bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decreased expression of DFF45/ICAD is correlated with a poor prognosis in patients with esophageal carcinoma
Authors: Konishi Shigeru , Ishiguro Hideyuki , Shibata Yasuyuki , Kudo Junzo , Terashita Yukio , Sugiura Hironori , Koyama Hiroshi , Kimura Masahiro , Sato Atsushi , Shinoda Noriyuki , Kuwabara Yoshiyuki , Fujii Yoshitaka 
Published: December 2002

AbstractBACKGROUNDDNA fragmentation factor 45 (DFF45)/inhibotor of caspase activated DNAse (ICAD) forms a complex with DFF40/CAD and inhibits its DNA cleaving function during apoptosis. DFF45 also functions as a chaperone for native DFF40 and is necessary for its function. It has been indicated that defects in the apoptotic pathway may exist in neoplastic cells.METHODSThe authors investigated mRNA expression of DFF45 in a series of 46 esophageal squamous cell carcinoma (ESCC) specimens using polymerase chain reaction amplification. The results were correlated with the patients' clinicopathologic characteristics.RESULTSDFF45 mRNA expression was significantly lower in tumors with higher pathologic stage, higher tumor status (T status), lymph node metastasis, or more extensive lymphatic invasion. Patients who had low DFF45 mRNA expression (indicated by the ratio of DFF45 mRNA expression in tumor to DFF45 mRNA expression in normal esophageal mucosa [tumor:normal] < 1) had a significantly shorter survival after undergoing surgery compared with patients who had high DFF45 mRNA expression (tumor:normal > 1, P = 0.0006; log‐rank test, P = 0.0003; median follow‐up, 14.6 months).CONCLUSIONSPatients with ESCC with decreased DFF45 mRNA expression levels had a poor prognosis compared with patients who had high DFF45 mRNA expression levels. Cancer 2002;95:2473–8. © 2002 American Cancer Society.DOI 10.1002/cncr.10987
Telomerase reverse transcriptase subunit immunoreactivity
Authors: Iczkowski Kenneth A. , Pantazis Cooley G. , McGregor Douglas H. , Wu Yaping , Tawfik Ossama W. 
Published: December 2002

AbstractBACKGROUNDTelomerase, a ribonucleoprotein complex that maintains telomeric DNA, has been detected in 67–93% of prostate carcinomas by telomeric repeat‐amplification protocol assay (involving polymerase chain reaction). One study used in situ hybridization in nine patients; however, to date, no immunohistochemical results have been published.METHODSFrom two hospitals, the authors compiled data on 62 patients who underwent prostatectomy from January 1996 to May 2001. Representative tissue sections were immunostained with a polyclonal antibody to telomerase reverse transcriptase (TERT), the catalytic subunit of telomerase. Staining was evaluated by two observers and was correlated with grade, stage, and biochemical failure. There were 28 sections from low‐grade to intermediate‐grade tumors (Gleason score, 3–6), 14 sections with a Gleason score of 3 + 4 = 7, 9 sections with a Gleason score of 4 + 3 = 7, and 11 sections from high‐grade tumors (Gleason score, 8–10).RESULTSFrom low‐grade to high‐grade tumors, the four groups described above disclosed nuclear reactivity in 64%, 100%, 100%, and 100% of sections, respectively. Mean percentages of 5%, 15%, 40%, and 51% of nuclei were reactive in the respective groups (P < 0.0001) with intratumoral heterogeneity. The percent of reactive tumor nuclei was not correlated with pathologic stage (P = 0.32) or margin status (P = 0.35). The basal cell layer in sections of high‐grade prostatic intraepithelial neoplasia (HGPIN) and benign/atrophic acini was reactive; secretory cells were reactive in 13 of 34 HGPIN foci (38%) in 1–20% of nuclei and were never reactive in benign acini. Lymphocytes and skeletal muscle were reactive. Weak, nonspecific, cytoplasmic staining was noted in benign and tumor acini.CONCLUSIONSLike cytokeratin 34βE12, nuclear anti‐TERT reactivity is a basal cell marker in nonneoplastic prostatic acini. Anti‐TERT reactivity is acquired by secretory cells in tumorigenesis, but consistent reactivity is restricted to high‐grade carcinoma (Gleason primary pattern ≥4). This histologic evidence suggests that higher grade tumors have maximally activated telomerase and may be most responsive to antitelomerase therapy. Cancer 2002;95:2487–93. © 2002 American Cancer Society.DOI 10.1002/cncr.10988
Urinary levels of urokinase‐type plasminogen activator and its receptor in the detection of bladder carcinoma
Authors: Casella Roberto , Shariat Shahrokh F. , Monoski Mara A. , Lerner Seth P. 
Published: December 2002

AbstractBACKGROUNDThe authors found previously that plasma levels of urokinase‐type plasminogen activator (uPA) and its receptor (uPAR) were elevated in patients with bladder carcinoma and were associated with features of biologically aggressive disease. In the current study, they tested the hypothesis that elevated urinary levels of uPA and uPAR would predict the presence of bladder malignancy by comparing the performance of uPA and uPAR with the performance of bladder wash‐out cytology in the noninvasive diagnosis of bladder tumors.METHODSAn enzyme‐linked immunosorbent assay was used to compare levels of uPA and uPAR in urine that was collected before cystoscopy from 122 patients with bladder carcinoma and from 107 participants in a control group. Seventy‐two patients had clinical Tis or Ta transitional cell carcinoma, and 50 patients had invasive disease (≥ T1); 85 patients had clinical Grade 1–2 tumors, and 37 patients had Grade 3 tumors. For cytology, only high grade was considered positive.RESULTSUrinary levels of uPA and uPAR were higher in patients with bladder carcinoma compared with levels in the control group (P < 0.001 and P = 0.016, respectively). However, only uPA levels were elevated in patients with abnormal urinary cytology (P = 0.006). After controlling for cytology (odds ratio [OR], 10.182; 95% confidence interval [95%CI], 4.451–23.291; P < 0.001), uPAR (P for trend = 0.168), and age (P = 0.091), those in the highest quartile for uPA had an increased risk of bladder carcinoma compared with those in the lowest quartile (OR, 3.022; 95%CI, 1.295–7.054; P for trend = 0.031).CONCLUSIONSThe current findings suggest that urinary levels of uPA, but not uPAR, are related to the risk of bladder carcinoma. The study confirmed the central role of urinary cytology in the noninvasive diagnosis of bladder carcinoma. Cancer 2002;95:2494–9. © 2002 American Cancer Society.DOI 10.1002/cncr.10989
Elevated focal adhesion kinase expression facilitates oral tumor cell invasion
Authors: Schneider Galen B. , Kurago Zoya , Zaharias Rebecca , Gruman Lynn M. , Schaller Michael D. , Hendrix Mary J. C. 
Published: December 2002

AbstractBACKGROUNDUnderstanding the molecular mechanisms of metastasis is critical with respect to oral tumorigenesis. The focal adhesion kinase (FAK) is an intracellular tyrosine kinase associated with the regulation of cell growth, migration, and survival. The purpose of the current study was to determine whether elevated FAK expression in oral malignancies was associated with increased invasiveness and oral carcinoma.METHODSImmunohistochemical analysis was used to assess levels of FAK expression in archived oral carcinoma tissue samples. Invasion assays after transfections were used to assess the effect of increased FAK expression on invasive potential of oral tumor cells.RESULTSThe human oral carcinoma cell line SCC25 was significantly more invasive (P < 0.05) and expressed higher levels of FAK compared with the less invasive human oral carcinoma cell line SCC15. FAK expression was 3.0‐fold higher in the SCC15 cell line and 5.0‐fold higher in the SCC25 cell line compared with normal epithelial cells. In the highly invasive SCC25 cell line, FAK expression was 1.5‐fold higher compared with the less invasive SCC15 cell line. FAK immunostaining in oral tumors was significantly more intense compared with the immunostaining in surrounding normal epithelium or chronic mucositis. Overexpression of FAK in low‐invading SCC15 cells resulted in a 4.5‐fold increase in the rate of invasion compared with untransfected or neotransfected control SCC15 cell lines and a nearly 1.5‐fold greater rate compared with the highly invasive untransfected SCC25 cell line.CONCLUSIONSThe current results suggest that enhanced expression of FAK in oral carcinoma cells may lead to a selective growth advantage and increased invasive potential of the primary oral tumor. Cancer 2002;95:2508–15. © 2002 American Cancer Society.DOI 10.1002/cncr.10992
Which dimensions of health‐related quality of life are altered in patients attending the different gynecologic oncology health care settings?
Authors: Capelli Giovanni , De Vincenzo Rosa I. , Addamo Alice , Bartolozzi Francesco , Braggio Nicola , Scambia Giovanni 
Published: December 2002

AbstractBACKGROUNDWe evaluated the feasibility of measuring health‐related quality of life (HRQOL) in a gynecologic oncology clinic by using an instrument that is nonspecific for cancer patients. Our aim was to study whether the HRQOL perception of cancer patients differed from general population norms for the same age and gender and if it varied across cancer type, cancer status, age, health care setting, and reason for the encounter.METHODSParticipants in this study included 115 women between the ages of 21 and 83 years who were referred to a university hospital for ovarian, endometrial, and cervical carcinoma. They completed the SF‐36 questionnaire. Mean results for the entire sample, for different disease status (primary vs. progressive/recurrent disease), and reason for encounter (surgery, preoperative, postoperative, palliative chemotherapy, and follow‐up) were compared with age‐specific expected mean values for each SF‐36 scale, based on published Italian reference values for the healthy population.RESULTSPatients' attitude to the questionnaire was generally good. Mean values on the SF‐36 scales varied. Role (Physical and Emotional) scales showed the highest differences from the expected age‐specific values in all situations. Patients with primary disease showed little or no differences for the other six scales from the expected values, whereas a significant 10‐point mean decrease in every SF‐36 scale was recorded for patients with progressive/recurrent disease. A biologic interaction among cervical carcinoma, age, and disease status was found in multivariate models, showing worst scores for patients with progressive/recurrent cervical carcinoma on almost all scales.CONCLUSIONSAdministration of generic HRQOL questionnaires in specialist health care delivery settings is feasible and well accepted and may help physicians and nurses to look beyond “what's wrong” in their patients. Cancer 2002;95:2500–7. © 2002 American Cancer Society.DOI 10.1002/cncr.10993
Chemotherapy with gemcitabine‐containing regimens for locally recurrent or metastatic nasopharyngeal carcinoma
Authors: Ma Brigette B. Y. , Tannock Ian F. , Pond Gregory R. , Edmonds Matthew R. , Siu Lillian L. 
Published: December 2002

AbstractBACKGROUNDResults from Phase II trials conducted in Asia have shown that gemcitabine alone (GEM) or with cisplatin (GC) is active among patients with metastatic or locally recurrent nasopharyngeal carcinoma (NPC).METHODSAt the Princess Margaret Hospital (PMH), Toronto, 32 patients with NPC were treated with GEM (n = 18) or GC (n = 14) from January 2000 to October 2001. Patients either received 1000 mg/m2 GEM on Days 1, 8, and 15 every 28 days as a single agent, or with cisplatin (CG) given on day 2 at 70 mg/m2.RESULTSMost patients (91%) were of Southeast Asian ancestry and 29 (91%) had Type 2 (World Health Organization 1991 classification) nonkeratinizing histology. Sixteen of the GEM (89%) and five (36%) of the GC patients had received chemotherapy before entering the study. Median follow‐up was 32 weeks (range, 2–97 weeks) for both groups. In the GEM group, there were five (28%) partial responses (PR) and one (6%) complete response (CR), giving an overall response rate of 34% (95% confidence interval [CI], 13.59). In the GC group, there were two (14%) CRs and seven PRs (50%), giving an overall response of 64% (95% CI, 35–87). Hematologic toxicity was dose limiting but uncomplicated. Nonhematologic toxicity included one patient with reversible reactivation of hepatitis, one with Grade 3 cisplatin‐related sensory neuropathy, and three with cardiovascular events that were possibly related to chemotherapy. The median duration of response for the GEM and GC patients was 17 and 24 weeks and the 1‐year survival rate was 48% (95% CI, 18–78) and 69% (95% CI, 40–99), respectively. Median survival has not been reached.CONCLUSIONSOur study confirms that GEM is an active and tolerable drug for patients with NPC. Cancer 2002;95:2516–23. © 2002 American Cancer Society.DOI 10.1002/cncr.10995
Loss of adhesion‐regulated proteinase production is correlated with invasive activity in oral squamous cell carcinoma
Authors: Ghosh Supurna , Munshi Hidayatullah. G. , Sen Ratna , Linz‐McGillem Laura A. , Goldman Robert D. , Lorch Jochen , Green Kathleen J. , Jones Jonathan C. R. , Stack M. Sharon 
Published: December 2002

AbstractBACKGROUNDOral squamous cell carcinoma (OSCC) is the most common malignancy of the oral cavity. However, the cellular and biochemical factors that underlie locoregional and distant spread of the disease are poorly understood. Invasion of OSCC requires multiple cellular events including dissolution of cell‐cell junctions, basement membrane attachment, extracellular matrix proteolysis, and migration.METHODSWe evaluated these properties in vitro using premalignant gingival keratinocytes (ppl26) and two OSCC lines (SCC15 and SCC68). Expression of adhesion molecules integrins and cadherins, cytoplasmic intermediate filaments (IF) vimentin and keratin as well as matrix degrading proteins were evaluated. Moreover, regulation of protease production by adhesion molecules was tested.RESULTSAll cell lines contained comparable levels of the epithelial cell‐cell adhesion molecule, E‐cadherin. Differential expression of cytoplasmic IF was evident between premalignant pp126 cells and OSCC cell lines. Expression levels of the α3β1 integrin, utilized for attachment to laminin‐5 and other matrix proteins, was high in SCC68 cells, moderate in SCC15 cells, and low in ppl26 cells. α3β1 integrin clustering up‐regulates expression of urinary‐type plasminogen activator (uPA) in ppl26 cells via a mechanism involving ERK activation. Both ppl26 and SCC15 cells were responsive to α3β1 clustering, resulting in enhanced uPA expression. However, basal uPA levels were high in SCC68 cells and integrin clustering did not further stimulate uPA production. ERK was constitutively activated in SCC68 cells and treatment of cells with an inhibitor of ERK activation (PD98059) reduced uPA expression. Consistent with the enhanced proteolytic potential, SCC68 cells readily penetrated Matrigel and invasion was blocked by an anticatalytic uPA antibody.CONCLUSIONSThese data suggest that loss of adhesion‐regulated proteinase production may lead to elevated pericellular proteinase activity and coincident alterations in cytoskeletal IF protein expression, thereby contributing to the invasive potential of OSCC. Cancer 2002;95:2524–33. © 2002 American Cancer Society.DOI 10.1002/cncr.10997
An elevated serum beta‐2‐microglobulin level is an adverse prognostic factor for overall survival in patients with early‐stage Hodgkin disease
Authors: Chronowski Gregory M. , Wilder Richard B. , Tucker Susan L. , Ha Chul S. , Sarris Andreas H. , Hagemeister Fredrick B. , Barista Ibrahim , Hess Mark A. , Cabanillas Fernando , Cox James D. 
Published: December 2002

AbstractBACKGROUNDThe relative importance of prognostic factors in patients with early‐stage Hodgkin disease remains controversial. The purpose of this study was to evaluate prognostic factors among patients who received chemotherapy before radiotherapy.METHODSFrom 1987 to 1995, 217 consecutive patients ranging in age from 16 to 88 years (median, 28 years) with Ann Arbor Stage I (n = 55) or II (n = 162) Hodgkin disease underwent chemotherapy before radiotherapy at a single center. Most were treated on prospective studies. Patients received a median of three cycles of induction chemotherapy. Mitoxantrone, vincristine, vinblastine, and prednisone (NOVP), doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), mechlorethamine, vincristine, procarbazine, and prednisone (MOPP), cyclophosphamide, vinblastine, procarbazine, prednisone, doxorubicin, bleomycin, dacarbazine, and CCNU (CVPP/ABDIC), or other chemotherapeutic regimens were given to 160, 18, 15, 10, and 14 patients, respectively. The median radiotherapy dose was 40 Gy. Serum β‐2‐microglobulin (β‐2M) levels ranged from 1.0 to 4.1 mg/L (median, 1.7 mg/L; upper limit of normal, 2.0 mg/L). We studied univariate and multivariate associations between survival and the following clinical features: serum β‐2M level above 1.25 times the upper limit of normal (n = 12), male gender (n = 113), hypoalbuminemia (n = 11), and bulky mediastinal disease (n = 94).RESULTSFollow‐up of surviving patients ranged from 0.9 to 13.4 years (median, 6.6 years) and 92% were observed for 3.0 or more years. Nineteen patients have died. Only elevation of the serum β‐2M level was an independent adverse prognostic factor for overall survival (P = 0.0009).CONCLUSIONSThe prognostic significance of a simple, widely available, and inexpensive blood test, β‐2M, has not been studied routinely in patients with Hodgkin disease and should be tested prospectively in large, cooperative group trials. Cancer 2002;95:2534–8. © 2002 American Cancer Society.DOI 10.1002/cncr.10998
Long‐term cognitive outcome, brain computed tomography scan, and magnetic resonance imaging in children cured for acute lymphoblastic leukemia
Authors: Iuvone Laura , Mariotti Paolo , Colosimo Cesare , Guzzetta Francesco , Ruggiero Antonio , Riccardi Riccardo 
Published: December 2002

AbstractBACKGROUNDPrevention of meningeal recurrence achieved by intrathecal methotrexate (MTX) and systemic chemotherapy is part of standard acute lymphoblastic leukemia (ALL) treatment. Cranial irradiation has been a routine part of past protocol treatment but is currently reserved only for select subsets of patients. Central nervous system (CNS) prophylaxis may cause brain abnormalities such as intracerebral calcifications, cerebral atrophy, and white matter alterations. In addition, long‐term neuropsychologic sequelae following CNS prophylaxis have been investigated marginally in children cured for ALL.METHODSTo explore possible correlations between neuroimaging findings and neuropsychologic outcome, we used detailed cognitive tests to evaluate 21 children with ALL who received cranial irradiation (range, 18–24 Gy) plus intrathecal MTX as CNS prophylaxis. All children were followed prospectively once a year by cerebral computed tomographic scan and magnetic resonance imaging. All patients had continuous complete disease remission for at least 4 years and cognitive tests were performed after neuroradiologic examinations.RESULTSWhite matter abnormalities were associated with poor performance only in a task exploring visual motor integration in about 50% of patients. Intracerebral calcifications correlate with the number of intrathecal MTX doses and with low scores in total intellectual quotient, performance intellectual quotient, and significant impairment in attention and visual motor integration tests. Girls are more vulnerable to the effects of CNS prophylaxis, whereas age at treatment and radiotherapy dose are not relevant to neuropsychologic outcome.CONCLUSIONSOur results indicate the need for careful follow‐up of children's cognitive abilities because global intellectual measures often fail to detect specific disorders that may cause learning difficulties. Moreover, as the clinical implications of neuroimaging findings are often limited, periodic extensive evaluation by specific neurocognitive tests of mental abilities is recommended to detect early signs of cognitive impairment. Cancer 2002;95:2562–70. © 2002 American Cancer Society.DOI 10.1002/cncr.10997
Serum insulin‐like growth factor I evaluation as a useful tool for predicting the risk of developing hepatocellular carcinoma in patients with hepatitis C virus‐related cirrhosis
Authors: Mazziotti Gherardo , Sorvillo Francesca , Morisco Filomena , Carbone Antonella , Rotondi Mario , Stornaiuolo Gianfranca , Precone Davide F. , Cioffi Michele , Gaeta Giovanni B. , Caporaso Nicola , Carella Carlo 
Published: December 2002

AbstractBACKGROUNDAlthough experimental studies have demonstrated an important role of insulin‐like growth factor I (IGF‐I) in hepatocarcinogenesis, the clinical data about IGF‐I in patients with hepatocellular carcinoma (HCC) are scarce and controversial. To the authors' knowledge, this is the first prospective study investigating the longitudinal correlation between modifications in serum IGF‐I levels and the development of HCC in a cohort of patients with hepatitis C virus (HCV)‐related cirrhosis.METHODSOne hundred fourteen consecutive patients with HCV‐related Child Grade A cirrhosis were followed prospectively at the Second University of Naples for 56.4 ± 12.0 months with ultrasound examinations of the liver and serum α‐fetoprotein determination every 6 months. At each clinical evaluation, the severity of disease was graded according to the established Child–Pugh scoring system. Serum IGF‐I levels were measured prospectively at the study entry and at least every 12 months throughout follow‐up.RESULTSTwenty patients (19.2%) developed HCC during follow‐up. Eleven of these patients had persistent Child Grade A cirrhosis for the whole study, whereas the other 9 patients developed HCC after their cirrhosis progressed from Child Grade A to Grade B. In patients who remained free of HCC for the whole study, serum IGF‐I concentrations did not modify significantly during follow‐up. Conversely, in patients who developed HCC, IGF‐I levels decreased significantly during follow‐up (from 72.6 ± 29.9 μg/L to 33.8 ± 14.5 μg/L; P = 0.001). In these patients, the significant decrease occurred both in patients with persistent Child Grade A cirrhosis and in patients with cirrhosis that progressed from Child Grade A to Grade B. The reduction in IGF‐I level preceded the diagnosis of HCC by 9.3 ± 3.1 months.CONCLUSIONSThis prospective study demonstrates that, in patients with HCV‐related cirrhosis, 1) the development of HCC is accompanied by a significant reduction of serum IGF‐I levels independent of the grade of impairment of liver function; and 2) modification of the IGF‐I level precedes the morphologic appearance of HCC, permitting a precocious diagnosis of the tumor. Cancer 2002;95:2539–45. © 2002 American Cancer Society.DOI 10.1002/cncr.11002