bluuebunny/crossref_metadata_2025_split huggingface dataset:
An unexplained sequestration of latrunculin A is required in neutrophils for inhibition of actin polymerization
Authors: Pring Martin , Cassimeris Lynne , Zigmond Sally H. 
Published: August 2002

AbstractLatrunculin A (LatA) is a toxic natural product that causes disruption of the actin cytoskeleton in many eukaryotic cells at submicromolar concentrations. LatA has been found to bind G‐actin with a dissociation constant of 0.2 μM, and more recently to bind profilin‐G‐actin and, weakly, thymosin β4‐G‐actin. A number of investigators have used LatA as a G‐actin sequestering agent. Thus, we studied neutrophil chemotaxis and its requisite conversion of G‐actin to F‐actin, supported by an extensive pool of G‐actin, mainly bound to thymosin β4. Calculations suggest that the affinity of LatA is insufficient to cause significant sequestration of this pool, and the pool's buffering action should protect neutrophils from depletion of productive G‐actin species by submicromolar LatA. Nonetheless, we found that both chemoattractant stimulated migration and F‐actin polymerization in neutrophils were inhibited by LatA at these concentrations. The latter effect was accompanied by sequestration of LatA and showed a cell density dependence that was consistent with G‐actin sequestration. The apparent contradiction between the calculations and the experimental observations could be reconciled by assuming the presence of an accessory species, of unknown normal function, which forms a high affinity ternary complex with LatA and G‐actin, thus causing the cells to concentrate LatA. Other models that could not be ruled out also invoke new actions of LatA, suggesting caution in the interpretation of its effects on cells. Cell Motil. Cytoskeleton 52:122–130, 2002. © 2002 Wiley‐Liss, Inc.
A prospective study of pulmonary function in patients treated with paclitaxel and carboplatin
Authors: Dimopoulou Ioanna , Galani Heleni , Dafni Urania , Samakovli Anastasia , Roussos Charis , Dimopoulos Meletios A. 
Published: August 2002

AbstractBACKGROUNDAdverse effects of paclitaxel and carboplatin have been well described; however, pulmonary toxicity after patients receive this regimen has not been investigated extensively.METHODSTo clarify this issue, 33 consecutive patients who were treated with paclitaxel and carboplatin underwent prospective evaluation of respiratory function, which included pulmonary symptoms, pulmonary function tests (PFTs), arterial blood gas levels, and radiographic studies. Assessment was performed before and after completion of chemotherapy in all patients. Patients with substantial declines in PFTs, defined as a decline ≥ 20 percent in forced expiratory volume in 1 second (FEV1), total lung capacity (TLC), or diffusion capacity for carbon monoxide (DLCO), were reassessed 5 months later.RESULTSAfter chemotherapy, there were no significant changes in forced vital capacity (FVC; 111% ± 21% of the predicted value before chemotherapy vs. 111 ± 20% of the predicted value after chemotherapy), FEV1 (108% ± 24% of the predicted value before chemotherapy vs. 107% ± 22% of the predicted value after chemotherapy), FEV1/FVC ratio (79% ± 8% before chemotherapy vs. 78% ± 6% after chemotherapy), alveolar volume (VA; 95% ± 14% of the predicted value before chemotherapy vs. 96% ± 14% of the predicted value after chemotherapy), or TLC (96% ± 14% of the predicted value before chemotherapy vs. 97% ± 13% of the predicted value after chemotherapy). In contrast, there was a significant decline in DLCO (101% ± 20% of the predicted value before chemotherapy vs. 96 ± 21% of the predicted value after chemotherapy; P < 0.05). Arterial blood gas levels did not change after treatment. No patient had decreased FEV1 or TLC levels by ≥ 20%, whereas 4 of 33 patients (12%) exhibited a substantial decline (≥ 20%) in DLCO that persisted 5 months after treatment (DLCO at baseline, immediately after chemotherapy, and 5 months after the completion of chemotherapy, respectively: 99% ± 36% of the predicted value vs. 75% ± 28% of the predicted value vs. 74% ± 31% of the predicted value; P < 0.05). None of the 33 patients developed respiratory symptoms or had radiologic signs suggestive of lung toxicity. Among the various risk factors examined, baseline DLCO and FEV1 levels were associated with changes in DLCO post‐treatment.CONCLUSIONSThis prospective analysis showed that the combination of paclitaxel with carboplatin induced an isolated decrease in DLCO level in the absence of clinical or radiologic evidence of toxicity. Further studies are needed to clarify whether this reduction in DLCO is predictive of subsequent pulmonary impairment. Cancer 2002;94:452–8. © 2002 American Cancer Society.
Liposome‐encapsulated doxorubicin compared with conventional doxorubicin in a randomized multicenter trial as first‐line therapy of metastatic breast carcinoma
Authors: Harris Lyndsay , Batist Gerald , Belt Robert , Rovira Douglas , Navari Rudolph , Azarnia Nozar , Welles Lauri , Winer Eric ,   TLC D‐99 Study Group
Published: August 2002

AbstractBACKGROUNDThe objective of this study was to compare the efficacy and toxicity of the liposome‐encapsulated doxorubicin, TLC D‐99 (Myocet, Elan Pharmaceuticals, Princeton, NJ), and conventional doxorubicin in first‐line treatment of metastatic breast carcinoma (MBC).METHODSTwo hundred twenty‐four patients with MBC and no prior therapy for metastatic disease were randomized to receive either TLC D‐99 (75 mg/m2) or doxorubicin (75 mg/m2) every 3 weeks, in the absence of disease progression or unacceptable toxicity. The primary efficacy endpoint was response rate. Responses were assessed using World Health Organization criteria and were required to be of at least 6 weeks' duration. The primary safety endpoint was cardiotoxicity. Cardiac function was monitored by multiple‐gated radionuclide cardioangiography scan, and the left ventricular ejection fraction (LVEF) was scored at a central laboratory. Patients were removed from study if LVEF declined 20 or more EF units from baseline to a final value of greater than or equal to 50%, or by 10 or more units to a final value of less than 50%, or onset of clinical congestive heart failure (CHF).RESULTSMedian age was 54 years in both treatment groups. All relevant prog nostic factors were balanced, with the exception that there were significantly more progesterone receptor positive patients in the doxorubicin‐treated group. Protocol‐defined cardiotoxicity was observed in 13% of TLC D‐99 patients (including 2 cases of CHF) compared to 29% of doxorubicin patients (including 9 cases of CHF). Median cumulative doxorubicin dose at onset of cardiotoxicity was 785 mg/m2 for TLC D‐99 versus 570 mg/m2 for doxorubicin (P = 0.0001; hazard ratio, 3.56). The overall response rate was 26% in both treatment groups. The median TTP was 2.9 months on TLC D‐99 versus 3.1 months on doxorubicin. Median survival was 16 versus 20 months with a nonsignificant trend in favor of doxorubicin (P = 0.09). Clinical toxicities, commonly associated with doxorubicin, appeared less common with TLC D‐99, although the difference was not statistically significant. There was only one report of palmar‐plantar erythrodysesthesia (Grade 2) with this liposomal formulation of doxorubicin.CONCLUSIONSSingle‐agent TLC D‐99 produces less cardiotoxicity than doxorubicin, while providing comparable antitumor activity. Cancer 2002;94:25–36. © 2002 American Cancer Society.
Percutaneous tumor ablation with radiofrequency
Authors: Wood Bradford J. , Ramkaransingh Jeffrey R. , Fojo Tito , Walther McClellan M. , Libutti Stephen K. 
Published: August 2002

AbstractBACKGROUNDRadiofrequency thermal ablation (RFA) is a new minimally invasive treatment for localized cancer. Minimally invasive surgical options require less resources, time, recovery, and cost, and often offer reduced morbidity and mortality, compared with more invasive methods. To be useful, image‐guided, minimally invasive, local treatments will have to meet those expectations without sacrificing efficacy.METHODSImage‐guided, local cancer treatment relies on the assumption that local disease control may improve survival. Recent developments in ablative techniques are being applied to patients with inoperable, small, or solitary liver tumors, recurrent metachronous hereditary renal cell carcinoma, and neoplasms in the bone, lung, breast, and adrenal gland.RESULTSRecent refinements in ablation technology enable large tumor volumes to be treated with image‐guided needle placement, either percutaneously, laparoscopically, or with open surgery. Local disease control potentially could result in improved survival, or enhanced operability.CONCLUSIONSConsensus indications in oncology are ill‐defined, despite widespread proliferation of the technology. A brief review is presented of the current status of image‐guided tumor ablation therapy. More rigorous scientific review, long‐term follow‐up, and randomized prospective trials are needed to help define the role of RFA in oncology. Cancer 2002;94:443–51. © 2002 American Cancer Society.
Sialosyl‐Lex expression defines invasive and metastatic properties of bladder carcinoma
Authors: Numahata Kenji , Satoh Makoto , Handa Kazuko , Saito Seiichi , Ohyama Chikara , Ito Akihiro , Takahashi Toshiko , Hoshi Senji , Orikasa Seiichi , Hakomori Sen‐itiroh 
Published: August 2002

AbstractBACKGROUNDTwo types of transitional bladder carcinoma have been distinguished based on macroscopic morphology: type A papillary carcinomas, with papillomatous surface outgrowth without infiltration into muscular layer, and type B nodular carcinomas, with a nonpapillomatous surface appearance, most of which display infiltrative growth through muscular layer, and some of which display lymphatic or blood‐borne metastasis. However, there is no specific predictor at early stages for later invasive and metastatic clinical outcome of patients with type B tumors.METHODSThe study included 1) glycosphingolipid (GSL) composition of type A and B tumors; 2) histologic and immunohistologic patterns of nodular (type B) bladder carcinoma from 44 patients based on a special sampling procedure termed whole‐layer core biopsy (WLCB) using the antisialosyl‐Lex (anti‐SLex; SLex: NeuAcα3Galβ4[Fucα3]GlcNAcβ3Galβ4GlcCer) SNH3 antibody or other antibodies; 3) comparison of the incidence of metastasis in patients with SNH3 positive versus SNH3 negative primary tumors and of 5‐year survival curves; 4) comparison of bladder carcinoma cell lines from tumors with high versus low malignancy in terms of expression patterns of SLex, SLea, and other carbohydrates, E‐selectin dependent adhesion, and transcript levels of five fucosyltransferases.RESULTSAnti‐SLex monoclonal antibody (mAb) SNH3 staining of WLCB samples from 44 type B tumors showed that the majority of tumors (n = 31 patients) were SNH3 positive and the minority (n = 13 patients) were SNH3 negative. SNH3 positive patients had more lymph node or blood‐borne metastasis and lower 5‐year and 7‐year survival rates, as indicated by Kaplan–Meier curves (P = 0.001). Staining of samples with other antibodies, including FH6 and CA19‐9, was not correlated with long‐term survival. Determination of GSL composition in extracts showed that SLex ganglioside was present in all three patients with nodular tumors but absent in all three patients with papillary tumors tested. Bladder carcinoma cell lines from invasive tumors that maintained their metastatic properties were SNH3 positive, showed high levels of α1,3‐fucosyltransferase VI (FT‐VI) and FT‐VII, and displayed E‐selectin dependent adhesion. Cell lines from noninvasive tumors or normal bladder epithelia were negative for SNH3 reactivity, FT‐VI, and FT‐VII, and E‐selectin dependent adhesion.CONCLUSIONSSLex expression in primary bladder carcinoma, defined by the mAb SNH3, is a predictor of invasive and metastatic outcome. No other carbohydrate epitope examined to date has equal prognostic value. Cancer 2002;94:673–85. © 2002 American Cancer Society.DOI 10.1002/cncr.10268
Brain metastases from esophageal carcinoma
Authors: Ogawa Kazuhiko , Toita Takafumi , Sueyama Hiroo , Fuwa Nobukazu , Kakinohana Yasumasa , Kamata Minoru , Adachi Genki , Saito Atsushi , Yoshii Yoshihiko , Murayama Sadayuki 
Published: August 2002

AbstractBACKGROUNDBrain metastases from esophageal carcinoma are extremely rare, and information regarding the natural history, results of treatment, and possible prognostic factors in these patients is limited.METHODSThe records of 36 patients with brain metastases from esophageal carcinoma who were treated between 1986 and 2000 were reviewed. For brain metastases, 12 patients (33%) were treated with surgical resection followed by radiation therapy (S+RT), and the remaining 24 patients were treated with radiation therapy alone.RESULTSAt the initial diagnosis of esophageal carcinoma, the median primary tumor length was 8 cm (range, 2–19 cm), and 26 of 32 available patients (81%) had clinical Stage III–IV tumors according to the International Union Against Cancer 1997 criteria. At time brain metastases appeared, lung metastases were not demonstrated in 25 of 36 patients (69%) who were assessed by chest computed tomography (CT) scans. The overall median survival for all patients was 3.9 months (range, 0.6–36.8 months), and the actuarial survival rates at 12 months and 24 months were 14% and 3%, respectively. In univariate analysis, treatment modality, Karnofsky performance status (KPS), and extracranial disease status each had a statistically significant impact on survival, and, in multivariate analysis, treatment modality and KPS were statistically significant prognostic factors for survival. Five patients (14%) survived more than 1 year, all of whom were treated with S+RT. These five patients had inactive extracranial disease and, four of five patients (80%) had a 90–100% KPS.CONCLUSIONSBrain metastases from esophageal carcinoma tended to occur in patients with a large primary tumors and/or disease in advanced clinical stages. With the appearance of brain metastases, an absence of lung metastasis frequently was observed on chest CT scans. The prognoses for these patients were generally poor, although selected patients may survive longer with intensive brain tumor treatment. Cancer 2002;94:759–64. © 2002 American Cancer Society.DOI 10.1002/cncr.10271
Breast carcinoma treatment received by women with disabilities compared with women without disabilities
Authors: Caban Mabel E. , Nosek Margaret A. , Graves Daniel , Esteva Francisco J. , McNeese Marsha 
Published: August 2002

AbstractBACKGROUNDDisability may make it difficult to lie flat or abduct the arm to deliver radiation therapy, imposing a high risk for radiation‐induced side effects or difficulty in positioning patients for mammography. The goal of the current study was to determine the differences in treatment options experienced by women with physical disabilities compared with those without disabilities.METHODSChart review of 234 women who underwent surgery for breast carcinoma between June and September 1998 in a national comprehensive cancer center was conducted. Thirty‐nine of the women had physical disabilities; the remaining 195 women were without disabilities. Hierarchical logistic regression was used to determine whether women with disabilities were less likely than women without disabilities to be treated with breast‐conservation surgery (BCS) or neoadjuvant chemotherapy.RESULTSWomen with disabilities underwent BCS 38% of the time, whereas women without disabilities underwent BCS 49% of the time. Neither the presence nor absence of disability (P = 0.146) nor patient age (P = 0.747) were found to be significant predictors of BCS. However, the disease stage at the time of the surgery was reported to be a significant predictor of BCS (P = 0.007). The group of patients with disabilities received neoadjuvant chemotherapy 13% of the time, whereas women without disabilities received it 29% of the time. Disability was not found to be a significant predictor of whether a patient received neoadjuvant chemotherapy. Using hierarchical logistic regression, patient age was found to be a significant predictor of neoadjuvant chemotherapy before the disease stage was entered into the regression equation. There were no data to support the hypothesis that breast carcinoma is at an advanced stage when diagnosed in women with disabilities.CONCLUSIONSThese findings are clinically significant in that they indicate that women with disabilities are less likely to undergo BCS and are less likely to receive neoadjuvant chemotherapy compared with women without disabilities, but the difference did not reach statistical significance. To the authors' knowledge, there are no data to support the hypothesis that disabled women are diagnosed at a more advanced stage of disease compared with women without disabilities. Cancer 2002;94:1391–6. © 2002 American Cancer Society.DOI 10.1002/cncr.10369
Soft tissue sarcoma of the upper extremity
Authors: Lohman Robert F. , Nabawi Ayman S. , Reece Gregory P. , Pollock Raphael E. , Evans Gregory R. D. 
Published: August 2002

AbstractBACKGROUNDThe objective of this study was to define the impact of soft tissue flap reconstruction on multimodality therapy for patients with soft tissue sarcomas of the upper extremity. Treatment standards continue to evolve for these patients, and, with multimodality therapy, most of them are candidates for limb‐preserving surgery. Consequently, the role of soft tissue flap reconstruction is expanding.METHODSA review was conducted of 100 consecutive patients with soft tissue sarcomas of the upper extremity who underwent surgery at several institutions between 1992 and 1997.RESULTSSeventy‐one patients underwent direct closure of defects after tumor resection, and 29 patients required soft tissue reconstruction with flaps. These groups were similar in most respects, except that 52% of the patients who required soft tissue reconstruction presented with recurrent disease (P = 0.0004), and 79% of them had tumors measuring > 5 cm in greatest dimension (P = 0.0003). The patients who required flap reconstruction had larger skin deficits after undergoing tumor resection (140 cm2) compared with the patients who had wounds that were managed by direct closure (40 cm2; P < 0.00001). Margins around the resected tumors were larger (1.62 cm) when flaps were employed compared with margins when defects were closed directly (0.87 cm; P = 0.0005). However, the number of patients with intralesional, marginal, wide, and radical resections was the same regardless of wound management. Major complications occurred in 14% of patients, but none led to death or amputation. The median follow‐up was 31 months, and 66% of patients had no evidence of disease at that time. Rates of local recurrence and survival were similar for patients who underwent flap reconstruction compared with patients who underwent direct closure.CONCLUSIONSSoft tissue flap reconstruction facilitates therapy for patients with soft tissue sarcomas of the upper extremity, so that patients with larger tumors can undergo resection, limiting complications and limb sacrifice. Cancer 2002;94:2256–64. © 2002 American Cancer Society.DOI 10.1002/cncr.10419
Physiological and morphological diversity of immunocytochemically defined parvalbumin‐ and cholecystokinin‐positive interneurones in CA1 of the adult rat hippocampus
Authors: Pawelzik Hannelore , Hughes David I. , Thomson Alex M. 
Published: August 2002

AbstractTo investigate the electrophysiological properties, synaptic connections, and anatomy of individual parvalbumin‐immunoreactive (PV‐IR) and cholecystokinin‐immunoreactive (CCK‐IR) interneurones in CA1, dual intracellular recordings using biocytin‐filled microelectrodes in slices of adult rat hippocampus were combined with fluorescence labelling of PV‐ and CCK‐containing cells. Of 36 PV‐IR cells, 29 were basket cells, with most of their axonal arbours in the stratum pyramidale (SP). Six were bistratified cells with axons ramifying throughout stratum oriens (SO) and stratum radiatum (SR). One was a putative axo‐axonic cell with an axonal arbour confined to half of the SP and a narrow adjacent region of the SO. Of 27 CCK‐IR neurones, 13 were basket cells, with most of their axonal arbours in the SP, and included basket cells with somata in the SP (6), SO (3), and SR (2) and at the border between the stratum lacunosum‐moleculare (SLM) and the SR (2). In addition, several dendrite‐targeting cell classes expressed CCK‐IR: 4 of 9 bistratified cells with axons ramifying in the SO and SR; all five Schaffer‐associated cells whose axons ramified extensively in the SR; both cells classified as quadrilaminar because their axons ramified in the SO, SP, SR, and SLM; one SO‐SO cell whose dendritic and axonal arbours were contained within the SO; and one perforant path‐associated cell with axonal and dendritic arbours within the distal SR and SLM. The majority (31 of 36) of PV‐IR neurones recorded were fast‐spiking, and most fast‐spiking cells tested (25 of 29 basket, 1 axo‐axonic, and 5 of 6 bistratified cells) were PV‐IR. However, 1 of 6 regular‐spiking basket, 1 of 4 regular‐spiking bistratified, and 3 of 5 burst‐firing basket cells were also PV‐IR. In contrast, the majority (17 of 27) of the CCK‐IR neurones recorded were regular‐spiking, 3 were burst‐firing, and 7 were fast‐spiking. These data confirm that the majority of PV‐IR and CCK‐IR axon terminals innervate proximal portions of CA1 pyramidal cells. Most PV‐IR cells are fast‐spiking, whereas most CCK‐IR cells are regular‐spiking. In both neurochemical classes basket cells predominate, but both groups included subpopulations of dendrite‐targeting cells. Despite these similarities, the two populations exhibited very different somatic distributions, and each contained cellular morphologies not represented in the other. J. Comp. Neurol. 443:346–367, 2002. © 2002 Wiley‐Liss, Inc.
Paraventricular nucleus of the human hypothalamus in primary hypertension: Activation of corticotropin‐releasing hormone neurons
Authors: Goncharuk Valeri D. , Van Heerikhuize Joop , Swaab Dick F. , Buijs Ruud M. 
Published: August 2002

AbstractBy using quantitative immunohistochemical and in situ hybridization techniques, we studied corticotropin‐releasing hormone (CRH) ‐producing neurons of the hypothalamic paraventricular nucleus (PVN) in patients who suffered from primary hypertension and died due to acute cardiac failure. The control group consisted of individuals who had normal blood pressure and died of acute heart failure due to mechanical trauma. Both magno‐ and parvocellular populations of CRH neurons appeared to be more numerous in the PVN of hypertensive patients. Quantitative analysis showed approximately a twofold increase in the total number of CRH neurons and a more than fivefold increase in the amount of CRH mRNA in the hypertensive PVN compared with the control. It is suggested that synthesis of CRH in hypertensive PVN is enhanced. Increased activity of CRH‐producing neurons in the PVN of hypertensive patients is proposed not only to entail hyperactivity of the hypothalamo‐pituitary‐adrenal axis, but also of the sympathetic nervous system and, thus, to be involved in the pathogenesis of hypertension. J. Comp. Neurol. 443:321–331, 2002. © 2002 Wiley‐Liss, Inc.