal noradrenergic A5 neurons did not contain DNPI/VGLUT2 mRNA. The RVLM of six unanesthetized rats subjected to 2 hours of hydralazine‐induced hypotension contained tenfold more c‐Fos‐ir DNPI/VGLUT2 neurons than that of six saline‐treated controls. c‐Fos‐ir DNPI/VGLUT2 neurons included C1 and non‐C1 neurons (3:2 ratio). In seven barbiturate‐anesthetized rats, 16 vasomotor presympathetic neurons were filled with biotinamide and analyzed for the presence of tyrosine hydroxylase immunoreactivity and/or DNPI/VGLUT2 mRNA. Biotinamide‐labeled neurons included C1 and non‐C1 cells. Most non‐C1 (9/10) and C1 presympathetic cells (5/6) contained DNPI/VGLUT2 mRNA. In conclusion, DNPI/VGLUT2 is expressed by most blood pressure‐regulating presympathetic cells of the RVLM. The data suggest that these neurons may be glutamatergic and that the C1 adrenergic phenotype is one of several secondary phenotypes that are differentially expressed by subgroups of these cells. J. Comp. Neurol. 444:207–220, 2002. © 2002 Wiley‐Liss, Inc.