bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quinidine impairs proliferation of neurofibromatosis type 2‐deficient human malignant mesothelioma cells
Authors: Utermark Tamara , Alekov Alexi , Lerche Holger , Abramowski Vincent , Giovannini Marco , Hanemann Clemens Oliver 
Published: April 2003

AbstractBACKGROUNDHuman malignant mesotheliomas (HMMs) are aggressive tumors that arise from the mesothelium. They respond poorly to conventional tumor treatment and outcome is often fatal. Inactivating mutations of the neurofibromatosis type 2 (NF2) tumor suppressor gene merlin have been described in nearly 60% of primary malignant mesothelioma and in approximately 20% of the mesothelioma cell lines. Studies regarding human NF2 schwannoma cells revealed a higher proliferation and a larger noninactivating K+ outward current compared with controls. The enhanced proliferation of merlin‐deficient NF2 schwannoma cells could be reduced in the presence of quinidine, a K+ channel blocker, whereas the proliferation of normal Schwann cells is not affected. The current study was undertaken to evaluate the effect of quinidine on the proliferation of HMM cell lines in relation to their NF2 status.METHODSProliferation analyses using bromodeoxyuridine incorporation was performed by immunocytochemical staining and fluorescence assisted cell sorting. The patch‐clamp technique was applied for electrophysiologic characterization of the HMM cell lines. The cytochrome P450 2D6 locus, known to be mutated at high frequencies in NF2 patients and to be specifically inhibited by quinidine, was screened for mutations by cycle sequencing.RESULTSQuinidine selectively reduces the proliferation of merlin‐deficient HMM cell lines by causing a G0/G1 arrest, whereas the proliferation rates of merlin‐expressing HMM cell lines remain unchanged. The effect of quinidine on the proliferation of HMM cell lines appears to be correlated with the NF2 gene status but not with the K+ outward current. No relation to cytochrome P450 2D6 mutations was detected.CONCLUSIONSQuinidine or quinidine analogs are of potential therapeutic interest for the subset of merlin‐deficient mesothelioma tumors. Cancer 2003;97:1955–62. © 2003 American Cancer Society.DOI 10.1002/cncr.11275
Angiosarcoma after breast‐conserving therapy
Authors: Monroe Alan T. , Feigenberg Steven J. , Mendenhall Nancy Price 
Published: April 2003

AbstractBACKGROUNDAngiosarcoma arising in the irradiated breast after breast‐conserving therapy is being reported with increasing frequency. As more women undergo breast‐conserving therapy, the incidence can be expected to increase. Surgeons, medical oncologists, and radiation oncologists will be faced with difficult management decisions for this aggressive disease.METHODSA comprehensive review of all English‐language reports of angiosarcomas after breast‐conserving therapy was performed. Approximately 100 cases were reviewed for treatment details and outcome analysis was performed.RESULTSSurgical excision is associated with very high rates of disease recurrence (55 of 75 patients with at least 1 year of follow‐up; 73%). Local disease recurrences in the tumor bed or along the mastectomy scar are a component of almost all recurrences (96%). Distant metastases develop simultaneously or shortly after local recurrences. Hyperfractionated radiotherapy has successfully prevented local disease recurrences in a limited number of patients.CONCLUSIONSAngiosarcoma after breast‐conserving therapy is increasingly diagnosed in a small but significant portion of breast carcinoma survivors. The aggressive nature of this disease demands further investigation of adjuvant therapy to prevent recurrence of disease after surgery. Cancer 2003;97:1832–40. © 2003 American Cancer Society.DOI 10.1002/cncr.11277
False‐negative core needle biopsies of the breast
Authors: Shah Varsha I. , Raju Usha , Chitale Dhananjay , Deshpande Vikram , Gregory Nancy , Strand Vernon 
Published: April 2003

AbstractBACKGROUNDA benign diagnosis in a core needle biopsy (CNBx) of the breast performed for a clinically and/or radiologically suspicious abnormality is often due to a nonrepresentative sample. However, the discordance may not be recognized, resulting in a logistic delay in the diagnosis.METHODSTwenty‐seven false‐negative CNBxs were identified in 952 consecutive CNBxs of the breast (653 benign, 266 malignant, and 33 atypical) performed during a 1‐year period. Biopsies were analyzed with respect to clinical and radiologic findings, biopsy type, type of malignancy, and interval between the original CNBx and final diagnosis. Four hundred thirty‐eight (67%) of the patients with a benign CNBx diagnosis either underwent excision or had a minimum of 1‐year follow‐up (mean, 35.6 months; median, 36 months).RESULTSThe cancers missed on CNBx included 6 ductal carcinomas in situ, 17 invasive ductal carcinomas, 3 invasive lobular carcinomas, and 1 non‐Hodgkin lymphoma. The overall false‐negative rate was 9.1%. For palpable lesions, ultrasound‐guided CNBx had a lower rate of missed cancer (3.6%) compared with CNBx without image guidance (13.3%). The false‐negative rate for vacuum assisted CNBx biopsy was 7.6% (3.3% for the 11‐gauge needle, 22.2% for the 14‐gauge needle; 5.6% for nonpalpable mass lesions, 8.2% for microcalcifications). In all seven false‐negative CNBxs performed by radiologists, the discordance between the radiologic and pathologic findings was promptly recognized due to their standard follow‐up protocol. The discordance between the degree of clinical suspicion, radiologic impression, and the pathologic findings was not immediately recognized in 5 of 20 false‐negative CNBxs performed by surgeons (4 without radiologic guidance and 1 with ultrasound guidance), resulting in a delay in the diagnosis ranging from 112–336 days.CONCLUSIONSA false‐negative diagnosis of breast carcinoma was found to be more common in CNBx performed without image guidance but occurred to a lesser degree in image‐guided biopsies. A delay in diagnosis can be avoided by establishing a standard post‐CNBx follow‐up protocol. Cancer 2003;97:1824–31. © 2003 American Cancer Society.DOI 10.1002/cncr.11278
Induction of intensive tumor suppression by antiangiogenic photodynamic therapy using polycation‐modified liposomal photosensitizer
Authors: Takeuchi Yoshito , Kurohane Kohta , Ichikawa Kanae , Yonezawa Sei , Nango Mamoru , Oku Naoto 
Published: April 2003

AbstractBACKGROUNDThe authors previously observed that antiangiogenic scheduling of photodynamic therapy (PDT) was effective in causing tumor regression through hemostasis. It would thus be expected that photosensitizer entrapped in polycation liposomes (PCLs) would be efficiently taken up in tumor‐derived angiogenic vascular endothelial cells due to the strong electrostatic adhesion between the polycation and the plasma membrane, thus resulting in enhanced phototherapeutic efficacy.METHODSTumors and angiogenesis were induced by subcutaneous injection of Meth‐A sarcoma cells into 5‐week‐old male BALB/c mice. PDT treatment was performed by an intravenous (i.v.) injection of benzoporphyrin derivative monoacid ring A (BPD‐MA)‐entrapped liposomes or the PCLs (0.25 mg/kg in terms of BPD‐MA), followed by exposure to a laser light of 689 nm with 150 J/cm2 of fluence 15 minutes post injection.RESULTSAs a result of PDT on angiogenesis‐model mice prepared by the dorsal air sac technique, neovascular destruction after laser irradiation was observed when BPD‐MA entrapped in PCLs was used. Furthermore, strong suppression of tumor growth was identified by the PCL‐mediated PDT treatment along with a prolonged life span for the mice. Destruction of angiogenic vessels and subsequent tumor cell apoptosis were observed after PCL‐mediated PDT treatment in an immunofluorescence study. Interestingly, the biodistribution of the injected BPD‐MA that was delivered by PCLs indicated invariable photosensitization levels in tumor tissues.CONCLUSIONSThe study revealed that antiangiogenic PDT treatment using a low dose of BPD‐MA entrapped in PCLs efficiently induced the destruction of angiogenic vessels and subsequent tumor suppression by vessel occlusion. Cancer 2003;97:2027–34. © 2003 American Cancer Society.DOI 10.1002/cncr.11283
Role of surgery for nonmetastatic abdominal rhabdomyosarcomas
Authors: Cecchetto Giovanni , Bisogno Gianni , Treuner Jorn , Ferrari Andrea , Mattke Adrian , Casanova Michela , Dall'Igna Patrizia , Zanetti Ilaria , Volpato Sandra , Siracusa Fortunato , Scarzello Gianni , Boglino Camillo , Carli Modesto 
Published: April 2003

AbstractBACKGROUNDIn the current study, the authors aim to evaluate clinical features and treatment results observed in patients from the German and Italian studies who had nonmetastatic abdominal rhabdomyosarcomas (RMS).METHODSOne hundred sixty‐one patients were observed; 78 registered in the German studies between October 1980 and August 1995, and 83 registered in the Italian studies between April 1975 and December 1995. The age range of the patients was 0–18 years (median, 4 yrs). The distribution of tumor sites was as follows: 32 intraperitoneal, 42 retroperitoneal, 75 pelvic, and 12 not otherwise specified (NOS). Most patients had a large and invasive primary mass (26 T1b, 114 T2b). The breakdown in histology was as follows: 116 embryonal, 34 alveolar, and 11 other (leiomyomatous, pleomorphic, and NOS); all cases were staged according to the Intergroup Rhabdomyosarcoma Studies (IRS) system. Nine Group I patients were treated after surgery with chemotherapy (CT) (radiotherapy [RT] was delivered to treat alveolar RMS in the 1991 German and 1988 Italian studies); 19 Group II patients received CT + RT (40–44 Gy); 133 Group III patients underwent neoadjuvant CT ± surgery and/or RT (54 Gy) + CT. Different CT regimens (based primarily on the administration of vincristine, dactinomycin, doxorubicin, and cyclophosphamide or ifosfamide) were adopted. RT was not recommended for patients age < 3 years.RESULTSThe 10‐year overall survival (OS) and progression‐free survival (PFS) were 47.2% and 43.9%, respectively. The OS was related significantly to the following variables: histology (alveolar, 29.4% vs. nonalveolar, 52.1% [P = 0.0156]), tumor size (> 5 cm, 42.1% vs. < 5 cm, 81% [P = 0.005]), age (< 10 yrs, 51.4% vs. ≥ 10 yrs, 27.8% [P = 0.02]), complete surgery at diagnosis or after CT (±RT) (70.4% vs. 34.4% without it [P = 0.0015]). Most patients who achieved the delayed local control had responded well to neoadjuvant CT.CONCLUSIONSTumor size, histology, age, and initial or delayed achievement of local control were important prognostic factors. Most relapsed patients had unfavorable outcomes. Cancer 2003;97:1974–80. © 2003 American Cancer Society.DOI 10.1002/cncr.11285
Phase II trial of gemcitabine in patients with advanced sarcomas (E1797)
Authors: Okuno Scott , Ryan Louise M. , Edmonson John H. , Priebat Dennis A. , Blum Ronald H. 
Published: April 2003

AbstractBACKGROUNDThe current study was conducted to evaluate the antitumor activity and toxicity of gemcitabine in patients with advanced sarcoma.METHODSTwenty‐five patients with advanced sarcomas, who previously were untreated for metastatic disease, were treated on an Eastern Cooperative Oncology Group Phase II study. Patients ranged in age from 27 to 79 years, with a median age of 59 years. The most common histology was leiomyosarcoma (54%). The grades of the tumors were high in 40%, moderate in 24% and low in 12%. Gemcitabine was given at a dose of 1250 mg/m2 as a 30‐minute infusion weekly for 3 weeks followed by 1 week of rest.RESULTSOne of the 25 patients (4%) (90% confidence interval [90% CI], 0–18%) achieved a partial response lasting 8 months. The estimated overall median survival was 15 months. The 1‐year estimated survival rate was 63% (90% CI, 47–84%). The estimated median progression‐free survival (PFS) was 13 months with a 1‐year PFS rate of 56% (90% CI, 41–76%). Grade 3–4 toxicities (by CTC criteria) were observed in all 25 patients. No lethal toxicity (Grade 5) related to treatment was found.CONCLUSIONSThe results of the current study demonstrated that gemcitabine given at this schedule and dose in this population of patients with advanced sarcoma had limited activity. Cancer 2003;97:1969–73. © 2003 American Cancer Society.DOI 10.1002/cncr.11290
Fibrolamellar hepatocellular carcinoma in children and adolescents
Authors: Katzenstein Howard M. , Krailo Mark D. , Malogolowkin Marcio H. , Ortega Jorge A. , Qu Wenchun , Douglass Edwin C. , Feusner James H. , Reynolds Marleta , Quinn John J. , Newman Kurt , Finegold Milton J. , Haas Joel E. , Sensel Martha G. , Castleberry Robert P. , Bowman Laura C. 
Published: April 2003

AbstractBACKGROUNDChildren with hepatocellular carcinoma (HCC) were treated on a prospective, randomized trial and were then analyzed to determine whether children with the fibrolamellar (FL) histologic variant of HCC have a more favorable presentation, increased surgical resectability, greater response to therapy, and improved outcome compared with children who have typical HCC.METHODSForty‐six patients were enrolled on Pediatric Intergroup Hepatoma Protocol INT‐0098 (Pediatric Oncology Group Study 8945/Children's Cancer Group Study 8881) between August 1989 and December 1992. After undergoing initial surgery or biopsy, children with Stage I HCC (n = 8 patients), Stage III HCC (n = 25 patients), and Stage IV HCC (n = 13 patients) were assigned randomly, regardless of histology, to receive treatment either with cisplatin, vincristine, and fluorouracil (n = 20 patients) or with cisplatin and continuous‐infusion doxorubicin (n = 26 patients).RESULTSTen of 46 patients (22%) had the fibrolamellar variant of HCC (FL‐HCC). For the entire cohort, the estimated 5‐year event free survival (EFS) rate (± standard deviation) was 17% ± 6%. There was no difference in outcome among patients who were treated with either regimen. The 5‐year EFS rate for patients with FL‐HCC was no different the rate for patients with typical HCC (30% ± 15% vs. 14% ± 6%, respectively; P = 0.18), although the median survival was longer in patients with FL‐HCC. There was no difference in the number of patients with advanced‐stage disease, the incidence of surgical resectability at diagnosis, or the response to treatment between patients with FL‐HCC and patients with typical HCC.CONCLUSIONSChildren with FL‐HCC do not have a favorable prognosis and do not respond any differently to current therapeutic regimens than patients with typical HCC. Children with initially resectable HCC have a good prognosis irrespective of histologic subtype, whereas outcomes are poor uniformly for children with advanced‐stage disease. The use of novel chemotherapeutic agents and the incorporation of other treatment modalities are indicated to improve the dismal survival of pediatric patients with all histologic variants of advanced‐stage HCC. Cancer 2003;97:2006–12. © 2003 American Cancer Society.DOI 10.1002/cncr.11292
Impact of radionecrosis on cognitive dysfunction in patients after radiotherapy for nasopharyngeal carcinoma
Authors: Cheung Mei‐Chun , Chan Agnes S. , Law Stephen C. , Chan John H. , Tse Vincent K. 
Published: April 2003

AbstractBACKGROUNDCognitive dysfunction is common in patients who develop radionecrosis after receiving radiotherapy for nasopharyngeal carcinoma (NPC). However, the impact of the location and volume of radionecrosis on cognitive dysfunction remains unclear. The authors found a significant association between the severity of cognitive impairment and the volume of radionecrosis; in turn, the volume of radionecrosis was affected by patient age at time radiotherapy was completed.METHODSFifty patients with NPC who received radiotherapy were evaluated by a battery of neuropsychologic tests of cognitive function. The brain lesion volume was quantified, and the lesion locations were identified by standardized brain templates. The results of the neuropsychologic tests were correlated with lesion volume. Gender, education, age at the completion of radiotherapy, brain volume, total dose, and fractional dose were evaluated as risk factors for lesion volume.RESULTSLesion volume was correlated significantly with the severity of cognitive deficits. Larger left‐hemisphere lesions were correlated with lower verbal memory (from P < 0.001 to P = 0.008) and language abilities (from P = 0.001 to P = 0.018), whereas larger right‐hemisphere lesions were associated with worse visual memory (from P = 0.009 to P = 0.039). Finally, patients who received radiotherapy at a younger age had smaller lesion volumes (P < 0.001).CONCLUSIONSThe volume and location of radionecrosis had an influential impact on the pattern of cognitive impairment found in patients with NPC, and patient age at the time radiotherapy was completed appeared to affect the volume of radionecrosis found after radiotherapy. Cancer 2003;97:2019–26. © 2003 American Cancer Society.DOI 10.1002/cncr.11295
Phase II study of SU5416—a small‐molecule, vascular endothelial growth factor tyrosine‐kinase receptor inhibitor—in patients with refractory myeloproliferative diseases
Authors: Giles Francis J. , Cooper Maureen A. , Silverman Lewis , Karp Judith E. , Lancet Jeffrey E. , Zangari Maurizio , Shami Paul J. , Khan Khuda D. , Hannah Alison L. , Cherrington Julie M. , Thomas Deborah A. , Garcia‐Manero Guillermo , Albitar Maher , Kantarjian Hagop M. , Stopeck Alison T. 
Published: April 2003

AbstractBACKGROUNDIncreased bone marrow angiogenesis and vascular endothelial growth factor (VEGF) levels are of adverse prognostic significance in patients with myeloproliferative disorders (MPD), including agnogenic myeloid metaplasia (AMM), chronic myeloid leukemia in blastic phase (CML‐BP), and chronic myelomonocytic leukemia (CMML). VEGF is a soluble, circulating, angiogenic molecule that acts through receptor tyrosine kinases (RTK), including VEGF receptor 2 (VEGFR‐2). SU5416 is a small‐molecule RTK inhibitor (RTKI) that targets VEGFR‐2, c‐kit, and fms‐related tyrosine kinase Flk2.METHODSAdult patients with advanced CMML, AMM, CML‐BP, or other BCR‐ABL negative MPD were entered on a multicenter, Phase II study.RESULTSThirty‐two patients (19 patients with BCR‐ABL negative MPD, 6 patients with CMML, 4 patients with CML‐BP, and 3 patients with AMM) with a median age of 66 years (range, 29–85 years) received SU5416 145 mg/m2 twice weekly intravenously for a median of three 4‐week cycles (maximum, 12 cycles). Drug‐related Grade 3–4 toxicities included acute abdominal pain (13%), bone pain (9%), infusion‐related dyspnea (9%) or headache (6%), fatigue (6%), diarrhea (3%), and catheter site reactions (3%). Eleven patients (34%) did not receive a second cycle of therapy (6 patients had progressive disease, 3 because of adverse events; 2 patients withdrew due to lack of response). One patient with AMM achieved a partial response. Eight patients received more than 6 months of therapy.CONCLUSIONSSU5416 had minimal clinical activity in patients with MPD. Long‐term administration of a twice‐weekly, hyperosmolar, intravenous solution containing polyoxyl 35 castor oil was difficult. More tolerable RTKI may be worthy of further investigation in patients with MPD. Cancer 2003;97:1920–8. © 2003 American Cancer Society.DOI 10.1002/cncr.11315
Attributable and absolute risk of lung cancer death by smoking status: Findings from the Japan collaborative cohort study
Authors: Ando Masahiko , Wakai Kenji , Seki Nao , Tamakoshi Akiko , Suzuki Koji , Ito Yoshinori , Nishino Yoshikazu , Kondo Takaaki , Watanabe Yoshiyuki , Ozasa Kotaro , Ohno Yoshiyuki ,   JACC Study Group
Published: April 2003

AbstractEstimating the proportion of lung cancer deaths that can be avoided is important in assessing the potential impact of antismoking efforts on the reduction of lung cancer deaths. We calculated the population attributable risk (PAR) and absolute risk of lung cancer death according to smoking status based on the Japan Collaborative Cohort (JACC) Study. The analytic cohort included 45,010 males and 55,724 females aged 40–79 years. Cox proportional hazards model was used to determine age‐adjusted relative risks and PAR according to smoking status. We also computed lung cancer mortality according to age and smoking status. In males, 52.2% and 14.8% of lung cancer deaths were attributable to current and former cigarette smoking, respectively. In females, the corresponding figures were 11.8% and 2.8%. Among current male smokers, the relative risk was strongly correlated with the intensity and duration of cigarette smoking. In contrast, the PAR was associated with an intermediate level of smoking except for the years of smoking: the largest PARs were observed in those with 20–29 cigarettes per day, 40–59 pack‐years and 20–22 years old at starting smoking. Absolute risks were estimated to increase with age and duration of smoking and not to decrease even after cessation. These findings suggest that avoidable lung cancer deaths are primarily among light to moderate smokers who are considered amenable to population‐based antismoking strategies. For all current smokers, immediate cessation is encouraged because it offers the only realistic way to avoid a substantial increase in lung cancer mortality brought about by further continuation of smoking. © 2003 Wiley‐Liss, Inc.
Ki‐67 index enhances the prognostic accuracy of the urothelial superficial bladder carcinoma risk group classification
Authors: Santos Lúcio , Amaro Teresina , Costa Céu , Pereira Sofia , Bento Maria José , Lopes Paula , Oliveira Jorge , Criado Begoña , Lopes Carlos 
Published: April 2003

AbstractApproximately 80% of bladder tumors are urothelial superficial papillary carcinomas (USPC). Despite a generally good prognosis, these tumors have a strong propensity to recur and about 1/3 of them compared to disease progression. Histological assessment of these superficial tumors is not sufficiently discriminator in predicting prognosis; therefore, we decided to evaluate the prognostic significance of p53 and Ki‐67 immunoexpression in low‐grade (GI‐II) USPC in order to predict the potential outcome of these tumors. P53 and Ki‐67 immunoexpression were studied in function of recurrence‐free and progression‐free survival in 159 primary superficial bladder tumors. A prognostic risk model based on grade, stage and multifocality was also evaluated. P53 accumulation was significantly related to tumor progression (p=0.006). High Ki‐67 index (≥18%) and multifocality were significantly related to recurrence (both p=0.0001) and progression‐free survival (both p=0.0001) and were independent prognostic factors in the multivariate analysis. The prognostic risk model based on grade, stage and multifocality was not an efficient discriminator of outcome. Adding the Ki‐67 index into the risk model, single pTa/T1‐GI Ki‐67 positive tumors, usually classified as low risk, were reclassified as of intermediate risk. After this reclassification, the risk group model identified a subgroup of pTa/T1‐G1 with a high risk of recurrence and progression. Ki‐67 index is a reliable prognostic marker in urothelial superficial bladder carcinoma and, when included into a risk profile classification of the low‐grade USPC, the accuracy of the prognostic discrimination is enhanced. © 2003 Wiley‐Liss, Inc.