bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phenotypic variation in eight extended CDKN2A germline mutation familial atypical multiple mole melanoma–pancreatic carcinoma–prone families
Authors: Lynch Henry T. , Brand Randall E. , Hogg David , Deters Carolyn A. , Fusaro Ramon M. , Lynch Jane F. , Liu Ling , Knezetic Joseph , Lassam Norman J. , Goggins Michael , Kern Scott 
Published: August 2002

AbstractBACKGROUNDHereditary pancreatic carcinoma shows extant phenotypic and genotypic heterogeneity as evidenced by its integral association with a variety of hereditary cancer syndromes inclusive of the familial atypical multiple mole melanoma (FAMMM) syndrome in concert with CDKN2A (p16) germline mutations.METHODSCreighton University's familial pancreatic carcinoma resource comprises 159 families of which 19 (12%) show the FAMMM cutaneous phenotypes. The authors describe eight families with the FAMMM–pancreatic carcinoma (FAMMM‐PC) association in concert with a CDKN2A germline mutation. Each family was thoroughly educated about all facets of the study, including the molecular genetics, reduced penetrance of CDKN2A mutations, and their variable expressivity. Genetic counseling was provided to each patient.RESULTSDiversity in cancer presentation within and among the families was noteworthy, wherein melanoma predominated in certain of the families whereas pancreatic carcinoma predominated in others. Early‐onset pancreatic carcinoma (at ages 35, 45, 46, and 49 years) appeared in some of the families whereas markedly later‐onset pancreatic carcinoma occurred in others. There were four incidences of melanoma and pancreatic carcinoma as double primaries in the same individuals. One patient with melanoma and pancreatic carcinoma had a third primary of breast carcinoma. Another patient had sarcoma, esophageal carcinoma, and two melanoma primaries, whereas his daughter had sarcoma and was a carrier of a CDKN2A mutation.CONCLUSIONSThe authors suggest that these tumors may collectively, in concert with CDKN2A mutations, constitute a “new” putative hereditary carcinoma syndrome referred to as FAMMM‐PC. More clinical and molecular genetic research on additional families with pancreatic carcinoma in concert with the FAMMM will be required. Cancer 2002;94:84–96. © 2002 American Cancer Society.
Neuropeptides bombesin and calcitonin inhibit apoptosis‐related elemental changes in prostate carcinoma cell lines
Authors: Salido Mercedes , Vilches Jose , López Antonio , Roomans Godfried M. 
Published: August 2002

AbstractBACKGROUNDEtoposide‐induced apoptosis in prostate carcinoma cells is associated with changes in the elemental content of the cells. The authors previously reported that calcitonin and bombesin inhibited etoposide‐induced apoptosis in these cells. In the current study, the authors investigated whether these neuropeptides block the etoposide‐induced changes in elemental content.METHODSCells from the PC‐3 and Du 145 prostate carcinoma cell lines were grown either on solid substrates or on thin plastic films on titanium electron microscopy grids, and they were exposed to etoposide for 48 hours in the absence or presence of calcitonin and bombesin. After the exposure, the cells were frozen and freeze dried, and their elemental content was analyzed by energy‐dispersive X‐ray microanalysis in both in the scanning electron microscope and the scanning transmission electron microscope.RESULTSEtoposide treatment consistently induced an increase in the cellular Na concentration and a decrease in the cellular K concentration, resulting in a marked increase of the Na/K ratio and also an increase in the phosphorus:sulphur (P/S) ratio. Both bombesin and calcitonin inhibited the etoposide‐induced changes in the cellular Na/K ratio, and calcitonin, but not bombesin, inhibited the changes in the P/S ratio. No significant elemental changes were found with bombesin or calcitonin alone.CONCLUSIONSThe neuropeptides bombesin and calcitonin, which inhibited etoposide‐induced apoptosis, also inhibited the etoposide‐induced elemental changes in prostate carcinoma cells. This important fact strengthens the link between apoptosis and changes in the intracellular elemental content. This correlation provides an objective basis for the study of neuropeptide target points and may be helpful for alternative therapeutic protocols using neuropeptide inhibitors in the treatment of patients with advanced prostatic carcinoma. Cancer 2002;94:368–77. © 2002 American Cancer Society.
ErbB2 expression is correlated with increased survival of patients with osteosarcoma
Authors: Akatsuka Tomohiro , Wada Takuro , Kokai Yasuo , Kawaguchi Satoshi , Isu Kazuo , Yamashiro Katsushige , Yamashita Toshihiko , Sawada Norimasa , Yamawaki Shinya , Ishii Seiichi 
Published: August 2002

AbstractBACKGROUNDElevated ErbB2 expression and gene amplification have been shown to be associated with poor prognosis in many cancers. Recently, it has been demonstrated that overexpression of ErbB2 protein in osteosarcoma is associated with the presence of pulmonary metastasis and decreased survival. By contrast, a previous study showed that the expression of ErbB2 declines in individual osteosarcomas as they become metastatic. In the current study, the authors determined the relation between ErbB2 status and outcome in a large number of selected patients with high‐grade osteosarcoma.METHODSErbB2 status was determined immunohistochemically in biopsy specimens of osteosarcoma of the extremities from 81 patients who were treated with surgery and chemotherapy. None of the patients had metastatic disease at presentation (Stage II), and all were followed‐up for at least five years. The ErbB2 status was analyzed in relation to the lengths of event‐free and overall survival.RESULTSOf the 81 tumors examined, 51 (61%) demonstrated high levels of ErbB2 expression. The presence of increased levels of ErbB2 in osteosarcoma was significantly associated with the increased probability of event‐free (72.2% v. 45.6% at 5 years, P = 0.03) and overall survival (79.7% v. 58.2% at 5 years, P = 0.03). Cox multivariate analysis showed that the risk of adverse events and death was increased substantially (rate ratio: 2.24 and 2.54; 95% confidence interval, 1.07–4.72 and 1.09–5.67, respectively) among patients with decreased levels of ErbB2 protein in tumor cells, as compared with patients who had increased levels of ErbB2 in tumor cells.CONCLUSIONSIn patients with high‐grade osteosarcoma without metastatic disease at presentation and treated with surgery and chemotherapy, the presence of increased levels of ErbB2 in tumor cells is associated with a significantly increased probability of event‐free and overall survival. Further data are needed before this marker can be used in making clinical decisions. Cancer 2002;94:1397–404. © 2002 American Cancer Society.DOI 10.1002/cncr.10360
Close association between high serum alanine aminotransferase levels and multicentric hepatocarcinogenesis in patients with hepatitis C virus‐associated cirrhosis
Authors: Tarao Kazuo , Rino Yasushi , Ohkawa Shinichi , Tamai Setsuo , Miyakawa Kaoru , Takakura Hideki , Endo Osamu , Yoshitsugu Michiyasu , Watanabe Norihito , Matsuzaki Shohei 
Published: August 2002

AbstractBACKGROUNDMulticentric development of hepatocellular carcinoma (HCC) is a characteristic feature of hepatitis C virus (HCV)‐associated cirrhosis (HCV‐LC). In this study, the objective was to determine whether the persistent elevation of the serum alanine aminotransferase (ALT) level, which represents the inflammatory necrosis of hepatocytes, is correlated with the multicentric development of hepatocellular carcinoma (HCC) in patients with early‐stage HCV‐LC.METHODSNinety‐three consecutive patients with biopsy proven HCV‐LC (Child Stage A) who had been followed for > 5 years for the development of HCC were studied. They were subdivided into three groups according to their serum ALT level: Group A included 33 patients with annual average serum ALT levels that were persistently high (≥ 80 IU; high ALT group), Group B included 41 patients with annual average serum ALT levels that were persistently low (< 80 IU; low ALT group), and Group C included 19 unclassified patients. The patients had been studied prospectively with frequent ultrasonography and magnetic resonance imaging or computed tomography (CT) scans for > 5years. When the development of HCC was suspected, angiography, infusion of lipiodol into the hepatic artery, and lipiodol‐CT scans were performed in all patients to determine the number of HCC nodules.RESULTSIn Group A, 27 patients (81.8%) developed HCC. Seventeen of 27 patients (63.0%) had multiple nodules. In contrast, in Group B, only 12 patients (29.3%) developed HCC, and only 1 of these 12 patients (8.3%) had multiple nodules. There was a significant difference between Groups A and B in the incidence of developing HCC (P < 0.001) and developing multiple nodules (P = 0.006). In addition, among the male patients, the incidence of developing multiple HCC nodules in Group A (12 of 19 patients; 63.2%) was significantly higher (P < 0.05) compared with the incidence in Group B (0 of 6 patients; 0%). The same tendency was observed among the female patients.CONCLUSIONSThese results showed a close correlation between multicentric hepatocarcinogenesis and sustained necroinflammation of the liver in patients with HCV‐LC. Cancer 2002;94:1787–95. © 2002 American Cancer Society.DOI 10.1002/cncr.10391
Increased proliferative activity caused by loss of p21WAF1/CIP1 expression and its clinical significance in patients with early‐stage gastric carcinoma
Authors: Noda Hiroshi , Maehara Yoshihiko , Irie Koji , Kakeji Yoshihiro , Yonemura Tomohiro , Sugimachi Keizo 
Published: August 2002

AbstractBACKGROUNDRecurrences of gastric carcinoma are likely to take on a variety forms, even after patients undergo curative resection for early‐stage gastric carcinoma. It is important to identify the biologic markers that predict tumor progression and survival in these patients. Proliferating cell nuclear antigen (PCNA) acts as a processivity factor for DNA polymerase δ, which is involved directly in DNA synthesis, and the PCNA level is correlated with the proliferative state of cells. p21WAF1/CIP1 interacts with PCNA to inhibit DNA synthesis and plays a central role in regulating the cell cycle. The authors investigated patients with early‐stage gastric carcinoma to determine the clinical significance of proliferative activity and p21 expression.METHODSTissue specimens from 133 Japanese patients with early‐stage gastric carcinoma that invaded the submucosal layer were immunostained with a monoclonal antibody against PCNA and p21WAF1/CIP1, and the correlations between the PCNA labeling index and p21WAF1/CIP1 expression as well as clinicopathologic factors were investigated.RESULTSThe PCNA labeling index varied from 9.9% to 81.4%, (mean, 31.2%). The incidence of p21 positive expression was 87 of 133 patients (65.4%). The patients with a high labeling index had a significantly higher rate of lymph node metastasis (P < 0.01) and loss of p21WAF1/CIP1 expression (P < 0.05) compared with the patients with a low labeling index. The 5‐year survival rate for patients in the high labeling index group (87.0%) was significantly lower compared with the 5‐year survival rate for the patients in the low labeling index group (98.6%; P < 0.05).CONCLUSIONSLoss of p21WAF1/CIP1 expression contributes to the amplification of proliferative activity in patients with early‐stage gastric carcinoma. Estimation of the proliferative activity of early‐stage gastric carcinoma provides information on lymph node metastasis and prognosis. Even after patients undergo curative resection, those with early‐stage gastric carcinoma should be followed closely. Cancer 2002;94:2107–12. © 2002 American Cancer Society.DOI 10.1002/cncr.10417
Multiple primary melanoma revisited
Authors: Blackwood M. Anne , Holmes Robin , Synnestvedt Marie , Young Megan , George Cicily , Yang Hannah , Elder David E. , Schuchter Lynn M. , Guerry DuPont , Ganguly Arupa 
Published: August 2002

AbstractBACKGROUNDIncidence of cutaneous melanoma continues to increase in the Caucasian population worldwide. Approximately 5% of melanoma patients develop additional primary melanoma. This rate is significantly higher than the estimated lifetime risk of an individual for developing the disease (1.4%). These features suggest that a genetic predisposition may underlie multiple primary melanomas (MPMs). Prior studies had identified CDKN2A mutations in a few MPM individuals. The objectives of this study were to determine the frequency of family history of melanoma in MPM cases, to characterize other clinical features including history of other cancer, and to determine the association with functional CDKN2A mutations.METHODSThis study used a case series design. All living patients who had been seen in the Pigmented Lesion Clinic at the University of Pennsylvania and who had more than one primary invasive malignant melanoma or an invasive primary followed by an in situ melanoma were eligible for participation.RESULTSIndividuals with MPM frequently had a family history of melanoma, dysplastic nevi (DN), and/or another cancer including basal cell carcinoma (BCC), and squamous cell carcinoma breast cancer, and a personal history of DN, and basal cell carcinoma. Germline mutations in CDKN2A gene were identified in 8 of 96 MPM cases (8.3%, 95% confidence interval, 6.7–9.9%).CONCLUSIONSThese data indicate that the presence of MPM is associated with a modest incidence of a family history of melanoma, DN, or BCC and a small association with CDKN2A mutations. Therefore, in addition to the MPM index case, other family members can benefit from screening and regular surveillance for melanoma, DN, and BCC. Cancer 2002;94:2248–55. © 2002 American Cancer Society.DOI 10.1002/cncr.10454
Survival analysis with p27 expression and apoptosis appears to estimate the prognosis of patients with synovial sarcoma more accurately
Authors: Kawauchi Shigeto , Goto Yoshinari , Ihara Koichiro , Furuya Tomoko , Oga Atsunori , Tsuneyoshi Masazumi , Kawai Shinya , Sasaki Kohsuke 
Published: August 2002

AbstractBACKGROUNDAlthough recent experimental studies have implicated p27 as a regulator of apoptosis in a number of neoplasms, to the authors' knowledge the relation between p27 expression and apoptosis has not yet been established in synovial sarcoma.METHODSThe relation between p27, apoptosis, and clinicopathologic features were examined in 62 synovial sarcoma cases.RESULTSp27 expression was found to be correlated inversely with the extent of apoptosis in synovial sarcomas. On survival analysis, p27 expression was found to be a significant and independent prognostic factor. Although the extent of apoptosis was determined to be prognostically significant, it failed to retain an independent and significant value on multivariate analysis. The combination of p27 expression and apoptosis allowed for the more accurate estimation of prognosis in patients with synovial sarcoma than either parameter alone.CONCLUSIONSA combination of p27 expression and extent of apoptosis permitted the more accurate estimation ofy the prognosis of patients with synovial sarcoma. Cancer 2002; 94:2712–8. © 2002 American Cancer Society.DOI 10.1002/cncr.10556
Mental state as a possible independent prognostic variable for survival in patients with advanced lung carcinoma
Authors: Nakahara Yasuharu , Mochizuki Yoshiro , Miyamoto Yoshihiro , Tanaka Akira , Kawamura Tetsuji , Sasaki Shin , Nakahara Yukiko , Katsura Yoshitaka 
Published: August 2002

AbstractBACKGROUNDAlthough psychologic factors have been reported to influence the progression of cancer, this theory remains controversial. A prospective study of patients with advanced lung carcinoma was performed to explore the influence of the patient's mental state on survival.METHODSThe patient's mental state was assessed with the Tokyo University Egogram. In a preliminary study, the egograms of long‐term survivors (survival > 3 years) with TNM Stage IIIB or Stage IV lung carcinoma were compared with the egograms of consecutive, newly diagnosed lung carcinoma patients (controls). Next, in a prospective study, 123 patients with nonsmall cell lung carcinoma and 56 patients with small cell lung carcinoma (Stage IIIB or Stage IV; Eastern Cooperative Oncology Group performance status of 0 or 1) completed the egogram. Based on the results of the preliminary study, the subjects in the prospective study were divided into Group A (Free Child [FC] ≥ 50th percentile and Adapted Child [AC] < 50th percentile) and Group B (FC < 50 percentile or AC ≥ 50 percentile). The survival of the two groups was compared. The Cox proportional hazards model was used to determine the joint effect of the patient's mental state and other prognostic factors.RESULTSIn the preliminary study, the FC score of the long‐term survivors was significantly higher and the AC score was significantly lower than those of the controls. In the prospective study, the survival of Group A was significantly longer than that of Group B both in the nonsmall cell lung carcinoma and small cell lung carcinoma patients (P = 0.002 and P = 0.005, respectively, by the log‐rank test). Multivariate analysis demonstrated that after adjustment for clinical factors, being in Group A was a significant predictor of survival both in the nonsmall cell and small cell lung carcinoma patients.CONCLUSIONSThe results of the current study demonstrate that the mental state of the patient as assessed by the egogram may have prognostic significance in patients with advanced lung carcinoma. Cancer 2002;94:3006–15. © 2002 American Cancer Society.DOI 10.1002/cncr.10608
The clinical course of nonsmall cell lung carcinoma in survivors of Hodgkin disease
Authors: Laurie Scott A. , Kris Mark G. , Portlock Carol S. , Rosenzweig Kenneth E. , Miller Vincent A. , Krug Lee M. , Rusch Valerie W. 
Published: August 2002

AbstractBACKGROUNDThe objective of this study was to document the natural history of second lung carcinomas, common second tumors that arise in survivors of Hodgkin disease (HD).METHODSThe data bases of the Memorial Sloan‐Kettering Cancer Center were searched to retrieve those patients who were listed with a diagnosis of both lung carcinoma and HD. Information was extracted regarding their HD (including age at diagnosis and treatment received) and their lung carcinoma (including smoking history, latency from HD, histology, disease stage, treatment received, treatment response, and survival).RESULTSTwenty‐one lung carcinomas were diagnosed in 19 patients, with a median latency of 13 years from the time of diagnosis of HD. Only five patients underwent complete resection, and four patients were alive and disease free at the last follow‐up. In contrast, the median survival of 14 patients with unresectable disease was 3 months. No major objective responses were documented after chemotherapy. Poor performance status and prior thoracic radiotherapy limited treatment in patients with advanced disease. All patients had either received radiotherapy to the chest for HD or had a history of smoking; 74% of patients had both risk factors for the development of lung carcinoma.CONCLUSIONSIn patients with a history of HD, survival after the development of lung carcinoma is poor. Because surgical resection can lead to long‐term survival, early detection is crucial. HD survivors, especially those with a history of smoking, should undergo careful surveillance for second primary lung carcinomas and other diseases. Patients who are diagnosed with HD should abstain from smoking. Physicians should assess specifically the smoking status of all HD patients and prescribe a smoking cessation program. Cancer 2002;95:119–26. © 2002 American Cancer Society.DOI 10.1002/cncr.10628
Differentiation of tyrosine hydroxylase‐synthesizing and/or aromatic L‐amino acid decarboxylase‐synthesizing neurons in the rat mediobasal hypothalamus: Quantitative double‐immunofluorescence study
Authors: Ershov Petr V. , Ugrumov Michael V. , Calas André , Krieger Monique , Thibault Jean 
Published: August 2002

AbstractIn this double‐immunofluorescence study, we first quantified the neurons of the arcuate nucleus as immunoreactive (+) for tyrosine hydroxylase (TH) and/or aromatic L‐amino acid decarboxylase (AADC) in rats at embryonic day 21 (E21), at postnatal day 9 (P9), and in adulthood by using conventional fluorescent or confocal microscopy. On E21, monoenzymatic (TH+AADC immunonegative (−) and TH−AADC+) neurons and bienzymatic (TH+AADC+) neurons accounted for 99% and 1%, respectively, of the whole neuron population expressing enzymes of dopamine synthesis. Further development was characterized by the dramatic increase in TH+AADC− dorsomedial and TH+AADC+ dorsomedial populations from E21 to P9 as well as by the increase in the TH+AADC+ dorsomedial population (in females) and a drop in the TH+AADC− ventrolateral and TH+AADC− dorsomedial (in males) populations from P9 to adulthood. In contrast to TH+AADC− (in males) and TH+AADC+ neurons, the TH−AADC+ neurons did not change in number from E21 to adulthood. Thus, in rat fetuses, the neurons synthesizing TH and/or AADC were mainly monoenzymatic, whereas during postnatal life the fraction of bienzymatic neurons increased by up to 60%. J. Comp. Neurol. 446:114–122, 2002. © 2002 Wiley‐Liss, Inc.
A‐fiber sensory input induces neuronal cell death in the dorsal horn of the adult rat spinal cord
Authors: Coggeshall Richard E. , Lekan Helena A. , White Fletcher A. , Woolf Clifford J. 
Published: August 2002

AbstractExcitoxicity due to excessive synaptic glutamate release is featured in many neurological conditions in which neuronal death occurs. Whether activation of primary sensory pathways can ever produce sufficient over‐activity in secondary sensory neurons in the dorsal horn of the spinal cord to induce cell death, however, has not been determined. In this study, we asked whether activity in myelinated afferents (A fibers), which use glutamate as a transmitter, can induce cell death in the dorsal horn. Using stereological estimates of neuron numbers from electron microscopic sections, we found that stimulation of A‐fibers in an intact sciatic nerve at 10 Hz, 20 Hz, and 50 Hz in 10‐minute intervals at a stimulus strength that activates both Aβ and Aδ fibers resulted in the loss of 25% of neurons in lamina III, the major site of termination of large Aβ fibers, but not in lamina I, where Aδ fibers terminate. Furthermore, sciatic nerve lesions did not result in detectable neuron loss, but activation of A fibers in a previously sectioned sciatic nerve did cause substantial cell death not only in lamina III but also in laminae I and II. The expansion of the territory of A‐fiber afferent‐evoked cell death is likely to reflect the sprouting of the fibers into these laminae after peripheral nerve injury. The data show, therefore, that primary afferent A‐fiber activity can cause neuronal cell death in the dorsal horn with an anatomical distribution that depends on whether intact or injured fibers are activated. Stimulation‐induced cell death potentially may contribute to the development of persistent pain. J. Comp. Neurol. 435:276–282, 2001. © 2001 Wiley‐Liss, Inc.