bluuebunny/crossref_metadata_2025_split huggingface dataset:
TP53 gene mutations and CCND1 gene amplification in head and neck squamous cell carcinoma cell lines
Authors: Xu Li , Davidson Bruce J. , Murty V. V. V. S. , Li Rong‐Guo , Sacks Peter G. , Garin‐Chesa Pilar , Schantz Stimson P. , Chaganti R. S. K. 
Published: February 2007

AbstractMutations of the tumor‐suppressor gene TP53 and amplification of CCNDI gene have been reported to occur frequently in head and neck squamous cell carcinomas (HNSQCC). In experimental systems, TP53 mutations have been shown to lead to genomic instability, including an increased propensity for gene amplification. We have examined I6 HNSQCC cell lines for the association between TP53 over‐expression/mutation and CCNDI amplification. p53 over‐expression was detected in 50% of the cell lines by immunohistochemistry using the monoclonal antibody (MAb) PAbI80l. TP53 mutations were also detected in 50% of the cell lines by analysis of single‐strand conformation polymorphism (SSCP) and DNA sequencing of exons 4 through 9. Six cell lines showed TP53 mutations and over‐expression of the protein, 2 cell lines showed TP53 mutations but no p53 expression, and 2 cell lines showed over‐expression of p53 protein but no TP53 gene mutations. CCNDI amplification was found in 38% of the cell lines by Southern blot analysis. Only I cell line showed both TP53 mutation and CCNDI amplification, whereas 7 of 8 cell lines with TP53 mutations had no CCNDI amplification. pRb expression was detected by Western blot analysis, and the level of pRb did not correlate with either CCNDI amplification or TP53 mutation. Our findings suggest that TP53 mutation and CCNDI amplification are common genetic alterations in HNSQCC and that the occurrence of either genetic event may be sufficient to abrogate normal cell cycle control. © 1994 Wiley‐Liss, Inc.
Low‐dose chemotherapy delays relapse of a dominated and resistant sub‐population in a heterogeneous human sclc xenograft in nude mice
Authors: Aabo Kristian , Vindeløv Lars L. , Christensen Ib J. , Spang‐Thomsen Mogens 
Published: February 2007

AbstractWe investigated the influence of cellular heterogeneity on the response to low‐dose BCNU chemotherapy of an artificially mixed human small‐cell lung cancer (SCLC) xenograft in nude mice containing a BCNU‐sensitive and dominating sub‐population and a BCNU‐resistant and undetectable (dominated) sub‐population. The cell lines differed in DNA content, making them distinguishable by DNA flow cytometry (FCM). After 3 weeks of tumor growth, the mice were stratified according to tumor size and randomized to 2 different low‐dose treatments with BCNU or no treatment. After a further 3 to 4 weeks, a high‐dose treatment (LD10) was given to both groups of treated tumors. Changes in the relative proportions of and cell lines in the tumors were measured by FCM on fine‐needle tumor aspirates. At the time of low‐dose treatment, all the tumors were totally dominated by the sensitive cells. A temporary response was seen after low‐dose treatment. After the highdose treatment, a similar short response was seen. In the non‐treated group, the sensitive cells continued to dominate. At the time of tumor regrowth after the low‐dose treatment, most of the tumors continued to be dominated by the sensitive population. At the time of progression after the response to the high‐dose treatment, the resistant cell line was the predominant population. If compared with a single high‐dose BCNU treatment, the response of tumors treated with a low dose was superior, indicating that the presence of a dominating and slower growing sub‐population influenced the outcome of the treatment. © 1994 Wiley‐Liss, Inc.
EGF modulation of the ras‐related rhoB gene expression in human breast‐cancer cell lines
Authors: De Cremoux Patricia , Gauville Christiane , Closson Violaine , Linares Gustavo , Calvo Fabian , Tavitian Armand , Olofsson Birgitta 
Published: February 2007

AbstractThe mRNA levels of the ras‐related human rhoA, rhoB and rhoC genes were studied in human breast‐cancer cell lines (HBCal), and in normal and immortalized mammary epithelial cells (HMEC) by Northern blot analysis and in situ hybridization. In contrast to the ubiquitous rhoA and rhoC gene expression, dramatic variations in the mRNA level of the rhoB gene were evidenced. The rhoB mRNA level appeared to be inversely correlated to the amounts of the epidermal‐growth‐factor(EGF) receptors in these cells. The rhoB transcripts were detected at high levels in ZR75‐1, MCF7, HSL 53, HSL 59, HSL 90, T47D and SKBR3 HBCal, at hardly detectable levels in BT 20, MDA‐MB 231 and H466B HBCal and at intermediate levels in normal and immortalized breast epithelial cells. Rapid and transient induction of the rhoB transcription was observed after EGF treatment in serum‐deprived MDA‐MB231, T47D and immortalized epithelial cells. In contrast, no modulation of rhoB expression by EGF could be objectified in the MCF7 and ZR75‐1 cell lines. Yet a normal function of EGF receptors was evidenced, since the immediate early gene c‐fos was rapidly induced, suggesting a constitutive expression of rhoB in these cell lines bypassing the regulation by EGF. In human mammary epithelial cells, rhoB mRNA is rapidly and transiently induced with EGF concentrations known to stimulate cell proliferation. This suggests that the rhoB product might be involved in a cascade that initiates or promotes cell proliferation, and plays an important role in EGF‐stimulated growth of breast normal and cancer cells. © 1994 Wiley‐Liss, Inc.
Family history and the risk of endometrial cancer
Authors: Parazzini Fabio , La Vecchia Carlo , Moroni Simona , Chatenoud Liliane , Ricci Elena 
Published: February 2007

AbstractThe association between a family history of endometrial, breast and ovarian cancer and the risk of endometrial cancer was analyzed on the basis of data from a case‐control study conducted in northern Italy between 1983 and 1993. A total of 726 histologically confirmed endometrial‐cancer patients (median age 61) admitted to a network of general and teaching hospitals in the Greater Milan area were interviewed. The controls were 2, 123 women (median age 59), admitted for acute, non‐neoplastic, non‐hormone‐related diseases to the same network of hospitals were the cases had been identified, with admission diaagnoses unrelated to any of the known or suspected risk factors for endometrial cancer. Among cases, 37 (5.1%) reported a history of endometrial cancer in first‐degree relatives. The corresponding figure among controls was 77 (3.6%). In comparison with women with no family history of endometrial cancer, the odds ration (OR) of endometrial cancer was 1.5 (95%CI[confidence interval], 1.0‐2.3) in women with a history of endometrial cancer in first‐degree relatives. NO relation emerged between endometrial cancer and a family history of breast or wvarian cace. These results suggest that a family history of endomertial cancer increases the risk of contracting the same disease. However, the proportion of cases attributable to this factor was small: less than 1%of endometrial cancers in this population were attributable to familial (and hence potentially genetic) factors. © 1994 Wiley‐Liss, Inc.
Human‐papillomavirus DNA in cholesteatomas
Authors: Bergmann Krister , Hoppe Florian , He Yukai , Helms Jan , Müller‐Hermelink Hans‐Konrad , Stremlau Armin , De Villiers Ethel‐Michele 
Published: February 2007

AbstractCholesteatoma of the middle ear is a relatively common disorder, often with severe consequences. Histologically, the aggressively growing, bone‐destructing form shows papillary growth and koilocytosis, which are characteristic of papillomavirus‐induced lesions. A PCR (polymerase chain reaction) method using degenerate primers for the detection of any known or as yet unknown HPV (human papillomavirus) type was applied in screening 51 biopsies from 42 patients. A resulting 36% (16/45) of the cholesteatomas were found to contain papillomavirus DNA, which hybridized under stringent conditions with an HPV‐II DNA probe. In 3 cases the presence of HPV‐II DNA could be confirmed by sequencing the PCR products. The mere presence of this HPV DNA does not prove an etiological role of this group of viruses in the induction of cholesteatomas. It does, however, identify another group of human proliferative lesions putatively linked to papillomavirus infections. © 1994 Wiley‐Liss, Inc.
Haemopoietic progenitor and myeloid cell kinetics in humans treated with interleukin‐3 and granulocyte/macrophage colony‐stimulating factor in combination
Authors: Lord Brian I. , Testa Nydia G. , Bretti Sergio , Chang James , Demuynck Hilda , Coutinho Lucia , De Campos Edson , Fitzsimmons Lesley , Howard Scarffe J. 
Published: February 2007

AbstractPatients with advanced adenocarcinoma of the colon, rectum or pancreas were entered into trials for evaluation of treatment with sequential doses of IL‐3 and GM‐CSF. They received 0.25 to 5μgIL‐3/kg/d for up to 7days, followed by I μgGM‐CSF/kg/day for a maximum of 10 further days. We assessed the kinetics of bone‐marrow cell proliferation and of blood production using tritiated thymidine labelling in vitro and in vivo. Megakaryocytic‐CFC were unaffected but proliferation rates of GM‐CFC and BFU‐E were increased. Progenitor cells were mobilized (12‐fold over baseline) into the peripheral blood. The proliferative activity of maturing cells in the marrow was increased (cell‐cycle times were reduced by at least 30%). This translated into amplified blood cell production (WCC ∼30 × 109/1), a 2.2‐fold increase in platelet counts and significant eosinophilia. Newly generated neutrophils appeared in the circulation at the normal time and their peripheral half‐life was also normal. The calculated 3.2‐fold amplification in neutrophil production required nearly 2 extra divisions in the marrow, shared between the progenitors and the proliferating granulocytic cells. The results were compared with those of a previous trial using GM‐CSF only, although at a 10‐fold higher dose level. Comparable levels of peripheral neutrophils were obtained in both trials but significant ineffective granulopoiesis developed in the earlier study. This was overcome in the present study, the priming dose of IL‐3 apparently giving the latitude to utilize lower doses of GM‐CSF with less risk of complications. © 1994 Wiley‐Liss, Inc.
At least one in seven cases of cancer is caused by smoking. Global estimates for 1985
Authors: Parkin D. M. , Pisani P. , Lopez A. D. , Masuyer E. 
Published: February 2007

AbstractTobacco smoking is accepted as a major cause of cancers of the lung, larynx, oral cavity and pharynx, oesophagus, pancreas, kidney and bladder. The proportions of these cancers that are due to smoking were estimated for the year 1985 for 24 areas of the world. Fifteen percent—1. 1 million new cases per year—of all cancer cases are attributed to cigarette smoking, 25% in men and 4% in women. In developed countries, the tobacco burden is estimated at 16% of all annual incident cases. In developing countries, the corresponding figure is 10%. In total, 85% of the 676 000 cases of lung cancer in men are attributable to tobacco smoking. The highest attributable fractions (AF: 90–93%) are estimated in areas where the habit of cigarette smoking in men has been longest established: North America, Europe, Australia/New Zealand and the former USSR. Among the other 6 cancer sites considered in this analysis, those with the largest fractions of tobacco‐related cases are the larynx, mouth and pharynx (excluding nasopharynx) and oesophagus. In regions where males have smoked for several decades, 30 to 40% of all cancers in this sex are attributable to tobacco. Unless tobacco‐control efforts in developing countries are strengthened, the massive rise in cigarette consumption over the last few decades will produce a comparable rise in cancer in these countries within the next 20 to 30 years. © 1994 Wiley‐Liss, Inc.
Expression of stromelysin‐1 and timp‐1 in the involuting mammary gland and in early invasive tumors of the mouse
Authors: Li Feng , Friis Robert R. , Djonov Valentin , Altermatt Hans‐Jörg , Saurer Susanne , Niemann Heiner , Andres Anne‐Catherine 
Published: February 2007

AbstractThe mammary gland, during post‐lactational involution, is subjected to extensive tissue reconstruction. This process is governed by the concerted expression of extracellular‐matrixdegrading enzymes and their inhibitors. During carcinogenesis, the invasive growth of tumor cells is characterized by the penetration of the basement membrane and stromal invasion. We compared the expression of the tissue‐remodeling enzymes stromelysin‐l, a matrix metalloproteinase, and its inhibitor, tissue inhibitor of metalloproteinase‐l (TIMP‐l), during mammary gland involution and carcinogenesis in mouse. In involuting mammary glands, stromelysin‐l was expressed in myoepithelial cells, whereas TIMP‐l was confined to the stromal tissue. To analyze the involvement of these tissue‐remodeling genes in tumor development, we examined mammary tumors of transgenic mice expressing either the activated Ha‐ras or c‐myc oncogene under the control of a milk‐protein gene promoter. In the undifferentiated and metastasizing Ha‐ras‐induced tumors, stromelysin‐l expression was comparable to that seen in involution, whereas TIMP‐l expression was greatly elevated. During Ha‐ras‐induced carcinogenesis, stromelysin‐l expression was first detected in the myo‐epithelial cells surrounding preneoplastic lesions. In contrast, in the well‐differentiated and non‐metastatic mammary tumors induced by c‐myc, no expression of either gene was observed. Thus, expression of stromelysin‐l and TIMP‐l is confined to the aggressively growing tumors and is induced in the earliest stages of carcinogenesis. © 1994 Wiley‐Liss, Inc.
Immunocytochemical localization of BCL‐2 protein in human breast cancers and its relationship to a series of prognostic markers and response to endocrine therapy
Authors: Gee Julia M. W. , Robertson John F. R. , Ellis Ian O. , Willsher Peter , McClelland Richard A. , Hoyle Helen B. , Kyme Susan R. , Finlay Pauline , Blamey Roger W. , Nicholson Robert I. 
Published: February 2007

AbstractThe protein product of the bcl‐2 gene is thought to be involved in inhibition of apoptosis; it may therefore be important in the modulation of hormonal/anti‐hormonal responsiveness exhibited by tumours. This study immunocytochemically investigates (i) relationships between bcl‐2 protein expression in primary breast cancers and other markers of prognostic and therapeutic value and (ii) associations of the bcl‐2 protein with breast cancer responsiveness to endocrine therapy. The bcl‐2 protein was found within the tumour epithelial cell cytoplasm of 32/46 breast cancer specimens; inter‐patient staining was heterogeneous. Immunostaining for steroid hormone receptors was strongly associated with that for the bcl‐2 protein, and it is thus possible that this protein, like progesterone receptor, is under oestrogen regulation via oestrogen receptor. The protein was inversely related to 2 markers of endocrine insensitivity, epidermal growth factor receptor (EGFR) and c‐erbB‐2 oncoprotein, while no associations were observed with either transforming growth factor (TGF)‐alpha or Ki‐67 proliferative status. A highly significant relationship was observed between response to endocrine therapy and the presence of bcl‐2 protein. Indeed, bcl‐2 immunostaining proved to be a more accurate predictor of response than oestrogen receptor status. Patients with elevated bcl‐2 immunostaining (particularly those who co‐expressed high oestrogen receptor levels) appeared to derive the greatest benefit from endocrine therapy. Our results are paradoxical since it was expected that the bcl‐2 protein would counteract the tumour inhibitory effects of endocrine therapies as it is thought to prevent programmed cell death.
Microvascular expression of mala‐2 correlates with In vivo lymphocyte trafficking and is preferentially enhanced in tumors by tumor necrosis factor‐α and interleukin‐1α
Authors: Dean Phillip A. , Ramsey Patrick S. , Donohue John H. , Nelson Heidi 
Published: February 2007

AbstractThe role of endothelial cell adhesion molecule expression in the immune response to tumors is unknown. We have investigated the expression of murine lymphocyte activation antigen (MALA‐2), the murine equivalent of intercellular adhesion molecule‐1 (ICAM‐1), in blood vessels of normal murine tissues and in melanoma tumors and evaluated the relationship between MALA‐2 expression and lymphocyte trafficking in vivo. C3H/HeN mice were injected both i.p. and s.c. with a clone of K‐1735 syngeneic melanoma cells. Day 11 tumor‐bearing mice were killed and vascular expression of MALA‐2 was quantified using immunohistochemistry. MALA‐2 expression was high in lung, liver and spleen and low in lymph node, small bowel, muscle and tumor. Systemic administration of either recombinant tumor necrosis factor α (rTNFα) or recombinant interleukin‐1α(rIL‐Iα) over 2 days prior to organ harvest resulted in an increase in the number of tumor vessels expressing MALA‐2, with no change in MALA‐2 expression in other tissues. In vivo lymphocyte trafficking was evaluated using cultured, activated splenocytes radiolabeled with 111In. 111In‐labeled splenocyte distribution correlated closely with MALA‐2 expression, with high localization to spleen, liver and lung and poor localization to lymph node, small bowel, muscle and tumor. Systemic administration of rTNFα, but not rIL‐Iα, resulted in a significant increase in 111In‐labeled splenocyte distribution to tumor, but neither rTNFα nor rIL‐Iα altered 111In‐labeled splenocyte distribution to normal organs. Our data demonstrate the in vivo pattern of vascular MALA‐2 expression in normal murine tissues and tumors and suggest that the expression of MALA‐2 can be preferentially enhanced in tumors by systemic administration of cytokines. Lymphocyte distribution in vivo correlates closely with the pattern of MALA‐2 expression, and these data support the conclusion that MALA‐2 plays an important role in the regulation of lymphocyte trafficking.
Lymphoproliferative disease in human peripheral‐blood‐mononuclear‐cell‐injected scid mice. II. Role of host and donor factors in tumor generation
Authors: Veronesi Arianna , Coppola Vincenzo , Veronese Maria Luisa , Menin Chiara , Bruni Laura , D'Andrea1 Emma , Mion Marta , Amadori Alberto , Chieco‐Bianchi Luigi 
Published: February 2007

AbstractIntraperitoneal injection of lymphoid cells from EBV+ donors into SCID mice might provide a useful tool for studying the pathways of B‐cell lymphomagenesis in man. Since previous studies showed that donor T cells greatly favor B‐cell proliferation and tumor generation in this model, we addressed the host and donor factors involved in limiting or promoting lymphoma development. The number of EBV‐infected B‐cell precursors was crucial, since purified B lymphocytes, which alone were unable to generate tumors, underwent expansion and established tumor masses when the animals were inoculated with an EBV‐containing supernatant. Host factors were critical in limiting tumor development; in vivo NK‐cell removal allowed purified B cells to expand and proceed to tumors in the absence of T lymphocytes, whereas potentiation of mouse NK‐cell activity prevented tumor generation in PBMC‐ and LCL‐injected animals. The T‐cell‐derived factors that favor lymphomagenesis could not be identified; IL‐2, IL‐4, IL‐6, and soluble CD23 were not able to promote B‐cell expansion, and treatment of PBMC‐injected mice with the relevant anti‐cytokine anti‐sera did not counteract lymphoma development. These experiments also showed that IL‐6 plays a minor role, if any, in B‐cell lymphoproliferation in this model. Our data indicate that reconstitution of SCID mice with PBMC from EBV+ donors may constitute a useful model for determining the events involved in lymphomagenesis in humans, provided that strict control of all the experimental variables is guaranteed.
Differential effects of protein kinase a sub‐units on chinese‐hamster‐ovary cell cycle and proliferation
Authors: Tortora Giampaolo , Pepe Stefano , Bianco Caterina , Damiano Vincenzo , Ruggiero Angela , Baldassarre Gustavo , Corbo Claudia , Cho‐Chung Yoon Sang , Bianco A. Raffaele , Ciardiello Fortunato 
Published: February 2007

AbstractIt has been shown that a marked increase in the levels of Rlα sub‐units and a decrease in RIIβ sub‐unit levels correlate with neoplastic transformation or with the mitogenic response of normal cells to hormones and growth factors. The selective down‐regulation of RIα and the following induction of RIIβ determine cell‐growth arrest and differentiation of several cancer cells. To directly address the question whether the 2 protein‐kinase‐A(PKA) isoforms play different roles in the control of proliferation and cell‐cycle distribution, we introduced and over‐expressed the different PKA sub‐units in Chinese‐hamster‐ovary (CHO) cells via retroviral‐vector‐mediated gene transfer. Whereas CHO cells treated with RIα anti‐sense oligodeoxynucleotides were growth arrested and accumulated in the G0/G1 phases of the cell cycle, infection of CHO cells with a retroviral vector in order to over‐express RIα determined growth advantages in monolayer conditions and substantially increased their cloning efficiency in soft agar. These events correlated with a sustained percentage of cells in S phase induced by RIα over‐expression in the infected cells. In contrast, CHO cells infected with retroviral vectors over‐expressing either a RIIβ sub‐unit or a Cα catalytic sub‐unit of PKA exhibited growth arrest within a few days of culture and accumulated in the G2‐M phase of the cell cycle. The results of our study demonstrate that the different PKA sub‐units play different and specific roles in the control of cell growth and cell‐cycle distribution.
Brain cancer incidence, mortality and case survival: Observations from two australian cancer registries
Authors: Shugg Dace , Allen Barry J. , Blizzard Leigh , Dwyer Terence , Roder David 
Published: February 2007

AbstractData from 2 Australian cancer registries covering a population of 1.7 million people were combined for the purposes of analysing brain cancer incidence, mortality and survival patterns for the time period 1978 through 1992. A total of 1,752 cases of primary brain cancer were registered, representing age‐standardised incidence rates of 6.7 per 100,000 in men and 4.6 in women. Histological confirmation was available for 94% of cases. The incidence rate among persons aged 75 or over was higher during 1986–1992 than during 1978–1985, the rate for men increasing from 16.3 to 26.2 and that for women increasing from 9.7 to 18.0. The largest increases in this age group occurred for cases of glioblastoma multiforme. During the study period, 1,411 brain cancer deaths were notified to the 2 registries at age‐standardised rates of 5.3 in men and 3.4 in women. Mortality rates among persons aged 75 years or older were higher during 1986–1992 than 1978–1985, increasing from 15.7 to 28.4 in men and from 10.1 to 15.3 in women. Only among men aged 15–49 years was a decline in mortality rates observed, from 3.3 to 2.4. Survival analyses indicated that age and histological type were the most powerful prognostic indicators. There was no improvement in 5‐year survival for any of the age groups or histological types. An improvement in 36‐month survival was noted for the 15–49 year age group diagnosed with gliomas other than glioblastoma multiforme.